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A.; Boivin, Guy title: Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model date: 2011-03-24 journal: PLoS One DOI: 10.1371/journal.pone.0014767 sha: doc_id: 346 cord_uid: 9b6yz3f4 file: cache/cord-000326-a18rch1f.json key: cord-000326-a18rch1f authors: Zhou, Jun-Wei; Tsui, Stephen K. W.; Ng, Maggie C. Y.; Geng, Hua; Li, Sai-Kam; So, Wing-Yee; Ma, Ronald C.; Wang, Ying; Tao, Qian; Chen, Zhen-Yu; Chan, Juliana C. N.; Ho, Yuan-Yuan title: Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes date: 2011-02-24 journal: PLoS One DOI: 10.1371/journal.pone.0017324 sha: doc_id: 326 cord_uid: a18rch1f file: cache/cord-000336-57es391o.json key: cord-000336-57es391o authors: Liao, Qiuyan; Cowling, Benjamin J.; Lam, Wendy Wing Tak; Fielding, Richard title: Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study date: 2011-03-11 journal: PLoS One DOI: 10.1371/journal.pone.0017713 sha: doc_id: 336 cord_uid: 57es391o file: cache/cord-000478-88wo4xen.json key: cord-000478-88wo4xen authors: Gowen, Brian B.; Ennis, Jane; Russell, Andrew; Sefing, Eric J.; Wong, Min-Hui; Turner, Jeffrey title: Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date: 2011-10-24 journal: PLoS One DOI: 10.1371/journal.pone.0026072 sha: doc_id: 478 cord_uid: 88wo4xen file: cache/cord-000715-zl1s82yi.json key: cord-000715-zl1s82yi authors: Shulman, Lester M.; Hindiyeh, Musa; Muhsen, Khitam; Cohen, Dani; Mendelson, Ella; Sofer, Danit title: Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition date: 2012-07-16 journal: PLoS One DOI: 10.1371/journal.pone.0039455 sha: doc_id: 715 cord_uid: zl1s82yi file: cache/cord-000208-th0wddvc.json key: cord-000208-th0wddvc authors: Cornelissen, Lisette A. 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G. title: Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro date: 2013-01-07 journal: PLoS One DOI: 10.1371/journal.pone.0053043 sha: doc_id: 851 cord_uid: uylgyhs8 file: cache/cord-000180-howix091.json key: cord-000180-howix091 authors: MacLeod, Iain J.; Minson, Tony title: Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry date: 2010-03-05 journal: PLoS One DOI: 10.1371/journal.pone.0009560 sha: doc_id: 180 cord_uid: howix091 file: cache/cord-000689-8lvzab4i.json key: cord-000689-8lvzab4i authors: Qi, Yilin; Operario, Darwin J.; Georas, Steve N.; Mosmann, Tim R. title: The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin date: 2012-06-14 journal: PLoS One DOI: 10.1371/journal.pone.0039072 sha: doc_id: 689 cord_uid: 8lvzab4i file: cache/cord-000877-usz7pnvu.json key: cord-000877-usz7pnvu authors: Abdel-Moneim, Ahmed S.; Kamel, Mahmoud M.; Al-Ghamdi, Abdullhamid S.; Al-Malky, Mater I. 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Bier, Frank F.; Nickisch-Rosenegk, Markus v. title: Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni date: 2013-05-29 journal: PLoS One DOI: 10.1371/journal.pone.0065837 sha: doc_id: 979 cord_uid: cav9n18w file: cache/cord-000322-8ctsa9sd.json key: cord-000322-8ctsa9sd authors: Ninove, Laetitia; Nougairede, Antoine; Gazin, Celine; Thirion, Laurence; Delogu, Ilenia; Zandotti, Christine; Charrel, Remi N.; De Lamballerie, Xavier title: RNA and DNA Bacteriophages as Molecular Diagnosis Controls in Clinical Virology: A Comprehensive Study of More than 45,000 Routine PCR Tests date: 2011-02-09 journal: PLoS One DOI: 10.1371/journal.pone.0016142 sha: doc_id: 322 cord_uid: 8ctsa9sd file: cache/cord-000947-psguw47w.json key: cord-000947-psguw47w authors: Feng, Jianyu; Guo, Hong; Li, Sen; Lu, Tun title: A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation date: 2013-04-24 journal: PLoS One DOI: 10.1371/journal.pone.0062147 sha: doc_id: 947 cord_uid: psguw47w file: cache/cord-000723-wo20st5w.json key: cord-000723-wo20st5w authors: Xu, Zhenqiang; 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B. D.; Othman, Rozana Binti; Tao, Xia; Huang, Meilan title: Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine date: 2015-12-04 journal: PLoS One DOI: 10.1371/journal.pone.0144171 sha: doc_id: 262748 cord_uid: v4xue7ha file: cache/cord-263464-fdosch11.json key: cord-263464-fdosch11 authors: Nuvey, Francis Sena; Edu-Quansah, Elijah Paa; Kuma, George Khumalo; Eleeza, John; Kenu, Ernest; Sackey, Samuel; Ameme, Donne; Abakar, Mahamat Fayiz; Kreppel, Katharina; Ngandolo, Richard Bongo; Afari, Edwin; Bonfoh, Bassirou title: Evaluation of the sentinel surveillance system for influenza-like illnesses in the Greater Accra region, Ghana, 2018 date: 2019-03-14 journal: PLoS One DOI: 10.1371/journal.pone.0213627 sha: doc_id: 263464 cord_uid: fdosch11 file: cache/cord-265812-1hcp36cw.json key: cord-265812-1hcp36cw authors: De Jong, Cornelis N.; Saes, Lotte; Klerk, Clara P. W.; Van der Klift, Marjolein; Cornelissen, Jan J.; Broers, Annoek E. 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A Study Comparing Two Areas with Different Management Models date: 2015-05-20 journal: PLoS One DOI: 10.1371/journal.pone.0126770 sha: doc_id: 281665 cord_uid: 6n7aq4k9 file: cache/cord-284016-zb6cv8ik.json key: cord-284016-zb6cv8ik authors: Li, Wei; Liu, Yan; Mukhtar, Muhammad Mahmood; Gong, Rui; Pan, Ying; Rasool, Sahibzada T.; Gao, Yecheng; Kang, Lei; Hao, Qian; Peng, Guiqing; Chen, Yanni; Chen, Xin; Wu, Jianguo; Zhu, Ying title: Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection date: 2008-04-16 journal: PLoS One DOI: 10.1371/journal.pone.0001985 sha: doc_id: 284016 cord_uid: zb6cv8ik file: cache/cord-286837-j2sqs20q.json key: cord-286837-j2sqs20q authors: Koetsier, Antonie; van Asten, Liselotte; Dijkstra, Frederika; van der Hoek, Wim; Snijders, Bianca E.; van den Wijngaard, Cees C.; Boshuizen, Hendriek C.; Donker, Gé A.; de Lange, Dylan W.; de Keizer, Nicolette F.; Peek, Niels title: Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics? date: 2013-12-31 journal: PLoS One DOI: 10.1371/journal.pone.0083854 sha: doc_id: 286837 cord_uid: j2sqs20q file: cache/cord-287784-f7usy52w.json key: cord-287784-f7usy52w authors: Maestre, Ana M.; 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P.; Bruzzone, Roberto; Altmeyer, Ralf title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro date: 2009-11-17 journal: PLoS One DOI: 10.1371/journal.pone.0007870 sha: doc_id: 334695 cord_uid: cjxlw1tu file: cache/cord-335245-1eksm537.json key: cord-335245-1eksm537 authors: Pattyn, Els; Verhee, Annick; Uyttendaele, Isabel; Piessevaux, Julie; Timmerman, Evy; Gevaert, Kris; Vandekerckhove, Joël; Peelman, Frank; Tavernier, Jan title: HyperISGylation of Old World Monkey ISG15 in Human Cells date: 2008-06-18 journal: PLoS One DOI: 10.1371/journal.pone.0002427 sha: doc_id: 335245 cord_uid: 1eksm537 file: cache/cord-337067-j8ebslif.json key: cord-337067-j8ebslif authors: Mades, Andreas; Gotthardt, Katherina; Awe, Karin; Stieler, Jens; Döring, Tatjana; Füser, Sabine; Prange, Reinhild title: Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date: 2012-11-15 journal: PLoS One DOI: 10.1371/journal.pone.0049243 sha: doc_id: 337067 cord_uid: j8ebslif file: cache/cord-339327-4422s317.json key: cord-339327-4422s317 authors: Norris, Susan L.; Sawin, Veronica Ivey; Ferri, Mauricio; Raques Sastre, Laura; Porgo, Teegwendé V. title: An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks date: 2018-05-30 journal: PLoS One DOI: 10.1371/journal.pone.0198125 sha: doc_id: 339327 cord_uid: 4422s317 file: cache/cord-340027-6l55rcfm.json key: cord-340027-6l55rcfm authors: Mamode Khan, Naushad; Soobhug, Ashwinee Devi; Heenaye-Mamode Khan, Maleika title: Studying the trend of the novel coronavirus series in Mauritius and its implications date: 2020-07-10 journal: PLoS One DOI: 10.1371/journal.pone.0235730 sha: doc_id: 340027 cord_uid: 6l55rcfm file: cache/cord-339724-roj8ksvc.json key: cord-339724-roj8ksvc authors: Lan, Jiaming; Deng, Yao; Chen, Hong; Lu, Guangwen; Wang, Wen; Guo, Xiaojuan; Lu, Zhuozhuang; Gao, George F.; Tan, Wenjie title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen date: 2014-11-18 journal: PLoS One DOI: 10.1371/journal.pone.0112602 sha: doc_id: 339724 cord_uid: roj8ksvc file: cache/cord-340763-cxnu9g8y.json key: cord-340763-cxnu9g8y authors: Grimm, Sebastian K.; Battles, Michael B.; Ackerman, Margaret E. title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies date: 2015-02-17 journal: PLoS One DOI: 10.1371/journal.pone.0117227 sha: doc_id: 340763 cord_uid: cxnu9g8y file: cache/cord-337913-eu2gn4bl.json key: cord-337913-eu2gn4bl authors: Stojanov, Ana; Bering, Jesse M.; Halberstadt, Jamin title: Does Perceived Lack of Control Lead to Conspiracy Theory Beliefs? 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F.; Bozza, Fernando A.; Mesquita, Milene; Soares, Márcio; Motta, Fernando C.; Pitrowsky, Melissa Tassano; de Lourdes Oliveira, Maria; Mishin, Vasiliy P.; Gubareva, Larissa V.; Whitney, Anne; Rocco, Sandra Amaral; Gonçalves, Vânia Maria C.; Marques, Venceslaine Prado; Velasco, Eduardo; Siqueira, Marilda M. title: H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis date: 2010-11-30 journal: PLoS One DOI: 10.1371/journal.pone.0014158 sha: doc_id: 342519 cord_uid: tjr6dvtt file: cache/cord-344782-ond1ziu5.json key: cord-344782-ond1ziu5 authors: Zhang, Jing; Finlaison, Deborah S.; Frost, Melinda J.; Gestier, Sarah; Gu, Xingnian; Hall, Jane; Jenkins, Cheryl; Parrish, Kate; Read, Andrew J.; Srivastava, Mukesh; Rose, Karrie; Kirkland, Peter D. title: Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi) date: 2018-10-24 journal: PLoS One DOI: 10.1371/journal.pone.0205209 sha: doc_id: 344782 cord_uid: ond1ziu5 file: cache/cord-343973-n5ogyxz7.json key: cord-343973-n5ogyxz7 authors: Ip, Andrew; 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Tortosa, Pablo; Boussaïd, Karim; Jaffar-Banjee, Marie-Christine; Filleul, Laurent; Flahault, Antoine; Carrat, Fabrice; Favier, Francois; de Lamballerie, Xavier title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009 date: 2011-09-29 journal: PLoS One DOI: 10.1371/journal.pone.0025738 sha: doc_id: 342730 cord_uid: b7y8mybg file: cache/cord-342639-vf9n2vf9.json key: cord-342639-vf9n2vf9 authors: Chang, Chung-ke; Chen, Chia-Min Michael; Chiang, Ming-hui; Hsu, Yen-lan; Huang, Tai-huang title: Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date: 2013-05-23 journal: PLoS One DOI: 10.1371/journal.pone.0065045 sha: doc_id: 342639 cord_uid: vf9n2vf9 file: cache/cord-345695-5vi9wibk.json key: cord-345695-5vi9wibk authors: Hicks, Lorin L.; Schwab, Nathan A.; Homyack, Jessica A.; Jones, Jay E.; Maxell, Bryce A.; Burkholder, Braden O. title: A statistical approach to white-nose syndrome surveillance monitoring using acoustic data date: 2020-10-22 journal: PLoS One DOI: 10.1371/journal.pone.0241052 sha: doc_id: 345695 cord_uid: 5vi9wibk file: cache/cord-345717-ktajrf7d.json key: cord-345717-ktajrf7d authors: Monagin, Corina; 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G. title: Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus) date: 2016-11-04 journal: PLoS One DOI: 10.1371/journal.pone.0166336 sha: doc_id: 348055 cord_uid: azlb1zy1 file: cache/cord-346089-u31n0qxa.json key: cord-346089-u31n0qxa authors: McDade, Thomas W.; McNally, Elizabeth M.; Zelikovich, Aaron S.; D’Aquila, Richard; Mustanski, Brian; Miller, Aaron; Vaught, Lauren A.; Reiser, Nina L.; Bogdanovic, Elena; Fallon, Katherine S.; Demonbreun, Alexis R. title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay date: 2020-08-14 journal: PLoS One DOI: 10.1371/journal.pone.0237833 sha: doc_id: 346089 cord_uid: u31n0qxa file: cache/cord-346067-zly8p0y7.json key: cord-346067-zly8p0y7 authors: Ruiz-Irastorza, Guillermo; Pijoan, Jose-Ignacio; Bereciartua, Elena; Dunder, Susanna; Dominguez, Jokin; Garcia-Escudero, Paula; Rodrigo, Alejandro; Gomez-Carballo, Carlota; Varona, Jimena; Guio, Laura; Ibarrola, Marta; Ugarte, Amaia; Martinez-Berriotxoa, Agustin title: Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data date: 2020-09-22 journal: PLoS One DOI: 10.1371/journal.pone.0239401 sha: doc_id: 346067 cord_uid: zly8p0y7 file: cache/cord-346347-r4ork18p.json key: cord-346347-r4ork18p authors: Borrion, Hervé; Kurland, Justin; Tilley, Nick; Chen, Peng title: Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China date: 2020-10-14 journal: PLoS One DOI: 10.1371/journal.pone.0240077 sha: doc_id: 346347 cord_uid: r4ork18p file: cache/cord-346819-11fkgzaa.json key: cord-346819-11fkgzaa authors: Khan, Mohd Imran; Khan, Zainul A.; Baig, Mohammad Hassan; Ahmad, Irfan; Farouk, Abd-ElAziem; Song, Young Goo; Dong, Jae-Jun title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 journal: PLoS One DOI: 10.1371/journal.pone.0238344 sha: doc_id: 346819 cord_uid: 11fkgzaa file: cache/cord-348807-9xxc5hyl.json key: cord-348807-9xxc5hyl authors: Cuomo, Raphael E.; Purushothaman, Vidya; Li, Jiawei; Cai, Mingxiang; Mackey, Timothy K. title: Sub-national longitudinal and geospatial analysis of COVID-19 tweets date: 2020-10-28 journal: PLoS One DOI: 10.1371/journal.pone.0241330 sha: doc_id: 348807 cord_uid: 9xxc5hyl file: cache/cord-346314-o9fjpqaj.json key: cord-346314-o9fjpqaj authors: Jarboui, Mohamed Ali; Bidoia, Carlo; Woods, Elena; Roe, Barbara; Wynne, Kieran; Elia, Giuliano; Hall, William W.; Gautier, Virginie W. title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date: 2012-11-15 journal: PLoS One DOI: 10.1371/journal.pone.0048702 sha: doc_id: 346314 cord_uid: o9fjpqaj file: cache/cord-347014-88zmtky7.json key: cord-347014-88zmtky7 authors: Esposito, Susanna; Di Gangi, Maria; Cardinale, Fabio; Baraldi, Eugenio; Corsini, Ilaria; Da Dalt, Liviana; Tovo, Pier Angelo; Correra, Antonio; Villani, Alberto; Sacco, Oliviero; Tenero, Laura; Dones, Piera; Gambino, Monia; Zampiero, Alberto; Principi, Nicola title: Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia date: 2016-11-15 journal: PLoS One DOI: 10.1371/journal.pone.0163262 sha: doc_id: 347014 cord_uid: 88zmtky7 file: cache/cord-348243-e5tdb08v.json key: cord-348243-e5tdb08v authors: Schermer, Bernhard; Fabretti, Francesca; Damagnez, Maximilian; Di Cristanziano, Veronica; Heger, Eva; Arjune, Sita; Tanner, Nathan A.; Imhof, Thomas; Koch, Manuel; Ladha, Alim; Joung, Julia; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Burst, Volker; Zhang, Feng; Klein, Florian; Benzing, Thomas; Müller, Roman-Ulrich title: Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay date: 2020-11-02 journal: PLoS One DOI: 10.1371/journal.pone.0238612 sha: doc_id: 348243 cord_uid: e5tdb08v file: cache/cord-346858-18q8rxzg.json key: cord-346858-18q8rxzg authors: Hossain, Md. Tanvir; Ahammed, Benojir; Chanda, Sanjoy Kumar; Jahan, Nusrat; Ela, Mahfuza Zaman; Islam, Md. Nazrul title: Social and electronic media exposure and generalized anxiety disorder among people during COVID-19 outbreak in Bangladesh: A preliminary observation date: 2020-09-11 journal: PLoS One DOI: 10.1371/journal.pone.0238974 sha: doc_id: 346858 cord_uid: 18q8rxzg file: cache/cord-347317-qcghtkk0.json key: cord-347317-qcghtkk0 authors: Russo, Lucia; Anastassopoulou, Cleo; Tsakris, Athanasios; Bifulco, Gennaro Nicola; Campana, Emilio Fortunato; Toraldo, Gerardo; Siettos, Constantinos title: Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach date: 2020-10-30 journal: PLoS One DOI: 10.1371/journal.pone.0240649 sha: doc_id: 347317 cord_uid: qcghtkk0 file: cache/cord-348499-7ll7sd3o.json key: cord-348499-7ll7sd3o authors: Manderstedt, Eric; Lind-Halldén, Christina; Lethagen, Stefan; Halldén, Christer title: Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients date: 2018-02-01 journal: PLoS One DOI: 10.1371/journal.pone.0192024 sha: doc_id: 348499 cord_uid: 7ll7sd3o file: cache/cord-349029-zyfop43z.json key: cord-349029-zyfop43z authors: Dobrovolny, Hana M. title: Modeling the role of asymptomatics in infection spread with application to SARS-CoV-2 date: 2020-08-10 journal: PLoS One DOI: 10.1371/journal.pone.0236976 sha: doc_id: 349029 cord_uid: zyfop43z file: cache/cord-349217-vpih1wvs.json key: cord-349217-vpih1wvs authors: Petropoulos, Fotios; Makridakis, Spyros title: Forecasting the novel coronavirus COVID-19 date: 2020-03-31 journal: PLoS One DOI: 10.1371/journal.pone.0231236 sha: doc_id: 349217 cord_uid: vpih1wvs file: cache/cord-350842-4m82l5t8.json key: cord-350842-4m82l5t8 authors: Xing, Jun; Sun, Ning; Xu, Jun; Geng, Shuling; Li, Yuqian title: Study of the mental health status of medical personnel dealing with new coronavirus pneumonia date: 2020-05-19 journal: PLoS One DOI: 10.1371/journal.pone.0233145 sha: doc_id: 350842 cord_uid: 4m82l5t8 file: cache/cord-349476-iac9fak3.json key: cord-349476-iac9fak3 authors: Mao, Liang title: Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior date: 2011-10-17 journal: PLoS One DOI: 10.1371/journal.pone.0024706 sha: doc_id: 349476 cord_uid: iac9fak3 file: cache/cord-349781-l93978vq.json key: cord-349781-l93978vq authors: Cong, Yu; Hart, Brit J.; Gross, Robin; Zhou, Huanying; Frieman, Matthew; Bollinger, Laura; Wada, Jiro; Hensley, Lisa E.; Jahrling, Peter B.; Dyall, Julie; Holbrook, Michael R. title: MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells date: 2018-03-22 journal: PLoS One DOI: 10.1371/journal.pone.0194868 sha: doc_id: 349781 cord_uid: l93978vq file: cache/cord-350443-ca5avyjf.json key: cord-350443-ca5avyjf authors: Zhang, Lei; Wilson, David P. title: Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy date: 2012-02-16 journal: PLoS One DOI: 10.1371/journal.pone.0031076 sha: doc_id: 350443 cord_uid: ca5avyjf file: cache/cord-351868-w4d45fue.json key: cord-351868-w4d45fue authors: Zuwała, Kaja; Golda, Anna; Kabala, Wojciech; Burmistrz, Michał; Zdzalik, Michal; Nowak, Paulina; Kedracka-Krok, Sylwia; Zarebski, Mirosław; Dobrucki, Jerzy; Florek, Dominik; Zeglen, Sławomir; Wojarski, Jacek; Potempa, Jan; Dubin, Grzegorz; Pyrc, Krzysztof title: The Nucleocapsid Protein of Human Coronavirus NL63 date: 2015-02-20 journal: PLoS One DOI: 10.1371/journal.pone.0117833 sha: doc_id: 351868 cord_uid: w4d45fue file: cache/cord-349911-dx8wvqkm.json key: cord-349911-dx8wvqkm authors: Dahl, Viktor; Tegnell, Anders; Wallensten, Anders title: Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013 date: 2015-09-23 journal: PLoS One DOI: 10.1371/journal.pone.0136353 sha: doc_id: 349911 cord_uid: dx8wvqkm file: cache/cord-351142-g20f6bxc.json key: cord-351142-g20f6bxc authors: Kiaghadi, Amin; Rifai, Hanadi S.; Liaw, Winston title: Assessing COVID-19 risk, vulnerability and infection prevalence in communities date: 2020-10-29 journal: PLoS One DOI: 10.1371/journal.pone.0241166 sha: doc_id: 351142 cord_uid: g20f6bxc file: cache/cord-352200-i05h8csb.json key: cord-352200-i05h8csb authors: Xu, Yi; Zhou, Wenwu; Zhou, Yijun; Wu, Jianxiang; Zhou, Xueping title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date: 2012-04-27 journal: PLoS One DOI: 10.1371/journal.pone.0036238 sha: doc_id: 352200 cord_uid: i05h8csb file: cache/cord-351387-i0zamkpd.json key: cord-351387-i0zamkpd authors: Witte, Katrin; Koch, Egon; Volk, Hans-Dieter; Wolk, Kerstin; Sabat, Robert title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date: 2015-09-25 journal: PLoS One DOI: 10.1371/journal.pone.0138075 sha: doc_id: 351387 cord_uid: i0zamkpd file: cache/cord-351185-3y3gou6v.json key: cord-351185-3y3gou6v authors: Buckles, Thomas C.; Ziemba, Brian P.; Djukovic, Danijel; Falke, Joseph J. title: Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating date: 2020-05-29 journal: PLoS One DOI: 10.1371/journal.pone.0233012 sha: doc_id: 351185 cord_uid: 3y3gou6v file: cache/cord-352222-zq9o66i4.json key: cord-352222-zq9o66i4 authors: Rajatonirina, Soatiana; Razanajatovo, Norosoa Harline; Ratsima, Elisoa Hariniana; Orelle, Arnaud; Ratovoson, Rila; Andrianirina, Zo Zafitsara; Andriatahina, Todisoa; Ramparany, Lovasoa; Herindrainy, Perlinot; Randrianirina, Frédérique; Heraud, Jean-Michel; Richard, Vincent title: Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012 date: 2013-09-12 journal: PLoS One DOI: 10.1371/journal.pone.0072839 sha: doc_id: 352222 cord_uid: zq9o66i4 file: cache/cord-352403-4591ewsa.json key: cord-352403-4591ewsa authors: Hartwig, Stacey M.; Holman, Kaitlyn M.; Varga, Steven M. title: Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection date: 2014-03-07 journal: PLoS One DOI: 10.1371/journal.pone.0090720 sha: doc_id: 352403 cord_uid: 4591ewsa file: cache/cord-351990-aham72b9.json key: cord-351990-aham72b9 authors: Radin, Jennifer M.; Hawksworth, Anthony W.; Kammerer, Peter E.; Balansay, Melinda; Raman, Rema; Lindsay, Suzanne P.; Brice, Gary T. title: Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations date: 2014-12-30 journal: PLoS One DOI: 10.1371/journal.pone.0114871 sha: doc_id: 351990 cord_uid: aham72b9 file: cache/cord-351918-pu7i1jfe.json key: cord-351918-pu7i1jfe authors: Baek, Yae Jee; Lee, Taeyong; Cho, Yunsuk; Hyun, Jong Hoon; Kim, Moo Hyun; Sohn, Yujin; Kim, Jung Ho; Ahn, Jin Young; Jeong, Su Jin; Ku, Nam Su; Yeom, Joon-Sup; Lee, Jeehyun; Choi, Jun Yong title: A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies date: 2020-10-26 journal: PLoS One DOI: 10.1371/journal.pone.0241169 sha: doc_id: 351918 cord_uid: pu7i1jfe file: cache/cord-351098-x729wpp7.json key: cord-351098-x729wpp7 authors: Long, Rachel B.; Krumlauf, Kristi; Young, Anna M. title: Characterizing trends in human-wildlife conflicts in the American Midwest using wildlife rehabilitation records date: 2020-09-11 journal: PLoS One DOI: 10.1371/journal.pone.0238805 sha: doc_id: 351098 cord_uid: x729wpp7 file: cache/cord-352564-2j4pjjwk.json key: cord-352564-2j4pjjwk authors: Dominguez, Samuel R.; Travanty, Emily A.; Qian, Zhaohui; Mason, Robert J. title: Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response date: 2013-07-24 journal: PLoS One DOI: 10.1371/journal.pone.0070129 sha: doc_id: 352564 cord_uid: 2j4pjjwk file: cache/cord-353200-5csewb1k.json key: cord-353200-5csewb1k authors: Jehi, Lara; Ji, Xinge; Milinovich, Alex; Erzurum, Serpil; Merlino, Amy; Gordon, Steve; Young, James B.; Kattan, Michael W. title: Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19 date: 2020-08-11 journal: PLoS One DOI: 10.1371/journal.pone.0237419 sha: doc_id: 353200 cord_uid: 5csewb1k file: cache/cord-350398-w75flrwv.json key: cord-350398-w75flrwv authors: Sampath, Rangarajan; Mulholland, Niveen; Blyn, Lawrence B.; Massire, Christian; Whitehouse, Chris A.; Waybright, Nicole; Harter, Courtney; Bogan, Joseph; Miranda, Mary Sue; Smith, David; Baldwin, Carson; Wolcott, Mark; Norwood, David; Kreft, Rachael; Frinder, Mark; Lovari, Robert; Yasuda, Irene; Matthews, Heather; Toleno, Donna; Housley, Roberta; Duncan, David; Li, Feng; Warren, Robin; Eshoo, Mark W.; Hall, Thomas A.; Hofstadler, Steven A.; Ecker, David J. title: Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry date: 2012-06-29 journal: PLoS One DOI: 10.1371/journal.pone.0036528 sha: doc_id: 350398 cord_uid: w75flrwv file: cache/cord-352511-gkm7i62s.json key: cord-352511-gkm7i62s authors: Yamada, Yoshiyuki; Liu, Xiao Bo; Fang, Shou Guo; Tay, Felicia P. L.; Liu, Ding Xiang title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells date: 2009-07-02 journal: PLoS One DOI: 10.1371/journal.pone.0006130 sha: doc_id: 352511 cord_uid: gkm7i62s file: cache/cord-353866-0r1b44id.json key: cord-353866-0r1b44id authors: Sun, Hongpeng; Zhang, Qiuju; Luo, Xiao; Quan, Hude; Zhang, Feng; Liu, Chang; Liu, Meina title: Changes of Adult Population Health Status in China from 2003 to 2008 date: 2011-12-02 journal: PLoS One DOI: 10.1371/journal.pone.0028411 sha: doc_id: 353866 cord_uid: 0r1b44id file: cache/cord-352219-z245sb3s.json key: cord-352219-z245sb3s authors: Tallam, Aravind; Perumal, Thaneer M.; Antony, Paul M.; Jäger, Christian; Fritz, Joëlle V.; Vallar, Laurent; Balling, Rudi; del Sol, Antonio; Michelucci, Alessandro title: Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date: 2016-02-12 journal: PLoS One DOI: 10.1371/journal.pone.0149050 sha: doc_id: 352219 cord_uid: z245sb3s file: cache/cord-352522-qnvgg2e9.json key: cord-352522-qnvgg2e9 authors: Langille, Morgan G. I.; Eisen, Jonathan A. title: BioTorrents: A File Sharing Service for Scientific Data date: 2010-04-14 journal: PLoS One DOI: 10.1371/journal.pone.0010071 sha: doc_id: 352522 cord_uid: qnvgg2e9 file: cache/cord-352720-z1cvjc2y.json key: cord-352720-z1cvjc2y authors: Díaz-Corvillón, Pilar; Mönckeberg, Max; Barros, Antonia; Illanes, Sebastián E.; Soldati, Arturo; Nien, Jyh-Kae; Schepeler, Manuel; Caradeux, Javier title: Routine screening for SARS CoV-2 in unselected pregnant women at delivery date: 2020-09-29 journal: PLoS One DOI: 10.1371/journal.pone.0239887 sha: doc_id: 352720 cord_uid: z1cvjc2y file: cache/cord-353245-es7b1rs0.json key: cord-353245-es7b1rs0 authors: Song, Deping; Huang, Dongyan; Peng, Qi; Huang, Tao; Chen, Yanjun; Zhang, Tiansheng; Nie, Xiaowei; He, Houjun; Wang, Ping; Liu, Qinglan; Tang, Yuxin title: Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013 date: 2015-03-19 journal: PLoS One DOI: 10.1371/journal.pone.0120310 sha: doc_id: 353245 cord_uid: es7b1rs0 file: cache/cord-352447-bc1pf272.json key: cord-352447-bc1pf272 authors: Nishida, Yu; Hosomi, Shuhei; Yamagami, Hirokazu; Fujimoto, Koji; Nakata, Rieko; Itani, Shigehiro; Nadatani, Yuji; Fukunaga, Shusei; Otani, Koji; Tanaka, Fumio; Nagami, Yasuaki; Taira, Koichi; Kamata, Noriko; Watanabe, Toshio; Iseki, Yasuhito; Fukuoka, Tatsunari; Shibutani, Masatsune; Nagahara, Hisashi; Ohfuji, Satoko; Fujiwara, Yasuhiro title: Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio date: 2020-10-26 journal: PLoS One DOI: 10.1371/journal.pone.0241322 sha: doc_id: 352447 cord_uid: bc1pf272 file: cache/cord-353869-l53ms3q8.json key: cord-353869-l53ms3q8 authors: Friesen, Robert H. E.; Koudstaal, Wouter; Koldijk, Martin H.; Weverling, Gerrit Jan; Brakenhoff, Just P. J.; Lenting, Peter J.; Stittelaar, Koert J.; Osterhaus, Albert D. M. E.; Kompier, Ronald; Goudsmit, Jaap title: New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets date: 2010-02-08 journal: PLoS One DOI: 10.1371/journal.pone.0009106 sha: doc_id: 353869 cord_uid: l53ms3q8 file: cache/cord-356132-1nisyl5r.json key: cord-356132-1nisyl5r authors: Wang, Huiyao; Xia, Qian; Xiong, Zhenzhen; Li, Zhixiong; Xiang, Weiyi; Yuan, Yiwen; Liu, Yaya; Li, Zhe title: The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey date: 2020-05-14 journal: PLoS One DOI: 10.1371/journal.pone.0233410 sha: doc_id: 356132 cord_uid: 1nisyl5r file: cache/cord-353253-kk2q71vg.json key: cord-353253-kk2q71vg authors: Itokawa, Kentaro; Sekizuka, Tsuyoshi; Hashino, Masanori; Tanaka, Rina; Kuroda, Makoto title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by multiplex tiling PCR date: 2020-09-18 journal: PLoS One DOI: 10.1371/journal.pone.0239403 sha: doc_id: 353253 cord_uid: kk2q71vg file: cache/cord-355874-nz6eqcdb.json key: cord-355874-nz6eqcdb authors: Wang, Le; Zhao, Mengchuan; Shi, Zhongren; Feng, Zhishan; Guo, Weiwei; Yang, Shuo; Liu, Lanping; Li, Guixia title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia date: 2016-09-14 journal: PLoS One DOI: 10.1371/journal.pone.0162411 sha: doc_id: 355874 cord_uid: nz6eqcdb file: cache/cord-353410-tbmtg88k.json key: cord-353410-tbmtg88k authors: Sharma, Shreela V.; Haidar, Amier; Noyola, Jacqueline; Tien, Jacqueline; Rushing, Melinda; Naylor, Brittni M.; Chuang, Ru-Jye; Markham, Christine title: Using a rapid assessment methodology to identify and address immediate needs among low-income households with children during COVID-19 date: 2020-10-01 journal: PLoS One DOI: 10.1371/journal.pone.0240009 sha: doc_id: 353410 cord_uid: tbmtg88k file: cache/cord-354000-jxqskt4k.json key: cord-354000-jxqskt4k authors: Warren, Cody J.; Griffin, Laura M.; Little, Alexander S.; Huang, I-Chueh; Farzan, Michael; Pyeon, Dohun title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 journal: PLoS One DOI: 10.1371/journal.pone.0096579 sha: doc_id: 354000 cord_uid: jxqskt4k file: cache/cord-356364-ipi81ce3.json key: cord-356364-ipi81ce3 authors: Ho, Bo-Lin; Cheng, Shu-Chun; Shi, Lin; Wang, Ting-Yun; Ho, Kuan-I; Chou, Chi-Yuan title: Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease date: 2015-12-14 journal: PLoS One DOI: 10.1371/journal.pone.0144865 sha: doc_id: 356364 cord_uid: ipi81ce3 file: cache/cord-354052-x4ckzw64.json key: cord-354052-x4ckzw64 authors: Li, Chunhua; Li, Zhen; Zou, Yong; Wicht, Oliver; van Kuppeveld, Frank J. M.; Rottier, Peter J. M.; Bosch, Berend Jan title: Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination date: 2013-08-02 journal: PLoS One DOI: 10.1371/journal.pone.0069997 sha: doc_id: 354052 cord_uid: x4ckzw64 file: cache/cord-354763-odzrco6q.json key: cord-354763-odzrco6q authors: Drake, John M.; Chew, Suok Kai; Ma, Stefan title: Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore date: 2006-12-20 journal: PLoS One DOI: 10.1371/journal.pone.0000020 sha: doc_id: 354763 cord_uid: odzrco6q file: cache/cord-355259-779czzzx.json key: cord-355259-779czzzx authors: Yang, Xiaoyun; Steukers, Lennert; Forier, Katrien; Xiong, Ranhua; Braeckmans, Kevin; Van Reeth, Kristien; Nauwynck, Hans title: A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus date: 2014-10-15 journal: PLoS One DOI: 10.1371/journal.pone.0110026 sha: doc_id: 355259 cord_uid: 779czzzx file: cache/cord-353596-8iqjugcx.json key: cord-353596-8iqjugcx authors: Bédubourg, Gabriel; Le Strat, Yann title: Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study date: 2017-07-17 journal: PLoS One DOI: 10.1371/journal.pone.0181227 sha: doc_id: 353596 cord_uid: 8iqjugcx file: cache/cord-354547-eomm1sl5.json key: cord-354547-eomm1sl5 authors: Wang, Jibin; Fang, Shouguo; Xiao, Han; Chen, Bo; Tam, James P.; Liu, Ding Xiang title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date: 2009-03-16 journal: PLoS One DOI: 10.1371/journal.pone.0004908 sha: doc_id: 354547 cord_uid: eomm1sl5 file: cache/cord-353730-owcapg8h.json key: cord-353730-owcapg8h authors: Dietrich, Jes; Andreasen, Lars Vibe; Andersen, Peter; Agger, Else Marie title: Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01 date: 2014-06-23 journal: PLoS One DOI: 10.1371/journal.pone.0100879 sha: doc_id: 353730 cord_uid: owcapg8h Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-plosOne-cord === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25772 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25605 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25804 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25274 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 24578 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 23754 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25658 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25880 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26668 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25997 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26658 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26755 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 25708 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26758 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26783 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26776 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26779 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26579 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26750 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26660 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26728 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26927 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26859 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26258 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33178 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33158 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33350 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 26821 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-000877-usz7pnvu author: Abdel-Moneim, Ahmed S. title: Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia date: 2013-01-30 pages: extension: .txt txt: ./txt/cord-000877-usz7pnvu.txt cache: ./cache/cord-000877-usz7pnvu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000877-usz7pnvu.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33416 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33785 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33863 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-000366-u4649rtx author: Shan, Tongling title: Genomic Characterization and High Prevalence of Bocaviruses in Swine date: 2011-04-15 pages: extension: .txt txt: ./txt/cord-000366-u4649rtx.txt cache: ./cache/cord-000366-u4649rtx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000366-u4649rtx.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33822 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34069 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-000063-tex6bgab author: Sui, Hong-Yan title: Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication date: 2009-05-22 pages: extension: .txt txt: ./txt/cord-000063-tex6bgab.txt cache: ./cache/cord-000063-tex6bgab.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000063-tex6bgab.txt' === file2bib.sh === id: cord-000721-leedutqo author: Nawaz, Sameena title: Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK date: 2012-07-24 pages: extension: .txt txt: ./txt/cord-000721-leedutqo.txt cache: ./cache/cord-000721-leedutqo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000721-leedutqo.txt' === file2bib.sh === id: cord-000720-5b936n3g author: Nannyonga, Betty title: The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks date: 2012-07-24 pages: extension: .txt txt: ./txt/cord-000720-5b936n3g.txt cache: ./cache/cord-000720-5b936n3g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000720-5b936n3g.txt' === file2bib.sh === id: cord-000609-dpcgl6ig author: Raju, Sammeta V. title: Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia date: 2012-03-19 pages: extension: .txt txt: ./txt/cord-000609-dpcgl6ig.txt cache: ./cache/cord-000609-dpcgl6ig.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000609-dpcgl6ig.txt' === file2bib.sh === id: cord-000478-88wo4xen author: Gowen, Brian B. title: Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date: 2011-10-24 pages: extension: .txt txt: ./txt/cord-000478-88wo4xen.txt cache: ./cache/cord-000478-88wo4xen.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000478-88wo4xen.txt' === file2bib.sh === id: cord-000809-9voqa1oy author: Archer, Brett N. title: Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa date: 2012-11-16 pages: extension: .txt txt: ./txt/cord-000809-9voqa1oy.txt cache: ./cache/cord-000809-9voqa1oy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000809-9voqa1oy.txt' === file2bib.sh === id: cord-000574-7eflwyxk author: Liu, Yanli title: Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20 date: 2012-02-07 pages: extension: .txt txt: ./txt/cord-000574-7eflwyxk.txt cache: ./cache/cord-000574-7eflwyxk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000574-7eflwyxk.txt' === file2bib.sh === id: cord-000255-73nlxqgk author: Hosseini, Parviez title: Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread date: 2010-09-15 pages: extension: .txt txt: ./txt/cord-000255-73nlxqgk.txt cache: ./cache/cord-000255-73nlxqgk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000255-73nlxqgk.txt' === file2bib.sh === id: cord-000556-uu1oz2ei author: Kumar, Ranjit title: RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336” date: 2012-01-20 pages: extension: .txt txt: ./txt/cord-000556-uu1oz2ei.txt cache: ./cache/cord-000556-uu1oz2ei.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000556-uu1oz2ei.txt' === file2bib.sh === id: cord-000715-zl1s82yi author: Shulman, Lester M. title: Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition date: 2012-07-16 pages: extension: .txt txt: ./txt/cord-000715-zl1s82yi.txt cache: ./cache/cord-000715-zl1s82yi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000715-zl1s82yi.txt' === file2bib.sh === id: cord-001014-8yrpcl94 author: Kitagawa, Hiroshi title: Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis date: 2013-07-03 pages: extension: .txt txt: ./txt/cord-001014-8yrpcl94.txt cache: ./cache/cord-001014-8yrpcl94.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001014-8yrpcl94.txt' === file2bib.sh === id: cord-001007-645zegcv author: Kim, Hak title: Identification of Recombinant Human Rhinovirus A and C in Circulating Strains from Upper and Lower Respiratory Infections date: 2013-06-27 pages: extension: .txt txt: ./txt/cord-001007-645zegcv.txt cache: ./cache/cord-001007-645zegcv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-001007-645zegcv.txt' === file2bib.sh === id: cord-000131-ugbwvy6j author: Jones, James Holland title: Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1) date: 2009-12-03 pages: extension: .txt txt: ./txt/cord-000131-ugbwvy6j.txt cache: ./cache/cord-000131-ugbwvy6j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000131-ugbwvy6j.txt' === file2bib.sh === id: cord-000375-fvfl0bn1 author: Shen, Ching-I title: The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus date: 2011-05-06 pages: extension: .txt txt: ./txt/cord-000375-fvfl0bn1.txt cache: ./cache/cord-000375-fvfl0bn1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000375-fvfl0bn1.txt' === file2bib.sh === id: cord-000851-uylgyhs8 author: Wang, Zhenya title: Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro date: 2013-01-07 pages: extension: .txt txt: ./txt/cord-000851-uylgyhs8.txt cache: ./cache/cord-000851-uylgyhs8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000851-uylgyhs8.txt' === file2bib.sh === id: cord-000374-gt2pwc9b author: Yang, Albert C. title: Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index date: 2011-05-04 pages: extension: .txt txt: ./txt/cord-000374-gt2pwc9b.txt cache: ./cache/cord-000374-gt2pwc9b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000374-gt2pwc9b.txt' === file2bib.sh === id: cord-000765-r7y1cqou author: Chang, Yu-Ming title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date: 2012-09-21 pages: extension: .txt txt: ./txt/cord-000765-r7y1cqou.txt cache: ./cache/cord-000765-r7y1cqou.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000765-r7y1cqou.txt' === file2bib.sh === id: cord-000588-3wok0n21 author: Sainz, Juan title: Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection date: 2012-02-27 pages: extension: .txt txt: ./txt/cord-000588-3wok0n21.txt cache: ./cache/cord-000588-3wok0n21.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000588-3wok0n21.txt' === file2bib.sh === id: cord-000077-d441jam3 author: Zhang, Hao-Jie title: The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability date: 2009-07-03 pages: extension: .txt txt: ./txt/cord-000077-d441jam3.txt cache: ./cache/cord-000077-d441jam3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000077-d441jam3.txt' === file2bib.sh === id: cord-000460-h3owwjao author: Xiong, Jing title: Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date: 2011-09-26 pages: extension: .txt txt: ./txt/cord-000460-h3owwjao.txt cache: ./cache/cord-000460-h3owwjao.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000460-h3owwjao.txt' === file2bib.sh === id: cord-000326-a18rch1f author: Zhou, Jun-Wei title: Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes date: 2011-02-24 pages: extension: .txt txt: ./txt/cord-000326-a18rch1f.txt cache: ./cache/cord-000326-a18rch1f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000326-a18rch1f.txt' === file2bib.sh === id: cord-000006-104sqoxz author: Bray, Daniel P. title: Composition and Function of Haemolymphatic Tissues in the European Common Shrew date: 2008-10-15 pages: extension: .txt txt: ./txt/cord-000006-104sqoxz.txt cache: ./cache/cord-000006-104sqoxz.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000006-104sqoxz.txt' === file2bib.sh === id: cord-001045-jm60nxc2 author: DeLisle, Sylvain title: Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy date: 2013-08-13 pages: extension: .txt txt: ./txt/cord-001045-jm60nxc2.txt cache: ./cache/cord-001045-jm60nxc2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001045-jm60nxc2.txt' === file2bib.sh === id: cord-000265-llilwq1u author: Gao, Rongbao title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case date: 2010-10-12 pages: extension: .txt txt: ./txt/cord-000265-llilwq1u.txt cache: ./cache/cord-000265-llilwq1u.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000265-llilwq1u.txt' === file2bib.sh === id: cord-000539-uh3q65we author: Zhang, Yi title: Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice date: 2012-01-03 pages: extension: .txt txt: ./txt/cord-000539-uh3q65we.txt cache: ./cache/cord-000539-uh3q65we.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000539-uh3q65we.txt' === file2bib.sh === id: cord-000050-tfcerilc author: Rao, Srinivas title: Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date: 2008-06-18 pages: extension: .txt txt: ./txt/cord-000050-tfcerilc.txt cache: ./cache/cord-000050-tfcerilc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000050-tfcerilc.txt' === file2bib.sh === id: cord-000501-qz68gtd4 author: Greatorex, Jane S. title: Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control date: 2011-11-22 pages: extension: .txt txt: ./txt/cord-000501-qz68gtd4.txt cache: ./cache/cord-000501-qz68gtd4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000501-qz68gtd4.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-000638-ss1435el author: Beq, Stephanie title: Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date: 2012-04-16 pages: extension: .txt txt: ./txt/cord-000638-ss1435el.txt cache: ./cache/cord-000638-ss1435el.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000638-ss1435el.txt' === file2bib.sh === id: cord-000581-ewx5xhrb author: Rudge, James W. title: Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories date: 2012-02-21 pages: extension: .txt txt: ./txt/cord-000581-ewx5xhrb.txt cache: ./cache/cord-000581-ewx5xhrb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000581-ewx5xhrb.txt' === file2bib.sh === id: cord-000079-533xlisc author: Huszthy, Peter C. title: Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy date: 2009-07-20 pages: extension: .txt txt: ./txt/cord-000079-533xlisc.txt cache: ./cache/cord-000079-533xlisc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000079-533xlisc.txt' === file2bib.sh === id: cord-000082-jy7j8sh0 author: Huang, Ting title: Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection date: 2009-07-27 pages: extension: .txt txt: ./txt/cord-000082-jy7j8sh0.txt cache: ./cache/cord-000082-jy7j8sh0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000082-jy7j8sh0.txt' === file2bib.sh === id: cord-000408-pt3b4yc7 author: Lu, Sydney X. title: Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation date: 2011-07-06 pages: extension: .txt txt: ./txt/cord-000408-pt3b4yc7.txt cache: ./cache/cord-000408-pt3b4yc7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000408-pt3b4yc7.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-000237-mticfoic author: Guan, Xuhua title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008 date: 2010-07-23 pages: extension: .txt txt: ./txt/cord-000237-mticfoic.txt cache: ./cache/cord-000237-mticfoic.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000237-mticfoic.txt' === file2bib.sh === id: cord-000434-ff2zadol author: Zhao, Rongmao title: Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus date: 2011-08-19 pages: extension: .txt txt: ./txt/cord-000434-ff2zadol.txt cache: ./cache/cord-000434-ff2zadol.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000434-ff2zadol.txt' === file2bib.sh === id: cord-000580-dcid9emx author: Sällman Almén, Markus title: The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date: 2012-02-20 pages: extension: .txt txt: ./txt/cord-000580-dcid9emx.txt cache: ./cache/cord-000580-dcid9emx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000580-dcid9emx.txt' === file2bib.sh === id: cord-000554-p4ufea6x author: Gao, Wei title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date: 2012-01-18 pages: extension: .txt txt: ./txt/cord-000554-p4ufea6x.txt cache: ./cache/cord-000554-p4ufea6x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000554-p4ufea6x.txt' === file2bib.sh === id: cord-000413-h2e6h076 author: Zhang, Jingyu title: A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13 date: 2011-07-11 pages: extension: .txt txt: ./txt/cord-000413-h2e6h076.txt cache: ./cache/cord-000413-h2e6h076.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-000413-h2e6h076.txt' === file2bib.sh === id: cord-000959-nk2thkme author: Downer, Eric J. title: Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date: 2013-05-06 pages: extension: .txt txt: ./txt/cord-000959-nk2thkme.txt cache: ./cache/cord-000959-nk2thkme.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000959-nk2thkme.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-000742-0r4z1zea author: Vittecoq, Marion title: High Influenza A Virus Infection Rates in Mallards Bred for Hunting in the Camargue, South of France date: 2012-08-27 pages: extension: .txt txt: ./txt/cord-000742-0r4z1zea.txt cache: ./cache/cord-000742-0r4z1zea.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000742-0r4z1zea.txt' === file2bib.sh === id: cord-000536-0mn1gbll author: Hu, Le-Le title: Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions date: 2011-12-29 pages: extension: .txt txt: ./txt/cord-000536-0mn1gbll.txt cache: ./cache/cord-000536-0mn1gbll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000536-0mn1gbll.txt' === file2bib.sh === id: cord-000180-howix091 author: MacLeod, Iain J. title: Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry date: 2010-03-05 pages: extension: .txt txt: ./txt/cord-000180-howix091.txt cache: ./cache/cord-000180-howix091.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000180-howix091.txt' === file2bib.sh === id: cord-000726-tonaaft2 author: Chang, Binggong title: Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-000726-tonaaft2.txt cache: ./cache/cord-000726-tonaaft2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000726-tonaaft2.txt' === file2bib.sh === id: cord-000261-ip32y0j5 author: Becker, Pablo D. title: Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice date: 2010-10-04 pages: extension: .txt txt: ./txt/cord-000261-ip32y0j5.txt cache: ./cache/cord-000261-ip32y0j5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000261-ip32y0j5.txt' === file2bib.sh === id: cord-000833-m6abyuvx author: Sekiguchi, Satoshi title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date: 2012-12-17 pages: extension: .txt txt: ./txt/cord-000833-m6abyuvx.txt cache: ./cache/cord-000833-m6abyuvx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000833-m6abyuvx.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-000008-3dgjv0x1 author: Vali, Bahareh title: HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date: 2008-10-20 pages: extension: .txt txt: ./txt/cord-000008-3dgjv0x1.txt cache: ./cache/cord-000008-3dgjv0x1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000008-3dgjv0x1.txt' === file2bib.sh === id: cord-000269-v4jochbe author: Wittekindt, Nicola E. title: Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date: 2010-10-18 pages: extension: .txt txt: ./txt/cord-000269-v4jochbe.txt cache: ./cache/cord-000269-v4jochbe.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000269-v4jochbe.txt' === file2bib.sh === id: cord-000224-2lz03oqb author: Porter, Kristen A. title: Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag date: 2010-06-24 pages: extension: .txt txt: ./txt/cord-000224-2lz03oqb.txt cache: ./cache/cord-000224-2lz03oqb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000224-2lz03oqb.txt' === file2bib.sh === id: cord-000666-je9t4i6q author: Verbist, Katherine C. title: IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection date: 2012-05-18 pages: extension: .txt txt: ./txt/cord-000666-je9t4i6q.txt cache: ./cache/cord-000666-je9t4i6q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000666-je9t4i6q.txt' === file2bib.sh === id: cord-000736-6f8vyziv author: Pripuzova, Natalia title: Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens date: 2012-08-17 pages: extension: .txt txt: ./txt/cord-000736-6f8vyziv.txt cache: ./cache/cord-000736-6f8vyziv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000736-6f8vyziv.txt' === file2bib.sh === id: cord-000208-th0wddvc author: Cornelissen, Lisette A. H. M. title: A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 date: 2010-05-14 pages: extension: .txt txt: ./txt/cord-000208-th0wddvc.txt cache: ./cache/cord-000208-th0wddvc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000208-th0wddvc.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-000182-ni6iyzdn author: He, Zhisong title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date: 2010-03-11 pages: extension: .txt txt: ./txt/cord-000182-ni6iyzdn.txt cache: ./cache/cord-000182-ni6iyzdn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000182-ni6iyzdn.txt' === file2bib.sh === id: cord-000140-5kapn32k author: Wang, Pei-Gang title: Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins date: 2009-12-15 pages: extension: .txt txt: ./txt/cord-000140-5kapn32k.txt cache: ./cache/cord-000140-5kapn32k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000140-5kapn32k.txt' === file2bib.sh === id: cord-000336-57es391o author: Liao, Qiuyan title: Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study date: 2011-03-11 pages: extension: .txt txt: ./txt/cord-000336-57es391o.txt cache: ./cache/cord-000336-57es391o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000336-57es391o.txt' === file2bib.sh === id: cord-000266-xwfptmmv author: Liao, Qiuyan title: Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study date: 2010-10-12 pages: extension: .txt txt: ./txt/cord-000266-xwfptmmv.txt cache: ./cache/cord-000266-xwfptmmv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-000266-xwfptmmv.txt' === file2bib.sh === id: cord-000540-bbjmcdo5 author: Hellard, Eléonore title: True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses date: 2012-01-03 pages: extension: .txt txt: ./txt/cord-000540-bbjmcdo5.txt cache: ./cache/cord-000540-bbjmcdo5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000540-bbjmcdo5.txt' === file2bib.sh === id: cord-000176-z76vjkxg author: Nguyen, Jack T. title: Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro date: 2010-02-22 pages: extension: .txt txt: ./txt/cord-000176-z76vjkxg.txt cache: ./cache/cord-000176-z76vjkxg.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000176-z76vjkxg.txt' === file2bib.sh === id: cord-000947-psguw47w author: Feng, Jianyu title: A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation date: 2013-04-24 pages: extension: .txt txt: ./txt/cord-000947-psguw47w.txt cache: ./cache/cord-000947-psguw47w.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000947-psguw47w.txt' === file2bib.sh === id: cord-000166-36bfeoqv author: Tracht, Samantha M. title: Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) date: 2010-02-10 pages: extension: .txt txt: ./txt/cord-000166-36bfeoqv.txt cache: ./cache/cord-000166-36bfeoqv.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000166-36bfeoqv.txt' === file2bib.sh === id: cord-000321-ee7q7jhv author: Powell, Michael L. title: Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA date: 2011-02-08 pages: extension: .txt txt: ./txt/cord-000321-ee7q7jhv.txt cache: ./cache/cord-000321-ee7q7jhv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000321-ee7q7jhv.txt' === file2bib.sh === id: cord-000346-9b6yz3f4 author: Holder, Benjamin P. title: Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model date: 2011-03-24 pages: extension: .txt txt: ./txt/cord-000346-9b6yz3f4.txt cache: ./cache/cord-000346-9b6yz3f4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000346-9b6yz3f4.txt' === file2bib.sh === id: cord-000143-2xvd5ogf author: Napthine, Sawsan title: Expression of the VP2 Protein of Murine Norovirus by a Translation Termination-Reinitiation Strategy date: 2009-12-22 pages: extension: .txt txt: ./txt/cord-000143-2xvd5ogf.txt cache: ./cache/cord-000143-2xvd5ogf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000143-2xvd5ogf.txt' === file2bib.sh === id: cord-000725-rafwlw0t author: Hindinger, Claudia title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-000725-rafwlw0t.txt cache: ./cache/cord-000725-rafwlw0t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000725-rafwlw0t.txt' === file2bib.sh === id: cord-000837-rdpsxb4n author: Perez-Pepe, Marcelo title: BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis date: 2012-12-20 pages: extension: .txt txt: ./txt/cord-000837-rdpsxb4n.txt cache: ./cache/cord-000837-rdpsxb4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000837-rdpsxb4n.txt' === file2bib.sh === id: cord-000642-mkwpuav6 author: Moreira, Rebeca title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date: 2012-04-19 pages: extension: .txt txt: ./txt/cord-000642-mkwpuav6.txt cache: ./cache/cord-000642-mkwpuav6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000642-mkwpuav6.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-000158-d08buwtu author: Corti, Davide title: Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals date: 2010-01-20 pages: extension: .txt txt: ./txt/cord-000158-d08buwtu.txt cache: ./cache/cord-000158-d08buwtu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000158-d08buwtu.txt' === file2bib.sh === id: cord-000013-pr9i9swk author: Croyle, Maria A. title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice date: 2008-10-29 pages: extension: .txt txt: ./txt/cord-000013-pr9i9swk.txt cache: ./cache/cord-000013-pr9i9swk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000013-pr9i9swk.txt' === file2bib.sh === id: cord-000425-isw6jeir author: Flori, Laurence title: Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date: 2011-07-29 pages: extension: .txt txt: ./txt/cord-000425-isw6jeir.txt cache: ./cache/cord-000425-isw6jeir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000425-isw6jeir.txt' === file2bib.sh === id: cord-000547-adfigzc1 author: Beniac, Daniel R. title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date: 2012-01-11 pages: extension: .txt txt: ./txt/cord-000547-adfigzc1.txt cache: ./cache/cord-000547-adfigzc1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000547-adfigzc1.txt' === file2bib.sh === id: cord-001078-5m29nugu author: Chen, Xiaorong title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study date: 2013-09-17 pages: extension: .txt txt: ./txt/cord-001078-5m29nugu.txt cache: ./cache/cord-001078-5m29nugu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001078-5m29nugu.txt' === file2bib.sh === id: cord-001120-fxd533b4 author: Everitt, Aaron R. title: Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model date: 2013-11-21 pages: extension: .txt txt: ./txt/cord-001120-fxd533b4.txt cache: ./cache/cord-001120-fxd533b4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001120-fxd533b4.txt' === file2bib.sh === id: cord-001142-puj74k7y author: Crescenzo-Chaigne, Bernadette title: The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression date: 2013-11-21 pages: extension: .txt txt: ./txt/cord-001142-puj74k7y.txt cache: ./cache/cord-001142-puj74k7y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001142-puj74k7y.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-001162-z8cbbit3 author: Yun, Heather C. title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection date: 2014-01-08 pages: extension: .txt txt: ./txt/cord-001162-z8cbbit3.txt cache: ./cache/cord-001162-z8cbbit3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001162-z8cbbit3.txt' === file2bib.sh === id: cord-001199-9khx93c0 author: Liu, Fengchen title: Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model date: 2014-02-06 pages: extension: .txt txt: ./txt/cord-001199-9khx93c0.txt cache: ./cache/cord-001199-9khx93c0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-001199-9khx93c0.txt' === file2bib.sh === id: cord-001117-llb4f74a author: Ji, Wen-Jie title: Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments date: 2013-11-19 pages: extension: .txt txt: ./txt/cord-001117-llb4f74a.txt cache: ./cache/cord-001117-llb4f74a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001117-llb4f74a.txt' === file2bib.sh === id: cord-001368-ymp1pj3r author: Zhang, Chao title: Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro date: 2014-07-28 pages: extension: .txt txt: ./txt/cord-001368-ymp1pj3r.txt cache: ./cache/cord-001368-ymp1pj3r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-001368-ymp1pj3r.txt' === file2bib.sh === id: cord-001213-gxqufddb author: Butt, Azeem Mehmood title: Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses date: 2014-03-04 pages: extension: .txt txt: ./txt/cord-001213-gxqufddb.txt cache: ./cache/cord-001213-gxqufddb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001213-gxqufddb.txt' === file2bib.sh === id: cord-001099-jirkkkvy author: Yousuf, Mohammad A. title: Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells date: 2013-10-11 pages: extension: .txt txt: ./txt/cord-001099-jirkkkvy.txt cache: ./cache/cord-001099-jirkkkvy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001099-jirkkkvy.txt' === file2bib.sh === id: cord-001207-yjaiybwf author: Sachsenröder, Jana title: The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium date: 2014-02-19 pages: extension: .txt txt: ./txt/cord-001207-yjaiybwf.txt cache: ./cache/cord-001207-yjaiybwf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001207-yjaiybwf.txt' === file2bib.sh === id: cord-001129-gi2kswai author: Lemos de Matos, Ana title: Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals date: 2013-11-27 pages: extension: .txt txt: ./txt/cord-001129-gi2kswai.txt cache: ./cache/cord-001129-gi2kswai.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001129-gi2kswai.txt' === file2bib.sh === id: cord-001126-uqr00nzd author: Zhang, Zhicheng title: Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1 date: 2013-11-26 pages: extension: .txt txt: ./txt/cord-001126-uqr00nzd.txt cache: ./cache/cord-001126-uqr00nzd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001126-uqr00nzd.txt' === file2bib.sh === id: cord-001251-forh7lw4 author: Jank, Johanna M. title: The Domain-Specific and Temperature-Dependent Protein Misfolding Phenotype of Variant Medium-Chain acyl-CoA Dehydrogenase date: 2014-04-09 pages: extension: .txt txt: ./txt/cord-001251-forh7lw4.txt cache: ./cache/cord-001251-forh7lw4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001251-forh7lw4.txt' === file2bib.sh === id: cord-001145-hc9ssruz author: Akazawa, Yuko title: Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis date: 2013-12-13 pages: extension: .txt txt: ./txt/cord-001145-hc9ssruz.txt cache: ./cache/cord-001145-hc9ssruz.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001145-hc9ssruz.txt' === file2bib.sh === id: cord-001186-jkg7qkj6 author: Skowronski, Danuta M. title: Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk date: 2014-01-27 pages: extension: .txt txt: ./txt/cord-001186-jkg7qkj6.txt cache: ./cache/cord-001186-jkg7qkj6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001186-jkg7qkj6.txt' === file2bib.sh === id: cord-001254-y2knt8g0 author: Parkhomenko, Taisiya A. title: Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis date: 2014-04-15 pages: extension: .txt txt: ./txt/cord-001254-y2knt8g0.txt cache: ./cache/cord-001254-y2knt8g0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001254-y2knt8g0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38865 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39512 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38117 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38379 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38576 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38511 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38773 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39019 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39400 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39541 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39441 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39482 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40096 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40822 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39606 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38450 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39173 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39462 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39473 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41010 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41232 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42454 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43600 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44338 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45785 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45929 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45936 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45985 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49109 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49353 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49356 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49706 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49833 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49815 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49983 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49986 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49399 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50130 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50089 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002890-g7aje88u author: Wood, Paul L. title: Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses date: 2018-02-23 pages: extension: .txt txt: ./txt/cord-002890-g7aje88u.txt cache: ./cache/cord-002890-g7aje88u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002890-g7aje88u.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49397 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50053 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50451 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50262 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50342 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50421 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-001571-drcfdv9z author: Alvarez, Julio title: Impact of Porcine Epidemic Diarrhea on Performance of Growing Pigs date: 2015-03-13 pages: extension: .txt txt: ./txt/cord-001571-drcfdv9z.txt cache: ./cache/cord-001571-drcfdv9z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-001571-drcfdv9z.txt' === file2bib.sh === id: cord-003125-iptisi1m author: Machablishvili, Ann title: Overview of three influenza seasons in Georgia, 2014–2017 date: 2018-07-27 pages: extension: .txt txt: ./txt/cord-003125-iptisi1m.txt cache: ./cache/cord-003125-iptisi1m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003125-iptisi1m.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-001620-yy5gq0ki author: Woo, Hye-Min title: Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5 date: 2015-04-22 pages: extension: .txt txt: ./txt/cord-001620-yy5gq0ki.txt cache: ./cache/cord-001620-yy5gq0ki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001620-yy5gq0ki.txt' === file2bib.sh === id: cord-002834-2htnywef author: Tsuchiaka, Shinobu title: Genetic diversity and recombination of enterovirus G strains in Japanese pigs: High prevalence of strains carrying a papain-like cysteine protease sequence in the enterovirus G population date: 2018-01-11 pages: extension: .txt txt: ./txt/cord-002834-2htnywef.txt cache: ./cache/cord-002834-2htnywef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002834-2htnywef.txt' === file2bib.sh === id: cord-002901-u4ybz8ds author: Yu, Chanki title: Acral melanoma detection using a convolutional neural network for dermoscopy images date: 2018-03-07 pages: extension: .txt txt: ./txt/cord-002901-u4ybz8ds.txt cache: ./cache/cord-002901-u4ybz8ds.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002901-u4ybz8ds.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-001455-n7quwr4s author: Rapin, Noreen title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans date: 2014-11-12 pages: extension: .txt txt: ./txt/cord-001455-n7quwr4s.txt cache: ./cache/cord-001455-n7quwr4s.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001455-n7quwr4s.txt' === file2bib.sh === id: cord-001716-lbtdex4p author: Gilca, Rodica title: Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015 date: 2015-07-22 pages: extension: .txt txt: ./txt/cord-001716-lbtdex4p.txt cache: ./cache/cord-001716-lbtdex4p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001716-lbtdex4p.txt' === file2bib.sh === id: cord-001910-6zfz2ns5 author: Zhang, Xianming title: Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome date: 2016-01-08 pages: extension: .txt txt: ./txt/cord-001910-6zfz2ns5.txt cache: ./cache/cord-001910-6zfz2ns5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001910-6zfz2ns5.txt' === file2bib.sh === id: cord-002180-gsdk5x3e author: Davies, Colin title: Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest date: 2016-08-24 pages: extension: .txt txt: ./txt/cord-002180-gsdk5x3e.txt cache: ./cache/cord-002180-gsdk5x3e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002180-gsdk5x3e.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-003507-22ylifqo author: Kelly, J. Daniel title: Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018 date: 2019-03-07 pages: extension: .txt txt: ./txt/cord-003507-22ylifqo.txt cache: ./cache/cord-003507-22ylifqo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003507-22ylifqo.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-001363-irysq6pf author: Liu, Zhenjiang title: SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects date: 2014-07-23 pages: extension: .txt txt: ./txt/cord-001363-irysq6pf.txt cache: ./cache/cord-001363-irysq6pf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001363-irysq6pf.txt' === file2bib.sh === id: cord-002705-ntokyoai author: Nasir, Nazrila Hairin title: Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study date: 2017-10-04 pages: extension: .txt txt: ./txt/cord-002705-ntokyoai.txt cache: ./cache/cord-002705-ntokyoai.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002705-ntokyoai.txt' === file2bib.sh === id: cord-001748-7e8px4vx author: Nobach, Daniel title: Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews date: 2015-08-27 pages: extension: .txt txt: ./txt/cord-001748-7e8px4vx.txt cache: ./cache/cord-001748-7e8px4vx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001748-7e8px4vx.txt' === file2bib.sh === id: cord-001280-skavefji author: Choi, Sang-Ho title: Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients date: 2014-05-13 pages: extension: .txt txt: ./txt/cord-001280-skavefji.txt cache: ./cache/cord-001280-skavefji.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001280-skavefji.txt' === file2bib.sh === id: cord-002624-59nznqsd author: Ti, Jinfeng title: Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies date: 2017-07-26 pages: extension: .txt txt: ./txt/cord-002624-59nznqsd.txt cache: ./cache/cord-002624-59nznqsd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002624-59nznqsd.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-002889-fie121ns author: White, Michael title: Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer date: 2018-02-23 pages: extension: .txt txt: ./txt/cord-002889-fie121ns.txt cache: ./cache/cord-002889-fie121ns.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002889-fie121ns.txt' === file2bib.sh === id: cord-003062-qm8kalyt author: Chowdhury, Fazle Rabbi title: The association between temperature, rainfall and humidity with common climate-sensitive infectious diseases in Bangladesh date: 2018-06-21 pages: extension: .txt txt: ./txt/cord-003062-qm8kalyt.txt cache: ./cache/cord-003062-qm8kalyt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003062-qm8kalyt.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-001343-3euy4u9k author: Wang, Yadong title: A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices date: 2014-06-27 pages: extension: .txt txt: ./txt/cord-001343-3euy4u9k.txt cache: ./cache/cord-001343-3euy4u9k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001343-3euy4u9k.txt' === file2bib.sh === id: cord-001546-ndz3oarf author: Ayithan, Natarajan title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 pages: extension: .txt txt: ./txt/cord-001546-ndz3oarf.txt cache: ./cache/cord-001546-ndz3oarf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001546-ndz3oarf.txt' === file2bib.sh === id: cord-002044-9xgt3tf4 author: Hendiger, Jacek title: Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms date: 2016-05-12 pages: extension: .txt txt: ./txt/cord-002044-9xgt3tf4.txt cache: ./cache/cord-002044-9xgt3tf4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002044-9xgt3tf4.txt' === file2bib.sh === id: cord-001761-yvd1n42f author: Yoshimura, Takeo title: Controlled Microwave Heating Accelerates Rolling Circle Amplification date: 2015-09-08 pages: extension: .txt txt: ./txt/cord-001761-yvd1n42f.txt cache: ./cache/cord-001761-yvd1n42f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-001761-yvd1n42f.txt' === file2bib.sh === id: cord-001359-c1uom5f7 author: Oslund, Karen L. title: Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells date: 2014-07-17 pages: extension: .txt txt: ./txt/cord-001359-c1uom5f7.txt cache: ./cache/cord-001359-c1uom5f7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001359-c1uom5f7.txt' === file2bib.sh === id: cord-001537-i34vmfpp author: Lima, Francisco Esmaile de Sales title: Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date: 2015-02-17 pages: extension: .txt txt: ./txt/cord-001537-i34vmfpp.txt cache: ./cache/cord-001537-i34vmfpp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001537-i34vmfpp.txt' === file2bib.sh === id: cord-003377-9vkhptas author: Wu, Tong title: The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia date: 2018-12-19 pages: extension: .txt txt: ./txt/cord-003377-9vkhptas.txt cache: ./cache/cord-003377-9vkhptas.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 210 resourceName b'cord-003377-9vkhptas.txt' === file2bib.sh === id: cord-004068-d66lwylf author: Shimoda, Tomoko title: Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections date: 2019-12-27 pages: extension: .txt txt: ./txt/cord-004068-d66lwylf.txt cache: ./cache/cord-004068-d66lwylf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004068-d66lwylf.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-001446-mpuovmeb author: Bratcher, Preston E. title: Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA date: 2014-11-03 pages: extension: .txt txt: ./txt/cord-001446-mpuovmeb.txt cache: ./cache/cord-001446-mpuovmeb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001446-mpuovmeb.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-001843-ceatyj3o author: Huang, Yong title: Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay date: 2015-11-06 pages: extension: .txt txt: ./txt/cord-001843-ceatyj3o.txt cache: ./cache/cord-001843-ceatyj3o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001843-ceatyj3o.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-001420-b4zcvd04 author: Crescenzo-Chaigne, Bernadette title: Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation date: 2014-09-30 pages: extension: .txt txt: ./txt/cord-001420-b4zcvd04.txt cache: ./cache/cord-001420-b4zcvd04.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001420-b4zcvd04.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-001421-6t5puo6p author: Marfà, Santiago title: Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date: 2014-10-02 pages: extension: .txt txt: ./txt/cord-001421-6t5puo6p.txt cache: ./cache/cord-001421-6t5puo6p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001421-6t5puo6p.txt' === file2bib.sh === id: cord-001387-2g9dc5z4 author: McIntyre, K. Marie title: A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe date: 2014-08-19 pages: extension: .txt txt: ./txt/cord-001387-2g9dc5z4.txt cache: ./cache/cord-001387-2g9dc5z4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001387-2g9dc5z4.txt' === file2bib.sh === id: cord-001605-8p06bpt1 author: Sapmak, Ariya title: The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei date: 2015-04-13 pages: extension: .txt txt: ./txt/cord-001605-8p06bpt1.txt cache: ./cache/cord-001605-8p06bpt1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001605-8p06bpt1.txt' === file2bib.sh === id: cord-002560-pue5q5wp author: Moreno, Paloma S. title: Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics date: 2017-06-01 pages: extension: .txt txt: ./txt/cord-002560-pue5q5wp.txt cache: ./cache/cord-002560-pue5q5wp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002560-pue5q5wp.txt' === file2bib.sh === id: cord-002426-5e1xn7kj author: Falcón-Lezama, Jorge Abelardo title: Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico date: 2017-02-22 pages: extension: .txt txt: ./txt/cord-002426-5e1xn7kj.txt cache: ./cache/cord-002426-5e1xn7kj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002426-5e1xn7kj.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-003712-mafz21no author: Perez Vidakovics, Maria Laura A. title: Junín virus induces autophagy in human A549 cells date: 2019-06-19 pages: extension: .txt txt: ./txt/cord-003712-mafz21no.txt cache: ./cache/cord-003712-mafz21no.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003712-mafz21no.txt' === file2bib.sh === id: cord-001601-tsuz3j40 author: Ngan, Luong Thi My title: Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses date: 2015-04-10 pages: extension: .txt txt: ./txt/cord-001601-tsuz3j40.txt cache: ./cache/cord-001601-tsuz3j40.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001601-tsuz3j40.txt' === file2bib.sh === id: cord-001275-a9o2dvke author: Chen, Xue title: A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types date: 2014-05-06 pages: extension: .txt txt: ./txt/cord-001275-a9o2dvke.txt cache: ./cache/cord-001275-a9o2dvke.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001275-a9o2dvke.txt' === file2bib.sh === id: cord-001263-hqxiyxfj author: Kam, Yiu-Wing title: Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development date: 2014-04-22 pages: extension: .txt txt: ./txt/cord-001263-hqxiyxfj.txt cache: ./cache/cord-001263-hqxiyxfj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001263-hqxiyxfj.txt' === file2bib.sh === id: cord-001447-oi7bkm4z author: Dhanasekaran, Sakthivel title: Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo date: 2014-11-04 pages: extension: .txt txt: ./txt/cord-001447-oi7bkm4z.txt cache: ./cache/cord-001447-oi7bkm4z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001447-oi7bkm4z.txt' === file2bib.sh === id: cord-002043-z1b7pj3s author: Wang, Xue-Yang title: Comparative Transcriptome Analysis of Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV in Susceptible and Near-Isogenic Resistant Strains date: 2016-05-11 pages: extension: .txt txt: ./txt/cord-002043-z1b7pj3s.txt cache: ./cache/cord-002043-z1b7pj3s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002043-z1b7pj3s.txt' === file2bib.sh === id: cord-002305-qq73gr9y author: Anson, Marie title: Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool date: 2016-11-23 pages: extension: .txt txt: ./txt/cord-002305-qq73gr9y.txt cache: ./cache/cord-002305-qq73gr9y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002305-qq73gr9y.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-002473-2kpxhzbe author: Das, Jayanta Kumar title: Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach date: 2017-03-31 pages: extension: .txt txt: ./txt/cord-002473-2kpxhzbe.txt cache: ./cache/cord-002473-2kpxhzbe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002473-2kpxhzbe.txt' === file2bib.sh === id: cord-002621-sq5iod1w author: Attia, Mohamed I. title: New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres date: 2017-07-25 pages: extension: .txt txt: ./txt/cord-002621-sq5iod1w.txt cache: ./cache/cord-002621-sq5iod1w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002621-sq5iod1w.txt' === file2bib.sh === id: cord-001432-d4zavkcn author: Nishida, Yoriko title: Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry date: 2014-10-16 pages: extension: .txt txt: ./txt/cord-001432-d4zavkcn.txt cache: ./cache/cord-001432-d4zavkcn.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001432-d4zavkcn.txt' === file2bib.sh === id: cord-001982-arczqdza author: Khajah, Maitham A. title: Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis date: 2016-03-10 pages: extension: .txt txt: ./txt/cord-001982-arczqdza.txt cache: ./cache/cord-001982-arczqdza.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-001982-arczqdza.txt' === file2bib.sh === id: cord-001898-ntqyjqqk author: Huang, Chih-Wei title: Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date: 2016-01-05 pages: extension: .txt txt: ./txt/cord-001898-ntqyjqqk.txt cache: ./cache/cord-001898-ntqyjqqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001898-ntqyjqqk.txt' === file2bib.sh === id: cord-002811-5hrydciz author: Hercik, Christine title: A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania date: 2017-12-29 pages: extension: .txt txt: ./txt/cord-002811-5hrydciz.txt cache: ./cache/cord-002811-5hrydciz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002811-5hrydciz.txt' === file2bib.sh === id: cord-001219-517gka4h author: Timpka, Toomas title: Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign date: 2014-03-07 pages: extension: .txt txt: ./txt/cord-001219-517gka4h.txt cache: ./cache/cord-001219-517gka4h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001219-517gka4h.txt' === file2bib.sh === id: cord-001909-yy9xp5ms author: Buß, O. title: Statistical Evaluation of HTS Assays for Enzymatic Hydrolysis of β-Keto Esters date: 2016-01-05 pages: extension: .txt txt: ./txt/cord-001909-yy9xp5ms.txt cache: ./cache/cord-001909-yy9xp5ms.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-001909-yy9xp5ms.txt' === file2bib.sh === id: cord-002094-7tewne3a author: Tago, Damian title: The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases date: 2016-06-14 pages: extension: .txt txt: ./txt/cord-002094-7tewne3a.txt cache: ./cache/cord-002094-7tewne3a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002094-7tewne3a.txt' === file2bib.sh === id: cord-003270-vu9b5a14 author: Panahi, Heidar Ali title: A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins date: 2018-10-24 pages: extension: .txt txt: ./txt/cord-003270-vu9b5a14.txt cache: ./cache/cord-003270-vu9b5a14.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003270-vu9b5a14.txt' === file2bib.sh === id: cord-001599-pfdnmzx2 author: Wee, Yin Shen title: Age-Related Onset of Obesity Corresponds with Metabolic Dysregulation and Altered Microglia Morphology in Mice Deficient for Ifitm Proteins date: 2015-04-09 pages: extension: .txt txt: ./txt/cord-001599-pfdnmzx2.txt cache: ./cache/cord-001599-pfdnmzx2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001599-pfdnmzx2.txt' === file2bib.sh === id: cord-003484-ylpa702c author: Blázquez, Elena title: Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma date: 2019-02-21 pages: extension: .txt txt: ./txt/cord-003484-ylpa702c.txt cache: ./cache/cord-003484-ylpa702c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003484-ylpa702c.txt' === file2bib.sh === id: cord-001958-2gt3fwpy author: Meseda, Clement A. title: Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines date: 2016-02-19 pages: extension: .txt txt: ./txt/cord-001958-2gt3fwpy.txt cache: ./cache/cord-001958-2gt3fwpy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001958-2gt3fwpy.txt' === file2bib.sh === id: cord-001964-iy6qzq58 author: Muñoz-González, Sara title: Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar date: 2016-02-26 pages: extension: .txt txt: ./txt/cord-001964-iy6qzq58.txt cache: ./cache/cord-001964-iy6qzq58.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001964-iy6qzq58.txt' === file2bib.sh === id: cord-002222-rgqwm3vb author: Olarte-Castillo, Ximena A. title: Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study date: 2016-09-23 pages: extension: .txt txt: ./txt/cord-002222-rgqwm3vb.txt cache: ./cache/cord-002222-rgqwm3vb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002222-rgqwm3vb.txt' === file2bib.sh === id: cord-004091-gex0zvoa author: Abdulkareem, Shaheen A. title: Risk perception and behavioral change during epidemics: Comparing models of individual and collective learning date: 2020-01-06 pages: extension: .txt txt: ./txt/cord-004091-gex0zvoa.txt cache: ./cache/cord-004091-gex0zvoa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-004091-gex0zvoa.txt' === file2bib.sh === id: cord-001383-hww0watl author: Li, Wenchao title: Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats date: 2014-08-12 pages: extension: .txt txt: ./txt/cord-001383-hww0watl.txt cache: ./cache/cord-001383-hww0watl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001383-hww0watl.txt' === file2bib.sh === id: cord-002141-9mxi4dzi author: Memczak, Henry title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding date: 2016-07-14 pages: extension: .txt txt: ./txt/cord-002141-9mxi4dzi.txt cache: ./cache/cord-002141-9mxi4dzi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002141-9mxi4dzi.txt' === file2bib.sh === id: cord-001781-afg1nmib author: Saksena, Sumeet title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam date: 2015-09-23 pages: extension: .txt txt: ./txt/cord-001781-afg1nmib.txt cache: ./cache/cord-001781-afg1nmib.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001781-afg1nmib.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-002100-dt5zvebj author: He, Yonghua title: Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date: 2016-06-17 pages: extension: .txt txt: ./txt/cord-002100-dt5zvebj.txt cache: ./cache/cord-002100-dt5zvebj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002100-dt5zvebj.txt' === file2bib.sh === id: cord-001435-ebl8yc92 author: Hoppe, Sebastian title: Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date: 2014-10-21 pages: extension: .txt txt: ./txt/cord-001435-ebl8yc92.txt cache: ./cache/cord-001435-ebl8yc92.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001435-ebl8yc92.txt' === file2bib.sh === id: cord-002602-2qvyhjlp author: Roy, Amrita title: Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants date: 2017-07-10 pages: extension: .txt txt: ./txt/cord-002602-2qvyhjlp.txt cache: ./cache/cord-002602-2qvyhjlp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002602-2qvyhjlp.txt' === file2bib.sh === id: cord-004017-gcmpatlb author: Errecaborde, Kaylee Myhre title: Factors that enable effective One Health collaborations - A scoping review of the literature date: 2019-12-04 pages: extension: .txt txt: ./txt/cord-004017-gcmpatlb.txt cache: ./cache/cord-004017-gcmpatlb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004017-gcmpatlb.txt' === file2bib.sh === id: cord-001249-awn9ayy6 author: Lasecka, Lidia title: The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space date: 2014-04-08 pages: extension: .txt txt: ./txt/cord-001249-awn9ayy6.txt cache: ./cache/cord-001249-awn9ayy6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001249-awn9ayy6.txt' === file2bib.sh === id: cord-003548-zuwt7gk5 author: Cai, Haiming title: Modulating the 3’ end-DNA and the fermentation process for enhanced production and biological activity of porcine interferon-gamma date: 2019-03-26 pages: extension: .txt txt: ./txt/cord-003548-zuwt7gk5.txt cache: ./cache/cord-003548-zuwt7gk5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003548-zuwt7gk5.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-251979-j3mme15e author: Kandeel, Amr title: Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014 date: 2016-09-08 pages: extension: .txt txt: ./txt/cord-251979-j3mme15e.txt cache: ./cache/cord-251979-j3mme15e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-251979-j3mme15e.txt' === file2bib.sh === id: cord-001734-bbeznd3r author: Gupta, Garvita title: NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics date: 2015-08-10 pages: extension: .txt txt: ./txt/cord-001734-bbeznd3r.txt cache: ./cache/cord-001734-bbeznd3r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001734-bbeznd3r.txt' === file2bib.sh === id: cord-048492-4z38v9rg author: Tang, Julian W. title: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006) date: 2008-07-23 pages: extension: .txt txt: ./txt/cord-048492-4z38v9rg.txt cache: ./cache/cord-048492-4z38v9rg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-048492-4z38v9rg.txt' === file2bib.sh === id: cord-011798-uss38ped author: Li, Guowei title: Intellectual capital and the efficiency of SMEs in the transition economy China; Do financial resources strengthen the routes? date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-011798-uss38ped.txt cache: ./cache/cord-011798-uss38ped.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011798-uss38ped.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53604 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55323 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54889 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54882 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55279 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55182 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55208 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55089 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55617 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55408 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55447 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55334 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55300 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55274 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56047 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56041 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55624 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55625 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57185 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-253436-dz84icdc author: Wille, Michelle title: High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl date: 2016-03-03 pages: extension: .txt txt: ./txt/cord-253436-dz84icdc.txt cache: ./cache/cord-253436-dz84icdc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-253436-dz84icdc.txt' === file2bib.sh === id: cord-256326-3ebcuzd6 author: Liotta, Giuseppe title: Is social connectedness a risk factor for the spreading of COVID-19 among older adults? The Italian paradox date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-256326-3ebcuzd6.txt cache: ./cache/cord-256326-3ebcuzd6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256326-3ebcuzd6.txt' === file2bib.sh === id: cord-267189-xq70rn1j author: Wang, Xinyu title: Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China date: 2016-01-15 pages: extension: .txt txt: ./txt/cord-267189-xq70rn1j.txt cache: ./cache/cord-267189-xq70rn1j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-267189-xq70rn1j.txt' === file2bib.sh === id: cord-258366-fu9b446y author: Couto, Carla R. title: Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project date: 2012-02-06 pages: extension: .txt txt: ./txt/cord-258366-fu9b446y.txt cache: ./cache/cord-258366-fu9b446y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258366-fu9b446y.txt' === file2bib.sh === id: cord-254000-pbzcupjg author: Suvannachart, Pukkapol title: Repeatability, reproducibility, agreement, and safety of Tono-Pen tip cover for intraocular measurement using latex and polyethylene wrap date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-254000-pbzcupjg.txt cache: ./cache/cord-254000-pbzcupjg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254000-pbzcupjg.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-254025-j1l0mder author: de Melo, Andreia C. title: Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute date: 2020-10-26 pages: extension: .txt txt: ./txt/cord-254025-j1l0mder.txt cache: ./cache/cord-254025-j1l0mder.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254025-j1l0mder.txt' === file2bib.sh === id: cord-272445-0xauff51 author: Naaber, Paul title: Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-272445-0xauff51.txt cache: ./cache/cord-272445-0xauff51.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-272445-0xauff51.txt' === file2bib.sh === id: cord-252795-x66zqmgv author: Islam, Md. Akhtarul title: Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-252795-x66zqmgv.txt cache: ./cache/cord-252795-x66zqmgv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252795-x66zqmgv.txt' === file2bib.sh === id: cord-260572-vd65ygtm author: Kim, Curi title: Comparison of Nasopharyngeal and Oropharyngeal Swabs for the Diagnosis of Eight Respiratory Viruses by Real-Time Reverse Transcription-PCR Assays date: 2011-06-30 pages: extension: .txt txt: ./txt/cord-260572-vd65ygtm.txt cache: ./cache/cord-260572-vd65ygtm.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260572-vd65ygtm.txt' === file2bib.sh === id: cord-258243-2utl2mfl author: Chen, Jeng-Wen title: Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study date: 2018-05-29 pages: extension: .txt txt: ./txt/cord-258243-2utl2mfl.txt cache: ./cache/cord-258243-2utl2mfl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258243-2utl2mfl.txt' === file2bib.sh === id: cord-254117-2ttwaegh author: Priest, Patricia C. title: Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study date: 2011-01-05 pages: extension: .txt txt: ./txt/cord-254117-2ttwaegh.txt cache: ./cache/cord-254117-2ttwaegh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254117-2ttwaegh.txt' === file2bib.sh === id: cord-253056-765rs3e7 author: Dionne, Audrey title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection date: 2018-10-17 pages: extension: .txt txt: ./txt/cord-253056-765rs3e7.txt cache: ./cache/cord-253056-765rs3e7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253056-765rs3e7.txt' === file2bib.sh === id: cord-252739-1manzf3l author: Zheng, Yueming title: Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants date: 2012-12-12 pages: extension: .txt txt: ./txt/cord-252739-1manzf3l.txt cache: ./cache/cord-252739-1manzf3l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252739-1manzf3l.txt' === file2bib.sh === id: cord-263276-keyu60in author: Zhou, Weimin title: Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia date: 2013-11-18 pages: extension: .txt txt: ./txt/cord-263276-keyu60in.txt cache: ./cache/cord-263276-keyu60in.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263276-keyu60in.txt' === file2bib.sh === id: cord-265812-1hcp36cw author: De Jong, Cornelis N. title: Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience date: 2017-10-26 pages: extension: .txt txt: ./txt/cord-265812-1hcp36cw.txt cache: ./cache/cord-265812-1hcp36cw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265812-1hcp36cw.txt' === file2bib.sh === id: cord-267519-a0bcmjkn author: Bravi, Francesca title: Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-267519-a0bcmjkn.txt cache: ./cache/cord-267519-a0bcmjkn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267519-a0bcmjkn.txt' === file2bib.sh === id: cord-267566-gdjl0qmu author: Kweon, Oh Joo title: Antibody kinetics and serologic profiles of SARS-CoV-2 infection using two serologic assays date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-267566-gdjl0qmu.txt cache: ./cache/cord-267566-gdjl0qmu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-267566-gdjl0qmu.txt' === file2bib.sh === id: cord-254825-c5d0wul9 author: Kim, Sei Won title: Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-254825-c5d0wul9.txt cache: ./cache/cord-254825-c5d0wul9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254825-c5d0wul9.txt' === file2bib.sh === id: cord-261908-olcuq6tm author: Lai, Ka-Man title: Propagation of Respiratory Aerosols by the Vuvuzela date: 2011-05-23 pages: extension: .txt txt: ./txt/cord-261908-olcuq6tm.txt cache: ./cache/cord-261908-olcuq6tm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-261908-olcuq6tm.txt' === file2bib.sh === id: cord-273764-itu39mln author: Li, Taisheng title: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus date: 2006-12-20 pages: extension: .txt txt: ./txt/cord-273764-itu39mln.txt cache: ./cache/cord-273764-itu39mln.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-273764-itu39mln.txt' === file2bib.sh === id: cord-048360-n9sih438 author: Villard, Viviane title: Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date: 2007-07-25 pages: extension: .txt txt: ./txt/cord-048360-n9sih438.txt cache: ./cache/cord-048360-n9sih438.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-048360-n9sih438.txt' === file2bib.sh === id: cord-266799-t7lqlv41 author: Rotejanaprasert, Chawarat title: Preliminary estimation of temporal and spatiotemporal dynamic measures of COVID-19 transmission in Thailand date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-266799-t7lqlv41.txt cache: ./cache/cord-266799-t7lqlv41.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266799-t7lqlv41.txt' === file2bib.sh === id: cord-254313-g2oc32dm author: Klink, Thomas title: Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-254313-g2oc32dm.txt cache: ./cache/cord-254313-g2oc32dm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254313-g2oc32dm.txt' === file2bib.sh === id: cord-013356-y6vceq2x author: Peace, Angela title: Orchard layout and plant traits influence fruit yield more strongly than pollinator behaviour and density in a dioecious crop date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-013356-y6vceq2x.txt cache: ./cache/cord-013356-y6vceq2x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013356-y6vceq2x.txt' === file2bib.sh === id: cord-257603-ov0b8yub author: Azlan, Arina Anis title: Public knowledge, attitudes and practices towards COVID-19: A cross-sectional study in Malaysia date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-257603-ov0b8yub.txt cache: ./cache/cord-257603-ov0b8yub.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-257603-ov0b8yub.txt' === file2bib.sh === id: cord-272655-qeojdpez author: Remolina, Yuly Andrea title: Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia date: 2015-11-17 pages: extension: .txt txt: ./txt/cord-272655-qeojdpez.txt cache: ./cache/cord-272655-qeojdpez.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272655-qeojdpez.txt' === file2bib.sh === id: cord-257217-f9sdt7ax author: Nunes, Marta C. title: Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children date: 2014-02-03 pages: extension: .txt txt: ./txt/cord-257217-f9sdt7ax.txt cache: ./cache/cord-257217-f9sdt7ax.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257217-f9sdt7ax.txt' === file2bib.sh === id: cord-255588-nh34lgdh author: Guo, Fang title: RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response date: 2012-10-03 pages: extension: .txt txt: ./txt/cord-255588-nh34lgdh.txt cache: ./cache/cord-255588-nh34lgdh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255588-nh34lgdh.txt' === file2bib.sh === id: cord-263464-fdosch11 author: Nuvey, Francis Sena title: Evaluation of the sentinel surveillance system for influenza-like illnesses in the Greater Accra region, Ghana, 2018 date: 2019-03-14 pages: extension: .txt txt: ./txt/cord-263464-fdosch11.txt cache: ./cache/cord-263464-fdosch11.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-263464-fdosch11.txt' === file2bib.sh === id: cord-254340-e1x0z3rh author: Cruz, Christian Joy Pattawi title: Exploring the young demographic profile of COVID-19 cases in Hong Kong: Evidence from migration and travel history data date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-254340-e1x0z3rh.txt cache: ./cache/cord-254340-e1x0z3rh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254340-e1x0z3rh.txt' === file2bib.sh === id: cord-265138-i5m3ax7g author: Wang, Xi-Ling title: Model Selection in Time Series Studies of Influenza-Associated Mortality date: 2012-06-20 pages: extension: .txt txt: ./txt/cord-265138-i5m3ax7g.txt cache: ./cache/cord-265138-i5m3ax7g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265138-i5m3ax7g.txt' === file2bib.sh === id: cord-260647-7bjhobg7 author: Coudray-Meunier, Coralie title: A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System date: 2016-01-29 pages: extension: .txt txt: ./txt/cord-260647-7bjhobg7.txt cache: ./cache/cord-260647-7bjhobg7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-260647-7bjhobg7.txt' === file2bib.sh === id: cord-255384-tljyx6ua author: Decaro, Nicola title: Full-Genome Analysis of a Canine Pneumovirus Causing Acute Respiratory Disease in Dogs, Italy date: 2014-01-06 pages: extension: .txt txt: ./txt/cord-255384-tljyx6ua.txt cache: ./cache/cord-255384-tljyx6ua.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255384-tljyx6ua.txt' === file2bib.sh === id: cord-255013-njpuc475 author: He, Xiaocui title: Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses date: 2014-10-08 pages: extension: .txt txt: ./txt/cord-255013-njpuc475.txt cache: ./cache/cord-255013-njpuc475.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255013-njpuc475.txt' === file2bib.sh === id: cord-261410-kb91eagd author: Park, Ji Young title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel date: 2017-01-23 pages: extension: .txt txt: ./txt/cord-261410-kb91eagd.txt cache: ./cache/cord-261410-kb91eagd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261410-kb91eagd.txt' === file2bib.sh === id: cord-013099-j816c3tw author: Blease, Charlotte title: US primary care in 2029: A Delphi survey on the impact of machine learning date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-013099-j816c3tw.txt cache: ./cache/cord-013099-j816c3tw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013099-j816c3tw.txt' === file2bib.sh === id: cord-273343-als886fe author: McClenahan, Shasta D. title: Discovery of a Bovine Enterovirus in Alpaca date: 2013-08-12 pages: extension: .txt txt: ./txt/cord-273343-als886fe.txt cache: ./cache/cord-273343-als886fe.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-273343-als886fe.txt' === file2bib.sh === id: cord-267307-kyh0xsrp author: Kasting, Monica L. title: Public perceptions of the effectiveness of recommended non-pharmaceutical intervention behaviors to mitigate the spread of SARS-CoV-2 date: 2020-11-04 pages: extension: .txt txt: ./txt/cord-267307-kyh0xsrp.txt cache: ./cache/cord-267307-kyh0xsrp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-267307-kyh0xsrp.txt' === file2bib.sh === id: cord-262759-ec2c25q3 author: Hsieh, Yi-Ting title: Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus date: 2013-11-04 pages: extension: .txt txt: ./txt/cord-262759-ec2c25q3.txt cache: ./cache/cord-262759-ec2c25q3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262759-ec2c25q3.txt' === file2bib.sh === id: cord-263453-7v4y02j6 author: Nishiura, Hiroshi title: Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic date: 2009-08-31 pages: extension: .txt txt: ./txt/cord-263453-7v4y02j6.txt cache: ./cache/cord-263453-7v4y02j6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-263453-7v4y02j6.txt' === file2bib.sh === id: cord-262876-civfvk45 author: Su, Tong title: Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China date: 2013-06-24 pages: extension: .txt txt: ./txt/cord-262876-civfvk45.txt cache: ./cache/cord-262876-civfvk45.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262876-civfvk45.txt' === file2bib.sh === id: cord-013334-cptu0k7s author: Holst-Hansen, Joachim A. title: Does the size of rewards influence performance in cognitively demanding tasks? date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-013334-cptu0k7s.txt cache: ./cache/cord-013334-cptu0k7s.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013334-cptu0k7s.txt' === file2bib.sh === id: cord-266797-uglsx7se author: Anastassopoulou, Cleo title: Data-based analysis, modelling and forecasting of the COVID-19 outbreak date: 2020-03-31 pages: extension: .txt txt: ./txt/cord-266797-uglsx7se.txt cache: ./cache/cord-266797-uglsx7se.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-266797-uglsx7se.txt' === file2bib.sh === id: cord-256424-t3dtabi4 author: Bousbia, Sabri title: Repertoire of Intensive Care Unit Pneumonia Microbiota date: 2012-02-28 pages: extension: .txt txt: ./txt/cord-256424-t3dtabi4.txt cache: ./cache/cord-256424-t3dtabi4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256424-t3dtabi4.txt' === file2bib.sh === id: cord-267605-efb10j3u author: Zheng, Li-Zhen title: Steroid-Associated Hip Joint Collapse in Bipedal Emus date: 2013-10-21 pages: extension: .txt txt: ./txt/cord-267605-efb10j3u.txt cache: ./cache/cord-267605-efb10j3u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267605-efb10j3u.txt' === file2bib.sh === id: cord-262748-v4xue7ha author: Xu, Yongtao title: Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine date: 2015-12-04 pages: extension: .txt txt: ./txt/cord-262748-v4xue7ha.txt cache: ./cache/cord-262748-v4xue7ha.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262748-v4xue7ha.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-259771-653opx0h author: Dwivedi, Varun title: Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs date: 2012-12-11 pages: extension: .txt txt: ./txt/cord-259771-653opx0h.txt cache: ./cache/cord-259771-653opx0h.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259771-653opx0h.txt' === file2bib.sh === id: cord-268524-lr51ubz5 author: Droit-Volet, Sylvie title: Time and Covid-19 stress in the lockdown situation: Time free, «Dying» of boredom and sadness date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-268524-lr51ubz5.txt cache: ./cache/cord-268524-lr51ubz5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-268524-lr51ubz5.txt' === file2bib.sh === id: cord-255351-vp19ydce author: Lanata, Claudio F. title: Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review date: 2013-09-04 pages: extension: .txt txt: ./txt/cord-255351-vp19ydce.txt cache: ./cache/cord-255351-vp19ydce.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255351-vp19ydce.txt' === file2bib.sh === id: cord-260653-5qwtvm9x author: Chikhlikar, Priya title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date: 2006-12-27 pages: extension: .txt txt: ./txt/cord-260653-5qwtvm9x.txt cache: ./cache/cord-260653-5qwtvm9x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260653-5qwtvm9x.txt' === file2bib.sh === id: cord-271660-5sfkhg19 author: Sun, Hsin-Yun title: Impact of introducing fluorescent microscopy on hospital tuberculosis control: A before-after study at a high caseload medical center in Taiwan date: 2020-04-03 pages: extension: .txt txt: ./txt/cord-271660-5sfkhg19.txt cache: ./cache/cord-271660-5sfkhg19.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271660-5sfkhg19.txt' === file2bib.sh === id: cord-048339-nzh87aux author: Caley, Peter title: The Waiting Time for Inter-Country Spread of Pandemic Influenza date: 2007-01-03 pages: extension: .txt txt: ./txt/cord-048339-nzh87aux.txt cache: ./cache/cord-048339-nzh87aux.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-048339-nzh87aux.txt' === file2bib.sh === id: cord-263684-3535k3op author: Tang, Julian W. title: Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms date: 2013-06-24 pages: extension: .txt txt: ./txt/cord-263684-3535k3op.txt cache: ./cache/cord-263684-3535k3op.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-263684-3535k3op.txt' === file2bib.sh === id: cord-260843-c97kctjz author: Dai, Lei title: Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake date: 2016-11-16 pages: extension: .txt txt: ./txt/cord-260843-c97kctjz.txt cache: ./cache/cord-260843-c97kctjz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-260843-c97kctjz.txt' === file2bib.sh === id: cord-260432-imslfm4l author: Marshall, Jenika D. title: THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-260432-imslfm4l.txt cache: ./cache/cord-260432-imslfm4l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260432-imslfm4l.txt' === file2bib.sh === id: cord-267973-uvz7kavu author: Do, Lien Anh Ha title: Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity date: 2016-08-08 pages: extension: .txt txt: ./txt/cord-267973-uvz7kavu.txt cache: ./cache/cord-267973-uvz7kavu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-267973-uvz7kavu.txt' === file2bib.sh === id: cord-262832-5iejckwx author: Yen, Muh-Yong title: Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease date: 2009-11-23 pages: extension: .txt txt: ./txt/cord-262832-5iejckwx.txt cache: ./cache/cord-262832-5iejckwx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-262832-5iejckwx.txt' === file2bib.sh === id: cord-268977-hcg2rrhl author: Feikin, Daniel R. title: Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007–2010 date: 2012-08-24 pages: extension: .txt txt: ./txt/cord-268977-hcg2rrhl.txt cache: ./cache/cord-268977-hcg2rrhl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268977-hcg2rrhl.txt' === file2bib.sh === id: cord-268816-nth3o6ot author: Roy, Satyaki title: Factors affecting COVID-19 infected and death rates inform lockdown-related policymaking date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-268816-nth3o6ot.txt cache: ./cache/cord-268816-nth3o6ot.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268816-nth3o6ot.txt' === file2bib.sh === id: cord-267042-nvwnbp2j author: Gaspard, Philippe title: Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents date: 2019-09-24 pages: extension: .txt txt: ./txt/cord-267042-nvwnbp2j.txt cache: ./cache/cord-267042-nvwnbp2j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-267042-nvwnbp2j.txt' === file2bib.sh === id: cord-270681-6ayciihs author: Bálint, Ádám title: Comparative In Vivo Analysis of Recombinant Type II Feline Coronaviruses with Truncated and Completed ORF3 Region date: 2014-02-20 pages: extension: .txt txt: ./txt/cord-270681-6ayciihs.txt cache: ./cache/cord-270681-6ayciihs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270681-6ayciihs.txt' === file2bib.sh === id: cord-267644-guzn0peq author: Livadiotis, George title: Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19 date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-267644-guzn0peq.txt cache: ./cache/cord-267644-guzn0peq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267644-guzn0peq.txt' === file2bib.sh === id: cord-279259-eu80ccm6 author: Pandey, Aseem title: Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine date: 2012-03-14 pages: extension: .txt txt: ./txt/cord-279259-eu80ccm6.txt cache: ./cache/cord-279259-eu80ccm6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279259-eu80ccm6.txt' === file2bib.sh === id: cord-268429-drejl99k author: Almberg, Emily S. title: A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community date: 2009-09-16 pages: extension: .txt txt: ./txt/cord-268429-drejl99k.txt cache: ./cache/cord-268429-drejl99k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268429-drejl99k.txt' === file2bib.sh === id: cord-048477-ze511t38 author: Patel, Mahomed S. title: General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries date: 2008-05-28 pages: extension: .txt txt: ./txt/cord-048477-ze511t38.txt cache: ./cache/cord-048477-ze511t38.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-048477-ze511t38.txt' === file2bib.sh === id: cord-258172-p54j4zzo author: Barker, Harlan title: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2 date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-258172-p54j4zzo.txt cache: ./cache/cord-258172-p54j4zzo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-258172-p54j4zzo.txt' === file2bib.sh === id: cord-260728-4w23kwzu author: Timmermans, Ans title: Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia date: 2016-03-30 pages: extension: .txt txt: ./txt/cord-260728-4w23kwzu.txt cache: ./cache/cord-260728-4w23kwzu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260728-4w23kwzu.txt' === file2bib.sh === id: cord-262846-1mhimfsf author: Gray, Nicholas title: Is “no test is better than a bad test”? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19 date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-262846-1mhimfsf.txt cache: ./cache/cord-262846-1mhimfsf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-262846-1mhimfsf.txt' === file2bib.sh === id: cord-262345-hti1jjpn author: Eddy, Lucy H. title: The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-262345-hti1jjpn.txt cache: ./cache/cord-262345-hti1jjpn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262345-hti1jjpn.txt' === file2bib.sh === id: cord-264880-0tmd9knh author: Li, Zhao title: Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date: 2016-04-13 pages: extension: .txt txt: ./txt/cord-264880-0tmd9knh.txt cache: ./cache/cord-264880-0tmd9knh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-264880-0tmd9knh.txt' === file2bib.sh === id: cord-255576-738khdwv author: Van Duyne, Rachel title: Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery date: 2012-07-10 pages: extension: .txt txt: ./txt/cord-255576-738khdwv.txt cache: ./cache/cord-255576-738khdwv.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255576-738khdwv.txt' === file2bib.sh === id: cord-256837-100ir651 author: Smith, Steven B. title: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date: 2012-03-14 pages: extension: .txt txt: ./txt/cord-256837-100ir651.txt cache: ./cache/cord-256837-100ir651.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256837-100ir651.txt' === file2bib.sh === id: cord-270408-4qqyb8sd author: Pane, Masdalina title: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings date: 2013-08-21 pages: extension: .txt txt: ./txt/cord-270408-4qqyb8sd.txt cache: ./cache/cord-270408-4qqyb8sd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270408-4qqyb8sd.txt' === file2bib.sh === id: cord-270647-vn4kirrx author: Romero-Espinoza, Jose A. title: Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015 date: 2018-02-15 pages: extension: .txt txt: ./txt/cord-270647-vn4kirrx.txt cache: ./cache/cord-270647-vn4kirrx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270647-vn4kirrx.txt' === file2bib.sh === id: cord-276898-ia80cy8j author: Yamanaka, Atsushi title: Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus date: 2014-03-25 pages: extension: .txt txt: ./txt/cord-276898-ia80cy8j.txt cache: ./cache/cord-276898-ia80cy8j.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276898-ia80cy8j.txt' === file2bib.sh === id: cord-278123-mq56em3z author: Hasan, Mohammad Rubayet title: Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-278123-mq56em3z.txt cache: ./cache/cord-278123-mq56em3z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-278123-mq56em3z.txt' === file2bib.sh === id: cord-277357-lpurk7pe author: González-González, Everardo title: Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-277357-lpurk7pe.txt cache: ./cache/cord-277357-lpurk7pe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-277357-lpurk7pe.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61947 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-280471-cqypwi5d author: Sun, Hua-Bao title: The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19 date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-280471-cqypwi5d.txt cache: ./cache/cord-280471-cqypwi5d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280471-cqypwi5d.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61951 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62141 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61957 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61989 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61963 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61960 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62020 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-276372-q1fzxt3r author: Conde, Dalia A. title: Zoos through the Lens of the IUCN Red List: A Global Metapopulation Approach to Support Conservation Breeding Programs date: 2013-12-11 pages: extension: .txt txt: ./txt/cord-276372-q1fzxt3r.txt cache: ./cache/cord-276372-q1fzxt3r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276372-q1fzxt3r.txt' === file2bib.sh === id: cord-278018-3qemb0x3 author: Li, Li title: Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy date: 2011-08-22 pages: extension: .txt txt: ./txt/cord-278018-3qemb0x3.txt cache: ./cache/cord-278018-3qemb0x3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278018-3qemb0x3.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62045 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62109 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-281815-zvs5qe8x author: Subramanian, Shoba title: Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3 date: 2009-04-09 pages: extension: .txt txt: ./txt/cord-281815-zvs5qe8x.txt cache: ./cache/cord-281815-zvs5qe8x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-281815-zvs5qe8x.txt' === file2bib.sh === id: cord-282303-idh7io9v author: Hassan, Md. Zakiul title: Contamination of hospital surfaces with respiratory pathogens in Bangladesh date: 2019-10-28 pages: extension: .txt txt: ./txt/cord-282303-idh7io9v.txt cache: ./cache/cord-282303-idh7io9v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-282303-idh7io9v.txt' === file2bib.sh === id: cord-263978-jk82bk1a author: Karaivanov, Alexander title: A social network model of COVID-19 date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-263978-jk82bk1a.txt cache: ./cache/cord-263978-jk82bk1a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263978-jk82bk1a.txt' === file2bib.sh === id: cord-282202-q2q4vies author: Banerjee, Amitava title: Clinical academic research in the time of Corona: A simulation study in England and a call for action date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-282202-q2q4vies.txt cache: ./cache/cord-282202-q2q4vies.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-282202-q2q4vies.txt' === file2bib.sh === id: cord-286065-x0g67pnb author: Metzgar, David title: The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood date: 2016-07-06 pages: extension: .txt txt: ./txt/cord-286065-x0g67pnb.txt cache: ./cache/cord-286065-x0g67pnb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286065-x0g67pnb.txt' === file2bib.sh === id: cord-285546-5tjhdczt author: Green, Manfred S. title: The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-285546-5tjhdczt.txt cache: ./cache/cord-285546-5tjhdczt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285546-5tjhdczt.txt' === file2bib.sh === id: cord-284275-bqo203pf author: Lu, Roujian title: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays date: 2012-06-15 pages: extension: .txt txt: ./txt/cord-284275-bqo203pf.txt cache: ./cache/cord-284275-bqo203pf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-284275-bqo203pf.txt' === file2bib.sh === id: cord-279421-rxocrgfu author: Zhang, Dan title: Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection date: 2016-04-04 pages: extension: .txt txt: ./txt/cord-279421-rxocrgfu.txt cache: ./cache/cord-279421-rxocrgfu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279421-rxocrgfu.txt' === file2bib.sh === id: cord-281161-u896icp9 author: Wang, Jing title: The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates date: 2012-05-17 pages: extension: .txt txt: ./txt/cord-281161-u896icp9.txt cache: ./cache/cord-281161-u896icp9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-281161-u896icp9.txt' === file2bib.sh === id: cord-280386-a8qr7nl6 author: Pires, Sara M. title: Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food date: 2015-12-03 pages: extension: .txt txt: ./txt/cord-280386-a8qr7nl6.txt cache: ./cache/cord-280386-a8qr7nl6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280386-a8qr7nl6.txt' === file2bib.sh === id: cord-281124-4nhy35xn author: Soowannayan, Chumporn title: RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date: 2011-08-03 pages: extension: .txt txt: ./txt/cord-281124-4nhy35xn.txt cache: ./cache/cord-281124-4nhy35xn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281124-4nhy35xn.txt' === file2bib.sh === id: cord-289873-6hivjqof author: Lu, Rui title: Patients with mild and general COVID-19 should be negative for at least 3 consecutive nucleic acid tests before discharged date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-289873-6hivjqof.txt cache: ./cache/cord-289873-6hivjqof.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-289873-6hivjqof.txt' === file2bib.sh === id: cord-274241-biqbsggu author: Shaw, Timothy I. title: Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date: 2012-11-15 pages: extension: .txt txt: ./txt/cord-274241-biqbsggu.txt cache: ./cache/cord-274241-biqbsggu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274241-biqbsggu.txt' === file2bib.sh === id: cord-283604-fqc9jp0l author: Chen, Meng title: Adenoviruses Associated with Acute Respiratory Diseases Reported in Beijing from 2011 to 2013 date: 2015-03-27 pages: extension: .txt txt: ./txt/cord-283604-fqc9jp0l.txt cache: ./cache/cord-283604-fqc9jp0l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283604-fqc9jp0l.txt' === file2bib.sh === id: cord-290773-kgb8r561 author: Ahn, Jong Gyun title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus date: 2018-07-03 pages: extension: .txt txt: ./txt/cord-290773-kgb8r561.txt cache: ./cache/cord-290773-kgb8r561.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290773-kgb8r561.txt' === file2bib.sh === id: cord-287739-58fth3xl author: Huang, Yhu-Chering title: Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign date: 2011-08-12 pages: extension: .txt txt: ./txt/cord-287739-58fth3xl.txt cache: ./cache/cord-287739-58fth3xl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287739-58fth3xl.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-286708-igu984oc author: Chua, Kaw Bing title: Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections date: 2008-11-25 pages: extension: .txt txt: ./txt/cord-286708-igu984oc.txt cache: ./cache/cord-286708-igu984oc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286708-igu984oc.txt' === file2bib.sh === id: cord-285433-ehnu83qe author: Sun, Hongliu title: Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry date: 2015-08-21 pages: extension: .txt txt: ./txt/cord-285433-ehnu83qe.txt cache: ./cache/cord-285433-ehnu83qe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-285433-ehnu83qe.txt' === file2bib.sh === id: cord-280846-bbv6f5gf author: Greninger, Alexander L. title: A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America date: 2010-10-18 pages: extension: .txt txt: ./txt/cord-280846-bbv6f5gf.txt cache: ./cache/cord-280846-bbv6f5gf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280846-bbv6f5gf.txt' === file2bib.sh === id: cord-281364-syg0wo77 author: Caì, Yíngyún title: CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection date: 2014-11-19 pages: extension: .txt txt: ./txt/cord-281364-syg0wo77.txt cache: ./cache/cord-281364-syg0wo77.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-281364-syg0wo77.txt' === file2bib.sh === id: cord-283976-jgae7r2q author: Armstrong, Melissa J. title: Research priorities of caregivers and individuals with dementia with Lewy bodies: An interview study date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-283976-jgae7r2q.txt cache: ./cache/cord-283976-jgae7r2q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-283976-jgae7r2q.txt' === file2bib.sh === id: cord-286613-cmtsu73g author: Lee, Sung Woo title: Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation date: 2015-10-15 pages: extension: .txt txt: ./txt/cord-286613-cmtsu73g.txt cache: ./cache/cord-286613-cmtsu73g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-286613-cmtsu73g.txt' === file2bib.sh === id: cord-290034-4b0mshqa author: Le, Yen H. title: Virus detections among patients with severe acute respiratory illness, Northern Vietnam date: 2020-05-12 pages: extension: .txt txt: ./txt/cord-290034-4b0mshqa.txt cache: ./cache/cord-290034-4b0mshqa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290034-4b0mshqa.txt' === file2bib.sh === id: cord-281665-6n7aq4k9 author: Qiu, Sangsang title: Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models date: 2015-05-20 pages: extension: .txt txt: ./txt/cord-281665-6n7aq4k9.txt cache: ./cache/cord-281665-6n7aq4k9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-281665-6n7aq4k9.txt' === file2bib.sh === id: cord-287761-73qgx58i author: Aly, Mahmoud title: Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update date: 2017-10-13 pages: extension: .txt txt: ./txt/cord-287761-73qgx58i.txt cache: ./cache/cord-287761-73qgx58i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287761-73qgx58i.txt' === file2bib.sh === id: cord-291756-ejh1r8h4 author: Pérez-Fuentes, María del Carmen title: Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population date: 2020-06-25 pages: extension: .txt txt: ./txt/cord-291756-ejh1r8h4.txt cache: ./cache/cord-291756-ejh1r8h4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291756-ejh1r8h4.txt' === file2bib.sh === id: cord-294023-knaxr7t0 author: Murri, Rita title: Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-294023-knaxr7t0.txt cache: ./cache/cord-294023-knaxr7t0.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-294023-knaxr7t0.txt' === file2bib.sh === id: cord-284016-zb6cv8ik author: Li, Wei title: Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection date: 2008-04-16 pages: extension: .txt txt: ./txt/cord-284016-zb6cv8ik.txt cache: ./cache/cord-284016-zb6cv8ik.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284016-zb6cv8ik.txt' === file2bib.sh === id: cord-288502-qqg41daz author: Martini, Katharina title: Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019 date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-288502-qqg41daz.txt cache: ./cache/cord-288502-qqg41daz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288502-qqg41daz.txt' === file2bib.sh === id: cord-294372-pec1886j author: Greene, Dina N. title: Decreasing median age of COVID-19 cases in the United States—Changing epidemiology or changing surveillance? date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-294372-pec1886j.txt cache: ./cache/cord-294372-pec1886j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294372-pec1886j.txt' === file2bib.sh === id: cord-289285-aof7xy13 author: Michaelis, Martin title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression date: 2011-05-17 pages: extension: .txt txt: ./txt/cord-289285-aof7xy13.txt cache: ./cache/cord-289285-aof7xy13.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289285-aof7xy13.txt' === file2bib.sh === id: cord-286837-j2sqs20q author: Koetsier, Antonie title: Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics? date: 2013-12-31 pages: extension: .txt txt: ./txt/cord-286837-j2sqs20q.txt cache: ./cache/cord-286837-j2sqs20q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-286837-j2sqs20q.txt' === file2bib.sh === id: cord-288440-w7g2agaf author: Jia, Rui title: The C-Terminal Sequence of IFITM1 Regulates Its Anti-HIV-1 Activity date: 2015-03-04 pages: extension: .txt txt: ./txt/cord-288440-w7g2agaf.txt cache: ./cache/cord-288440-w7g2agaf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288440-w7g2agaf.txt' === file2bib.sh === id: cord-282668-bs634hti author: Niang, Mbayame Ndiaye title: Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses date: 2017-03-22 pages: extension: .txt txt: ./txt/cord-282668-bs634hti.txt cache: ./cache/cord-282668-bs634hti.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282668-bs634hti.txt' === file2bib.sh === id: cord-292777-oztmw8jo author: Wong, Michelle title: Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia date: 2013-07-16 pages: extension: .txt txt: ./txt/cord-292777-oztmw8jo.txt cache: ./cache/cord-292777-oztmw8jo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292777-oztmw8jo.txt' === file2bib.sh === id: cord-000248-zueoyesj author: Berretta, Regina title: Cancer Biomarker Discovery: The Entropic Hallmark date: 2010-08-18 pages: extension: .txt txt: ./txt/cord-000248-zueoyesj.txt cache: ./cache/cord-000248-zueoyesj.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000248-zueoyesj.txt' === file2bib.sh === id: cord-290833-m0wodqr3 author: Yuan, Lvfeng title: Synthetic surfactin analogues have improved anti-PEDV properties date: 2019-04-11 pages: extension: .txt txt: ./txt/cord-290833-m0wodqr3.txt cache: ./cache/cord-290833-m0wodqr3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-290833-m0wodqr3.txt' === file2bib.sh === id: cord-295352-b8kztgt8 author: Maksimowski, Nicholas title: Kidney ACE2 expression: Implications for chronic kidney disease date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-295352-b8kztgt8.txt cache: ./cache/cord-295352-b8kztgt8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295352-b8kztgt8.txt' === file2bib.sh === id: cord-291417-p49ukyhx author: Mikulska, Malgorzata title: Tocilizumab and steroid treatment in patients with COVID-19 pneumonia date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-291417-p49ukyhx.txt cache: ./cache/cord-291417-p49ukyhx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291417-p49ukyhx.txt' === file2bib.sh === id: cord-295339-nzc47itk author: Baker, Marissa G. title: Estimating the burden of United States workers exposed to infection or disease: A key factor in containing risk of COVID-19 infection date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-295339-nzc47itk.txt cache: ./cache/cord-295339-nzc47itk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295339-nzc47itk.txt' === file2bib.sh === id: cord-286404-eggkqq3b author: Strayer, David R. title: Effect of disease duration in a randomized Phase III trial of rintatolimod, an immune modulator for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-286404-eggkqq3b.txt cache: ./cache/cord-286404-eggkqq3b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286404-eggkqq3b.txt' === file2bib.sh === id: cord-292396-8w06oc5i author: Leger, Thomas title: Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-292396-8w06oc5i.txt cache: ./cache/cord-292396-8w06oc5i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-292396-8w06oc5i.txt' === file2bib.sh === id: cord-282194-0sjmf1yn author: Cherak, Stephana J. title: Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-282194-0sjmf1yn.txt cache: ./cache/cord-282194-0sjmf1yn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282194-0sjmf1yn.txt' === file2bib.sh === id: cord-292237-45hi4iz2 author: Calvo-Pinilla, Eva title: Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the Alpha/Beta Interferon Receptor date: 2009-04-09 pages: extension: .txt txt: ./txt/cord-292237-45hi4iz2.txt cache: ./cache/cord-292237-45hi4iz2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-292237-45hi4iz2.txt' === file2bib.sh === id: cord-293794-vudufao5 author: Cuthbertson, Leah title: Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children date: 2019-10-17 pages: extension: .txt txt: ./txt/cord-293794-vudufao5.txt cache: ./cache/cord-293794-vudufao5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-293794-vudufao5.txt' === file2bib.sh === id: cord-290539-8ak2tths author: Cagno, Valeria title: Novel broad spectrum virucidal molecules against enveloped viruses date: 2018-12-07 pages: extension: .txt txt: ./txt/cord-290539-8ak2tths.txt cache: ./cache/cord-290539-8ak2tths.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290539-8ak2tths.txt' === file2bib.sh === id: cord-294768-bs6thjw2 author: Alonso-Fernández, Alberto title: Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-294768-bs6thjw2.txt cache: ./cache/cord-294768-bs6thjw2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294768-bs6thjw2.txt' === file2bib.sh === id: cord-295293-ickp2n47 author: Latsuzbaia, Ardashel title: Evolving social contact patterns during the COVID-19 crisis in Luxembourg date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-295293-ickp2n47.txt cache: ./cache/cord-295293-ickp2n47.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295293-ickp2n47.txt' === file2bib.sh === id: cord-291360-z19ri377 author: Lan, Fan-Yun title: COVID-19 symptoms predictive of healthcare workers’ SARS-CoV-2 PCR results date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-291360-z19ri377.txt cache: ./cache/cord-291360-z19ri377.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291360-z19ri377.txt' === file2bib.sh === id: cord-291176-evb6yt0r author: Giorgi Rossi, Paolo title: Characteristics and outcomes of a cohort of COVID-19 patients in the Province of Reggio Emilia, Italy date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-291176-evb6yt0r.txt cache: ./cache/cord-291176-evb6yt0r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291176-evb6yt0r.txt' === file2bib.sh === id: cord-290120-fd26t8ja author: Tan, Chew Yee title: First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-290120-fd26t8ja.txt cache: ./cache/cord-290120-fd26t8ja.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-290120-fd26t8ja.txt' === file2bib.sh === id: cord-293072-giakcaki author: Xu, Wan-Xiang title: A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date: 2017-10-12 pages: extension: .txt txt: ./txt/cord-293072-giakcaki.txt cache: ./cache/cord-293072-giakcaki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293072-giakcaki.txt' === file2bib.sh === id: cord-289555-1z4vbldd author: Mühldorfer, Kristin title: Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates date: 2011-12-28 pages: extension: .txt txt: ./txt/cord-289555-1z4vbldd.txt cache: ./cache/cord-289555-1z4vbldd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289555-1z4vbldd.txt' === file2bib.sh === id: cord-294645-yzh8h7zo author: Freeman, David W. title: Association between GDF15, poverty and mortality in urban middle-aged African American and white adults date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-294645-yzh8h7zo.txt cache: ./cache/cord-294645-yzh8h7zo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294645-yzh8h7zo.txt' === file2bib.sh === id: cord-289892-yh1lioyz author: Bai, Bingke title: Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells date: 2008-07-16 pages: extension: .txt txt: ./txt/cord-289892-yh1lioyz.txt cache: ./cache/cord-289892-yh1lioyz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289892-yh1lioyz.txt' === file2bib.sh === id: cord-289510-spmknns5 author: Curado, Evaldo M. F. title: A discrete-time-evolution model to forecast progress of Covid-19 outbreak date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-289510-spmknns5.txt cache: ./cache/cord-289510-spmknns5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289510-spmknns5.txt' === file2bib.sh === id: cord-295536-dbpt4dhr author: Shook, Natalie J. title: Disease avoidance in the time of COVID-19: The behavioral immune system is associated with concern and preventative health behaviors date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-295536-dbpt4dhr.txt cache: ./cache/cord-295536-dbpt4dhr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-295536-dbpt4dhr.txt' === file2bib.sh === id: cord-284501-5i0w74q4 author: Armesto, Maria title: The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity date: 2009-10-09 pages: extension: .txt txt: ./txt/cord-284501-5i0w74q4.txt cache: ./cache/cord-284501-5i0w74q4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284501-5i0w74q4.txt' === file2bib.sh === id: cord-294568-12eyo13f author: Fernandes-Matano, Larissa title: Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico date: 2017-05-03 pages: extension: .txt txt: ./txt/cord-294568-12eyo13f.txt cache: ./cache/cord-294568-12eyo13f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294568-12eyo13f.txt' === file2bib.sh === id: cord-278099-ypov9ha3 author: Kumar, Surender title: Molecular characterization of a novel cryptic virus infecting pigeonpea plants date: 2017-08-03 pages: extension: .txt txt: ./txt/cord-278099-ypov9ha3.txt cache: ./cache/cord-278099-ypov9ha3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278099-ypov9ha3.txt' === file2bib.sh === id: cord-292537-9ra4r6v6 author: Liu, Fenglin title: Predicting and analyzing the COVID-19 epidemic in China: Based on SEIRD, LSTM and GWR models date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-292537-9ra4r6v6.txt cache: ./cache/cord-292537-9ra4r6v6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292537-9ra4r6v6.txt' === file2bib.sh === id: cord-289017-vwye3pk9 author: Comach, Guillermo title: Sentinel Surveillance of Influenza-Like Illness in Two Hospitals in Maracay, Venezuela: 2006–2010 date: 2012-09-11 pages: extension: .txt txt: ./txt/cord-289017-vwye3pk9.txt cache: ./cache/cord-289017-vwye3pk9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-289017-vwye3pk9.txt' === file2bib.sh === id: cord-285749-0ejhd9nw author: Hoffmann, Markus title: The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells date: 2016-03-30 pages: extension: .txt txt: ./txt/cord-285749-0ejhd9nw.txt cache: ./cache/cord-285749-0ejhd9nw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285749-0ejhd9nw.txt' === file2bib.sh === id: cord-289305-mfjyjjer author: Lee, Min Hye title: A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control date: 2020-03-10 pages: extension: .txt txt: ./txt/cord-289305-mfjyjjer.txt cache: ./cache/cord-289305-mfjyjjer.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289305-mfjyjjer.txt' === file2bib.sh === id: cord-291104-6chpmgry author: Leung, Danny T. M. title: Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients date: 2016-08-05 pages: extension: .txt txt: ./txt/cord-291104-6chpmgry.txt cache: ./cache/cord-291104-6chpmgry.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291104-6chpmgry.txt' === file2bib.sh === id: cord-296635-8r3tm966 author: Breed, Andrew C. title: Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management date: 2011-12-14 pages: extension: .txt txt: ./txt/cord-296635-8r3tm966.txt cache: ./cache/cord-296635-8r3tm966.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296635-8r3tm966.txt' === file2bib.sh === id: cord-293393-kbndie8e author: Braesch-Andersen, Sten title: ApoD Mediates Binding of HDL to LDL and to Growing T24 Carcinoma date: 2014-12-16 pages: extension: .txt txt: ./txt/cord-293393-kbndie8e.txt cache: ./cache/cord-293393-kbndie8e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293393-kbndie8e.txt' === file2bib.sh === id: cord-297835-ukrz8tlv author: Leith, Douglas J. title: Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-297835-ukrz8tlv.txt cache: ./cache/cord-297835-ukrz8tlv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297835-ukrz8tlv.txt' === file2bib.sh === id: cord-289093-si8btsab author: Beard, Philippa M. title: A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference date: 2014-06-05 pages: extension: .txt txt: ./txt/cord-289093-si8btsab.txt cache: ./cache/cord-289093-si8btsab.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289093-si8btsab.txt' === file2bib.sh === id: cord-296550-wkmnfph3 author: Hossain, Mohammad Anwar title: Knowledge, attitudes, and fear of COVID-19 during the Rapid Rise Period in Bangladesh date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-296550-wkmnfph3.txt cache: ./cache/cord-296550-wkmnfph3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296550-wkmnfph3.txt' === file2bib.sh === id: cord-293946-4bquxdqa author: Huong, Nguyen Quynh title: Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014 date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-293946-4bquxdqa.txt cache: ./cache/cord-293946-4bquxdqa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-293946-4bquxdqa.txt' === file2bib.sh === id: cord-296691-cg463fbn author: Wang, Ren title: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing date: 2013-04-09 pages: extension: .txt txt: ./txt/cord-296691-cg463fbn.txt cache: ./cache/cord-296691-cg463fbn.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296691-cg463fbn.txt' === file2bib.sh === id: cord-287784-f7usy52w author: Maestre, Ana M. title: Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells date: 2011-06-15 pages: extension: .txt txt: ./txt/cord-287784-f7usy52w.txt cache: ./cache/cord-287784-f7usy52w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287784-f7usy52w.txt' === file2bib.sh === id: cord-292475-jrl1fowa author: Abry, Patrice title: Spatial and temporal regularization to estimate COVID-19 reproduction number R(t): Promoting piecewise smoothness via convex optimization date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-292475-jrl1fowa.txt cache: ./cache/cord-292475-jrl1fowa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292475-jrl1fowa.txt' === file2bib.sh === id: cord-299491-8rfm0jxh author: Xiao, Shenglan title: Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong date: 2017-07-20 pages: extension: .txt txt: ./txt/cord-299491-8rfm0jxh.txt cache: ./cache/cord-299491-8rfm0jxh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-299491-8rfm0jxh.txt' === file2bib.sh === id: cord-299953-sasfvcun author: Whitehead, Ashley B. R. title: Burden of exposure to infectious bursal disease virus, infectious bronchitis virus, Newcastle disease virus, Mycoplasma gallisepticum, and intestinal parasites in introduced broiler chickens on the Galapagos date: 2018-09-24 pages: extension: .txt txt: ./txt/cord-299953-sasfvcun.txt cache: ./cache/cord-299953-sasfvcun.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-299953-sasfvcun.txt' === file2bib.sh === id: cord-290446-43h1r4pm author: Vazquez, Leonardo title: Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus date: 2017-07-27 pages: extension: .txt txt: ./txt/cord-290446-43h1r4pm.txt cache: ./cache/cord-290446-43h1r4pm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-290446-43h1r4pm.txt' === file2bib.sh === id: cord-297287-0i4nc353 author: Braun, Benjamin title: Simulating phase transitions and control measures for network epidemics caused by infections with presymptomatic, asymptomatic, and symptomatic stages date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-297287-0i4nc353.txt cache: ./cache/cord-297287-0i4nc353.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297287-0i4nc353.txt' === file2bib.sh === id: cord-302189-3xab3yxc author: Tillmann, Ramona Liza title: Sensitive Commercial NASBA Assay for the Detection of Respiratory Syncytial Virus in Clinical Specimen date: 2007-12-26 pages: extension: .txt txt: ./txt/cord-302189-3xab3yxc.txt cache: ./cache/cord-302189-3xab3yxc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302189-3xab3yxc.txt' === file2bib.sh === id: cord-302529-43pd2qsp author: El Moussi, Awatef title: Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia date: 2013-09-19 pages: extension: .txt txt: ./txt/cord-302529-43pd2qsp.txt cache: ./cache/cord-302529-43pd2qsp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302529-43pd2qsp.txt' === file2bib.sh === id: cord-301180-ndiwmnv0 author: Lin, Min-Hsuan title: Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking date: 2012-12-10 pages: extension: .txt txt: ./txt/cord-301180-ndiwmnv0.txt cache: ./cache/cord-301180-ndiwmnv0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301180-ndiwmnv0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68031 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67447 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68197 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-302200-9gekjgr0 author: Kilich, Eliz title: Factors that influence vaccination decision-making among pregnant women: A systematic review and meta-analysis date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-302200-9gekjgr0.txt cache: ./cache/cord-302200-9gekjgr0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302200-9gekjgr0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67290 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-305547-e66o5j85 author: Bénet, Thomas title: Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study date: 2015-12-22 pages: extension: .txt txt: ./txt/cord-305547-e66o5j85.txt cache: ./cache/cord-305547-e66o5j85.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305547-e66o5j85.txt' === file2bib.sh === id: cord-306466-y4yg42p8 author: Nofal, Ahmed Maged title: Who complies with COVID-19 transmission mitigation behavioral guidelines? date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-306466-y4yg42p8.txt cache: ./cache/cord-306466-y4yg42p8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306466-y4yg42p8.txt' === file2bib.sh === id: cord-302355-3se1wp8o author: Chen, Yi-Shiuan title: The conserved stem-loop II structure at the 3' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA date: 2018-07-26 pages: extension: .txt txt: ./txt/cord-302355-3se1wp8o.txt cache: ./cache/cord-302355-3se1wp8o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302355-3se1wp8o.txt' === file2bib.sh === id: cord-298078-uqrwq5qk author: Kwak, Hoyun title: Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus date: 2011-08-30 pages: extension: .txt txt: ./txt/cord-298078-uqrwq5qk.txt cache: ./cache/cord-298078-uqrwq5qk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298078-uqrwq5qk.txt' === file2bib.sh === id: cord-299852-t0mqe7yy author: Janssen, Loes H. C. title: Does the COVID-19 pandemic impact parents’ and adolescents’ well-being? An EMA-study on daily affect and parenting date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-299852-t0mqe7yy.txt cache: ./cache/cord-299852-t0mqe7yy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-299852-t0mqe7yy.txt' === file2bib.sh === id: cord-305071-4ck8nd24 author: Calvo, Cristina title: Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses date: 2015-07-06 pages: extension: .txt txt: ./txt/cord-305071-4ck8nd24.txt cache: ./cache/cord-305071-4ck8nd24.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305071-4ck8nd24.txt' === file2bib.sh === id: cord-301811-ykpiorgo author: Tanaka, Takuma title: Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-301811-ykpiorgo.txt cache: ./cache/cord-301811-ykpiorgo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301811-ykpiorgo.txt' === file2bib.sh === id: cord-295559-yc8q62z8 author: Qian, Zhaohui title: Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation date: 2013-10-03 pages: extension: .txt txt: ./txt/cord-295559-yc8q62z8.txt cache: ./cache/cord-295559-yc8q62z8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-295559-yc8q62z8.txt' === file2bib.sh === id: cord-303331-xolksoy3 author: Pourghasemi, Hamid Reza title: Assessment of the outbreak risk, mapping and infection behavior of COVID-19: Application of the autoregressive integrated-moving average (ARIMA) and polynomial models date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-303331-xolksoy3.txt cache: ./cache/cord-303331-xolksoy3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303331-xolksoy3.txt' === file2bib.sh === id: cord-302962-qw6s1t7j author: Hause, Ben M. title: Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease date: 2015-03-19 pages: extension: .txt txt: ./txt/cord-302962-qw6s1t7j.txt cache: ./cache/cord-302962-qw6s1t7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-302962-qw6s1t7j.txt' === file2bib.sh === id: cord-306958-8bx8kxxh author: Christensen, Sarah R. title: Political and personal reactions to COVID-19 during initial weeks of social distancing in the United States date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-306958-8bx8kxxh.txt cache: ./cache/cord-306958-8bx8kxxh.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306958-8bx8kxxh.txt' === file2bib.sh === id: cord-309981-4p3ybrn1 author: Dai, Ling-Ling title: Anxiety and depressive symptoms among COVID-19 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-309981-4p3ybrn1.txt cache: ./cache/cord-309981-4p3ybrn1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309981-4p3ybrn1.txt' === file2bib.sh === id: cord-310061-nro623aa author: Valitutto, Marc T. title: Detection of novel coronaviruses in bats in Myanmar date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-310061-nro623aa.txt cache: ./cache/cord-310061-nro623aa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-310061-nro623aa.txt' === file2bib.sh === id: cord-306278-c4q4la5c author: Esposito, Susanna title: Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014 date: 2016-04-05 pages: extension: .txt txt: ./txt/cord-306278-c4q4la5c.txt cache: ./cache/cord-306278-c4q4la5c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306278-c4q4la5c.txt' === file2bib.sh === id: cord-305274-mcsdem7y author: Beniac, Daniel R. title: Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion date: 2007-10-24 pages: extension: .txt txt: ./txt/cord-305274-mcsdem7y.txt cache: ./cache/cord-305274-mcsdem7y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305274-mcsdem7y.txt' === file2bib.sh === id: cord-304993-t4rua95e author: Jung, Kwonil title: The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals date: 2012-07-23 pages: extension: .txt txt: ./txt/cord-304993-t4rua95e.txt cache: ./cache/cord-304993-t4rua95e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304993-t4rua95e.txt' === file2bib.sh === id: cord-309621-6jj19xpr author: Yu, Pin title: Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus date: 2017-02-24 pages: extension: .txt txt: ./txt/cord-309621-6jj19xpr.txt cache: ./cache/cord-309621-6jj19xpr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309621-6jj19xpr.txt' === file2bib.sh === id: cord-309194-jtouafgd author: Lu, Xiao title: Lung ultrasound score in establishing the timing of intubation in COVID-19 interstitial pneumonia: A preliminary retrospective observational study date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-309194-jtouafgd.txt cache: ./cache/cord-309194-jtouafgd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-309194-jtouafgd.txt' === file2bib.sh === id: cord-310678-33c3mp1o author: Morgantini, Luca A. title: Factors contributing to healthcare professional burnout during the COVID-19 pandemic: A rapid turnaround global survey date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-310678-33c3mp1o.txt cache: ./cache/cord-310678-33c3mp1o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310678-33c3mp1o.txt' === file2bib.sh === id: cord-304616-k92fa15l author: Izes, Aaron M. title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-304616-k92fa15l.txt cache: ./cache/cord-304616-k92fa15l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-304616-k92fa15l.txt' === file2bib.sh === id: cord-306135-pt4jsr6d author: Chan, Kamfai title: A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics date: 2016-02-12 pages: extension: .txt txt: ./txt/cord-306135-pt4jsr6d.txt cache: ./cache/cord-306135-pt4jsr6d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306135-pt4jsr6d.txt' === file2bib.sh === id: cord-308344-ao9z00t7 author: Diep, Nguyen Van title: Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation date: 2017-01-17 pages: extension: .txt txt: ./txt/cord-308344-ao9z00t7.txt cache: ./cache/cord-308344-ao9z00t7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308344-ao9z00t7.txt' === file2bib.sh === id: cord-303034-w72oeoxq author: Haischer, Michael H. title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-303034-w72oeoxq.txt cache: ./cache/cord-303034-w72oeoxq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303034-w72oeoxq.txt' === file2bib.sh === id: cord-312367-24huwt3y author: Coelho, Camila title: Biochemical screening for SARS-CoV-2 main protease inhibitors date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-312367-24huwt3y.txt cache: ./cache/cord-312367-24huwt3y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312367-24huwt3y.txt' === file2bib.sh === id: cord-303490-rixuuytu author: Pazos, Michael A. title: Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice date: 2012-07-05 pages: extension: .txt txt: ./txt/cord-303490-rixuuytu.txt cache: ./cache/cord-303490-rixuuytu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303490-rixuuytu.txt' === file2bib.sh === id: cord-310466-0lbbiq7u author: Fu, Yang-chih title: Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan date: 2012-10-03 pages: extension: .txt txt: ./txt/cord-310466-0lbbiq7u.txt cache: ./cache/cord-310466-0lbbiq7u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310466-0lbbiq7u.txt' === file2bib.sh === id: cord-311074-j3fw4dfc author: Alviset, Sophie title: Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-311074-j3fw4dfc.txt cache: ./cache/cord-311074-j3fw4dfc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-311074-j3fw4dfc.txt' === file2bib.sh === id: cord-310790-3ikgmiof author: Cherrak, Sabri Ahmed title: Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-310790-3ikgmiof.txt cache: ./cache/cord-310790-3ikgmiof.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310790-3ikgmiof.txt' === file2bib.sh === id: cord-308261-hxlebas8 author: Broekhuis, Femke title: Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya date: 2019-04-03 pages: extension: .txt txt: ./txt/cord-308261-hxlebas8.txt cache: ./cache/cord-308261-hxlebas8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-308261-hxlebas8.txt' === file2bib.sh === id: cord-303845-y6ws3u6x author: DeLisle, Sylvain title: Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections date: 2010-10-14 pages: extension: .txt txt: ./txt/cord-303845-y6ws3u6x.txt cache: ./cache/cord-303845-y6ws3u6x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303845-y6ws3u6x.txt' === file2bib.sh === id: cord-310438-744r7gc3 author: Chan, Ta-Chien title: The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly date: 2010-06-25 pages: extension: .txt txt: ./txt/cord-310438-744r7gc3.txt cache: ./cache/cord-310438-744r7gc3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-310438-744r7gc3.txt' === file2bib.sh === id: cord-308249-es948mux author: Dokuka, Sofia title: How academic achievement spreads: The role of distinct social networks in academic performance diffusion date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-308249-es948mux.txt cache: ./cache/cord-308249-es948mux.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-308249-es948mux.txt' === file2bib.sh === id: cord-312493-wbhji81g author: Tay, Ee Laine title: Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance date: 2013-10-11 pages: extension: .txt txt: ./txt/cord-312493-wbhji81g.txt cache: ./cache/cord-312493-wbhji81g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312493-wbhji81g.txt' === file2bib.sh === id: cord-308480-t2vukbwp author: Liang, Zhongjie title: Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant date: 2011-08-24 pages: extension: .txt txt: ./txt/cord-308480-t2vukbwp.txt cache: ./cache/cord-308480-t2vukbwp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308480-t2vukbwp.txt' === file2bib.sh === id: cord-307540-dr5m9pfk author: Coelho, Flávio C. title: Assessing the spread of COVID-19 in Brazil: Mobility, morbidity and social vulnerability date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-307540-dr5m9pfk.txt cache: ./cache/cord-307540-dr5m9pfk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307540-dr5m9pfk.txt' === file2bib.sh === id: cord-311531-wezrs7gc author: Parčina, Marijo title: Multicenter evaluation of the QIAstat Respiratory Panel—A new rapid highly multiplexed PCR based assay for diagnosis of acute respiratory tract infections date: 2020-03-12 pages: extension: .txt txt: ./txt/cord-311531-wezrs7gc.txt cache: ./cache/cord-311531-wezrs7gc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311531-wezrs7gc.txt' === file2bib.sh === id: cord-317244-4su5on6s author: Maganga, Gael D. title: Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity date: 2014-12-31 pages: extension: .txt txt: ./txt/cord-317244-4su5on6s.txt cache: ./cache/cord-317244-4su5on6s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317244-4su5on6s.txt' === file2bib.sh === id: cord-303187-ny4qr2a2 author: Belo, Vinícius Silva title: Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil date: 2017-11-01 pages: extension: .txt txt: ./txt/cord-303187-ny4qr2a2.txt cache: ./cache/cord-303187-ny4qr2a2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303187-ny4qr2a2.txt' === file2bib.sh === id: cord-300859-nqklx0vn author: Henderson, Kelley C. title: Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection date: 2015-06-29 pages: extension: .txt txt: ./txt/cord-300859-nqklx0vn.txt cache: ./cache/cord-300859-nqklx0vn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300859-nqklx0vn.txt' === file2bib.sh === id: cord-312033-iarl77n0 author: López Barreda, Rodrigo title: Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-312033-iarl77n0.txt cache: ./cache/cord-312033-iarl77n0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312033-iarl77n0.txt' === file2bib.sh === id: cord-305811-987dhnf7 author: Cho, Che-Pei title: Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins date: 2013-04-29 pages: extension: .txt txt: ./txt/cord-305811-987dhnf7.txt cache: ./cache/cord-305811-987dhnf7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305811-987dhnf7.txt' === file2bib.sh === id: cord-313107-6cfenpxm author: Singh, Anirudh K. title: Evaluation of pooled sample analysis strategy in expediting case detection in areas with emerging outbreaks of COVID-19: A pilot study date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-313107-6cfenpxm.txt cache: ./cache/cord-313107-6cfenpxm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-313107-6cfenpxm.txt' === file2bib.sh === id: cord-307934-84zfabti author: Lai, Chao-Kuen title: Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date: 2014-06-06 pages: extension: .txt txt: ./txt/cord-307934-84zfabti.txt cache: ./cache/cord-307934-84zfabti.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307934-84zfabti.txt' === file2bib.sh === id: cord-311065-ie3gty6e author: Gaddi, Pamela J. title: IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection date: 2012-08-03 pages: extension: .txt txt: ./txt/cord-311065-ie3gty6e.txt cache: ./cache/cord-311065-ie3gty6e.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311065-ie3gty6e.txt' === file2bib.sh === id: cord-312002-4qhvljpv author: Pacheco-Barrios, Kevin title: COVID-19 pandemic and Farr’s law: A global comparison and prediction of outbreak acceleration and deceleration rates date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-312002-4qhvljpv.txt cache: ./cache/cord-312002-4qhvljpv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312002-4qhvljpv.txt' === file2bib.sh === id: cord-319538-bawzonq1 author: Krause, Martin title: Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-319538-bawzonq1.txt cache: ./cache/cord-319538-bawzonq1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319538-bawzonq1.txt' === file2bib.sh === id: cord-305303-82n96ukr author: Shapira, Assaf title: Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date: 2012-02-16 pages: extension: .txt txt: ./txt/cord-305303-82n96ukr.txt cache: ./cache/cord-305303-82n96ukr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305303-82n96ukr.txt' === file2bib.sh === id: cord-307036-n44yml79 author: Ng, Oi-Wing title: Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody date: 2014-07-14 pages: extension: .txt txt: ./txt/cord-307036-n44yml79.txt cache: ./cache/cord-307036-n44yml79.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307036-n44yml79.txt' === file2bib.sh === id: cord-316319-m6uha1qn author: Daleno, Cristina title: Phylogenetic Analysis of Human Rhinovirus Isolates Collected from Otherwise Healthy Children with Community-Acquired Pneumonia during Five Successive Years date: 2013-11-19 pages: extension: .txt txt: ./txt/cord-316319-m6uha1qn.txt cache: ./cache/cord-316319-m6uha1qn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316319-m6uha1qn.txt' === file2bib.sh === id: cord-310947-aqau2n7q author: Pan, Ji'An title: Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date: 2008-10-01 pages: extension: .txt txt: ./txt/cord-310947-aqau2n7q.txt cache: ./cache/cord-310947-aqau2n7q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310947-aqau2n7q.txt' === file2bib.sh === id: cord-317912-v2wovcqd author: Akmatov, Manas K. title: Equivalence of Self- and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens date: 2012-11-14 pages: extension: .txt txt: ./txt/cord-317912-v2wovcqd.txt cache: ./cache/cord-317912-v2wovcqd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317912-v2wovcqd.txt' === file2bib.sh === id: cord-315343-ywgoqlxj author: Ribeiro, Haroldo V. title: City size and the spreading of COVID-19 in Brazil date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-315343-ywgoqlxj.txt cache: ./cache/cord-315343-ywgoqlxj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315343-ywgoqlxj.txt' === file2bib.sh === id: cord-314651-e4uaw5fy author: Zhao, Guangyu title: Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus date: 2015-12-23 pages: extension: .txt txt: ./txt/cord-314651-e4uaw5fy.txt cache: ./cache/cord-314651-e4uaw5fy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314651-e4uaw5fy.txt' === file2bib.sh === id: cord-310396-jitao9k0 author: Lei, Yu title: MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins date: 2009-03-07 pages: extension: .txt txt: ./txt/cord-310396-jitao9k0.txt cache: ./cache/cord-310396-jitao9k0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310396-jitao9k0.txt' === file2bib.sh === id: cord-311941-0dpm35dd author: Jones, Bryony A. title: Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study date: 2013-12-02 pages: extension: .txt txt: ./txt/cord-311941-0dpm35dd.txt cache: ./cache/cord-311941-0dpm35dd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311941-0dpm35dd.txt' === file2bib.sh === id: cord-316703-8kxx3034 author: Parera, Mariona title: Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date: 2012-08-01 pages: extension: .txt txt: ./txt/cord-316703-8kxx3034.txt cache: ./cache/cord-316703-8kxx3034.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-316703-8kxx3034.txt' === file2bib.sh === id: cord-312678-81gnmxbk author: Elayeh, Eman title: Before and after case reporting: A comparison of the knowledge, attitude and practices of the Jordanian population towards COVID-19 date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-312678-81gnmxbk.txt cache: ./cache/cord-312678-81gnmxbk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312678-81gnmxbk.txt' === file2bib.sh === id: cord-305900-ht7hb2rc author: van den Brand, Judith M. A. title: Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets date: 2012-08-08 pages: extension: .txt txt: ./txt/cord-305900-ht7hb2rc.txt cache: ./cache/cord-305900-ht7hb2rc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305900-ht7hb2rc.txt' === file2bib.sh === id: cord-321855-7b1c2xdh author: Alshami, Alanoud title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-321855-7b1c2xdh.txt cache: ./cache/cord-321855-7b1c2xdh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321855-7b1c2xdh.txt' === file2bib.sh === id: cord-308764-9z4qcoqz author: Wei, Lin title: Transcriptome Analysis of Houttuynia cordata Thunb. by Illumina Paired-End RNA Sequencing and SSR Marker Discovery date: 2014-01-02 pages: extension: .txt txt: ./txt/cord-308764-9z4qcoqz.txt cache: ./cache/cord-308764-9z4qcoqz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308764-9z4qcoqz.txt' === file2bib.sh === id: cord-298131-zolwjl9u author: Xiao, Shuqi title: Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date: 2010-06-29 pages: extension: .txt txt: ./txt/cord-298131-zolwjl9u.txt cache: ./cache/cord-298131-zolwjl9u.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298131-zolwjl9u.txt' === file2bib.sh === id: cord-318614-518giv0m author: Tsai, Jih-Jin title: A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos date: 2019-07-10 pages: extension: .txt txt: ./txt/cord-318614-518giv0m.txt cache: ./cache/cord-318614-518giv0m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318614-518giv0m.txt' === file2bib.sh === id: cord-316853-vaea6siv author: Xie, Nanzhen title: Prevalence of depressive symptoms among nurses in China: A systematic review and meta-analysis date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-316853-vaea6siv.txt cache: ./cache/cord-316853-vaea6siv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316853-vaea6siv.txt' === file2bib.sh === id: cord-319706-2e9jrv0s author: Ebinger, Joseph E. title: Pre-existing traits associated with Covid-19 illness severity date: 2020-07-23 pages: extension: .txt txt: ./txt/cord-319706-2e9jrv0s.txt cache: ./cache/cord-319706-2e9jrv0s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319706-2e9jrv0s.txt' === file2bib.sh === id: cord-312817-gskbu0oh author: Witte, Carmel title: Spatiotemporal network structure among “friends of friends” reveals contagious disease process date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-312817-gskbu0oh.txt cache: ./cache/cord-312817-gskbu0oh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312817-gskbu0oh.txt' === file2bib.sh === id: cord-315531-2gc2dc46 author: McGarvey, Peter B. title: Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date: 2009-09-25 pages: extension: .txt txt: ./txt/cord-315531-2gc2dc46.txt cache: ./cache/cord-315531-2gc2dc46.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315531-2gc2dc46.txt' === file2bib.sh === id: cord-309010-tmfm5u5h author: Dietert, Kristina title: Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia date: 2017-11-20 pages: extension: .txt txt: ./txt/cord-309010-tmfm5u5h.txt cache: ./cache/cord-309010-tmfm5u5h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309010-tmfm5u5h.txt' === file2bib.sh === id: cord-311288-6ttux2uu author: Luo, Chen title: What triggers online help-seeking retransmission during the COVID-19 period? Empirical evidence from Chinese social media date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-311288-6ttux2uu.txt cache: ./cache/cord-311288-6ttux2uu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311288-6ttux2uu.txt' === file2bib.sh === id: cord-318008-4s9eoae3 author: Parsons Leigh, Jeanna title: A national cross-sectional survey of public perceptions of the COVID-19 pandemic: Self-reported beliefs, knowledge, and behaviors date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-318008-4s9eoae3.txt cache: ./cache/cord-318008-4s9eoae3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318008-4s9eoae3.txt' === file2bib.sh === id: cord-320466-l7017jis author: Akgun, Emel title: Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-320466-l7017jis.txt cache: ./cache/cord-320466-l7017jis.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320466-l7017jis.txt' === file2bib.sh === id: cord-313506-6bb4q7nv author: Sano, Akiko title: Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle date: 2013-10-24 pages: extension: .txt txt: ./txt/cord-313506-6bb4q7nv.txt cache: ./cache/cord-313506-6bb4q7nv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313506-6bb4q7nv.txt' === file2bib.sh === id: cord-319675-mwy3t1ny author: Gu, Li title: Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia date: 2016-08-17 pages: extension: .txt txt: ./txt/cord-319675-mwy3t1ny.txt cache: ./cache/cord-319675-mwy3t1ny.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319675-mwy3t1ny.txt' === file2bib.sh === id: cord-309471-lr68epyb author: Xia, Jingya title: Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs date: 2014-12-08 pages: extension: .txt txt: ./txt/cord-309471-lr68epyb.txt cache: ./cache/cord-309471-lr68epyb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-309471-lr68epyb.txt' === file2bib.sh === id: cord-322414-dpx191xh author: Harke, Nina N. title: To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-322414-dpx191xh.txt cache: ./cache/cord-322414-dpx191xh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322414-dpx191xh.txt' === file2bib.sh === id: cord-319190-esjfhztp author: Lu, Xi title: In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus date: 2013-07-02 pages: extension: .txt txt: ./txt/cord-319190-esjfhztp.txt cache: ./cache/cord-319190-esjfhztp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319190-esjfhztp.txt' === file2bib.sh === id: cord-309043-dlmx12vt author: von Brunn, Albrecht title: Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date: 2007-05-23 pages: extension: .txt txt: ./txt/cord-309043-dlmx12vt.txt cache: ./cache/cord-309043-dlmx12vt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309043-dlmx12vt.txt' === file2bib.sh === id: cord-319845-oob2ktnz author: Proença-Modena, José Luiz title: Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea date: 2011-06-20 pages: extension: .txt txt: ./txt/cord-319845-oob2ktnz.txt cache: ./cache/cord-319845-oob2ktnz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319845-oob2ktnz.txt' === file2bib.sh === id: cord-321705-6a7avlro author: Hou, Tianya title: Social support and mental health among health care workers during Coronavirus Disease 2019 outbreak: A moderated mediation model date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-321705-6a7avlro.txt cache: ./cache/cord-321705-6a7avlro.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321705-6a7avlro.txt' === file2bib.sh === id: cord-305393-96mrxt8a author: Lai, Yvonne title: Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date: 2011-10-10 pages: extension: .txt txt: ./txt/cord-305393-96mrxt8a.txt cache: ./cache/cord-305393-96mrxt8a.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305393-96mrxt8a.txt' === file2bib.sh === id: cord-323433-9km824uh author: van den Wijngaard, Cees C. title: Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work? date: 2010-04-29 pages: extension: .txt txt: ./txt/cord-323433-9km824uh.txt cache: ./cache/cord-323433-9km824uh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323433-9km824uh.txt' === file2bib.sh === id: cord-319921-uxtydu60 author: Meli, Marina L. title: Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus) date: 2009-03-09 pages: extension: .txt txt: ./txt/cord-319921-uxtydu60.txt cache: ./cache/cord-319921-uxtydu60.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319921-uxtydu60.txt' === file2bib.sh === id: cord-321624-z2mntwef author: Kowitdamrong, Ekasit title: Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-321624-z2mntwef.txt cache: ./cache/cord-321624-z2mntwef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321624-z2mntwef.txt' === file2bib.sh === id: cord-321834-n5w88l23 author: Huang, Cheng-Yang title: Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases date: 2015-05-19 pages: extension: .txt txt: ./txt/cord-321834-n5w88l23.txt cache: ./cache/cord-321834-n5w88l23.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321834-n5w88l23.txt' === file2bib.sh === id: cord-314908-kp2jznwb author: Roczniewska, Marta title: I believe I can craft! introducing Job Crafting Self-Efficacy Scale (JCSES) date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-314908-kp2jznwb.txt cache: ./cache/cord-314908-kp2jznwb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314908-kp2jznwb.txt' === file2bib.sh === id: cord-324359-88vy3dre author: Kamara, Foday Mamoud title: How villagers in central Sierra Leone understand infection risks under threat of Covid-19 date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-324359-88vy3dre.txt cache: ./cache/cord-324359-88vy3dre.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-324359-88vy3dre.txt' === file2bib.sh === id: cord-317779-j67vb7f3 author: Irizarry, Kristopher J. L. title: RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date: 2017-08-28 pages: extension: .txt txt: ./txt/cord-317779-j67vb7f3.txt cache: ./cache/cord-317779-j67vb7f3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-317779-j67vb7f3.txt' === file2bib.sh === id: cord-324410-be2ith3z author: Wang, Qi title: Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry date: 2007-06-13 pages: extension: .txt txt: ./txt/cord-324410-be2ith3z.txt cache: ./cache/cord-324410-be2ith3z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-324410-be2ith3z.txt' === file2bib.sh === id: cord-327257-doygrgrc author: Zhu, Jocelyn title: Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-327257-doygrgrc.txt cache: ./cache/cord-327257-doygrgrc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-327257-doygrgrc.txt' === file2bib.sh === id: cord-322533-adqqm0n9 author: Sha, Dexuan title: Spatiotemporal analysis of medical resource deficiencies in the U.S. under COVID-19 pandemic date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-322533-adqqm0n9.txt cache: ./cache/cord-322533-adqqm0n9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322533-adqqm0n9.txt' === file2bib.sh === id: cord-322827-h33su548 author: Guan, Lili title: Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives date: 2015-04-07 pages: extension: .txt txt: ./txt/cord-322827-h33su548.txt cache: ./cache/cord-322827-h33su548.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-322827-h33su548.txt' === file2bib.sh === id: cord-326011-5rmhjbri author: Cui, Dawei title: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study date: 2016-11-01 pages: extension: .txt txt: ./txt/cord-326011-5rmhjbri.txt cache: ./cache/cord-326011-5rmhjbri.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326011-5rmhjbri.txt' === file2bib.sh === id: cord-323330-ghwhgkdm author: Ekundayo, Temitope Cyrus title: A global bibliometric analysis of Plesiomonas-related research (1990 – 2017) date: 2018-11-29 pages: extension: .txt txt: ./txt/cord-323330-ghwhgkdm.txt cache: ./cache/cord-323330-ghwhgkdm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323330-ghwhgkdm.txt' === file2bib.sh === id: cord-321438-llnqzkqt author: Ma, Ruili title: Proteome Profile of Swine Testicular Cells Infected with Porcine Transmissible Gastroenteritis Coronavirus date: 2014-10-21 pages: extension: .txt txt: ./txt/cord-321438-llnqzkqt.txt cache: ./cache/cord-321438-llnqzkqt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321438-llnqzkqt.txt' === file2bib.sh === id: cord-331885-8zmuhebu author: Xu, Xiuyan title: Risk factor analysis combined with deep learning in the risk assessment of overseas investment of enterprises date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-331885-8zmuhebu.txt cache: ./cache/cord-331885-8zmuhebu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331885-8zmuhebu.txt' === file2bib.sh === id: cord-324091-nljd2ok1 author: Gordon, Jennifer L. title: The psychological impact of fertility treatment suspensions during the COVID-19 pandemic date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-324091-nljd2ok1.txt cache: ./cache/cord-324091-nljd2ok1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324091-nljd2ok1.txt' === file2bib.sh === id: cord-328206-iylw1bvw author: Yu, Daojun title: Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date: 2012-11-09 pages: extension: .txt txt: ./txt/cord-328206-iylw1bvw.txt cache: ./cache/cord-328206-iylw1bvw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328206-iylw1bvw.txt' === file2bib.sh === id: cord-318845-w7q5o8wc author: Pendell, Dustin L. title: Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility date: 2015-06-26 pages: extension: .txt txt: ./txt/cord-318845-w7q5o8wc.txt cache: ./cache/cord-318845-w7q5o8wc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318845-w7q5o8wc.txt' === file2bib.sh === id: cord-325113-sou8xyld author: Kuiper, Johannes W. P. title: Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-325113-sou8xyld.txt cache: ./cache/cord-325113-sou8xyld.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325113-sou8xyld.txt' === file2bib.sh === id: cord-330749-xt4aa2ur author: Schilling, Stefan title: Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries date: 2014-10-28 pages: extension: .txt txt: ./txt/cord-330749-xt4aa2ur.txt cache: ./cache/cord-330749-xt4aa2ur.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330749-xt4aa2ur.txt' === file2bib.sh === id: cord-320938-f526k9q1 author: Chen, Hongjun title: Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses date: 2012-09-28 pages: extension: .txt txt: ./txt/cord-320938-f526k9q1.txt cache: ./cache/cord-320938-f526k9q1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320938-f526k9q1.txt' === file2bib.sh === id: cord-334218-bkjfy66e author: Lin, Jung-Da title: Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak date: 2016-01-15 pages: extension: .txt txt: ./txt/cord-334218-bkjfy66e.txt cache: ./cache/cord-334218-bkjfy66e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334218-bkjfy66e.txt' === file2bib.sh === id: cord-329727-h47q76y8 author: Sisó-Almirall, Antoni title: Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-329727-h47q76y8.txt cache: ./cache/cord-329727-h47q76y8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329727-h47q76y8.txt' === file2bib.sh === id: cord-326568-twv2i3fb author: Bruminhent, Jackrapong title: Clinical characteristics and risk factors for coronavirus disease 2019 (COVID-19) among patients under investigation in Thailand date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-326568-twv2i3fb.txt cache: ./cache/cord-326568-twv2i3fb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326568-twv2i3fb.txt' === file2bib.sh === id: cord-327199-ggomuomb author: Moerdyk-Schauwecker, Megan title: Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date: 2014-08-08 pages: extension: .txt txt: ./txt/cord-327199-ggomuomb.txt cache: ./cache/cord-327199-ggomuomb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327199-ggomuomb.txt' === file2bib.sh === id: cord-323133-gdg50omp author: Buzatto, G. P. title: The pathogens profile in children with otitis media with effusion and adenoid hypertrophy date: 2017-02-23 pages: extension: .txt txt: ./txt/cord-323133-gdg50omp.txt cache: ./cache/cord-323133-gdg50omp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323133-gdg50omp.txt' === file2bib.sh === id: cord-335505-s013j5ex author: Zhang, Chen title: Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China date: 2013-08-22 pages: extension: .txt txt: ./txt/cord-335505-s013j5ex.txt cache: ./cache/cord-335505-s013j5ex.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335505-s013j5ex.txt' === file2bib.sh === id: cord-335859-k37jivp6 author: Wu, Daphne C. title: Predictors of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-335859-k37jivp6.txt cache: ./cache/cord-335859-k37jivp6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335859-k37jivp6.txt' === file2bib.sh === id: cord-324405-6uanhe2p author: Burke, Rachel M. title: Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-324405-6uanhe2p.txt cache: ./cache/cord-324405-6uanhe2p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324405-6uanhe2p.txt' === file2bib.sh === id: cord-333853-p2kbjwpy author: Smee, Donald F. title: Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) date: 2011-10-13 pages: extension: .txt txt: ./txt/cord-333853-p2kbjwpy.txt cache: ./cache/cord-333853-p2kbjwpy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333853-p2kbjwpy.txt' === file2bib.sh === id: cord-332922-2qjae0x7 author: Mbuvha, Rendani title: Bayesian inference of COVID-19 spreading rates in South Africa date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-332922-2qjae0x7.txt cache: ./cache/cord-332922-2qjae0x7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332922-2qjae0x7.txt' === file2bib.sh === id: cord-320091-2lrqubdl author: Badawi, Alaa title: Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis date: 2018-07-10 pages: extension: .txt txt: ./txt/cord-320091-2lrqubdl.txt cache: ./cache/cord-320091-2lrqubdl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320091-2lrqubdl.txt' === file2bib.sh === id: cord-333208-tibtngy8 author: Muñoz-Moreno, Raquel title: Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date: 2016-04-26 pages: extension: .txt txt: ./txt/cord-333208-tibtngy8.txt cache: ./cache/cord-333208-tibtngy8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333208-tibtngy8.txt' === file2bib.sh === id: cord-323185-n0rubc72 author: Varshney, Bhavna title: SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b date: 2012-01-12 pages: extension: .txt txt: ./txt/cord-323185-n0rubc72.txt cache: ./cache/cord-323185-n0rubc72.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323185-n0rubc72.txt' === file2bib.sh === id: cord-327534-f2wvh6la author: Zhou, Peng title: IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation date: 2014-08-06 pages: extension: .txt txt: ./txt/cord-327534-f2wvh6la.txt cache: ./cache/cord-327534-f2wvh6la.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327534-f2wvh6la.txt' === file2bib.sh === id: cord-339157-wj47xeqj author: Zhang, Chao title: Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease date: 2018-05-23 pages: extension: .txt txt: ./txt/cord-339157-wj47xeqj.txt cache: ./cache/cord-339157-wj47xeqj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-339157-wj47xeqj.txt' === file2bib.sh === id: cord-336420-1a2u9p4t author: Söderman, Martina title: Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study date: 2016-06-16 pages: extension: .txt txt: ./txt/cord-336420-1a2u9p4t.txt cache: ./cache/cord-336420-1a2u9p4t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336420-1a2u9p4t.txt' === file2bib.sh === id: cord-330079-pdaowkop author: Xu, Lin title: Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China date: 2012-09-11 pages: extension: .txt txt: ./txt/cord-330079-pdaowkop.txt cache: ./cache/cord-330079-pdaowkop.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330079-pdaowkop.txt' === file2bib.sh === id: cord-335880-m8gecsf0 author: Peci, Adriana title: Epidemiology of Enterovirus D68 in Ontario date: 2015-11-23 pages: extension: .txt txt: ./txt/cord-335880-m8gecsf0.txt cache: ./cache/cord-335880-m8gecsf0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335880-m8gecsf0.txt' === file2bib.sh === id: cord-337585-kpghvb6u author: Moustaqim-Barrette, Amina title: Accessing Take-Home Naloxone in British Columbia and the role of community pharmacies: Results from the analysis of administrative data date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-337585-kpghvb6u.txt cache: ./cache/cord-337585-kpghvb6u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337585-kpghvb6u.txt' === file2bib.sh === id: cord-336843-c0sr3six author: Gerritsen, M. G. title: Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography date: 2017-02-24 pages: extension: .txt txt: ./txt/cord-336843-c0sr3six.txt cache: ./cache/cord-336843-c0sr3six.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336843-c0sr3six.txt' === file2bib.sh === id: cord-316287-4i1grvlr author: Yim, Sung Sun title: Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS) date: 2014-10-10 pages: extension: .txt txt: ./txt/cord-316287-4i1grvlr.txt cache: ./cache/cord-316287-4i1grvlr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-316287-4i1grvlr.txt' === file2bib.sh === id: cord-333248-5342lyeu author: Elenius, Varpu title: The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response date: 2017-02-24 pages: extension: .txt txt: ./txt/cord-333248-5342lyeu.txt cache: ./cache/cord-333248-5342lyeu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333248-5342lyeu.txt' === file2bib.sh === id: cord-335404-s48psqth author: Mukandavire, Zindoga title: Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-335404-s48psqth.txt cache: ./cache/cord-335404-s48psqth.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335404-s48psqth.txt' === file2bib.sh === id: cord-333955-bnzbppof author: Biesold, Susanne E. title: Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date: 2011-11-30 pages: extension: .txt txt: ./txt/cord-333955-bnzbppof.txt cache: ./cache/cord-333955-bnzbppof.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333955-bnzbppof.txt' === file2bib.sh === id: cord-337795-khqx4t4q author: Pellecchia, Umberto title: Social Consequences of Ebola Containment Measures in Liberia date: 2015-12-09 pages: extension: .txt txt: ./txt/cord-337795-khqx4t4q.txt cache: ./cache/cord-337795-khqx4t4q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-337795-khqx4t4q.txt' === file2bib.sh === id: cord-330537-xz0wt1sz author: Biermann, Olivia title: Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-330537-xz0wt1sz.txt cache: ./cache/cord-330537-xz0wt1sz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-330537-xz0wt1sz.txt' === file2bib.sh === id: cord-333650-4towah1t author: Malmo, Jostein title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date: 2016-05-12 pages: extension: .txt txt: ./txt/cord-333650-4towah1t.txt cache: ./cache/cord-333650-4towah1t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333650-4towah1t.txt' === file2bib.sh === id: cord-329468-vjsurl60 author: Okino, Cintia Hiromi title: Early immune responses and development of pathogenesis of avian infectious bronchitis viruses with different virulence profiles date: 2017-02-15 pages: extension: .txt txt: ./txt/cord-329468-vjsurl60.txt cache: ./cache/cord-329468-vjsurl60.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329468-vjsurl60.txt' === file2bib.sh === id: cord-338067-vjyad10p author: Hao, Yan title: Prediction and analysis of Corona Virus Disease 2019 date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-338067-vjyad10p.txt cache: ./cache/cord-338067-vjyad10p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338067-vjyad10p.txt' === file2bib.sh === id: cord-336364-2ust3qoq author: Artigas, Laura title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-336364-2ust3qoq.txt cache: ./cache/cord-336364-2ust3qoq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336364-2ust3qoq.txt' === file2bib.sh === id: cord-339578-eg19rfvi author: Garcia-Garcia, Maria Luz title: Role of viral coinfections in asthma development date: 2017-12-05 pages: extension: .txt txt: ./txt/cord-339578-eg19rfvi.txt cache: ./cache/cord-339578-eg19rfvi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339578-eg19rfvi.txt' === file2bib.sh === id: cord-339327-4422s317 author: Norris, Susan L. title: An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks date: 2018-05-30 pages: extension: .txt txt: ./txt/cord-339327-4422s317.txt cache: ./cache/cord-339327-4422s317.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339327-4422s317.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-322446-ddv86eoy author: Sharma, Kulbhushan title: SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus date: 2011-05-27 pages: extension: .txt txt: ./txt/cord-322446-ddv86eoy.txt cache: ./cache/cord-322446-ddv86eoy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322446-ddv86eoy.txt' === file2bib.sh === id: cord-333413-8buawes0 author: Liebing, J. title: Health status of free-ranging ring-necked pheasant chicks (Phasianus colchicus) in North-Western Germany date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-333413-8buawes0.txt cache: ./cache/cord-333413-8buawes0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333413-8buawes0.txt' === file2bib.sh === id: cord-340027-6l55rcfm author: Mamode Khan, Naushad title: Studying the trend of the novel coronavirus series in Mauritius and its implications date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-340027-6l55rcfm.txt cache: ./cache/cord-340027-6l55rcfm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-340027-6l55rcfm.txt' === file2bib.sh === id: cord-339789-151d1j4n author: Hong, Hyokyoung G. title: Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-339789-151d1j4n.txt cache: ./cache/cord-339789-151d1j4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-339789-151d1j4n.txt' === file2bib.sh === id: cord-331652-oc5s1if2 author: Trudeau, Michaela P. title: Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) date: 2016-06-24 pages: extension: .txt txt: ./txt/cord-331652-oc5s1if2.txt cache: ./cache/cord-331652-oc5s1if2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-331652-oc5s1if2.txt' === file2bib.sh === id: cord-339026-eu11larc author: Ryals, Renee C. title: The effects of PEGylation on LNP based mRNA delivery to the eye date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-339026-eu11larc.txt cache: ./cache/cord-339026-eu11larc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339026-eu11larc.txt' === file2bib.sh === id: cord-336441-m6pur6td author: Wang, Changjian title: Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model date: 2019-02-11 pages: extension: .txt txt: ./txt/cord-336441-m6pur6td.txt cache: ./cache/cord-336441-m6pur6td.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336441-m6pur6td.txt' === file2bib.sh === id: cord-329223-f84gjxm1 author: Kouokam, Joseph Calvin title: Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate date: 2011-08-02 pages: extension: .txt txt: ./txt/cord-329223-f84gjxm1.txt cache: ./cache/cord-329223-f84gjxm1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329223-f84gjxm1.txt' === file2bib.sh === id: cord-328633-c31xsyeo author: Moser, Michael J. title: Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date: 2012-06-04 pages: extension: .txt txt: ./txt/cord-328633-c31xsyeo.txt cache: ./cache/cord-328633-c31xsyeo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328633-c31xsyeo.txt' === file2bib.sh === id: cord-328627-cf8f71dr author: Jando, Julia title: Expression and regulation of the neutral amino acid transporter B(0)AT1 in rat small intestine date: 2017-09-15 pages: extension: .txt txt: ./txt/cord-328627-cf8f71dr.txt cache: ./cache/cord-328627-cf8f71dr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328627-cf8f71dr.txt' === file2bib.sh === id: cord-338594-wft7yy6j author: Winkler, Michael title: Rhesus macaque IFITM3 gene polymorphisms and SIV infection date: 2017-03-03 pages: extension: .txt txt: ./txt/cord-338594-wft7yy6j.txt cache: ./cache/cord-338594-wft7yy6j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338594-wft7yy6j.txt' === file2bib.sh === id: cord-333522-zsdymkjd author: Gruse, Jeannine title: Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits date: 2016-01-11 pages: extension: .txt txt: ./txt/cord-333522-zsdymkjd.txt cache: ./cache/cord-333522-zsdymkjd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333522-zsdymkjd.txt' === file2bib.sh === id: cord-336615-jfnj6l41 author: Wong, Sarah Sze Wah title: In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections date: 2014-01-22 pages: extension: .txt txt: ./txt/cord-336615-jfnj6l41.txt cache: ./cache/cord-336615-jfnj6l41.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336615-jfnj6l41.txt' === file2bib.sh === id: cord-340718-amfs4zay author: Zhu, Gengping title: Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus date: 2014-04-01 pages: extension: .txt txt: ./txt/cord-340718-amfs4zay.txt cache: ./cache/cord-340718-amfs4zay.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340718-amfs4zay.txt' === file2bib.sh === id: cord-330110-pamxy4av author: Teissier, Elodie title: Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date: 2011-01-25 pages: extension: .txt txt: ./txt/cord-330110-pamxy4av.txt cache: ./cache/cord-330110-pamxy4av.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330110-pamxy4av.txt' === file2bib.sh === id: cord-335441-bj3me7p8 author: Jourdain, Elsa title: Influenza Virus in a Natural Host, the Mallard: Experimental Infection Data date: 2010-01-28 pages: extension: .txt txt: ./txt/cord-335441-bj3me7p8.txt cache: ./cache/cord-335441-bj3me7p8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-335441-bj3me7p8.txt' === file2bib.sh === id: cord-335245-1eksm537 author: Pattyn, Els title: HyperISGylation of Old World Monkey ISG15 in Human Cells date: 2008-06-18 pages: extension: .txt txt: ./txt/cord-335245-1eksm537.txt cache: ./cache/cord-335245-1eksm537.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335245-1eksm537.txt' === file2bib.sh === id: cord-339724-roj8ksvc author: Lan, Jiaming title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen date: 2014-11-18 pages: extension: .txt txt: ./txt/cord-339724-roj8ksvc.txt cache: ./cache/cord-339724-roj8ksvc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339724-roj8ksvc.txt' === file2bib.sh === id: cord-340195-425rd7ul author: Smith, Kristine M. title: Zoonotic Viruses Associated with Illegally Imported Wildlife Products date: 2012-01-10 pages: extension: .txt txt: ./txt/cord-340195-425rd7ul.txt cache: ./cache/cord-340195-425rd7ul.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340195-425rd7ul.txt' === file2bib.sh === id: cord-339869-euikj8fv author: Cebey-López, Miriam title: Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children? date: 2016-04-20 pages: extension: .txt txt: ./txt/cord-339869-euikj8fv.txt cache: ./cache/cord-339869-euikj8fv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339869-euikj8fv.txt' === file2bib.sh === id: cord-337879-liqhbqxl author: Kriesel, John D. title: Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain date: 2012-03-08 pages: extension: .txt txt: ./txt/cord-337879-liqhbqxl.txt cache: ./cache/cord-337879-liqhbqxl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337879-liqhbqxl.txt' === file2bib.sh === id: cord-334955-gnu92up6 author: Sutton, Jeannette title: COVID-19: Retransmission of official communications in an emerging pandemic date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-334955-gnu92up6.txt cache: ./cache/cord-334955-gnu92up6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334955-gnu92up6.txt' === file2bib.sh === id: cord-335272-jypxi99z author: Sharma, Anupam Joya title: A cross-sectional study of psychological wellbeing of Indian adults during the Covid-19 lockdown: Different strokes for different folks date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-335272-jypxi99z.txt cache: ./cache/cord-335272-jypxi99z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335272-jypxi99z.txt' === file2bib.sh === id: cord-340656-ltd6ueoi author: Grant, Michael C. title: The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-340656-ltd6ueoi.txt cache: ./cache/cord-340656-ltd6ueoi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-340656-ltd6ueoi.txt' === file2bib.sh === id: cord-334695-cjxlw1tu author: Kam, Yiu-Wing title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro date: 2009-11-17 pages: extension: .txt txt: ./txt/cord-334695-cjxlw1tu.txt cache: ./cache/cord-334695-cjxlw1tu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334695-cjxlw1tu.txt' === file2bib.sh === id: cord-340937-6mpob1nx author: Varshney, Mohit title: Initial psychological impact of COVID-19 and its correlates in Indian Community: An online (FEEL-COVID) survey date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-340937-6mpob1nx.txt cache: ./cache/cord-340937-6mpob1nx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340937-6mpob1nx.txt' === file2bib.sh === id: cord-340627-xyvzgkxl author: Ornaghi, Sara title: Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-340627-xyvzgkxl.txt cache: ./cache/cord-340627-xyvzgkxl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340627-xyvzgkxl.txt' === file2bib.sh === id: cord-340766-aic570x8 author: Kim, Se Jin title: Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia date: 2015-04-15 pages: extension: .txt txt: ./txt/cord-340766-aic570x8.txt cache: ./cache/cord-340766-aic570x8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340766-aic570x8.txt' === file2bib.sh === id: cord-343135-m0pdixw5 author: Marguet, Christophe title: In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses date: 2009-02-25 pages: extension: .txt txt: ./txt/cord-343135-m0pdixw5.txt cache: ./cache/cord-343135-m0pdixw5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343135-m0pdixw5.txt' === file2bib.sh === id: cord-342476-0rupk21u author: van Rijn, Anneloes L. title: The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease date: 2019-10-24 pages: extension: .txt txt: ./txt/cord-342476-0rupk21u.txt cache: ./cache/cord-342476-0rupk21u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342476-0rupk21u.txt' === file2bib.sh === id: cord-337630-ojhk5opy author: Tasic, Velibor title: Clinical and Functional Characterization of URAT1 Variants date: 2011-12-16 pages: extension: .txt txt: ./txt/cord-337630-ojhk5opy.txt cache: ./cache/cord-337630-ojhk5opy.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337630-ojhk5opy.txt' === file2bib.sh === id: cord-340703-vtuy806l author: Cascio, Antonio title: Low bone mineral density in HIV-positive young Italians and migrants date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-340703-vtuy806l.txt cache: ./cache/cord-340703-vtuy806l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340703-vtuy806l.txt' === file2bib.sh === id: cord-342133-khrljehj author: Principi, Nicola title: Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease date: 2015-08-12 pages: extension: .txt txt: ./txt/cord-342133-khrljehj.txt cache: ./cache/cord-342133-khrljehj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342133-khrljehj.txt' === file2bib.sh === id: cord-339392-2ocz784l author: Sharma, Kulbhushan title: Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation date: 2011-06-15 pages: extension: .txt txt: ./txt/cord-339392-2ocz784l.txt cache: ./cache/cord-339392-2ocz784l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339392-2ocz784l.txt' === file2bib.sh === id: cord-340713-v5sdowb7 author: Bird, Jordan J. title: Country-level pandemic risk and preparedness classification based on COVID-19 data: A machine learning approach date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-340713-v5sdowb7.txt cache: ./cache/cord-340713-v5sdowb7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340713-v5sdowb7.txt' === file2bib.sh === id: cord-341914-l2bomgji author: Flies, Andrew S. title: Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity date: 2015-10-07 pages: extension: .txt txt: ./txt/cord-341914-l2bomgji.txt cache: ./cache/cord-341914-l2bomgji.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341914-l2bomgji.txt' === file2bib.sh === id: cord-337913-eu2gn4bl author: Stojanov, Ana title: Does Perceived Lack of Control Lead to Conspiracy Theory Beliefs? Findings from an online MTurk sample date: 2020-08-17 pages: extension: .txt txt: ./txt/cord-337913-eu2gn4bl.txt cache: ./cache/cord-337913-eu2gn4bl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-337913-eu2gn4bl.txt' === file2bib.sh === id: cord-346089-u31n0qxa author: McDade, Thomas W. title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-346089-u31n0qxa.txt cache: ./cache/cord-346089-u31n0qxa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346089-u31n0qxa.txt' === file2bib.sh === id: cord-342519-tjr6dvtt author: Souza, Thiago Moreno L. title: H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis date: 2010-11-30 pages: extension: .txt txt: ./txt/cord-342519-tjr6dvtt.txt cache: ./cache/cord-342519-tjr6dvtt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342519-tjr6dvtt.txt' === file2bib.sh === id: cord-340763-cxnu9g8y author: Grimm, Sebastian K. title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies date: 2015-02-17 pages: extension: .txt txt: ./txt/cord-340763-cxnu9g8y.txt cache: ./cache/cord-340763-cxnu9g8y.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340763-cxnu9g8y.txt' === file2bib.sh === id: cord-344357-ocyaqs1y author: Fu, Yue-Qiang title: Effect of blood analysis and immune function on the prognosis of patients with COVID-19 date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-344357-ocyaqs1y.txt cache: ./cache/cord-344357-ocyaqs1y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344357-ocyaqs1y.txt' === file2bib.sh === id: cord-337067-j8ebslif author: Mades, Andreas title: Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date: 2012-11-15 pages: extension: .txt txt: ./txt/cord-337067-j8ebslif.txt cache: ./cache/cord-337067-j8ebslif.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337067-j8ebslif.txt' === file2bib.sh === id: cord-339920-dr5bvpm0 author: Soberman, Roy J. title: CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2 date: 2012-10-17 pages: extension: .txt txt: ./txt/cord-339920-dr5bvpm0.txt cache: ./cache/cord-339920-dr5bvpm0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339920-dr5bvpm0.txt' === file2bib.sh === id: cord-344839-r05p9h0e author: Majmundar, Monil title: Efficacy of corticosteroids in non-intensive care unit patients with COVID-19 pneumonia from the New York Metropolitan region date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-344839-r05p9h0e.txt cache: ./cache/cord-344839-r05p9h0e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344839-r05p9h0e.txt' === file2bib.sh === id: cord-343973-n5ogyxz7 author: Ip, Andrew title: Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—An observational study date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-343973-n5ogyxz7.txt cache: ./cache/cord-343973-n5ogyxz7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-343973-n5ogyxz7.txt' === file2bib.sh === id: cord-345717-ktajrf7d author: Monagin, Corina title: Serologic and behavioral risk survey of workers with wildlife contact in China date: 2018-04-03 pages: extension: .txt txt: ./txt/cord-345717-ktajrf7d.txt cache: ./cache/cord-345717-ktajrf7d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345717-ktajrf7d.txt' === file2bib.sh === id: cord-340387-ohkjheat author: Wynne, James W. title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date: 2013-01-07 pages: extension: .txt txt: ./txt/cord-340387-ohkjheat.txt cache: ./cache/cord-340387-ohkjheat.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340387-ohkjheat.txt' === file2bib.sh === id: cord-347465-yu6oj30v author: Kurskaya, Olga title: Viral etiology of acute respiratory infections in hospitalized children in Novosibirsk City, Russia (2013 – 2017) date: 2018-09-18 pages: extension: .txt txt: ./txt/cord-347465-yu6oj30v.txt cache: ./cache/cord-347465-yu6oj30v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347465-yu6oj30v.txt' === file2bib.sh === id: cord-345019-i7zm9bt1 author: Al-Waleedi, Ali Ahmed title: The first 2 months of the SARS-CoV-2 epidemic in Yemen: Analysis of the surveillance data date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-345019-i7zm9bt1.txt cache: ./cache/cord-345019-i7zm9bt1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345019-i7zm9bt1.txt' === file2bib.sh === id: cord-346586-fxxceffl author: Razanajatovo, Norosoa Harline title: Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013 date: 2018-11-21 pages: extension: .txt txt: ./txt/cord-346586-fxxceffl.txt cache: ./cache/cord-346586-fxxceffl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346586-fxxceffl.txt' === file2bib.sh === id: cord-344782-ond1ziu5 author: Zhang, Jing title: Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi) date: 2018-10-24 pages: extension: .txt txt: ./txt/cord-344782-ond1ziu5.txt cache: ./cache/cord-344782-ond1ziu5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-344782-ond1ziu5.txt' === file2bib.sh === id: cord-341097-c96hm610 author: Mayer, Craig S. title: Analysis of data dictionary formats of HIV clinical trials date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-341097-c96hm610.txt cache: ./cache/cord-341097-c96hm610.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341097-c96hm610.txt' === file2bib.sh === id: cord-344152-pb1e2w7s author: Kolatkar, Anand title: C-ME: A 3D Community-Based, Real-Time Collaboration Tool for Scientific Research and Training date: 2008-02-20 pages: extension: .txt txt: ./txt/cord-344152-pb1e2w7s.txt cache: ./cache/cord-344152-pb1e2w7s.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344152-pb1e2w7s.txt' === file2bib.sh === id: cord-350842-4m82l5t8 author: Xing, Jun title: Study of the mental health status of medical personnel dealing with new coronavirus pneumonia date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-350842-4m82l5t8.txt cache: ./cache/cord-350842-4m82l5t8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350842-4m82l5t8.txt' === file2bib.sh === id: cord-346858-18q8rxzg author: Hossain, Md. Tanvir title: Social and electronic media exposure and generalized anxiety disorder among people during COVID-19 outbreak in Bangladesh: A preliminary observation date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-346858-18q8rxzg.txt cache: ./cache/cord-346858-18q8rxzg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346858-18q8rxzg.txt' === file2bib.sh === id: cord-341880-wxliz485 author: Mottaleb, Khondoker Abdul title: COVID-19 induced economic loss and ensuring food security for vulnerable groups: Policy implications from Bangladesh date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-341880-wxliz485.txt cache: ./cache/cord-341880-wxliz485.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-341880-wxliz485.txt' === file2bib.sh === id: cord-348243-e5tdb08v author: Schermer, Bernhard title: Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-348243-e5tdb08v.txt cache: ./cache/cord-348243-e5tdb08v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-348243-e5tdb08v.txt' === file2bib.sh === id: cord-339796-gccnvh0z author: Zhang, Si Min title: Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins date: 2015-07-31 pages: extension: .txt txt: ./txt/cord-339796-gccnvh0z.txt cache: ./cache/cord-339796-gccnvh0z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-339796-gccnvh0z.txt' === file2bib.sh === id: cord-342639-vf9n2vf9 author: Chang, Chung-ke title: Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date: 2013-05-23 pages: extension: .txt txt: ./txt/cord-342639-vf9n2vf9.txt cache: ./cache/cord-342639-vf9n2vf9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342639-vf9n2vf9.txt' === file2bib.sh === id: cord-345695-5vi9wibk author: Hicks, Lorin L. title: A statistical approach to white-nose syndrome surveillance monitoring using acoustic data date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-345695-5vi9wibk.txt cache: ./cache/cord-345695-5vi9wibk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-345695-5vi9wibk.txt' === file2bib.sh === id: cord-348807-9xxc5hyl author: Cuomo, Raphael E. title: Sub-national longitudinal and geospatial analysis of COVID-19 tweets date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-348807-9xxc5hyl.txt cache: ./cache/cord-348807-9xxc5hyl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348807-9xxc5hyl.txt' === file2bib.sh === id: cord-346067-zly8p0y7 author: Ruiz-Irastorza, Guillermo title: Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-346067-zly8p0y7.txt cache: ./cache/cord-346067-zly8p0y7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346067-zly8p0y7.txt' === file2bib.sh === id: cord-348499-7ll7sd3o author: Manderstedt, Eric title: Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients date: 2018-02-01 pages: extension: .txt txt: ./txt/cord-348499-7ll7sd3o.txt cache: ./cache/cord-348499-7ll7sd3o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348499-7ll7sd3o.txt' === file2bib.sh === id: cord-344870-tbgqulpu author: Lloyd-Smith, James O. title: Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases date: 2007-02-14 pages: extension: .txt txt: ./txt/cord-344870-tbgqulpu.txt cache: ./cache/cord-344870-tbgqulpu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344870-tbgqulpu.txt' === file2bib.sh === id: cord-346819-11fkgzaa author: Khan, Mohd Imran title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-346819-11fkgzaa.txt cache: ./cache/cord-346819-11fkgzaa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346819-11fkgzaa.txt' === file2bib.sh === id: cord-349029-zyfop43z author: Dobrovolny, Hana M. title: Modeling the role of asymptomatics in infection spread with application to SARS-CoV-2 date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-349029-zyfop43z.txt cache: ./cache/cord-349029-zyfop43z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-349029-zyfop43z.txt' === file2bib.sh === id: cord-349217-vpih1wvs author: Petropoulos, Fotios title: Forecasting the novel coronavirus COVID-19 date: 2020-03-31 pages: extension: .txt txt: ./txt/cord-349217-vpih1wvs.txt cache: ./cache/cord-349217-vpih1wvs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-349217-vpih1wvs.txt' === file2bib.sh === id: cord-342730-b7y8mybg author: Dellagi, Koussay title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009 date: 2011-09-29 pages: extension: .txt txt: ./txt/cord-342730-b7y8mybg.txt cache: ./cache/cord-342730-b7y8mybg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342730-b7y8mybg.txt' === file2bib.sh === id: cord-352403-4591ewsa author: Hartwig, Stacey M. title: Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection date: 2014-03-07 pages: extension: .txt txt: ./txt/cord-352403-4591ewsa.txt cache: ./cache/cord-352403-4591ewsa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352403-4591ewsa.txt' === file2bib.sh === id: cord-352222-zq9o66i4 author: Rajatonirina, Soatiana title: Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012 date: 2013-09-12 pages: extension: .txt txt: ./txt/cord-352222-zq9o66i4.txt cache: ./cache/cord-352222-zq9o66i4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352222-zq9o66i4.txt' === file2bib.sh === id: cord-329999-flzqm3wh author: Buchanan, Tom title: Why do people spread false information online? The effects of message and viewer characteristics on self-reported likelihood of sharing social media disinformation date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-329999-flzqm3wh.txt cache: ./cache/cord-329999-flzqm3wh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329999-flzqm3wh.txt' === file2bib.sh === id: cord-349476-iac9fak3 author: Mao, Liang title: Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior date: 2011-10-17 pages: extension: .txt txt: ./txt/cord-349476-iac9fak3.txt cache: ./cache/cord-349476-iac9fak3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349476-iac9fak3.txt' === file2bib.sh === id: cord-353866-0r1b44id author: Sun, Hongpeng title: Changes of Adult Population Health Status in China from 2003 to 2008 date: 2011-12-02 pages: extension: .txt txt: ./txt/cord-353866-0r1b44id.txt cache: ./cache/cord-353866-0r1b44id.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353866-0r1b44id.txt' === file2bib.sh === id: cord-349911-dx8wvqkm author: Dahl, Viktor title: Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013 date: 2015-09-23 pages: extension: .txt txt: ./txt/cord-349911-dx8wvqkm.txt cache: ./cache/cord-349911-dx8wvqkm.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349911-dx8wvqkm.txt' === file2bib.sh === id: cord-351387-i0zamkpd author: Witte, Katrin title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date: 2015-09-25 pages: extension: .txt txt: ./txt/cord-351387-i0zamkpd.txt cache: ./cache/cord-351387-i0zamkpd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351387-i0zamkpd.txt' === file2bib.sh === id: cord-353253-kk2q71vg author: Itokawa, Kentaro title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by multiplex tiling PCR date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-353253-kk2q71vg.txt cache: ./cache/cord-353253-kk2q71vg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353253-kk2q71vg.txt' === file2bib.sh === id: cord-347014-88zmtky7 author: Esposito, Susanna title: Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia date: 2016-11-15 pages: extension: .txt txt: ./txt/cord-347014-88zmtky7.txt cache: ./cache/cord-347014-88zmtky7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347014-88zmtky7.txt' === file2bib.sh === id: cord-349781-l93978vq author: Cong, Yu title: MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells date: 2018-03-22 pages: extension: .txt txt: ./txt/cord-349781-l93978vq.txt cache: ./cache/cord-349781-l93978vq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-349781-l93978vq.txt' === file2bib.sh === id: cord-352522-qnvgg2e9 author: Langille, Morgan G. I. title: BioTorrents: A File Sharing Service for Scientific Data date: 2010-04-14 pages: extension: .txt txt: ./txt/cord-352522-qnvgg2e9.txt cache: ./cache/cord-352522-qnvgg2e9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352522-qnvgg2e9.txt' === file2bib.sh === id: cord-351990-aham72b9 author: Radin, Jennifer M. title: Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations date: 2014-12-30 pages: extension: .txt txt: ./txt/cord-351990-aham72b9.txt cache: ./cache/cord-351990-aham72b9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351990-aham72b9.txt' === file2bib.sh === id: cord-355874-nz6eqcdb author: Wang, Le title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia date: 2016-09-14 pages: extension: .txt txt: ./txt/cord-355874-nz6eqcdb.txt cache: ./cache/cord-355874-nz6eqcdb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355874-nz6eqcdb.txt' === file2bib.sh === id: cord-352447-bc1pf272 author: Nishida, Yu title: Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio date: 2020-10-26 pages: extension: .txt txt: ./txt/cord-352447-bc1pf272.txt cache: ./cache/cord-352447-bc1pf272.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352447-bc1pf272.txt' === file2bib.sh === id: cord-346347-r4ork18p author: Borrion, Hervé title: Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-346347-r4ork18p.txt cache: ./cache/cord-346347-r4ork18p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346347-r4ork18p.txt' === file2bib.sh === id: cord-352564-2j4pjjwk author: Dominguez, Samuel R. title: Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response date: 2013-07-24 pages: extension: .txt txt: ./txt/cord-352564-2j4pjjwk.txt cache: ./cache/cord-352564-2j4pjjwk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352564-2j4pjjwk.txt' === file2bib.sh === id: cord-356132-1nisyl5r author: Wang, Huiyao title: The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey date: 2020-05-14 pages: extension: .txt txt: ./txt/cord-356132-1nisyl5r.txt cache: ./cache/cord-356132-1nisyl5r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356132-1nisyl5r.txt' === file2bib.sh === id: cord-352200-i05h8csb author: Xu, Yi title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date: 2012-04-27 pages: extension: .txt txt: ./txt/cord-352200-i05h8csb.txt cache: ./cache/cord-352200-i05h8csb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352200-i05h8csb.txt' === file2bib.sh === id: cord-353410-tbmtg88k author: Sharma, Shreela V. title: Using a rapid assessment methodology to identify and address immediate needs among low-income households with children during COVID-19 date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-353410-tbmtg88k.txt cache: ./cache/cord-353410-tbmtg88k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353410-tbmtg88k.txt' === file2bib.sh === id: cord-348055-azlb1zy1 author: Patel, Mira C. title: Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus) date: 2016-11-04 pages: extension: .txt txt: ./txt/cord-348055-azlb1zy1.txt cache: ./cache/cord-348055-azlb1zy1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348055-azlb1zy1.txt' === file2bib.sh === id: cord-354000-jxqskt4k author: Warren, Cody J. title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 pages: extension: .txt txt: ./txt/cord-354000-jxqskt4k.txt cache: ./cache/cord-354000-jxqskt4k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354000-jxqskt4k.txt' === file2bib.sh === id: cord-353200-5csewb1k author: Jehi, Lara title: Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19 date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-353200-5csewb1k.txt cache: ./cache/cord-353200-5csewb1k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353200-5csewb1k.txt' === file2bib.sh === id: cord-352720-z1cvjc2y author: Díaz-Corvillón, Pilar title: Routine screening for SARS CoV-2 in unselected pregnant women at delivery date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-352720-z1cvjc2y.txt cache: ./cache/cord-352720-z1cvjc2y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352720-z1cvjc2y.txt' === file2bib.sh === id: cord-353245-es7b1rs0 author: Song, Deping title: Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013 date: 2015-03-19 pages: extension: .txt txt: ./txt/cord-353245-es7b1rs0.txt cache: ./cache/cord-353245-es7b1rs0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353245-es7b1rs0.txt' === file2bib.sh === id: cord-351868-w4d45fue author: Zuwała, Kaja title: The Nucleocapsid Protein of Human Coronavirus NL63 date: 2015-02-20 pages: extension: .txt txt: ./txt/cord-351868-w4d45fue.txt cache: ./cache/cord-351868-w4d45fue.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351868-w4d45fue.txt' === file2bib.sh === id: cord-353869-l53ms3q8 author: Friesen, Robert H. E. title: New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets date: 2010-02-08 pages: extension: .txt txt: ./txt/cord-353869-l53ms3q8.txt cache: ./cache/cord-353869-l53ms3q8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353869-l53ms3q8.txt' === file2bib.sh === id: cord-351098-x729wpp7 author: Long, Rachel B. title: Characterizing trends in human-wildlife conflicts in the American Midwest using wildlife rehabilitation records date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-351098-x729wpp7.txt cache: ./cache/cord-351098-x729wpp7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351098-x729wpp7.txt' === file2bib.sh === id: cord-351142-g20f6bxc author: Kiaghadi, Amin title: Assessing COVID-19 risk, vulnerability and infection prevalence in communities date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-351142-g20f6bxc.txt cache: ./cache/cord-351142-g20f6bxc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351142-g20f6bxc.txt' === file2bib.sh === id: cord-350443-ca5avyjf author: Zhang, Lei title: Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy date: 2012-02-16 pages: extension: .txt txt: ./txt/cord-350443-ca5avyjf.txt cache: ./cache/cord-350443-ca5avyjf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350443-ca5avyjf.txt' === file2bib.sh === id: cord-351918-pu7i1jfe author: Baek, Yae Jee title: A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies date: 2020-10-26 pages: extension: .txt txt: ./txt/cord-351918-pu7i1jfe.txt cache: ./cache/cord-351918-pu7i1jfe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351918-pu7i1jfe.txt' === file2bib.sh === id: cord-352511-gkm7i62s author: Yamada, Yoshiyuki title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells date: 2009-07-02 pages: extension: .txt txt: ./txt/cord-352511-gkm7i62s.txt cache: ./cache/cord-352511-gkm7i62s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352511-gkm7i62s.txt' === file2bib.sh === id: cord-354052-x4ckzw64 author: Li, Chunhua title: Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination date: 2013-08-02 pages: extension: .txt txt: ./txt/cord-354052-x4ckzw64.txt cache: ./cache/cord-354052-x4ckzw64.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354052-x4ckzw64.txt' === file2bib.sh === id: cord-356364-ipi81ce3 author: Ho, Bo-Lin title: Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease date: 2015-12-14 pages: extension: .txt txt: ./txt/cord-356364-ipi81ce3.txt cache: ./cache/cord-356364-ipi81ce3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356364-ipi81ce3.txt' === file2bib.sh === id: cord-347317-qcghtkk0 author: Russo, Lucia title: Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-347317-qcghtkk0.txt cache: ./cache/cord-347317-qcghtkk0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347317-qcghtkk0.txt' === file2bib.sh === id: cord-353596-8iqjugcx author: Bédubourg, Gabriel title: Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study date: 2017-07-17 pages: extension: .txt txt: ./txt/cord-353596-8iqjugcx.txt cache: ./cache/cord-353596-8iqjugcx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353596-8iqjugcx.txt' === file2bib.sh === id: cord-354547-eomm1sl5 author: Wang, Jibin title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date: 2009-03-16 pages: extension: .txt txt: ./txt/cord-354547-eomm1sl5.txt cache: ./cache/cord-354547-eomm1sl5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354547-eomm1sl5.txt' === file2bib.sh === id: cord-346314-o9fjpqaj author: Jarboui, Mohamed Ali title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date: 2012-11-15 pages: extension: .txt txt: ./txt/cord-346314-o9fjpqaj.txt cache: ./cache/cord-346314-o9fjpqaj.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346314-o9fjpqaj.txt' === file2bib.sh === id: cord-354763-odzrco6q author: Drake, John M. title: Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore date: 2006-12-20 pages: extension: .txt txt: ./txt/cord-354763-odzrco6q.txt cache: ./cache/cord-354763-odzrco6q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354763-odzrco6q.txt' === file2bib.sh === id: cord-355259-779czzzx author: Yang, Xiaoyun title: A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus date: 2014-10-15 pages: extension: .txt txt: ./txt/cord-355259-779czzzx.txt cache: ./cache/cord-355259-779czzzx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355259-779czzzx.txt' === file2bib.sh === id: cord-352219-z245sb3s author: Tallam, Aravind title: Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date: 2016-02-12 pages: extension: .txt txt: ./txt/cord-352219-z245sb3s.txt cache: ./cache/cord-352219-z245sb3s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352219-z245sb3s.txt' === file2bib.sh === id: cord-351185-3y3gou6v author: Buckles, Thomas C. title: Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-351185-3y3gou6v.txt cache: ./cache/cord-351185-3y3gou6v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-351185-3y3gou6v.txt' === file2bib.sh === id: cord-353730-owcapg8h author: Dietrich, Jes title: Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01 date: 2014-06-23 pages: extension: .txt txt: ./txt/cord-353730-owcapg8h.txt cache: ./cache/cord-353730-owcapg8h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353730-owcapg8h.txt' === file2bib.sh === id: cord-350398-w75flrwv author: Sampath, Rangarajan title: Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry date: 2012-06-29 pages: extension: .txt txt: ./txt/cord-350398-w75flrwv.txt cache: ./cache/cord-350398-w75flrwv.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350398-w75flrwv.txt' Que is empty; done journal-plosOne-cord === reduce.pl bib === id = cord-000366-u4649rtx author = Shan, Tongling title = Genomic Characterization and High Prevalence of Bocaviruses in Swine date = 2011-04-15 pages = extension = .txt mime = text/plain words = 2887 sentences = 161 flesch = 55 summary = Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Presently, the bocavirus genus contains eight members: bovine parvovirus, canine minute virus (CnMV), human bocavirus 1-4 (HBoV1-4), a gorilla bocavirus and a partially sequenced chimpanzee bocavirus [1, 6, 7] . In 2009, a porcine bocalike virus (PBo-likeV) was reported in swine feces with postweaning multisystemic wasting syndrome in Sweden and 1854 bp of its partial genome sequenced [27] . Finally, partial genome sequences of 2.4 Kb from another clade of porcine bocaviruses labeled 6V and 7V where also identified yielding three major bocavirus groups in swine (PBo-likeV, PBoV1/PBoV2, and 6V/7V). cache = ./cache/cord-000366-u4649rtx.txt txt = ./txt/cord-000366-u4649rtx.txt === reduce.pl bib === id = cord-000013-pr9i9swk author = Croyle, Maria A. title = Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice date = 2008-10-29 pages = extension = .txt mime = text/plain words = 6509 sentences = 272 flesch = 37 summary = We have previously found that a single dose of a recombinant adenovirus expressing Ebola Zaire GP given by either the oral or the nasal route is capable of affording protection against lethal challenge in naïve mice and that mucosal immunization can stimulate a broad, prolonged T cell-mediated immune response in both the systemic and mucosal compartments [37] . In an effort to correlate markers of immunity with protection against Ebola infection after mucosal immunization, T and B cell specific immune responses against Ebola glycoprotein were analyzed in mice in the presence or absence of pre-existing immunity (PEI) to adenovirus 10 days after vaccination with a first generation adenovirus serotype 5 vector expressing the Zaire Ebola glycoprotein (Ad5-ZGP). A single intranasal dose of a recombinant Ad5 vaccine expressing the Zaire Ebola glycoprotein conferred 100% protection in both naïve mice and those with pre-existing immunity despite the fact that the strength of the immune response generated by this route of administration was quantitatively lower than that seen in animals vaccinated by intramuscular injection. cache = ./cache/cord-000013-pr9i9swk.txt txt = ./txt/cord-000013-pr9i9swk.txt === reduce.pl bib === id = cord-000006-104sqoxz author = Bray, Daniel P. title = Composition and Function of Haemolymphatic Tissues in the European Common Shrew date = 2008-10-15 pages = extension = .txt mime = text/plain words = 5701 sentences = 259 flesch = 46 summary = Here, we examined the unique haemolymphatic system of the European common shrew (Sorex araneus) to investigate the capacity of this short-lived mammal, restricted by a fast metabolism and extremely limited fat reserves, to defend against its unusually diverse parasite fauna, both as a young animal and an adult. We examined and compared the structure, composition and function of relevant haemolymphatic tissues including the pancreas of Aselli, in wild-caught common shrews of different ages pre and post maturation, and the extent and type of inflammatory reactions produced in response to naturally occurring parasitic infections. While some degree of lymphatic exhaustion was obvious in adult animals (perhaps as a result of age-related changes, or reduced investment in immunity as a consequence of breeding effort), there was also evidence of some degree of compensation, in the form of storage of plasma cells particularly in the pancreas of Aselli, possibly as a defence against previously encountered parasites. cache = ./cache/cord-000006-104sqoxz.txt txt = ./txt/cord-000006-104sqoxz.txt === reduce.pl bib === id = cord-000050-tfcerilc author = Rao, Srinivas title = Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date = 2008-06-18 pages = extension = .txt mime = text/plain words = 5605 sentences = 256 flesch = 44 summary = METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. After optimization of injection conditions, alternative multivalent DNA vaccine regimens were analyzed and compared for magnitude and breadth of neutralizing antibodies, as well as protective efficacy after challenge in mouse and chicken models of HPAI H5N1 infection. The ability of chickens to generate specific antibodies was assessed with three strains that showed broad cross protection in mouse studies (A/Vietnam/1203/2004, A/Anhui/ 1/2005 and A/Indonesia/05/2005), administered individually or in combination, by different injection methods. cache = ./cache/cord-000050-tfcerilc.txt txt = ./txt/cord-000050-tfcerilc.txt === reduce.pl bib === id = cord-000082-jy7j8sh0 author = Huang, Ting title = Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection date = 2009-07-27 pages = extension = .txt mime = text/plain words = 6190 sentences = 271 flesch = 57 summary = Most surprisingly, 20 of the 34 strains classified as HRV-C by comparative analysis of VP4/P2 sequences ( Table 2) were related more closely to HRV-A strains when their 59UTRs were analyzed, and showed incongruent clustering in phylogenetic trees (Figs. When sequencing the VP4/VP2 region of the HRV genome, several recent studies have identified new strains of viruses from children and adults with ARI, asthma, or otitis, which are clustered differently from HRV-A and HRV-B, and have been classified into a novel HRV-C species [7, 8, 17, 18, 19, 20, 21, 25, 26, 27, 28] . In our study, we identified 34 HRVs (51.5%) that clustered differently from HRV-A and HRV-B in a phylogenetic tree that was established on the basis of VP4/VP2 sequences, which were related to recent strains classified in the novel HRV-C species (Fig. 1, Table 2 ). cache = ./cache/cord-000082-jy7j8sh0.txt txt = ./txt/cord-000082-jy7j8sh0.txt === reduce.pl bib === id = cord-000140-5kapn32k author = Wang, Pei-Gang title = Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins date = 2009-12-15 pages = extension = .txt mime = text/plain words = 7780 sentences = 396 flesch = 53 summary = METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Our data demonstrate that newly synthesized proteins need 8 hours to be translocated through the secretory pathway and released into the supernatant as mature RSPs. To further characterize secreted DV1 RSPs, we performed sucrose gradient fractionation on RSPs concentrated from supernatant of HeLa-prME cells. To identify host factors that could either enhance or reduce production of DV RSPs, we first developed a quantitative assay to relatively quantify levels of secreted particles in supernatant of HeLa-prME cells. cache = ./cache/cord-000140-5kapn32k.txt txt = ./txt/cord-000140-5kapn32k.txt === reduce.pl bib === id = cord-000224-2lz03oqb author = Porter, Kristen A. title = Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag date = 2010-06-24 pages = extension = .txt mime = text/plain words = 6986 sentences = 313 flesch = 44 summary = METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. We hypothesized that recapitulating endogenous expression of the entire class II antigen presentation pathway in producer cells via expression of CIITA would restore infectious virus release and provide a more physiologically relevant model for HIV-1 assembly studies. Virus release, both infectious and particle titers) were reduced when cells were transfected with either HLA-DR or other components of the MHC class II antigen presentation pathway ( Figure S2 ), confirming a correlation between Gag retention and reduced virus titers in the presence of HLA-DR, as previously demonstrated [8] . Together, these data suggest CIITA has two effects on the HIV replicative cycle in producer cells, both of which are independent of the MHC II antigen processing pathway; i) it does not induce HLA-DR, mediated intracellular retention of Gag and ii) it increases the infectivity of HIV virions. cache = ./cache/cord-000224-2lz03oqb.txt txt = ./txt/cord-000224-2lz03oqb.txt === reduce.pl bib === id = cord-000255-73nlxqgk author = Hosseini, Parviez title = Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread date = 2010-09-15 pages = extension = .txt mime = text/plain words = 4022 sentences = 184 flesch = 50 summary = CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Of all the models evaluated, a multivariate model with three predictors, (1) total country-level healthcare spending per capita, (2) estimated passenger volume arriving from Mexico via direct flights (direct flight capacity), and (3) passenger volume from Mexico via indirect, or two-leg, flights (indirect flight capacity), provided the best fit to the data using AIC, as detailed under Methods (Table 1 , DAIC = 0, overall x 2 = 54.33 on 5 degrees of freedom, p-value,0.0001). We validated the model by determining how well a model fit to data up until May 8th predicted reporting dates for fourteen countries where the disease was detected between May 9 th and May 19 th (Supplemental Online Figure S2 ). cache = ./cache/cord-000255-73nlxqgk.txt txt = ./txt/cord-000255-73nlxqgk.txt === reduce.pl bib === id = cord-000176-z76vjkxg author = Nguyen, Jack T. title = Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro date = 2010-02-22 pages = extension = .txt mime = text/plain words = 7331 sentences = 295 flesch = 45 summary = Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadineand oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. In an earlier study, we explored the in vitro antiviral activity and synergy of single, double, and triple combinations of amantadine, ribavirin and oseltamivir against a panel of influenza A viruses that were susceptible to these drugs [10] . Statistical analysis of the variability across all replicates from the six experiments for each virus revealed that amantadine made a significant contribution to the synergy of the TCAD regimen at concentrations 0.1 mg/mL and 0.32 mg/mL and above against CA05 and CA10, respectively, compared to the double combination of ribavirin/oseltamivir carboxylate without amantadine ( Figure 1B ). cache = ./cache/cord-000176-z76vjkxg.txt txt = ./txt/cord-000176-z76vjkxg.txt === reduce.pl bib === id = cord-000131-ugbwvy6j author = Jones, James Holland title = Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1) date = 2009-12-03 pages = extension = .txt mime = text/plain words = 4322 sentences = 216 flesch = 48 summary = Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the outbreak during the first few days of widespread media coverage (April 29 -May 5, 2009) of the emergence of novel swine-origin Influenza A(H1N1). To evaluate the hypothesis that respondents' affective state (subjective anxiety, fatalism about infection) predicts protective measures, we include in the model demographic (age, gender), epidemiological (household size, number of contacts, survey day), and media (source of information on the outbreak) conditioning variables. While our sampling design is subject to many of the usual criticisms of internet-based surveys and is not necessarily representative of the general population, the unparalleled immediacy, longitudinal nature, and the large number of respondents it contains make our data set unique and scientifically important for the study of the spread of information and distribution of risk perception and behavioral change during the most uncertain time (i.e. the initial phase) of an epidemic of a virus novel to the human population. cache = ./cache/cord-000131-ugbwvy6j.txt txt = ./txt/cord-000131-ugbwvy6j.txt === reduce.pl bib === id = cord-000269-v4jochbe author = Wittekindt, Nicola E. title = Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date = 2010-10-18 pages = extension = .txt mime = text/plain words = 5886 sentences = 314 flesch = 44 summary = cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. The microbial community of mule deer lymph nodes Detection of protein-coding and ribosomal RNA transcripts provides strong support for the presence of viable and replicating microorganisms. As an alternative approach to identifying bacterial microorganisms present in lymph node tissue, we utilized amplicon DNA library sequencing technology. cache = ./cache/cord-000269-v4jochbe.txt txt = ./txt/cord-000269-v4jochbe.txt === reduce.pl bib === id = cord-000143-2xvd5ogf author = Napthine, Sawsan title = Expression of the VP2 Protein of Murine Norovirus by a Translation Termination-Reinitiation Strategy date = 2009-12-22 pages = extension = .txt mime = text/plain words = 6886 sentences = 300 flesch = 50 summary = In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity. Recent studies of termination-reinitiation in the expression of the orthomyxovirus influenza BM2 protein have revealed a requirement for a shorter stretch of mRNA (45 nt) upstream of the stop-start window, but nevertheless, the RNA contains a similar TURBS Motif 1 [19] . Whilst in principle, reinitiation of translation of the MNV 49.7 VP2fluc ORF, following termination, could occur at the next available AUG, this is located 54 amino acids from the natural stop-start signal and initiation here would produce a substantially shorter product that would have been detectable by SDS-PAGE. cache = ./cache/cord-000143-2xvd5ogf.txt txt = ./txt/cord-000143-2xvd5ogf.txt === reduce.pl bib === id = cord-000742-0r4z1zea author = Vittecoq, Marion title = High Influenza A Virus Infection Rates in Mallards Bred for Hunting in the Camargue, South of France date = 2012-08-27 pages = extension = .txt mime = text/plain words = 5923 sentences = 304 flesch = 53 summary = We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife. Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions. However, to our knowledge no study ever aimed at investigating the potential role of hand-reared Mallards released for hunting in the epidemiology of AIV, despite the very large number of ducks being released in the wild annually. Our results highlighted that: i) GBF represent an epidemiological compartment into which important AIV outbreaks can occur; ii) a significant proportion of Mallards wintering in the Camargue are infected by LPAIV, including H5 strains that are known to be able to evolve to HPAIV in domestic birds [30] . cache = ./cache/cord-000742-0r4z1zea.txt txt = ./txt/cord-000742-0r4z1zea.txt === reduce.pl bib === id = cord-000008-3dgjv0x1 author = Vali, Bahareh title = HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date = 2008-10-20 pages = extension = .txt mime = text/plain words = 5253 sentences = 236 flesch = 47 summary = In response to stimulation with HIV peptide pool, untreated co-infected individuals showed significantly higher frequencies of intra-hepatic CD4 + T-cells producing IFN-c, compared to HCV mono-infected [0.1660.05% vs 0.0260.01%, p,0.05], and HAART-treated co-infected individuals [0.1660.05% vs 0.0360.05%, p,0.05] (Figure 2a ). Therapy naïve co-infected subjects had greater IFN-c producing CD8 + T-cells in response to HIV peptides compared to HCV mono-infected individuals [1.3960.37% vs 0.0260.0%, p,0.05], and HAART was associated with a significant reduction in the frequencies of these cells [1.3960.37% vs 0.3060.26%, p,0.05] (figure 2b). The tetramer cytokine response pattern was shown to be different in the liver compared to blood of the same individual, with diminished intra-hepatic tetramer-specific IFN-c responses and an increase in both CD107a and TNF-a responses, with the majority of SL9 tetramer positive cells expressing these two markers. Therapy naïve co-infected individuals demonstrated a higher frequency of intra-hepatic CD8 + T-cells that produce TNF-a in response to both HCV and HIV antigen stimulation compared to HCV mono-infected individuals. cache = ./cache/cord-000008-3dgjv0x1.txt txt = ./txt/cord-000008-3dgjv0x1.txt === reduce.pl bib === id = cord-000540-bbjmcdo5 author = Hellard, Eléonore title = True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses date = 2012-01-03 pages = extension = .txt mime = text/plain words = 7597 sentences = 397 flesch = 45 summary = By combining logistic regressions and chi-square tests, we are able to calculate the expected frequencies of co-infected individuals if parasites are independent considering their risk factors, and to compare them to the observed ones. The corrected chi-square approach is based on the idea that the coefficients of the logistic regression of the two viruses can be used to estimate the number of seronegative, single-and double-seropositive individuals expected if the two pathogens are independent. The two approaches (corrected chi-square and logistic regression) were used for the analysis of the interactions between four cat viruses ( Table 2) . Correcting for all risk factors, no pair of viruses involving the Feline Immunodeficiency Virus (FIV-FHV, FIV-FCV, FIV-FPV) was significantly associated. Table S1 Corrected chi-square tests and logistic regressions to search for feline viruses' interactions using subsets randomly sampled in cat data such that the N F / n ratio takes various values. cache = ./cache/cord-000540-bbjmcdo5.txt txt = ./txt/cord-000540-bbjmcdo5.txt === reduce.pl bib === id = cord-000574-7eflwyxk author = Liu, Yanli title = Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20 date = 2012-02-07 pages = extension = .txt mime = text/plain words = 3919 sentences = 216 flesch = 52 summary = The non-conservative N-terminal domain of the protein phosphatase1 (PP1), with 1-8 residues deleted, showed higher sensitivity to three substrates and influenced the structure and properties of PP1 [10] , whereas the truncation of the Cterminal region improved the thermal stability of endo-bglucanase from Bacillus subtilis JA18 [11] . The TIM barrel domain, which is one of the most common catalytic domains, is adopted by about 10% of the enzymes; thus, sequence modification inside or outside the domain to improve the enzymatic property and determine the catalytic mechanism was reported in many studies. In the present research, Atgus and the partial sequence [Atgus(-3t)] without Cterminal non-conservative sequence behind the TIM barrel domain were amplified in order to investigate effects of nonconservative sequence on enzymatic property. Based on the same hydrolyzing mode, relatively higher thermal stability, and especially the enhanced affinity and catalytic efficiency for GL, deletion of the non-conservative sequence behind the TIM barrel domain was a successful evolution of AtGUS. cache = ./cache/cord-000574-7eflwyxk.txt txt = ./txt/cord-000574-7eflwyxk.txt === reduce.pl bib === id = cord-000166-36bfeoqv author = Tracht, Samantha M. title = Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) date = 2010-02-10 pages = extension = .txt mime = text/plain words = 5846 sentences = 336 flesch = 59 summary = We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. With the implementation of N95 respirators Table 3 exhibits a reduction in the cumulative number of cases of almost 200,000, or a 19% decrease, when 10% of the population wears masks and they are 20% effective. With 10% of the population wearing N95 respirators with effectiveness at 20% in reducing both susceptibility and infectivity there is a 19% reduction in the cumulative number of cases. Even at 50% effectiveness in reducing both susceptibility and infectivity and with 50% of the population wearing surgical masks only a 6% reduction in the number of cumulative cases is seen. cache = ./cache/cord-000166-36bfeoqv.txt txt = ./txt/cord-000166-36bfeoqv.txt === reduce.pl bib === id = cord-000063-tex6bgab author = Sui, Hong-Yan title = Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication date = 2009-05-22 pages = extension = .txt mime = text/plain words = 3501 sentences = 189 flesch = 50 summary = Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. It was further demonstrated that no siRNA-resistant viral mutation appeared in siM2 targeting sequence even after the virus was cultured in the shRNA expressing stable cell line for 40 passages. A recent report by Zhou et al [30] also showed that several siRNAs targeting NP and M genes exhibited effective inhibition against influenza A virus replication in cultured MDCK cells and in animal models. Taken together, all the findings about effective RNAi target, lentiviral vector delivery and the establishment of stable shRNA expressing cell lines in our study provide rational information for the development of siRNAs as prophylaxis and therapy for influenza virus infection in humans. cache = ./cache/cord-000063-tex6bgab.txt txt = ./txt/cord-000063-tex6bgab.txt === reduce.pl bib === id = cord-000720-5b936n3g author = Nannyonga, Betty title = The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks date = 2012-07-24 pages = extension = .txt mime = text/plain words = 4405 sentences = 250 flesch = 57 summary = The models designed are fit to data from the Kitgum outbreak, to estimate the basic reproduction number and to relate them to the level of contamination of the environment. Susceptible individuals without bore hole access become infected with the Hepatitis E virus at a rate bc, where b is the transmission rate of HEV from the contaminated environment c, to the human. To estimate model parameters and determine the critical level of control needed to eradicate the epidemic, the model described by the equations in (7) is fit to the data collected during the Kitgum outbreak ( Figure 1 ) During the invasion phase of HEV, the prevalence is approximately Under the above assumption, equations (7) are rewritten to incorporate the malaria dynamics in equation (11) where j is a parameter that models change the increase (or decrease) in susceptibility to Hepatitis E of malaria infected individuals [12] . cache = ./cache/cord-000720-5b936n3g.txt txt = ./txt/cord-000720-5b936n3g.txt === reduce.pl bib === id = cord-000765-r7y1cqou author = Chang, Yu-Ming title = Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date = 2012-09-21 pages = extension = .txt mime = text/plain words = 5770 sentences = 317 flesch = 54 summary = title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. IcaR DNA1 probe duplex of 1 mM was pre-incubated with 2 mM TcaR (dimer) at room temperature for 15 min before mixing with increasing concentration of GC33 ssDNA, followed by the same procedure as described in the legend to Figure 1B . In the EMSA analysis, 1 mM IcaR DNA1 probe duplex was pre-incubated with 1 mM GC33 ssDNA fragment for 15 min at room temperature before mixing with TcaR protein of increasing concentration. cache = ./cache/cord-000765-r7y1cqou.txt txt = ./txt/cord-000765-r7y1cqou.txt === reduce.pl bib === id = cord-000588-3wok0n21 author = Sainz, Juan title = Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection date = 2012-02-27 pages = extension = .txt mime = text/plain words = 5506 sentences = 293 flesch = 41 summary = The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. Based on these observations, the objective of the present study was to investigate the role of tagging and potentially functional single-nucleotide polymorphisms (SNPs) located within the DC-SIGN, Dectin-1, Dectin-2, MCP-1/CCL2 and CCR2 genes on IPA susceptibility. Of note is that two SNPs showing genetic interaction in this model were not significantly associated with an increased risk of IPA infection in the univariate analysis (CCR2 rs3918358 and Dectin-2 rs7134303 ). cache = ./cache/cord-000588-3wok0n21.txt txt = ./txt/cord-000588-3wok0n21.txt === reduce.pl bib === id = cord-000501-qz68gtd4 author = Greatorex, Jane S. title = Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control date = 2011-11-22 pages = extension = .txt mime = text/plain words = 4311 sentences = 194 flesch = 47 summary = METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. The potential for transmission of influenza by indirect contact (i.e. via fomites) is linked to the ability of virus to survive in transmissible titres on commonly touched surfaces; however few data exist on this subject. We evaluate the survival of influenza A (H1N1) viruses deliberately applied to a range of commonly touched household and workplace surfaces, using RT-PCR for genome detection and culture methods to determine viability. Our data are consistent with recent findings from a study of environmental deposition of pandemic H1N1 virus in the homes of infected patients, involving our laboratory, when almost 10% of tested surfaces yielded viable virus [15] . cache = ./cache/cord-000501-qz68gtd4.txt txt = ./txt/cord-000501-qz68gtd4.txt === reduce.pl bib === id = cord-000460-h3owwjao author = Xiong, Jing title = Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date = 2011-09-26 pages = extension = .txt mime = text/plain words = 4313 sentences = 212 flesch = 41 summary = However, with LPS stimulation numbers of platelets staining positive for both plateletand leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. Alternatively, comparable activation of leukocyte as well as platelet result in formation of cell-derived microvesicles (MV) which may contribute to increased thrombogenic propensity of the blood, pro-inflammatory immune processes and thus cardiovascular risk [15, 16, 17, 18, 19, 20, 21, 22] . Therefore, the present study was designed to test the hypothesis that acute exposure to a sentinel dose of LPS would induce MV production and exchange of specific proteins/ receptors between platelets and leukocytes via TLR4 activation. The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice. cache = ./cache/cord-000460-h3owwjao.txt txt = ./txt/cord-000460-h3owwjao.txt === reduce.pl bib === id = cord-000266-xwfptmmv author = Liao, Qiuyan title = Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study date = 2010-10-12 pages = extension = .txt mime = text/plain words = 7129 sentences = 356 flesch = 44 summary = METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. We report on a theoretical model that incorporated elements of influenza causal knowledge, perceived self-efficacy and also social and affective influences ( Figure 1 ) because these latter variables have been less frequently studied in combination, but have theoretical and logical support for their potential importance in the context of RIDs. We tested this model against data collected in the early phase of the influenza A/H1N1 pandemic (Table S1 ) to examine how levels of trust in formal and informal sources of risk/prevention information associated with hand washing and social distancing. cache = ./cache/cord-000266-xwfptmmv.txt txt = ./txt/cord-000266-xwfptmmv.txt === reduce.pl bib === id = cord-000556-uu1oz2ei author = Kumar, Ranjit title = RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336” date = 2012-01-20 pages = extension = .txt mime = text/plain words = 4407 sentences = 235 flesch = 46 summary = Whole genome transcriptome analysis is a complementary method to identify "novel" genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. Therefore, genome structural annotation or the identification and demarcation of boundaries of functional elements in a genome (e.g., genes, non-coding RNAs, proteins, and regulatory elements) are critical elements in infectious disease systems biology. Whole genome transcriptome studies (such as whole genome tiling arrays [13, 14, 15] and high throughput sequencing [16, 17] ) are complementary experimental approaches for bacterial genome annotation and can identify ''novel'' genes, gene boundaries, regulatory regions, intergenic regions, and operon structures. We compared the RNA-Seq based transcriptome map with the available genome annotation to identify expressed, novel, and intergenic regions in the genome. The single nucleotide resolution map helped uncover the structure and complexity of this pathogen's transcriptome and led to the identification of novel, small RNAs and protein coding genes as well as gene co-expression. cache = ./cache/cord-000556-uu1oz2ei.txt txt = ./txt/cord-000556-uu1oz2ei.txt === reduce.pl bib === id = cord-000609-dpcgl6ig author = Raju, Sammeta V. title = Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia date = 2012-03-19 pages = extension = .txt mime = text/plain words = 4083 sentences = 253 flesch = 43 summary = Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. The current report directly measured the adenosineinduced chloride secretion of airway epithelia under the exposure of physiologically relevant concentrations of alcohol and found that ethanol attenuates epithelial CFTR-mediated chloride transport by modulating cellular cAMP levels. To explore if ethanol affects adenosine-activated ion transport function of airway epithelium, we employed air-liquid interface cultures of Calu-3 cells, a system widely used to investigate airway epithelial electrophysiological properties [27, 28] . These results not only confirm that ethanol modulates adenosine-cAMP signaling but also suggest that phosphodiesterase inhibitors may be useful as the potential therapeutic agents for improving the airway epithelial ion transport and mucociliary clearance in alcoholic patients. cache = ./cache/cord-000609-dpcgl6ig.txt txt = ./txt/cord-000609-dpcgl6ig.txt === reduce.pl bib === id = cord-000079-533xlisc author = Huszthy, Peter C. title = Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy date = 2009-07-20 pages = extension = .txt mime = text/plain words = 5427 sentences = 268 flesch = 45 summary = Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. Furthermore, we showed a significant therapeutic effect of LCMV-GP pseudotyped lentiviral vectors in the cell-line based 9L rat glioma model using the suicide gene HSV-1-tk. In the presented work, we showed that both, VSV-G and LCMV-GP pseudotyped lentiviruses efficiently transduced human glioma cells in vitro and in vivo, whereas gammaretroviral transduction was inefficient. When analyzed at higher magnification, both LCMV-GP and VSV-G pseudotyped lentiviral vectors showed efficient transgene delivery to nestin-positive tumor cells in solid ( Figure 3B ,E) and invasive tumor areas ( Figure 3C ,F). cache = ./cache/cord-000079-533xlisc.txt txt = ./txt/cord-000079-533xlisc.txt === reduce.pl bib === id = cord-000077-d441jam3 author = Zhang, Hao-Jie title = The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability date = 2009-07-03 pages = extension = .txt mime = text/plain words = 5426 sentences = 267 flesch = 54 summary = Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. As shown in Fig. 3A , similar levels of Pr160 gag-pol , Gag protein (Pr55 Gag ) and capsid protein p24 (CA p24) were found in cells transfected with the wild type or mutant constructs, indicating that the expression and stability of RT precursor protein were not affected by the mutations. To study if the RTs in the viral particles of Y271A and I274A mutants were degraded by proteolysis that made them undetectable, pseudoviruses of wild type and mutants were generated in the presence or absence of indinavir, a highly specific inhibitor of HIV-1 protease. cache = ./cache/cord-000077-d441jam3.txt txt = ./txt/cord-000077-d441jam3.txt === reduce.pl bib === id = cord-000666-je9t4i6q author = Verbist, Katherine C. title = IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection date = 2012-05-18 pages = extension = .txt mime = text/plain words = 7210 sentences = 302 flesch = 47 summary = ( Figure 2E) ; however, these animals seemed to regain control of viral replication by day 4 p.i., which perhaps corresponds with the early entry of cells of the adaptive immune response as anti-influenza specific CD8 T cells are first detectable in the lung airways by d6 post infection by flow cytometry ( [34] and data not shown). We observed significant reductions in the numbers of NK cells in the lung airways of influenza-infected animals in which IL-15 was blocked at time points associated with their arrival at the site of infection, and failure of these cell populations to accumulate had implications in early viral control (Figure 2) . doi:10.1371/journal.pone.0037539.g002 frequencies, numbers, CD122 expression, and BrdU incorporation were specific to the lung airways (the sight of treatment), as NK cells isolated from spleens were similar in control and IL-15ctreated animals ( Figure 3C and data not shown). cache = ./cache/cord-000666-je9t4i6q.txt txt = ./txt/cord-000666-je9t4i6q.txt === reduce.pl bib === id = cord-000434-ff2zadol author = Zhao, Rongmao title = Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus date = 2011-08-19 pages = extension = .txt mime = text/plain words = 5752 sentences = 307 flesch = 51 summary = The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs. Influenza A viruses (IAVs), members of the Orthomyxoviridae family, are highly contagious to a variety of avian and mammalian species. To confirm that these antibodies can recognize the HA antigen, the reactivity of the anti-peptide sera were evaluated by Western blot and ELISA against the purified HA0 protein of H1N1pdm virus. The sensitivity and specificity of peptide-ELISA versus HI test was 96.5% and 74.4%, respectively, indicating the potential of the peptide-ELISA method in detecting antibody against H1-subtype IAVs. In the present study, we identified immunodominant linear B cell epitopes on the H1N1pdm virus HA protein by a peptide scanning approach using H1N1pdm patients sera. To screen the H1-subtype specific epitopes, a set of 50 peptides spanning the amino acid sequences of the HA protein ectodomain of pandemic A/H1N1 2009 (H1N1pdm) influenza virus strain A/ California/04/2009 were synthesized. cache = ./cache/cord-000434-ff2zadol.txt txt = ./txt/cord-000434-ff2zadol.txt === reduce.pl bib === id = cord-000408-pt3b4yc7 author = Lu, Sydney X. title = Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation date = 2011-07-06 pages = extension = .txt mime = text/plain words = 5433 sentences = 262 flesch = 48 summary = The accelerated early mortality of Ceacam1 2/2 allo-BMT recipients, together with increased accumulation of donor T cells in GI tract and mesenteric lymph nodes, but decreased numbers peripheral lymph nodes ( Figure 3C ), led us to ask whether Ceacam1 had differential effects in regulating GVHD target organ damage for various target organs and tissues. We analyzed donor WT and Ceacam1 2/2 alloactivated splenic T cells on day 14 after allo-BMT for trafficking molecules, and found that Ceacam1 2/2 CD8 + CD44 + CD62L 2 effector T cells expressed higher levels of integrin b 7 subunit and the gut homing integrin a 4 b 7 ( Figure 5A) , which is important for intestinal GVHD [31, 32, 33] . Ceacam12/2 CD4 effector T cells had similar integrin b 7 subunit expression, yet also accumulated in greater numbers in the gut ( Figure 3A) , suggesting that regulation of target organ damage by Ceacam1 is very likely to involve multiple additional mechanisms beyond trafficking molecule expression. cache = ./cache/cord-000408-pt3b4yc7.txt txt = ./txt/cord-000408-pt3b4yc7.txt === reduce.pl bib === id = cord-000346-9b6yz3f4 author = Holder, Benjamin P. title = Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model date = 2011-03-24 pages = extension = .txt mime = text/plain words = 7494 sentences = 323 flesch = 49 summary = In order to obtain two complementary views of the infection kinetics for the A/Brisbane/59/2007 WT and H275Y mutant strains, virus growth over time was observed in two different in vitro systems: the viral plaque assay and the multiple-cycle viral yield assay. We are left then with two experimental measures -the viral titer growth rate and the plaque velocity -whose values may depend on three unknown infection kinetics parameters: the infecting time, t inf ; the latent infection period, t L ; and the infectious lifespan of a cell, t I . To demonstrate this concept using the A/ Brisbane/59/2007 (H1N1) WT and H275Y mutant strains, we have plotted the experimentally-measured values of plaque velocity and viral titer growth rate as functions of the infecting time and latent infection period, using the model dependence determined above ( Figure 6 ). cache = ./cache/cord-000346-9b6yz3f4.txt txt = ./txt/cord-000346-9b6yz3f4.txt === reduce.pl bib === id = cord-000580-dcid9emx author = Sällman Almén, Markus title = The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date = 2012-02-20 pages = extension = .txt mime = text/plain words = 4662 sentences = 237 flesch = 48 summary = We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. By combining the results of the phylogenetic analysis and BLAST classification, we created a schematic overview of the organisms' gene repertoire and a schematic picture of the Dispanin family's evolutionary history, which suggests that the invertebrate Dispanins share more similarity towards the DSPC and D subfamilies than DSPA and B ( Figure 2 ). We provide evidence that the four IFITM genes together with ten additional human genes, known as TUSC5, TMEM233, PRRT2, TMEM90A, DSPC2, TMEM90B, TMEM91, AC023157, AL160276 and AC068580, form a novel gene family that we call the Dispanins, which refers to the 2TM membrane topology that is common to all identified members. cache = ./cache/cord-000580-dcid9emx.txt txt = ./txt/cord-000580-dcid9emx.txt === reduce.pl bib === id = cord-000182-ni6iyzdn author = He, Zhisong title = Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date = 2010-03-11 pages = extension = .txt mime = text/plain words = 6037 sentences = 305 flesch = 46 summary = title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou's pseudo amino acid composition: an approach from discrete wavelet transform cache = ./cache/cord-000182-ni6iyzdn.txt txt = ./txt/cord-000182-ni6iyzdn.txt === reduce.pl bib === id = cord-000547-adfigzc1 author = Beniac, Daniel R. title = The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date = 2012-01-11 pages = extension = .txt mime = text/plain words = 7782 sentences = 392 flesch = 51 summary = METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes ( Figure 5 ) to a resolution of 14 Å as measured by the Fourier Shell Correlation (FSC) 0.5 criterion. Analysis of 2090 distinct intact virions with a nucleocapsid from cryo-electron micrographs shows that the most common class length (53%) of virus particles is 982679 nm ( Figure 1A , Table S1 ). cache = ./cache/cord-000547-adfigzc1.txt txt = ./txt/cord-000547-adfigzc1.txt === reduce.pl bib === id = cord-000736-6f8vyziv author = Pripuzova, Natalia title = Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens date = 2012-08-17 pages = extension = .txt mime = text/plain words = 6818 sentences = 328 flesch = 54 summary = FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). The analytical sensitivity of each primer set was determined in the single virus testing using FDA/CBER panels (kindly provided by Dr. Stephen Kerby, FDA/CBER) consisting of various amounts of the viruses (0-1,000 genome copies/ml) spiked into the ''normal'' human plasma. The results of sensitivity testing of the real-time PCR array primer sets specific for HIV-1, HIV-2, HBV, HCV, and WNV the with FDA/CBER analytical plasma panels. Tm and C(t) values obtained with primer sets specific for HIV-1, HCV, or HBV in testing of 17 human clinical samples in the format of PCR array targeting eight different viruses. cache = ./cache/cord-000736-6f8vyziv.txt txt = ./txt/cord-000736-6f8vyziv.txt === reduce.pl bib === id = cord-000725-rafwlw0t author = Hindinger, Claudia title = IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date = 2012-07-27 pages = extension = .txt mime = text/plain words = 5114 sentences = 243 flesch = 37 summary = Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). cache = ./cache/cord-000725-rafwlw0t.txt txt = ./txt/cord-000725-rafwlw0t.txt === reduce.pl bib === id = cord-000336-57es391o author = Liao, Qiuyan title = Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study date = 2011-03-11 pages = extension = .txt mime = text/plain words = 7649 sentences = 383 flesch = 39 summary = Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). The model proposed that attitudes towards vaccination (perceived benefits of pH1N1 vaccination and concerns regarding possible adverse effects of pH1N1 vaccination), perceived social pressures from significant others and other people around regarding pH1N1 vaccination (social norms regarding pH1N1 vaccination), perceived self-efficacy in taking vaccination (perceived self-efficacy), anticipated regret for not taking the pH1N1 vaccination (anticipated regret) and seasonal influenza vaccination history would predict vaccination intention, which in turn predicts vaccination planning and future vaccination uptake; anticipated regret and perceived self-efficacy could also predict vaccination status directly; finally, vaccination planning was proposed to bridge the intention-behavior gap and predict vaccination status directly ( Figure 3 ). cache = ./cache/cord-000336-57es391o.txt txt = ./txt/cord-000336-57es391o.txt === reduce.pl bib === id = cord-000638-ss1435el author = Beq, Stephanie title = Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date = 2012-04-16 pages = extension = .txt mime = text/plain words = 5142 sentences = 237 flesch = 47 summary = The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. In contrast, Arizcorreta and colleagues showed that IFNa and ribavirin therapy induces a substantial reduction of circulating sjTRECs, in HIV/HCV co-infected patients, accompanied by sustained naïve CD4 + T-cell defect, suggesting thymic dysfunction [10] . While the number of RTEs was similar in HCV-infected patients at study entry and healthy individuals ( These data demonstrate that, as early as one month following treatment initiation, IFNa induces stronger alterations of naïve Tcell subsets, and more specifically in the RTE compartment than in any other T-cell subset, suggesting a specific effect on thymopoiesis. cache = ./cache/cord-000638-ss1435el.txt txt = ./txt/cord-000638-ss1435el.txt === reduce.pl bib === id = cord-000321-ee7q7jhv author = Powell, Michael L. title = Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA date = 2011-02-08 pages = extension = .txt mime = text/plain words = 9458 sentences = 433 flesch = 51 summary = The features identified in caliciviral TURBS suggest a model for termination-reinitiation in which post-termination 40S subunits are tethered to the mRNA through interactions between the mRNA (through motif 1) and 18S rRNA, initiation factors are recruited and the AUG restart codon located, processes which may require precise RNA folding (involving motif 2) within the TURBS. Analysis of primary and secondary structural features of the BM2 signal has revealed that it contains a short TURBS (of 45 nt) which is largely single-stranded, with motif 1 likely to be located in the apical loop of a metastable stem-loop structure when the ribosome is positioned at the termination codon of the upstream ORF [11] . Importantly, mutation of the motif 1 homologue such that it was fully complementary to yeast 18S rRNA led to a significant (p,0.01) increase in BM2fluc synthesis relative to the wild-type BM2 reporter ( Figure 4C ), supporting the view that mRNA:rRNA base pairing is a key determinant in BM2 ORF expression. cache = ./cache/cord-000321-ee7q7jhv.txt txt = ./txt/cord-000321-ee7q7jhv.txt === reduce.pl bib === id = cord-000715-zl1s82yi author = Shulman, Lester M. title = Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition date = 2012-07-16 pages = extension = .txt mime = text/plain words = 4786 sentences = 248 flesch = 50 summary = These samples were selected from among archived stool samples previously tested for enterovirus and MS2 after extraction by QIAamp Viral RNA Mini Kit. A sufficient number of samples with high, intermediate, and low levels of inhibitors were chosen for re-analysis to enable comparison between extraction procedures at each of these levels of inhibition. Analysis of variance ( Fig. 3 , part 2), indicated that there was no significant difference (paired t-test, P.0.05) between the inhibition of rRT-PCR of the MS2 external control and the added enterovirus (P.0.05) for protocols A, C, and D. Stool suspensions (N = 185) prepared for routine analysis of clinical stool samples sent to the Central Virology Laboratory (CVL) at Chaim Sheba Medical Center in Israel were used to evaluate the efficiency of four different RNA extraction systems in excluding inhibitors of rRT-PCR. cache = ./cache/cord-000715-zl1s82yi.txt txt = ./txt/cord-000715-zl1s82yi.txt === reduce.pl bib === id = cord-000208-th0wddvc author = Cornelissen, Lisette A. H. M. title = A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 date = 2010-05-14 pages = extension = .txt mime = text/plain words = 5671 sentences = 290 flesch = 49 summary = title: A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 Such HA trimers, expressed either in insect or mammalian cells, were indeed shown to elicit neutralizing antibodies [16] and to partially protect mice against HPAI H5N1 challenge infection [19] . In view of their promising potential we have evaluated recombinant soluble HA trimers in chickens and mice for their ability to induce protective immunity against infection with HPAI H5N1. Subsequently, vaccination with the sH5 3 preparation was shown to provide complete protection against challenge with HPAI H5N1 both in mice and in chickens, in the latter already after a single immunization. In the present study we evaluated the vaccine potential of a recombinant soluble H5 protein (sH5 3 ) to protect chickens and mice against a lethal infection with HPAI H5N1. A pseudotype baculovirusmediated vaccine confers protective immunity against lethal challenge with H5N1 avian influenza virus in mice and chickens cache = ./cache/cord-000208-th0wddvc.txt txt = ./txt/cord-000208-th0wddvc.txt === reduce.pl bib === id = cord-000326-a18rch1f author = Zhou, Jun-Wei title = Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes date = 2011-02-24 pages = extension = .txt mime = text/plain words = 4829 sentences = 276 flesch = 50 summary = This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. Several additional lines of evidence also indicated the possible involvement of APOM in the development of diabetes and metabolic disturbances: 1) the human APOM gene is located within a high susceptibility region (6q21-q23) to type 2 diabetes (T2D) in genome-wide linkage analyses [6] . 2) SNP rs805296 (T-778C) in APOM promoter has been associated with the levels of plasma total cholesterol (TC) and fasting plasma glucose (FPG) in non-diabetic participants, 3) SNP rs805296 has also been associated with the susceptibility to T2D and coronary artery disease among the Northern Chinese [7, 8] . While our results did not support an association between APOM and T2D susceptibility in Hong Kong Chinese, subgroup analyses found SNP as well as haplotype associations between APOM and metabolic traits in T2D. cache = ./cache/cord-000326-a18rch1f.txt txt = ./txt/cord-000326-a18rch1f.txt === reduce.pl bib === id = cord-000554-p4ufea6x author = Gao, Wei title = Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date = 2012-01-18 pages = extension = .txt mime = text/plain words = 5516 sentences = 289 flesch = 54 summary = title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus We have also observed cross-talk between MAP kinase and NFkB pathways, and our data indicate that MAP kinase ERK1/2 and JNK1/2 may impact the activation of NFkB through the induction of RIG-1, leading to IFN-b induction in H1N1pdm-infected swine macrophages. To understand the mechanism of proinflammatory cytokine and TNF family ligand induction in H1N1pdm-infected swine macrophages, we investigated how MAP kinases were activated and whether their signaling pathways were involved in the regulation of various cytokines and TNF family ligands in pig immune cells. To evaluate the role of MAP kinases in the regulation of proinflammatory cytokine responses in H1N1pdm-infected swine macrophages, we pre-treated 3D/4 cells with specific inhibitors for ERK1/2, p38, and JNK1/2 1 hr prior to infection. cache = ./cache/cord-000554-p4ufea6x.txt txt = ./txt/cord-000554-p4ufea6x.txt === reduce.pl bib === id = cord-000581-ewx5xhrb author = Rudge, James W. title = Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories date = 2012-02-21 pages = extension = .txt mime = text/plain words = 5718 sentences = 218 flesch = 36 summary = This study was conducted as part of the AsiaFluCap project (www.asiaflucap.org), the overall aim of which is to conduct health systems analyses to support capacity development for responding to pandemic influenza across six countries and territories in Asia, specifically: Cambodia, Indonesia, Lao PDR, Taiwan, Thailand and Vietnam. Estimating resource needs, gaps, and associated mortality In our baseline scenario, resource gaps were estimated assuming that 12% of ''general'' hospital resources (beds, ventilators and human resources) are available for care of pandemic influenza cases, with the remaining 88% required for maintaining essential healthcare services, as in a previous pilot study for Thailand [20] , and based on previous reports [25] [26] . Figure 1 presents the geographical distribution of estimated resource gaps across provinces (or districts in the case of Indonesia) in each study country for the modeled pandemic influenza scenario, under our baseline assumptions and point estimates for parameter values. cache = ./cache/cord-000581-ewx5xhrb.txt txt = ./txt/cord-000581-ewx5xhrb.txt === reduce.pl bib === id = cord-000721-leedutqo author = Nawaz, Sameena title = Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK date = 2012-07-24 pages = extension = .txt mime = text/plain words = 3199 sentences = 162 flesch = 50 summary = Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). The prevalence of HBoV-2 in children in the UK was significantly lower than that reported in a study in Australia, in which HBoV-2 was detected in 17.2% and 8.1% of the cases and controls, respectively [22] . Human bocavirus in children hospitalized for acute gastroenteritis: a case-control study cache = ./cache/cord-000721-leedutqo.txt txt = ./txt/cord-000721-leedutqo.txt === reduce.pl bib === id = cord-001014-8yrpcl94 author = Kitagawa, Hiroshi title = Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis date = 2013-07-03 pages = extension = .txt mime = text/plain words = 4451 sentences = 288 flesch = 57 summary = title: Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. Expression of IL-4 mRNA was significantly decreased in the ear skin of intra-nasally rhPIV2/Ag85B treatment group compared to that of PBS treated mice (Fig. 4A) . mRNA expressions of TNF-a and MIP-2 were significantly decreased in both of intra-nasally and subcutaneously rhPIV2/Ag85B treated groups compared with PBS or vector treated group (Fig. 4E, F) . Ag85B is a conserved protein in mycobacterial species and can elicit a strong Th1-type immune Expressions of IL-4, TNF-a and MIP2-a mRNA were significantly decreased in the ear skin treated with intranasally rhPIV2/Ag85B treated group compared to those of control groups. cache = ./cache/cord-001014-8yrpcl94.txt txt = ./txt/cord-001014-8yrpcl94.txt === reduce.pl bib === === reduce.pl bib === id = cord-000478-88wo4xen author = Gowen, Brian B. title = Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date = 2011-10-24 pages = extension = .txt mime = text/plain words = 4407 sentences = 221 flesch = 49 summary = Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. Interestingly, the 10 7 and 10 8 pfu DEF201 groups presented with little to no day-7 virus burden in the serum, liver, or spleen, while the 10 6 group developed viral titers that were comparable to the rAd EV and placebo controls ( Figure 2B-D) . This may not be the case with hamsters treated with DEF201 24 h prior to challenge since most had no detectable virus titers in spleen, liver, or serum on day 7 of PICV infection ( Figure 2B-D) . Animals were treated i.n. with a single dose 10 8 pfu of DEF201, the rAd EV control virus, or PBS placebo 7 or 14 days prior to PICV infection. cache = ./cache/cord-000478-88wo4xen.txt txt = ./txt/cord-000478-88wo4xen.txt === reduce.pl bib === id = cord-001007-645zegcv author = Kim, Hak title = Identification of Recombinant Human Rhinovirus A and C in Circulating Strains from Upper and Lower Respiratory Infections date = 2013-06-27 pages = extension = .txt mime = text/plain words = 4060 sentences = 189 flesch = 48 summary = This study analyzed parts of the viral genes spanning the 5′ noncoding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples. This study aimed to understand and characterize the various recombination events between 5' NCR and VP4/VP2 region of field strains of HRV including species A, B and C, using 105 HRVs identified from two distinctive laboratory surveillance systems, the Acute Respiratory Infectious Network (ARINET) and Severe Lower Respiratory Tract Infections (SLRI) surveillances undertaken from October 2008 to March 2009. In conclusion, this study is the first report describing intraand interspecies genomic recombination in circulating HRV-A and -C isolated from patients with acute or severe respiratory illness and these results will assist in investigating the causes of the diversity and evolution of HRVs arising through recombination events. cache = ./cache/cord-001007-645zegcv.txt txt = ./txt/cord-001007-645zegcv.txt === reduce.pl bib === id = cord-000413-h2e6h076 author = Zhang, Jingyu title = A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13 date = 2011-07-11 pages = extension = .txt mime = text/plain words = 4445 sentences = 233 flesch = 56 summary = To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. We showed that the decreased amount of the high and intermediate molecular weight multimers were dramatically reduced by mAb SZ34 in a concentration-dependent manner under shear stress (Figure 2 ), further confirming the role of SZ34 in decreasing the susceptibility of VWF to proteolytic cleavage by ADAMTS13 under physiologically relevant conditions. cache = ./cache/cord-000413-h2e6h076.txt txt = ./txt/cord-000413-h2e6h076.txt === reduce.pl bib === id = cord-000837-rdpsxb4n author = Perez-Pepe, Marcelo title = BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis date = 2012-12-20 pages = extension = .txt mime = text/plain words = 7079 sentences = 366 flesch = 50 summary = title: BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins. To assess the suitability of BUHO for the analysis of additional cell structures, we investigated several examples of cytoplasmic foci stained with different strategies, including SGs and PBs in mammalian and insect cells, and synapses and Smaug 1-mRNA silencing foci (S-foci) in primary neurons. Moreover, as expected given that SGs and PBs are morphologically similar, we found that prototype SGs were useful to identify PBs. To test the performance of BUHO in analyzing distances between objects, we focused on the presence of synaptic mRNA silencing foci at the synapse surroundings. With minor modifications, we have successfully applied it for processing images of different magnification and resolution of synapses, SGs, PBs and similar foci in mammalian and Drosophila cell lines as well as in primary cultured neurons. cache = ./cache/cord-000837-rdpsxb4n.txt txt = ./txt/cord-000837-rdpsxb4n.txt === reduce.pl bib === id = cord-000237-mticfoic author = Guan, Xuhua title = Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008 date = 2010-07-23 pages = extension = .txt mime = text/plain words = 5405 sentences = 266 flesch = 51 summary = We conducted a systematic review of the Chinese-and Englishlanguage literature in order to describe pneumonia incidence and mortality in China, evaluate the quality of published studies, and identify gaps in the literature that can be addressed through surveillance and epidemiologic research projects in the future. Based on published recommendations for measuring quality of epidemiologic studies of pneumonia [15] , we assessed quality using the following six criteria: (1) geographic location was reported, (2) study was conducted for a period of at least one year or multiples of one year to account for seasonal factors, (3) site of case detection or surveillance location was reported, (4) age and population size of cohort of at least 50 cases were reported, (5) quality assurance and monitoring methods were employed to assure that data was complete and high quality, and (6) a clearly defined case definition (e.g., not based solely on clinical diagnosis) was used and reported. In children aged ,5 years, the highest mortality rates were reported by four studies that were each conducted in multiple regions throughout mainland China (9.55±14.40 deaths from pneumonia per 1,000 live births; Table S3 ) [21, 23, 38, 48] . cache = ./cache/cord-000237-mticfoic.txt txt = ./txt/cord-000237-mticfoic.txt === reduce.pl bib === id = cord-000248-zueoyesj author = Berretta, Regina title = Cancer Biomarker Discovery: The Entropic Hallmark date = 2010-08-18 pages = extension = .txt mime = text/plain words = 33594 sentences = 1678 flesch = 43 summary = These authors cite, for example, ''mitochondrial dysfunction'' [5, 6] (including, but not limited to ''glucose avidity'' [7] and ''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'' [6, 8] , ''altered glycolysis'' [9] , ''altered bioenergetic function of mitochondria'' [10] ), ''dysregulation of cell cycle and defective genome-integrity checkpoints'' [11] , ''aberrant DNA methylation'' [12] (''promoter hypermethylation of hallmark cancer genes'' [13] and ''CpG island hypermethylation and global genomic hypomethylation'' [14] ), ''shift in cellular metabolism'' [15, 16, 17] , ''regional hypoxia'' [18] , ''microenviroment acidosis'' [19] , ''abnormal microRNA regulation'' [20, 21] , ''aneuploidy'' and ''chromosome aberrations'' [22, 23, 24, 25, 26] , ''disruption of cellular junctions'' [27] , ''avoidance of the immune response'' [28] , ''pre-existing chronic inflammatory conditions'' [29, 30] , ''cancerrelated inflammation'' [29] , ''disabled autophagy'' [28] , ''impaired cellular senescence'' [31] , ''altered NF-kappaB signalling'' [32] , ''altered growth patterns, not altered growth per se'' [33] , ''disregulated DNA methylation and histone modifications'' [34] , ''tissue dedifferentiation'' [35, 36] , and ''somatically heritable molecular alterations'' [37] . cache = ./cache/cord-000248-zueoyesj.txt txt = ./txt/cord-000248-zueoyesj.txt === reduce.pl bib === id = cord-000158-d08buwtu author = Corti, Davide title = Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals date = 2010-01-20 pages = extension = .txt mime = text/plain words = 8060 sentences = 343 flesch = 44 summary = The 2G12 epitope is not present in the majority of clade C isolates [27] , but, of more concern, no 2G12-like activity has been detected in the sera of HIV-1 infected individuals [21, 22] , suggesting that this type of neutralizing antibody may not be generally amenable to elicitation by B cells. By using an improved memory B cell immortalization method [41] , combined with highthroughput parallel screening with a panel of recombinant Envbased antigens, we isolated a panel of 58 human mAbs which we have characterized with regard to epitope specificity and breadth of neutralization. The mAbs were purified and further characterized for binding specificity and neutralizing activity using an extended panel of recombinant Env proteins and pseudoviruses representative of several HIV-1 clades with diverse coreceptor usage, geographic origin and conformation. cache = ./cache/cord-000158-d08buwtu.txt txt = ./txt/cord-000158-d08buwtu.txt === reduce.pl bib === === reduce.pl bib === id = cord-000375-fvfl0bn1 author = Shen, Ching-I title = The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus date = 2011-05-06 pages = extension = .txt mime = text/plain words = 4026 sentences = 208 flesch = 55 summary = This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry. In contrast to the finding for MAA/MAL-I, abundant SNA signals were mainly restricted to the mucin + cells (ratio of SNA + /mucin + cells, 0.8560.09, n = 368) ( Fig. 2A) , indicating that the goblet cells expressed SAa2-6Gal terminal glycan. To determine whether a single basal cells can express both SAa2-3Gal and SAa2-6Gal, CTE cells were triple-stained with K14 primary antibody (Cy5-2u Ab, purple), FITC-conjugated MAA (green) and biotin-labeled SNA (detected by Cy3-Streptovidin, red) (Figs. In humans, by contrast, both ciliated and goblet cells can be labeled with MAA/MAL-I and SNA [19, 20] , indicating that these two epithelial cells have both types of influenza viral receptors. cache = ./cache/cord-000375-fvfl0bn1.txt txt = ./txt/cord-000375-fvfl0bn1.txt === reduce.pl bib === id = cord-000265-llilwq1u author = Gao, Rongbao title = A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case date = 2010-10-12 pages = extension = .txt mime = text/plain words = 4896 sentences = 253 flesch = 46 summary = Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Although H5N1 virus infection of humans is primarily one of the lower respiratory tract, more recent reports suggested that influenza A H5N1 may in rare, severe cases, disseminate beyond the lungs and infect brain [26, 27] , intestines [20, 27] and lymphoid tissues [27] , and result in extra-pulmonary clinical manifestations including encephalopathy or encephalitis [15, 28] . To better understand the pathogenesis of human H5N1 virus infection, and investigate the route of virus dissemination in vivo, we report on the use of different techniques to detect virus distribution and infection of 5 organ systems in a laboratory confirmed fatal human H5N1 virus infection, and analyze the relationship between viral load in tissues and host response. cache = ./cache/cord-000265-llilwq1u.txt txt = ./txt/cord-000265-llilwq1u.txt === reduce.pl bib === id = cord-000851-uylgyhs8 author = Wang, Zhenya title = Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro date = 2013-01-07 pages = extension = .txt mime = text/plain words = 4519 sentences = 213 flesch = 47 summary = faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased. The results from quantitative RT-PCR shown in Fig. 5 reveal a decreased expression of these mediators when compared to the non-treated samples (SwIV-infected 3D4/21-cells without E. faecium effectively protects host cells from swine influenza virus infection and are in support of the above author's hypothesis, that probiotics are not only useful to inhibit enteric viruses, but may also have potential for the control of respiratory viruses. faecium before SwIV-infection and a 1 h treatment after completion of virus infection also led to a 2-3 log-unit loss of virus titer, the probiotic must alter host cell factors which apparently results in an inhibition of influenza virus multiplication. faecium in SwIV-infected 3D4/21 cells, the reduced inflammatory response caused by some cytokines at the cellular level may contribute to the antiviral effect of the probiotic. cache = ./cache/cord-000851-uylgyhs8.txt txt = ./txt/cord-000851-uylgyhs8.txt === reduce.pl bib === id = cord-000180-howix091 author = MacLeod, Iain J. title = Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry date = 2010-03-05 pages = extension = .txt mime = text/plain words = 6788 sentences = 316 flesch = 49 summary = By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. As induction of the NF-kB reporter construct occurred within one hour of inoculation with DgH virions and peaked at around two-and-a-half hours post-inoculation, then the transcripts previHFFs were stimulated with 1000 particles/cell of DgB, DgD or DgH HSV-1 for six hours and a cDNA microarray corresponding to targets of 19 signalling pathways was used to detect changes in cellular gene expression when compared to mock-infected. Real-time PCR confirmed that changes in transcription associated with the NF-kB, JAK/STAT, JAK/Src and PI3K pathways were modulated as a result of virion binding, all of which required gD on the envelope surface To demonstrate that signalling occurred at physiologically relevant multiplicities of infection, HFFs were inoculated with either 1000, 100, 10 or 1 particles per cell of entry-defective HSV-1. cache = ./cache/cord-000180-howix091.txt txt = ./txt/cord-000180-howix091.txt === reduce.pl bib === === reduce.pl bib === id = cord-001045-jm60nxc2 author = DeLisle, Sylvain title = Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy date = 2013-08-13 pages = extension = .txt mime = text/plain words = 4332 sentences = 209 flesch = 45 summary = METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The ARI CDA flagged an outpatient visit if the provider assigned it an ARI-related International Disease Classification, 9 th Revision, Clinical Modification (ICD-9) diagnostic code OR issued a prescription for a cough remedy OR documented at least two symptoms from the above ARI case definition in his/her clinical note, as retrieved by computerized text analysis [10] . Discussion Automated text analyses of chest imaging reports improved the performance of EMR-based CDAs that included structured data elements and free-text search for ARI symptoms. cache = ./cache/cord-001045-jm60nxc2.txt txt = ./txt/cord-001045-jm60nxc2.txt === reduce.pl bib === id = cord-000809-9voqa1oy author = Archer, Brett N. title = Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa date = 2012-11-16 pages = extension = .txt mime = text/plain words = 3885 sentences = 208 flesch = 50 summary = We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial R(t)) and the temporal variation of R(t). In this work we incorporate data collected on all laboratory-confirmed cases detected during the 2009 pH1N1 epidemic in South Africa with the aim of describing the transmissibility characteristics (initial R t and temporal variation of R t ) of the epidemic in the country and compare its dynamics with those observed in other countries in the same year. When estimating initial R t , we focus our analysis on the exponential growth phase of the epidemic in South Africa (i.e. the period from the first occurrence of five consecutive days with confirmed cases reported to the epidemic peak). cache = ./cache/cord-000809-9voqa1oy.txt txt = ./txt/cord-000809-9voqa1oy.txt === reduce.pl bib === id = cord-000536-0mn1gbll author = Hu, Le-Le title = Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions date = 2011-12-29 pages = extension = .txt mime = text/plain words = 5134 sentences = 265 flesch = 48 summary = In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. In this study, we proposed a multi-target model based on chemical-chemical interactions for predicting the metabolic pathways where compounds participate in. Listed in Table 2 are the accuracies by each of the 11 prediction orders for the 3,137 compounds about their involvement in the 11 metabolic pathway classes using the 5-fold crossvalidation test. cache = ./cache/cord-000536-0mn1gbll.txt txt = ./txt/cord-000536-0mn1gbll.txt === reduce.pl bib === id = cord-000726-tonaaft2 author = Chang, Binggong title = Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems date = 2012-07-27 pages = extension = .txt mime = text/plain words = 4986 sentences = 239 flesch = 50 summary = Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy). We compared the effect of individual PrP-specific monoclonal antibodies (Mabs) on the PrP C -PrP Sc conversion process using both an N2a/22L cell culture model and the test-tube PMCA system. To more completely explore the possible therapeutic effect of anti-PrP antibodies, and to establish another system to analyze the influence of Abs on the conversion process, we screened Mabs produced in our laboratory for their capacity to inhibit PrP Sc formation. cache = ./cache/cord-000726-tonaaft2.txt txt = ./txt/cord-000726-tonaaft2.txt === reduce.pl bib === id = cord-000261-ip32y0j5 author = Becker, Pablo D. title = Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice date = 2010-10-04 pages = extension = .txt mime = text/plain words = 5816 sentences = 270 flesch = 48 summary = Following immunization, human CD19 + B cells were sorted based on surface CD27 expression, as a marker of memory phenotype, and the isotype of surface Igs. The sorted B cell populations were immortalized in vitro by retroviral transduction with human B cell lymphoma (BCL)-6 and BCL-XL genes and antigen-specific B cell clones were established and characterized. The obtained results provided the proof-of-concept for the usefulness of this generic approach based on HIS mice combined with immortalization of human B cells for the rapid and inexpensive development of human mAbs against a wide range of antigens. Since HIS mice contained broad naïve B cell repertoires, we analyzed the induction of human antigen-specific B cell responses after immunization with commercially available human vaccines. So far, humanized mouse models based on the transplantation of human HSC only -i.e. without additional human tissues -share these limitations, and immunization strategies result in the limited generation of class-switched antigen-specific B cell responses [14, 31, 32] . cache = ./cache/cord-000261-ip32y0j5.txt txt = ./txt/cord-000261-ip32y0j5.txt === reduce.pl bib === id = cord-000959-nk2thkme author = Downer, Eric J. title = Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date = 2013-05-06 pages = extension = .txt mime = text/plain words = 5396 sentences = 268 flesch = 48 summary = METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The purpose of the study was to compare the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and the response of these cells to LPS in samples prepared from the LP cohort and a cohort which we classified as IQ memory-consistent (high-performing, HP) individuals. P) TLR4 expression on CD11b + MDMs was increased in the LP group compared with the HP group (P,0.05) and this is also shown in the representative dot plots of TLR4 + cells ( and following LPS stimulation [6] , while pro-inflammatory cytokine [52] and chemokine [53, 54] levels are elevated in peripheral blood monocytes isolated from the elderly after LPS stimulation. cache = ./cache/cord-000959-nk2thkme.txt txt = ./txt/cord-000959-nk2thkme.txt === reduce.pl bib === id = cord-000877-usz7pnvu author = Abdel-Moneim, Ahmed S. title = Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia date = 2013-01-30 pages = extension = .txt mime = text/plain words = 1826 sentences = 101 flesch = 51 summary = title: Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV. Human bocavirus (HBoV) was first found in children with acute respiratory tract infections in 2005 [1] . The current study aims to screen the epidemiological status and molecular phylogeny of HBoV isolates prevailing in pediatric patients with respiratory infection in Saudi Arabia. The current study investigated the prevalence of HBoV in patients suffering from respiratory tract infections in Saudi Arabia. Furthermore, the phylogenetic analysis results of three selected sequences showed that the Saudi HBoV1 strains obtained from respiratory samples belonged to group I human bocaviruses (Fig. 1) . Detection of human bocavirus in Japanese children with lower respiratory tract infections Frequent detection of viral coinfection in children hospitalized with acute respiratory tract infection using a real-time polymerase chain reaction cache = ./cache/cord-000877-usz7pnvu.txt txt = ./txt/cord-000877-usz7pnvu.txt === reduce.pl bib === id = cord-000642-mkwpuav6 author = Moreira, Rebeca title = Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date = 2012-04-19 pages = extension = .txt mime = text/plain words = 6848 sentences = 372 flesch = 45 summary = title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. Moreover, a few transcripts encoded by genes putatively involved in the clam immune response against Perkinsus olseni have been reported by cDNA library sequencing [18] . philippinarum transcriptome and another four bivalve species sequences were analyzed by comparative genomics (Crassostrea gigas of the family Ostreidae, Bathymodiolus azoricus and Mytilus galloprovincialis of the family Mytilidae and Laternula elliptica of the family Laternulidae). cache = ./cache/cord-000642-mkwpuav6.txt txt = ./txt/cord-000642-mkwpuav6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000425-isw6jeir author = Flori, Laurence title = Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date = 2011-07-29 pages = extension = .txt mime = text/plain words = 7831 sentences = 388 flesch = 46 summary = A study on Yorkshire pigs selected for eight generations for high and low adaptive IR (HIR and LIR, respectively) on an index combining four standardized measures of specific antibodies and cellmediated IR, after stimulation with specific antigens (bacillus Calmette-Guérin and hen egg white lysozyme), has revealed that HIR and LIR animals differ in response to immunization and infection [2, 11, 12, 13, 14] . Finally, several significant QTLs for total leukocyte count ( [20, 21] ; Animal-QTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/index), mitogen-induced proliferation [20] , antibody response [20, 22] , cytokine production (IL10 and IFNc) [23] , complement activity [22] , and acute phase protein serum concentration [22] have been detected and mapped to different pig chromosomes. In this report, we present the results of a global genetic study, combining principal component analysis (PCA), and genetic parameter estimation applied to a large number of innate and adaptive ITs in a pig population vaccinated against Mycoplasma hyopneumoniae (M. cache = ./cache/cord-000425-isw6jeir.txt txt = ./txt/cord-000425-isw6jeir.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000539-uh3q65we author = Zhang, Yi title = Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice date = 2012-01-03 pages = extension = .txt mime = text/plain words = 4620 sentences = 247 flesch = 51 summary = BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. In the present mouse model, the number of leukocytes observed in the BALF of virus-infected mice significantly increased compared with the control mice on day 8 p.i. Different counts in BALF showed that the proportion of neutrophils dramatically increased. cache = ./cache/cord-000539-uh3q65we.txt txt = ./txt/cord-000539-uh3q65we.txt === reduce.pl bib === === reduce.pl bib === id = cord-000833-m6abyuvx author = Sekiguchi, Satoshi title = Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date = 2012-12-17 pages = extension = .txt mime = text/plain words = 5915 sentences = 348 flesch = 50 summary = The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. These observations, in addition to the modified histology activity index (HAI) scores, indicated that expression of HCV proteins caused chronic hepatitis in the CN2-29 (+/2) /MxCre (+/2) mice because a weak, though persistent, immune response followed an initial bout of acute hepatitis ( Figure S1 ). To determine whether activation of the host immune response caused the reduction with HCV protein levels in the livers of CN2-29 (+/2) /MxCre (+/2) mice, we used a highly attenuated VV strain, LC16m8, to generate three rVVs [12] . To determine whether rVV-N25 treatment induced the same effect in other strains of HCV transgenic mice, we analyzed RzCN5-15 (+/2) /MxCre (+/2) mice, which express all HCV proteins; in these mice, chronic hepatitis was resolved within 28 days of immunization with rVV-N25. cache = ./cache/cord-000833-m6abyuvx.txt txt = ./txt/cord-000833-m6abyuvx.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000374-gt2pwc9b author = Yang, Albert C. title = Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index date = 2011-05-04 pages = extension = .txt mime = text/plain words = 5304 sentences = 279 flesch = 43 summary = With these considerations in mind, in the present study, we introduce a bottom-up genotype-phenotype analysis to investigate the association between genetic polymorphisms and autonomic control of heart rate dynamics, using three common polymorphisms in genes encoding b-adrenergic receptor (b-AR) as an example. The analyses of the present study were two-fold: 1) a nonrandomness index [17] derived from the IBS method was applied to quantify the nonlinear aspect of HRV according to b-AR genotype and to test the correlation of this index with standard HRV indices; and 2) using agglomerative hierarchical cluster analysis, we unsupervisedly categorized these subjects into clusters based on pairwise dissimilarity among heart rate dynamics, and then we investigated the association of these clustering patterns with b-AR gene polymorphisms. The data presented in this study demonstrate a significant association of a common b 2 -AR polymorphism, Arg16Gly, with the non-randomness index, a nonlinear HRV measure derived from the IBS method. cache = ./cache/cord-000374-gt2pwc9b.txt txt = ./txt/cord-000374-gt2pwc9b.txt === reduce.pl bib === === reduce.pl bib === id = cord-000947-psguw47w author = Feng, Jianyu title = A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation date = 2013-04-24 pages = extension = .txt mime = text/plain words = 4685 sentences = 270 flesch = 54 summary = We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. To elucidate why scFv-A4 had the chaperone-like function, we combined computer modeling and peptide array membrane technique to study the interactions between scFv-A4 and HCK. Firstly, bioinformatics software tools were used to predict the interacting sites between scFv-A4 and HCK and then the results were combined with the peptide array membrane experiment results to build the 3D models of the binding complex. In complex model-I, scFv-A4 exhibits chaperone-like function by assisting the folding of HCK and stabilizing the whole structure. In this study we combined computer modeling and the peptide array membrane method to investigate the interaction between scFv-A4 and HCK. cache = ./cache/cord-000947-psguw47w.txt txt = ./txt/cord-000947-psguw47w.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-001078-5m29nugu author = Chen, Xiaorong title = Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study date = 2013-09-17 pages = extension = .txt mime = text/plain words = 3930 sentences = 200 flesch = 47 summary = title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection. Factors analyzed for possible correlation with clinical features and treatment outcomes in patients included 1) baseline characteristics of patients, such as age, sex, occupation, underlying conditions, exposure to poultry and/or wild birds in the past seven days, date of symptom onset and hospital admission, date of specimen collection, and date of positive diagnosis; 2) results from laboratory tests and imaging examinations; 3) treatment regimen including basic supporting therapy, antibiotic therapy, antiviral therapy, traditional Chinese medicine (TCM) therapy, and other therapies if applicable; and 4) current condition of patients including the length of stay in the hospital. cache = ./cache/cord-001078-5m29nugu.txt txt = ./txt/cord-001078-5m29nugu.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-001120-fxd533b4 author = Everitt, Aaron R. title = Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model date = 2013-11-21 pages = extension = .txt mime = text/plain words = 4874 sentences = 252 flesch = 47 summary = We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. Here we sought therefore to expand and define the role of Ifitm3 in pathogen restriction by assessing the susceptibility of Ifitm3-deficient (Ifitm3 -/-) mice to bacteria (Salmonella Typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis), a parasite (Plasmodium berghei) and a virus (respiratory syncytial virus, RSV) to determine the specificity of this crucial antimicrobial protein. Similarly, bacterial counts revealed no significant differences between wild type and Ifitm3 -/-mice; together showing that Ifitm3 does not play a role in resistance or susceptibility to Salmonella infection. The experimental challenge revealed there to be no significant difference in phenotype seen in Ifitm3 -/-mice compared with wild type littermate controls, with both showing susceptibility to ECM ( Figure 5A ). cache = ./cache/cord-001120-fxd533b4.txt txt = ./txt/cord-001120-fxd533b4.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-001099-jirkkkvy author = Yousuf, Mohammad A. title = Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells date = 2013-10-11 pages = extension = .txt mime = text/plain words = 7110 sentences = 372 flesch = 46 summary = Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling. Initial binding is followed by a secondary interaction between the arginine-glycine-aspartic acid (RGD) motif in the viral capsid penton base and cellular integrins α v β 3 , α v β 5, and α V β 1 [42] [43] [44] [45] This secondary interaction is thought to induce a host cell signaling cascade resulting in clathrin mediated endocytosis [46] [47] [48] , and possibly, activation of the rab5 dependent classical endosomal pathway [49] . Herein, we show that HAdV-D37, an etiologic agent of epidemic keratoconjunctivitis, enters primary human corneal fibroblasts predominantly via lipid rafts and caveolae, suggesting both redundancy and cell specificity in mechanisms of adenoviral entry. To further examine the role of lipid raft microdomains in HAdV-D37 entry, we treated corneal cells with both Cy3-labeled virus and 488-CTXB, and tracked their cellular localization over time ( Figure 1C ). cache = ./cache/cord-001099-jirkkkvy.txt txt = ./txt/cord-001099-jirkkkvy.txt === reduce.pl bib === === reduce.pl bib === id = cord-001199-9khx93c0 author = Liu, Fengchen title = Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model date = 2014-02-06 pages = extension = .txt mime = text/plain words = 6871 sentences = 300 flesch = 48 summary = Changes in household structure and the proportion of children in the population as a result of the one-child policy could have more effects on the AR, and the difference in AR could be as high as 60% under a scenario of very high immunity loss rate per year ( Figures 5(A) ). For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average annual attack rates over 10 years (2015 to 2024) between two policies. For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average annual attack rates over 10 years (2015 to 2024) between two policies. For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average secondary attack rates over 10 years (2015 to 2024) between two policies. cache = ./cache/cord-001199-9khx93c0.txt txt = ./txt/cord-001199-9khx93c0.txt === reduce.pl bib === id = cord-001186-jkg7qkj6 author = Skowronski, Danuta M. title = Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk date = 2014-01-27 pages = extension = .txt mime = text/plain words = 8871 sentences = 412 flesch = 40 summary = During spring-summer 2009, several observational studies from Canada reported that prior receipt of the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness, with estimated risk or odds ratios of 1.4-2.5 compared to those unvaccinated [1] . Protein microarray results were consistent with ELISA but in addition showed vaccine-induced HA1 antibody to the seasonal H1 antigen, for which values were significantly higher in vaccinated animals relative to pre-immunization and compared to placebo from day 28, most pronounced from day 49 after the first TIV dose (i.e. three weeks after two-dose vaccine series completion) ( Figure 2 ). Lower neutralizing antibody to A(H1N1)pdm09 even at Ch+14 among vaccinated versus placebo ferrets, although not statistically significant, is consistent with human immunogenicity trials showing blunting of pandemic H1N1 vaccine-induced responses in association with prior seasonal vaccine receipt [53] [54] [55] [56] . cache = ./cache/cord-001186-jkg7qkj6.txt txt = ./txt/cord-001186-jkg7qkj6.txt === reduce.pl bib === id = cord-001213-gxqufddb author = Butt, Azeem Mehmood title = Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses date = 2014-03-04 pages = extension = .txt mime = text/plain words = 7178 sentences = 371 flesch = 54 summary = Therefore, from the similarity index analysis, we observed that selection pressure from hosts and vectors have contributed to shaping the molecular evolution of CHIKV at the respectively, on the formation of the overall codon usage patterns of CHIKV (Figure 2 ). Although, the nucleotide composition correlation analysis showed that codon usage in CHIKV genomes is mainly caused by compositional constraints or mutational pressure, we were interested to determine the possible influence of other factors, such as natural selection. However, in case of CHIKV genomes, variations in nucleotide base compositions were noted (Table 1 ), indicating that other factors, such as natural selection, could also influence overall synonymous codon usage bias. The RSCU values for all the coding sequences of CHIKV genomes were calculated to determine the characteristics of synonymous codon usage without the confounding influence of amino acid composition and the size of coding sequence of different gene samples, following a previously described method [18] . cache = ./cache/cord-001213-gxqufddb.txt txt = ./txt/cord-001213-gxqufddb.txt === reduce.pl bib === id = cord-001117-llb4f74a author = Ji, Wen-Jie title = Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments date = 2013-11-19 pages = extension = .txt mime = text/plain words = 4964 sentences = 257 flesch = 34 summary = Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. Based on current evidence, we speculated that pharmacological inhibition of MR with clinically approved drug, may regulate lung macrophage phenotype switching, as well as their progenitors, bone marrow-derived circulating monocytes, and may confer novel therapeutic potential in a murine model of bleomycin-induced acute pulmonary injury and fibrosis. cache = ./cache/cord-001117-llb4f74a.txt txt = ./txt/cord-001117-llb4f74a.txt === reduce.pl bib === id = cord-001251-forh7lw4 author = Jank, Johanna M. title = The Domain-Specific and Temperature-Dependent Protein Misfolding Phenotype of Variant Medium-Chain acyl-CoA Dehydrogenase date = 2014-04-09 pages = extension = .txt mime = text/plain words = 7785 sentences = 553 flesch = 51 summary = Here we established a comprehensive experimental setup to analyze the structural consequences of eight ACADM missense mutations (p.Ala52Val, p.Tyr67His, p.Tyr158His, p.Arg206Cys, p.Asp266Gly, p.Lys329Glu, p.Arg334Lys, p.Arg413Ser) identified after newborn screening and linked the corresponding protein misfolding phenotype to the site of side-chain replacement with respect to the domain. In a previous study, we provided first experimental evidence for the impact of eight additional ACADM mutations identified in NBS on MCAD structure and function and all of these were clearly associated with conformational derangement and decreased protein stability [16] . Moreover, we summarized and quantified the structural data and visualized the molecular protein misfolding phenotype of the variant MCAD proteins in a 3D plot comparing them to the wild-type, to p.Lys329Glu, the classical severe mutation, and to p.Tyr67His, discussed to be a mild mutation. To visualize results from experiments investigating thermal stability, kinetic stability, and conformation of MCAD wild-type and variants, we combined data and developed relative scores assessing the severity of mutation-induced changes. cache = ./cache/cord-001251-forh7lw4.txt txt = ./txt/cord-001251-forh7lw4.txt === reduce.pl bib === id = cord-001207-yjaiybwf author = Sachsenröder, Jana title = The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium date = 2014-02-19 pages = extension = .txt mime = text/plain words = 5919 sentences = 302 flesch = 49 summary = faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. However, it is not known so far, whether probiotic bacteria can also influence the general composition of the faecal virome, e.g. by changing the composition of the bacterial community, which represents the host population for bacteriophages, or by direct interactions with specific viruses. Faecal samples from sows and their piglets experimentally fed with or without the probiotic bacterium were analyzed using a process-controlled deep sequencing method. As the detection rate of the bacteriophages is -besides technical factors -also dependent on the amount of viruses initially present in the analyzed sample, improved deep sequencing methods enabling quantitative analyses should be developed in future for comparative virome investigations. cache = ./cache/cord-001207-yjaiybwf.txt txt = ./txt/cord-001207-yjaiybwf.txt === reduce.pl bib === id = cord-001129-gi2kswai author = Lemos de Matos, Ana title = Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals date = 2013-11-27 pages = extension = .txt mime = text/plain words = 6978 sentences = 342 flesch = 47 summary = Because viruses are responsible for a great number of severe and lethal diseases, together with the important role that RLRs play in mammalian innate immune system, we expect that RIG-I, MDA5 and LGP2 genes may have been under intense selective pressures in all mammals. Evidence for positive selection on mammalian orthologous for RIG-I ( Figure S7 ), MDA5 ( Figure S8 ) and LGP2 ( Figure S9 ) genes was detected using PAML package [54, 55] site-specific models M1a versus M2a and M7 versus M8. (C) Positively-selected codons are exhibited in the table and numbered according to the mammalian LGP2 deduced protein sequences alignment ( Figure S6 downstream RIG-I and MDA5 signaling, which implies functional constraints, the observed variability across species can be perceived as a great structural plasticity for mammalian CARDs. The helicase domain in the RLR family is generally described as exhibiting affinity for dsRNA [78] . cache = ./cache/cord-001129-gi2kswai.txt txt = ./txt/cord-001129-gi2kswai.txt === reduce.pl bib === id = cord-001162-z8cbbit3 author = Yun, Heather C. title = Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection date = 2014-01-08 pages = extension = .txt mime = text/plain words = 3365 sentences = 160 flesch = 41 summary = title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection While coinfections with viral pathogens including 2009 H1N1 have been described in patients with respiratory infections, few prospective studies have related these to clinical presentation and outcomes in adults since molecular diagnostics became available, and none in the setting of high background rates of adenovirus. [12] [13] [14] [15] [16] [17] We sought to describe the epidemiology of 2009 H1N1 and adenovirus in a basic training population, and to correlate differences in clinical presentations and outcomes with each respective pathogen and in coinfections. Subject enrollment was variable throughout the study period, depending on rates of clinical illness within the training population, as well as availability of study personnel to enroll trainees, and given that 2009 H1N1 influenza virus PCR was done as part of clinical care, there could have been some differences in those who enrolled vs. cache = ./cache/cord-001162-z8cbbit3.txt txt = ./txt/cord-001162-z8cbbit3.txt === reduce.pl bib === id = cord-001145-hc9ssruz author = Akazawa, Yuko title = Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis date = 2013-12-13 pages = extension = .txt mime = text/plain words = 6256 sentences = 407 flesch = 52 summary = We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. pylori-positive gastric mucosa, as well as transcriptional up-regulation of Bim in AZ-521 cells treated with VacA plus NH 4 Cl. Since knockdown of PERK decreased VacA-mediated Bim mRNA expression, activation of Bim likely occurred downstream of ER stress. cache = ./cache/cord-001145-hc9ssruz.txt txt = ./txt/cord-001145-hc9ssruz.txt === reduce.pl bib === id = cord-001368-ymp1pj3r author = Zhang, Chao title = Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro date = 2014-07-28 pages = extension = .txt mime = text/plain words = 4430 sentences = 236 flesch = 50 summary = title: Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro Scorpions are a rich source of antimicrobial peptides: (1) androctonin isolated from the hemolymph of Androctonus australis, shows marked sequence similarity to tachyplesins, polyphemusins and gomesin [3, 4] ; (2) hadrurin from the venom of Hadrurus aztecus, which is hemolytic [5] ; (3) opistoporin-1, which possesses hemolytic activity, and opistoporin-2, both from the venom of the South African scorpion Opistophtalmus carinatus [6] ; (4) scorpine, which is the subject of this study, arising from the venom of Pandinus imperator, was shown to have anti-bacterial and anti-plasmodial activity in vitro [7] , and has shown a potent toxic effect on sexual and asexual stages of Plasmodium berghei and Plasmodium falciparum, respectively, and also a strong inhibition of dengue 2 virus (DENV-2) infection [8] . cache = ./cache/cord-001368-ymp1pj3r.txt txt = ./txt/cord-001368-ymp1pj3r.txt === reduce.pl bib === id = cord-001126-uqr00nzd author = Zhang, Zhicheng title = Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1 date = 2013-11-26 pages = extension = .txt mime = text/plain words = 4902 sentences = 226 flesch = 45 summary = In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. To explore whether the evolution of codon usage bias in TTSuV2 CDS had been driven by mutation pressure alone or whether translation selection from its host has also contributed, we first compared the correlation between general nucleotide composition (A%, T%, G%, C%, GC%) and nucleotide composition at the third codon position (A 3S %, T 3S %, G 3S %, C 3S %, GC 3S %) using the Spearman's rank correlation analysis method (Table 4) . These results further support the conclusion that composition constraints under mutational bias is an important factor determining synonymous codon usage pattern in TTSuV2, and but that other factors, such as natural selection, contributed. cache = ./cache/cord-001126-uqr00nzd.txt txt = ./txt/cord-001126-uqr00nzd.txt === reduce.pl bib === id = cord-001254-y2knt8g0 author = Parkhomenko, Taisiya A. title = Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis date = 2014-04-15 pages = extension = .txt mime = text/plain words = 6739 sentences = 325 flesch = 50 summary = Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Finally, the relative concentration of total anti-DNA Abs correlated with the relative specific IgG DNase activity better in the sera (CC = +0.51; columns 6 and 12) than in CSF (CC = + 0.11; columns 5 and 11) (Tables 2 and 3 ). cache = ./cache/cord-001254-y2knt8g0.txt txt = ./txt/cord-001254-y2knt8g0.txt === reduce.pl bib === id = cord-001142-puj74k7y author = Crescenzo-Chaigne, Bernadette title = The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression date = 2013-11-21 pages = extension = .txt mime = text/plain words = 3355 sentences = 183 flesch = 55 summary = To investigate whether, or not, and how the complete NC regions of a given segment are involved in type specificity, we attempted to rescue, by reverse genetics, type A and C influenza viruses with chimeric non-coding sequences. The sole difference between 5'A/3'C(C5U) and wild-type 5'A/3'A viruses being the 3' distal extremity of the NS segment suggested that the level of NS encoded proteins (i.e. NS1 or/and NS2/NEP) was affected at early stages of infection for this virus (5'A/3'C(C5U)). The major role of the proximal panhandle in type specificity that we identified and the hypothesized involvement of the distal panhandle in transcription need to be tested on the other (2 PFU/cell), viral vRNA and mRNA levels for each segment were evaluated by specific two-step RT-qPCRs previously described [23] . cache = ./cache/cord-001142-puj74k7y.txt txt = ./txt/cord-001142-puj74k7y.txt === reduce.pl bib === id = cord-001219-517gka4h author = Timpka, Toomas title = Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign date = 2014-03-07 pages = extension = .txt mime = text/plain words = 5805 sentences = 247 flesch = 37 summary = We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. A hypothetical explanatory model was constructed to inform the analysis of the main research question; i.e. to what extent selfreported intentions to perform protective behaviors during influenza outbreaks can be explained by perceptions of threat and the ability to cope as outlined in the PMT, self-assessments of health status, trust in official information, and sociodemiographic factors. cache = ./cache/cord-001219-517gka4h.txt txt = ./txt/cord-001219-517gka4h.txt === reduce.pl bib === id = cord-001280-skavefji author = Choi, Sang-Ho title = Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients date = 2014-05-13 pages = extension = .txt mime = text/plain words = 4136 sentences = 204 flesch = 35 summary = This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. Exclusion criteria were as follows: (1) patients in whom the pathogen was not identified, (2) patients in whom BAL fluid analysis was impossible (due to severe neutropenia or clotting of specimen) or not performed, (3) patients with a mixed infection (identification of bacteria and virus), (4) patients who were treated with antimicrobial agents for more than 24 hours before bronchoscopic BAL, (5) patients with invasive pulmonary aspergillosis, (6) patients with mycobacterial infection, and (7) patients with Pneumocystis jirovecii pneumonia. Several authors of the current study previously investigated the diagnostic utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in BAL fluid of various patient populations with bilateral lung infiltrates. cache = ./cache/cord-001280-skavefji.txt txt = ./txt/cord-001280-skavefji.txt === reduce.pl bib === id = cord-001359-c1uom5f7 author = Oslund, Karen L. title = Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells date = 2014-07-17 pages = extension = .txt mime = text/plain words = 4567 sentences = 290 flesch = 53 summary = In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level. In this study, we demonstrate synergistic induction of CXCL10 in well differentiated primary human bronchial epithelial (HBE) cells following influenza virus infection and the treatment with IFN c. As shown in Fig. 1A , well differentiated HBE cells demonstrated significant synergistic induction of CXCL10 mRNA following infection with the MEM influenza virus and treatment with IFN c. These results demonstrate that influenza virus in combination with IFN c synergistically induce CXCL10 mRNA and protein production from primary human airway epithelial cells. cache = ./cache/cord-001359-c1uom5f7.txt txt = ./txt/cord-001359-c1uom5f7.txt === reduce.pl bib === id = cord-001249-awn9ayy6 author = Lasecka, Lidia title = The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space date = 2014-04-08 pages = extension = .txt mime = text/plain words = 9953 sentences = 453 flesch = 50 summary = ERp57 while the structure of the ER, ERGIC and Golgi remains unchanged Two isolates of NSDV have been previously described by us [29] : a multiple-times passaged isolate of NSDV from Uganda, which appeared attenuated upon infection of a susceptible animal, and an isolate of GV from India which had been passaged a limited number of times in mouse brain or BHK21 clone 13 cells and which caused haemorrhagic gastroenteritis in sheep upon experimental inoculation. No change to the cellular distribution of calnexin was observed (Figure 2 j-l), indicating that, despite the disappearance of PDI and ERp57, the overall structure of the ER remains unchanged in NSDV-infected cells. Another flavivirus, Dengue virus (DENV) (which, like NSDV, can cause a haemorrhagic fever), increased surface levels of PDI in infected endothelial cells [86] . In this study we have demonstrated that NSDV induces the redistribution of soluble ER oxidoreductases, specifically PDI and ERp57, in infected cells, and that the viral PreGn glycoprotein appears to be involved in this process. cache = ./cache/cord-001249-awn9ayy6.txt txt = ./txt/cord-001249-awn9ayy6.txt === reduce.pl bib === id = cord-001275-a9o2dvke author = Chen, Xue title = A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types date = 2014-05-06 pages = extension = .txt mime = text/plain words = 5558 sentences = 254 flesch = 47 summary = title: A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. In this study, we showed for the first time that fusing HPV16 L2 aa 17-36 epitope repeats to a recombinant ligand for FccRs (designated L2R4, see Figure 1A -B) could significantly increase the immunogenicity of the L2 peptide and induce cross-neutralizing antibodies and protective immunity against a range of phylogenetically distant HPV types. cache = ./cache/cord-001275-a9o2dvke.txt txt = ./txt/cord-001275-a9o2dvke.txt === reduce.pl bib === id = cord-001432-d4zavkcn author = Nishida, Yoriko title = Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry date = 2014-10-16 pages = extension = .txt mime = text/plain words = 5268 sentences = 306 flesch = 48 summary = PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Actin-related protein 3 (ACTR3) was over-expressed in the cytoplasm and nucleus of MNCs infiltrated to the islets in FT1DM-affected pancreas tissue. Signal transducer and activator of transcription 1-alpha/beta (STAT1) was highly expressed in islet endocrine cells and MNCs in FT1DM tissue ( Figure 2Q, R) . cache = ./cache/cord-001432-d4zavkcn.txt txt = ./txt/cord-001432-d4zavkcn.txt === reduce.pl bib === id = cord-001421-6t5puo6p author = Marfà, Santiago title = Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date = 2014-10-02 pages = extension = .txt mime = text/plain words = 5057 sentences = 229 flesch = 46 summary = The serum proteomic profile and routine liver and renal function tests were initially analyzed in a training set of 10 HCV-RNA recurrent LT patients 6 months post LT that showed a fibrosis stage F$1 at 1 year after LT. HVPG was assessed in 53 of these patients and the average value was of 5.560.8 mm Hg. All the serum samples showed a quite similar expression pattern and coincidences included both the different peptide fragments detected and the signal intensity of these fragments (Data S4). All serum samples included in the test set showed an intensity m/z 5905 peak well below the values found in both healthy subjects and non recurrent HCV patients. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. cache = ./cache/cord-001421-6t5puo6p.txt txt = ./txt/cord-001421-6t5puo6p.txt === reduce.pl bib === id = cord-001387-2g9dc5z4 author = McIntyre, K. Marie title = A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe date = 2014-08-19 pages = extension = .txt mime = text/plain words = 4582 sentences = 215 flesch = 40 summary = By coupling the H-index method with the EID2, the primary aim of this study was to establish priority lists of human and domestic animal pathogens (including zoonoses) present in Europe. Its potential as a quantitative One Health indicator (i.e. a single measure applicable to both human and animal diseases) was investigated by comparing scores for human-only, zoonotic, and animal-only pathogen groups, including emerging status as this would likely drive research impact. We investigated its value as a proxy for animal disease impact by comparing domestic animal pathogen H-indices with other measures of impact including presence on the OIE list [10] , and inclusion in DISCONTOOLS [11] . The study establishes priority lists of human and domestic animal pathogens (including zoonoses) present in Europe, using the H-index as a proxy measure for impact. cache = ./cache/cord-001387-2g9dc5z4.txt txt = ./txt/cord-001387-2g9dc5z4.txt === reduce.pl bib === id = cord-001537-i34vmfpp author = Lima, Francisco Esmaile de Sales title = Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date = 2015-02-17 pages = extension = .txt mime = text/plain words = 3874 sentences = 195 flesch = 53 summary = The predicted protein sequences encoded by ORF2 (cap) and ORF1 (rep) of BatCV I-VI genomes were used for phylogenetic analysis with representative and recently discovered circoviruses/cycloviruses; Pepper golden mosaic virus was used as outgroup, as they are somewhat related to other members in the Circoviridae family (Fig. 3A, 3B and 3C ). The phylogenetic analysis constructed based on the alignments of the complete REP and CAP protein confirms that BatCV POA/II and VI cluster into the genus Cyclovirus along with the Chinese cycloviruses sequences clade detected in bat feces [18] and sharing less than 65% of identity at the CAP/REP amino acid level. BatCV POA I and V had a low amino acid identity with CAP (<20%) and REP (<10%) sequences of two other sequences detected in bat feces in this study with known circoviruses/cycloviruses (Table 2) . cache = ./cache/cord-001537-i34vmfpp.txt txt = ./txt/cord-001537-i34vmfpp.txt === reduce.pl bib === id = cord-001435-ebl8yc92 author = Hoppe, Sebastian title = Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date = 2014-10-21 pages = extension = .txt mime = text/plain words = 9619 sentences = 545 flesch = 50 summary = Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. Incubation with antibodies reactive to either of those two bacterial species resulted in signal intensities in the neighbourhood of the negative control independent of sequence alterations, see Figure 11 . In contrast, the other two proteins displaying linear epitopes, KPN_00363 and KPN_00459, indicated some specificity with the antibodies tested and two linear consensus sequences could be derived, GAVVALSTTFA and GIAFGAVELFD, respectively. cache = ./cache/cord-001435-ebl8yc92.txt txt = ./txt/cord-001435-ebl8yc92.txt === reduce.pl bib === id = cord-001420-b4zcvd04 author = Crescenzo-Chaigne, Bernadette title = Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation date = 2014-09-30 pages = extension = .txt mime = text/plain words = 6267 sentences = 296 flesch = 56 summary = Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication. The sequence of both ends of each segment of each rescued virus was verified as described [9] , and no Influenza NP Non Coding Region Role in Translation PLOS ONE | www.plosone.org genetics, type A and type C viruses with one or both heterotypic ends. These data based on type A influenza virus NP segment showed that it is possible to obtain virus by reverse genetics when a homotypic proximal panhandle and a homotypic strength of the initial distal panhandle are maintained, and that the length of the 59 end plays an important role in the efficiency of rescue. cache = ./cache/cord-001420-b4zcvd04.txt txt = ./txt/cord-001420-b4zcvd04.txt === reduce.pl bib === id = cord-001455-n7quwr4s author = Rapin, Noreen title = Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans date = 2014-11-12 pages = extension = .txt mime = text/plain words = 3719 sentences = 198 flesch = 50 summary = title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses. We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23. We used samples collected during the experiment to address the question: Can hibernating bats respond to infection by activating genes responsible for innate immune and stress responses? We determined levels of transcripts for several immune and stress response genes (Table 1) in lungs from infected and control bats. cache = ./cache/cord-001455-n7quwr4s.txt txt = ./txt/cord-001455-n7quwr4s.txt === reduce.pl bib === id = cord-001599-pfdnmzx2 author = Wee, Yin Shen title = Age-Related Onset of Obesity Corresponds with Metabolic Dysregulation and Altered Microglia Morphology in Mice Deficient for Ifitm Proteins date = 2015-04-09 pages = extension = .txt mime = text/plain words = 6017 sentences = 327 flesch = 45 summary = Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. As we maintain these animals as homozygous deletion lines, over time we have observed a pronounced enhanced weight gain and an obesity phenotype (e.g., [21] [22] [23] ) in older IfitmDel mice compared to C57BL/6 controls. In this report we quantify the obesity phenotype and link this to altered leptin/neuropeptide signaling, and demonstrate abnormal microglia morphology in the IfitmDel animal. Based upon the previously described findings that the absence of the Ifitm proteins can alter cellular induction pathways following type I interferon treatment, we tested whether or not the IfitmDel animals would have an altered response, compared to WT, to chronic Poly I:C treatment. cache = ./cache/cord-001599-pfdnmzx2.txt txt = ./txt/cord-001599-pfdnmzx2.txt === reduce.pl bib === id = cord-001263-hqxiyxfj author = Kam, Yiu-Wing title = Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development date = 2014-04-22 pages = extension = .txt mime = text/plain words = 5676 sentences = 282 flesch = 46 summary = title: Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development In addition to the anti-E2 glycoprotein responses, we also identified new linear B-cell epitopes that were recognized by anti-CHIKV antibodies from CHIKV-infected macaques. Results showed two structural proteins (Capsid protein and E2 glycoprotein) and three nonstructural proteins (nsP1, nsP3 and nsP4 proteins) contained linear epitopes that were recognized by macaque anti-CHIKV antibodies. Here, E2EP3 is one of the major B-cell linear epitopes recognized by antibodies from the sera of all CHIKV-infected macaques during the early phase of disease (amino acids 2800-2818, Table 1 ). Infection of macaques with the LR2006-OPY1 isolate, which encodes K 252 in the E2 glycoprotein, strongly induced anti-CHIKV antibodies against a particular linear B-cell epitope (amino acids 3025-3066) at 16 dpi. cache = ./cache/cord-001263-hqxiyxfj.txt txt = ./txt/cord-001263-hqxiyxfj.txt === reduce.pl bib === id = cord-001343-3euy4u9k author = Wang, Yadong title = A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices date = 2014-06-27 pages = extension = .txt mime = text/plain words = 4088 sentences = 161 flesch = 40 summary = In recognition of the national need for an in-service program to target the''level four'' health staff as defined by WADEM, i.e.'h ealth workers who played lead roles in disaster health management'' [20] , China's Ministry of Health (MoH) commissioned the Capital Medical University in 2010 to develop and implement a competency-based curriculum to help strengthen the performance of the new cadre of HERO staff. We assessed tasks, roles and responsibilities, and training needs of HERO staff through face-to-face interviews of eleven experienced key informants; they included health emergency experts from the government, the military and the academic sector, and senior staff of HEROs. We also explored their awareness of existing training activities and the associated relative strengths and weaknesses, their preferences on modes of curriculum delivery and the optimal duration of in-service training. cache = ./cache/cord-001343-3euy4u9k.txt txt = ./txt/cord-001343-3euy4u9k.txt === reduce.pl bib === id = cord-001446-mpuovmeb author = Bratcher, Preston E. title = Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA date = 2014-11-03 pages = extension = .txt mime = text/plain words = 4873 sentences = 226 flesch = 43 summary = Circulating levels of SP-D have been examined for their potential use as a biomarker in various diseases including dermatitis [2, 3] , acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] , periodontitis [14] , interstitial pulmonary fibrosis (IPF) [10, 12, [15] [16] [17] [18] [19] [20] [21] [22] [23] , chronic obstructive pulmonary disease (COPD) [15, [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] , emphysema [37] , cystic fibrosis (CF) [15, 38, 39] , coronary disease [40, 41] , sclerosis [42] [43] [44] [45] [46] , cancer [47, 48] , sarcoidosis [21, 49] , allergies [28, [50] [51] [52] , rheumatoid arthritis [53, 54] , and respiratory infections [18, [55] [56] [57] [58] [59] [60] . Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis cache = ./cache/cord-001446-mpuovmeb.txt txt = ./txt/cord-001446-mpuovmeb.txt === reduce.pl bib === id = cord-001571-drcfdv9z author = Alvarez, Julio title = Impact of Porcine Epidemic Diarrhea on Performance of Growing Pigs date = 2015-03-13 pages = extension = .txt mime = text/plain words = 3100 sentences = 133 flesch = 60 summary = Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs' performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014. Collected data included information on the site in which pigs were located, site production type (nursery or wean to finish (WF)), pig source (sow farm from which pigs originated), start and close period on each site, number of pigs per batch, mortality (defined by percentage of total pigs started), average daily gain (ADG), average daily feed intake (ADFI), feed conversion (FCR), and status of the sow farm from which pigs were weaned for PRRS and PED. cache = ./cache/cord-001571-drcfdv9z.txt txt = ./txt/cord-001571-drcfdv9z.txt === reduce.pl bib === id = cord-001363-irysq6pf author = Liu, Zhenjiang title = SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects date = 2014-07-23 pages = extension = .txt mime = text/plain words = 5113 sentences = 271 flesch = 49 summary = Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a breakthrough in clinical proteomics, and can detect different protein expression patterns of body fluid and tissue specimens between patients and healthy subjects, and its rapid development provides an alternative tool to search for biomarkers. The purpose of this pilot study was to preliminarily explore the differential protein expression pattern between NTD case mothers and normal control mothers using SELDI-TOF-MS protein profiling and Classification and Regression Tree (CART) analysis, in order to differentiate pregnancies complicated by the presence of an NTD-affected fetus from healthy controls. Analysis of amniotic fluid samples from mothers of NTDaffected fetuses and normal control mothers revealed two major, differentially expressed proteins at 14700 and 13776 Da used in the classification pattern to generate 3 terminal nodes (Fig. 7) . However, when we analyzed the data, we found that only four protein/peptide biomarkers, 4188, 6451, 11744 and 23425 Da, were detected in all serum, urine and amniotic fluid samples. cache = ./cache/cord-001363-irysq6pf.txt txt = ./txt/cord-001363-irysq6pf.txt === reduce.pl bib === id = cord-001447-oi7bkm4z author = Dhanasekaran, Sakthivel title = Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo date = 2014-11-04 pages = extension = .txt mime = text/plain words = 6012 sentences = 318 flesch = 51 summary = We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Infection of peripheral blood mononuclear cells (PBMC) from four breeds of goats and water buffalo resulted in differential viral replication kinetics and inflammatory cytokine profile including IFNa, IFNc and TNFa with differential activation of TLR3 and TLR7. To determine whether the differential IFN and pro-inflammatory cytokine production between Kanni/Salem vs Barbari/ Tellicherry breeds of goats are dependent on single nucleotide polymorphisms (SNPs) in TLR genes, we examined the complete gene sequence of TLR7. cache = ./cache/cord-001447-oi7bkm4z.txt txt = ./txt/cord-001447-oi7bkm4z.txt === reduce.pl bib === id = cord-001546-ndz3oarf author = Ayithan, Natarajan title = Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date = 2015-02-26 pages = extension = .txt mime = text/plain words = 5128 sentences = 298 flesch = 52 summary = Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. cache = ./cache/cord-001546-ndz3oarf.txt txt = ./txt/cord-001546-ndz3oarf.txt === reduce.pl bib === id = cord-001734-bbeznd3r author = Gupta, Garvita title = NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics date = 2015-08-10 pages = extension = .txt mime = text/plain words = 9729 sentences = 418 flesch = 53 summary = Taken together, CD and NMR results define the 172-residue NS3pro domain to be an intrinsically disordered protein which is lacking of both stable secondary and tertiary structures in the absence of the NS2B cofactor [22, [31] [32] [33] [34] [35] [36] . On the other hand, only a small set of broad peaks could be detected in its HSQC spectrum (Fig 4B) , indicating that the NS3B (1-130) in the LMPC micelle undergoes significant conformational exchanges on μs-ms time scale, or/and dynamic aggregation, which thus prevents from further high-resolution NMR studies. Interestingly, although NMR characterization deciphers that the NS3pro domains have different dynamics on the μs-ms time scale in the contexts of being complexed with NS (48-100) in buffer and with NS2B (1-130) in the LMPC micelle, they have very similar enzymatic activities. cache = ./cache/cord-001734-bbeznd3r.txt txt = ./txt/cord-001734-bbeznd3r.txt === reduce.pl bib === id = cord-001605-8p06bpt1 author = Sapmak, Ariya title = The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei date = 2015-04-13 pages = extension = .txt mime = text/plain words = 5165 sentences = 308 flesch = 53 summary = title: The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type. marneffei MCO participates in conidial DHN-melanin synthesis, we combined 55 fungal MCO sequences and performed alignments using CLUSTALW (http://www.genome.jp/ tools/clustalw/). marneffei PbrB, this clade comprises of characterized laccases functioning in conidial DHN-melanin synthesis. Talaromyces (Penicillium) marneffei pbrB Gene Cytoplasmic protein extracts from the wild type and ΔpbrB mutant cultured in brain heart infusion broth at 37°C for 3 days were capable of catalyzing L-DOPA (data not shown). cache = ./cache/cord-001605-8p06bpt1.txt txt = ./txt/cord-001605-8p06bpt1.txt === reduce.pl bib === id = cord-001781-afg1nmib author = Saksena, Sumeet title = Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam date = 2015-09-23 pages = extension = .txt mime = text/plain words = 7626 sentences = 395 flesch = 49 summary = We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. The results presented here highlight three main findings: 1) when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor; but in peri-urban landscapes emergence factors converge, including higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture; 2) high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks; as are 3) landscapes where intensive and extensive forms of poultry production are co-located. Hence diseases associated with rice production are likely to peak in peri-urban areas given other risk factors such as land-use diversity, CTI, and distance to infrastructure. cache = ./cache/cord-001781-afg1nmib.txt txt = ./txt/cord-001781-afg1nmib.txt === reduce.pl bib === id = cord-001748-7e8px4vx author = Nobach, Daniel title = Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews date = 2015-08-27 pages = extension = .txt mime = text/plain words = 4873 sentences = 249 flesch = 47 summary = The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). In animals caught in 2013 (group 1: female #2, male #5, female #6), after an adaption phase of one month, samples of saliva, lacrimal fluid, skin surface, urine and excrements from the BoDV-1-infected shrews were taken weekly over a period of 4 weeks as necessary veterinary care. The five other shrews did not exhibit any evidence for BoDV-1-infection, neither infectious virus nor viral RNA was detected at any time point investigated. Current data from living shrews provide reliable evidence that natural BoDV-1-infection in these animals is indeed clinically inconspicuous over a long time period as already previously assumed [15, 18] despite persistent infection with shedding of infectious virus via various sites. Distribution of Borna Disease Virus Antigen and RNA in Tissues of naturally infected Bicolored White-Toothed Shrews, Crocidura leucodon, supporting their role as Reservoir Host Species cache = ./cache/cord-001748-7e8px4vx.txt txt = ./txt/cord-001748-7e8px4vx.txt === reduce.pl bib === id = cord-001958-2gt3fwpy author = Meseda, Clement A. title = Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines date = 2016-02-19 pages = extension = .txt mime = text/plain words = 8161 sentences = 361 flesch = 43 summary = Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. In the work described here, we demonstrate in mouse models that percutaneous inoculation of MVA elicited protective immune responses against lethal intranasal challenge with the Western Reserve (WR) strain of vaccinia virus, and at low doses of MVA, lower morbidity was recorded in mice that were vaccinated via the percutaneous route than in those immunized via the intramuscular or subcutaneous routes. In a preliminary experiment to investigate the utility of the percutaneous route for the delivery of MVA, we observed that MVA delivered by tail scarification, while statistically insignificant (p = 0.298), elicited a higher vaccinia-specific IgG response and protection in mice than the same dose (10 6 pfu) delivered by the intramuscular route (S1 Fig) . cache = ./cache/cord-001958-2gt3fwpy.txt txt = ./txt/cord-001958-2gt3fwpy.txt === reduce.pl bib === id = cord-001601-tsuz3j40 author = Ngan, Luong Thi My title = Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses date = 2015-04-10 pages = extension = .txt mime = text/plain words = 6157 sentences = 328 flesch = 53 summary = An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. In the presence of 100 μg/mL PA or 20 μg/mL PGG in MRC5 cell cultures infected with HRV-2, the RNA replication levels were reduced by 30.1 and 14.3 fold, respectively, compared to the levels in the cell cultures without the compounds (Fig 4A) . cache = ./cache/cord-001601-tsuz3j40.txt txt = ./txt/cord-001601-tsuz3j40.txt === reduce.pl bib === id = cord-001620-yy5gq0ki author = Woo, Hye-Min title = Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5 date = 2015-04-22 pages = extension = .txt mime = text/plain words = 3871 sentences = 213 flesch = 55 summary = These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus. Subtype H5 is known as highly pathogenic in protein (GST-H5-HA1) was incubated with 100 μL of glutathione agarose beads in 100 μL of binding buffer (50 mM Tris/HCl; pH 8.0, 150 mM NaCl, 1.5 mM MgCl 2 , 2 mM DTT, and 1% [w/v] BSA) for 30 min at room temperature with occasional shaking. To select specific ssDNA aptamers that can distinguish H1-HA1 from H5-HA1, counter-SELEX was performed with an ssDNA library of 88-mers containing a randomized sequence region of 45 nucleotides in the center, followed by lambda exonuclease digestion, as shown in Fig 1A. To confirm that the selected aptamers were bound to the sialic acid-binding region of HA1, we performed a flow cytometry analysis (Fig 7) . cache = ./cache/cord-001620-yy5gq0ki.txt txt = ./txt/cord-001620-yy5gq0ki.txt === reduce.pl bib === id = cord-001383-hww0watl author = Li, Wenchao title = Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats date = 2014-08-12 pages = extension = .txt mime = text/plain words = 6541 sentences = 291 flesch = 48 summary = title: Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, we found that the major structural genes of PPRV can be efficiently expressed in recombinant baculovirus-infected Sf21 insect cells and that these genes can then support the production of PPRV VLPs. The expression of M protein was necessary and sufficient for the formation of VLPs (data not shown); the additional expression of the H or F glycoproteins allowed formation of budding particles with the typical morphology and size of PPRV and related paramyxoviruses. cache = ./cache/cord-001383-hww0watl.txt txt = ./txt/cord-001383-hww0watl.txt === reduce.pl bib === === reduce.pl bib === id = cord-001716-lbtdex4p author = Gilca, Rodica title = Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015 date = 2015-07-22 pages = extension = .txt mime = text/plain words = 4070 sentences = 189 flesch = 37 summary = Canada's Sentinel Physician Surveillance Network (SPSN) measured vaccine effectiveness (VE) against medically-attended laboratory-confirmed outpatient A(H3N2) illness of -8% (95%CI:-50-23%) overall and 2% (95%CI:-49-36%) in non-elderly (<65-year-old) adults, indicating little or no vaccine protection even among individuals capable of mounting an effective immune response [2] . Although Canadian mid-season inpatient and outpatient VE findings for the 2014/15 season have been consistent with null vaccine effects (statistically non-significant and spanning zero) in both age groups, the CIRN finding of a lower and negative point estimate of VE against A(H3N2) hospitalization in the elderly, more closely broaching statistical significance, warrants further clarification. Multivariable analyses by logistic regression adjusted for age, underlying comorbidity placing individuals at higher risk of influenza-related complications [13] , interval between symptom onset and specimen collection (4 days, 5-7 days), hospital site, epidemic week based on hospital admission date (49-51, 52, 53 and 1-2), and primary residence (community, LTCF or other institutional/group setting). cache = ./cache/cord-001716-lbtdex4p.txt txt = ./txt/cord-001716-lbtdex4p.txt === reduce.pl bib === id = cord-001964-iy6qzq58 author = Muñoz-González, Sara title = Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar date = 2016-02-26 pages = extension = .txt mime = text/plain words = 6933 sentences = 319 flesch = 48 summary = The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Interestingly, the RNA of the vaccinal C-strain was undetectable by specific RT-PCR [8] in any of the samples analysed after vaccination, including blood, nasal and rectal swabs, or organs throughout the experiment, suggesting a phenomenon of homologous interference, also known as superinfection exclusion (SIE), between the high viral load generated by the primary persistent infection and the CSFV vaccine strain. cache = ./cache/cord-001964-iy6qzq58.txt txt = ./txt/cord-001964-iy6qzq58.txt === reduce.pl bib === id = cord-002141-9mxi4dzi author = Memczak, Henry title = Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding date = 2016-07-14 pages = extension = .txt mime = text/plain words = 8780 sentences = 476 flesch = 51 summary = title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding We used complementary experimental and theoretical approaches to select HA binding VH-CDR peptides and to improve their potential to inhibit binding, and finally, infection of cells by influenza A virus. Contribution to the total binding free energy change of every amino acid of PeB GF binding to HA of Aichi H3N2 obtained by MD-simulations is shown in Fig 2B. Our aim was to obtain peptide inhibitors that recognize the conserved region of the sialic acid binding pocket of HA with a broader specificity to cover several influenza virus strains. The three CDRs of the VH-chain of antibody HC19 against hemagglutinin of influenza virus Aichi H3N2 were used as templates to design peptides being a potential inhibitor of virus binding to host cells. As a consequence, the hemagglutination inhibition efficiency may not necessarily be stronger against Aichi H3N2, even though the peptide was derived from an antibody binding to this influenza strain. cache = ./cache/cord-002141-9mxi4dzi.txt txt = ./txt/cord-002141-9mxi4dzi.txt === reduce.pl bib === id = cord-001909-yy9xp5ms author = Buß, O. title = Statistical Evaluation of HTS Assays for Enzymatic Hydrolysis of β-Keto Esters date = 2016-01-05 pages = extension = .txt mime = text/plain words = 6998 sentences = 414 flesch = 49 summary = Two of the tested high throughput screening (HTS) assays depend on coupled enzymatic reactions which detect the alcohol released during ester hydrolysis by luminescence or absorption. The objective of this study is to select an HTS assay to screen for one enzyme for a two-step reaction cascade for the synthesis of β-amino acids. One assay relies on the change of the pH-value, the second is based on enzymatic oxidation of the released ethanol to acetic acid and the third, which we expected to be most sensitive, is based on the oxidation of ethanol to ethanal and hydrogen peroxide which is then converted by horseradish peroxidase (HRP) in a luminescence reaction. According to the other assays a positive control for the evaluation test contained only 2.0 mM ethanol without ester and hydrolase (see also subsection statistical analysis). cache = ./cache/cord-001909-yy9xp5ms.txt txt = ./txt/cord-001909-yy9xp5ms.txt === reduce.pl bib === id = cord-002044-9xgt3tf4 author = Hendiger, Jacek title = Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms date = 2016-05-12 pages = extension = .txt mime = text/plain words = 4537 sentences = 238 flesch = 56 summary = This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. In health care facilities, this way of ventilation system operation is utilized in both the Airborne Infection Isolation and Protective Environment Rooms, however, the key difference is the required direction of airflow between the room and the adjacent space, such as a corridor, which determines the application of negative or positive pressure in the protected room, respectively. The research described in the available literature, concerning migration of air between rooms in the conditions of pressure difference was conducted using tracer gases, CFD simulations and smoke visualization. The tests were made with dense smoke visualization in order to investigate the relation between the value of pressure difference, door swing and migration level of heavy contaminants between the rooms. cache = ./cache/cord-002044-9xgt3tf4.txt txt = ./txt/cord-002044-9xgt3tf4.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-002094-7tewne3a author = Tago, Damian title = The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases date = 2016-06-14 pages = extension = .txt mime = text/plain words = 6293 sentences = 303 flesch = 53 summary = Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The idea behind control strategies such as the MRP and vaccination [7] is that removing infected nodes or immunizing susceptible ones are efficient mechanisms to fight the spread of a disease. If an infectious disease is detected at t = 1, a farmer sufficiently close to the infected zone will face the risk that the restricted zone (RZ) will expand to include his location by the next period (with probability q). In the case of non-vector-borne diseases, i.e. when the transmission channel is restricted to the trade network, the MRP is an effective control strategy. The MRP becomes significantly less efficient when infected nodes that have not been detected spread the disease through both trade and geographic networks. cache = ./cache/cord-002094-7tewne3a.txt txt = ./txt/cord-002094-7tewne3a.txt === reduce.pl bib === === reduce.pl bib === id = cord-002043-z1b7pj3s author = Wang, Xue-Yang title = Comparative Transcriptome Analysis of Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV in Susceptible and Near-Isogenic Resistant Strains date = 2016-05-11 pages = extension = .txt mime = text/plain words = 5879 sentences = 359 flesch = 42 summary = obtained numerous differentially expressed genes (DEGs) involved in metabolism, immunity, and inflammatory responses in Microtus fortis following infection with Schistosoma japonicum based on comparative transcriptome analysis [20] . reported that several genes related to physical barriers, immune response, proteolytic/metabolic enzymes, heat-shock proteins, and hormonal signaling were possibly involved in silkworm resistance against Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) infection; although these genes might be induced by the virus in order to increase infectivity [21] . After BmNPV infection, the expression levels of 4 genes were down-regulation in BC9 and A35 (resistant strain) (Fig 6) , which was consistent with the transcriptome data. Based on their role in apoptosis activation, hosts need to increase the expression level of these genes to promote apoptosis when exposed to a virus; this supposition explains the up-regulation of genes involved in apoptosis in the transcriptome following BmNPV infection. cache = ./cache/cord-002043-z1b7pj3s.txt txt = ./txt/cord-002043-z1b7pj3s.txt === reduce.pl bib === === reduce.pl bib === id = cord-001982-arczqdza author = Khajah, Maitham A. title = Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis date = 2016-03-10 pages = extension = .txt mime = text/plain words = 6218 sentences = 313 flesch = 56 summary = It is thought that the beneficial effects of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on blood pressure control and in delaying/inhibiting the cardiac remodeling process is through increasing serum levels of Ang1-7 [9] [10] [11] [12] . A seven fold decrease in the plasma level of Ang 1-7 was demonstrated in DSS treated mice compared to untreated (UT) group at day 7 post colitis induction (Fig 1A) . The level of phosphorylated forms of three key signaling intermediates, ERK1/2 (Fig 8) , p38 MAPK (Fig 9) and Akt (Fig 10) , were measured by immunofluorescence in sections from resected colon tissue of untreated mice or mice treated with DSS (for 7 days) plus daily Ang 1-7 or saline (vehicle) treatment. cache = ./cache/cord-001982-arczqdza.txt txt = ./txt/cord-001982-arczqdza.txt === reduce.pl bib === id = cord-001761-yvd1n42f author = Yoshimura, Takeo title = Controlled Microwave Heating Accelerates Rolling Circle Amplification date = 2015-09-08 pages = extension = .txt mime = text/plain words = 4411 sentences = 223 flesch = 48 summary = Analysis of the temperature profiles of each RCA component subjected to microwave heating revealed the selectivity heating of buffer components compared with primers, template DNA, dNTP, and RNase-free water. To determine the component of RCA by microwave selectivity heating, we measured the temperatures of the five components (circularized template with primers, dNTPs, ThermoPol Buffer, Bst-LF, and RNase-free water) of the RCA and MW-RCA mixtures for 10 min from 13°C to 60°C. To reveal the effect of the selectivity heating in MW-RCA, we compared the efficiency of DNA amplification in the RCA and MW-RCA reactions mixtures containing a 4-fold excess concentration of each RCA component (dNTP, template-primers, Bst-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ). We performed MW-RCA reactions containing a four-fold higher concentration of each RCA component [dNTP, template-primers, Bst DNA polymerase-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ] to identify a link between microwave selective heating and DNA amplification. cache = ./cache/cord-001761-yvd1n42f.txt txt = ./txt/cord-001761-yvd1n42f.txt === reduce.pl bib === === reduce.pl bib === id = cord-002834-2htnywef author = Tsuchiaka, Shinobu title = Genetic diversity and recombination of enterovirus G strains in Japanese pigs: High prevalence of strains carrying a papain-like cysteine protease sequence in the enterovirus G population date = 2018-01-11 pages = extension = .txt mime = text/plain words = 2976 sentences = 154 flesch = 52 summary = title: Genetic diversity and recombination of enterovirus G strains in Japanese pigs: High prevalence of strains carrying a papain-like cysteine protease sequence in the enterovirus G population Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C–3A junction site. The insertion sequences were aligned and compared with those of the PL-CP of EV-G strains from the USA and Belgium and with the PL-VP sequences in the genome of nidoviruses including porcine and bovine toroviruses by phylogenetic analysis and pairwise sequence comparison (Fig 2 and S2 Table) . The G2-PL-CP strain HgYa2-1 showed high homology Genetic diversity and recombination of enterovirus G strains in Japanese pigs to G2 strains in the tree for VP4-VP3 and VP1, whereas HgYa2-1 showed high similarity with G1-PL-CP lineage 1 strains in regions P2 and P3 (Fig 3A) . cache = ./cache/cord-002834-2htnywef.txt txt = ./txt/cord-002834-2htnywef.txt === reduce.pl bib === id = cord-001898-ntqyjqqk author = Huang, Chih-Wei title = Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date = 2016-01-05 pages = extension = .txt mime = text/plain words = 6578 sentences = 337 flesch = 47 summary = The changes in tryptophan fluorescence were Dilution of monomeric K315A mutant protein denatured in 5 M GdmCl resulted in refolding to a similar conformation as the original monomeric state (Fig 5A and 5B) . Since refolding of partly unfolded monomeric mutant δ-crystallin resulted in a conformation with high exposure of hydrophobic regions, the occurrence of protein aggregation in the process was determined using light scattering measurement. An increase in fluorescence intensity resulting from binding of ThT with the aggregates over time was observed following dilution of 0.84 and 3 M GdmCl denatured monomeric mutant δ-crystallin into buffer (Fig 6B) . The unique stable conformation from unfolding of K315A mutant protein in the presence of urea suggests that the interactions provided by this residue at the interfaces may play a critical role in stabilization of the quaternary structure of δ-crystallin. cache = ./cache/cord-001898-ntqyjqqk.txt txt = ./txt/cord-001898-ntqyjqqk.txt === reduce.pl bib === === reduce.pl bib === id = cord-002473-2kpxhzbe author = Das, Jayanta Kumar title = Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach date = 2017-03-31 pages = extension = .txt mime = text/plain words = 4613 sentences = 285 flesch = 61 summary = Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. The primary protein sequence is read as consecutive order pairs serially from first amino acid to the end of sequence, and each order pair is nothing but a connected edge between the two nodes where nodes in the graph are involved with different chemical groups of amino acids. Our method of phylogenetic tree formation used the dissimilarity matrix which is obtained for every pair of sequence on the basis of chemical group specific score of amino acids. Based on the phylogenetic tree of five members, we find that the PpcA and PpcD, PpcB and PpcE are mostly closed with regards to the frequency of amino acids of respective eight chemical groups. cache = ./cache/cord-002473-2kpxhzbe.txt txt = ./txt/cord-002473-2kpxhzbe.txt === reduce.pl bib === id = cord-002222-rgqwm3vb author = Olarte-Castillo, Ximena A. title = Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study date = 2016-09-23 pages = extension = .txt mime = text/plain words = 7544 sentences = 339 flesch = 46 summary = By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. A total of 20 partial RdRp gene sequences (16 from spotted hyenas, 3 from African lions and 1 from bat-eared foxes) were obtained and used for the phylogenetic analysis, together with publically available sequence data from 25 representatives of all sapovirus genogroups, divergent unclassified sapoviruses, and other genera in the Caliciviridae family, including Norovirus and Vesivirus. cache = ./cache/cord-002222-rgqwm3vb.txt txt = ./txt/cord-002222-rgqwm3vb.txt === reduce.pl bib === id = cord-002100-dt5zvebj author = He, Yonghua title = Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date = 2016-06-17 pages = extension = .txt mime = text/plain words = 6795 sentences = 336 flesch = 45 summary = Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. Epidermal growth factor protein from humans was produced in soybean seeds by constructing a plant gene expression cassette that involved a synthetic codon optimized EGF nucleotide sequence (protein sequence from Genbank accession CCQ43157). To assess the bioactivity of soybean-produced hEGF, samples were prepared from both ShEGF transgenic soybean lines and nontransgenic controls that were used to stimulate HeLa cells to induce EGFR internalization, degradation and phosphorylation. In contrast, samples prepared from control nontransgenic soybeans exhibited no apparent bioactivity showing the degradation and phosphorylation of EGFR is the result of EGF binding of either commercial rhEGF added to the media or from the hEGF produced by the transgenic soybeans. cache = ./cache/cord-002100-dt5zvebj.txt txt = ./txt/cord-002100-dt5zvebj.txt === reduce.pl bib === id = cord-002602-2qvyhjlp author = Roy, Amrita title = Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants date = 2017-07-10 pages = extension = .txt mime = text/plain words = 8987 sentences = 456 flesch = 57 summary = Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Therefore, our results suggest that in the Zika NS2B-NS3pro complex, NS2B has a portion of residues undergo μs-ms dynamics which made their NMR peaks too broad to be detectable; while the rest of NS2B is highly disordered and lacks tight tertiary packing, which results in a narrowly-dispersed HSQC spectrum (S2B Fig) . Together with recent reports on the crystal structures of Zika NS2B-NS3pro complexes in both open and closed conformations [34, 43] , our current results reveal that in solution the NS2B residues over Arg73-Lys100 are highly disordered in the open conformation. Unfortunately, as previously observed on Dengue-2 NS2B-NS3pro complexes [21, 30, 43] , our linked Zika complex also underwent significant μs-ms dynamics, thus making its NMR signals too broad to be detected (Fig 1A and 1B) . cache = ./cache/cord-002602-2qvyhjlp.txt txt = ./txt/cord-002602-2qvyhjlp.txt === reduce.pl bib === id = cord-001843-ceatyj3o author = Huang, Yong title = Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay date = 2015-11-06 pages = extension = .txt mime = text/plain words = 5184 sentences = 231 flesch = 50 summary = PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. The duplex UNDP-PCR assay is suitable for simultaneous detection of RNA and DNA viruses in early viral infection, providing an effective approach for diagnosis of swine diseases. The duplex UNDP-PCR assay developed in this study provided a useful tool for simultaneous detection of RNA (TGEV) and DNA viruses (PCV2) without the need for viral nucleic acid extraction, purification and reverse transcription. cache = ./cache/cord-001843-ceatyj3o.txt txt = ./txt/cord-001843-ceatyj3o.txt === reduce.pl bib === id = cord-002305-qq73gr9y author = Anson, Marie title = Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool date = 2016-11-23 pages = extension = .txt mime = text/plain words = 5422 sentences = 248 flesch = 51 summary = In conclusion, the adoptive cell transfer strategy allowed the development of a primary immune response with B cell activation and expansion, induction of AID expression, class switch recombination, antigen-specific IgM and IgG antibody production and germinal center formation. In this study we show that it is possible to fully reconstitute a primary response and the establishment of antibody memory in immune deficient mice after adoptive transfer of antigen-specific monoclonal B cells together with a population of monoclonal helper T cells. In contrast we showed that after adoptive transfer in immune deficient hosts antigen immunization induced B cell activation and expansion, induction of AID expression, class switch recombination, antigen-specific IgM and IgG antibody production, germinal center formation and the generation of two subsets of AID/YFP + IgM + IgGand AID/YFP + Ig-M -IgG + antigen-experienced B cell subsets able to persist in a lymphopenic environment by cell division mimicking responses obtained in intact non-Tg mice [4] . cache = ./cache/cord-002305-qq73gr9y.txt txt = ./txt/cord-002305-qq73gr9y.txt === reduce.pl bib === === reduce.pl bib === id = cord-002811-5hrydciz author = Hercik, Christine title = A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania date = 2017-12-29 pages = extension = .txt mime = text/plain words = 6511 sentences = 310 flesch = 42 summary = Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. The objective of this hospital-based syndromic surveillance study was to examine exposure and epidemiologic associations with detection of bloodstream and respiratory agents among patients presenting to clinical settings with acute febrile illness (AFI) in Kilombero, Tanzania. Given the high frequency of detection of Plasmodium, we further examined detection status across three diagnostic platforms, and conducted a non-parametric tests Kruskal-Wallis test to compare mean C t values, as determined by qPCR, for patients grouped within each level of parasite intensity (1+, 2+, 3+, or 4+), as determined by blood smear. Clinical and epidemiologic correlates of agents detected among at least 10% of our patient population were evaluated using an agent-specific filtered multivariate logistic regression approach to determine statistically significant factors among test-positive participants against a test-negative control group. cache = ./cache/cord-002811-5hrydciz.txt txt = ./txt/cord-002811-5hrydciz.txt === reduce.pl bib === id = cord-002901-u4ybz8ds author = Yu, Chanki title = Acral melanoma detection using a convolutional neural network for dermoscopy images date = 2018-03-07 pages = extension = .txt mime = text/plain words = 3513 sentences = 180 flesch = 52 summary = We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist's and non-expert's evaluation. CONCLUSION: Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet. In the result of group B by the training of group A images, CNN also showed a higher diagnostic accuracy (80.23%) than that of the non-expert (62.71%) but was similar to that of the expert (81.64%). cache = ./cache/cord-002901-u4ybz8ds.txt txt = ./txt/cord-002901-u4ybz8ds.txt === reduce.pl bib === id = cord-002624-59nznqsd author = Ti, Jinfeng title = Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies date = 2017-07-26 pages = extension = .txt mime = text/plain words = 4050 sentences = 210 flesch = 53 summary = title: Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked immunosorbent assay (ELISA). In this study, one linear B-cell epitope was identified and characterized with one monoclonal antibody against TMUV NS1 protein. To screen the antigenic epitope of TMUV NS1 mAb, 35 short peptide fusion proteins were successfully expressed in prokaryotic expression system and purified. A pane of 16-AA polypeptides of NS1 protein was expressed and one 16-AA polypeptide NS1-27 was screened and identified by 3G2 mAb. In order to accurately map the B-cell epitope, a set of truncated fusion oligopeptides of NS1-27 were expressed. The B-cell epitope of TMUV NS1 protein could apply into the development of detection methods to investigate whether the detected antibody was a result of inactivated vaccine immunization or live virus infection. cache = ./cache/cord-002624-59nznqsd.txt txt = ./txt/cord-002624-59nznqsd.txt === reduce.pl bib === === reduce.pl bib === id = cord-002705-ntokyoai author = Nasir, Nazrila Hairin title = Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study date = 2017-10-04 pages = extension = .txt mime = text/plain words = 4464 sentences = 229 flesch = 56 summary = However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. A non-randomized controlled study was conducted in Taiwan comparing the effects of oral rehydration with intravenous fluid replacement in adult patients with non-shock dengue haemorrhagic fever [7] . Most importantly, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. Thus, this pilot randomized controlled study aimed to assess the feasibility of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. cache = ./cache/cord-002705-ntokyoai.txt txt = ./txt/cord-002705-ntokyoai.txt === reduce.pl bib === id = cord-003507-22ylifqo author = Kelly, J. Daniel title = Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018 date = 2019-03-07 pages = extension = .txt mime = text/plain words = 4481 sentences = 246 flesch = 53 summary = As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. We modeled Ebola virus transmission using a stochastic branching process model, parameterized by transmission rates estimated from the dynamics of prior EVD outbreaks, and conditioned on agreement with reported case counts from the 2018 EVD outbreak to date. cache = ./cache/cord-003507-22ylifqo.txt txt = ./txt/cord-003507-22ylifqo.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-002621-sq5iod1w author = Attia, Mohamed I. title = New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres date = 2017-07-25 pages = extension = .txt mime = text/plain words = 5948 sentences = 280 flesch = 47 summary = Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC(50) values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC(50) value of 8.11 μM. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC(50) value less than 0.8 μM. The human lung cancer A549 cell line was incubated with various concentrations (0.8, 1.6, 3.13, 6.25, 12.5, 25 and 50 μM) of both free 7e and 7e-loaded microspheres to evaluate the anti-proliferative activity by assessing their effect on cell viability. Synthesis and anticancer activity of certain hydrazonoindolin-2-ones Fig 13B illustrates the obtained results when 7e-loaded microspheres were incubated with the human lung cancer cell lineA549for incubation periods and concentrations similar to that of the free 7e. cache = ./cache/cord-002621-sq5iod1w.txt txt = ./txt/cord-002621-sq5iod1w.txt === reduce.pl bib === === reduce.pl bib === id = cord-002560-pue5q5wp author = Moreno, Paloma S. title = Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics date = 2017-06-01 pages = extension = .txt mime = text/plain words = 5137 sentences = 265 flesch = 50 summary = Recently, due to the advent of molecular enrichment protocols, high throughput sequencing and new metagenomic analytical methods we are now able to explore, identify and characterise viruses from different biological and environmental samples with a greater capacity [2, [5] [6] [7] [8] [9] [10] [11] In studies of human faeces, the virome has been shown to include viruses that infect eukaryotic organisms and viruses that infect prokaryotes (bacteriophages) [2, 5, [12] [13] [14] [15] [16] [17] [18] . Another eukaryotic viral family found in one healthy dog sample was Parvoviridae, genetic analysis of the 3 contigs/singletons showed a coverage of approximately 3.5% of the complete genome of canine parvovirus reference sequence (NC_001539), or 9.3% of the polyprotetin Ns1-Ns2. Nucleic acids from a single faecal sample from a dog with acute diarrhoea (DD1), which had 18 contigs/singletons of canine astrovirus (after tBLASTx analysis) was used to determine the complete genome sequence. cache = ./cache/cord-002560-pue5q5wp.txt txt = ./txt/cord-002560-pue5q5wp.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004017-gcmpatlb author = Errecaborde, Kaylee Myhre title = Factors that enable effective One Health collaborations - A scoping review of the literature date = 2019-12-04 pages = extension = .txt mime = text/plain words = 9215 sentences = 458 flesch = 34 summary = The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment). In this study, a multidisciplinary team of researchers reviewed a broad scope of literature describing collaborative and multi-sectoral approaches to past health events to understand how such collaborations are commonly described and evaluated and to identify and synthesize enabling factors for One Health collaborations. Starting condition factors reported to enable collaboration at the network level included network structures, existing relationships, available resources in the face of a health event, and the political environment in place to support these efforts. cache = ./cache/cord-004017-gcmpatlb.txt txt = ./txt/cord-004017-gcmpatlb.txt === reduce.pl bib === id = cord-002180-gsdk5x3e author = Davies, Colin title = Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest date = 2016-08-24 pages = extension = .txt mime = text/plain words = 4491 sentences = 223 flesch = 52 summary = Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5. Several RNA viruses, including murine norovirus 1 (MNV-1) have been characterized to manipulate cell cycle progression at the G 1 /S restriction point, often creating favorable conditions for viral replication [14] [15] [16] [17] [18] [19] [20] [21] . The effect of NS5 on the host cell cycle was therefore determined by transfection of RAW-Blue cells with RNA transcripts, encoding individual viral genes, NS1-2 from MNV-1 was included as a negative control (Fig 1A) . Furthermore, the NS5(F123A) variant decreased cyclin A protein expression by 67% when compared to the mocktransfected population in a synonymous manner to NS5, strongly implying that the host eukaryotic initiation factor binding domain of NS5 does not play a role in its cell cycle manipulation (Fig 3D) . cache = ./cache/cord-002180-gsdk5x3e.txt txt = ./txt/cord-002180-gsdk5x3e.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-002426-5e1xn7kj author = Falcón-Lezama, Jorge Abelardo title = Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico date = 2017-02-22 pages = extension = .txt mime = text/plain words = 5944 sentences = 261 flesch = 49 summary = MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority's administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Sample: 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with age older than 12, and residents in Axochiapan, Morelos State, México, were selected from the cohort "Peridomestic infection as determinant for Dengue virus transmission" [13] . cache = ./cache/cord-002426-5e1xn7kj.txt txt = ./txt/cord-002426-5e1xn7kj.txt === reduce.pl bib === id = cord-003377-9vkhptas author = Wu, Tong title = The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia date = 2018-12-19 pages = extension = .txt mime = text/plain words = 4969 sentences = 267 flesch = 49 summary = title: The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). The indicator for wild bird habitat used in this study was the set of "Important Bird and Biodiversity Areas" (IBAs) for "migratory and congregatory waterbirds" identified by BirdLife The live poultry trade poses different avian influenza risks in different regions of the world Table 1 . Our first specification (Model 1) included a number of factors related to disease risk but excluded both live poultry imports and biosecurity measures. cache = ./cache/cord-003377-9vkhptas.txt txt = ./txt/cord-003377-9vkhptas.txt === reduce.pl bib === === reduce.pl bib === id = cord-002890-g7aje88u author = Wood, Paul L. title = Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses date = 2018-02-23 pages = extension = .txt mime = text/plain words = 3276 sentences = 177 flesch = 39 summary = In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. In this study, we asked if differences in host's responses to live, multiplying Leptospira versus killed leptospires, present in the vaccine, are reflected in the serum lipidome of these two groups of horses. Our results show that serum levels of cyclic phosphatidic acids (cPA), diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens were elevated in both vaccinated and naturally infected horses. Our data indicate that the immune response induced by vaccination has a more dramatic effect than leptospiral infection on sphingomyelin synthesis in horses. cache = ./cache/cord-002890-g7aje88u.txt txt = ./txt/cord-002890-g7aje88u.txt === reduce.pl bib === id = cord-003548-zuwt7gk5 author = Cai, Haiming title = Modulating the 3’ end-DNA and the fermentation process for enhanced production and biological activity of porcine interferon-gamma date = 2019-03-26 pages = extension = .txt mime = text/plain words = 6848 sentences = 447 flesch = 56 summary = In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry. The expression of pIFN-γ protein was maximal when the concentration of DO in the substrate was 30%, especially for the recombinant Pichia pastoris with the optimized pIFN-γ gene and the 3' signaling peptide mutation, which had significantly higher expression than that of the other treatment groups (p<0.05). cache = ./cache/cord-003548-zuwt7gk5.txt txt = ./txt/cord-003548-zuwt7gk5.txt === reduce.pl bib === id = cord-003270-vu9b5a14 author = Panahi, Heidar Ali title = A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins date = 2018-10-24 pages = extension = .txt mime = text/plain words = 7005 sentences = 377 flesch = 50 summary = In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens' analyses were carried out successively by different tools. For the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and for the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens analyses were considered. In this study, the binding ability of the first step selected peptides to human and mouse MHC molecules, was analyzed by CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock/) server. In cancer immunotherapy, the CTL-mediated responses play the central role in eradication of malignant cells, and the binding of epitopes to MHC-I molecules is an essential step for antigen presentation to CTLs. Thus, in this study, predicted epitopes were primarily selected by their MHC-I binding and processing scores. cache = ./cache/cord-003270-vu9b5a14.txt txt = ./txt/cord-003270-vu9b5a14.txt === reduce.pl bib === id = cord-001910-6zfz2ns5 author = Zhang, Xianming title = Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome date = 2016-01-08 pages = extension = .txt mime = text/plain words = 3991 sentences = 241 flesch = 53 summary = title: Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Therefore, we hypothesized that abdominal muscle activity during mechanically ventilation increases lung injury in severe acute respiratory distress syndrome. In an oleic acid-induced model of experimental ARDS in beagles, our findings suggested that abdominal muscle activity during mechanically ventilation increases lung injury in severe acute respiratory distress syndrome. In an oleic acid-induced ARDS model, our study showed that BIPAP AP had lower mRNA expression of IL-6 and IL-8 in lung tissues and less total cumulative histopathological lung injury scores compared with BIPAP SB group. cache = ./cache/cord-001910-6zfz2ns5.txt txt = ./txt/cord-001910-6zfz2ns5.txt === reduce.pl bib === === reduce.pl bib === id = cord-003125-iptisi1m author = Machablishvili, Ann title = Overview of three influenza seasons in Georgia, 2014–2017 date = 2018-07-27 pages = extension = .txt mime = text/plain words = 3714 sentences = 196 flesch = 48 summary = We aimed to present Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) surveillance data and characterize influenza viruses circulating in the country over three influenza seasons. The objectives were to: (1) define periods of influenza activity in Georgia; (2) assess the proportions of influenza infections among ILI and SARI cases; (3) determine most affected age groups; (4) describe epidemiological characteristics of influenza-associated fatal cases; and (5) determine antigenic and genetic profiles of influenza viruses circulating in the country. Influenza virus detection rates among hospitalized patients were highest, almost equally, in the age groups 30-64 years (55%, OR = 3.48, CI 2.58-4.69, p<0.001) and 15-29 years (53%, OR = 3.03, CI 2.14-4.28, p<0.001) ( Table 1) Among 1,997 sampled SARI cases, only 25 were vaccinated against influenza; of these, three tested positive for A/H1N1pdm09 and three for A/H3N2. cache = ./cache/cord-003125-iptisi1m.txt txt = ./txt/cord-003125-iptisi1m.txt === reduce.pl bib === id = cord-004091-gex0zvoa author = Abdulkareem, Shaheen A. title = Risk perception and behavioral change during epidemics: Comparing models of individual and collective learning date = 2020-01-06 pages = extension = .txt mime = text/plain words = 8379 sentences = 432 flesch = 50 summary = For this study, we ran eight ABMs to test various combinations of individual and group learning, using different information sources-with or without interactions among agents-as factors in the BNs. We investigate the extent to which the epidemic spreads, depending on these different learning approaches regarding risk perception and coping decisions. The empirically-driven BNs model a two-stage decision process of people facing a disease risk: learning to update risk perceptions (threat appraisal, BN1 in Fig 1) and making decisions about how to adapt their behavior during the epidemic (coping appraisal, BN2 in Fig 1) . To evaluate the impact of individual and social intelligence on agents' learning processes regarding risk perception and coping appraisal and the resulting patterns of disease spread, we used four output measures: disease diffusion, risk perception, spatial patterns, and model performance. Finally, in M7, where household agents learned risk perception in decentralized groups and learned to cope individually, 2,911 infected cases were recorded (Table 3) . cache = ./cache/cord-004091-gex0zvoa.txt txt = ./txt/cord-004091-gex0zvoa.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-003712-mafz21no author = Perez Vidakovics, Maria Laura A. title = Junín virus induces autophagy in human A549 cells date = 2019-06-19 pages = extension = .txt mime = text/plain words = 6151 sentences = 333 flesch = 47 summary = We found that JUNV infection induces an increment of the LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cells and the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosome formation. Either with the early autophagy inhibitor (3-MA) or the late inhibitor (BAF), the treatment pre or post-infection resulted in reduced expression of N and lower viral titre as compared to JUNV-infected cells that received no treatment (NT) (Fig 4B-4D) . In parallel, experiments performed adding Rap post-infection resulted in a similar increase in viral yields of JUNV, which indicates that the activation of autophagy benefits both viral entry/uncoating and later steps as assembling and viral budding (Fig 4) . When compared to control cells, an increase in the number of mCherry puncta following rapamycin treatment was observed, indicating promoted autophagy and fusion between autophagosomes and acidic compartments (Fig 5C) . cache = ./cache/cord-003712-mafz21no.txt txt = ./txt/cord-003712-mafz21no.txt === reduce.pl bib === id = cord-003062-qm8kalyt author = Chowdhury, Fazle Rabbi title = The association between temperature, rainfall and humidity with common climate-sensitive infectious diseases in Bangladesh date = 2018-06-21 pages = extension = .txt mime = text/plain words = 4997 sentences = 274 flesch = 50 summary = This observational study examined the association of temperature, humidity and rainfall with six common climate-sensitive infectious diseases in adults (malaria, diarrheal disease, enteric fever, encephalitis, pneumonia and bacterial meningitis) in northeastern Bangladesh. Unfortunately, very few studies on the relationship between various environmental variables and trends of infectious disease incidence have been performed so far in Bangladesh, although there are reports of some infections increasing sporadically in different regions of the country [17] [18] [19] . This study examined six infectious diseases based on clinical syndromes and laboratory support (malaria, enteric fever, encephalitis, diarrheal disease, pneumonia and meningitis) to offer a broader scope on the trend of these infectious diseases and their possible relation to climate change in Bangladesh. W.H.O reported dengue, viral encephalitis, diarrheal disease, enteric fever, pneumonia and meningitis as most sensitive to climate factors, and predicted a huge rise of cases in tropical countries [25] . cache = ./cache/cord-003062-qm8kalyt.txt txt = ./txt/cord-003062-qm8kalyt.txt === reduce.pl bib === id = cord-002889-fie121ns author = White, Michael title = Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer date = 2018-02-23 pages = extension = .txt mime = text/plain words = 4872 sentences = 222 flesch = 47 summary = Human and mouse mesothelin share sequence similarity, expression patterns, and biochemical characteristics, [7] , and the homeostatic function of mesothelin in mammals is unknown: the gene can be deleted without apparent effect in mice PLOS C57Bl6 mice and thus can be grown in syngeneic mice to allow for study of an anti-tumor immune response in an immunocompetent mouse model. In order to create a putative therapeutic anti-mesothelin vaccine, we inserted the mouse mesothelin gene into the poxvirus MVA genome under a viral promoter so that mesothelin would be expressed in any cells infected with the recombinant virus. To determine whether the viruses expressing mesothelin protein were able to induce an immune response in mice, we first attempted to measure anti-mesothelin antibody in vaccinated mouse sera. In comparison, there were very few spots (1-3) in response to stimulation with Lewis Lung cells that do not express mouse mesothelin, and mice vaccinated with MVA, MVAmeso and MVAmesoA35Del viruses all had good responses to restimulation with vaccinia virus (124, 147, and 148 spots respectively). cache = ./cache/cord-002889-fie121ns.txt txt = ./txt/cord-002889-fie121ns.txt === reduce.pl bib === === reduce.pl bib === id = cord-004068-d66lwylf author = Shimoda, Tomoko title = Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections date = 2019-12-27 pages = extension = .txt mime = text/plain words = 4676 sentences = 221 flesch = 43 summary = A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. Furthermore, we propose that fomites warmed to human body core temperature may help to control bacterial survival in dry environments, and that such a strategy may prohibit the emergence of human pathogenic bacteria in hospital environments, eventually reducing the need for antibiotics as well as disinfectants. A heatmap generated with the high-resolution infrared sensor showed that in contrast to the stainless steel pipe without the heater, the surface temperature on the heated pipe was maintained at body core temperature (Fig 5A) , indicating that it is an effective tool to monitor the influence of temperature on bacterial survival on a dry surface. Taken together, we concluded that the handrail device warmed to human body core temperature prohibited the prolonged survival of some bacteria and a yeast-like fungus responsible for nosocomial infections on a dry surface. cache = ./cache/cord-004068-d66lwylf.txt txt = ./txt/cord-004068-d66lwylf.txt === reduce.pl bib === id = cord-003484-ylpa702c author = Blázquez, Elena title = Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma date = 2019-02-21 pages = extension = .txt mime = text/plain words = 6990 sentences = 352 flesch = 53 summary = Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The objective of this study was to assess inactivation efficiency of the SurePure Turbulator UV-C irradiation system with selected swine enveloped viruses Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Swine influenza A virus (SIV) and Classical swine fever virus (CSFV) and non-enveloped viruses Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus 2 (PCV-2) and Senecavirus A (SVA) inoculated in liquid bovine or porcine plasma. cache = ./cache/cord-003484-ylpa702c.txt txt = ./txt/cord-003484-ylpa702c.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-011798-uss38ped author = Li, Guowei title = Intellectual capital and the efficiency of SMEs in the transition economy China; Do financial resources strengthen the routes? date = 2020-07-02 pages = extension = .txt mime = text/plain words = 8759 sentences = 490 flesch = 38 summary = Despite the bourgeoning literature, studies have not yet unleashed the influence of each dimension of intellectual capital; human capital, structural capital and customer capital on SMEs' efficiency with financial resources as a moderator. A survey method was used and collected evidence from 264 Chinese SMEs. The findings exhibit that human capital directly enhances SMEs' efficiency but the presence of financial resources as a moderator weakens the influence. This research recommends that owners and managers of SMEs need to use their financial resources complementary with structural and customer capital while human capital should be used exclusively. Studies have also discussed the role of intellectual capital (IC) (human capital, customer capital and structural capital) in firm competitive advantage and performance in emerging and developed economies [12, 13] Also, studies have assessed the direct and indirect influence of IC on performance [14] [15] [16] . cache = ./cache/cord-011798-uss38ped.txt txt = ./txt/cord-011798-uss38ped.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-251979-j3mme15e author = Kandeel, Amr title = Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014 date = 2016-09-08 pages = extension = .txt mime = text/plain words = 4716 sentences = 272 flesch = 43 summary = METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. The aims of this study were to (1) assess the proportion of SARI cases having influenza infection in Egypt; (2) examine the types and subtypes of detected influenza viruses in Egypt; (3) compare demographic and clinical characteristics of influenza-positive SARI cases to those of influenza-negative SARI cases in Egypt; (4) quantify influenza deaths and assess influenza mortality risk factors in Egypt; and (5) establish a defined period of influenza seasonality in Egypt. The odds of death among influenza-positive cases were modeled with logistic regression using different explanatory variables (age group: pediatric <15 years old versus adult 15 years old; sex: male versus female; days from symptom onset to hospitalization: 0-2 versus 3-4 versus 5; chronic conditions: at least one versus none; and influenza type: A versus B). cache = ./cache/cord-251979-j3mme15e.txt txt = ./txt/cord-251979-j3mme15e.txt === reduce.pl bib === === reduce.pl bib === id = cord-048492-4z38v9rg author = Tang, Julian W. title = Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006) date = 2008-07-23 pages = extension = .txt mime = text/plain words = 4458 sentences = 202 flesch = 48 summary = In this study, an analysis is presented of 281 Hong Kong influenza A(H3N2) hemagglutinin (HA) and neuraminidase (NA) full-length, dated sequences collected over 10 years (1997-2006) to assist the ongoing efforts to elucidate the underlying basis for the seasonality of influenza A(H3N2). One example of such possible viral persistence between influenza seasons was found, with HA and NA sequences from the same viruses (5251Jan02 and 5267Jan03, as indicated in Figures S1 and S2 for the HA and NA phylogenetic trees, respectively), showing a similar clustering pattern for both these genes, separated by at least one year. A similar analysis was recently performed using dated whole genome influenza A(H3N2) sequences from New York, New Zealand and Australia, downloaded from publicly available databases, in an attempt to test two competing hypotheses: whether seasonal influenza A(H3N2) viruses continuously 'migrate' around the world, particularly between Northern and Southern hemispheres; or whether the virus remains 'latent' in one location and reactivates each year to produce the familiar pattern of influenza seasonality [19] . cache = ./cache/cord-048492-4z38v9rg.txt txt = ./txt/cord-048492-4z38v9rg.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-252739-1manzf3l author = Zheng, Yueming title = Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants date = 2012-12-12 pages = extension = .txt mime = text/plain words = 4007 sentences = 250 flesch = 56 summary = The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. Consistent with previous reports, the effects of KCNE1 on KCNQ1 include increase in overall current amplitude, slowing of the activation and deactivation kinetics, and removal of inactivation (Fig. 4A) . The common phenotype of these mutants is reduction of IKs current, which are commonly thought to be mediated by the KCNQ1/KCNE1 complex [2, 3] , as a result of decrease in either channel activity or trafficking efficiency. cache = ./cache/cord-252739-1manzf3l.txt txt = ./txt/cord-252739-1manzf3l.txt === reduce.pl bib === id = cord-254117-2ttwaegh author = Priest, Patricia C. title = Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study date = 2011-01-05 pages = extension = .txt mime = text/plain words = 4187 sentences = 186 flesch = 44 summary = The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). This evaluation of thermal image scanning was carried out as part of a larger study to measure the prevalence of seasonal influenza infection in arriving airline travellers and the effectiveness of a screening questionnaire for detecting those with influenza infection. To assess the utility of fever as a screening test for influenza infection (MT-PCR result), sensitivity, specificity, and population PPV for influenza were estimated for each tympanic temperature threshold, and the ITIS threshold used above. The greatest potential for the use of ITIS to screen incoming or departing travellers for infectious diseases such as a pandemic strain of influenza would be as the first stage of screening; that is, to identify and select out a high risk group for further assessment, for example by questionnaire, body core temperature measurement, and/or respiratory sample collection. cache = ./cache/cord-254117-2ttwaegh.txt txt = ./txt/cord-254117-2ttwaegh.txt === reduce.pl bib === id = cord-048360-n9sih438 author = Villard, Viviane title = Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date = 2007-07-25 pages = extension = .txt mime = text/plain words = 4794 sentences = 228 flesch = 45 summary = To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. Here, we focus on the Pf parasite erythrocytic stage, a target of protective antibodies and describe a straightforward, rapid procedure based on bioinformatic analysis of a-helical coiled-coil motifs and peptide synthesis. With regard to the structural features and cellular location prediction of the proteins corresponding to the peptides selected for ADCI assays ( Table 1) , 15 of the proteins contain a pentapeptide conforming to the PEXEL consensus [19, 20; 21, 22] , but that none of these have a position within the amino acid sequence that conforms to the location of known active PEXEL motifs (see Materials and Methods and membrane segments, and none of them has a GPI anchor. In conclusion, an approach combining a genome-wide search by bioinformatics of a-helical coiled coil protein motifs and chemical synthesis can lead to the rapid identification and development of new malaria vaccine candidates. cache = ./cache/cord-048360-n9sih438.txt txt = ./txt/cord-048360-n9sih438.txt === reduce.pl bib === id = cord-013099-j816c3tw author = Blease, Charlotte title = US primary care in 2029: A Delphi survey on the impact of machine learning date = 2020-10-08 pages = extension = .txt mime = text/plain words = 5698 sentences = 303 flesch = 54 summary = To address this research gap, we designed a Delphi survey to explore leading health informaticians' predictions about the impact of machine learning on primary care in the US in 2029. Acknowledging that heterogeneous panels have been shown to result in more accurate estimates [33] , and that what counts as an expert can be influenced by goals, values, and the manner in which knowledge is generated, we aimed to recruit diverse participants from across academia, healthcare, non-profit organizations, and industry; and to strive for panelists with a varied complementarity of interests within health informatics. In the first round, the Delphi survey requested demographic information; this was followed by 5 sections, with 7 open-ended questions, on the impact of machine learning on primary care by 2029 (see S1 Appendix; Table 1 We also included a final comment-box for feedback on the survey. cache = ./cache/cord-013099-j816c3tw.txt txt = ./txt/cord-013099-j816c3tw.txt === reduce.pl bib === id = cord-013334-cptu0k7s author = Holst-Hansen, Joachim A. title = Does the size of rewards influence performance in cognitively demanding tasks? date = 2020-10-21 pages = extension = .txt mime = text/plain words = 6101 sentences = 326 flesch = 55 summary = Empirical studies in sports settings show that athletes generally perform worse when the stakes are higher, while a range of lab studies involving cognitively demanding tasks have led to diverging results, supporting positive, negative and null-effects of higher (vs. Third, if the given task can't be solved more efficiently than the level of performance a low monetary incentive allows, a higher stake can't have an additional positive effect due to a ceiling effect [3] . Studies that have asked participants to solve various forms of cognitively demanding tasks have led to ambiguous findings; some studies find a positive effect on performance of higher stakes compared to lower [6, 16, 17] , some find a negative effect [5, 18] while others find no clear effect when comparing high vs. In order to further investigate how the reward size might influence behavior, we also assess if self-reported measures of effort [6] , intrinsic motivation [7] and focus [5] vary depending on the reward structure the participants have been exposed to. cache = ./cache/cord-013334-cptu0k7s.txt txt = ./txt/cord-013334-cptu0k7s.txt === reduce.pl bib === id = cord-254025-j1l0mder author = de Melo, Andreia C. title = Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute date = 2020-10-26 pages = extension = .txt mime = text/plain words = 3366 sentences = 178 flesch = 50 summary = According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p <0.001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). As shown in Table 3 , mortality related to COVID-19 was significantly associated to older age (P < .001 for patients between 60 to 74 years and P = .002 for patients aged 75 years or older), metastatic cancer (P < .001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). cache = ./cache/cord-254025-j1l0mder.txt txt = ./txt/cord-254025-j1l0mder.txt === reduce.pl bib === id = cord-255013-njpuc475 author = He, Xiaocui title = Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses date = 2014-10-08 pages = extension = .txt mime = text/plain words = 4516 sentences = 263 flesch = 54 summary = The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. myotis cell lines present a valuable in vitro model to study the interactions between lyssaviruses and their natural host, and to shed light on the mechanisms of resistance in bat's central nervous system (CNS). To further evaluate the cell line models for study of the different susceptibility between MmBr and other cell lines, mRNA expressions of PRRs and IFN induced genes were investigated in MmTo and MmBr after RABV infection (MOI 0.01 to 1.0). The increased expression of dsRNA receptor TLR3 and IFN induced genes ISG56, ISG43, Mx1 and IFIT3 after stimulation with poly I:C mimicking a viral infection indicates that these cell lines can be used as effective in vitro models to study the bat's innate immune responses to virus infection [32, 44] . cache = ./cache/cord-255013-njpuc475.txt txt = ./txt/cord-255013-njpuc475.txt === reduce.pl bib === id = cord-254313-g2oc32dm author = Klink, Thomas title = Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons date = 2020-04-30 pages = extension = .txt mime = text/plain words = 4499 sentences = 215 flesch = 49 summary = Several studies, including at least nine in the Eastern Mediterranean region, have been published since 2011 using the SARI case definition as inclusion criteria to report a combination of clinical characteristics, risk factors, viral burden, or outcomes in adult and pediatric populations for flu and other respiratory viruses [5] [6] [7] [8] [9] [10] [11] [12] [13] . Only a handful of studies have evaluated the effectiveness of the criteria by including both SARI-positive and SARI-negative patients, allowing them to calculate the diagnostic accuracy of the criteria for detecting flu and respiratory syncytial virus (RSV) [14] [15] [16] [17] [18] [19] . The age distribution differences likely explain these discrepancies as our cohort consists only of children under two years, and the SARI criteria were the least sensitive (15.9%) and most specific (80.5%) for detecting flu in our patients under three months, who make up 45.4% of our study population. cache = ./cache/cord-254313-g2oc32dm.txt txt = ./txt/cord-254313-g2oc32dm.txt === reduce.pl bib === id = cord-253056-765rs3e7 author = Dionne, Audrey title = Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection date = 2018-10-17 pages = extension = .txt mime = text/plain words = 3725 sentences = 208 flesch = 45 summary = title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with concurrent infection had higher rates of IVIG resistance (19 (33%) versus 17 (18%) patients, p = 0.04), and higher temperature at 48 hours (Fig 1) . In this retrospective series, the presence of a concomitant infection was associated with a higher rate of resistance to IVIG treatment. In this study, patients with concomitant infection had a higher rate of resistance to IVIG treatment. cache = ./cache/cord-253056-765rs3e7.txt txt = ./txt/cord-253056-765rs3e7.txt === reduce.pl bib === id = cord-254000-pbzcupjg author = Suvannachart, Pukkapol title = Repeatability, reproducibility, agreement, and safety of Tono-Pen tip cover for intraocular measurement using latex and polyethylene wrap date = 2020-09-28 pages = extension = .txt mime = text/plain words = 3623 sentences = 264 flesch = 60 summary = PURPOSE: To evaluate repeatability, reproducibility, and agreement of intraocular pressure measurement with Tono-Pen using Ocufilm and polyethylene wrap tip cover in human eyes. For the right eye, 4 measurements using polyethylene wrap tip cover were done by two examiners (A and B) in random order to assess intra-observer repeatability and inter-observer reproducibility. For the left eye, 4 measurements were done by examiner A using both polyethylene wrap tip cover and Ocufilm in random order to assess intra-observer repeatability and agreement. RESULTS: For examiner A, the repeatability of polyethylene wrap tip cover was -0.34, 95% limits of agreement (LOA) were -3.04 to 2.36, and ICC was 0.93 in the right eyes. For IOP measurement with TP, our previous eye model and study conducted in canine eyes showed good repeatability and agreement between the custom-made polyethylene wrap (PW) tip cover and OF without causing any ocular surface complications [13, 14] . cache = ./cache/cord-254000-pbzcupjg.txt txt = ./txt/cord-254000-pbzcupjg.txt === reduce.pl bib === id = cord-048339-nzh87aux author = Caley, Peter title = The Waiting Time for Inter-Country Spread of Pandemic Influenza date = 2007-01-03 pages = extension = .txt mime = text/plain words = 5739 sentences = 253 flesch = 45 summary = On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. In this paper we demonstrate how the delay to importation of an epidemic of pandemic strain influenza may be quantified in terms of the growing infection incidence in the source region, traveler volumes, border screening measures, travel duration, inflight transmission and the delay until an infected arrival initiates a chain of transmission that gathers momentum. For example, if R = 1.5, and we reduce the number of intending travelers from 400 to 10 per day, implement 100% flight-based quarantining, implement compulsory mask wearing during travel and presentation at 6 hours following symptom onset then there is a substantial probability (0.74) that the pandemic strain will never be imported (assuming the epidemic is confined to the source country). cache = ./cache/cord-048339-nzh87aux.txt txt = ./txt/cord-048339-nzh87aux.txt === reduce.pl bib === id = cord-255576-738khdwv author = Van Duyne, Rachel title = Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery date = 2012-07-10 pages = extension = .txt mime = text/plain words = 9845 sentences = 517 flesch = 56 summary = We have previously shown that Tax interacts directly with the cellular Rb (Retinoblastoma) protein and targets Rb for degradation via the proteasome pathway, resulting in a decrease in Rb protein expression in HTLV-1 infected cells and a dysregulation of the cell cycle [47] . Collectively, these data indicate that the Drosha in Tax-containing and HTLV-1 infected cells is mostly functionally inactive and the functional suppression of Drosha is dependent on its interaction with a small region of the N-terminus of Tax. We have shown above that Drosha is downregulated, degraded, and mostly inactive in HTLV-1 infected cells, however, it was not clear what effect this dysregulation of Drosha would have on viral replication. Collectively, these data indicate that proteins, such as IKK-b, among others, may directly be regulated by the Tax/Drosha interaction in HTLV infected cells. cache = ./cache/cord-255576-738khdwv.txt txt = ./txt/cord-255576-738khdwv.txt === reduce.pl bib === id = cord-013356-y6vceq2x author = Peace, Angela title = Orchard layout and plant traits influence fruit yield more strongly than pollinator behaviour and density in a dioecious crop date = 2020-10-23 pages = extension = .txt mime = text/plain words = 5864 sentences = 313 flesch = 57 summary = The predictive model provides strategies for improving crop management, such as choosing cultivars which have their peak bloom on the same day, increasing the number of flowers with approximately 70% female flowers in the orchard, and placing enough hives to maintain more than 6 bees per 1000 flowers to optimize yield. We expected that male-female kiwifruit flower ratio and pollinator density will influence fruit yield, along with various parameters of pollinator behavior. The model explicitly tracks pollinators (parameterized here based on data from honey bees), with varying pollen loads as they preferentially visit male and female flowers, as well as A major model output measure is the predicted yield, which is defined as the number of female flowers per ha that became fully pollinated fruit. The model includes preference parameters for pollinators to remain on the type of flower they are visiting, based again on data from honey bee observations. cache = ./cache/cord-013356-y6vceq2x.txt txt = ./txt/cord-013356-y6vceq2x.txt === reduce.pl bib === id = cord-260432-imslfm4l author = Marshall, Jenika D. title = THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation date = 2020-05-21 pages = extension = .txt mime = text/plain words = 5851 sentences = 287 flesch = 47 summary = Thus, we hypothesized that one or more specific fatty acids that exist within the total FFA component of lipoprotein hydrolysis products that are generated by LPL impair cholesterol efflux through the activation of Akt. To test this hypothesis, using THP-1 macrophages, we examined the activation of Akt in response to various FFA mixtures that contain the concentrations of FFA species that we previously reported to be found within LPL hydrolysis products from total lipoproteins [16] . Lastly, we examined the molecular species of phosphoinositides (PIPx) of THP-1 macrophages treated with palmitoleate, to determine if there were changes to select PIPx species that may contribute to a preferential activation of Akt. We previously showed using antibody arrays that the hydrolysis products liberated by LPL from total lipoproteins (ρ<1.21 g/ml), as well as the reconstituted total FFA component matching that liberated by LPL at a physiological concentration of 0.68 mM, significantly increased the phosphorylation of Akt after 30 minutes within THP-1 macrophages [16] . cache = ./cache/cord-260432-imslfm4l.txt txt = ./txt/cord-260432-imslfm4l.txt === reduce.pl bib === id = cord-257603-ov0b8yub author = Azlan, Arina Anis title = Public knowledge, attitudes and practices towards COVID-19: A cross-sectional study in Malaysia date = 2020-05-21 pages = extension = .txt mime = text/plain words = 4685 sentences = 256 flesch = 54 summary = To measure practices, participants were asked yes/no questions on whether they had avoided going to crowded places such as weddings; wore a face mask when leaving home; and whether they practiced proper hand hygiene in the week before the movement control order (MCO). The first question asked whether or not they agreed that the COVID-19 situation would be successfully controlled; second, whether they thought Malaysia would be able to win its battle against the virus; and third, whether they thought the Malaysian government was handling the health crisis well [Fig 1] . Practices toward COVID-19 were measured using three questions enquiring on: 1) avoidance of crowded places, 2) wearing of face masks; and 3) practising proper hand hygiene in the week before the Movement Control Order (MCO) was implemented in Malaysia [Fig 2] . Public knowledge, attitudes and practices towards COVID-19 in Malaysia residents in the Eastern region and retirees were among the highest percentage of participants who had not practised good hand hygiene in the week before the MCO. cache = ./cache/cord-257603-ov0b8yub.txt txt = ./txt/cord-257603-ov0b8yub.txt === reduce.pl bib === id = cord-254825-c5d0wul9 author = Kim, Sei Won title = Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience date = 2020-08-14 pages = extension = .txt mime = text/plain words = 3554 sentences = 205 flesch = 49 summary = In this study, we retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing, contact history, and presence of respiratory symptoms in a single center with a healthcare-associated COVID-19 outbreak. We reviewed the history of patients to assess whether they visited China or other high-risk countries within two weeks prior to the outbreak of healthcare-associated COVID-19, or if they came into contact with confirmed COVID-19 cases. After SARS-CoV-2 infection was confirmed, the Seoul city government announced the closure of the hospital on February 21, 2020, to prevent a healthcare-associated outbreak. After the hospital staff member responsible for transporting patients was confirmed as the first COVID-19 case, people with contact history, fever, or respiratory symptoms were tested for SARS-CoV-2 infection with RT-PCR (Fig 2) . After the first case was reported, epidemiologists from KCDC and the infection control unit of our hospital reviewed electronic medical charts, CCTV, and personal movements to identify individuals with potential contact with confirmed COVID-19 patients. cache = ./cache/cord-254825-c5d0wul9.txt txt = ./txt/cord-254825-c5d0wul9.txt === reduce.pl bib === id = cord-260653-5qwtvm9x author = Chikhlikar, Priya title = DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date = 2006-12-27 pages = extension = .txt mime = text/plain words = 6117 sentences = 278 flesch = 49 summary = Thomas; Marques, Ernesto T.A. title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. This study demonstrates that Rhesus macaques immunized with a DNA plasmid vaccine-encoding gag as an hLAMP/gag chimera develops strong antigen-specific humoral responses as well as CD4 + and CD8 + T-cell responses. cache = ./cache/cord-260653-5qwtvm9x.txt txt = ./txt/cord-260653-5qwtvm9x.txt === reduce.pl bib === id = cord-254340-e1x0z3rh author = Cruz, Christian Joy Pattawi title = Exploring the young demographic profile of COVID-19 cases in Hong Kong: Evidence from migration and travel history data date = 2020-06-26 pages = extension = .txt mime = text/plain words = 4963 sentences = 227 flesch = 59 summary = Using detailed case data from Hong Kong's Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong's high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Our study includes an examination of the age and sex distribution of the COVID-19 confirmed cases in Hong Kong and an exploration of how the different measures to combat this outbreak resulted in a relatively low number of cases and deaths. In this paper, we highlight the potential impact of the young profile of the confirmed cases on the total number of mortalities and the effect of early, aggressive policy measures including travel bans, enforced quarantines and contact-tracing imposed by the Hong Kong government as early as January 27, 2020 in containing the spread of the COVID-19. cache = ./cache/cord-254340-e1x0z3rh.txt txt = ./txt/cord-254340-e1x0z3rh.txt === reduce.pl bib === id = cord-259771-653opx0h author = Dwivedi, Varun title = Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs date = 2012-12-11 pages = extension = .txt mime = text/plain words = 5900 sentences = 290 flesch = 45 summary = In a pre-challenge study, intranasal delivery of Nano-KAg resulted in induction of innate immune response at both mucosal and systemic sites, indicated by a significant increase in the frequency of NK cells, DCs, and cd T cells in the lung MNC ( Figure 2 , A-C); and cd T cells and DCs in the PBMC compared to K-Ag vaccinated pigs (Figure 2, H & I) . Lung homogenates of Nano-KAg immunized pigs contained significantly higher levels of virus specific IgA and IgG antibodies compared to unvaccinated and K-Ag vaccinated, MN184 challenged pigs (Figure 4, A & B) . The frequency of cd T cells and CD4 + (but not CD8 + ) T cells in the lungs of Nano-KAg vaccinated animals were significantly increased compared to K-Ag and unvaccinated, virus challenged pigs ( Figure 5 , D, E & F). cache = ./cache/cord-259771-653opx0h.txt txt = ./txt/cord-259771-653opx0h.txt === reduce.pl bib === id = cord-260572-vd65ygtm author = Kim, Curi title = Comparison of Nasopharyngeal and Oropharyngeal Swabs for the Diagnosis of Eight Respiratory Viruses by Real-Time Reverse Transcription-PCR Assays date = 2011-06-30 pages = extension = .txt mime = text/plain words = 3515 sentences = 173 flesch = 52 summary = BACKGROUND: Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach. To evaluate the comparative yields of NP and OP swabs in detecting key respiratory viruses by real-time RT-PCR (qRT-PCR), we conducted a prospective study using paired NP and OP specimens from patients at two respiratory disease surveillance sites in Kenya. NP and OP specimens from each patient were separately tested by singleplex qRT-PCR for eight viral pathogens: adenovirus, influenza A virus, influenza B virus, human metapneumovirus (hMPV), parainfluenza viruses (PIV) 1-3, and respiratory syncytial virus (RSV). cache = ./cache/cord-260572-vd65ygtm.txt txt = ./txt/cord-260572-vd65ygtm.txt === reduce.pl bib === id = cord-256424-t3dtabi4 author = Bousbia, Sabri title = Repertoire of Intensive Care Unit Pneumonia Microbiota date = 2012-02-28 pages = extension = .txt mime = text/plain words = 5641 sentences = 294 flesch = 39 summary = Recently, the bacterial microbiota of patients with cystic fibrosis and ventilator-associated pneumonia (VAP) were studied using 16S rDNA gene amplification followed by clone libraries sequencing [9] [10] [11] . Bacterial microbiota as evaluated by 16S rDNA Molecular assays were positive for at least one bacterium for 129 out of 185 bronchoalveolar lavage (BAL) samples from patients with pneumonia as well as from 13 out of 25 from control individuals (p = 0.07). Fungal microbiota obtained from patients showed the presence of 22 different species belonging to 2 phyla (8 orders, 11 families and 12 genera) among which 6 phylotypes had not been previously identified in BAL fluids from pneumonia. Indeed, our study reveals that some pathogens that till now had been considered typical for ICU pneumonia, such as Pseudomonas aeruginosa and Streptococcus species, or viruses, such CMV and HSV, can be detected as commonly in controls as in patients (Fig. S1 and S2 ). cache = ./cache/cord-256424-t3dtabi4.txt txt = ./txt/cord-256424-t3dtabi4.txt === reduce.pl bib === id = cord-252795-x66zqmgv author = Islam, Md. Akhtarul title = Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey date = 2020-08-26 pages = extension = .txt mime = text/plain words = 4011 sentences = 214 flesch = 47 summary = title: Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey Following the detection of first COVID-19 case on March 8, 2020 [6] , Bangladesh like many other countries put the lockdown strategy into effect on March 26, 2020 , to ensure 'social distance' through 'home quarantine' to curb the 'spread' among its population [7] [8] [9] , since a precise treatment or vaccine for the infected and people at risk are yet to achieved by the global health community [10, 11] . The ongoing COVID-19 pandemic is creating a psycho-emotional chaotic situation as countries have been reporting a sharp rise of mental health problems, including anxiety, depression, stress, sleep disorder as well as fear, among its citizens [15] [16] [17] [18] [19] , that eventually increased the substance use [15] and sometimes suicidal behavior [20] [21] [22] . Researchers in China observed that the greater exposure to 'misinformation' through social media are more likely contributing to the development of anxiety, depression, and other mental health problems among its population of different socioeconomic background [23] [24] [25] [26] . cache = ./cache/cord-252795-x66zqmgv.txt txt = ./txt/cord-252795-x66zqmgv.txt === reduce.pl bib === id = cord-262345-hti1jjpn author = Eddy, Lucy H. title = The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review date = 2020-08-25 pages = extension = .txt mime = text/plain words = 8728 sentences = 470 flesch = 50 summary = title: The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review METHODS: A pre-search of 'fundamental movement skills' OR 'fundamental motor skills' in seven online databases (PubMed, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, EBSCO SPORTDiscus, Ovid PsycINFO and Web of Science) identified 24 assessment tools for school-aged children that: (i) assess FMS; (ii) measure actual motor competence and (iii) evaluate performance on a standard battery of tasks. The psychometric properties of observational assessments of fundamental movement skills for school children correlations to evaluate the concurrent validity between the MOT 4-6 and the KTK, with results showing moderate correlations for children aged 5-6 (mean r = .63), as was hypothesised prior to testing (r >. cache = ./cache/cord-262345-hti1jjpn.txt txt = ./txt/cord-262345-hti1jjpn.txt === reduce.pl bib === id = cord-253436-dz84icdc author = Wille, Michelle title = High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl date = 2016-03-03 pages = extension = .txt mime = text/plain words = 2019 sentences = 103 flesch = 54 summary = In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. Despite few studies, small samples sizes and differences in prevalence, what is clear, is that in the Northern Hemisphere waterfowl species, especially dabbling and diving ducks are important in the epidemiology of avian CoVs. It is interesting to note that these patterns are very similar to those found in low pathogenic influenza A viruses: high prevalence in waterfowl and gulls in the Northern Hemisphere [30] , and little host species and temporal structuring within waterfowl derived viruses in the conserved polymerase genes (such as PB2, PB1) [31] . cache = ./cache/cord-253436-dz84icdc.txt txt = ./txt/cord-253436-dz84icdc.txt === reduce.pl bib === id = cord-258366-fu9b446y author = Couto, Carla R. title = Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project date = 2012-02-06 pages = extension = .txt mime = text/plain words = 3287 sentences = 180 flesch = 49 summary = At Hospital das Clinicas, University of Sã o Paulo School of Medical Sciences, a previous study showed a 34% compliance with influenza vaccination among HCWs. In the mentioned study, the main reasons for non-compliance were the perception of vaccine inefficacy and the fear of adverse reactions [4] . To diminish the arguments of fear of adverse events or perception of vaccine inefficacy, this prospective study was conducted to demonstrate to a subset of HCWs from our hospital, that severe adverse events following influenza vaccination are rare and the episodes of respiratory symptoms occurring in the first four months after vaccination are generally caused by other respiratory viruses and not by influenza virus. As expected, no severe adverse event was observed in the present study, and the events more frequently reported, such as headache, myalgia and malaise could be related to influenza vaccine itself as well as to other causes, given their unspecificity. cache = ./cache/cord-258366-fu9b446y.txt txt = ./txt/cord-258366-fu9b446y.txt === reduce.pl bib === id = cord-261908-olcuq6tm author = Lai, Ka-Man title = Propagation of Respiratory Aerosols by the Vuvuzela date = 2011-05-23 pages = extension = .txt mime = text/plain words = 3983 sentences = 199 flesch = 53 summary = The fate of the droplet nuclei on inhalation also depends on their size; particles greater than five microns are likely to remain in the upper airways but smaller particles are more likely to deposit in the alveoli and so may transmit infections of the lower respiratory tract such as tuberculosis [22, 23] . The large number of aerosols emitted by the vuvuzela raises the possibility that, if used by persons with an infection of the respiratory tract, they could act a conduit for the spread of infectious particles. To obtain the desired trumpet sound when blowing the vuvuzela air is forced through the lips into the opening of the instrument which may serve to create further aerosols, or alter the size of droplets produced elsewhere in the respiratory tract. Exhale duration, peak air velocity, particle concentration and mean particle diameter recorded during playing the vuvuzela and shouting by four male and four female volunteers. cache = ./cache/cord-261908-olcuq6tm.txt txt = ./txt/cord-261908-olcuq6tm.txt === reduce.pl bib === id = cord-258243-2utl2mfl author = Chen, Jeng-Wen title = Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study date = 2018-05-29 pages = extension = .txt mime = text/plain words = 4350 sentences = 230 flesch = 44 summary = We investigated the distribution of the three major categories of surgical indication according to sex, age group (<5 years, 5-11 years, 11-17 years, 18-40 years, and >40 years), hospital level (medical centers, regional hospitals, and local hospitals), and insured residence areas according to the NHI divisions (Taipei, Northern, Central, Southern, Kaoping, and Eastern). In the adult subgroup (Figs 2B and 3B) , the incidence and proportion of AT performed for RICI decreased from 46 (78%) in 1997 to 32 Table 3 indicates the number and percentage of the three categories of surgical indications according to sex, age groups, hospital level, and insured residence areas in the total study population. The trend in the AT rate and the proportion of surgical indications by the calendar year according to sex, age groups, hospital level, and insured residence areas in the total study population are shown in the supplemental data (S1 File). cache = ./cache/cord-258243-2utl2mfl.txt txt = ./txt/cord-258243-2utl2mfl.txt === reduce.pl bib === id = cord-258172-p54j4zzo author = Barker, Harlan title = Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2 date = 2020-10-28 pages = extension = .txt mime = text/plain words = 8453 sentences = 409 flesch = 48 summary = Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Analysis of ACE2 promoter regions was performed using the TFBSfootprinter tool (https:// github.com/thirtysix/TFBS_footprinting) which uses transcription-relevant data from several major databases to enhance prediction of putative TFBSs, including: all cell types aggregated and merged human ATAC-Seq data from ENCODE [43] , transcription start sites and expression data from FANTOM5 [44] , expression quantitative trail loci from GTEx [39] , TFBS metacluster data from GTRD [45] , TFBS binding profile data from JASPAR [46] , and sequence and conservation data from Ensembl [47] . cache = ./cache/cord-258172-p54j4zzo.txt txt = ./txt/cord-258172-p54j4zzo.txt === reduce.pl bib === id = cord-255351-vp19ydce author = Lanata, Claudio F. title = Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review date = 2013-09-04 pages = extension = .txt mime = text/plain words = 5451 sentences = 221 flesch = 48 summary = We present the results of a systematic literature review of studies of diarrhea etiology in hospitalized children and use these results to estimate the global burden of diarrhea mortality by pathogen for children under 5 years of age for 2011. From 22 643 citations identified in the electronic search, 1 003 articles were selected for further evaluation (Fig. 1) ; 840 articles were excluded because they had one or more of the exclusion criteria (About 35% because they were not longitudinal studies or inappropriate laboratory methods were used, 31% because no data was given for children ,5 years of age, 23% for studies that lasted less than 12 months of duration, and the rest because data were reported after rotavirus vaccine introduction, duplicate publications or reporting results on a pathogen not included in our list). cache = ./cache/cord-255351-vp19ydce.txt txt = ./txt/cord-255351-vp19ydce.txt === reduce.pl bib === id = cord-255588-nh34lgdh author = Guo, Fang title = RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response date = 2012-10-03 pages = extension = .txt mime = text/plain words = 4776 sentences = 268 flesch = 51 summary = Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 ('2'-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. In order to discover compounds with the expected pharmacological property, we set out to establish reporter cell lines for high throughput screening of small molecules that selectively enhance TLR3 ligand-induced IFN-b gene expression, but do not affect NFkB activation, which is a central player in the induction of proinflammatory cytokines, but plays a less prominent role in type I IFN gene expression [25] . cache = ./cache/cord-255588-nh34lgdh.txt txt = ./txt/cord-255588-nh34lgdh.txt === reduce.pl bib === id = cord-260843-c97kctjz author = Dai, Lei title = Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake date = 2016-11-16 pages = extension = .txt mime = text/plain words = 4635 sentences = 255 flesch = 46 summary = In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Therefore, in the study, we aimed to examine the in vitro effects of TGEV infection on glucose uptake and the expression of SGLT1 and GLUT2 in porcine intestinal columnar epithelial (IPEC-J2) cells, which have been shown to offer a practical model for studying TGEV infection [11, 12] . Together, these results indicate that EGFR and p-EGFR regulates glucose uptake in mock-infected IPEC-J2 cells by modulation of SGLT1 protein expression. Together, these results indicate that EGFR influences glucose uptake in TGEV-infected cells by promoting both SGLT1 and GLUT2 expression. cache = ./cache/cord-260843-c97kctjz.txt txt = ./txt/cord-260843-c97kctjz.txt === reduce.pl bib === id = cord-260728-4w23kwzu author = Timmermans, Ans title = Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia date = 2016-03-30 pages = extension = .txt mime = text/plain words = 7411 sentences = 381 flesch = 50 summary = Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. Between May 2010 and December 2012, we collected specimens and surveillance data for influenza and other viral respiratory pathogens from a subset of outpatients presenting with influenza-like-illness (ILI) at four sentinel sites-located in five health centers and hospitals in Battambang, Oddar Meanchey, Pailin and Banteay Meanchey provinces in Cambodia (Fig 1) . A subset of 164 culture-negative specimens (collected between May 2010 and April 2012), where we found a higher proportion (5.6%) of non-polio enteroviruses in children less than 5 years old as compared with previous studies (1%) in Cambodia [2] , were tested for enterovirus and rhinovirus by two separate nested RT-PCR methods adapted from Coiras et al., 2004 and Singh et al., 2002 [29,30] , one for simultaneous detection of pan-enteroviruses and rhinoviruses, and the other specific for enterovirus 71 (EV71). cache = ./cache/cord-260728-4w23kwzu.txt txt = ./txt/cord-260728-4w23kwzu.txt === reduce.pl bib === id = cord-260647-7bjhobg7 author = Coudray-Meunier, Coralie title = A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System date = 2016-01-29 pages = extension = .txt mime = text/plain words = 5581 sentences = 278 flesch = 48 summary = A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The aim of this study was to develop real time RT-PCR assays for detection of a total of 19 human enteric viruses (including 3 genogroupes of norovirus and 4 coronaviruses) and two control process viruses (mengovirus and murine norovirus) generally used for monitoring the recovery of viral foodstuff extraction methods. The sensitivity of conventional qPCR assays targeting 21 viral genomes was compared to the quantitative digital RT-PCR array and to the qualitative nanofluidic real-time PCR array performed on Fluidigm's BioMark System. Similarly, by testing genomes from viruses in stools and RNA from virus production in cells, the limit of detection (LOD) as determined by RT-dPCR was respectively 1.5 to 3.4 log 10 and 1.6 to 2.1 log 10 lower than the expected copy numbers calculated via the standard curve by RT-qPCR. cache = ./cache/cord-260647-7bjhobg7.txt txt = ./txt/cord-260647-7bjhobg7.txt === reduce.pl bib === id = cord-262759-ec2c25q3 author = Hsieh, Yi-Ting title = Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus date = 2013-11-04 pages = extension = .txt mime = text/plain words = 4838 sentences = 223 flesch = 40 summary = The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. We hypothesized that G6PD-deficient cells are less tolerant to oxidative stress upon bacterial infection, leading to the accumulation of more intracellular ROS when compared to the control scramble cells. To determine whether the reduced ROS accumulation and apoptotic activity, particularly in G6PD-deficient cells, was due to deceased αhemolysin expression upon VRSA infection in the presence of vancomycin, the production of intracellular ROS and cell apoptosis when the α-hemolysin inhibitor Oroxylin A was added to the media was quantified by flow cytometry. Our results presented here indicate that expression of active caspase-9, as well as the downstream caspase-3, was much higher in G6PD-deficient cells than in control scramble cells upon VRSA infection, suggesting that mitochondrial dysfunction may be the major cause of the increase in cell apoptosis (Figure 4) . cache = ./cache/cord-262759-ec2c25q3.txt txt = ./txt/cord-262759-ec2c25q3.txt === reduce.pl bib === id = cord-048477-ze511t38 author = Patel, Mahomed S. title = General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries date = 2008-05-28 pages = extension = .txt mime = text/plain words = 6918 sentences = 343 flesch = 41 summary = The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. Although there is little evidence linking specific preparedness activities to effective system-wide responses to pandemic influenza [5, 6] , change management theories point to a need for dynamic partnerships between general practices and other ambulatory care services, hospitals and public health departments [10] . We aimed to develop a framework that will facilitate systematic planning for the general practice response to pandemic influenza and used it to appraise coverage of key elements in publicly available pandemic plans from Australia, England, USA, New Zealand and Canada. This calls for coordination across general practices and other ambulatory care services to ensure primary health care needs within the community are effectively monitored and addressed; with hospitals to avoid/delay hospitalisation and facilitate early discharge; and with public health units to share responsibilities for contact tracing, monitoring and treating people in home isolation or quarantine, dispensing of anti-viral medications, and participation in mass immunisations against pandemic strains of the virus (when these become available). cache = ./cache/cord-048477-ze511t38.txt txt = ./txt/cord-048477-ze511t38.txt === reduce.pl bib === id = cord-261410-kb91eagd author = Park, Ji Young title = Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel date = 2017-01-23 pages = extension = .txt mime = text/plain words = 3504 sentences = 205 flesch = 43 summary = The clinical features of respiratory adenoviral infection among military personnel were described previously; however, HAdV pneumonia in immunocompetent individuals and risk factors of disease progression to severe pneumonia or acute respiratory failure have not been well studied. All military trainees or active duty members, but not officers, were eligible for enrollment if they were !18 years old and had been admitted to the study hospital for pneumonia, defined by acute respiratory symptoms (fever, cough, sputum, dyspnea, and pleuritic chest pain) and pulmonary infiltrates on chest X-rays or computed tomography (CT) scans. Most HAdV pneumonia patients were basic military trainees or personnel who had recently completed training; active duty service personnel were not usually affected, even during outbreak peaks. Our results show that an outbreak of HAdV pneumonia occurred in Korean military training centers and indicate that emergent-type HAdV-55 infections might have caused the outbreak. cache = ./cache/cord-261410-kb91eagd.txt txt = ./txt/cord-261410-kb91eagd.txt === reduce.pl bib === id = cord-256326-3ebcuzd6 author = Liotta, Giuseppe title = Is social connectedness a risk factor for the spreading of COVID-19 among older adults? The Italian paradox date = 2020-05-21 pages = extension = .txt mime = text/plain words = 2364 sentences = 114 flesch = 57 summary = We analyzed several variables to test this hypothesis, such as the percentage of infected patients aged >80 years, available nursing home beds, COVID-19 incidence rate, and the number of days from when the number of positive tests exceeded 50 (epidemic maturity). While there is a very clear association between the case fatality rate and age demographics (Italy has the second oldest population worldwide and has the highest ageing index in Europe [4] with a value of 168.9), we wanted to test the hypothesis that the supposed closeness between younger and older generations in Italian families may have played a major role in the pandemic spread. Additionally, we explored the relationship between the proportion of infected patients aged >80 years and social connectedness indicators, such as the percentage of family comprising one members and household size [5] . cache = ./cache/cord-256326-3ebcuzd6.txt txt = ./txt/cord-256326-3ebcuzd6.txt === reduce.pl bib === id = cord-256837-100ir651 author = Smith, Steven B. title = Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date = 2012-03-14 pages = extension = .txt mime = text/plain words = 8447 sentences = 415 flesch = 38 summary = Several recent studies have generated multiple mRNA microarray gene expression datasets derived from experiments involving the infection of human cell-lines or animal models with one or more of the major respiratory viruses [21] [22] [23] . Through a systematic analysis of these respiratory virus-human host gene expression datasets, we determined common sets of genes and pathways involved in host responses to viral infections. A total of seven different respiratory viruses were analyzed, represented by fifteen unique Gene Expression Omnibus (GEO) datasets (indicated by GEO Series or GSE accession numbers), nine different human cell types, and seven different array platforms for a total of 28 unique comparisons. This assumption is based on the occurrence of genes that are differentially expressed in infection models for at least five of the seven respiratory viruses, have involvement in a number of relevant pathways related to host immune response, and encode for known drug targets. cache = ./cache/cord-256837-100ir651.txt txt = ./txt/cord-256837-100ir651.txt === reduce.pl bib === === reduce.pl bib === id = cord-262846-1mhimfsf author = Gray, Nicholas title = Is “no test is better than a bad test”? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19 date = 2020-10-21 pages = extension = .txt mime = text/plain words = 6023 sentences = 337 flesch = 55 summary = This strategy would involve detecting those who have successfully overcome the virus, and are likely to have some level of immunity (or at least reduced susceptibility to more serious illness if they are infected again), so are relatively safe to relax their personal lockdown measures. To explore the effect of imperfect testing on the disease dynamics when strategies testing regimes are employed to relax lockdown measures, three new classes were added to the model. implement quarantine in their model but do not incorporate the effects on the dynamics from imperfect testing, nor do they consider how the quality and scale of an available test affect the spread of a disease. Wide-scale screening for antibodies in the general population promises significant scientific value, and targeted antibody testing is likely to have value for reducing risks to NHS and care-sector staff, and other key workers who will need to have close contact with COVID-19 sufferers. cache = ./cache/cord-262846-1mhimfsf.txt txt = ./txt/cord-262846-1mhimfsf.txt === reduce.pl bib === id = cord-263276-keyu60in author = Zhou, Weimin title = Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia date = 2013-11-18 pages = extension = .txt mime = text/plain words = 3813 sentences = 191 flesch = 50 summary = METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. The present study was undertaken to describe the profiles of HHVs and other respiratory viruses associated with hospital-based CAP and non-CAP among infants and young children in a rural area of China using comprehensive and sensitive molecular diagnostic techniques. In this study, the viral prevalence in sputum specimens of childhood with non typical bacterial CAP was investigated using sensitive molecular diagnostic methods for HHVs and 15 respiratory viruses, and viruses were detected in 99.6% of the children. In summary, our study on the prevalence of HHVs and other respiratory viruses in infants and young children with CAP identified a detectable virus in more than 99.6% of case participants, in which CMV, HHV-6, EBV, RSV and HBoV were clearly predominant (.25%) and contributed significantly to the spectrum of CAP in a rural area of China. cache = ./cache/cord-263276-keyu60in.txt txt = ./txt/cord-263276-keyu60in.txt === reduce.pl bib === id = cord-263453-7v4y02j6 author = Nishiura, Hiroshi title = Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic date = 2009-08-31 pages = extension = .txt mime = text/plain words = 5350 sentences = 231 flesch = 55 summary = We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Nevertheless, a much-used crude estimate of the cCFR, i.e. the ratio of the cumulative number of deaths to cases at calendar time t, tends to yield a biased (and mostly underestimated) cCFR due to the time-delay from onset to death [8] ; similar estimates of such a biased cCFR for severe acute respiratory syndrome (SARS) have shown how such estimates can vary substantially as an epidemic progresses, stabilizing only in the later stages of the outbreak [8, 9] . doi:10.1371/journal.pone.0006852.g003 Figure 6 shows the time course of biased cCFR estimates in the USA and Canada based on the reporting date of confirmed cases and deaths to the World Health Organization. cache = ./cache/cord-263453-7v4y02j6.txt txt = ./txt/cord-263453-7v4y02j6.txt === reduce.pl bib === id = cord-263978-jk82bk1a author = Karaivanov, Alexander title = A social network model of COVID-19 date = 2020-10-29 pages = extension = .txt mime = text/plain words = 11398 sentences = 576 flesch = 57 summary = The proposed network-augmented (NSIR) model allows the evaluation, via simulations, of (i) health and economic policies and outcomes for all or subset of the population: lockdown/distancing, herd immunity, testing, contact tracing; (ii) behavioral responses and/or imposing or lifting policies at specific times or conditional on observed states. I construct and compute a dynamic social network-based model of the COVID-19 epidemic and use it to evaluate a range of simulated health and economic policies-herd immunity, distancing, lockdown, testing, quarantine, and contact tracing. While helpful for simplifying the dynamics and computing outcomes, this population-level random matching assumption abstracts from important elements of realism and locality: (i) people are more likely to interact with members of their social network, broadly defined (e.g., family, work, or distance based); (ii) health and economic policies targeting disease mitigation, as well as individual behavioral responses, can affect the rate of viral transmission via a person's network of contacts vs. cache = ./cache/cord-263978-jk82bk1a.txt txt = ./txt/cord-263978-jk82bk1a.txt === reduce.pl bib === id = cord-257217-f9sdt7ax author = Nunes, Marta C. title = Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children date = 2014-02-03 pages = extension = .txt mime = text/plain words = 4629 sentences = 215 flesch = 43 summary = We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. The aim of this study was to identify the prevalence of hBoV, hRV, WUPyV, KIPyV, CoV-OC43, CoV-NL63, CoV-HKU1 and CoV-229E among HIV-infected and -uninfected children who were hospitalized for LRTI using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Very few viral aetiology studies have been conducted in Africa: in a Mozambican study of virus-associated acute respiratory infections (ARI) in infants with an estimated 3-5% HIV prevalence, the most frequently detected viruses were hRV (26%), influenza (15%) and adenovirus (14%) [27] . cache = ./cache/cord-257217-f9sdt7ax.txt txt = ./txt/cord-257217-f9sdt7ax.txt === reduce.pl bib === id = cord-255384-tljyx6ua author = Decaro, Nicola title = Full-Genome Analysis of a Canine Pneumovirus Causing Acute Respiratory Disease in Dogs, Italy date = 2014-01-06 pages = extension = .txt mime = text/plain words = 4629 sentences = 243 flesch = 55 summary = The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. In order to obtain new insights into the genetic diversity of CnPnV, the Italian prototype strain dog/Bari/100-12/ITA/2012 was submitted to RT-PCR amplification and subsequent sequence analysis of the full-length genome, using oligonucleotide retrieved from previous studies [13] [14] . When the analysis was restricted to the 8,600 and 8,598 nt available for reference CnPnV strains Brne17 and Ane4, respectively, that span from the very 39 end of the L gene to the 59end of the leader region (genome sense), an overall sequence identity of 96.5-96.6% was found against the canine strains. cache = ./cache/cord-255384-tljyx6ua.txt txt = ./txt/cord-255384-tljyx6ua.txt === reduce.pl bib === id = cord-265138-i5m3ax7g author = Wang, Xi-Ling title = Model Selection in Time Series Studies of Influenza-Associated Mortality date = 2012-06-20 pages = extension = .txt mime = text/plain words = 4196 sentences = 240 flesch = 45 summary = METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. Four model selection criteria were considered in this study: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV). Two recent studies in Canada and Hong Kong have demonstrated the estimates of influenza-associated hospitalization derived from Poisson regression models reasonably matched the numbers of patients with laboratory confirmed influenza infections [17, 29] . cache = ./cache/cord-265138-i5m3ax7g.txt txt = ./txt/cord-265138-i5m3ax7g.txt === reduce.pl bib === id = cord-263464-fdosch11 author = Nuvey, Francis Sena title = Evaluation of the sentinel surveillance system for influenza-like illnesses in the Greater Accra region, Ghana, 2018 date = 2019-03-14 pages = extension = .txt mime = text/plain words = 4094 sentences = 227 flesch = 47 summary = We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system's attributes and its performance on set objectives. In collaboration with the Ghana Health Service (GHS) and the Ministry of Defense (MOD), it currently operates sentinel surveillance for influenza in 27 sites across all regions in Ghana with support from the U.S. Naval Medical Research Unit No. 3 (NAMRU-3), Centers for Disease Control and Prevention (CDC) and WHO [8] . We found that data on patients meeting the ILI case definition (S2 Table) from the sentinel sites are collected together with nasopharyngeal or oropharyngeal specimen. Our study provides evidence, that the ILI sentinel surveillance system in the Greater Accra Region (GAR), Ghana, is only partially meeting its objectives because it did not have thresholds for alerting the health system and does not perform antiviral resistance testing. cache = ./cache/cord-263464-fdosch11.txt txt = ./txt/cord-263464-fdosch11.txt === reduce.pl bib === id = cord-265812-1hcp36cw author = De Jong, Cornelis N. title = Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience date = 2017-10-26 pages = extension = .txt mime = text/plain words = 3168 sentences = 186 flesch = 53 summary = W.; Van der Klift, Marjolein; Cornelissen, Jan J.; Broers, Annoek E. High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients. High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients [2, 3] . Studies evaluating second-line treatment with the anti-TFNα agent etanercept have shown promising results with overall response rates of 50-80% [8] [9] [10] . In conclusion, although second-line treatment of SR-aGVHD of the gut with etanercept was associated with a promising initial response rate, overall survival appeared very poor, mainly due to progression of GVHD and opportunistic infections. cache = ./cache/cord-265812-1hcp36cw.txt txt = ./txt/cord-265812-1hcp36cw.txt === reduce.pl bib === id = cord-262832-5iejckwx author = Yen, Muh-Yong title = Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease date = 2009-11-23 pages = extension = .txt mime = text/plain words = 5998 sentences = 285 flesch = 51 summary = In launching countermeasures to bring the AHC outbreak under control, the Taipei Department of Health was also able to test its system and fine-tune its public health response for future EIDs. To evaluate the effectiveness of these intervention measures, daily surveillance was conducted to analyze the incidence rate and temporal-spatial distribution of new AHC cases. This risk communication program focused on communicating directly to the public through three routes: (1) schools delivered a Taipei Department of Health letter signed by the mayor (that detailed AHC information and prevention methods) for students to take home to their parents, (2) the mayor held a press conference to discuss the epidemic and offer guidance to citizens for preventing the spread of the disease, and (3) over 2.2 million short message services (SMS) messages, a communication tool for exchanging short text messages between mobile telephonic devices, were delivered to all Taipei mobile phone numbers. cache = ./cache/cord-262832-5iejckwx.txt txt = ./txt/cord-262832-5iejckwx.txt === reduce.pl bib === id = cord-267189-xq70rn1j author = Wang, Xinyu title = Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China date = 2016-01-15 pages = extension = .txt mime = text/plain words = 3037 sentences = 156 flesch = 56 summary = To trace the evolution of canine coronavirus (CCoV), 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs) targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity. A phylogenetic analysis using partial S gene sequences demonstrated that the 26 CCoV-IIa strains were closely related to three reference strains, 5281 (Japan), TN-449 (USA), and 1086-IIa (Brazil), and differed genetically from reference strains from China and other countries (Fig 2A) . This result demonstrated that vaccination for other canine viruses did not effect CCoV infections in the dog population in Heilongjiang province, northeast China. cache = ./cache/cord-267189-xq70rn1j.txt txt = ./txt/cord-267189-xq70rn1j.txt === reduce.pl bib === id = cord-263684-3535k3op author = Tang, Julian W. title = Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms date = 2013-06-24 pages = extension = .txt mime = text/plain words = 5292 sentences = 211 flesch = 52 summary = Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. This study is part of a longer-term project that aims to demonstrate the effects of door-opening motions using a variety of doors, with and without the passage of a human figure, on the movement of potentially contaminated air into and out of an isolation room, using both a small-scale, Reynolds-number-equivalent model in water, and a full-scale model in air. In the small-scale water-tank models used in these experiments, the compartment outside the isolation room, into or from which The series of 4 snapshots with each dooropening, manikin movement scenario were taken with respect to the following events, rather than at specific times: food dye movement due to door-opening motions alone then with any initial manikin movement -manikin interaction and any entrainment food dye -final food dye movements once the manikin had come to rest at its destination position. cache = ./cache/cord-263684-3535k3op.txt txt = ./txt/cord-263684-3535k3op.txt === reduce.pl bib === id = cord-267644-guzn0peq author = Livadiotis, George title = Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19 date = 2020-05-29 pages = extension = .txt mime = text/plain words = 6525 sentences = 326 flesch = 54 summary = We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. First, we derive the exponential growth rates of the infected cases characterizing each examined region of US and Italy; then, we plot these values against the environmental temperatures of each region, and perform the corresponding statistical analysis. cache = ./cache/cord-267644-guzn0peq.txt txt = ./txt/cord-267644-guzn0peq.txt === reduce.pl bib === id = cord-267519-a0bcmjkn author = Bravi, Francesca title = Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date = 2020-06-24 pages = extension = .txt mime = text/plain words = 3303 sentences = 144 flesch = 44 summary = AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5] [6] [7] [8] , and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and ACE inhibitors (more consistently on animals than in humans) [9] [10] [11] [12] [13] [14] [15] [16] , some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), thus the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17] [18] [19] . cache = ./cache/cord-267519-a0bcmjkn.txt txt = ./txt/cord-267519-a0bcmjkn.txt === reduce.pl bib === id = cord-267973-uvz7kavu author = Do, Lien Anh Ha title = Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity date = 2016-08-08 pages = extension = .txt mime = text/plain words = 5921 sentences = 476 flesch = 61 summary = title: Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. However, information on detailed clinical, epidemiological features and virological characteristics of RSV infections (e.g. disease burden, demographics, seasonal variations of RSV and other viral infections, circulating genotypes and subgroups, viral load) or on the frequency / impact of other respiratory viruses among Vietnamese children under two years old are limited [6] . Here, we aimed to describe the viral etiologies and the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a LRTI, focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. cache = ./cache/cord-267973-uvz7kavu.txt txt = ./txt/cord-267973-uvz7kavu.txt === reduce.pl bib === id = cord-267307-kyh0xsrp author = Kasting, Monica L. title = Public perceptions of the effectiveness of recommended non-pharmaceutical intervention behaviors to mitigate the spread of SARS-CoV-2 date = 2020-11-04 pages = extension = .txt mime = text/plain words = 4343 sentences = 230 flesch = 54 summary = Public health efforts should focus on increasing perceived severity and threat of SARS-CoV-2-related disease, while promoting NPI as effective in reducing threat. A six-item measure was used to assess participants' perceptions of the effectiveness of NPIs to prevent SARS-CoV-2 infection and spread. Three of the six items measured the perceived effectiveness of preventing yourself from spreading COVID-19 to others and included: 1) wearing a mask anytime you leave the house to go out in public, 2) practicing social distancing by leaving at least six feet between you and other people (this does not include people you live with), and 3) covering your mouth when you cough. Any variable that was significant at p<0.01 in bivariate comparisons was included in an adjusted logistic regression model with the binary lower/ higher perceived effectiveness of COVID-19 prevention measures as the outcome. cache = ./cache/cord-267307-kyh0xsrp.txt txt = ./txt/cord-267307-kyh0xsrp.txt === reduce.pl bib === id = cord-266799-t7lqlv41 author = Rotejanaprasert, Chawarat title = Preliminary estimation of temporal and spatiotemporal dynamic measures of COVID-19 transmission in Thailand date = 2020-09-24 pages = extension = .txt mime = text/plain words = 5033 sentences = 265 flesch = 45 summary = This study thus aims to estimate and compare disease dynamic measures in several dimensions that can be augmented with epidemiological summary statistics to monitor the COVID-19 situation for each location and time at different stages of the epidemic. The data in this study were from confirmed COVID-19 cases in 77 provinces of Thailand from January 12 th 2020 through June 30 th 2020 provided in the daily reports of the Department of Disease Control, Thai Ministry of Public Health (MOPH). During the early stage of an epidemic curve caused by emerging diseases, the exponential growth (EG) rate, denoted by r, can be related to the initial reproduction rate and can be described as the change in number of new cases per time unit [15] . We wanted to provide information that could be used to help design effective control strategies for the current COVID-19 situation in Thailand after the disease has spread to different provinces across the country much of which was from cluster outbreaks originating from several super spreader events. cache = ./cache/cord-266799-t7lqlv41.txt txt = ./txt/cord-266799-t7lqlv41.txt === reduce.pl bib === id = cord-262748-v4xue7ha author = Xu, Yongtao title = Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine date = 2015-12-04 pages = extension = .txt mime = text/plain words = 4636 sentences = 253 flesch = 40 summary = Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The predictive support vector machine model for selfderived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process. In view of the important role of E proteins in virus fusion process and common mechanism of action of self-derived peptides, we developed a SVM model to predict the antiviral activities of self-derived peptides using sequence-based statistical scores as input features. Because similar sequences are often associated with similar structure and function, the sequence-based property AVPalign would account for the activities of the self-derived peptide inhibitors which regulate the virus fusion by mimicking the binding to E proteins. The prominent performance of EAPscoring model indicates the sequence-based stability feature of self-derived peptides may reflect their potential of binding to E proteins so as to regulate the virus entry process. cache = ./cache/cord-262748-v4xue7ha.txt txt = ./txt/cord-262748-v4xue7ha.txt === reduce.pl bib === id = cord-266797-uglsx7se author = Anastassopoulou, Cleo title = Data-based analysis, modelling and forecasting of the COVID-19 outbreak date = 2020-03-31 pages = extension = .txt mime = text/plain words = 5420 sentences = 235 flesch = 55 summary = Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Based on the released data, we attempted to estimate the mean values of the main epidemiological parameters, i.e. the basic reproduction number R 0 , the case fatality (ĝ) and case recovery (b) ratios, along with their 90% confidence intervals. Then, as described above, we provide coarse estimations of the "effective" per day recovery and mortality rates of the SIRD model based on the reported data by solving the corresponding least squares problems. cache = ./cache/cord-266797-uglsx7se.txt txt = ./txt/cord-266797-uglsx7se.txt === reduce.pl bib === id = cord-267566-gdjl0qmu author = Kweon, Oh Joo title = Antibody kinetics and serologic profiles of SARS-CoV-2 infection using two serologic assays date = 2020-10-22 pages = extension = .txt mime = text/plain words = 3599 sentences = 232 flesch = 51 summary = This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays. METHODS: A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI(™) Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA). The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI(™) Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results. cache = ./cache/cord-267566-gdjl0qmu.txt txt = ./txt/cord-267566-gdjl0qmu.txt === reduce.pl bib === id = cord-268816-nth3o6ot author = Roy, Satyaki title = Factors affecting COVID-19 infected and death rates inform lockdown-related policymaking date = 2020-10-23 pages = extension = .txt mime = text/plain words = 5733 sentences = 363 flesch = 56 summary = The features in the order shown under "Feature name" are: GDP, inter-state distance based on lat-long coordinates, gender, ethnicity, quality of health care facility, number of homeless people, total infected and death, population density, airport passenger traffic, age group, days for infection and death to peak, number of people tested for COVID-19, days elapsed between first reported infection and the imposition of lockdown measures at a given state. Unless otherwise stated, the feature set comprises GDP, gender, ethnicity, health care, homeless, lockdown type, population density, airport activity, and age groups, whereas the output labels consist of infected and death scores on a scale of 0-6. Although proposing a machine learning algorithm that works best on COVID-19 data is not the purpose of this study, it is worth reporting that decision tree classifier (DT) slightly outperforms the other algorithms for both cases of infected and death scores. cache = ./cache/cord-268816-nth3o6ot.txt txt = ./txt/cord-268816-nth3o6ot.txt === reduce.pl bib === id = cord-267605-efb10j3u author = Zheng, Li-Zhen title = Steroid-Associated Hip Joint Collapse in Bipedal Emus date = 2013-10-21 pages = extension = .txt mime = text/plain words = 5851 sentences = 249 flesch = 46 summary = The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. Accordingly, the aim of the current study was to establish a SAON model in bipedal emus, with potentials to bone structural deterioration with subsequent femoral head collapse, a condition seen in SAON patients attributed to similar biomechanics or loading ratio imposed onto the hip joint [23, 24] . Using a combined pulsed LPS and MPS induction protocol previously established for SAON quadrupedal rabbits [11, 13] , the present study established a SAON model in bipedal emus characterized with subchondral bone deterioration and hip joint collapse, an experimental model mimicking human ON often developed at hip joint with femoral head collapse. cache = ./cache/cord-267605-efb10j3u.txt txt = ./txt/cord-267605-efb10j3u.txt === reduce.pl bib === id = cord-272655-qeojdpez author = Remolina, Yuly Andrea title = Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia date = 2015-11-17 pages = extension = .txt mime = text/plain words = 4309 sentences = 204 flesch = 42 summary = OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Under this initiative, countries have developed surveillance systems by following cases of influenza-like illness and severe acute respiratory infections (SARIs), which are clinically diagnosed among patients with fever, coughing or sore throat, difficulty breathing and the need for hospitalization [3] . In our study, viruses were identified as the most frequent causal agents of SARI requiring hospitalization in 2012, with most cases showing a high rate of viral co-infection, a high degree of morbidity, prolonged hospital stays and frequent needs for ICU management and mechanical ventilation. cache = ./cache/cord-272655-qeojdpez.txt txt = ./txt/cord-272655-qeojdpez.txt === reduce.pl bib === id = cord-268977-hcg2rrhl author = Feikin, Daniel R. title = Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007–2010 date = 2012-08-24 pages = extension = .txt mime = text/plain words = 6440 sentences = 402 flesch = 53 summary = METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings. Compared with other regions, the mortality rate among older children and adults remains several-fold higher in sub-Saharan Africa, where acute respiratory infections (ARI) are a leading cause of this high mortality, as well as associated morbidity [1] . cache = ./cache/cord-268977-hcg2rrhl.txt txt = ./txt/cord-268977-hcg2rrhl.txt === reduce.pl bib === id = cord-262876-civfvk45 author = Su, Tong title = Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China date = 2013-06-24 pages = extension = .txt mime = text/plain words = 4492 sentences = 244 flesch = 43 summary = title: Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration. Three groups of participants in Shanghai, China, were enrolled in this cross-sectional epidemiological study: health professionals, medical students, and community residents. Moreover, the knowledge level was also significantly different among clinicians, public health physicians, nurses, and medical technicians, especially in correctly answering 5 questions (Table S2) . Figure 3 presents the key contents concerning disaster medicine training prioritized by health professionals, medical students, and community residents. Figure 4 presents the most interested contents of disaster medicine training prioritized by health professionals, medical students, and community residents. In this study, we evaluated the current knowledge levels and training needs of disaster medicine among health professionals, medical students, and community residents in Shanghai, China. cache = ./cache/cord-262876-civfvk45.txt txt = ./txt/cord-262876-civfvk45.txt === reduce.pl bib === id = cord-264880-0tmd9knh author = Li, Zhao title = Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date = 2016-04-13 pages = extension = .txt mime = text/plain words = 5347 sentences = 260 flesch = 46 summary = We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. To avoid thermal cycling, different isothermal amplification methods have been developed that rapidly amplify nucleic acids to detectable levels at a single temperature [42, 43] , such as loop-mediated amplification (LAMP) [44] , rolling circle amplification (RCA) [45] , helicasedependent amplification (HDA) [46] , nucleic acid sequence-based amplification (NASBA) [47] , recombinase polymerase amplification (RPA) [48] , transcription-mediated amplification (TMA) [49] , multiple displacement amplification (MDA) [50] , and strand-displacement amplification (SDA) [51] . Finally, we sealed the PWA chip in a homemade copper chamber filled with oil and successfully performed real-time dRPA on an isothermal incubation setup for the absolute quantification of serial dilutions of a Listeria monocytogenes gDNA stock solution. cache = ./cache/cord-264880-0tmd9knh.txt txt = ./txt/cord-264880-0tmd9knh.txt === reduce.pl bib === id = cord-273343-als886fe author = McClenahan, Shasta D. title = Discovery of a Bovine Enterovirus in Alpaca date = 2013-08-12 pages = extension = .txt mime = text/plain words = 4596 sentences = 214 flesch = 51 summary = A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Analysis of the full polyprotein and the individual capsid, 2A protease, 3C protease, and polymerase proteins of the alpaca-infecting virus relative to sequences of other representative enteroviruses from bovine EV-E (BEV-A serotypes 1-4) and EV-F (BEV-B serotypes 1-4), and sequences from three unclassified EV-F viruses [16] , two from bovine sources (AY724744 and AY724745) [20] , and one from a capped langur (JX538037) [21] , possum, porcine (PEV), and human (HEV) hosts. cache = ./cache/cord-273343-als886fe.txt txt = ./txt/cord-273343-als886fe.txt === reduce.pl bib === id = cord-272445-0xauff51 author = Naaber, Paul title = Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data date = 2020-10-27 pages = extension = .txt mime = text/plain words = 2751 sentences = 150 flesch = 50 summary = title: Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data The specificity and sensitivity of SARS-CoV-2 antibody tests are known to vary and very few studies have addressed the performance of these tests in COVID-19 patient groups at different time points. We here compared the sensitivity and specificity of seven commercial (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor) and two in-house LIPS assays (LIPS N and LIPS S-RBD) IgG/total Ab tests in serum samples from 97 COVID-19 patients and 100 controls, and correlated the results with the patients' clinical data and the time-point the test was performed. Our study aimed to compare the performance characteristics of seven commercial and two in-house IgG/total Ab tests, which analyze the reactivity to several target proteins, and to correlate the results with the patients' clinical data (with different symptoms score and age), and time from disease onset. cache = ./cache/cord-272445-0xauff51.txt txt = ./txt/cord-272445-0xauff51.txt === reduce.pl bib === id = cord-268429-drejl99k author = Almberg, Emily S. title = A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community date = 2009-09-16 pages = extension = .txt mime = text/plain words = 7276 sentences = 349 flesch = 52 summary = METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. Thus we sought to use long-term serological data to identify temporal, spatial, and demographic patterns of pathogen exposure among wolves, coyotes (Canis latrans), and foxes (Vulpes vulpes) in YNP. In summary, the constant high canid exposure to CPV, CAV-1, and CHV in YNP suggest that these pathogens are established in the wolf and coyote populations and that they are unlikely to be causing acute mortality in their hosts [50, 51] . cache = ./cache/cord-268429-drejl99k.txt txt = ./txt/cord-268429-drejl99k.txt === reduce.pl bib === id = cord-273764-itu39mln author = Li, Taisheng title = Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus date = 2006-12-20 pages = extension = .txt mime = text/plain words = 2660 sentences = 120 flesch = 49 summary = In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. As show in Fig. 1 , recovered patients clearly experienced two distinct phases of cell restoration in the peripheral blood; an initial rapid phase for all the cell populations studied in the first 3 months after the onset of symptoms followed by a significant slower phase during the subsequent months. To study the sequential changes in CTL responses against SARS-CoV, we used ELISPOT-based technique to quantify the number of INF-c releasing cells in the peripheral blood against peptide pools covering the entire N protein derived from the Urbani strain [3] . We have shown for the first time that recovered patients have persistent and robust binding as well as neutralizing antibody and CTL responses throughout the study period with a moderate decline one year after the onset of symptoms. cache = ./cache/cord-273764-itu39mln.txt txt = ./txt/cord-273764-itu39mln.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-267042-nvwnbp2j author = Gaspard, Philippe title = Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents date = 2019-09-24 pages = extension = .txt mime = text/plain words = 5624 sentences = 290 flesch = 50 summary = This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). Our objective was to describe GE and RTI infection and all-cause lethality rates according to the individual characteristics of nursing home residents (sex, age, length of stay, autonomy status), and to identify specific susceptibility patterns related to these types of viral outbreaks in these facilities. In the present study, surveillance data obtained during GE and RTI outbreaks in nursing homes were used to construct stratified analyses and to identify specific infection and all-cause lethality rates according to the residents' individual characteristics. cache = ./cache/cord-267042-nvwnbp2j.txt txt = ./txt/cord-267042-nvwnbp2j.txt === reduce.pl bib === id = cord-271660-5sfkhg19 author = Sun, Hsin-Yun title = Impact of introducing fluorescent microscopy on hospital tuberculosis control: A before-after study at a high caseload medical center in Taiwan date = 2020-04-03 pages = extension = .txt mime = text/plain words = 3884 sentences = 192 flesch = 40 summary = METHODS: We measured the impact of switch to fluorescent microscopy on the smear detection rate of culture-confirmed pulmonary TB, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately 400 TB cases annually) in Taipei. Hospitalized patients had typical presentations of pulmonary TB if they had: (a) a prolonged cough for >3 weeks; (b) clinical suspicion of pulmonary TB based on chest radiography, such as cavitary pulmonary lesions, upper lobe diseases, or miliary lesions; or (c) already received a confirmed diagnosis of pulmonary TB by a positive sputum culture of Mycobacterium tuberculosis, positive acid-fast stain (AFS), or positive TB PCR, before the hospitalization. Our previous survey on age/sex-standardised TB incidence ratio of HCWs (using general population as reference)---the excess TB risk that are attributable to nosocomial TB transmission---in Medical Center A showed a drop of this risk, from 3.11 in 2006 to 1.37 in 2012 [23] , and the decrease in time-to-isolation and total non-isolated infectious patient-days was in parallel in the present study. cache = ./cache/cord-271660-5sfkhg19.txt txt = ./txt/cord-271660-5sfkhg19.txt === reduce.pl bib === id = cord-268524-lr51ubz5 author = Droit-Volet, Sylvie title = Time and Covid-19 stress in the lockdown situation: Time free, «Dying» of boredom and sadness date = 2020-08-10 pages = extension = .txt mime = text/plain words = 5266 sentences = 262 flesch = 56 summary = This time experience was not explained by the levels of perceived stress or anxiety, although these were considerable, but rather by the increase in boredom and sadness felt in the lockdown situation. The aim of the present study was thus to conduct a scale survey on a large sample of an as yet untested population-French people-in order to assess not only the perceived stress related to Covid-19 but also the emotions (happiness, boredom, arousal) felt during as compared to before the lockdown and their links to the subjective experience of time. There is thus a risk in this period of pandemic that the chronic stress related to Covid-19 and its corollaries (anxiety, fear of death) are particularly high and therefore impact the subjective experience of time by speeding up the perceived passage of time. cache = ./cache/cord-268524-lr51ubz5.txt txt = ./txt/cord-268524-lr51ubz5.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-279259-eu80ccm6 author = Pandey, Aseem title = Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine date = 2012-03-14 pages = extension = .txt mime = text/plain words = 4876 sentences = 249 flesch = 47 summary = The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. To determine the level of vector immunity that can be tolerated without significantly affecting the vaccine efficacy, we primed groups of mice with varying doses of wild type (WT) HAd5 via intranasal (i.n.) or intramuscular (i.m.) route of inoculation to generate different levels of HAd5-neutralizing antibody titers. Further increase in the level of vector-specific neutralizing antibody titer to 3040 by i.m. priming with HAd5 only provided partial protection even in the groups receiving a high vaccine dose. cache = ./cache/cord-279259-eu80ccm6.txt txt = ./txt/cord-279259-eu80ccm6.txt === reduce.pl bib === id = cord-270681-6ayciihs author = Bálint, Ádám title = Comparative In Vivo Analysis of Recombinant Type II Feline Coronaviruses with Truncated and Completed ORF3 Region date = 2014-02-20 pages = extension = .txt mime = text/plain words = 4679 sentences = 230 flesch = 49 summary = Our previous in vitro comparative study on a feline coronavirus (FCoV) pair, differing only in the intactness of their ORF3abc regions, showed that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II feline infectious peritonitis virus (FIPV). In the present study using the parent FIPV DF-2 strain and its recombinant derivates we aimed to collect in vivo data how the completed ORF3abc alters virulence, virus shedding, viremia, viral load of organs and humoral immune response against type II FCoV. Shedding of FIPV DF-2 and PBFIPV-DF-2 was detected from day 3 p.i. to euthanasia of the PIP diseased animals at very low and variable amounts of an average value close to the detection limit of the genomic qRT-PCR (1.9610 1 FCoV RNA copies per ml fecal extract) ( Fig. 1) with undetectable virus replication using the subgenomic qRT-PCR assay (data not shown). cache = ./cache/cord-270681-6ayciihs.txt txt = ./txt/cord-270681-6ayciihs.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-276898-ia80cy8j author = Yamanaka, Atsushi title = Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus date = 2014-03-25 pages = extension = .txt mime = text/plain words = 3833 sentences = 190 flesch = 48 summary = Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. Here, we report an imported case of an RTI associated with an orthoreovirus, which is classified to the species of Nelson Bay orthoreovirus, in a patient who returned to Japan from Bali, Indonesia in November 2007. Interestingly, S1segment of Miyazaki-Bali/2007 showed 94% homology to that of Kampar virus originated in Malaysia, while it did 48-59% homology to those of the other orthoreoviruses in the genus of Nelson Bay orthoreovirus. S2-segment of Miyazaki-Bali/2007 had the highest homology with being approximately 92-94% in nucleotide sequences to those of HK23629/07, HK46886/09, and HK50842/10, which also seem to have originated in Indonesia [6, 20] , while it showed 83-90% homology to those of Kampar, Melaka, Pulau, Sikamat, and Nelson Bay viruses. cache = ./cache/cord-276898-ia80cy8j.txt txt = ./txt/cord-276898-ia80cy8j.txt === reduce.pl bib === id = cord-280846-bbv6f5gf author = Greninger, Alexander L. title = A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America date = 2010-10-18 pages = extension = .txt mime = text/plain words = 8023 sentences = 327 flesch = 44 summary = To determine whether a pan-viral microarray assay was capable of identifying novel 2009 H1N1 in the absence of a priori sequence information, we used the Virochip to comprehensively screen for viruses in 29 nasopharyngeal swab samples from individuals with influenza-like illness. To further characterize the metagenomics of 2009 H1N1 infection in humans, we labeled the 17 influenza samples positive for 2009 H1N1 by Virochip with distinct molecular barcodes and analyzed them by paired-end deep sequencing on three lanes of an Illumina Genome Analyzer IIx. After trimming reads to remove barcodes and exclude low-complexity or primer sequences, 11,427,212 high-quality 60-bp sequence reads were subjected to an iterative BLASTN analysis pipeline (Fig. 1B) . After stratifying by originating location and corresponding method of sample processing (pre-DNase and/or post-DNase treatment), the percentage of total reads aligning to influenza was linearly correlated with calculated viral titers by realtime quantitative RT-PCR for sites in the United States (California) and Canada but not in Mexico (Fig. 5A ). cache = ./cache/cord-280846-bbv6f5gf.txt txt = ./txt/cord-280846-bbv6f5gf.txt === reduce.pl bib === id = cord-278123-mq56em3z author = Hasan, Mohammad Rubayet title = Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA date = 2020-07-24 pages = extension = .txt mime = text/plain words = 3924 sentences = 259 flesch = 58 summary = Nasopharyngeal specimens positive for SARS-CoV-2 and other coronaviruses collected in universal viral transport (UVT) medium were pre-processed by several commercial and laboratory-developed methods and tested by RT-qPCR assays without RNA extraction using different RT-qPCR master mixes. Standard approach for detection of SARS-CoV-2 RNA from nasopharyngeal specimens in our laboratory involves extraction of total nucleic acids from specimens in an IVD-labeled, automated extraction platform followed by RT-qPCR, based on one of the assays (Table 1) suggested by World Health Organization (WHO) [11] . Based on these results, the optimal pre-treatment and reaction conditions for the direct approach were: i) transfer and dilute (4-fold) 10 μl of NPFS specimen in NFW; ii) incubate at 65˚C for 10 min; and iii) test 8 μl of heat lysed specimen in a 20 μl reaction using TaqPath™ 1-Step RT-qPCR Master Mix. The analytical sensitivity of the direct RT-qPCR assay using specimens prepared in this manner was determined by serially diluting a specimen positive for SARS-CoV-2 with a negative specimen as a diluent. cache = ./cache/cord-278123-mq56em3z.txt txt = ./txt/cord-278123-mq56em3z.txt === reduce.pl bib === id = cord-280386-a8qr7nl6 author = Pires, Sara M. title = Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food date = 2015-12-03 pages = extension = .txt mime = text/plain words = 5931 sentences = 252 flesch = 45 summary = The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. To identify and prioritize targeted interventions to reduce the public health impact of foodborne diseases, public health policy makers and other stakeholders need aetiology-specific regional and global estimates of the incidence and mortality of diarrhoeal diseases caused by pathogens that are commonly transmitted through foods. While approach 1 analysed national incidence and mortality of disease by pathogens commonly transmitted through foods estimated primarily by correcting surveillance data to account for underreporting and under-diagnosis, approach 2 relied on systematic reviews of studies identifying causative agents in patients with diarrhoea. cache = ./cache/cord-280386-a8qr7nl6.txt txt = ./txt/cord-280386-a8qr7nl6.txt === reduce.pl bib === id = cord-270408-4qqyb8sd author = Pane, Masdalina title = Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings date = 2013-08-21 pages = extension = .txt mime = text/plain words = 3456 sentences = 182 flesch = 52 summary = title: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. In the last two decades, the mortality rate of Indonesian pilgrims, excluding years in which disasters such as stampedes occurred, fluctuated between 200-380 deaths per 100,000 persons during the ten-week Hajj period [5] . The cause of death based on this verbal autopsy method was then recorded in the database and compared to that reported by the hospital or flight doctor death certificate. A greater proportion of deaths were attributed to cardiovascular disease by the flight doctor or hospital death certificate (66%) compared to the cause of death ascertained using the verbal autopsy method (49%, p<0.001). Based on both the death certificates and verbal autopsy categories, cardiovascular disease was the leading cause of Indonesian pilgrim mortality in 2008. cache = ./cache/cord-270408-4qqyb8sd.txt txt = ./txt/cord-270408-4qqyb8sd.txt === reduce.pl bib === id = cord-270647-vn4kirrx author = Romero-Espinoza, Jose A. title = Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015 date = 2018-02-15 pages = extension = .txt mime = text/plain words = 3513 sentences = 201 flesch = 48 summary = OBJECTIVES: To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. Both groups differ with respect to the associated virus and bacteria: while asthma exacerbations have been associated to a specific rhinovirus infection, pneumonia can be related to a wide range of bacterial, fungal and viral agents, with a high prevalence of Respiratory Syncytial Virus (RSV) [2, 7] . Here we describe the virome and bacteriome present in the Upper Respiratory Tract of hospitalized children clinically diagnosed with asthma and pneumonia, during an acute exacerbation and an ARI episode respectively, at the National Institute of Respiratory Diseases (INER, Mexico City) during 2014 and 2015 winter seasons. Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations cache = ./cache/cord-270647-vn4kirrx.txt txt = ./txt/cord-270647-vn4kirrx.txt === reduce.pl bib === id = cord-277357-lpurk7pe author = González-González, Everardo title = Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection date = 2020-08-13 pages = extension = .txt mime = text/plain words = 3999 sentences = 211 flesch = 49 summary = title: Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection containing the amplification products of each one of three experiments, where the three different sets of primers (namely N1, N2, and N3) were used to amplify the same range of concentrations of template. Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection others), we observe differences in the performance of each primer pair. cache = ./cache/cord-277357-lpurk7pe.txt txt = ./txt/cord-277357-lpurk7pe.txt === reduce.pl bib === id = cord-278099-ypov9ha3 author = Kumar, Surender title = Molecular characterization of a novel cryptic virus infecting pigeonpea plants date = 2017-08-03 pages = extension = .txt mime = text/plain words = 11403 sentences = 622 flesch = 55 summary = The four dsRNAs eluted from the agarose gel were purified and have been used as templates for RT-PCR amplification employed in SISPA to generate fulllength cDNAs. It is of interest to examine if ArCV-1 RNA dependent RNA polymerase (RdRp) structurally resembles the known RdRp of the dsRNA bacteriophage Փ-6, reovirus, or with other viruses like calciviruses and picornaviruses [12] [13] [14] [15] [16] . We report here the results of elaborated computer-assisted analysis of ArCV-1 replicase which revealed the presence of conserved sequence motifs (A to G) present in the fingers and palm subdomains of the polymerase that are shared in most of the RdRps. Interestingly, ArCV-1 replicase has more structural resemblances with several members of ssRNA (+) mono-partite Picornaviruses (viral replication by primer-dependent initiation), than the de novo dsRNA bacteriophage Փ-6 and reovirus polymerases. Possible functions of the residues of the A to G motifs described for identical RdRps was conserved with respect to the ArCV-1 3Dpol structure and was discussed in structural analysis of ArCVTable 1 ) and the 3' terminus contained the sequence "GCA CCCATATTC". cache = ./cache/cord-278099-ypov9ha3.txt txt = ./txt/cord-278099-ypov9ha3.txt === reduce.pl bib === id = cord-280471-cqypwi5d author = Sun, Hua-Bao title = The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19 date = 2020-09-25 pages = extension = .txt mime = text/plain words = 4324 sentences = 202 flesch = 57 summary = To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. Characteristic chest CT imaging patterns, positive nucleic acid detection in nasal and throat swab samples, normal or decreased numbers of peripheral white blood cells, decreased numbers of lymphocytes and increased levels of inflammatory cytokines are the key factors in the diagnosis of COVID-19 [3] . The total number of lymphocytes, the percentages of lymphocyte subtypes and the levels of inflammatory cytokines (TNF-α and IL-6) secreted by CD4+ helper T lymphocytes in the peripheral blood were detected by hematology counter and flow cytometer, respectively. In the COVID-19 patients in the general, severe and critical groups, the numbers of peripheral lymphocytes and CD4+ T lymphocytes and the ratio of CD4+/CD8+ lymphocytes were significantly lower than those in the normal control group. cache = ./cache/cord-280471-cqypwi5d.txt txt = ./txt/cord-280471-cqypwi5d.txt === reduce.pl bib === id = cord-278018-3qemb0x3 author = Li, Li title = Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy date = 2011-08-22 pages = extension = .txt mime = text/plain words = 5980 sentences = 332 flesch = 57 summary = In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. The phenotypic and functional analysis of CD69-expressing cells strongly suggested that CD69 could be a useful marker for the identification or enrichment of antigen specific Th1 cells at local sites following MTB infection. However, following stimulation with MTB-specific peptides of ESAT-6/CFP-10, CD4 + CD69 + T cells from the same patients expressed high levels of IFN-c, IL-2 and TNF-a (data not shown). However, following stimulation with MTB-specific peptides of ESAT-6/ CFP-10, CD4 + CD69 + T cells from the same patients with tuberculous pleurisy expressed high levels of IFN-c, IL-2 and TNF-a, indicating that the response was MTB-specific. cache = ./cache/cord-278018-3qemb0x3.txt txt = ./txt/cord-278018-3qemb0x3.txt === reduce.pl bib === id = cord-274241-biqbsggu author = Shaw, Timothy I. title = Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date = 2012-11-15 pages = extension = .txt mime = text/plain words = 6003 sentences = 339 flesch = 52 summary = Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. To address some of these deficiencies, we have performed transcriptome sequencing and analysis of spleen, lung, kidney and poly-IC-stimulated primary kidney cells to identify genes of interest for assessing the host response to TCRV infection. There were 20,145 contigs that mapped to Pteropus alecto, Australian flying fruit bat, and 18,359 that overlapped between genomic and transcriptome sequences for all three datasets ( Figure 5 ). cache = ./cache/cord-274241-biqbsggu.txt txt = ./txt/cord-274241-biqbsggu.txt === reduce.pl bib === id = cord-281815-zvs5qe8x author = Subramanian, Shoba title = Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3 date = 2009-04-09 pages = extension = .txt mime = text/plain words = 5953 sentences = 267 flesch = 45 summary = The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Treatment of erythrocytic parasites with cysteine protease inhibitors or disruption of the falcipain-2 gene results in accumulation of undegraded hemoglobin in the food vacuole, confirming a role for this enzyme in hemoglobin hydrolysis [6, 10] . To better characterize the roles of falcipain-2 and falcipain-3, we evaluated activities of these proteases against a library of small peptide substrates, a series of larger peptides spanning the sequences of a and b globin, and intact human hemoglobin. Falcipain-2 and falcipain-3 demonstrated a marked preference for cleavage of small peptide substrates with P 2 Leu, but the enzymes showed less specificity against larger peptides and intact hemoglobin, with hydrolysis at multiple sites. Despite the presence of multiple proteases in the food vacuole, it is noteworthy that treatment of cultured parasites with specific inhibitors of cysteine proteases fully blocked the hydrolysis of hemoglobin, highlighting the key role for the falcipains in this process [22] . cache = ./cache/cord-281815-zvs5qe8x.txt txt = ./txt/cord-281815-zvs5qe8x.txt === reduce.pl bib === id = cord-282303-idh7io9v author = Hassan, Md. Zakiul title = Contamination of hospital surfaces with respiratory pathogens in Bangladesh date = 2019-10-28 pages = extension = .txt mime = text/plain words = 4158 sentences = 203 flesch = 39 summary = With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. Respiratory viral and bacterial pathogens, including Staphylococcus aureus, Streptococcus pyogenes, influenza viruses, respiratory syncytial virus, adenovirus, rhinoviruses and novel coronavirus strains, can survive on hospital surfaces for days, weeks or even months. This study identified that hospital surfaces in these Bangladeshi hospitals, were frequently contaminated with respiratory pathogens and pose a potential threat for fomite-borne transmission of respiratory infections to patients, healthcare workers and family caregivers. cache = ./cache/cord-282303-idh7io9v.txt txt = ./txt/cord-282303-idh7io9v.txt === reduce.pl bib === id = cord-281161-u896icp9 author = Wang, Jing title = The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates date = 2012-05-17 pages = extension = .txt mime = text/plain words = 6854 sentences = 317 flesch = 49 summary = We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. As shown in Table 2 , similar IgG1 and IgG2a humoral immune responses against the influenza viruses were induced in the mice vaccinated previously with rRBD plus rOv-ASP-1 adjuvant and those administered with PBS only. As shown in Table 3 , all of the NHPs vaccinated with rRBD protein plus 50 mg (n = 2), 100 mg rOv-ASP-1 (n = 2) or 500 mg CpG (n = 1) as the adjuvant developed RBDspecific IgG antibody response with increasing antibody level after each boost. Secondly, using two concentration of the rOv-ASP-1 adjuvant, 50 or 100 mg, and rRBD as the vaccine antigen, we were able to induce after three immunizations high titers of neutralizing antibodies (1:3,500-1:6,392) that much exceed what is needed for protection against SARS-CoV infection in vivo (.1:500) [56] . cache = ./cache/cord-281161-u896icp9.txt txt = ./txt/cord-281161-u896icp9.txt === reduce.pl bib === id = cord-276372-q1fzxt3r author = Conde, Dalia A. title = Zoos through the Lens of the IUCN Red List: A Global Metapopulation Approach to Support Conservation Breeding Programs date = 2013-12-11 pages = extension = .txt mime = text/plain words = 4780 sentences = 225 flesch = 48 summary = To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. To understand the complexity of maintaining CBPs of threatened species across the ISIS zoo network, we developed a second algorithm to find the optimal radial distance from any given zoo at which the probability of finding a metapopulation size of at least 50, 100 or 250 recruited living individuals was highest relative to that radial distance. As expected, the optimal distance radii and the number of zoos required to maximize the probability of reaching a given population increase with the metapopulation size threshold (.50, .100 and .250 individuals) ( Figure 3) . Therefore, for the zoo community, one of the main challenges of managing their threatened species in CBPs is the complexity of moving individuals across borders and the coordination of conservation efforts among zoos and other institutions at a global level. cache = ./cache/cord-276372-q1fzxt3r.txt txt = ./txt/cord-276372-q1fzxt3r.txt === reduce.pl bib === id = cord-286065-x0g67pnb author = Metzgar, David title = The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood date = 2016-07-06 pages = extension = .txt mime = text/plain words = 5925 sentences = 240 flesch = 38 summary = We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. During the clinical sample study, performed following the sterility and personal protective equipment recommendations of the manufacturer, 61 negative controls were tested and yielded no Other reportable organisms excluding potential contaminants (n = 550) 0 0 0 207 A These 11 culture-negative, IRIDICA BAC BSI Assay-positive detections were supported by later organism-specific ID data which identified the same species as agents of infection (as noted on the subjects' charts). The broad-spectrum nature of the IRIDICA BAC BSI Assay primers, paired with a signal analysis method capable of sensitive and specific detection and identification of one or more species signatures in samples with high background levels of human DNA, make it uniquely suited as a molecular test for bacterial and Candida DNA in blood samples. cache = ./cache/cord-286065-x0g67pnb.txt txt = ./txt/cord-286065-x0g67pnb.txt === reduce.pl bib === id = cord-281124-4nhy35xn author = Soowannayan, Chumporn title = RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date = 2011-08-03 pages = extension = .txt mime = text/plain words = 5596 sentences = 259 flesch = 53 summary = To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. In a preliminary attempt to identify an RNA packaging signal in the GAV genome, EMSAs were performed using ssRNAs synthesized to various genome regions including (i) an ORF1b gene 39-region spanning the relative position to the genome packaging signal identified in MHV [28] , (ii) a 39-terminal genome region corresponding in position to the region in the infectious bronchitis virus (IBV) genome reported to contain an RNA binding domain [29] and (iii) the 59-genomic RNA terminus which, in coronaviruses, has also been reported to interact specifically with N protein [30] . cache = ./cache/cord-281124-4nhy35xn.txt txt = ./txt/cord-281124-4nhy35xn.txt === reduce.pl bib === id = cord-282202-q2q4vies author = Banerjee, Amitava title = Clinical academic research in the time of Corona: A simulation study in England and a call for action date = 2020-08-13 pages = extension = .txt mime = text/plain words = 4106 sentences = 229 flesch = 46 summary = DESIGN: A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics). "Learning is difficult in the midst of an emergency" [7] , but our ability to deliver timely, high-impact clinical research, relevant to patients and populations, is critical across the academic spectrum [8] , from "bench to bedside to big data", whether basic biology, repurposed and novel therapeutic approaches, vaccines or modelling. Our aims were to: (i) model potential impact of the pandemic on clinical academic capacity in England relating to COVID-19; and (ii) develop evidence-based recommendations to inform the optimal scientific response to COVID-19. cache = ./cache/cord-282202-q2q4vies.txt txt = ./txt/cord-282202-q2q4vies.txt === reduce.pl bib === id = cord-286708-igu984oc author = Chua, Kaw Bing title = Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections date = 2008-11-25 pages = extension = .txt mime = text/plain words = 4359 sentences = 219 flesch = 53 summary = Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Here, we report the discovery and characterization of Kampar virus (KamV), the fourth member in the NBV species group and its isolation from a human patient with fever and acute respiratory illness. Due to the similar CPE morphology ( Figure 1 ) and cell line susceptibility patterns between KamV and the recently discovered Melaka virus (MelV), which also causes acute respiratory diseases in humans [5] , immunofluorescent antibody testing was conducted to examine cross reactivity. cache = ./cache/cord-286708-igu984oc.txt txt = ./txt/cord-286708-igu984oc.txt === reduce.pl bib === id = cord-284275-bqo203pf author = Lu, Roujian title = Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays date = 2012-06-15 pages = extension = .txt mime = text/plain words = 2978 sentences = 165 flesch = 52 summary = title: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. In our retrospective study, a 16.0% detection rate for HCoVs infection was found in adults with URTI; 229E was the most common infection (9.8% of all cases), followed by OC43 (4.3%), HKU1 (1.6%) and NL63 (1.1%). cache = ./cache/cord-284275-bqo203pf.txt txt = ./txt/cord-284275-bqo203pf.txt === reduce.pl bib === id = cord-283976-jgae7r2q author = Armstrong, Melissa J. title = Research priorities of caregivers and individuals with dementia with Lewy bodies: An interview study date = 2020-10-07 pages = extension = .txt mime = text/plain words = 4111 sentences = 208 flesch = 37 summary = BACKGROUND: Funding bodies are placing increased emphasis on patient and public involvement in research, but the research priorities of individuals and caregivers living with dementia with Lewy bodies (DLB) are unknown. Funding should be informed by the priorities of all relevant stakeholders and support research investigating causes, natural history, biomarkers, and treatment in addition to research targeting themes regarding living with disease (e.g. independence, quality of life, caregiving, and education). The study guide queried a variety of research categories and individuals with DLB and caregivers identified topics important for research in all of them-focusing on awareness, determining the cause of DLB, improving diagnosis, investigating what to expect and disease stages, DLB symptoms needing additional research, therapies to prevent, cure, or slow the progression of DLB, targeting daily function and quality of life, caregiving, and improving education. cache = ./cache/cord-283976-jgae7r2q.txt txt = ./txt/cord-283976-jgae7r2q.txt === reduce.pl bib === id = cord-285546-5tjhdczt author = Green, Manfred S. title = The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries date = 2020-10-21 pages = extension = .txt mime = text/plain words = 2390 sentences = 142 flesch = 64 summary = title: The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries BACKGROUND: Crude case-fatality rates (CFRs) for COVID-19 vary widely between countries. We examined how the age distribution of the cases is responsible for the COVID-19 CFR differences between countries. METHODS: COVID-19 cases and deaths, by ten-year age-groups, were available from the reports of seven countries. The age-adjusted CFRs were computed by the direct method, using the combined number of cases in all seven countries in each age group as the standard population. CONCLUSIONS: The age structure of the cases explains much of differences in the crude CFRs between countries and adjusting for age substantially reduces this variation. The age-specific number of cases, number of deaths and the crude CFRs by country are given in Table 1 . cache = ./cache/cord-285546-5tjhdczt.txt txt = ./txt/cord-285546-5tjhdczt.txt === reduce.pl bib === id = cord-287739-58fth3xl author = Huang, Yhu-Chering title = Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign date = 2011-08-12 pages = extension = .txt mime = text/plain words = 3821 sentences = 188 flesch = 42 summary = CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important pathogens of bacteremia in the intensive care units (ICU). To reduce and control healthcare-associated infections (HAIs) caused by MRSA, a ''search and destroy'' strategy, which first detects the patients with MRSA colonization and then decolonizes the MRSA with certain antimicrobial agents, was recently proposed and implemented in some hospitals of different countries, with inconsistent effects [12] [13] [14] [15] [16] . Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units cache = ./cache/cord-287739-58fth3xl.txt txt = ./txt/cord-287739-58fth3xl.txt === reduce.pl bib === id = cord-279421-rxocrgfu author = Zhang, Dan title = Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection date = 2016-04-04 pages = extension = .txt mime = text/plain words = 2863 sentences = 134 flesch = 48 summary = title: Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection In the present study, an improved single-tube multiplex reverse transcription PCR assay for simultaneous detection of 13 respiratory viruses was evaluated and compared with a previously reported two-tube assay as the reference method using clinical nasopharyngeal aspirates samples. In conclusion, our results demonstrates the one-tube assay revealed significant improvements over the two-tube assay in terms of the better sensitivity, more accurate quality control, less nonspecific amplification, more cost-effective and shorter turn-around time and will be a valuable tool for routine surveillance of respiratory virus infection in China. In the present study, we adopted the two-tube assay as a reference, and have been progressively optimized and substantially improved the performance of simultaneous detection of thirteen respiratory viruses types/subtypes, the most frequently detected viral agents of respiratory tract infections documented by Beijing Monitoring Network for Pneumonia between 2012-2014 (unpublished data), in a single-tube assay while maintaining excellent sensitivity and specificity. cache = ./cache/cord-279421-rxocrgfu.txt txt = ./txt/cord-279421-rxocrgfu.txt === reduce.pl bib === id = cord-281364-syg0wo77 author = Caì, Yíngyún title = CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection date = 2014-11-19 pages = extension = .txt mime = text/plain words = 3827 sentences = 178 flesch = 49 summary = title: CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Finally, we demonstrate that persistent MERS-CoV infections can be established in permissive bat cell lines after sequential virus passage, leading to downregulation of natural CD26/DPP4 cellsurface expression. None of the four MERS-CoV-resistant cell lines tested in this study (PESU-B5L, R05T, R06E, and Tb1Lu) were recognized by anti-human CD26/DPP4 antibody in this assay, whereas all susceptible bat cells (EidNi/41.3, EpoNi/22.1, HypLu/45.1, HypNi/1.1, RoNi/7.1, and RoNi/7.2) tested positive for CD26/DPP4 expression (Figure 2 ). Our study confirms the role of CD26/DPP4 as receptor for two divergent MERS-CoV isolates and correlates its presence or absence on the surface of bat cells directly with bat cell susceptibility or resistance to productive MERS-CoV infection (Figures 2 and 3 ). cache = ./cache/cord-281364-syg0wo77.txt txt = ./txt/cord-281364-syg0wo77.txt === reduce.pl bib === id = cord-284501-5i0w74q4 author = Armesto, Maria title = The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity date = 2009-10-09 pages = extension = .txt mime = text/plain words = 7792 sentences = 322 flesch = 54 summary = The IBV cDNA within pGPT-BeauR-Rep-M41-Struct-3UTR was introduced, by homologous recombination using the transient dominant selection (TDS) ( [25, 37] ), into the IBV Beaudette cDNA within the vaccinia virus genome in rVV-BeauR-Rep-DStruct containing Beau-R-derived sequence corresponding to the replicase gene followed by the first 376 nt of the S gene, part of the N gene and the 39-UTR (Fig. 1) . The samples were analysed for the presence of viable IBV by titration in TOCs or used for RNA extraction using the RNeasy method and analysed by RTThe M41-CK-derived cDNA, representing the M41 structural and accessory genes and the M41 39-UTR, within pGPT-BeauR-Rep-M41-Struct-3UTR was fused to the Beau-R replicase gene in the rVV by a homologous recombination event between the Beau-R replicase sequence common to both constructs. Analysis of the tracheal epithelial cells isolated from the infected chickens, for the presence of IBV by titration on TOCs, had indicated that either there was no Beau-R or rBeauR-Rep-M41-Struct-2 present or that the levels of both viruses were below detection. cache = ./cache/cord-284501-5i0w74q4.txt txt = ./txt/cord-284501-5i0w74q4.txt === reduce.pl bib === id = cord-282668-bs634hti author = Niang, Mbayame Ndiaye title = Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses date = 2017-03-22 pages = extension = .txt mime = text/plain words = 4623 sentences = 243 flesch = 47 summary = In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenzalike Illness cases. From January 2012 to December 2015 we collected specimens (nasal-pharyngeal and oral-pharyngeal swabs) and surveillance data for influenza and other viral respiratory pathogens from outpatients presenting with influenza-like-illness (ILI) at different sentinel sites in Senegal. So the circulation of such HAdV genome types in Senegal emphasizes the need to reinforce HAdV surveillance, especially in hospitalized patients, by including HAdV genome detection and genotyping in the documentation of severe respiratory infections. Molecular epidemiology of human adenovirus isolated from children hospitalized with acute respiratory infection in São Paulo, Brazil cache = ./cache/cord-282668-bs634hti.txt txt = ./txt/cord-282668-bs634hti.txt === reduce.pl bib === id = cord-284016-zb6cv8ik author = Li, Wei title = Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection date = 2008-04-16 pages = extension = .txt mime = text/plain words = 4188 sentences = 258 flesch = 48 summary = Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. It has been reported that influenza virus can activate the expression of COX-2 in cell culture systems [26] and that dsRNA can induce the production of COX-2, followed by PGE 2 release [5] . To identify the viral components which play important roles in IV-stimulated pro-inflammatory factors COX-2 and IL-32 expression, we screened all ten proteins of influenza virus: HA, NA, NP, NS1, NS2, M1, M2, PA, PB1, PB2 and poly(IC) (to mimic viral replicative intermediate dsRNA) by luciferase assays. Both influenza A virus infection and poly(IC)+IFN-c treatment in A549 human lung epithelial cells were able to induce COX-2/ IL-32 mRNA and protein expression as well as PGE 2 and IL-32 accumulation in the cell culture supernatants. cache = ./cache/cord-284016-zb6cv8ik.txt txt = ./txt/cord-284016-zb6cv8ik.txt === reduce.pl bib === id = cord-281665-6n7aq4k9 author = Qiu, Sangsang title = Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models date = 2015-05-20 pages = extension = .txt mime = text/plain words = 3982 sentences = 213 flesch = 49 summary = This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. This study describes the economic burden on patients with tuberculosis, identifies related factors by comparing two areas with different management models, and provides a policy recommendation for the tuberculosis control system in China. Significant factors related to the total out-of-pocket costs were study setting (t = -3.10, P = 0.002), age (t = -4.04, P < 0.001), number of clinical visits (t = 4.46, P < 0.001), residence (t = 3.19, P = 0.002), diagnosis delay (t = 3.47, P = 0.001), hospitalization (t = 15.04, P < 0.001), intake of liver protective drugs (t = 2.78, P = 0.006) and intake of second-line drugs (t = 2.87, P = 0.004) ( Table 5) . cache = ./cache/cord-281665-6n7aq4k9.txt txt = ./txt/cord-281665-6n7aq4k9.txt === reduce.pl bib === id = cord-287784-f7usy52w author = Maestre, Ana M. title = Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells date = 2011-06-15 pages = extension = .txt mime = text/plain words = 8981 sentences = 395 flesch = 45 summary = Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We did not observe any CPE on the cells treated with UV-inactivated virus (data not shown), and neither of the two caspase substrates was processed in these cells (Fig. 5B) , suggesting that BEV apoptosis triggering is dependent upon viral replication. As a whole, these results indicate that although both cell death receptor and mitochondrial pathways are implicated in the BEV induction of apoptosis, the mitochondrial pathway could be secondarily activated by caspase-8-mediated cleavage of Bid. To further ascertain the involvement of the mitochondrial pathway in BEV-induced apoptosis we analyzed the cellular distribution of cytochrome c at different times postinfection. cache = ./cache/cord-287784-f7usy52w.txt txt = ./txt/cord-287784-f7usy52w.txt === reduce.pl bib === id = cord-289305-mfjyjjer author = Lee, Min Hye title = A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control date = 2020-03-10 pages = extension = .txt mime = text/plain words = 7550 sentences = 417 flesch = 47 summary = title: A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control Three studies on gastrointestinal infection, in which adherence to hand hygiene among HCWs was crucial to prevent its spread, reported control measures including stringent hand hygiene practice and reinforcement of standard precautions [23, 27, 31] . The study on the RSV and HMPV outbreak reported various measures including active surveillance, isolation, contact precaution, antiviral prophylaxis for residents and work restriction for ill staff to control respiratory pathogen transmission [50] . This update for understanding outbreaks in LTCFs by reviewing recent studies indicates that staff members and residents are still at risk for contagious disease outbreaks including influenza, gastroenteritis, and GAS infection. Influenza outbreak control practices and the effectiveness of interventions in long-term care facilities: a systematic review cache = ./cache/cord-289305-mfjyjjer.txt txt = ./txt/cord-289305-mfjyjjer.txt === reduce.pl bib === id = cord-286837-j2sqs20q author = Koetsier, Antonie title = Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics? date = 2013-12-31 pages = extension = .txt mime = text/plain words = 4526 sentences = 210 flesch = 49 summary = METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In the season 2009/2010 as well as in the season 2010/2011, ILI incidence as measured by GP sentinel practices, reached the epidemic threshold of 5.1 consultations per 10.000 enlisted patients at a time when already more than 100 patients had been hospitalized, with several ICU admissions and deaths from laboratory confirmed Influenza (National Institute for Public Health and the Environment, unpublished surveillance data). In our study we built three additive Poisson GEE regression models with ICU data to predict the incidence of ILI patients, thereby detecting influenza epidemics and aimed at detecting opportunities for enhancing the current national surveillance method. cache = ./cache/cord-286837-j2sqs20q.txt txt = ./txt/cord-286837-j2sqs20q.txt === reduce.pl bib === id = cord-287761-73qgx58i author = Aly, Mahmoud title = Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update date = 2017-10-13 pages = extension = .txt mime = text/plain words = 3389 sentences = 164 flesch = 55 summary = Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. The emergence of MERS-CoV dates back to July 2012 when an elderly patient of age 60 years died from an acute pneumonia in Saudi Arabia, and a new coronavirus strain was isolated from his lung tissue [1] . With regard to viral origin and transmission, the first case of MERS-CoV infection did not relate it to any particular contact with animals before the disease onset; however, other studies did link it to Dromedary camels [5] [6] [7] [8] . cache = ./cache/cord-287761-73qgx58i.txt txt = ./txt/cord-287761-73qgx58i.txt === reduce.pl bib === id = cord-285433-ehnu83qe author = Sun, Hongliu title = Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry date = 2015-08-21 pages = extension = .txt mime = text/plain words = 4698 sentences = 265 flesch = 54 summary = METHODS: An antibody analysis method is reported for the detection and identification of CMV antibodies in serum using a biosensor based on high spatial resolution imaging ellipsometry (BIE). As such, the concentration of CMV antibody in serum was quantitatively detected by BIE and then compared using ELISAs. Silicon wafers were purchased from the General Research Institute for Nonferrous Metals (China). Compared to blank controls areas, the purified CMV antibody and patient serum sample detection areas had markedly thicker films, with the average grayscale value displaying significant increases, while negative control areas did not (Fig 1) . Quantitative detection of CMV antibodies in clinical serum 41 CMV patients (Table A in S2 File) with quantitative results by ELISA were tested with BIE (Fig 4) . Thus, this label-free method may avoid some Detection of CMV antibodies in patient serum using BIE. cache = ./cache/cord-285433-ehnu83qe.txt txt = ./txt/cord-285433-ehnu83qe.txt === reduce.pl bib === id = cord-283604-fqc9jp0l author = Chen, Meng title = Adenoviruses Associated with Acute Respiratory Diseases Reported in Beijing from 2011 to 2013 date = 2015-03-27 pages = extension = .txt mime = text/plain words = 3060 sentences = 127 flesch = 39 summary = To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination. The comparison results of the penton base, hexon, and fiber gene sequences between the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and the strains from the GenBank database indicated significant conservation and stability of the sequences within the genome across time and space. cache = ./cache/cord-283604-fqc9jp0l.txt txt = ./txt/cord-283604-fqc9jp0l.txt === reduce.pl bib === id = cord-286613-cmtsu73g author = Lee, Sung Woo title = Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation date = 2015-10-15 pages = extension = .txt mime = text/plain words = 3601 sentences = 203 flesch = 57 summary = title: Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The cut-off values of SAPS2, serum sodium level, and ECMO pump speed for in-hospital mortality were a score of 69.5, 147.6 mmol/L, and 2.19 x 10 3 rpm, respectively (Table 3) . We showed that AKI, especially stage 3 AKI, was a significant risk factor for in-hospital mortality in patients receiving ECMO support. In conclusion, AKI is a significant risk factor for in-hospital mortality in patients receiving ECMO support. cache = ./cache/cord-286613-cmtsu73g.txt txt = ./txt/cord-286613-cmtsu73g.txt === reduce.pl bib === id = cord-289555-1z4vbldd author = Mühldorfer, Kristin title = Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates date = 2011-12-28 pages = extension = .txt mime = text/plain words = 5764 sentences = 303 flesch = 44 summary = Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats. In this study, we provide new data on infectious diseases in European bat species, considering factors likely to affect the susceptibility of bats to infectious agents including effects of seasonality, individual and species-specific heterogeneities, and possible intra-and inter-species transmission dynamics. Comparative bacteriologic and histo-pathologic analysis identified 22 different bacterial species that were clearly associated with pathological lesions and/or systemic infection, found in 17% (n = 73) of bats investigated bacteriologically ( Table 5) . cache = ./cache/cord-289555-1z4vbldd.txt txt = ./txt/cord-289555-1z4vbldd.txt === reduce.pl bib === id = cord-289285-aof7xy13 author = Michaelis, Martin title = Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression date = 2011-05-17 pages = extension = .txt mime = text/plain words = 4282 sentences = 270 flesch = 42 summary = title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Glycyrrhizin 200 mg/ml (the maximum tested concentration) did not affect A549 cell viability (data not shown) but clearly decreased CPE formation in A549 cells infected with the H5N1 influenza strain A/Thailand/1(Kan-1)/04 at MOIs of 0.01, 0.1 or 1 ( Figure 1A ). Here, we show that glycyrrhizin inhibits the replication of highly pathogenic H5N1 influenza A virus, H5N1-induced apoptosis, and H5N1-induced expression of pro-inflammatory cytokines in lung-derived A549 cells. cache = ./cache/cord-289285-aof7xy13.txt txt = ./txt/cord-289285-aof7xy13.txt === reduce.pl bib === id = cord-288440-w7g2agaf author = Jia, Rui title = The C-Terminal Sequence of IFITM1 Regulates Its Anti-HIV-1 Activity date = 2015-03-04 pages = extension = .txt mime = text/plain words = 4902 sentences = 276 flesch = 53 summary = This inhibition appears to be specific to HIV-1, since neither the WT IFITM1 nor its C-terminal truncations affected entry that was mediated by the G protein of vesicular stomatitis virus (VSV) ( Fig. 2A and 2B) . Removing the last 9 or 14 amino acids from C-terminal sequence re-localized the majority of IFITM1 to the cell periphery (Fig. 3A) , indicating that these C-terminus truncated IFITM1 mutants are mostly positioned at the plasma membrane where HIV-1 entry occurs. We recently reported that HIV-1 BH10 became resistant to IFITM1 restriction in the spread infection through acquiring mutations in viral Env and Vpu proteins that together enhance the virus transmission between cells [27] . One possible scenario is that HIV-1 Env protein may modulate virus sensitivity to human IFITM1 restriction by virtue of its ability to mediate and regulate virus cell-to-cell transmission. cache = ./cache/cord-288440-w7g2agaf.txt txt = ./txt/cord-288440-w7g2agaf.txt === reduce.pl bib === id = cord-286404-eggkqq3b author = Strayer, David R. title = Effect of disease duration in a randomized Phase III trial of rintatolimod, an immune modulator for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome date = 2020-10-29 pages = extension = .txt mime = text/plain words = 5439 sentences = 266 flesch = 47 summary = CONCLUSION/SIGNIFICANCE: Analysis of ETT from a Phase III trial has identified within the ITT population, a subset of ME/CFS patients with ≥2 fold increased exercise response to rintatolimod. In the AMP-516 Phase III clinical trial, patients with severe ME/CFS demonstrated significant improvement in the primary endpoint, exercise treadmill tolerance (ETT), compared to placebo controls following the twice weekly for 40 weeks systemic administration [12] of the selective TLR3 dsRNA agonist, rintatolimod (Ampligen 1 ) [10, 11]. Effect of ME/CFS duration in response to rintatolimod fewer patients and reduced statistical power compared to the ITT population (n = 208), the placebo-adjusted mean increase in ETT (Δ = 23.6) within the Target Subset (n = 75) was statistically significant. This post-hoc analysis of the successful AMP-516 double-blind, placebo-controlled, randomized, Phase III trial has identified a subgroup of patients defined primarily by the length of ME/CFS symptoms (2-8 years) with an increased likelihood of a clinically beneficial response to rintatolimod. cache = ./cache/cord-286404-eggkqq3b.txt txt = ./txt/cord-286404-eggkqq3b.txt === reduce.pl bib === id = cord-290773-kgb8r561 author = Ahn, Jong Gyun title = Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus date = 2018-07-03 pages = extension = .txt mime = text/plain words = 2594 sentences = 148 flesch = 47 summary = title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus Therefore, in this study, we investigated the epidemiological, clinical, and virological characteristics of HRV infections in children with acute lower respiratory tract infections. This study demonstrates that HRV is an important cause of lower respiratory infection in young children that is associated with symptoms of respiratory distress, such as chest retraction and wheezing. In our study, there were no significant differences in the clinical features, laboratory data or NPA cytokine levels between HRV-A and -C infections. High prevalence of human rhinovirus C infection in Thai children with acute lower respiratory tract disease Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions Rhinovirus load and disease severity in children with lower respiratory tract infections cache = ./cache/cord-290773-kgb8r561.txt txt = ./txt/cord-290773-kgb8r561.txt === reduce.pl bib === id = cord-289093-si8btsab author = Beard, Philippa M. title = A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference date = 2014-06-05 pages = extension = .txt mime = text/plain words = 6578 sentences = 310 flesch = 49 summary = To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. The methodology in the previously published VACV screens varied considerably; Mercer et al [32] measured the growth of a thymidine-kinase-deficient VACV (strain Western Reserve) after only 8 h of infection, thereby identifying cellular proteins involved in the initial stages of virus replication but excluding analysis of viral spread. cache = ./cache/cord-289093-si8btsab.txt txt = ./txt/cord-289093-si8btsab.txt === reduce.pl bib === id = cord-289873-6hivjqof author = Lu, Rui title = Patients with mild and general COVID-19 should be negative for at least 3 consecutive nucleic acid tests before discharged date = 2020-10-02 pages = extension = .txt mime = text/plain words = 1693 sentences = 80 flesch = 51 summary = The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests of these patients was 21 days. Thus, we suggested that the patient should be negative for at least 3 consecutive nucleic acid tests before discharge, and the test time should be no earlier than the 23rd day since the onset of the disease. According to the latest COVID-19 clinical diagnosis and treatment guideline [3] , patients who meet the following four criteria can be discharged: (1) the body temperature has returned to normal for more than 3 days; (2) the respiratory symptoms have improved significantly; (3) the pulmonary imaging examination shows that the acute exudative lesions have improved significantly, (4) two consecutive negative nucleic acid test for respiratory specimens such as sputum and nasopharyngeal swabs (sampling interval at least 24 hours). The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests in 845 patients with COVID-19 was 21 days (range: 1-56 days). cache = ./cache/cord-289873-6hivjqof.txt txt = ./txt/cord-289873-6hivjqof.txt === reduce.pl bib === id = cord-289017-vwye3pk9 author = Comach, Guillermo title = Sentinel Surveillance of Influenza-Like Illness in Two Hospitals in Maracay, Venezuela: 2006–2010 date = 2012-09-11 pages = extension = .txt mime = text/plain words = 6262 sentences = 301 flesch = 47 summary = CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Recent prospective studies, which utilized more sensitive methods for detecting respiratory viruses such as multiplex polymerase chain reaction (PCR), have similarly demonstrated that the highest rates of viral respiratory infection occur among children and the frequency of infection tends to decrease with age due to increasing acquired immunity [8] . On the other hand, the percentage of influenza viruses (not including pH1N1) detected in our study during a similar period of time, but in different years accounted for the significant differences found in both studies: a) the collection, preservation and further processing of respiratory samples, and b) the type of cells and IFA reagents used for virus isolation and identification. In contrast, a prospective study of ILI among Brazilian adults, which utilized viral isolation and RT-PCR testing on respiratory samples, detected rhinoviruses in 19.6% of patients [14] . cache = ./cache/cord-289017-vwye3pk9.txt txt = ./txt/cord-289017-vwye3pk9.txt === reduce.pl bib === id = cord-290446-43h1r4pm author = Vazquez, Leonardo title = Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus date = 2017-07-27 pages = extension = .txt mime = text/plain words = 8840 sentences = 422 flesch = 53 summary = This spacer provided a reasonably dynamic loop, according to our NMR data, which included narrow chemical shift dispersion (S2A Fig As depicted in Fig 1A, we designed the nsp1 constructs so as to avoid truncating their secondary-structure elements. The full-length nsp1 fusion protein has only a few missing peaks, indicating a well-folded 3D domain, which causes a wide dispersion of chemical shifts and allows straightforward identification of backbone HN signals. The SSP indicates the propensity ranging from -1 to 1 to adopt backbone conformations typical for extended β-strands or helical structures, respectively, according to the effect of these conformations on the chemical shifts of backbone atoms, [39] [40] [41] As shown in Fig 7, with the SSP algorithm it was possible to define very well the secondarystructure elements of the folded globular domain of nsp1 (orange bars in the uppermost graph). cache = ./cache/cord-290446-43h1r4pm.txt txt = ./txt/cord-290446-43h1r4pm.txt === reduce.pl bib === id = cord-289510-spmknns5 author = Curado, Evaldo M. F. title = A discrete-time-evolution model to forecast progress of Covid-19 outbreak date = 2020-10-29 pages = extension = .txt mime = text/plain words = 5920 sentences = 325 flesch = 67 summary = Here, we present a model that can easily incorporate these available data sets and is based on discrete-time equations to forecast the number of confirmed cases by Covid-19 in any given country for the next 14 days. Among its strengths, the presented model: (i) presents low relative error rates, as tested in data from Brazil, South Korea and UK; (ii) provides easily interpretable results, specifically the predicted number of infected people in the next 14 days; (iii) presents results that are directly comparable across countries; and (iv) incorporates the average time related to the disease incubation period (asymptomatic phase) and the average time related to the symptomatic phase, both parameters adjustable according to the pandemics' characteristics. With the intention to test the method and find good values for the parameters α and β, we considered our fictitious t f N ¼ 102-th day, so it is possible to compare the total number of infected people as provided by the original source (JHU) with the predicted data generated by the model. cache = ./cache/cord-289510-spmknns5.txt txt = ./txt/cord-289510-spmknns5.txt === reduce.pl bib === id = cord-285749-0ejhd9nw author = Hoffmann, Markus title = The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells date = 2016-03-30 pages = extension = .txt mime = text/plain words = 6025 sentences = 329 flesch = 49 summary = Generation of VSV pseudotypes (VSVpp) was performed as follows: HEK-293T cells were transfected by calcium-phosphate precipitation with expression plasmids encoding viral surface proteins, VSV-G (positive control) , NiV-F/G, FLUAV-HA and/or NA and bat-FLUAV-HAL and/or NAL, or empty plasmid (pCAGGS) as negative control. In order to investigate the potential of human TTSPs to proteolytically activate batFLUAV-HAL for host cell entry, we additionally cotransfected the cells with expression plasmids for TMPRSS2, DESC-1 or MSPL. Notably, three bat cell lines (EidNi/41, HypNi/1.1 and EpoNi/22.1) were susceptible to entry of pseudotypes bearing HAL and NAL of batFLUAV (Fig 2B) , demonstrating that surface glycoproteins of batFLUAV can mediate cellular entry. To assess proteolytic activation of HA/HAL proteins, vesicular stomatitis virus-based pseudotypes (VSVpp) were produced in cells transfected to express the indicated type II transmembrane serine proteases (B) or different amounts of TMPRSS2 (C). cache = ./cache/cord-285749-0ejhd9nw.txt txt = ./txt/cord-285749-0ejhd9nw.txt === reduce.pl bib === id = cord-291756-ejh1r8h4 author = Pérez-Fuentes, María del Carmen title = Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population date = 2020-06-25 pages = extension = .txt mime = text/plain words = 3766 sentences = 197 flesch = 49 summary = title: Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population AIMS: The objective of this study was therefore to analyze the effect of exceptionally stressful situations, such as the current health risk, on the cognitive and emotive state of the individual, that is, perceived threat and emotional state on affect and mood. RESULTS: The results showed that the perception of threat from COVID-19 was related positively to negative affect and emotional signs, that is, sadness-depression, anxiety and anger-hostility. The starting hypothesis was that perception of threat in the exceptional state of health emergency caused by COVID-19, affects one's emotional situation (Model 1), and this, in turn, affects perception of risk (Model 2), in which positive and negative affect balances act as mediators in these relationships (Fig 1) . cache = ./cache/cord-291756-ejh1r8h4.txt txt = ./txt/cord-291756-ejh1r8h4.txt === reduce.pl bib === id = cord-289892-yh1lioyz author = Bai, Bingke title = Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells date = 2008-07-16 pages = extension = .txt mime = text/plain words = 5451 sentences = 300 flesch = 55 summary = Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. In addition, because in vitro infection model of bat SL-CoV has not so far been established, we intended to use VLPs as an alternative to study the immune responses induced in DCs. Therefore, we compared the phenotypic and functional changes of immature DCs inoculated with BVLPs or with SARS CoV VLPs. The S-specific immune activation was further confirmed in mice using S DNA vaccines. Combining the flow cytometry results in Fig. 2 , it is reasonable to draw a conclusion that the structure of BVLPs, not LPS contamination, contributed to cytokine production in BVLPs-treated DCs. We previously constructed SARS CoV VLPs and investigated the humoral and cellular immune responses induced by SARS CoV VLPs in mice [29] . cache = ./cache/cord-289892-yh1lioyz.txt txt = ./txt/cord-289892-yh1lioyz.txt === reduce.pl bib === id = cord-290120-fd26t8ja author = Tan, Chew Yee title = First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia date = 2020-07-24 pages = extension = .txt mime = text/plain words = 6606 sentences = 358 flesch = 53 summary = title: First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia Given that PCV3 is increasingly reported in countries including Thailand and U.S. with whom Malaysia shares trade and geographical relationship; and that PCV3 is associated with several clinical presentations that affect productivity, there is a need to study the presence and molecular characteristics of PCV3 in Malaysian swine farms. Results revealed that PCV3 is present in Peninsular Malaysia at a molecular prevalence of 17.02%, with inguinal lymph nodes and lungs showing the highest molecular detection rates of 81.82% and 71.43% respectively. To test for association between PCV3 molecular detection status and age group, health status, farm standing sow population and distance from neighbouring farms, Chi-square tests were performed with statistical significance level set at p < 0.05. PCV3 infection susceptibility has been suggested to be associated with the age of wild boar, with juvenile animals showing statistically lower detection rates, unlike reports described in domestic pigs [37, 48] . cache = ./cache/cord-290120-fd26t8ja.txt txt = ./txt/cord-290120-fd26t8ja.txt === reduce.pl bib === id = cord-288502-qqg41daz author = Martini, Katharina title = Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019 date = 2020-10-05 pages = extension = .txt mime = text/plain words = 3613 sentences = 207 flesch = 47 summary = BACKGROUND: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension. Therefore, the purpose of the study was to investigate possible typical parenchymal lung changes resembling patterns of infarct pneumonia or OP as surrogate for microscopic thromboembolic events in COVID-19 patients. Our hypothesis is further strengthened by the higher presence of CT signs for pulmonary artery hypertension and right heart failure in patients undergoing CT-PA or with CT patterns resembling infarct pneumonia. However, our COVID-19 cohort showed lung changes resembling those of infarct pneumonia and OP as well as CT-signs of pulmonary-artery hypertension. cache = ./cache/cord-288502-qqg41daz.txt txt = ./txt/cord-288502-qqg41daz.txt === reduce.pl bib === id = cord-282194-0sjmf1yn author = Cherak, Stephana J. title = Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review date = 2020-09-11 pages = extension = .txt mime = text/plain words = 5411 sentences = 276 flesch = 42 summary = title: Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review The purpose of this scoping review was to summarize existing research on the impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit (ICU). For the purposes of this review, we defined: (1) a caregiver as any informal (i.e., non-clinical) person who regularly provides support to the patient and is in some way directly implicated in the patient's care or directly affected by the patient's health problem (e.g., family, friend); (2) social media as any form of electronic communication that allow users to share information and other content and create online communities; and (3) critically ill patients as any persons who are currently admitted to an intensive care unit (ICU) or had previously been admitted to an ICU. cache = ./cache/cord-282194-0sjmf1yn.txt txt = ./txt/cord-282194-0sjmf1yn.txt === reduce.pl bib === id = cord-290833-m0wodqr3 author = Yuan, Lvfeng title = Synthetic surfactin analogues have improved anti-PEDV properties date = 2019-04-11 pages = extension = .txt mime = text/plain words = 3580 sentences = 195 flesch = 51 summary = In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The production of designer surfactins, made by changing the number and composition of amino acids and fatty acids has proven to be an effective strategy for screening large numbers of lipopeptides for biological activity, but most current research focuses on their anticancer [4] , antimicrobial [5] and insulin delivery [6] properties but not on their antiviral potential. Time of addition assays were performed to determine whether the SLP5 exerts its anti-PEDV effect at the same stage during infection as surfactin. As expected for a normal component of the cell membrane, DEPE did not affect PEDV replication at any stage, while SLP5 and surfactin exhibited antiviral activity at specific stages. SLP5 also has two fewer hydrophobic amino acids than surfactin, this reduces the cost of synthesis while having little effect on antiviral activity. cache = ./cache/cord-290833-m0wodqr3.txt txt = ./txt/cord-290833-m0wodqr3.txt === reduce.pl bib === id = cord-290034-4b0mshqa author = Le, Yen H. title = Virus detections among patients with severe acute respiratory illness, Northern Vietnam date = 2020-05-12 pages = extension = .txt mime = text/plain words = 2833 sentences = 145 flesch = 43 summary = To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. There was one case of co-infection with enterovirus and coronavirus 229E including a female military hospital patient 28 years of age. Additionally, our results display enterovirus, adenovirus and coronavirus infections among the SARI cases, suggesting that cities in northern Vietnam could benefit also from local surveillance of non-influenza respiratory viruses. cache = ./cache/cord-290034-4b0mshqa.txt txt = ./txt/cord-290034-4b0mshqa.txt === reduce.pl bib === id = cord-290539-8ak2tths author = Cagno, Valeria title = Novel broad spectrum virucidal molecules against enveloped viruses date = 2018-12-07 pages = extension = .txt mime = text/plain words = 5524 sentences = 276 flesch = 51 summary = To further elucidate the mechanism of action we performed a virucidal assay in which 9d was incubated with the virus at 10 μM 5μM or 1μM concentration for different times (Fig 6A) or for 1h with serial dilutions of compound ( Fig 6B) ; subsequently, the mixture was titrated on cells and the viral titer was evaluated at dilutions at which the compound concentration was known not to be active in plaquing efficiency assays. The irreversibility of the mechanism was also tested with an assay in which the compound was incubated with the virus for 1h and subsequently the mixture has been diluted in drug free medium for additional 1, 2, 3 or 4 hours before the addition on cells (S2 Fig) . cache = ./cache/cord-290539-8ak2tths.txt txt = ./txt/cord-290539-8ak2tths.txt === reduce.pl bib === id = cord-292237-45hi4iz2 author = Calvo-Pinilla, Eva title = Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the Alpha/Beta Interferon Receptor date = 2009-04-09 pages = extension = .txt mime = text/plain words = 4735 sentences = 251 flesch = 53 summary = Furthermore, IFNAR((−/−)) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. All these data, and the presence of an otherwise intact immune system in these mice [20, 22] suggest that IFNAR (2/2) mice could be a good animal model to study BTV infections and to evaluate vaccine strategies against this virus. By contrast, IFNAR (2/2) mice were susceptible to BTV-4 infection (Fig. 1A) , showing disease symptoms characterized by ocular discharges and apathy starting at 48 h.p.i. Disease progression led to animal death within 60 h.p.i. The LD 50 value was obtained by i.v. inoculation with 10-fold dilutions of BTV-4, resulting in a LD 50 value of 10 2.6 PFU (Fig. 1B) . Infectious viral titers were analyzed in the blood of immunized and nonimmunized IFNAR (2/2) mice by plaque assay after intravenous infection with BTV-4 (Fig. 5C ). cache = ./cache/cord-292237-45hi4iz2.txt txt = ./txt/cord-292237-45hi4iz2.txt === reduce.pl bib === id = cord-291417-p49ukyhx author = Mikulska, Malgorzata title = Tocilizumab and steroid treatment in patients with COVID-19 pneumonia date = 2020-08-20 pages = extension = .txt mime = text/plain words = 4441 sentences = 219 flesch = 44 summary = METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. We hypothesized that outcomes such as no need for intubation and survival of patients with severe COVID-19 pneumonia in whom tocilizumab and/or methylprednisolone were administered in addition to standard of care (SOC) could be better than in those who received only SOC. In this observational study in non-intubated patients with mainly severe COVID-19 pneumonia, the early addition of tocilizumab and/or methylprednisolone to SOC resulted in adjusted failure-free survival of 86.5% and 80.8% at day 14 and 30, which was, respectively, 10.7% and 16.7% higher than in SOC patients. cache = ./cache/cord-291417-p49ukyhx.txt txt = ./txt/cord-291417-p49ukyhx.txt === reduce.pl bib === id = cord-293794-vudufao5 author = Cuthbertson, Leah title = Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children date = 2019-10-17 pages = extension = .txt mime = text/plain words = 4820 sentences = 255 flesch = 48 summary = No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Using 16s rRNA gene sequencing of respiratory samples from children presenting to hospital with acute wheezing, this study aimed to examine whether the bacterial community in the airways of children with acute respiratory wheeze was altered compared with that of nonwheezing children. However, when the microbiota in children with bronchiolitis were compared to those closest in age there was a significant reduction in alpha diversity (richness; p = 0.01, Shannon-Weiner, p = 0.003, inverse Simpsons, p = 0.005) that was not associated with change in bacterial biomass (p = 0.874). When those with a diagnosis of bronchiolitis were compared to other cases that wheezed or age matched control subjects, significant differences in alpha and beta diversity were observed however this may have been driven by subjects with bronchiolitis being significantly younger than other groups of subjects. cache = ./cache/cord-293794-vudufao5.txt txt = ./txt/cord-293794-vudufao5.txt === reduce.pl bib === id = cord-293072-giakcaki author = Xu, Wan-Xiang title = A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date = 2017-10-12 pages = extension = .txt mime = text/plain words = 5303 sentences = 227 flesch = 52 summary = The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. cache = ./cache/cord-293072-giakcaki.txt txt = ./txt/cord-293072-giakcaki.txt === reduce.pl bib === id = cord-291360-z19ri377 author = Lan, Fan-Yun title = COVID-19 symptoms predictive of healthcare workers’ SARS-CoV-2 PCR results date = 2020-06-26 pages = extension = .txt mime = text/plain words = 4339 sentences = 251 flesch = 52 summary = Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8–99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. Therefore, we investigated the presenting symptoms most predictive of positive/negative SARS-CoV-2 RT-PCR results among HCWs. Since March 9, 2020, the occupational health service of a Massachusetts community healthcare system has implemented a staff "hotline" system to maintain a viable/healthy workforce and operational continuity during the pandemic. The clinical COVID-19 attack rate during the study period was calculated as: (the number of initial positive SARS-CoV-2 assays + the number of false negatives) divided by the system's estimated total HCW population (n = 4600). cache = ./cache/cord-291360-z19ri377.txt txt = ./txt/cord-291360-z19ri377.txt === reduce.pl bib === id = cord-292396-8w06oc5i author = Leger, Thomas title = Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score date = 2020-11-03 pages = extension = .txt mime = text/plain words = 3373 sentences = 209 flesch = 57 summary = OBJECTIVES: The purpose is to assess the ability of low-dose CT (LDCT) to determine lung involvement in SARS-CoV-2 pneumonia and to describe a COVID19-LDCT severity score. The objective is to evaluate the ability of (LDCT) to analyze well-known imaging abnormalities as well as to establish a COVID19-LDCT score reflecting disease severity and correlate it with clinical risk scores to allow better selection and follow-up of patients. For each patient, the following clinical parameters were recorded: age, sex, date of first symptoms, date of chest CT scan, delay between the first symptom and chest CT scan, fever, cough, dyspnea, diarrhea, myalgia, rhinorrhea, abnormalities at lung auscultation, temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, and oxygen needed. The main findings of the presented work are that 1) LDCT scans can depict the typical features of SARS-CoV-2 pneumonia with limited irradiation; and 2) the COVID19-LDCT score is correlated with the NEWS used routinely to assess disease severity and patient prognosis. cache = ./cache/cord-292396-8w06oc5i.txt txt = ./txt/cord-292396-8w06oc5i.txt === reduce.pl bib === id = cord-291176-evb6yt0r author = Giorgi Rossi, Paolo title = Characteristics and outcomes of a cohort of COVID-19 patients in the Province of Reggio Emilia, Italy date = 2020-08-27 pages = extension = .txt mime = text/plain words = 4559 sentences = 213 flesch = 46 summary = In this report, based on the cohort of all residents in the province of Reggio Emilia who were SARS-CoV-2-positive at nasal and pharyngeal swab and with symptoms (COVID-19 cases) since the inception of the epidemic, we describe patient characteristics and explore their role as putative prognostic factors in predicting the occurrence of hospital admission or death. We considered the following patient characteristics: age, sex, place of birth (Italy or abroad), time span (in days) from symptom onset to diagnosis/ hospitalization, and comorbidities, whose prognostic role was explored both singly (chronic obstructive pulmonary disease, arrhythmia, diabetes, coronary heart disease, heart failure, vascular diseases, obesity) and by computing the Charlson Comorbidity Index, which provides an overall measure of an individual patient's complexity [12] . While in this study we focused on the risk of hospitalization and death in a cohort of COVID-19 patients diagnosed during the epidemic in Northern Italy, it also provided us with the opportunity to describe the pattern of distribution of the disease in the whole population. cache = ./cache/cord-291176-evb6yt0r.txt txt = ./txt/cord-291176-evb6yt0r.txt === reduce.pl bib === id = cord-293393-kbndie8e author = Braesch-Andersen, Sten title = ApoD Mediates Binding of HDL to LDL and to Growing T24 Carcinoma date = 2014-12-16 pages = extension = .txt mime = text/plain words = 6253 sentences = 386 flesch = 60 summary = To investigate the presence of particles containing both apoD and apoB, we performed a dual-specific ELISA using the anti-apoD mAb D554 as a capture antibody and a biotinylated anti-apoB mAb, LDL20, for detection. To determine the importance of having intact lipoprotein particles, we repeated the dual-specific apoD/B ELISA in the presence of detergent, using anti-apoD-D544 as the capture mAb and anti-apoB-LDL20 as the detecting mAb. As seen in Fig. 4A , only small amounts of apoB bound to D544 when detergent was present, indicating that intact lipoprotein particles are needed for the apoD-LDL interaction. In agreement with this latter finding, apoD production was high in confluent, growth-arrested T24 cell cultures (2,5 million cells in 9 ml), but was not detectable in non-confluent proliferating Anti-apoD (D544) was used as the capture antibody and anti-apoB (LDL20-biotin) was used as the detection antibody in a detergent free dualspecific ELISA. cache = ./cache/cord-293393-kbndie8e.txt txt = ./txt/cord-293393-kbndie8e.txt === reduce.pl bib === id = cord-292475-jrl1fowa author = Abry, Patrice title = Spatial and temporal regularization to estimate COVID-19 reproduction number R(t): Promoting piecewise smoothness via convex optimization date = 2020-08-20 pages = extension = .txt mime = text/plain words = 7470 sentences = 386 flesch = 53 summary = The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. In that spirit, the overarching goal of the present work is twofold: (1) proposing a new, more versatile framework for the estimation of R(t) within the semi-parametric model of [8, 10] , reformulating its estimation as an inverse problem whose functional is minimized by using non smooth proximal-based convex optimization; (2) inserting this approach in an extended multivariate framework, with applications to various complementary datasets corresponding to different geographical regions. cache = ./cache/cord-292475-jrl1fowa.txt txt = ./txt/cord-292475-jrl1fowa.txt === reduce.pl bib === id = cord-292537-9ra4r6v6 author = Liu, Fenglin title = Predicting and analyzing the COVID-19 epidemic in China: Based on SEIRD, LSTM and GWR models date = 2020-08-27 pages = extension = .txt mime = text/plain words = 5662 sentences = 259 flesch = 52 summary = For the study of infectious diseases like COVID-19, SARS, and Ebola, most of the literature used descriptive research or model methods to assess indicators and analyze the effect of interventions, such as combining migration data to evaluate the potential infection rate [18, 19] , understanding the impact of factors like environmental temperature and vaccines that might be potentially linked to the diseases [20, 21] , using basic and time-varying reproduction number (R 0 & R t ) to estimate changeable transmission dynamics of epidemic conditions [22] [23] [24] [25] [26] [27] , calculating and predicting the fatal risk to display any stage of outbreak [28] [29] [30] , or providing suggestions and interventions from risk management and other related aspects based on the results of modeling tools or historical lessons [31] [32] [33] [34] [35] [36] [37] [38] [39] . cache = ./cache/cord-292537-9ra4r6v6.txt txt = ./txt/cord-292537-9ra4r6v6.txt === reduce.pl bib === id = cord-294568-12eyo13f author = Fernandes-Matano, Larissa title = Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico date = 2017-05-03 pages = extension = .txt mime = text/plain words = 4930 sentences = 240 flesch = 45 summary = Influenza viruses are one of the main causative agents of ARIs worldwide; however, many other respiratory viruses for which insufficient epidemiological information is available can also cause ARIs. Studies performed at the international level have frequently identified human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), influenza virus (flu), human mastadenovirus (HMdV), rhinovirus (RV), and enterovirus (EV) and less frequently identified human metapneumovirus (HMPV), primate bocaparvovirus (PBpV), and human coronavirus (HCoV) [12] . Therefore, the objective of this study was to determine the viral aetiology of these infections and to analyse the behaviour of non-influenza respiratory viruses in the Mexican population. The importance of the differential diagnosis of other respiratory viruses in samples with negative influenza results becomes apparent when we observe the prevalence of the three main viruses identified in this study as well as their associations with severe cases and deaths, especially in the child population. cache = ./cache/cord-294568-12eyo13f.txt txt = ./txt/cord-294568-12eyo13f.txt === reduce.pl bib === id = cord-294768-bs6thjw2 author = Alonso-Fernández, Alberto title = Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study date = 2020-08-25 pages = extension = .txt mime = text/plain words = 4652 sentences = 278 flesch = 49 summary = title: Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion. [12] found, in a retrospective study in 184 intensive care unit (ICU) patients with severe COVID-19 pneumonia, a high prevalence of thrombotic complications and, by far, pulmonary embolism (PE) was the most frequent. Pulmonary embolism in COVID-19 pneumonia with high D-dimer values: A prospective study procoagulant (D-dimer) markers that correlated with the extend of the thromboembolic episode compared to those patients without PE. We included patients with D-dimer values higher than 1 μg/mL, which have been associated with disease severity and in-hospital mortality in patients with COVID-19 infection. Pulmonary embolism in COVID-19 pneumonia with high D-dimer values: A prospective study of our patients, allocated in the non-PE group, was not on enoxaparin prophylaxis during hospitalization. cache = ./cache/cord-294768-bs6thjw2.txt txt = ./txt/cord-294768-bs6thjw2.txt === reduce.pl bib === id = cord-293946-4bquxdqa author = Huong, Nguyen Quynh title = Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014 date = 2020-08-10 pages = extension = .txt mime = text/plain words = 6229 sentences = 292 flesch = 51 summary = In this study we investigated the presence and diversity of coronavirus sequences in the field rat trade distribution chain, wildlife farms specializing in raising rodents for human consumption, and bat guano "farms" and roosts near human dwellings to better understand the natural hosts of coronaviruses and the risk for these interfaces to facilitate spillover into humans. Out of 70 sites, coronavirus positives were detected at 58 including 100% (24/24) of live rat trade sites, 60.7% (17/28) of rodent wildlife farm sites, 94.1% (16/17) of bat guano farm sites, and at the one natural pteropid bat roost. Significant findings of this study are the high proportion of coronavirus positive wildlife (bats and rodents) and the increasing proportion of positives found along the rat trade supply chain from sub-interfaces close to the capture site (rat traders) to restaurants. cache = ./cache/cord-293946-4bquxdqa.txt txt = ./txt/cord-293946-4bquxdqa.txt === reduce.pl bib === id = cord-291104-6chpmgry author = Leung, Danny T. M. title = Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients date = 2016-08-05 pages = extension = .txt mime = text/plain words = 6269 sentences = 313 flesch = 58 summary = The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients' plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. Similar results were found when the serum of these individuals was examined: the cancer patients (424 +/-121 ng/ mL) had significantly (P = 0.0002) higher levels of OPN than healthy subjects (314 +/-98 ng/ mL) (Fig 5B) , the assay sensitivity and specificity being 18% and 97%, respectively. The finding that the mAb 446 inhibition ELISA and the commercial OPN kit could not detect elevated OPN levels in the cancer patients suggested the possibility that the OPN present could be fragmented i.e. the target sites for the antibodies used in these assays could be missing, whereas, by virtue of the design of the mAb 659-based assay, the thrombin-sensitive site must be present. cache = ./cache/cord-291104-6chpmgry.txt txt = ./txt/cord-291104-6chpmgry.txt === reduce.pl bib === id = cord-294645-yzh8h7zo author = Freeman, David W. title = Association between GDF15, poverty and mortality in urban middle-aged African American and white adults date = 2020-08-07 pages = extension = .txt mime = text/plain words = 4977 sentences = 221 flesch = 43 summary = Multivariable adjusted Cox regression models were used to assess the association between log-transformed GDF15 (logGDF15) and 12-year mortality outcomes (all-cause, cardiovascularand cancer-specific outcomes) and interactions with sex, race and poverty status. The objectives of the present study were to assess the association between serum GDF15 and all-cause and cause-specific mortality, and to identify interactions between GDF15 and sex, race and poverty status in a large cohort of community-based middle-aged adults recruited from Baltimore, Maryland. In a community-dwelling cohort of younger urban adults (mean age 49.6) with diverse racial and socioeconomic status, we found that elevated serum GDF15 level was strongly associated with all-cause mortality, CVD-and cancer-specific mortality risk. Our findings of increased risk of mortality due to all-causes and CVD and elevated GDF15 levels in a diverse cohort are consistent with results of previous studies conducted in apparently healthy, community-dwelling adults [12-15, 17, 18] . cache = ./cache/cord-294645-yzh8h7zo.txt txt = ./txt/cord-294645-yzh8h7zo.txt === reduce.pl bib === id = cord-295352-b8kztgt8 author = Maksimowski, Nicholas title = Kidney ACE2 expression: Implications for chronic kidney disease date = 2020-10-30 pages = extension = .txt mime = text/plain words = 3517 sentences = 212 flesch = 54 summary = Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. Tubulointerstitial and glomerular median-centered log2 mRNA expression of ACE2 or TMPRSS2 from renal biopsy samples were compared in CKD and HLD, as well as in male and female subgroups. Mean values for ACE2 mRNA expression in both the tubulointerstitial and glomerular compartments were similar in all of the disease categories represented in the CKD cohort (S1 Fig) . cache = ./cache/cord-295352-b8kztgt8.txt txt = ./txt/cord-295352-b8kztgt8.txt === reduce.pl bib === id = cord-294023-knaxr7t0 author = Murri, Rita title = Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy date = 2020-09-03 pages = extension = .txt mime = text/plain words = 2073 sentences = 115 flesch = 51 summary = title: Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy Seventy percent (n = 261) of respondents reported that their use of social media to find medical information increased during the current pandemic (Fig 1) . In terms of COVID-19 medical practice, information coming from social media were considered "enough" or "much" or "very much" useful by 82.9% (n = 306) of the sample. To the question "During the last week, do you think that information shared on social media had an impact on your clinical practice for patients with COVID?" 28.7% (n = 106) answered "enough" and 47.1% (n = 174) "much" or "very much". Our survey shows that, at the time of COVID pandemic, many clinicians react to their urgent need for updates by seeking information through unconventional sources instead of academic journals publications. cache = ./cache/cord-294023-knaxr7t0.txt txt = ./txt/cord-294023-knaxr7t0.txt === reduce.pl bib === id = cord-292777-oztmw8jo author = Wong, Michelle title = Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia date = 2013-07-16 pages = extension = .txt mime = text/plain words = 3300 sentences = 179 flesch = 38 summary = In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. In this study we thus sought to determine the contribution of microbial translocation to FUO episodes in an adult febrile neutropaenic cohort using endotoxin and sCD14 concentrations in the plasma as markers for microbial translocation. In this cohort of iatrogenic neutropaenic adults, we found elevated plasma levels of endotoxin and sCD14 in febrile neutropaenic episodes where no other microbiological findings have been documented, implicating microbial translocation as a potential contributor towards their febrile status. Adding to the field, we have, in our study, in addition to measuring plasma endotoxin concentrations, also measured the host receptor for LPS, sCD14 in an attempt to determine the contribution of microbial translocation to fever as a clinical outcome. cache = ./cache/cord-292777-oztmw8jo.txt txt = ./txt/cord-292777-oztmw8jo.txt === reduce.pl bib === id = cord-295339-nzc47itk author = Baker, Marissa G. title = Estimating the burden of United States workers exposed to infection or disease: A key factor in containing risk of COVID-19 infection date = 2020-04-28 pages = extension = .txt mime = text/plain words = 3320 sentences = 139 flesch = 41 summary = METHODS: To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. Given the proportion of the United States workforce exposed to disease or infection at work, this analysis also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve. To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. cache = ./cache/cord-295339-nzc47itk.txt txt = ./txt/cord-295339-nzc47itk.txt === reduce.pl bib === id = cord-294372-pec1886j author = Greene, Dina N. title = Decreasing median age of COVID-19 cases in the United States—Changing epidemiology or changing surveillance? date = 2020-10-15 pages = extension = .txt mime = text/plain words = 1698 sentences = 103 flesch = 60 summary = Result distributions by age and positivity were compared between early period (March-April 2020) and late periods (June-July 2020) of the COVID-19 pandemic. Overall, this suggests that observed age-related trends are driven by changes in testing patterns rather than true changes in the epidemiology of SARS-CoV-2 infection. In the United States, surveillance data suggest that mean age of infected patients is decreasing compared to the early stages of the COVID-19 pandemic. We used SARS-CoV-2 testing data from a national reference laboratory to characterize the age distribution of detected cases between March and July of 2020. Surveillance data in the United States have shown a trend toward decreasing age among persons with laboratory-confirmed SARS-CoV-2 infection. This study found a similar pattern among patients tested by a national reference laboratory, with the median age among patients testing positive being five years lower in June and early July compared to March and April. cache = ./cache/cord-294372-pec1886j.txt txt = ./txt/cord-294372-pec1886j.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-295536-dbpt4dhr author = Shook, Natalie J. title = Disease avoidance in the time of COVID-19: The behavioral immune system is associated with concern and preventative health behaviors date = 2020-08-20 pages = extension = .txt mime = text/plain words = 4592 sentences = 270 flesch = 40 summary = This study examined whether individual differences in BIS reactivity (germ aversion, pathogen disgust sensitivity) were associated with concern about COVID-19 and engagement in recommended preventative health behaviors (social distancing, handwashing, cleaning/disinfecting, avoiding touching face, wearing facemasks). Germ aversion and pathogen disgust sensitivity were the two variables most consistently associated with COVID-19 concern and preventative health behaviors, while accounting for demographic, health, and psychosocial covariates. In general, younger age, higher income, more populated location of residence, more recent illness, better perceived health, having/had COVID-19, greater religiosity, greater extraversion, greater conscientiousness, greater perceived infectability, greater germ aversion, and greater pathogen disgust sensitivity were associated with engaging in most (at least three) of the preventative health behaviors more frequently. When demographic, health, social, personality, and BIS variables were considered simultaneously, greater germ aversion and pathogen disgust sensitivity were most consistently associated with COVID-19 concern and preventative behaviors. cache = ./cache/cord-295536-dbpt4dhr.txt txt = ./txt/cord-295536-dbpt4dhr.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-297835-ukrz8tlv author = Leith, Douglas J. title = Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram date = 2020-09-30 pages = extension = .txt mime = text/plain words = 5591 sentences = 264 flesch = 58 summary = title: Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram Contact tracing apps based on the Google/Apple Exposure Notification (GAEN) API [4] are currently being rolled out across Europe, with apps already deployed in Italy, Switzerland and Germany. We observe that changing the people holding a pair of handsets, with the location of the handsets otherwise remaining unchanged, can cause variations of ±10dB in the attenuation level reported by the GAEN API. To provide baseline data on the radio propagation environment we also used the standard Android Bluetooth LE scanner API to collect measurements of RSSI as the distance was varied between two Google Pixel 2 handsets placed at a height of approximately 0.5m (about the same height as the tram seating) in the centre aisle of the tram carriage. cache = ./cache/cord-297835-ukrz8tlv.txt txt = ./txt/cord-297835-ukrz8tlv.txt === reduce.pl bib === id = cord-295293-ickp2n47 author = Latsuzbaia, Ardashel title = Evolving social contact patterns during the COVID-19 crisis in Luxembourg date = 2020-08-06 pages = extension = .txt mime = text/plain words = 2976 sentences = 153 flesch = 52 summary = While the number of social contacts was substantially lower during the lockdown by more than 80% compared to the pre-pandemic period, we observed a more recent 121% increase during the post lockdown period showing an increased potential for COVID-19 spread. We repeatedly conducted an internet survey to follow up the impact of the local government interventions on social contact patterns in Luxembourg shortly after the lockdown was implemented due to the rapid local spread of the COVID-19. The average number of contacts reported by Luxembourg residents in a study before the pandemic was 17.5 [4] , suggesting that contacts during lockdown had decreased by 81.7%. Our study suggests that the strict physical distancing measures implemented in Luxembourg had a substantial and immediate impact on social mixing patterns resulting in a large reduction of the average number of contacts per day. In conclusion, our stud shows that physical distance measures resulted in significant reduction in social contacts and therefore decreased the spread of COVID-19 in Luxembourg. cache = ./cache/cord-295293-ickp2n47.txt txt = ./txt/cord-295293-ickp2n47.txt === reduce.pl bib === === reduce.pl bib === id = cord-299852-t0mqe7yy author = Janssen, Loes H. C. title = Does the COVID-19 pandemic impact parents’ and adolescents’ well-being? An EMA-study on daily affect and parenting date = 2020-10-16 pages = extension = .txt mime = text/plain words = 8570 sentences = 476 flesch = 51 summary = In this ecological momentary assessment study, we investigated if the COVID-19 pandemic affected positive and negative affect of parents and adolescents and parenting behaviors (warmth and criticism). However, Intolerance of uncertainty, nor any pandemic related characteristics (i.e. living surface, income, relatives with COVID-19, hours of working at home, helping children with school and contact with COVID-19 patients at work) were linked to the increase of parents' negative affect during COVID-19. In addition, we asked parents and adolescents about daily difficulties and helpful activities during the COVID-19 pandemic that possibly influenced their affect in positive and negative ways. During the COVID-19 pandemic, the most reported daily difficulties across the 14 days of EMA for parents were (1) missing social contact with friends (14.6%), (2) concerns about the coronavirus in general (13.5%), (3) irritations with family members (12.8%), (4) worrying about health of others (8.3%), and (5) coronavirus-related news items (8.0%). cache = ./cache/cord-299852-t0mqe7yy.txt txt = ./txt/cord-299852-t0mqe7yy.txt === reduce.pl bib === id = cord-296635-8r3tm966 author = Breed, Andrew C. title = Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management date = 2011-12-14 pages = extension = .txt mime = text/plain words = 4573 sentences = 199 flesch = 47 summary = title: Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. Hendra virus (HeV) and Nipah virus (NiV) are paramyxoviruses of the genus Henipavirus with pteropid bats (i.e. flying-foxes; Pteropus sp., Family Pteropodidae) being the primary wildlife reservoir [1] . Henipaviruses have the potential to infect a wide range of mammalian species, and Hendra virus has spread from flying-foxes to horses in Australia on at least 20 reported separate occasions (five involving horse-human transmission), most recently in 2011 [5, 6, 7] . [14] on the infection dynamics of HeV in the little red flying-fox, Pteropus scapulatus, in the Northern Territory of Australia suggested that viral transmission may be predominantly horizontal, with pregnancy and lactation suggested as risk factors for infection. cache = ./cache/cord-296635-8r3tm966.txt txt = ./txt/cord-296635-8r3tm966.txt === reduce.pl bib === id = cord-296550-wkmnfph3 author = Hossain, Mohammad Anwar title = Knowledge, attitudes, and fear of COVID-19 during the Rapid Rise Period in Bangladesh date = 2020-09-24 pages = extension = .txt mime = text/plain words = 4576 sentences = 239 flesch = 53 summary = The study aims to determine the level of Knowledge, Attitude, and Practice (KAP) related to COVID-19 preventive health habits and perception of fear towards COVID-19 in subjects living in Bangladesh. The study objectives were to determine the level of knowledge, attitudes, and practices related to COVID-19 preventive health habits and the underlying fear of COVID-19 in the Bangladeshi population and how they are affected by socio-demographic factors. The KAP section of the questionnaire related to a total of 12 score knowledge questions on COVID-19, categorical answers to attitudes towards the control of the pandemic, and practices of wearing masks and avoiding public gatherings. This study is similar to one study in China that found a significant relationship between knowledge and age and knowledge and educational level, with males reporting higher levels of knowledge than females regarding COVID-19 symptoms, precautions, and health advisory practices [16] . However, in our study, subjects living in Bangladesh reported similar knowledge for both males and females regarding COVID-19 symptoms, precautions, and health advisory practices. cache = ./cache/cord-296550-wkmnfph3.txt txt = ./txt/cord-296550-wkmnfph3.txt === reduce.pl bib === id = cord-302200-9gekjgr0 author = Kilich, Eliz title = Factors that influence vaccination decision-making among pregnant women: A systematic review and meta-analysis date = 2020-07-09 pages = extension = .txt mime = text/plain words = 6662 sentences = 345 flesch = 38 summary = Previous reviews have established a narrative of evidence that suggests a broad range of factors (vaccine cost, accessibility, maternal knowledge, social influences, context, healthcare professional (HCP) recommendation and the perception of risks and benefits) all contribute to vaccine uptake. Thus, we performed a systematic review and meta-analysis of qualitative and quantitative literature to provide comprehensive evidence on the magnitude of effect that factors influence maternal vaccination decisions globally with the aim to inform policy makers, public health strategists and researchers involved in designing vaccine interventions to increase uptake. For seasonal influenza, the data is inconclusive since women who believed that the disease could be harmful to their pregnancy or baby had four-times greater odds of being vaccinated than those who did not (OR 3.70, 95% CI 1.37-9.94) yet there was no evidence to suggest belief in the risk of the disease generally (OR 1.56, 95% CI 0.88-2.76) or its ability to result in hospitalisation (OR 0.57, 95% CI 0.22-1.45) were related to vaccine uptake. cache = ./cache/cord-302200-9gekjgr0.txt txt = ./txt/cord-302200-9gekjgr0.txt === reduce.pl bib === id = cord-299491-8rfm0jxh author = Xiao, Shenglan title = Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong date = 2017-07-20 pages = extension = .txt mime = text/plain words = 4765 sentences = 218 flesch = 53 summary = Like many other respiratory viruses, the SARS-CoV is suspected to spread from an infected person to the susceptible via three basic transmission routes, i.e., the long-range airborne, close contact and fomite routes [14] [15] [16] , as shown in Fig 1. Several studies have proposed probable evidence for the airborne spread of the SARS-CoV based on the consistencies between bio-aerosol concentration distributions and reported attack rates [19] [20] [21] , but no mechanism-based investigations exist for the fomite route. To investigate the role the fomite route plays in SARS-CoV transmission, we conducted a detailed modelling study of the largest hospital outbreak in Hong Kong [20] , in which the distribution of reported attack rates of inpatients showed a statistically significant spatial pattern. A multi-agent model ( Fig 2) was developed to simulate the possible spread of the viruses from the index patient to the susceptible by air flow and surface touching, and to calculate the possible exposure doses and infection risks for each hypothesis. cache = ./cache/cord-299491-8rfm0jxh.txt txt = ./txt/cord-299491-8rfm0jxh.txt === reduce.pl bib === id = cord-295559-yc8q62z8 author = Qian, Zhaohui title = Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation date = 2013-10-03 pages = extension = .txt mime = text/plain words = 7303 sentences = 303 flesch = 50 summary = Coronavirus S proteins are Class I viral fusion proteins like the HIV envelope (env), influenza hemagglutinin (HA) and paramyxovirus fusion (F) glycoproteins [17] , which typically require protease cleavage between the S1 and S2 domains ( Figure 1A ) to permit conformational changes in S2, activated by receptor binding and/or low pH, that mediate membrane fusion leading to virus entry and syncytia formation [3, 17, 18] . In addition to entry by endocytosis, we showed that, like SARS-CoV [21, 22] , MERS pseudovirions could enter susceptible Vero E6 cells at the plasma membrane if virions were first bound to cell surface receptors at 4°C at neutral pH in the presence of NH 4 Cl to inhibit acidification of endosomes, and also treated briefly at room temperature with trypsin to cleave the viral S protein. cache = ./cache/cord-295559-yc8q62z8.txt txt = ./txt/cord-295559-yc8q62z8.txt === reduce.pl bib === id = cord-296691-cg463fbn author = Wang, Ren title = De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing date = 2013-04-09 pages = extension = .txt mime = text/plain words = 5831 sentences = 334 flesch = 46 summary = title: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. They have played significant roles in functional genomics research for discovery of novel genes together with identifying different protein groups (e.g. proteins with signal peptides) other than the whole genome [27] [28] [29] , developing SSRs and SNPs markers [30] [31] [32] [33] [34] , allowing large-scale expression analysis [35] , improving genome annotation [36] , and elucidating phylogenetic relationships [37] . Hence, determination of the genetic pathways and specific genes involved in Amaryllidaceae alkaloids biosynthesis and some other aspects of Lycoris could be beneficial for humans and enrich our knowledge and understanding of functional genomics and biological research. cache = ./cache/cord-296691-cg463fbn.txt txt = ./txt/cord-296691-cg463fbn.txt === reduce.pl bib === id = cord-299953-sasfvcun author = Whitehead, Ashley B. R. title = Burden of exposure to infectious bursal disease virus, infectious bronchitis virus, Newcastle disease virus, Mycoplasma gallisepticum, and intestinal parasites in introduced broiler chickens on the Galapagos date = 2018-09-24 pages = extension = .txt mime = text/plain words = 4442 sentences = 220 flesch = 55 summary = The objective of the study reported here was to measure the burden of exposure to infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), Mycoplasma gallisepticum (MG), and intestinal parasites in a sample of broiler chickens on 13 farms on Santa Cruz Island and San Cristobal Island in July 2017. Study results are relevant because (i) they provide new baseline data on the burden of exposure to avian pathogens in broiler farms, (ii) justify the need to verify standard operating procedures in hatcheries that supply (non-vaccinated) day-old chicks to the Galapagos and (iii) to implement enhanced biosecurity standards on broiler chicken farms to mitigate risk of disease transmission between broilers, backyard poultry, and wild birds on the Galapagos. cache = ./cache/cord-299953-sasfvcun.txt txt = ./txt/cord-299953-sasfvcun.txt === reduce.pl bib === id = cord-302355-3se1wp8o author = Chen, Yi-Shiuan title = The conserved stem-loop II structure at the 3' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA date = 2018-07-26 pages = extension = .txt mime = text/plain words = 6004 sentences = 292 flesch = 53 summary = Although XRN1 digestion of a 3'-terminal 800-nt RNA could stall at a position to generate the sfRNA in vitro, we found that knocking out XRN1 had no effect on the accumulation of sfRNA in Japanese encephalitis virus (JEV) infected cells. Furthermore, the minus-strand templates covering the putative promoter region used for an in vitro RdRp assay gave rise to synthetic products, suggesting that the JEV sfRNA could be initially transcribed from the antigenome and may be further trimmed by XRN1 or other unidentified exoribonucleases. Although efficient RNA replication is required for the detection of any flaviviral RNAs despite which mechanism used for the sfRNA formation, our results were clearly different from the observations from WNV that BHK-21 cells transfected with replicon constructs containing various deletions had no effect on the accumulation of sfRNA when compared to the WT [8] . cache = ./cache/cord-302355-3se1wp8o.txt txt = ./txt/cord-302355-3se1wp8o.txt === reduce.pl bib === id = cord-301180-ndiwmnv0 author = Lin, Min-Hsuan title = Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking date = 2012-12-10 pages = extension = .txt mime = text/plain words = 5161 sentences = 233 flesch = 39 summary = Importantly, treatment of Myc-Rev and Nullbasic-mCherry expressing cells with LMB resulted in the complete restoration of Myc-Rev nucleolar accumulation (Fig. 3, row 6) , suggesting that Nullbasic requires functional CRM1 to mislocalize Rev most likely by an indirect interaction. While expression of Nullbasic-mCherry alone had no apparent effect on the nucleolar localization of either protein (Fig. 6 , rows 2 and 5), coexpression of Nullbasic-mCherry with Myc-Rev induced relocalization of C23 but not fibrillarin from the nucleolus to the nucleoplasm, in a manner concomitant with the redistribution of Myc-Rev (Fig. 6, rows 3 and 6 , respectively). CRM1 is a cellular receptor that recognizes and binds to the leucine-rich NES domain of Rev, an interaction which facilitates the egress of Rev/viral mRNA complexes through nuclear pores [3, 4, 42] and is readily visualized in cells as a colocalization in the nucleolus (Fig. 3, row 2 ). cache = ./cache/cord-301180-ndiwmnv0.txt txt = ./txt/cord-301180-ndiwmnv0.txt === reduce.pl bib === id = cord-304993-t4rua95e author = Jung, Kwonil title = The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals date = 2012-07-23 pages = extension = .txt mime = text/plain words = 7069 sentences = 369 flesch = 50 summary = At 12 hours after treatment with 80 mM simvastatin, LDLR gene expression levels in IPEC-J2 cells were significantly increased compared to 0 to 20 mM treated groups (Fig. 1B) . Simvastatin Impaired TLR3-mediated Induction of IFN-a in Macrophages or Dendritic Cells, Possibly Due to Lowered Expression of TLR3 after Treatment Our in vivo data showing enhanced early infectivity of HuNoV suggested potential subversion of innate immunity related to simvasatin treatment. Oral treatment of Gn pigs with natural human IFN-a (nhIFN-a) [300 international unit (IU)/ kg/day] reduced or curtailed virus shedding in treated animals during the treatment period (PID 1 to 4), compared to untreated animals ( Fig. 7A-C) . In conclusion, simvastatin treatment increased HuNoV infectivity in the Gn pig model, possibly due to its inhibitory effect on innate immunity as well as its cholesterol lowering effect as reported previously [20] . cache = ./cache/cord-304993-t4rua95e.txt txt = ./txt/cord-304993-t4rua95e.txt === reduce.pl bib === id = cord-300859-nqklx0vn author = Henderson, Kelley C. title = Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection date = 2015-06-29 pages = extension = .txt mime = text/plain words = 8223 sentences = 331 flesch = 41 summary = title: Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection pneumoniae with statistically significant specificity and sensitivity in simulated and true clinical throat swab samples, and the ability to distinguish between reference strains of the two main genotypes of M. pneumoniae clinical isolates from globally diverse origins and distinguished these from a panel of 12 other human commensal and pathogenic mycoplasma species with 100% cross-validated statistical accuracy. A total of n = 390 pre-processed NA-SERS spectra collected from both substrates were included in the model, consisting of 20 nanorod substrate background spectra, 20 growth medium control spectra, 25 M129 spectra, 25 FH spectra, and 10 spectra per additional clinical isolate. pneumoniae strains from all 12 other human Mollicutes species and the growth medium control with 100% cross-validated sensitivity and specificity (Fig 3A-3C ). cache = ./cache/cord-300859-nqklx0vn.txt txt = ./txt/cord-300859-nqklx0vn.txt === reduce.pl bib === id = cord-298078-uqrwq5qk author = Kwak, Hoyun title = Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus date = 2011-08-30 pages = extension = .txt mime = text/plain words = 5346 sentences = 318 flesch = 56 summary = The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs. Ribosomal frameshifing is a recoding process of translation where a specific messenger RNA (mRNA)-mediated signal directs a ribosome to shift its reading frame and to continue in the new frame. To search for cellular proteins that directly interacted with IBV pseudoknot RNA, a RNA pull down assay was performed in the presence of cell extracts (Figure 2A ). Through the RNA-immunoprecipitation assay, we showed that ANXA2 specifically interacted with wild-type IBV pseudoknot RNA but not with mutant IBV RNA in LNCaP and HEK293T cells ( Figure 3C and 3D). To test how ANXA2 regulates the frameshifting efficiency of IBV pseudoknot RNA, we first overexpressed ANXA2 protein in the presence of the reporters and measured the luciferase activities. cache = ./cache/cord-298078-uqrwq5qk.txt txt = ./txt/cord-298078-uqrwq5qk.txt === reduce.pl bib === id = cord-305303-82n96ukr author = Shapira, Assaf title = Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date = 2012-02-16 pages = extension = .txt mime = text/plain words = 10132 sentences = 431 flesch = 42 summary = As shown in Figure 2 , similar numbers of surviving colonies were observed when the cells were transfected with the plasmids encoding mCherry-NS3 activated MazF or the red fluorescent protein alone, suggesting that expression of NS3-activable ribonuclease in naïve HEK293 T-REx cells (that do not express NS3) cause minimal toxicity, if any. The ER membrane-targeted zymoxin colocalizes with NS3 protease in vivo Previously we described a HEK293 cell line which inducibly expresses (by addition of tetracycline) a fusion between EGFP and the coding sequence of the full length NS3 (including the helicase domain) followed by NS4A from HCV 1a genotype [10] . When infection reached ,50% (about 50% of the cultured cells showed expression of the HCV-core protein, as detected by immuno-staining and fluorescence microscopy), the mixed culture and a culture of uninfected cells were treated with NS3 activated MazF or uncleavable-MazF encoding adenoviruses at MOI of ,3. cache = ./cache/cord-305303-82n96ukr.txt txt = ./txt/cord-305303-82n96ukr.txt === reduce.pl bib === id = cord-306466-y4yg42p8 author = Nofal, Ahmed Maged title = Who complies with COVID-19 transmission mitigation behavioral guidelines? date = 2020-10-08 pages = extension = .txt mime = text/plain words = 5717 sentences = 292 flesch = 36 summary = Particularly, we examine if major personality traits (i.e. conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability) [12] , yield differences in the tendency of people to comply with 21 implemented COVID-19 transmission mitigation behavioral guidelines (see S1 Appendix). However, there has been no work examining the influence of personality traits, such as the big five (i.e. conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability) on the tendency of people to comply with COVID-19 transmission mitigation behavioral guidelines. Connecting literatures of emotional responses to COVID-19 messages, and personalized/tailored communication, we believe that this research not only supports prior work in highlighting the importance of pro-social messages, but also the importance of knowing the specific personality traits that may make individuals less likely to comply with COVID-19 transmission mitigation behavioral guidelines. First, drawing from research on persuasive mass communication [e.g., 19] , we aim to demonstrate if personality traits, specifically, conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability, relate to the tendency of people to comply with COVID-19 transmission mitigation behavioral guidelines. cache = ./cache/cord-306466-y4yg42p8.txt txt = ./txt/cord-306466-y4yg42p8.txt === reduce.pl bib === id = cord-297287-0i4nc353 author = Braun, Benjamin title = Simulating phase transitions and control measures for network epidemics caused by infections with presymptomatic, asymptomatic, and symptomatic stages date = 2020-09-10 pages = extension = .txt mime = text/plain words = 4005 sentences = 204 flesch = 49 summary = Using agent-based simulations on small world networks, we observe phase transitions for epidemic spread related to: 1) Global social distancing with a fixed probability of adherence. Phase transitions and control measures for network epidemics self-isolate in response to one infected social contact) all the way up to 97% with low levels of any type of social distancing. Because our goal is to understand the behavior of phase transitions regarding total number of infections in our model, we conducted secondary simulations on a refined parameter space based on the results of our regression tree analysis. There is also a clear interaction between the social distance probability and viral shedding parameters and the resulting number of infected agents and the length of the epidemic. Social distancing controls in this model exhibit a phase transition regarding total number of infections, either when imposed globally or when based on individual response to infected contacts. cache = ./cache/cord-297287-0i4nc353.txt txt = ./txt/cord-297287-0i4nc353.txt === reduce.pl bib === id = cord-302529-43pd2qsp author = El Moussi, Awatef title = Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia date = 2013-09-19 pages = extension = .txt mime = text/plain words = 3251 sentences = 163 flesch = 45 summary = METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. A subset of sentinel primary care physicians participating in virological surveillance schemes in the community submits respiratory samples for virological testing from patients presenting in primary health care with an ILI, as well as all regional emergency centres and hospitals that take on surveillance of influenza from community, hospitalized and fatal cases. Phylogenetic analysis of the HA1 nucleotid sequence of 23 influenza A(H1N1)pdm09 viruses from mild, severe (patients hospitalized with severe pneumonia and severe acute respiratory syndrome) and fatal cases, shows that all viruses characterised in Tunisia during season 2009-2010 were outside the seven genetic groups described in the European Centre for Disease Prevention and Control (ECDC) report [19] . cache = ./cache/cord-302529-43pd2qsp.txt txt = ./txt/cord-302529-43pd2qsp.txt === reduce.pl bib === id = cord-301811-ykpiorgo author = Tanaka, Takuma title = Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing date = 2020-10-28 pages = extension = .txt mime = text/plain words = 5530 sentences = 296 flesch = 55 summary = title: Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing We estimated the numbers of undiagnosed symptomatic patients and the lower bound of the number of total infected individuals per diagnosed patient before and after the declaration of the state of emergency in Hokkaido, Japan. The present analysis uses the distributions of the cluster size and patients' time from onset to diagnosis, which are released by the health officials, to estimate the model parameters. At the same time, the nodes in the connected component containing the diagnosed node are also removed from the network, which corresponds to the contact tracing of the infected individuals (Fig 2, gray open circles) . In this paper, we have formulated a model to describe the spreading of infection and the quarantine of infected individuals, and estimated the number of undiagnosed symptomatic and asymptomatic COVID-19 patients in Hokkaido. cache = ./cache/cord-301811-ykpiorgo.txt txt = ./txt/cord-301811-ykpiorgo.txt === reduce.pl bib === id = cord-305547-e66o5j85 author = Bénet, Thomas title = Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study date = 2015-12-22 pages = extension = .txt mime = text/plain words = 4161 sentences = 227 flesch = 43 summary = title: Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. The primary objective of this prospective case-control study was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children in Mali. pneumoniae, human metapneumovirus, RSV, and influenza A were the main microbial agents associated with pneumonia among children in Mali, independently of patient age, gender, period, and other pathogens. recently observed, in a pneumonia cases-control study implemented in hospitals of Utah, that detection respiratory syncytial virus, human metapneumovirus and influenza from nasopharyngeal or oropharyngeal sample of patients with pneumonia probably indicates an etiologic role [24] . cache = ./cache/cord-305547-e66o5j85.txt txt = ./txt/cord-305547-e66o5j85.txt === reduce.pl bib === id = cord-303331-xolksoy3 author = Pourghasemi, Hamid Reza title = Assessment of the outbreak risk, mapping and infection behavior of COVID-19: Application of the autoregressive integrated-moving average (ARIMA) and polynomial models date = 2020-07-28 pages = extension = .txt mime = text/plain words = 5988 sentences = 312 flesch = 55 summary = A geographic information system (GIS)-based machine learning algorithm (MLA), support vector machine (SVM), was used for the assessment of the outbreak risk of COVID-19 in Fars Province, Iran whereas the daily observations of infected cases were tested in the—polynomial and the autoregressive integrated moving average (ARIMA) models to examine the patterns of virus infestation in the province and in Iran. The aims of the present study were to analyze the risk factors of coronavirus outbreak and test the SVM model for mapping areas with a high risk of human infection with the virus in Fars Province, Iran. Accordingly, in this research, we selected sixteen most relevant effective factors for the outbreak risk mapping of COVID-19 in Fars Province of Iran, which includes minimum temperature of coldest month (MTCM), maximum temperature of warmest month (MTWM), precipitation in wettest month (PWM), precipitation of driest month (PDM), distance from roads, distance from mosques, distance from hospitals, distance from fuel stations, human footprint, density of cities, distance from bus cache = ./cache/cord-303331-xolksoy3.txt txt = ./txt/cord-303331-xolksoy3.txt === reduce.pl bib === id = cord-298131-zolwjl9u author = Xiao, Shuqi title = Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date = 2010-06-29 pages = extension = .txt mime = text/plain words = 9349 sentences = 429 flesch = 39 summary = Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. To investigate the regulation of the host response to the N-PRRSV virus, we considered the global gene expression profiles in lungs using Solexa/Illumina's DGE system, a tag-based transcriptome sequencing method. From the data presented in the paper, a model for the relationship between pulmonary gene expression profiles and infection pathology can be surmised in Figure 7 , N-PRRSV virus replicates and spreads by subverting host innate immune response and hijacking host lipid metabolism as well as inducing an antiapoptotic and anti-inflammatory state, as indicated by suppression expression of SPI IFN, IFN-a, down-regulation expression of proapoptotic genes for BAK, APR-1, SARP3, high levels expression of genes involved in lipid metabolism, such as APOE, LDLB, PIK3C3, anti-apoptotic genes for MCL1, BCL2A1, CHFR, ADM, NFKB, IL10, and anti-inflammatory molecule PGE2 as well as CD163. cache = ./cache/cord-298131-zolwjl9u.txt txt = ./txt/cord-298131-zolwjl9u.txt === reduce.pl bib === id = cord-303187-ny4qr2a2 author = Belo, Vinícius Silva title = Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil date = 2017-11-01 pages = extension = .txt mime = text/plain words = 7691 sentences = 410 flesch = 44 summary = Despite the perceived need and usefulness of such parameter estimates and recommendations for the most appropriate approaches applicable under such study designs [30] , survival and recruitment estimates of free-ranging dogs had not been obtained using methods of capture and recapture. In this study, we present estimates of abundance, survival and recruitment rates, and the probabilities of capture of two free-roaming dog populations by means of analytical models for open populations, so far unexplored in previous studies. We estimated critical parameters (survival, recruitment and abundance) that describe the population dynamics of free-roaming dogs based on a capture and recapture study design and on models suitable for open populations. Our study demonstrated the increase in population size in both areas, the predominance and greater recruitment of males, the temporal variability in recruitment and in survival probabilities, the lack of effect of sterilization on population dynamics, the influence of abandon and of density-independent factors and a high demographic turnover. cache = ./cache/cord-303187-ny4qr2a2.txt txt = ./txt/cord-303187-ny4qr2a2.txt === reduce.pl bib === id = cord-303490-rixuuytu author = Pazos, Michael A. title = Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice date = 2012-07-05 pages = extension = .txt mime = text/plain words = 6624 sentences = 385 flesch = 43 summary = These data suggest that despite significant morbidity associated with fetal gestation, pregnant mice have an impaired ability to control influenza virus infection in both lethal and nonlethal models. We did not observe any significant differences in the absolute number of cells infiltrating lung tissue during infection with X31 in pregnant ( Figure 5A ) or E2-treated mice (data not shown). In order to determine whether emigration from the lung was impaired, we investigated the number of dendritic cells in the draining mediastinal lymph node at key time points of infection and found no significant differences between pregnant mice and their non-pregnant controls ( Figure 5B ), or between E2-pelleted mice and their placebo controls (data not shown). We found strongly reduced levels of CD86 expression on CD11c+ cells at critical early time points after infection in both pregnancy ( Figure 5C ) and estrogen-treatment ( Figure 5D ), suggesting a deficiency in proper DC maturation. cache = ./cache/cord-303490-rixuuytu.txt txt = ./txt/cord-303490-rixuuytu.txt === reduce.pl bib === id = cord-302962-qw6s1t7j author = Hause, Ben M. title = Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease date = 2015-03-19 pages = extension = .txt mime = text/plain words = 4948 sentences = 280 flesch = 56 summary = Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations. The PCR assay specificity was confirmed using bovine rhinitis virus positive samples as determined by metagenomic sequencing as well as with cultures of common BRDC pathogens BVDV, BHV-1, BRSV, BCV, Mannheimia haemolytica, Histophilus somni, Pasteurella multocida and Mycoplasma bovis. As metagenomic sequencing of a nasal swab from a calf with acute respiratory disease identified concurrent infection with two bovine rhinitis virus species, we designed a 5'-nuclease reverse transcription PCR (rtPCR) assay targeting the conserved 3D polymerase gene to investigate the incidence of BRV in BRDC diagnostic submissions. cache = ./cache/cord-302962-qw6s1t7j.txt txt = ./txt/cord-302962-qw6s1t7j.txt === reduce.pl bib === id = cord-307934-84zfabti author = Lai, Chao-Kuen title = Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date = 2014-06-06 pages = extension = .txt mime = text/plain words = 8211 sentences = 465 flesch = 55 summary = Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. Both NS5A and Core proteins are found to be closely associated with and co-transported along the microtubules from the perinuclear region of cells via the LDs and endosomes to the plasma membrane. (A) The HCV-infected cells (at day 10 p.i.) were labeled with antibodies specific for Core protein (red) and NS5A (green) (upper row) or NS4B (green) (lower row). cache = ./cache/cord-307934-84zfabti.txt txt = ./txt/cord-307934-84zfabti.txt === reduce.pl bib === id = cord-306278-c4q4la5c author = Esposito, Susanna title = Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014 date = 2016-04-05 pages = extension = .txt mime = text/plain words = 4660 sentences = 220 flesch = 48 summary = To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. To evaluate the circulation of the different HAdV types and the possible relationship between viral load, viral genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children consecutively attending the Emergency Room of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection. However, further studies are needed to identify the potential pathogenetic role of the different species and types of HAdV and the importance of viral load in the severity of infection. cache = ./cache/cord-306278-c4q4la5c.txt txt = ./txt/cord-306278-c4q4la5c.txt === reduce.pl bib === id = cord-306958-8bx8kxxh author = Christensen, Sarah R. title = Political and personal reactions to COVID-19 during initial weeks of social distancing in the United States date = 2020-09-24 pages = extension = .txt mime = text/plain words = 4271 sentences = 223 flesch = 45 summary = This study examines individual attitudes, behaviors, anxieties, mental health impacts, and knowledge early in the pandemic response, as well as those outcomes by sociodemographic characteristics and political ideology. Four items asked respondents to indicate agreement on a 7-point scale that "events related to COVID-19 had interrupted" their social life, home life, work or vocational life, and/or hurt their mental health. Chi-square, t, and F tests were used to examine the influence of demographic characteristics, political ideology, and mental health on attitudes, knowledge, anxieties, behavior change, and impact variables. Initial covariate selection included all variables that were significant (p <0.05) in bivariate tests, including: political ideology, bias score for consumed news media, attitudes toward global warming and vaccination, sex, race, poverty level, and education. In the adjusted logistic regression model ( Table 2 ) liberals had 5.7 (95%CI: 3.3-9.7) and moderates had 2.5 (95%CI 1.5-4.3) times the odds of responding that the government had not done enough in response to COVID-19 compared to conservatives. cache = ./cache/cord-306958-8bx8kxxh.txt txt = ./txt/cord-306958-8bx8kxxh.txt === reduce.pl bib === id = cord-302189-3xab3yxc author = Tillmann, Ramona Liza title = Sensitive Commercial NASBA Assay for the Detection of Respiratory Syncytial Virus in Clinical Specimen date = 2007-12-26 pages = extension = .txt mime = text/plain words = 1777 sentences = 90 flesch = 45 summary = Thereby, NASBA turned out to be the most sensitive method with a total number of 80 RSV positive samples out of a cohort of 251 nasopharyngeal washings from patients suffering from clinical symptoms, followed by the inhouse RT-PCR (62/251) and ELISA (52/251). Despite an increasing number of newly detected respiratory pathogen the human Respiratory syncytial virus (RSV) remains the single most prevalent etiologic agent in pediatric viral respiratory tract infection [1, 2, 3] . In relation to the positive test results obtained with the NucliSENSH EasyQ NASBA, the relative sensitivity of the RT-PCR was 77,5% compared to 65% obtained with the NOWH RSV ELISA. The results showed that from the three tested methods for molecular diagnosis of RSV the NucliSENSH EasyQ NASBA (bioMerieux, Nürtingen, Germany) detected the most RSV positive samples in a cohort of 251 nasopharyngeal samples of pediatric patients hospitalized with respiratory disease. cache = ./cache/cord-302189-3xab3yxc.txt txt = ./txt/cord-302189-3xab3yxc.txt === reduce.pl bib === id = cord-305274-mcsdem7y author = Beniac, Daniel R. title = Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion date = 2007-10-24 pages = extension = .txt mime = text/plain words = 5463 sentences = 254 flesch = 51 summary = We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis. The structures of ACE2 bound to a fragment of the SARS spike containing the receptor-binding domain and the pre-and postfusion configurations of the fusion core heptad repeats of the spike have been solved to atomic resolution [2, 3, [24] [25] [26] . In addition, the atomic resolution structures of two neutralizing antibodies bound to the SARS spike receptor-binding domain have been solved [27, 28] showing that blocking of the receptor binding domain, preventing attachment of virions to cell-surface ACE2, is the likely mechanism of virus neutralization by these antibodies. cache = ./cache/cord-305274-mcsdem7y.txt txt = ./txt/cord-305274-mcsdem7y.txt === reduce.pl bib === id = cord-305071-4ck8nd24 author = Calvo, Cristina title = Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses date = 2015-07-06 pages = extension = .txt mime = text/plain words = 3527 sentences = 205 flesch = 49 summary = Human adenovirus (HAdV), a double-stranded DNA virus, causes a wide range of clinical syndromes and is a well-recognized agent of upper and lower respiratory infections in children [1, 2] . Although the literature on adenoviral infections in children is increasing, there are few prospective, long term studies, designed specifically to evaluate the role of HAdV in acute respiratory infections requiring hospitalization. Patients with influenza have fever more frequently (p = 0.028) and have a lower leukocytes count in blood (p<0.001), than children infected by HAdV. HAdV frequently (11% of cases) caused lengthy hospitalizations (more than 7 days) 21% of the single infections were diagnosed with pneumonia. Jin et al [13] , in China, describe similar findings, that children with RSV are younger than patients with HAdV, and have lower respiratory tract infections such as bronchiolitis and bronchitis more frequently. cache = ./cache/cord-305071-4ck8nd24.txt txt = ./txt/cord-305071-4ck8nd24.txt === reduce.pl bib === id = cord-305900-ht7hb2rc author = van den Brand, Judith M. A. title = Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets date = 2012-08-08 pages = extension = .txt mime = text/plain words = 9461 sentences = 442 flesch = 47 summary = Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. To this end, we inoculated ferrets with either seasonal human H3N2, pH1N1, or HPAI H5N1 virus, and performed detailed virological and pathological analyses at time points from 0.5 to 14 dpi, as well as measuring virus excretion, clinical signs, and hematological parameters. Comparable with the pattern of antigen expression in the respiratory tissues, high virus titers were seen in the nasal concha from 0.5 to 4 dpi with a peak on 1 dpi (Figure 3) . However, in the current study, we found very little H3N2 infection (based on virus antigen expression) in any cell types of the ferret lower respiratory tract ( Figure 3 ). cache = ./cache/cord-305900-ht7hb2rc.txt txt = ./txt/cord-305900-ht7hb2rc.txt === reduce.pl bib === id = cord-306135-pt4jsr6d author = Chan, Kamfai title = A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics date = 2016-02-12 pages = extension = .txt mime = text/plain words = 6292 sentences = 284 flesch = 56 summary = Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. This thermos thermal cycler (TTC) uses a very simple design that performs PCR amplification based on the "archaic" method of hand-transferring reaction tubes through a series of water baths, minimizing the temperature ramping time needed for PCR tubes to reach thermal equilibrium (Fig 1) . The TTC RT-PCR was performed using protocols similar to the HIV test, with PCR tubes transferred between three thermoses (reverse transcription, denaturation, and annealing/extension) and an optional room-temperature water bath. The gel photo in Fig 3 shows that the TTC can produce multiplexed amplicons with the correct sizes and that the yield is similar to a three-step reaction performed in the commercial cycler with same number of PCR cycles. cache = ./cache/cord-306135-pt4jsr6d.txt txt = ./txt/cord-306135-pt4jsr6d.txt === reduce.pl bib === id = cord-309621-6jj19xpr author = Yu, Pin title = Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus date = 2017-02-24 pages = extension = .txt mime = text/plain words = 4645 sentences = 214 flesch = 41 summary = The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. Although there have been several studies in animal models on the pathogenic mechanisms of MERS-CoV infection, little is known about the comparative pathology and inflammatory cell response in rhesus macaques or common marmosets infected with this virus. Pathological findings in the rhesus macaque tissues HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A) , pulmonary oedema (Fig 1B) , haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C) , and the infiltration of inflammatory cells. Using immunohistochemical techniques and an ISH analysis, we confirmed that MERS-CoV protein and viral RNA were distributed in the lungs of rhesus macaques and common marmosets and that they were primarily located in the pneumocytes and inflammatory cells. cache = ./cache/cord-309621-6jj19xpr.txt txt = ./txt/cord-309621-6jj19xpr.txt === reduce.pl bib === id = cord-303845-y6ws3u6x author = DeLisle, Sylvain title = Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections date = 2010-10-14 pages = extension = .txt mime = text/plain words = 5608 sentences = 246 flesch = 44 summary = Several factors, some of which have already been mentioned, may limit the generalizability of our results: 1) factors related to the performance of our study at the VA health care system: a) the veterans study population is mostly male and excludes the pediatric population, a key target for ARI surveillance [44] ; b) veterans health care utilization may differ from that observed in uninsured or privately insured individuals; c) clinical practices, documentation and coding habits by VA practitioners may differ from those observed in solo or group practices or in health systems subject to different financial or quality-control incentives; 2) factors related to our study period: optimal CDAs could differ outside the respiratory infection season, or during periods of heightened apprehension for an influenza epidemic; 3) factors related to our iterative CDA development process, which may have over adapted CDAs to VA's particular EMR implementation and to our sample dataset in particular, this despite our efforts to maintain a separation between development and validation data subsets; 4) factors related to our text mining approach: a) we did not employ a spell checker prior to applying the NegEx algorithm. cache = ./cache/cord-303845-y6ws3u6x.txt txt = ./txt/cord-303845-y6ws3u6x.txt === reduce.pl bib === id = cord-305811-987dhnf7 author = Cho, Che-Pei title = Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins date = 2013-04-29 pages = extension = .txt mime = text/plain words = 5837 sentences = 301 flesch = 49 summary = Because both 59CC-WT and 13363-13520 constructs share 27 identical nucleotides upstream of their slippery sites, the attenuation activity difference is not likely to be caused by an E-site flanking sequences effect [12, 13] but rather by the disruption of the two potential AU base pairs. We noticed a potential to form four extra base pairs between 59and 39-flanking sequences (GACG and CGUU, respectively) of the 6BPGC hairpin stem (and other deletion mutants) due to the existence of a 59 SalI cloning site (Fig. S1A ). The results (Fig. S1C ) indicate that the two potential base pairs involving E-site sequences are not the main cause of observed attenuation activity in 293T cell cultures. Furthermore, mutating two nucleotides (27 nucleotides upstream of the E site) to disrupt Watson-Crick base pairs in the lower hairpin stem dramatically impairs attenuation activity (Fig. 2) , indicating that attenuation is not caused by primary sequencemediated flanking-sequences effects [12, 13] . cache = ./cache/cord-305811-987dhnf7.txt txt = ./txt/cord-305811-987dhnf7.txt === reduce.pl bib === id = cord-308344-ao9z00t7 author = Diep, Nguyen Van title = Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation date = 2017-01-17 pages = extension = .txt mime = text/plain words = 4179 sentences = 193 flesch = 52 summary = title: Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. In this study, variants with large deletions in the S gene were found in eight primary and nine recurrent outbreaks from 16 pig farms, and they mostly (94.1%) coexisted with PEDV strains with an intact S gene. Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene New porcine epidemic diarrhoea virus variant with a large deletion in the spike gene identified in domestic pigs cache = ./cache/cord-308344-ao9z00t7.txt txt = ./txt/cord-308344-ao9z00t7.txt === reduce.pl bib === id = cord-305393-96mrxt8a author = Lai, Yvonne title = Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date = 2011-10-10 pages = extension = .txt mime = text/plain words = 9604 sentences = 587 flesch = 60 summary = Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. Transfection of two plasmids, one containing an interferon stimulated response element (ISRE) promoter-driven firefly luciferase and a second encoding a constitutively expressed Renilla luciferase allow the analysis of TLR3 activation by different RNAs. HEK 293T cells expressing WT TLR3 responded to poly(I:C) (1-2 mg/ml), better than viral dsRNAs (1-2 mg/ml) purified from Reovirus and BPEV (Fig. 1B) . cache = ./cache/cord-305393-96mrxt8a.txt txt = ./txt/cord-305393-96mrxt8a.txt === reduce.pl bib === id = cord-309194-jtouafgd author = Lu, Xiao title = Lung ultrasound score in establishing the timing of intubation in COVID-19 interstitial pneumonia: A preliminary retrospective observational study date = 2020-09-03 pages = extension = .txt mime = text/plain words = 3668 sentences = 191 flesch = 46 summary = PURPOSE: To investigate the role of lung ultrasound score (LUS) in assessing intubation timing for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Lung ultrasound was performed on days 1, 2, 3, 5, and 7 after patients were admitted to the ICU; if the patient was intubated, LUS determination was performed before intubation within 24 h (T1) and on days 1, 2, 5, and 7 after intubation (T2, T3, T4, and T5, respectively).The goal of this study was to evaluate the severity of lung aeration loss in intubated and non-intubated patients with SARS-CoV-2 pneumonia by ultrasound at different time points within one week. Few studies have addressed the timing of intubation for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia due to the high mortality of patients treated with invasive ventilation. The patient's gender, age, body mass index (BMI index), sequential organ failure assessment (SOFA score), and 28-day mortality rate were recorded; and the evolution of respiratory parameters between the two groups on time point T1 (lung ultrasound performed before intubation within 24 h) were also recorded. cache = ./cache/cord-309194-jtouafgd.txt txt = ./txt/cord-309194-jtouafgd.txt === reduce.pl bib === id = cord-310438-744r7gc3 author = Chan, Ta-Chien title = The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly date = 2010-06-25 pages = extension = .txt mime = text/plain words = 5083 sentences = 226 flesch = 40 summary = This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. The aims of this study were: (1) to evaluate the effectiveness of matching or mismatching influenza vaccine strains on influenzaassociated mortality, (2) to assess whether public health improvements during the post-SARS period might have decreased elderly mortality, and (3) to investigate molecular variation among vaccine-mismatched influenza viruses that may be associated with increased excess influenza-associated mortality. Explanatory variables for the above three outcome measures include monthly meteorological parameters (monthly means of temperature and humidity), annual periodic cycle (i.e., sine/cosine function of seasonal periodicity), monthly virus isolation rates for different subtypes/types of influenza viruses [A (H3N2) or A (H1N1) or B], matching status of different vaccine strains for each subtype/type in each of the studied years, post-SARS effect, and linear temporal monthly trends. cache = ./cache/cord-310438-744r7gc3.txt txt = ./txt/cord-310438-744r7gc3.txt === reduce.pl bib === id = cord-311074-j3fw4dfc author = Alviset, Sophie title = Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study date = 2020-10-14 pages = extension = .txt mime = text/plain words = 4842 sentences = 254 flesch = 49 summary = title: Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study From 27th March to 23rd April, consecutive patients who had respiratory failure or were unable to maintain an SpO2 > 90%, despite receiving 10–15 l/min of oxygen with a non-rebreather mask, were treated by continuous positive airway pressure (CPAP) unless the ICU physician judged that immediate intubation was indicated. The following baseline patient characteristics were retrieved from patient electronic medical record: sex, age, comorbidities, body mass index (BMI), withholding / withdrawal of lifesustaining therapies, associated COVID-19 therapies administered before the primary outcome under study occurred (antivirals, corticosteroids, immuno-modulating therapies, prone positioning), oxygen flow rate and SpO2 before and after starting CPAP treatment, duration of CPAP treatment, medical unit where CPAP treatment was performed, duration of invasive mechanical ventilation, SAPS2 score for patients admitted in ICU, driving pressure and P/F ratio on first day of mechanical ventilation. cache = ./cache/cord-311074-j3fw4dfc.txt txt = ./txt/cord-311074-j3fw4dfc.txt === reduce.pl bib === id = cord-307036-n44yml79 author = Ng, Oi-Wing title = Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody date = 2014-07-14 pages = extension = .txt mime = text/plain words = 8528 sentences = 392 flesch = 57 summary = Next, to determine if mAb 1A9 exhibits cross-neutralizing activity, S-pseudotyped virus particles, or S-pps, carrying the human SARS-CoV S or the various RBD-modified chimeric S of civet SARS-CoV SZ3 strain and bat SL-CoV Rp3 and Rf1 strains were generated and used to infect CHO-ACE2 cells in the absence or presence of different concentrations (100, 150 and 200 mg/ml) of mAb 1A9. Wild-type S, substitution S mutants, namely D1128A, N1056K, and that containing both D1128A and N1056K, were then expressed in 293 FT cells and Western Blot analysis was performed to determine the effects of these mutations on the binding of the S protein to mAb 1A9. (A) S-pp expressing S protein of humans SARS-CoV HKU39849, civet SARS-CoV SZ3, bat SL-CoV Rp3 and Rf1 and (B) S-pp containing wild-type or mutant D1128A, N1056K or D1128A/ N1056K S were generated and used to infect CHO-ACE2 cells at equal amount (as quantitated using P24 ELISA). cache = ./cache/cord-307036-n44yml79.txt txt = ./txt/cord-307036-n44yml79.txt === reduce.pl bib === id = cord-310061-nro623aa author = Valitutto, Marc T. title = Detection of novel coronaviruses in bats in Myanmar date = 2020-04-09 pages = extension = .txt mime = text/plain words = 3678 sentences = 192 flesch = 48 summary = Historically, bats have been linked to highly pathogenic viruses that pose a serious threat to human health, including the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the hemorrhagic ebola and Marburg filoviruses, and paramyxoviruses such as Nipah virus [10, 11, [13] [14] [15] [16] [17] [18] . The 2002-2003 SARS epidemic, the emergence of MERS in people in 2012, and the ongoing COVID-19 pandemic have prompted substantial interest in detecting coronaviruses of bat origin due to public health concern and their pandemic potential [10, [13] [14] [15] [16] [17] [18] . In addition to human-associated CoVs, bats are also hosts of coronaviruses that infect production animals, and have been implicated in the emergence and origin of swine acute diarrhea syndrome (SADS), transmissible gastroenteritis virus (TGEV) in pigs, and porcine epidemic diarrhea (PED), which can cause considerable losses [23] [24] [25] [26] . cache = ./cache/cord-310061-nro623aa.txt txt = ./txt/cord-310061-nro623aa.txt === reduce.pl bib === id = cord-310678-33c3mp1o author = Morgantini, Luca A. title = Factors contributing to healthcare professional burnout during the COVID-19 pandemic: A rapid turnaround global survey date = 2020-09-03 pages = extension = .txt mime = text/plain words = 3491 sentences = 214 flesch = 54 summary = INTERPRETATION: Burnout is present at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, and support for family, PPE, and mental health resources. assessed 376 Italian HCPs who interacted with COVID-19 infected patients for their reported burnout, psychosomatic symptoms and self-perceived general health, finding in their study population high emotional burnout, physical symptoms, and work-related pressure [7] . Across all countries (Fig 2) , in the multivariable regression analysis, reported burnout was associated with work impacting household activities (RR = 1�57, 95% CI = 1�39-1�78, P<0�001), feeling pushed beyond training (RR = 1�32, 95% CI = 1�20-1�47, P<0�001), exposure to COVID-19 patients (RR = 1�18, 95% CI = 1�05-1�32, P = 0�005), and making life prioritizing decisions due to supply shortages (RR = 1�16, 95% CI = 1�02-1�31, P = 0�03). cache = ./cache/cord-310678-33c3mp1o.txt txt = ./txt/cord-310678-33c3mp1o.txt === reduce.pl bib === id = cord-309981-4p3ybrn1 author = Dai, Ling-Ling title = Anxiety and depressive symptoms among COVID-19 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China date = 2020-08-28 pages = extension = .txt mime = text/plain words = 3554 sentences = 179 flesch = 43 summary = From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. As with other infectious diseases, preliminary evidence suggests that COVID-19 also causes public panic and mental health stress; symptoms of anxiety and depression are common psychological reactions to the COVID-19 pandemic, and may be associated with sociodemographic factors and sleep quality [6] [7] [8] [9] . This cross-sectional study examined the prevalence of anxiety, depression, and poor sleep quality among 307 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China, 2 months after the start of the COVID-19 pandemic. In addition, using one-sample-tests, it was determined that both SAS (42.92±7.30) and SDS (39.77±10.11) scores of the participants of our study were higher than Chinese norms (SAS, 29.78±10.07, n = 1158; SDS, 33.46±8.55, n = 1340) (both P<0.001) [26] , indicating more severe levels of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang hospitals, compared with the general public. cache = ./cache/cord-309981-4p3ybrn1.txt txt = ./txt/cord-309981-4p3ybrn1.txt === reduce.pl bib === id = cord-304616-k92fa15l author = Izes, Aaron M. title = Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date = 2020-08-05 pages = extension = .txt mime = text/plain words = 4208 sentences = 234 flesch = 50 summary = title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. Consequently, the aim of this study was two-fold: first, to develop and validate a high pressure liquid chromatography (HPLC) method to detect mefloquine in feline plasma, and second, to determine the in vitro plasma protein binding of mefloquine in both clinically normal and FIP-affected cats. Here, although a significant difference was found between the plasma protein binding of mefloquine in clinically normal and FIP-affected cats, due to the unknown biological variability of the assay, it is likely that this difference is equivocal. This study has validated an accurate and reliable assay to detect mefloquine in feline plasma and demonstrated that mefloquine is highly plasma protein bound in both clinically normal and FIP-affected cats. cache = ./cache/cord-304616-k92fa15l.txt txt = ./txt/cord-304616-k92fa15l.txt === reduce.pl bib === id = cord-309010-tmfm5u5h author = Dietert, Kristina title = Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia date = 2017-11-20 pages = extension = .txt mime = text/plain words = 7842 sentences = 414 flesch = 34 summary = Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. Transnasal infection with MERS-CoV following adenoviral transduction of human DPP4 yielded an expansive, (Fig 7A) interstitial pneumonia with severe alveolar epithelial cell necrosis and infiltration of mainly macrophages, lymphocytes, and fewer neutrophils (Fig 7B) . Different mouse models of acute pneumonia differ widely, with an obvious strong dependence on pathogen-specific features of virulence and spread, route of infection, infectious dose and other factors. cache = ./cache/cord-309010-tmfm5u5h.txt txt = ./txt/cord-309010-tmfm5u5h.txt === reduce.pl bib === id = cord-308261-hxlebas8 author = Broekhuis, Femke title = Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya date = 2019-04-03 pages = extension = .txt mime = text/plain words = 4771 sentences = 223 flesch = 52 summary = title: Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya To determine the static interactions between male cheetahs we calculated their space use and the amount of overlap for each dyad to determine the possibility that individuals could encounter each other either directly or indirectly. In general, cheetahs were closer to the encounter location after a possible encounter compared to before for all four time lags, apart from individual M03 in Dyad 3 where the opposite trend was Intraspecific interactions among carnivores: A case study of male cheetahs observed, however none of the results were significant (S1 Table) . Using GPS collar data we documented static and dynamic interactions between male cheetahs in Kenya's Maasai Mara and investigated the outcomes of these interactions in terms of movement behaviour and mortalities. cache = ./cache/cord-308261-hxlebas8.txt txt = ./txt/cord-308261-hxlebas8.txt === reduce.pl bib === id = cord-308249-es948mux author = Dokuka, Sofia title = How academic achievement spreads: The role of distinct social networks in academic performance diffusion date = 2020-07-27 pages = extension = .txt mime = text/plain words = 5043 sentences = 297 flesch = 48 summary = We examine the spread of academic achievements of first-year undergraduate students through friendship and study assistance networks, applying stochastic actor-oriented modeling. In this paper, we analyze the diffusion of academic performance across different types of student social networks. We analyze the spread of academic achievements within two different social networks of first-year undergraduate students. It was shown that achievements spread well within friendship networks, while other types of ties (e.g. online relationships) do not serve as channels for the performance transmission. In this paper, we examine the diffusion of academic achievements in two distinct social networks: friendship and study assistance. We analyze the longitudinal data on friendship and study assistance networks and GPA of a first-year student cohort of the Economics department in one of the leading Russian universities in 2013-2014 academic year. In this paper we explore the academic performance diffusion through two social networks of different natures: friendship and study assistance. cache = ./cache/cord-308249-es948mux.txt txt = ./txt/cord-308249-es948mux.txt === reduce.pl bib === id = cord-310466-0lbbiq7u author = Fu, Yang-chih title = Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan date = 2012-10-03 pages = extension = .txt mime = text/plain words = 4415 sentences = 204 flesch = 49 summary = To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation, we collected contact diaries from a representative national sample in Taiwan and extracted realistic parameters for our simulation modeling of disease infections. Our diary-based survey in Taiwan emphasizes the rigorous requirements on both systematic probability sampling and in-person (face-to-face) household interviews to ensure proper inference to the population as a whole. cache = ./cache/cord-310466-0lbbiq7u.txt txt = ./txt/cord-310466-0lbbiq7u.txt === reduce.pl bib === id = cord-312493-wbhji81g author = Tay, Ee Laine title = Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance date = 2013-10-11 pages = extension = .txt mime = text/plain words = 4303 sentences = 216 flesch = 49 summary = For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. Four independent surveillance data sources were used: (i) the Victorian GPSS, (ii) sentinel data from the Melbourne Medical Deputising Service (MMDS), (iii) routine laboratoryconfirmed influenza (LAB data) from the Victorian Infectious Diseases Reference Laboratory (VIDRL) and the (iv) Victoria Admitted Episode Dataset (VAED) for hospital admissions. Comparison of thresholds derived from different datasets revealed variations in defining the start of a season but relatively good agreement in describing the end and intensity of influenza seasons, except in the hospital data after the pandemic year. cache = ./cache/cord-312493-wbhji81g.txt txt = ./txt/cord-312493-wbhji81g.txt === reduce.pl bib === id = cord-310790-3ikgmiof author = Cherrak, Sabri Ahmed title = Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies date = 2020-10-15 pages = extension = .txt mime = text/plain words = 3471 sentences = 226 flesch = 50 summary = title: Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. The three compounds with highest affinity (Fig 2) for the active site are quercetin 3-rhamonoside, myricetin 3-rutinoside and rutin with binding energies of -9.7, -9,3 and -9.2 kcal.mol -1 respectively. Thirty eight flavonoids have been tested in this study by molecular docking against the active site of the SARS-CoV-2Mpro. Glycosylated flavonoids as SARS-CoV-2 Inhibitors: A molecular docking and simulation studies Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies cache = ./cache/cord-310790-3ikgmiof.txt txt = ./txt/cord-310790-3ikgmiof.txt === reduce.pl bib === id = cord-311065-ie3gty6e author = Gaddi, Pamela J. title = IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection date = 2012-08-03 pages = extension = .txt mime = text/plain words = 6591 sentences = 328 flesch = 46 summary = Further work has described a role for IL-10 in reducing systemic IFN-c production, CD4+ and CD8+ T cell cytokine responses and viral elimination in the spleen during MCMV infection [28] . The absence of IL-10 during acute MCMV infection results in elevated levels of systemic and local proinflammatory cytokines and chemokines, as well as increased inflammatory cell infiltration into infected livers. MCMV infection in the liver results in increased infiltration of NK cells, T cells and macrophages that contribute to viral clearance through cytokine and chemokine production [20, 23, 27, [38] [39] [40] . Virus-specific CD8+ T cells are recruited to the liver within 4 days of infection and control viral replication through release of cytotoxic molecules and production of cytokines such as IFN-c and TNF-a [18, [21] [22] [23] 26] . cache = ./cache/cord-311065-ie3gty6e.txt txt = ./txt/cord-311065-ie3gty6e.txt === reduce.pl bib === id = cord-310396-jitao9k0 author = Lei, Yu title = MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins date = 2009-03-07 pages = extension = .txt mime = text/plain words = 6031 sentences = 325 flesch = 46 summary = The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. Currently, there are no reports of viral proteins targeting MAVS for inhibition of virus-induced cell death responses. In this report, we describe a novel function of MAVS in mediating virus-induced apoptosis, and identify viral proteins as inhibitors of this response. In addition, the involvement of proteins on IFN axis in virusinduced host cell apoptosis has been implicated in another previous report, in which MAVS has been shown to be critical for reovirus-triggered caspase-3/7 activation in HEK293T cells [46] , however, the study did not evaluate whether MAVS mediates virus-induced apoptosis and what roles type 1 IFNs play in MAVS-mediated apoptosis. cache = ./cache/cord-310396-jitao9k0.txt txt = ./txt/cord-310396-jitao9k0.txt === reduce.pl bib === id = cord-312367-24huwt3y author = Coelho, Camila title = Biochemical screening for SARS-CoV-2 main protease inhibitors date = 2020-10-06 pages = extension = .txt mime = text/plain words = 3351 sentences = 210 flesch = 49 summary = As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 M(pro). As viral proteases, following polymerases, are the most prominent targets for antiviral drug design [9] , here we describe initial biochemical screenings with recombinant purified SARS-CoV-2 M pro performed in order to define possible candidates which could serve as lead compounds for the design of future COVID-19 therapies. In order to contribute to the ongoing worldwide research and development efforts to contain COVID-19, we cloned, expressed recombinantly in E.coli BL21(DE3) and purified an important drug target of SARS-CoV-2, its main protease (M pro ). From these obtained compounds, esculetin-4-carboxylic acid ethyl ester (IC 50 = 46 μM in M pro inhibition assays), a coumarin derivative and natural product, demonstrated an EC 50 of 112 μM (median toxic concentration TC 50 >800μM) in Vero-cell SARS-CoV assays [13] and MP576 (IC 50 = 2.5 μM), a quinolinecarboxylate, demonstrated an EC 50 of 7 μM (TC 50 >50μM) [15, 17] , thus validating the M pro biochemical screening approach for the development of SARS-CoV drugs. cache = ./cache/cord-312367-24huwt3y.txt txt = ./txt/cord-312367-24huwt3y.txt === reduce.pl bib === id = cord-312033-iarl77n0 author = López Barreda, Rodrigo title = Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile date = 2020-10-08 pages = extension = .txt mime = text/plain words = 4058 sentences = 235 flesch = 51 summary = The objective of this study was to assess the quality of life and psychological wellbeing of adults with congenital heart disease (CHD) in Chile, and to identify other associated factors. They completed a questionnaire, which included a quality of life assessment tool (the Medical Outcome Study 36-Item Short Form Health Survey), a number of psychological scales (the General Health Questionnaire, the Basic Psychological Needs Scales and the Beck Hopelessness Scale), a socioeconomic survey, and some clinical data. The primary aim of this study was to assess the QoL and psychological wellbeing of a population of adults suffering from CHD in Chile. Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile general population [5, 11, 38] . cache = ./cache/cord-312033-iarl77n0.txt txt = ./txt/cord-312033-iarl77n0.txt === reduce.pl bib === id = cord-308480-t2vukbwp author = Liang, Zhongjie title = Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant date = 2011-08-24 pages = extension = .txt mime = text/plain words = 4279 sentences = 206 flesch = 48 summary = In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. Taking two typical antibiotics, imipenem and carbapenem as example, the docked complex structures revealed that although the antibiotics adopted diverse conformations in the active site, the lactam motifs were positioned in the same orientation by coordinating with zinc ions tightly ( Figure 2C ), which suggested that the catalytic mechanisms were highly conserved among B1 subclass enzymes, as shown in Figure 3 . To gain the structural insight into the mechanism of the potent hydrolysis of NDM-1, the intermolecular interactions of three models of NDM-1, VIM-2 and FEZ-1 in complex with antibiotics meropenem were compared and analyzed in details ( Figure 4A -C). cache = ./cache/cord-308480-t2vukbwp.txt txt = ./txt/cord-308480-t2vukbwp.txt === reduce.pl bib === id = cord-303034-w72oeoxq author = Haischer, Michael H. title = Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic date = 2020-10-15 pages = extension = .txt mime = text/plain words = 4429 sentences = 216 flesch = 55 summary = To understand the demographics of mask wearers and resistors, and the impact of mandates on mask-wearing behavior, we observed shoppers (n = 9935) entering retail stores during periods of June, July, and August 2020. Wearing a mask in public is currently a controversial and politicized issue in the United States, even with case evidence from other countries that face coverings help to control the spread of coronavirus disease 2019 (COVID-19) [1] . To facilitate greater understanding and reliable experimental data on whether gender, age, location, and the presence of mask mandates influence mask wearing in the United States, we conducted a direct observational study at retail stores in Wisconsin. It is not surprising that our June data showed that older individuals wear masks more than middle-age and young people because older adults are at higher risk for more severe cases of COVID-19. cache = ./cache/cord-303034-w72oeoxq.txt txt = ./txt/cord-303034-w72oeoxq.txt === reduce.pl bib === id = cord-307540-dr5m9pfk author = Coelho, Flávio C. title = Assessing the spread of COVID-19 in Brazil: Mobility, morbidity and social vulnerability date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3517 sentences = 201 flesch = 52 summary = Probabilistic models were used to calculate the probability of COVID-19 spread from São Paulo and Rio de Janeiro, the initial hotspots, using mobility data from the pre-epidemic period, while multivariate cluster analysis of socio-economic indices was done to identify areas with similar social vulnerability. To identify regions with high geographical and social vulnerability, we proposed a classification scheme based on three main criteria: population mobility, socio-demographic-economic characteristics, and the available health care infrastructure in terms of hospital capacity. To assess the probability of COVID-19 spreading within Brazil, in the absence of mobility restrictions, we first calculated the effective distance (E f (i,j)) between micro-regions using the air travel data. We computed the effective distance, E f (i,j), between each micro-region and the two COVID-19's hotspots, Rio de Janeiro and Sao Paulo. Mostly urban micro-regions, with above-average life expectancy, with comparatively less social inequality, less population living in extreme poverty, better access to water supply and sewage disposal services, higher education. cache = ./cache/cord-307540-dr5m9pfk.txt txt = ./txt/cord-307540-dr5m9pfk.txt === reduce.pl bib === id = cord-312002-4qhvljpv author = Pacheco-Barrios, Kevin title = COVID-19 pandemic and Farr’s law: A global comparison and prediction of outbreak acceleration and deceleration rates date = 2020-09-17 pages = extension = .txt mime = text/plain words = 5434 sentences = 252 flesch = 56 summary = However, a 150-year old epidemics law promulgated by William Farr might be useful as a simple arithmetical model (percent increase [R1] and acceleration [R2] of new cases and deaths) to provide a first sight of the epidemic behavior and to detect regions with high predicted dynamics. In this study, we will model COVID-19 current data (until April 10, 2020) of new confirmed cases and deaths, from 210 countries as to test the assumptions of the 1840 Farr's law, to describe the epidemic dynamics, and also to make predictions to identify areas with high dynamic and suggest preparation and actions of health system in those regions. cache = ./cache/cord-312002-4qhvljpv.txt txt = ./txt/cord-312002-4qhvljpv.txt === reduce.pl bib === id = cord-308764-9z4qcoqz author = Wei, Lin title = Transcriptome Analysis of Houttuynia cordata Thunb. by Illumina Paired-End RNA Sequencing and SSR Marker Discovery date = 2014-01-02 pages = extension = .txt mime = text/plain words = 5253 sentences = 298 flesch = 51 summary = cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata and used Illumina paired-end sequencing technology to generate a large-scale EST database and develop a set of SSR markers. For further assessment of the assembly quality and development of new molecular markers, all 63,954 unigenes generated in this study were used to mine potential microsatellites, which were defined as di-to hexa-nucleotide SSRs with a minimum of four repetitions for all motifs. Here, the N50 length of the unigenes was 1,051 bp and the average length was 679 bp, which suggests that the relatively short reads from Illumina paired-end sequencing for this non-model organism have been effectively and accurately assembled. cache = ./cache/cord-308764-9z4qcoqz.txt txt = ./txt/cord-308764-9z4qcoqz.txt === reduce.pl bib === id = cord-311531-wezrs7gc author = Parčina, Marijo title = Multicenter evaluation of the QIAstat Respiratory Panel—A new rapid highly multiplexed PCR based assay for diagnosis of acute respiratory tract infections date = 2020-03-12 pages = extension = .txt mime = text/plain words = 3584 sentences = 179 flesch = 48 summary = The QIAstat Respiratory Panel(®) assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. The FilmArray RP is a multiplex sample-to-answer PCR panel that tests for 20 viral and bacterial pathogens on nasopharyngeal swabs in UTM at a time. Before resolution by discrepancy testing, QIAstat RP and FilmArray RP agreed on the detection of 376 pathogens in the 445 samples (Table 3) . After resolution by discrepancy testing on the Allplex RP, a total of 402 pathogen results were considered as true positive (Table 4) , of which QIAstat RP detected 394, for an overall PPA of 98.0% (95%CI 96.0%-99.1%). cache = ./cache/cord-311531-wezrs7gc.txt txt = ./txt/cord-311531-wezrs7gc.txt === reduce.pl bib === id = cord-311941-0dpm35dd author = Jones, Bryony A. title = Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study date = 2013-12-02 pages = extension = .txt mime = text/plain words = 5745 sentences = 253 flesch = 56 summary = Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A case had 18 times the odds of being born to a dam that was PregSurevaccinated rather than unvaccinated compared with a control, if the dam was first lactation and the calf did not receive colostrum from other cows, adjusting for type of milk fed (amOR 17.8; ci. A case had 3 times the odds of having been fed raw milk only from its dam rather than other types of milk (with or without dams milk) compared with a control (amOR 3.4; ci 1.6, 7.5; p = 0.002) when adjusting for dam PregSure-vaccination, lactation number and source of colostrum. Case control study to investigate risk factors for bovine neonatal pancytopenia (BNP) in young calves in southern Germany cache = ./cache/cord-311941-0dpm35dd.txt txt = ./txt/cord-311941-0dpm35dd.txt === reduce.pl bib === id = cord-310947-aqau2n7q author = Pan, Ji'An title = Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date = 2008-10-01 pages = extension = .txt mime = text/plain words = 6821 sentences = 302 flesch = 43 summary = In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. However, the viral protein interaction maps have been generated until now only for a limited number of viruses, including T7 bacteriophage [1] , vaccinia virus [2] , potato virus A [3] , pea seed-borne mosaic virus [3] , wheat steak mosaic virus [4] , hepatitis C virus [5, 6] , porcine teschovirus [7] , Kaposi sarcoma-associated herpesvirus [8] , and very recently severe acute respiratory syndrome coronavirus (SARS-CoV) [9, 10] . cache = ./cache/cord-310947-aqau2n7q.txt txt = ./txt/cord-310947-aqau2n7q.txt === reduce.pl bib === id = cord-309471-lr68epyb author = Xia, Jingya title = Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs date = 2014-12-08 pages = extension = .txt mime = text/plain words = 7010 sentences = 312 flesch = 42 summary = Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The presence of memory B cells in the culture is therefore detected as a TLR-agonist-induced increase in the number of antigen-specific, ASCs. To test for the presence of memory B cells at peripheral tissues, we stimulated lymphocyte populations isolated from bone marrow, spleen, vagina/cervix, or spinal cord/sensory ganglia of previously infected guinea pigs with a combination of LPS and CpG oligonucleotides and quantified HSV-specific ASC by ELISPOT. On day 7 post infection, HSV-specific, IFN-c-secreting T cells from the spleen, vagina/cervix, and lumbosacral ganglia and the adjacent spinal cord were quantified using a pair Peripheral Tissue-Resident Immune Memory to HSV-2 of previously described anti-guinea pig IFN-c -specific monoclonal antibodies [27] in an IFN-c ELISPOT assay. cache = ./cache/cord-309471-lr68epyb.txt txt = ./txt/cord-309471-lr68epyb.txt === reduce.pl bib === id = cord-311288-6ttux2uu author = Luo, Chen title = What triggers online help-seeking retransmission during the COVID-19 period? Empirical evidence from Chinese social media date = 2020-11-03 pages = extension = .txt mime = text/plain words = 6202 sentences = 385 flesch = 43 summary = We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion of help-seeking messages. For example, harness the social media posts to predict infected case counts and inform timely responses under the infoveillance or infodemiology framework [3, 4] ; analyze the help-seeking posts to identify the characteristics of COVID-19 patients [5] ; More retransmission means more users receiving the message, thus increasing the chance of getting help. There is plenty of research providing conceptual references, such as the depth of self-disclosure [16, 28] , different types of support messages [16, 29] , physical and emotional proximity to the target [30] , the social capital stock of the help seeker [22] . Enlightened by existing experience, we will summarize the impelling factors of help-seeking information diffusion into five dimensions: completeness, proximity, support typology, disease severity, emotion, and elaborate them in the following sections. cache = ./cache/cord-311288-6ttux2uu.txt txt = ./txt/cord-311288-6ttux2uu.txt === reduce.pl bib === id = cord-312678-81gnmxbk author = Elayeh, Eman title = Before and after case reporting: A comparison of the knowledge, attitude and practices of the Jordanian population towards COVID-19 date = 2020-10-15 pages = extension = .txt mime = text/plain words = 5442 sentences = 266 flesch = 52 summary = Our research group initiated a study to ascertain the knowledge, attitude and practices (KAP) of Jordanians toward COVID-19 prior to any initial case report in Jordan. Therefore, the initial aim of this study was to evaluate the overall knowledge, attitude and practices (KAP) of Jordanian citizens to the ongoing international situation regarding the emergence and pandemic nature of COVID-19. where N is the sample size, Zα: type one error = 1.96 when α = 5%; Zβ: type two error = 1.28 when β = 10%; Q = 1-P: expected non-prevalence; P = proportion in the population possessing the characteristic of interest (based on the estimate that 50% of the respondents knew general information about COVID-19, its routes of transmission and the main preventative measures), d = one-half of the desired interval of confidence, in this study d = 5%. cache = ./cache/cord-312678-81gnmxbk.txt txt = ./txt/cord-312678-81gnmxbk.txt === reduce.pl bib === id = cord-314651-e4uaw5fy author = Zhao, Guangyu title = Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus date = 2015-12-23 pages = extension = .txt mime = text/plain words = 4167 sentences = 184 flesch = 44 summary = After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. To assess viral replication and histopathologic damage following MERS-CoV infection, mice were euthanized with overdose inhalational carbon dioxide, and tissues included lungs, kidneys, livers, spleens, intestines and brains were harvested on indicated time points. Although a transgenic mouse model expressing human DPP4 was also established, and its immune response was studied after infection with MERS-CoV [16] , the transgenic mice in the study died on day 6 with only progressive pneumonia and mild perivascular cuffing in brain, and no neurological disorder or other multi-organ damage was observed. cache = ./cache/cord-314651-e4uaw5fy.txt txt = ./txt/cord-314651-e4uaw5fy.txt === reduce.pl bib === id = cord-315531-2gc2dc46 author = McGarvey, Peter B. title = Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date = 2009-09-25 pages = extension = .txt mime = text/plain words = 7016 sentences = 335 flesch = 39 summary = (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods. Here we describe in detail a protein-centric approach for systems integration of such a large and heterogeneous set of data from the NIAID Biodefense Proteomics program, and present scientific case studies to illustrate its application to facilitate the basic understanding of pathogen-host interactions and for the identification of potential candidates for therapeutic or diagnostic targets. cache = ./cache/cord-315531-2gc2dc46.txt txt = ./txt/cord-315531-2gc2dc46.txt === reduce.pl bib === id = cord-313107-6cfenpxm author = Singh, Anirudh K. title = Evaluation of pooled sample analysis strategy in expediting case detection in areas with emerging outbreaks of COVID-19: A pilot study date = 2020-09-22 pages = extension = .txt mime = text/plain words = 2889 sentences = 124 flesch = 50 summary = In this context, a pooled sample testing strategy was evaluated in the setting of emerging disease outbreak in 3 central Indian districts to assess if the cost of the test and turn-around time could be reduced without compromising its diagnostic characteristics and thus lead to early containment of the outbreak. At the reported point prevalence of 4.8% in this study, the negative predictive value of qRT-PCR on pooled samples was around 96% suggesting that the adoption of this strategy as an effective screening tool for COVID-19 needs to be carefully evaluated. We hypothesized that testing of pooled respiratory samples, collected from potentially infected individuals, could lead to faster laboratory confirmation and quicker containment of the emerging infection in these districts and, thus, undertook this study to evaluate the diagnostic concordance between the strategies of pooled vs. cache = ./cache/cord-313107-6cfenpxm.txt txt = ./txt/cord-313107-6cfenpxm.txt === reduce.pl bib === id = cord-313506-6bb4q7nv author = Sano, Akiko title = Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle date = 2013-10-24 pages = extension = .txt mime = text/plain words = 6695 sentences = 313 flesch = 54 summary = We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). Therefore, in an effort to improve B cell development and hIgG production in Tc cattle, we sought to enhance pre-BCR function by engineering a new HAC into which, in addition to the hIGH, hIGK and hIGL chromosome loci that carry the entire human immunoglobulin gene repertoire, the human VpreB (hVPREB1) and λ5 (hIGLL1) genomic loci from human chromosome 22 (hChr22) was incorporated, and part of CH and TM domains, CH2-TM, of hIGHM gene, was replaced by the corresponding bovine gene sequence (bovinization of the CH2-TM domains of hIGHM). doi: 10.1371/journal.pone.0078119.g002 DT40 colonies were screened with genomic PCR (data not shown) for the correctly modified hChr2, and clone K53 was identified and selected for the final HAC construction ( Figure 5 ). cache = ./cache/cord-313506-6bb4q7nv.txt txt = ./txt/cord-313506-6bb4q7nv.txt === reduce.pl bib === id = cord-309043-dlmx12vt author = von Brunn, Albrecht title = Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date = 2007-05-23 pages = extension = .txt mime = text/plain words = 6706 sentences = 341 flesch = 52 summary = The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. There are reports that a number of MHV and SARS-CoV replicase proteins colocalize and eventually interact in cytoplasmic membrane bound complexes, in which viral RNA synthesis occurs [18, 19] . We therefore cloned the SARS-CoV ORFeome by recombinatorial cloning (GATEWAY technology) and performed a genome-wide analysis for viral protein interactions by yeast-two-hybrid (Y2H) matrix screen. To systematically study the subcellular localization of viral proteins within eukaryotic HeLa cells the SARS-CoV ORFs were transfected in eukaryotic vectors with either N-or C-terminal Flag tags and detected with an anti-Flag antibody. In this study we report the cloning of the complete ORFeome of SARS-CoV and the results of a matrix-based yeast two-hybrid screen of pairwise viral protein-protein interactions. cache = ./cache/cord-309043-dlmx12vt.txt txt = ./txt/cord-309043-dlmx12vt.txt === reduce.pl bib === id = cord-315343-ywgoqlxj author = Ribeiro, Haroldo V. title = City size and the spreading of COVID-19 in Brazil date = 2020-09-23 pages = extension = .txt mime = text/plain words = 5473 sentences = 233 flesch = 58 summary = Our results indicate small towns are proportionally more affected by COVID-19 during the initial spread of the disease, such that the cumulative numbers of cases and deaths per capita initially decrease with population size. However, during the long-term course of the pandemic, this urban advantage vanishes and large cities start to exhibit higher incidence of cases and deaths, such that every 1% rise in population is associated with a 0.14% increase in the number of fatalities per capita after about four months since the first two daily deaths. Investigating whether this behavior generalizes to other places and how different quantities such as the number of cases and deaths scale with city size are thus important elements for a better understanding of the spreading of COVID-19 in urban areas. To test for an increasing urban advantage for the treatment of COVID-19 during the initial spread of the disease, we investigate the scaling relation between the number of hospital intensive care unit (ICU) beds and city population. cache = ./cache/cord-315343-ywgoqlxj.txt txt = ./txt/cord-315343-ywgoqlxj.txt === reduce.pl bib === id = cord-314908-kp2jznwb author = Roczniewska, Marta title = I believe I can craft! introducing Job Crafting Self-Efficacy Scale (JCSES) date = 2020-08-10 pages = extension = .txt mime = text/plain words = 9293 sentences = 532 flesch = 53 summary = To better predict these behaviors, we introduce the concept of job crafting self-efficacy (JCSE) and define it as an individual's beliefs about their capability to modify the demands and resources of their job to better fit their needs. In this project we integrate Social Cognitive Theory and the Job Demands-Resources model [6, 7] to introduce the concept of job crafting self-efficacy (JCSE). Based on the assumptions of Social Cognitive Theory, we also expect that these specific beliefs predict matching job-crafting behaviors, for example, individuals who feel self-efficacious with respect to increasing challenging job demands are more likely to start new projects or learn about new developments at work and try them out. cache = ./cache/cord-314908-kp2jznwb.txt txt = ./txt/cord-314908-kp2jznwb.txt === reduce.pl bib === id = cord-312817-gskbu0oh author = Witte, Carmel title = Spatiotemporal network structure among “friends of friends” reveals contagious disease process date = 2020-08-06 pages = extension = .txt mime = text/plain words = 5924 sentences = 274 flesch = 44 summary = These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown. Thus, the population represents a group of birds for which 1) a near-complete social network could be assembled from housing records that tracked dynamic movement over time, and 2) avian mycobacteriosis disease status could be determined for any bird that died. Although disease clustering among friends of friends could represent a contagious process, there is a possibility that some of the association could be explained by homophily, i.e., that connected birds could be more alike than the general bird population in terms of species, behavior, susceptibility, enclosure characteristics, etc. For this test, we evaluated disease clustering between a subject and its friends of friends from different enclosures that could not have transmitted infection based on the timing of the contact. cache = ./cache/cord-312817-gskbu0oh.txt txt = ./txt/cord-312817-gskbu0oh.txt === reduce.pl bib === id = cord-317244-4su5on6s author = Maganga, Gael D. title = Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity date = 2014-12-31 pages = extension = .txt mime = text/plain words = 3476 sentences = 191 flesch = 50 summary = In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. To further investigate the presence of the virus in bat populations, a strain-specific real-time RT-PCR assay (primers: GB09-478-F, 59-GGCGGCTCTTAAAAGT-GAATG-39; GB09-478-R, 59-GCGGGGTCAAATTGGTCAT-39; probe: GB09-478-P, 59-TCCAGCACAAACATATCCGAGAAGGCTAG-39) was designed within the initial PCR fragment and was used to test total RNA extracted from mixed liver and spleen samples from each of all the other bat species. In order to determine the organ distribution of this virus in infected bats, total RNA was extracted from heart, liver, spleen, kidney, lung, intestine and brain samples from all 14 real-time RT-PCR-positive bats, as described previously, and screened, using the same strain-specific real-time RT-PCR assay shown above. cache = ./cache/cord-317244-4su5on6s.txt txt = ./txt/cord-317244-4su5on6s.txt === reduce.pl bib === === reduce.pl bib === id = cord-316319-m6uha1qn author = Daleno, Cristina title = Phylogenetic Analysis of Human Rhinovirus Isolates Collected from Otherwise Healthy Children with Community-Acquired Pneumonia during Five Successive Years date = 2013-11-19 pages = extension = .txt mime = text/plain words = 3942 sentences = 177 flesch = 53 summary = In order to evaluate the circulation of the different human rhinovirus (HRV) species and genotypes in Italian children with radiographically confirmed community-acquired pneumonia (CAP), a nasopharyngeal swab was obtained from 643 children admitted to hospital because of CAP during five consecutive winter and early spring seasons (2007-2012). However, most of these studies were carried out in a single year and involved a relatively small number of patients, and only a few analysed specific LRTIs. Consequently, there are few data concerning the circulation of HRVs over a long period of time or the real role of the different species and genotypes in causing LRTIs. The aim of this study was to evaluate the circulation of the different HRV species and genotypes in Italian children with radiographically confirmed CAP during the winter and early spring of five consecutive years as this information could help to develop tailored strategies for the prevention and treatment of pediatric HRV infections. cache = ./cache/cord-316319-m6uha1qn.txt txt = ./txt/cord-316319-m6uha1qn.txt === reduce.pl bib === id = cord-316853-vaea6siv author = Xie, Nanzhen title = Prevalence of depressive symptoms among nurses in China: A systematic review and meta-analysis date = 2020-07-07 pages = extension = .txt mime = text/plain words = 4363 sentences = 229 flesch = 47 summary = Therefore, the primary aim of this study is to quantitatively assess the prevalence of depressive symptoms in nurses from Chinese mainland and its primary related influencing factors by systematic review and meta-analysis. The following information was extracted from all included studies: title, year of publication, province, sample size, number of positive cases, diagnostic methods and other potential factors that may affect the prevalence of depressive symptoms in nurses and that was provided in the studies. In addition, subgroup analysis was performed based on other potential sources of heterogeneity, such as province, regions (Northwest, Southwest, Northeast, South, Central, East and North China), severity of depressive symptoms, department, gender, age, job title, marriage, education background, shift work and hospital grade (if available). cache = ./cache/cord-316853-vaea6siv.txt txt = ./txt/cord-316853-vaea6siv.txt === reduce.pl bib === id = cord-316703-8kxx3034 author = Parera, Mariona title = Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date = 2012-08-01 pages = extension = .txt mime = text/plain words = 4193 sentences = 220 flesch = 52 summary = The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The target specificity for the MAVS and TRIF cleavage sites was tested by coexpressing them with CHV or HCV NS3/4A protease constructs. coli cells coexpressing the lambda cI repressor with either MAVS or TRIF cleavage site and a CHV NS3/4A construct, lambda phage replicated up to 2,000-fold more efficiently than in cells expressing a CHV protease variant that included a substitution in catalytic residue S139 ( Fig. 3A and 3B). In this study, we tested the ability of CHV NS3/4A protease to specifically cleave the human adaptor proteins MAVS and TRIF. Canine orthologs of human MAVS and TRIF differ in sequence at the cleavage site processed by HCV NS3/4A protease; therefore, they were not tested in this study. cache = ./cache/cord-316703-8kxx3034.txt txt = ./txt/cord-316703-8kxx3034.txt === reduce.pl bib === === reduce.pl bib === id = cord-318614-518giv0m author = Tsai, Jih-Jin title = A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos date = 2019-07-10 pages = extension = .txt mime = text/plain words = 4825 sentences = 213 flesch = 49 summary = A pan-dengue virus (DENV) RT-iiPCR, targeting the 5' untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease. Testing with the pan-DENV RT-iiPCR, the analytical and clinical performance of the fully automatic POCKIT Central system was comparable to those of the semi-automatic POCKI combo system, which was validated previously to offer performances equivalent to the CDC DENV1-4 real-time RT-PCR for the detection of DENV in human serum [7, 24, 26] . cache = ./cache/cord-318614-518giv0m.txt txt = ./txt/cord-318614-518giv0m.txt === reduce.pl bib === id = cord-317912-v2wovcqd author = Akmatov, Manas K. title = Equivalence of Self- and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens date = 2012-11-14 pages = extension = .txt mime = text/plain words = 3488 sentences = 176 flesch = 57 summary = found similar detection rates for respiratory pathogens between self-and staffcollected midturbinate swabs when one staff-collected and one selfcollected swab were taken from opposite nostrils during the same visit to a campus health center [5] . In the study center, a trained staff member (A.G.) obtained a nasal swab (regular flocked swab, Copan, Brescia, Italy, product number 359C) from the participant's left nostril and instructed him/her how to perform a self-swab. Sensitivity and specificity of self-collected swabs, obtained in the study center, to detect viral respiratory pathogens (compared to staff-collected swabs)*. The detection of a viral pathogen was independent of the amount of b-actin DNA in both staff-and self-swabs collected on day 1 (Fig. 4) . This prospective study comparing staff-and self-collected nasal swabs for the detection of ARI pathogens clearly demonstrated the validity of self-swabbing; specifically, self-swabbing was not inferior in terms of acceptance, satisfaction, sample adequacy, and viral detection rate. cache = ./cache/cord-317912-v2wovcqd.txt txt = ./txt/cord-317912-v2wovcqd.txt === reduce.pl bib === id = cord-318008-4s9eoae3 author = Parsons Leigh, Jeanna title = A national cross-sectional survey of public perceptions of the COVID-19 pandemic: Self-reported beliefs, knowledge, and behaviors date = 2020-10-23 pages = extension = .txt mime = text/plain words = 5682 sentences = 268 flesch = 48 summary = We assessed self-reported public perceptions related to COVID-19 including, beliefs (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) to understand perspectives in Canada and to inform future public health initiatives. We conducted a national survey of adults residing in Canada to gain a better understanding of public perceptions in several important domains-beliefs (e.g. severity of pandemic, concerns, impact on health), knowledge acquisition (e.g. sources, topics), and behaviors (e.g. isolation and physical distancing)-related to the COVID-19 pandemic. Our study provides a national cross-sectional description of public perceptions, knowledge and behaviors related to COVID-19 in the context of the evolving pandemic, adding to survey data published early in the outbreak [16] [17] [18] . In our survey, respondents from Ontario and Québec reported the least amount of trust in Canadian government and news sources and these were also the same provinces with the highest number of confirmed COVID-19 cases in Canada (32% and 51%, respectively). cache = ./cache/cord-318008-4s9eoae3.txt txt = ./txt/cord-318008-4s9eoae3.txt === reduce.pl bib === id = cord-319706-2e9jrv0s author = Ebinger, Joseph E. title = Pre-existing traits associated with Covid-19 illness severity date = 2020-07-23 pages = extension = .txt mime = text/plain words = 4904 sentences = 219 flesch = 40 summary = For all patients considered to have Covid-19, based on direct or documented laboratory test result and suggestive signs and/or symptoms, we obtained information from the electronic health record (EHR) and verified data for the following demographic and clinical characteristics: age at the time of diagnosis; sex; race; ethnicity; smoking status defined as current versus prior, never, or unknown; comorbidities, including obesity, as clinically assessed and documented by a provider with ICD-10 coding; and, chronic use of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) medications. For the primary outcome of illness severity, categorized by escalating levels of care (i.e., hospitalization, intensive care, intubation), the pre-existing characteristics that demonstrated statistical significance in age-and sex-adjusted models included older age, male sex, African American race, obesity, hypertension, diabetes mellitus, and the Elixhauser comorbidity score ( Table 2 ; Fig 3) . cache = ./cache/cord-319706-2e9jrv0s.txt txt = ./txt/cord-319706-2e9jrv0s.txt === reduce.pl bib === === reduce.pl bib === id = cord-319538-bawzonq1 author = Krause, Martin title = Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients date = 2020-09-18 pages = extension = .txt mime = text/plain words = 2565 sentences = 138 flesch = 35 summary = Based on observational studies from the epicenters of the pandemic in Wuhan, China, the Lombardy region in Italy, and the New York City area in the United States, a significant portion of patients diagnosed with coronavirus disease 2019 (COVID19) were admitted to the intensive care unit (ICU) for ventilatory support: Between 17%-24% of hospitalized patients and up to 72% of patients admitted to the ICU have required invasive mechanical ventilation [2] [3] [4] [5] . We aimed to identify if plasma procalcitonin levels on admission are associated with the duration of mechanical ventilation (primary outcome), 28-day mortality, and time to intubation (secondary outcomes) in a cohort of COVID-19 patients requiring mechanical ventilation. In the univariate analysis of our observational cohort study, procalcitonin levels >0.1 ng/ml on admission were associated with prolonged mechanical ventilation in critically ill COVID-19 patients. cache = ./cache/cord-319538-bawzonq1.txt txt = ./txt/cord-319538-bawzonq1.txt === reduce.pl bib === id = cord-319845-oob2ktnz author = Proença-Modena, José Luiz title = Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea date = 2011-06-20 pages = extension = .txt mime = text/plain words = 5857 sentences = 269 flesch = 51 summary = Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. This article reports a cross-sectional study of HBoV in ARI patients from Ribeirão Preto, Brazil, in which the shedding of VP1 mRNA in respiratory secretions was used as surrogate marker for active HBoV replication, to look for correlations with viral load, and presence of particular clinical manifestations and simultaneous detection of other respiratory viruses. The results of this cross-sectional study of HBoV in ARI patients from Ribeirão Preto, Brazil, indicate that shedding of VP1 mRNA in respiratory secretions, as a marker of HBoV replication, correlates positively with high viral load, presence of diarrhea, and lack of co-infection by other respiratory viruses. cache = ./cache/cord-319845-oob2ktnz.txt txt = ./txt/cord-319845-oob2ktnz.txt === reduce.pl bib === id = cord-321705-6a7avlro author = Hou, Tianya title = Social support and mental health among health care workers during Coronavirus Disease 2019 outbreak: A moderated mediation model date = 2020-05-29 pages = extension = .txt mime = text/plain words = 5372 sentences = 281 flesch = 46 summary = The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Thus, the present research employed a sample of Chinese health care workers during COVID-19 outbreak to explore a conceptual model in which, on the one hand, resilience mediated the association between social support and mental health; On the other hand, the indirect relationships between social support and mental health via resilience were moderated by age group. Considering the present study was to compare the indirect effect of social support on mental health via resilience between the young and middle-aged heath care workers, participants aged 50 or over were excluded. cache = ./cache/cord-321705-6a7avlro.txt txt = ./txt/cord-321705-6a7avlro.txt === reduce.pl bib === id = cord-317779-j67vb7f3 author = Irizarry, Kristopher J. L. title = RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date = 2017-08-28 pages = extension = .txt mime = text/plain words = 9733 sentences = 443 flesch = 42 summary = Our experimental design leveraged an initial 6 day window for monocytes to differentiate into macrophages, which was followed by IFNγ stimulation between 1 and 24 h to further characterize subsequent RNA gene expression and the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages The t-3 day time point, representing 3 days of differentiation in cell culture, exhibited the greatest expression of genes with a total of 11,429 expressed in both B19 and B2 birds while just 4068 genes lacked evidence of expression in both haplotypes. Overall, the gene enrichment analysis of the RNA sequence data provides a cellular-level picture of the specific biological processes that occur over time following activation of monocyte-derived macrophages. cache = ./cache/cord-317779-j67vb7f3.txt txt = ./txt/cord-317779-j67vb7f3.txt === reduce.pl bib === === reduce.pl bib === id = cord-319921-uxtydu60 author = Meli, Marina L. title = Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus) date = 2009-03-09 pages = extension = .txt mime = text/plain words = 5506 sentences = 259 flesch = 48 summary = METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. Furthermore, the presence of feline leukemia virus (FeLV) provirus was recently reported in six samples originating from both the Doñ ana and Sierra Morena areas in southern Spain between 1994 and 2003 [29] . Thus, in the present study, we report on the prevalence of the aforementioned pathogens and we describe a dramatic FeLV epidemic, which most likely led to the death of 6 Iberian lynxes within a 6-months period in 2007, its possible origin, and its relationship to other infectious agents. However, endogenous FeLV sequences related to those of domestic cats are apparently not present in Iberian lynxes: only 5 of the 77 lynxes tested displayed weak signals by quantitative realtime PCR, which is not compatible with presence of enFeLV sequences. cache = ./cache/cord-319921-uxtydu60.txt txt = ./txt/cord-319921-uxtydu60.txt === reduce.pl bib === id = cord-320938-f526k9q1 author = Chen, Hongjun title = Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses date = 2012-09-28 pages = extension = .txt mime = text/plain words = 8614 sentences = 455 flesch = 60 summary = In order to determine whether a Flu PCR amplicon could be transfected into cells and be amplified by the influenza polymerase complex, a PCR product was produced encoding the GFP reporter gene in negative orientation flanked by the influenza segment 7 untranslated regions (UTRs) and further flanked by the human pol1 promoter and the mouse t1 termination signal, pol1EGFPt1 (Fig. 1A, Fig. S1A , Table S1 ). doi:10.1371/journal.pone.0046378.g001 Efficient influenza virus rescue using Flu PCR amplicons in either ''1+7'' or ''2+6'' modes The pol1HA pdm t1 or pol1HA D072 t1 HA PCR amplicons (Table 1) were co-transfected into co-cultured 293T/MDCK cells in a ''1+7'' mode along with 7 RG plasmids encoding the corresponding additional gene segments from the influenza A/Puerto Rico/ 8/1934 (H1N1) strain (PR8). cache = ./cache/cord-320938-f526k9q1.txt txt = ./txt/cord-320938-f526k9q1.txt === reduce.pl bib === id = cord-321855-7b1c2xdh author = Alshami, Alanoud title = Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date = 2020-10-30 pages = extension = .txt mime = text/plain words = 3380 sentences = 190 flesch = 56 summary = title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. have examined 24 asymptomatic infected individuals with a history of close contact with SARS-COV-2 confirmed cases and found that only 20% of them developed symptoms. Our findings are in light with a recent study that reported a 59% prevalence of loss of taste and smell in a cohort of COVID-19 patients [15] . Sudden onset of loss of smell and taste were prevalent in our study and were key symptoms of mild disease. cache = ./cache/cord-321855-7b1c2xdh.txt txt = ./txt/cord-321855-7b1c2xdh.txt === reduce.pl bib === id = cord-320466-l7017jis author = Akgun, Emel title = Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients date = 2020-10-20 pages = extension = .txt mime = text/plain words = 3722 sentences = 226 flesch = 42 summary = Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified up-regulated proteins Myeloperoxidase, Myeloblastin, Neutrophil Elastase, Cathepsin G, and Azurocidin (MPO, PRTN3, ELANE, CTSG, and AZU1) in nasooropharyngeal swab samples are discussed to highlight the molecular mechanism changes in the site of infection. Pathway analysis of the significantly altered protein levels between COVID-19 positive and negative patients' naso-oropharyngeal swab samples were analyzed using the STRING online database. In SARS-CoV-2 patients' naso-oropharyngeal samples, we have identified azurophilic granule (AG) proteins like Myeloperoxidase (MPO), elastase (ELANE), cathepsin G (CTSG), azurocidin 1 (AZU1) and proteinase 3 (PRTN3) to be highly overexpressed. The alterations of various proteins in SARS-CoV-2 infected patients' naso-oropharyngeal samples depict the molecular changes that govern the host antiviral defense system. cache = ./cache/cord-320466-l7017jis.txt txt = ./txt/cord-320466-l7017jis.txt === reduce.pl bib === id = cord-321438-llnqzkqt author = Ma, Ruili title = Proteome Profile of Swine Testicular Cells Infected with Porcine Transmissible Gastroenteritis Coronavirus date = 2014-10-21 pages = extension = .txt mime = text/plain words = 7110 sentences = 310 flesch = 43 summary = The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV)-infected swine testicular (ST) cells in order to determine potential virus-host interactions. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Moreover, at the later time point, 64 hpi, our GO term analysis also indicated that a significant number of the differentially expressed proteins were related to cellular stress (p = 8.18E-4), generation of precursor metabolites and energy (p = 2.74E-3), cell motility (p = 6.71E-3), protein complex assembly (p = 4.69E-2), growth (p = 3.87E-2), developmental maturation (p = 1.53E-2), and immune system processes (p = 4.67E-2) ( Table 2) . Prior to proteomic analysis, we determined which time points to investigate following infection by observing the morphological changes and analyzing viral gene expression dynamics in the TGEV infected cells. cache = ./cache/cord-321438-llnqzkqt.txt txt = ./txt/cord-321438-llnqzkqt.txt === reduce.pl bib === id = cord-321834-n5w88l23 author = Huang, Cheng-Yang title = Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases date = 2015-05-19 pages = extension = .txt mime = text/plain words = 5231 sentences = 297 flesch = 47 summary = Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. In this study, we investigated the effects of the substrates and inhibitors of allantoinase and dihydroorotase, including the flavonols myricetin, quercetin, kaempferol, and galangin, on inhibiting the catalytic activity of a putative dihydropyrimidinase from P. Although dihydromyricetin and myricetin were docked Inhibition of Dihydropyrimidinase by Flavonoids into the active site pocket of dihydropyrimidinase, their binding modes differed. In this study, we showed that dihydromyricetin, a flavonol, significantly inhibited the catalytic activities of dihydropyrimidinase toward both the natural substrate dihydrouracil and xenobiotic substrate 5-propyl-hydantoin (Fig 3) . For example, as shown in Fig 3, the inhibitory effect of kaempferol on the activity of dihydropyrimidinase was significant only with dihydrouracil as a substrate (with IC 50 value of 50 ± 2 μM), but not with 5-propyl-hydantoin. cache = ./cache/cord-321834-n5w88l23.txt txt = ./txt/cord-321834-n5w88l23.txt === reduce.pl bib === id = cord-320091-2lrqubdl author = Badawi, Alaa title = Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis date = 2018-07-10 pages = extension = .txt mime = text/plain words = 8511 sentences = 411 flesch = 46 summary = The objective of this study is to systematically review the existing literature on the prevalence of the most common non-communicable comorbidities related to the cluster of metabolic syndromes-associated diseases, such as diabetes mellitus, heart diseases, hypertension, asthma, stroke and obesity in flavivirus infections and to evaluate the difference of their prevalence in severe vs. Data extracted from the selected studies in duplicate by two reviewers and included the first author's name, publication date, country, dates of recruitment, total sample size (divided to males and females), age estimates (from reported mean, median or the mid-point for age range of the highest subject frequency), procedures for case identification, type of flavivirus infection, severity of infection, prevalence of clinical manifestations (mild symptoms such as fever, headache, muscle pain, rash, and malaise together with severe symptoms as described below) and percentage of comorbidities including diabetes (both type I and type II, if mentioned), hypertension, heart diseases (due to the small sample size of individual conditions, we (Table 1) . cache = ./cache/cord-320091-2lrqubdl.txt txt = ./txt/cord-320091-2lrqubdl.txt === reduce.pl bib === id = cord-319190-esjfhztp author = Lu, Xi title = In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus date = 2013-07-02 pages = extension = .txt mime = text/plain words = 3288 sentences = 185 flesch = 45 summary = title: In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. In this study, we examined the in vitro activity of SNH and its potential for synergy when combined with antibiotics against a collection of hospital-associated MRSA (HA-MRSA) isolates recovered from various clinical samples in recent years. This study evaluated activity of SNH against MRSA and its potential for synergistic effect when combined with antibiotics. SNH in combination with OXA exhibited synergistic effect for all the five MRSA strains tested in time-kill analysis. cache = ./cache/cord-319190-esjfhztp.txt txt = ./txt/cord-319190-esjfhztp.txt === reduce.pl bib === id = cord-322414-dpx191xh author = Harke, Nina N. title = To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic date = 2020-09-15 pages = extension = .txt mime = text/plain words = 3778 sentences = 168 flesch = 43 summary = MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16(th)-22(nd) and April 20(th)-26(th) 2020. The complete survey (S1 File) included detailed queries on numbers of available hospital beds and operating room (OR) capacity, staff members, surgical caseloads with subcategorization of surgeries at three different time points: week 1) baseline week that portrays the numbers of a regular/representative week before the outbreak of COVID-19, week 2) March 16 th to 22 nd 2020 which represent the first week after the lockdown in Germany (confirmed cases in Germany on March 16 th 2020: 6,012 with 13 deaths) and week 3) April 20 th to 26 th (confirmed cases in Germany on April 20 th 2020: 141,672; 4,404 deaths and approximately 91,500 recovered) [1] . cache = ./cache/cord-322414-dpx191xh.txt txt = ./txt/cord-322414-dpx191xh.txt === reduce.pl bib === id = cord-318845-w7q5o8wc author = Pendell, Dustin L. title = Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility date = 2015-06-26 pages = extension = .txt mime = text/plain words = 8168 sentences = 409 flesch = 48 summary = This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. To assess the economic impacts of unintentional FMDv releases from NBAF, we follow [4, 7, [21] [22] to link supply shocks from an animal disease spread model with a multi-commodity, multi-market partial equilibrium model. To determine the total economic impact for a scenario, the changes in producer returns to capital and management and consumer welfare, government indemnification and non-indemnification expenditures, and the costs to the non-agricultural regional sector were summed together. Because the duration of the FMD outbreaks and number of animals culled and vaccinated are similar to the aerosol scenarios, the total economic impacts of the transference release scenarios are similar to impacts of an aerosol release, including the distribution of impacts by production types across time. cache = ./cache/cord-318845-w7q5o8wc.txt txt = ./txt/cord-318845-w7q5o8wc.txt === reduce.pl bib === id = cord-319675-mwy3t1ny author = Gu, Li title = Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia date = 2016-08-17 pages = extension = .txt mime = text/plain words = 3081 sentences = 164 flesch = 56 summary = At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). Our results suggest that a higher initial viral load (10 8 copy/ml) in the respiratory tract samples on day 5-7 after disease onset is a predictor for fatal clinical outcome. In one case, as shown in Fig 2, even though the patient presented with a higher viral load (10 8.32 copies / ml) in tracheal aspiration, which may be associated fatal outcome, his clinical manifestation recovered gradually with a downward trend in the viral load in respiratory tract and whole blood samples. A higher initial viral load (10 8 copy/ml) in the respiratory tract on day 5-7 after disease onset and sustained viremia for 2 weeks or more may be associated with fatal clinical outcomes. cache = ./cache/cord-319675-mwy3t1ny.txt txt = ./txt/cord-319675-mwy3t1ny.txt === reduce.pl bib === id = cord-323433-9km824uh author = van den Wijngaard, Cees C. title = Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work? date = 2010-04-29 pages = extension = .txt mime = text/plain words = 4787 sentences = 244 flesch = 49 summary = We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks. Geographic analysis methods -such as space-time scan statistics -may further increase the sensitivity of syndromic surveillance for detection of local outbreaks or of regional differences in regular seasonal epidemic diseases [2, 6] . The objective of this study was to evaluate to what extent syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. Of these, 6 belonged to influenza and/ or RSV related clusters (Figure 2a When repeating the weekly analyses with restricted time or spatial windows, both Legionnaires' disease outbreaks were still detected with the same timeliness. cache = ./cache/cord-323433-9km824uh.txt txt = ./txt/cord-323433-9km824uh.txt === reduce.pl bib === id = cord-324405-6uanhe2p author = Burke, Rachel M. title = Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States date = 2020-09-02 pages = extension = .txt mime = text/plain words = 6616 sentences = 242 flesch = 41 summary = To interrupt transmission and facilitate early identification of secondary cases (i.e., transmissions of SARS-CoV-2 from the original travel-related case patient to a close contact), public health authorities at the state, county, and local levels, in consultation with subject-matter experts from the U.S. Centers for Disease Control and Prevention (CDC), mobilized rapidly to place the patients under appropriate isolation and identify contacts exposed to these patients. To understand the prevalence of asymptomatic or pre-symptomatic infection, a convenience sample of actively monitored close contacts was selected from whom to request respiratory (nasopharyngeal [NP] and oropharyngeal [OP]) samples outside of diagnostic specimen collection procedures (i.e., while contacts were asymptomatic or, in some cases, symptomatic with � 1 previous negative SARS-CoV-2 result); some sites were able to request at least one set of samples from all close contacts, but most sites targeted sample collection mainly to close contacts determined to have had high-risk exposures, such as household members and some healthcare personnel. cache = ./cache/cord-324405-6uanhe2p.txt txt = ./txt/cord-324405-6uanhe2p.txt === reduce.pl bib === id = cord-322827-h33su548 author = Guan, Lili title = Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives date = 2015-04-07 pages = extension = .txt mime = text/plain words = 5056 sentences = 232 flesch = 50 summary = BACKGROUND: In 2005, China implemented a demonstration program known as "686" to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. This program has contributed to improving care for patients with severe mental disorders, including schizophrenia, psychosis, bipolar disorder and schizoaffective disorder, through increasing access to treatment and integrating hospital and community services designed to provide continuity of evidence-based care and to address patients' rights. Patients with severe mental disorders were followed-up about their medication adherence, mental health status, social functioning and family burden in 2009 and 2012 to investigate the changes over time following the unlocking efforts. The finding that more than 92% of those unlocked and entered into continuous treatment by the 686 Program remained free of restraints by 2012 demonstrates the feasibility of improving the human rights of persons with severe mental illness by increasing access to mental health care in the community [22] , even with limited societal resources. cache = ./cache/cord-322827-h33su548.txt txt = ./txt/cord-322827-h33su548.txt === reduce.pl bib === id = cord-322533-adqqm0n9 author = Sha, Dexuan title = Spatiotemporal analysis of medical resource deficiencies in the U.S. under COVID-19 pandemic date = 2020-10-14 pages = extension = .txt mime = text/plain words = 5189 sentences = 232 flesch = 49 summary = The study duration was mainly from February 15, 2020 to May 1, 2020 in the U.S. Multiple data sources were used to extract local population, hospital beds, critical care staff, COVID-19 confirmed case numbers, and hospitalization data at county level. Then, we developed two medical resource deficiency indices that measured the local medical burden based on the number of accumulated active confirmed cases normalized by local maximum potential medical resources, and the number of hospitalized patients that can be supported per ICU bed per critical care staff, respectively. In this report, three fundamental elements or features, i.e. ventilators, ICU beds, and critical care staff (CCS) were identified as medical resources to plan for or manage a COVID-19 pandemic, and it would be wise to consider the interconnections among these factors in a spatiotemporal data analysis framework. cache = ./cache/cord-322533-adqqm0n9.txt txt = ./txt/cord-322533-adqqm0n9.txt === reduce.pl bib === id = cord-323330-ghwhgkdm author = Ekundayo, Temitope Cyrus title = A global bibliometric analysis of Plesiomonas-related research (1990 – 2017) date = 2018-11-29 pages = extension = .txt mime = text/plain words = 4900 sentences = 279 flesch = 40 summary = Here, we carried out a bibliometric survey that aimed to examine publication trends in Plesiomonas-related research by time and place, international collaborative works, identify gaps and suggest directions for future research. The articles were evaluated in terms of annual and country-specific output, theme, domain clusters, international collaboration networks, citations, topical evolution related to keywords and co-occurrence networks, co-authorship, and funding. We used the search term "Plesiomonas shigelloides" to identify primary research articles published between 1990 and 2017. Health emergencies (e.g., outbreaks of infection) relating to emerging viral pathogens including Zika and Chikungunya viruses have driven the generation of new scientific knowledge, resulting in a significant increase in the number of research articles on these subjects [68] . The United States and Sweden dominated the list of top 20 countries most actively researching Plesiomonas in terms of numbers of articles and citations. cache = ./cache/cord-323330-ghwhgkdm.txt txt = ./txt/cord-323330-ghwhgkdm.txt === reduce.pl bib === id = cord-324410-be2ith3z author = Wang, Qi title = Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry date = 2007-06-13 pages = extension = .txt mime = text/plain words = 3772 sentences = 160 flesch = 48 summary = These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce the crystal structures of small-molecule guest-host complexes. Herein we report the results of our docking studies with 161 selected crystal structures of small-molecule guest-host complexes using the EUDOC program. These results show that the program is able to reproduce all 161 crystal structures and that the average interaction energy of these small-molecule complexes (250.1 kcal/mol) is nearly half of that of the 153 small molecule-bound protein complexes we studied in previous tests (2108.5 kcal/mol). The results also demonstrate the significant influence of crystal packing on small-molecule complex crystal structures and suggest that the EUDOC program is able to predict 3D structures of small-molecule guest-host complexes with reasonable reliability. cache = ./cache/cord-324410-be2ith3z.txt txt = ./txt/cord-324410-be2ith3z.txt === reduce.pl bib === id = cord-327199-ggomuomb author = Moerdyk-Schauwecker, Megan title = Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date = 2014-08-08 pages = extension = .txt mime = text/plain words = 6425 sentences = 288 flesch = 43 summary = In another example, the presence of host complement control proteins such as CD46, CD55 and CD59 in the viral envelope has been shown to protect against antibody dependent complement mediated virus lysis in several viruses including human T cell leukemia/ lymphoma virus type I [16] , human cytomegalovirus [16] , hepatitis C virus [17] , HIV-1 [18, 19] , extracellular enveloped vaccinia virus [20] , simian virus 5 [21] and mumps virus [21] . As discussed in the previous section, proteins not associated with the interior of the virion, including proteins embedded in the host derived viral envelope, can be identified by their absence in ProK treated samples or by a size shift upon ProK treatment. While many of the proteins identified in VSV virions appear to be associated with viral assembly, budding or the host-derived viral envelope, they may also have additional functions that affect virus replication. cache = ./cache/cord-327199-ggomuomb.txt txt = ./txt/cord-327199-ggomuomb.txt === reduce.pl bib === id = cord-321624-z2mntwef author = Kowitdamrong, Ekasit title = Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date = 2020-10-09 pages = extension = .txt mime = text/plain words = 3382 sentences = 184 flesch = 57 summary = AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. The objective of this study was to investigate the response of IgA and IgG antibodies to SARS--CoV-2 in serial blood samples collected from a population of Thai patients with confirmed COVID-19, and the association of these responses with the severity of the illness. The second subgroup included 49 plasma samples collected from May 1 to May 31, 2020, from patients under investigation (PUI) for COVID-19 with RT-PCR results that were negative for SARS-CoV-2. In the present study, 30% of COVID-19 patients developed positive IgA antibodies very early, within 3 days after the onset of symptoms. In the present study, 20% of the patients with mild symptoms did not develop any IgG antibodies specific to COVID-19, even after 2 weeks after the onset of symptoms. cache = ./cache/cord-321624-z2mntwef.txt txt = ./txt/cord-321624-z2mntwef.txt === reduce.pl bib === id = cord-326011-5rmhjbri author = Cui, Dawei title = Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study date = 2016-11-01 pages = extension = .txt mime = text/plain words = 3508 sentences = 172 flesch = 44 summary = title: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. Respiratory syncytial virus (RSV) is a leading cause of viral infection in children and older adults worldwide, particularly young children aged <5 years [1] . In this study, we aimed to evaluate the epidemiology, clinical characteristics and management of ALRIs caused by RSV infection among hospitalized patients of all age groups in eastern China between 2009 and 2013 in a hospital-based surveillance study. Clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants cache = ./cache/cord-326011-5rmhjbri.txt txt = ./txt/cord-326011-5rmhjbri.txt === reduce.pl bib === id = cord-325113-sou8xyld author = Kuiper, Johannes W. P. title = Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification date = 2020-11-02 pages = extension = .txt mime = text/plain words = 4973 sentences = 241 flesch = 51 summary = The use of unprocessed swap samples is enabled by employing a heat-stable RNAand DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. A RNA-and DNA-reading heat-stable polymerase reverse transcribes and amplifies viral RNA Evidence of an acute SARS-CoV-2 infection depends on the detection of viral RNA species in patient samples, which necessitates reverse transcription of RNA followed by PCR amplification of the resulting DNA. To evaluate the potential of the high-temperature RT-PCR protocol using Volvano3G for the detection of viral RNAs in patient material, we assessed the presence of SARS-CoV-2 in RNA isolated from a small cohort of COVID-19 suspected cases. Interestingly, for most positive samples detected by the high-temperature RT-PCR with Volcano3G, the cq-values were lower compared to the standard RT-PCR (Fig 3C and 3D) , indicating that the detection of SARS-CoV-2 from unprocessed patient material is not limited by the sensitivity of this direct approach. cache = ./cache/cord-325113-sou8xyld.txt txt = ./txt/cord-325113-sou8xyld.txt === reduce.pl bib === id = cord-324091-nljd2ok1 author = Gordon, Jennifer L. title = The psychological impact of fertility treatment suspensions during the COVID-19 pandemic date = 2020-09-18 pages = extension = .txt mime = text/plain words = 4497 sentences = 263 flesch = 49 summary = PURPOSE: To examine the psychological impact of fertility treatment suspensions resulting from the COVID-19 pandemic and to clarify psychosocial predictors of better or worse mental health. Participants completed a battery of questionnaires assessing depressive symptoms, perceived mental health impact, and change in quality of life related to treatment suspensions. Table 2 depicts the correlation between three personality traits (trait optimism, defensive pessimism, and intolerance of uncertainty) that were considered potentially relevant under the current circumstances, in relation to the overall change in quality of life and the mental health impact attributed to fertility treatment suspensions. The psychological impact of fertility treatment suspensions during the COVID-19 pandemic the final subscales are as follows: 1) avoidance, α = 0.82, 2) active coping, α = 0.71, 3) finding meaning, α = 0.72, 4) defensive pessimism, α = 0.66, 5) optimism, α = 0.80, 6) seek social support, α = 0.77, and 7) behavioural engagement, α = 0.67. cache = ./cache/cord-324091-nljd2ok1.txt txt = ./txt/cord-324091-nljd2ok1.txt === reduce.pl bib === id = cord-327534-f2wvh6la author = Zhou, Peng title = IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation date = 2014-08-06 pages = extension = .txt mime = text/plain words = 7736 sentences = 377 flesch = 52 summary = To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Regions containing putative IRF3 or IRF7 binding sites were identified from 2221 to 270 bp from the ATG of the bat IFN-b gene by comparison with human IFN promoters and cloned into the pGL4.1 expression vector (Promega). Analysis of the putative bat IRF7 promoter region around 1000 bp upstream of the start site of the ORF resulted in the identification of two IFN stimulated response elements (ISREs) and one nuclear factor kappa B (NF-kB) binding site. Our results demonstrate that even with a significant difference in its MyD88 binding region, bat IRF7 is still capable of inducing IFN-a transcription via MyD88 ( Figure 5 ). cache = ./cache/cord-327534-f2wvh6la.txt txt = ./txt/cord-327534-f2wvh6la.txt === reduce.pl bib === id = cord-322446-ddv86eoy author = Sharma, Kulbhushan title = SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus date = 2011-05-27 pages = extension = .txt mime = text/plain words = 8437 sentences = 512 flesch = 56 summary = We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. Analysis of 9b-YFP localization showed that in addition to the extranuclear region, some amount of 9b was also present within the nucleus similar to the SARS-CoV infected cells (Fig. S1 , panel (i), (ii) and (iii)). Panel (ii) shows that even in in-vitro transport assay, SARS-CoV 9b protein localizes in both cytoplasm as well as nucleus. As shown in panel (v), the SARS-CoV 9b protein was able to enter the nucleus even in the presence of WGA showing that its entry is independent of active transport pathway. The SARS-CoV 9b protein triggers caspase 3 mediated apoptosis when retained in the nucleus of mammalian cells While performing pulse-chase assays, we found that a significant number of Vero E6 cells, in which nuclear export of 9b has been inhibited (either by treating with LMB or using NES deficient 9b), were showing caspase 3 dependent apoptosis. cache = ./cache/cord-322446-ddv86eoy.txt txt = ./txt/cord-322446-ddv86eoy.txt === reduce.pl bib === id = cord-327257-doygrgrc author = Zhu, Jocelyn title = Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs date = 2020-07-28 pages = extension = .txt mime = text/plain words = 3686 sentences = 221 flesch = 50 summary = title: Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs This study employed deep-learning convolutional neural networks to stage lung disease severity of Coronavirus Disease 2019 (COVID-19) infection on portable chest x-ray (CXR) with radiologist score of disease severity as ground truth. Deep-learning convolutional neural network (CNN) was used to predict lung disease severity scores. In conclusion, deep-learning CNN accurately stages disease severity on portable chest x-ray of COVID-19 lung infection. This study tested the hypothesis that deep-learning convolutional neural networks accurately stage disease severity on portable chest x-rays using radiologists' severity scores as ground truths associated with COVID-19 lung infection. Deep-learning AI, specifically a convolutional neural network, is well suited to extract information from CXR and stage disease severity by training using chest radiologist determination of disease severity scores. In conclusion, deep-learning convolutional neural networks accurately stage lung disease severity on portable chest x-rays associated with COVID-19 lung infection. cache = ./cache/cord-327257-doygrgrc.txt txt = ./txt/cord-327257-doygrgrc.txt === reduce.pl bib === id = cord-323185-n0rubc72 author = Varshney, Bhavna title = SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b date = 2012-01-12 pages = extension = .txt mime = text/plain words = 5667 sentences = 345 flesch = 51 summary = Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. In this study, we confirmed the putative interaction of 3b and RUNX1b and observed in vivo recruitment of 3b on the RUNX1 binding element on the IL2 promoter in transiently transfected human T, jurkat cells. We next determined the positive effect of 3b-RUNX1b interaction on the expression of RUNX1b regulated chemokine MIP-1a, reported to be upregulated in SARS-CoV infected monocyte derived dendritic cells. To investigate whether 3b-RUNX1b interaction leads to the recruitment of 3b on RUNX1 binding elements on the endogenous IL2 promoter, ChIP assays were performed in RUNX1b/CBFb endogenously expressing jurkat cells that are abortively infected by SARS-CoV. To investigate the effect of SARS-CoV 3b protein on the RUNX1b transcriptional activity, reporter gene assays were performed using the mouse IL2 promoter. cache = ./cache/cord-323185-n0rubc72.txt txt = ./txt/cord-323185-n0rubc72.txt === reduce.pl bib === id = cord-324359-88vy3dre author = Kamara, Foday Mamoud title = How villagers in central Sierra Leone understand infection risks under threat of Covid-19 date = 2020-06-24 pages = extension = .txt mime = text/plain words = 2949 sentences = 163 flesch = 59 summary = We undertook fieldwork in two villages in central Sierra Leone to gain insight into how rural people faced with Covid-19 assess epidemic infection risks. Asked to explain their choices 48% of players cited information on infection risks modelled by the game and 31% stated that their choices reflected awareness of the need for personal action and respect for local regulations. The data relate to rural populations in Sierra Leone exposed both to Ebola Virus Disease (EVD) in 2014-15 and now to Covid-19 in 2020. Three kinds of responses (Table 5 , 89% of all remarks) dominated comments after people made choices in the game-need for rules governing e.g. quarantine, comments on personal capacities to prevent or avoid infection (often made in the context of justifying a choice for disease "mango"), and comments about the relative risks to be inferred from "reading the stones" (i.e. recognition of a pattern in the way the stones were cast, as in divination practices). cache = ./cache/cord-324359-88vy3dre.txt txt = ./txt/cord-324359-88vy3dre.txt === reduce.pl bib === id = cord-328627-cf8f71dr author = Jando, Julia title = Expression and regulation of the neutral amino acid transporter B(0)AT1 in rat small intestine date = 2017-09-15 pages = extension = .txt mime = text/plain words = 8971 sentences = 389 flesch = 50 summary = Protein abundance of B 0 AT1, ACE2 and CD13 along the small intestine was measured by Western blotting performed on brush-border membrane vesicles (bbmv) prepared from duodenum, proximal-, middle-and distal jejunum as well as ileum and quantified relative to the microvilli cytoskeletal protein β-actin,. Additionally, rats fed different diets (NP, HP and AA) were euthanized 3 h after light-onset (ZT3) or 3 h after light-offset The three proteins tested in these bbmv showed a clearly increasing expression level in distal direction along the small intestine, as shown for distal versus proximal jejunum at both time points (Fig 1C, right panels) . This suggested the possibility that rats on a HP or AA diet may have expressed more functional B 0 AT1 along the small intestine and performed a more efficient absorption of neutral amino acids like L-isoleucine. cache = ./cache/cord-328627-cf8f71dr.txt txt = ./txt/cord-328627-cf8f71dr.txt === reduce.pl bib === id = cord-331885-8zmuhebu author = Xu, Xiuyan title = Risk factor analysis combined with deep learning in the risk assessment of overseas investment of enterprises date = 2020-10-02 pages = extension = .txt mime = text/plain words = 3796 sentences = 208 flesch = 43 summary = To evaluate the overseas investment risks of enterprises and expand the application and development of deep learning methods in risk assessment, 15 national clusters are utilized as samples to analyze and discuss the overseas investment risk indicators of enterprises. Second, the Deep Neural Network (DNN) is introduced; a risk evaluation model is constructed for enterprise overseas investment. The results show that the major source of overseas investment risks includes basic resources, political systems, economic and financial development, and environmental protection. To build a risk assessment model for overseas investment of enterprises and evaluate investment risks scientifically and effectively, the Deep Neural Network (DNN) based on deep learning is introduced, which is an innovation. The above analysis suggests that a country's infrastructure, health care conditions, economic development level, environmental protection conditions, and political system are the key components that affect its risks of enterprise overseas investment [29, 30] . cache = ./cache/cord-331885-8zmuhebu.txt txt = ./txt/cord-331885-8zmuhebu.txt === reduce.pl bib === id = cord-326568-twv2i3fb author = Bruminhent, Jackrapong title = Clinical characteristics and risk factors for coronavirus disease 2019 (COVID-19) among patients under investigation in Thailand date = 2020-09-15 pages = extension = .txt mime = text/plain words = 4402 sentences = 245 flesch = 48 summary = To manage coronavirus disease 2019 (COVID-19), a national health authority has implemented a case definition of patients under investigation (PUIs) to guide clinicians' diagnoses. Multivariate analysis identified close contact with an index case (OR, 3.49; 95%CI, 1.49–8.15; P = 0.004), visiting high-risk places (OR, 1.92; 95%CI, 1.03–3.56; P = 0.039), productive cough (OR, 2.03; 95%CI, 1.05–3.92; P = 0.034), and no medical coverage (OR, 3.91; 95%CI, 1.35–11.32; P = 0.012) as independent risk factors for COVID-19 among the PUIs. The majority had favorable outcomes, though one (1.9%) died from severe pneumonia. Apart from close contact with an infected case and visiting high-risk places, we found that having no medical coverage and presenting with productive cough were predictors of being diagnosed with COVID-19 among PUIs. SARS-CoV-2 is an emerging respiratory virus that commonly causes no or mild respiratory tract infection and is occasionally complicated by severe pneumonia [1] . cache = ./cache/cord-326568-twv2i3fb.txt txt = ./txt/cord-326568-twv2i3fb.txt === reduce.pl bib === id = cord-329223-f84gjxm1 author = Kouokam, Joseph Calvin title = Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate date = 2011-08-02 pages = extension = .txt mime = text/plain words = 8837 sentences = 382 flesch = 47 summary = In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. When freshly-isolated PBMC were pre-incubated for 24 hrs with GRFT at various concentrations, washed and then infected with HIV-1 R5 strain BaL (without adding new compound), GRFT inhibited viral replication for 9 days of cell culture (Fig. 2) . In addition, the numbers of CD4 2 /CD25 + cells were elevated when PBMC were cultured in presence of PHA or ConA compared to their PBS and GRFT counterpart (Fig. 6 , left panel and data not shown). The heat map shown in Fig. 9A indicates that cells exposed for 24 hours to GRFT Lec-(1 and 8 mM), and low concentrations of GRFT (0.1 mM ) and CV-N (0.05 mM) showed comparable gene expression profiles to those that were incubated in presence of PBS alone. cache = ./cache/cord-329223-f84gjxm1.txt txt = ./txt/cord-329223-f84gjxm1.txt === reduce.pl bib === id = cord-328633-c31xsyeo author = Moser, Michael J. title = Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date = 2012-06-04 pages = extension = .txt mime = text/plain words = 7868 sentences = 441 flesch = 54 summary = Most RT-PCR protocols rely on two DNA polymerase (Pol) enzymes; a retroviral reverse transcriptase (RT) to copy RNA into cDNA and a thermostable DNA Pol to amplify the target sequence. Despite their wide use and general reliability, existing twoenzyme RT-PCR systems have several documented performance problems attributed to deficiencies inherent in retroviral RTs: 1) poor reagent stability, 2) low fidelity, 3) frequent rearrangements during cDNA synthesis, 4) secondary enzymatic activities (i.e. RNase H and strand switching), 5) bias for specific primers and templates, and 6) inhibition of PCR Pol enzymes [3, 4, 5, 6, 7] . We describe the discovery and biochemical attributes of one of these, 3173 Pol, its inherent RT activity and its incorporation into a single-enzyme PyroScriptH 2X RT-PCR Master Mix. The sensitivity, specificity and overall performance of this mix were compared to available one-and two-enzyme systems using a control MS2 RNA bacteriophage template, the clinically-relevant influenza A RNA and commonly used reference mRNA transcripts. cache = ./cache/cord-328633-c31xsyeo.txt txt = ./txt/cord-328633-c31xsyeo.txt === reduce.pl bib === id = cord-333208-tibtngy8 author = Muñoz-Moreno, Raquel title = Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date = 2016-04-26 pages = extension = .txt mime = text/plain words = 5867 sentences = 311 flesch = 45 summary = The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. Thus, our goal in the current work was to test whether the IFITM family of proteins affected early entry steps of ASFV infection in Vero cell cultures using the cell-adapted Ba71V isolate. Confocal microscopy experiments revealed that, IFITM1 was mainly distributed at the plasma membrane and to a lesser extent in perinuclear compartments, resembling endosomal structures (Fig 3C, lower left panel) , while endogenous IFITM1 was barely detected in Vero cells containing the empty vector (Fig 3C, upper left panel) . cache = ./cache/cord-333208-tibtngy8.txt txt = ./txt/cord-333208-tibtngy8.txt === reduce.pl bib === id = cord-328206-iylw1bvw author = Yu, Daojun title = Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date = 2012-11-09 pages = extension = .txt mime = text/plain words = 4070 sentences = 209 flesch = 48 summary = In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. So AllGlo quadruplex quantitative PCR has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, it is easy for designing the probes and primers of multiplex qPCR and can increase the detection throughput. Two aliquots were used for the detection of HPV6-11 and HPV16-18 mixed types by TaqMan uniplex probe fluorescence quantitative PCR (Guangzhou Da'an Diagnostic Co., Ltd., China). Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. cache = ./cache/cord-328206-iylw1bvw.txt txt = ./txt/cord-328206-iylw1bvw.txt === reduce.pl bib === id = cord-316287-4i1grvlr author = Yim, Sung Sun title = Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS) date = 2014-10-10 pages = extension = .txt mime = text/plain words = 6372 sentences = 281 flesch = 51 summary = During the cultivation for regeneration of sorted cells, differential growth rates among various clones (particularly non-specific clones) due to unregulated protein expression and differing cell viability can decrease the library screening efficiency, resulting in more rounds of sorting (longer duration) to isolate the potential antibody candidate [12] . The whole FACS screening rounds of the synthetic human antibody library against each viral antigen could be done in one day, and these results show that repeated FACS screening without regeneration of the sorted cells can be a rapid and efficient method to isolate potential antibody candidates in case of urgent requirements. For the FACS screening of a human synthetic antibody (scFv) library, three fluorescent antigen probes were chemically synthesized: (i) FITC-CRDNWHGSNRPW as an N1 epitope of H1N1 influenza virus [13] ; (ii) FITC-NSTTFHQALLDPRVRGLYF-PAGG as a PreS2 epitope of HBV [14] ; and (iii) FITC-PVTNVRGDLQVLAQK as a VP1 epitope of FMDV [15] . cache = ./cache/cord-316287-4i1grvlr.txt txt = ./txt/cord-316287-4i1grvlr.txt === reduce.pl bib === id = cord-330110-pamxy4av author = Teissier, Elodie title = Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date = 2011-01-25 pages = extension = .txt mime = text/plain words = 9268 sentences = 438 flesch = 48 summary = Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. By combining surface plasmon resonance, fluorescence and NMR spectroscopy approaches, we showed that Arb directly interacts with the phospholipid membrane interface, with an affinity in the micromolar range, comparable to the concentration inhibiting HCVpp membrane fusion by 50% (IC50). Altogether our results demonstrate that Arb interacts with the polar head of phospholipid membranes and protein motifs enriched in aromatic residues, suggesting that the inhibitory activity of Arb on HCV entry and fusion could involve both types of interactions. Conversely, Arb inhibition of HCVpp membrane fusion, as assessed by a in vitro model system where the only proteins present are the viral glycoproteins, could merely reflect the interaction of Arb on lipids and/or on motifs present in HCV glycoproteins of any genotype. cache = ./cache/cord-330110-pamxy4av.txt txt = ./txt/cord-330110-pamxy4av.txt === reduce.pl bib === id = cord-323133-gdg50omp author = Buzatto, G. P. title = The pathogens profile in children with otitis media with effusion and adenoid hypertrophy date = 2017-02-23 pages = extension = .txt mime = text/plain words = 4243 sentences = 209 flesch = 45 summary = OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Therefore, the present study was carried out to compare the detection of common respiratory viruses and bacteria in adenoids and middle ear fluid in children with OME and in controls. In our study, we used a sensitive method to detect nucleic acid of a comprehensive panel of respiratory viruses and bacteria to compare the microbial colonization of adenoid and its correspondence in the middle ear in both OME children and controls. Concluding, in children with OME and adenoid hypertrophy we observed higher detection rates of potentially pathogenic bacteria, but not respiratory viruses, by real-time PCR in middle ear samples, as compared to control patients without adenoid hypertrophy. cache = ./cache/cord-323133-gdg50omp.txt txt = ./txt/cord-323133-gdg50omp.txt === reduce.pl bib === id = cord-330749-xt4aa2ur author = Schilling, Stefan title = Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries date = 2014-10-28 pages = extension = .txt mime = text/plain words = 4124 sentences = 192 flesch = 41 summary = The term highly infectious diseases (HID) defines mostly viral and bacterial infections that (i) are easily transmissible from person to person; (ii) cause a life-threatening clinical illness with no or few treatment options; and (iii) pose a threat for both health care workers and the public, thus requiring specific infection control measures and public health planning [1] . Despite such efforts, no pooled data on isolation facilities resources, such as infrastructure design, technical equipment, capacity and access to intensive care, do exist. The study presented was performed by the European Network for Highly Infectious Diseases, EuroNHID, and set up to compare the operational management, resources, and technical equipment among isolation facilities with recommendations published. Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries cache = ./cache/cord-330749-xt4aa2ur.txt txt = ./txt/cord-330749-xt4aa2ur.txt === reduce.pl bib === id = cord-333522-zsdymkjd author = Gruse, Jeannine title = Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits date = 2016-01-11 pages = extension = .txt mime = text/plain words = 7010 sentences = 333 flesch = 46 summary = Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Basal blood samples were taken before the morning feeding on days 1, 2, 4 and 7 from the jugular vein using evacuated tubes containing either potassium-EDTA (1.2-2 mg/mL EDTA) for analyses of plasma metabolites, insulin, glucagon, immunoglobulins and acute-phase proteins or Li-heparin (12-30 IU heparin) for the determination of the cortisol and flavonol concentrations and the antioxidative status in the plasma. Feed intake, body temperature, heart and respiratory rate and plasma concentrations of metabolites, hormones, flavonols and markers of antioxidative status were analyzed by repeated measurement ANOVA using the MIXED procedure of SAS/STAT software and a model with the fixed factors diet, quercetin and day of life (repeated variable) and all interactions between the fixed factors. cache = ./cache/cord-333522-zsdymkjd.txt txt = ./txt/cord-333522-zsdymkjd.txt === reduce.pl bib === id = cord-335272-jypxi99z author = Sharma, Anupam Joya title = A cross-sectional study of psychological wellbeing of Indian adults during the Covid-19 lockdown: Different strokes for different folks date = 2020-09-03 pages = extension = .txt mime = text/plain words = 9794 sentences = 515 flesch = 52 summary = Moreover, both qualitative and quantitative study findings suggested that greater frequency of calling family members during lockdown could strengthen social relationships and increase social empathy. In response, our study of Indian adults unpacks how social factors such as sexual orientation, relationship status, and residence in high-infection areas, could be linked with several psychological outcomes during the lockdown. Next, we fitted separate multivariable linear regression models to estimate the association of the independent variables (sexual orientation, relationship status, high-risk group, and living in a state with high number of cases) with psychological outcomes (anxiety, depressive symptoms, Internet addiction and pornography consumption) adjusted for the sociodemographic covariates-age, gender, annual income, educational qualification, place of residence-and for individual personal resources (optimism and resilience). Our quantitative and qualitative findings both suggest that LGBT adults, compared to the heterosexuals, are at a higher risk of developing anxiety, depressive symptoms, and using pornography during the lockdown. cache = ./cache/cord-335272-jypxi99z.txt txt = ./txt/cord-335272-jypxi99z.txt === reduce.pl bib === id = cord-333853-p2kbjwpy author = Smee, Donald F. title = Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) date = 2011-10-13 pages = extension = .txt mime = text/plain words = 4585 sentences = 222 flesch = 48 summary = title: Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. Ad5-vectored mouse interferon (mDEF201) resulted in sustained IFN levels [16] , that completely protected mice from a lethal Western equine encephalitis virus infection when given intramuscularly at 10 7 plaque forming units (PFU)/ mouse up to 7 days prior to virus challenge [16] . The extent of inhibition of lung Intranasal treatments with mDEF201 (10 7 PFU/mouse) were given one time only on the indicated day prior to virus exposure. cache = ./cache/cord-333853-p2kbjwpy.txt txt = ./txt/cord-333853-p2kbjwpy.txt === reduce.pl bib === id = cord-334955-gnu92up6 author = Sutton, Jeannette title = COVID-19: Retransmission of official communications in an emerging pandemic date = 2020-09-16 pages = extension = .txt mime = text/plain words = 7800 sentences = 324 flesch = 41 summary = In this research, we examine message features shown in prior disasters to increase or decrease message retransmission under imminent threat conditions to develop models of official risk communicators' messages shared online from February 1, 2020-April 30, 2020. We develop a lexicon of keywords associated with risk communication about the pandemic response, then use automated coding to identify message content and message structural features. They found that actionable and instructive messages and those that included a visual image were highly shared regardless of the time period; however, daily updates in the form of forecasts or current weather conditions involving little uncertainty, as well as message features that increase interaction, such as direct replies and URLs, decreased message passing. Messages that include information sharing decreases retransmission; however, this content increased post emergency declaration by 61%. cache = ./cache/cord-334955-gnu92up6.txt txt = ./txt/cord-334955-gnu92up6.txt === reduce.pl bib === id = cord-333955-bnzbppof author = Biesold, Susanne E. title = Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date = 2011-11-30 pages = extension = .txt mime = text/plain words = 5016 sentences = 275 flesch = 51 summary = Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. Cells from Pteropus species have been shown to produce high amounts of interferon (IFN)-l after stimulation with the double-strand (ds)RNA analogue poly IC, and after infection with the bat-associated paramyxovirus, Tioman [13] . In accordance with the IFN mRNA induction, the highest equivalent amount of bioactive secreted IFN upon RVFV 13 virus infection and poly IC transfection was measured in EidNi/41.3 cells, followed by MEF and MA104 (Figure 3 ). Increases of infectious virus formation were about 1000-fold within 24 hpi, and specific infectivities, expressed as PFU per genome equivalent (PCR units), were highly comparable between cell cultures ( Figure 4C) . cache = ./cache/cord-333955-bnzbppof.txt txt = ./txt/cord-333955-bnzbppof.txt === reduce.pl bib === id = cord-334218-bkjfy66e author = Lin, Jung-Da title = Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak date = 2016-01-15 pages = extension = .txt mime = text/plain words = 3619 sentences = 176 flesch = 57 summary = title: Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak The objectives of the present study were to investigate the effects between a 1-year period before and after PEDV outbreak on a sow's reproductive traits on a commercial pig farm in Taiwan. The average number of mated females, average parity of farrowed sows, number of matings, number of farrowings, FR, RR, number of abortions, LMFY, percentage of sows mated by 7 days after weaning, WFSI, FI, NPDs, replacement rates of sows and sow culling rates of preand post-PEDV outbreak periods were compared using a Mann-Whitney test. In the present study, we compared the productivity index of gilts and sows between 1 year pre-and post-PEDV outbreak in a Taiwanese breeding herd. Impact of porcine epidemic diarrhea virus infection at different periods of pregnancy on subsequent reproductive performance in gilts and sows cache = ./cache/cord-334218-bkjfy66e.txt txt = ./txt/cord-334218-bkjfy66e.txt === reduce.pl bib === id = cord-329727-h47q76y8 author = Sisó-Almirall, Antoni title = Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona date = 2020-08-21 pages = extension = .txt mime = text/plain words = 3441 sentences = 201 flesch = 53 summary = CONCLUSION: Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts. Therefore, this study aimed to describe the clinical, biological and radiological manifestations, the evolution, treatments and mortality rate of patients with COVID-19 infection in the population of Barcelona city and determine the most important predictors of a poor prognosis. Signs and symptoms, the main available haematological and biochemical data and the results of imaging tests were recorded, as were comorbidities, the evolution, the hospitalization rate, intensive care unit (ICU) admission and the treatments received. This study summarizes the clinical, biological and radiological characteristics, evolution and prognostic factors of patients with COVID-19 disease in primary and community healthcare. https://doi.org/10.1371/journal.pone.0237960.t002 In bold, statistically significant independent predictive factors associated with hospitalization, death or ICU admission (logistic multivariate regression adjusted for age and sex). cache = ./cache/cord-329727-h47q76y8.txt txt = ./txt/cord-329727-h47q76y8.txt === reduce.pl bib === id = cord-329468-vjsurl60 author = Okino, Cintia Hiromi title = Early immune responses and development of pathogenesis of avian infectious bronchitis viruses with different virulence profiles date = 2017-02-15 pages = extension = .txt mime = text/plain words = 5853 sentences = 261 flesch = 48 summary = This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken. In this study, we found a suppressive effect on expression of some early innate and adaptive cell-mediated immune genes in the primary site of virus replication (trachea) from chickens infected with one of the tested IBV isolates (B). cache = ./cache/cord-329468-vjsurl60.txt txt = ./txt/cord-329468-vjsurl60.txt === reduce.pl bib === id = cord-329999-flzqm3wh author = Buchanan, Tom title = Why do people spread false information online? The effects of message and viewer characteristics on self-reported likelihood of sharing social media disinformation date = 2020-10-07 pages = extension = .txt mime = text/plain words = 13812 sentences = 728 flesch = 50 summary = Four studies (total N = 2,634) explored the effect of message attributes (authoritativeness of source, consensus indicators), viewer characteristics (digital literacy, personality, and demographic variables) and their interaction (consistency between message and recipient beliefs) on self-reported likelihood of spreading examples of disinformation. Descriptive statistics for participant characteristics (personality, conservatism, new media literacy and age) and their reactions to the stimuli (likelihood of sharing, belief the stories were likely to be true, and rating of likelihood that they had seen them before) are summarised in Table 2 . This evaluated the extent to which digital media literacy (NMLS), authority of the message source, consensus, belief in veracity of the messages, consistency with participant beliefs (operationalised as the total SECS conservatism scale score), age and personality (Extraversion, Conscientiousness, Agreeableness, Openness to Experience and Neuroticism), predicted self-rated likelihood of sharing the posts. cache = ./cache/cord-329999-flzqm3wh.txt txt = ./txt/cord-329999-flzqm3wh.txt === reduce.pl bib === id = cord-333413-8buawes0 author = Liebing, J. title = Health status of free-ranging ring-necked pheasant chicks (Phasianus colchicus) in North-Western Germany date = 2020-06-16 pages = extension = .txt mime = text/plain words = 5556 sentences = 306 flesch = 51 summary = Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. In 2014 and 2015, the Institute for Terrestrial and Aquatic Wildlife Research (ITAW), University of Veterinary Medicine Hannover, Foundation, Hannover and the Wildlife Research Institute, State Office for Nature, Environment and Consumer Protection of North Rhine-Westphalia caught free-living Ring-necked Pheasant chicks from Lower Saxony (Cuxhaven, Grafschaft Bentheim, Emsland, Osnabrück, Vechta), North Rhine-Westphalia (Coesfeld, Warendorf) and Schleswig-Holstein (Dithmarschen) to assess the health state by means of pathological, microbiological, virological, parasitological and toxicological investigations. cache = ./cache/cord-333413-8buawes0.txt txt = ./txt/cord-333413-8buawes0.txt === reduce.pl bib === id = cord-331652-oc5s1if2 author = Trudeau, Michaela P. title = Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) date = 2016-06-24 pages = extension = .txt mime = text/plain words = 5988 sentences = 294 flesch = 52 summary = title: Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. Therefore, the objective of this study was to determine if thermal and non-thermal methods of microbial inactivation, as well as the use of selected feed additives, are effective in reducing the survival of PEDV in experimentally contaminated swine feed. The PEDV showed a high thermal resistance in the dry feed samples and it was completely inactivated (3.0 log reduction) at each of the tested temperatures within 30 min. cache = ./cache/cord-331652-oc5s1if2.txt txt = ./txt/cord-331652-oc5s1if2.txt === reduce.pl bib === id = cord-330537-xz0wt1sz author = Biermann, Olivia title = Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review date = 2020-10-28 pages = extension = .txt mime = text/plain words = 5668 sentences = 307 flesch = 49 summary = title: Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review BACKGROUND: The World Health Organization (WHO) stresses the importance of active case-finding (ACF) for early detection of tuberculosis (TB), especially in the 30 high-burden countries that account for almost 90% of cases globally. OBJECTIVE: To describe the attitudes of National TB Programme (NTP) managers related to ACF policy development, implementation and scale-up in the 30 high-burden countries, and to review national TB strategic plans. Moreover, this study focuses on National TB Programme (NTP) managers, key stakeholders in developing and implementing ACF policies [13] . The study comprised a cross-sectional survey with NTP managers from 30 high TB burden countries, which included closed and open-ended questions designed to elicit quantitative and qualitative information, enhancing each other [15] . cache = ./cache/cord-330537-xz0wt1sz.txt txt = ./txt/cord-330537-xz0wt1sz.txt === reduce.pl bib === id = cord-336364-2ust3qoq author = Artigas, Laura title = In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date = 2020-10-02 pages = extension = .txt mime = text/plain words = 5858 sentences = 295 flesch = 45 summary = title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm This has provided 3 sets of proteins related with the infection process: 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lungcells infection set, and 3) acute respiratory distress (ARD) set. According to the findings by GUILDify, we confirm the effect of the combination of pirfenidone and melatonin in the entry points of the SARS-CoV-2 infection, specifically the neighbours of furin and GRP-78, and some proteins associated with ARD. 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lung-cells infection set, and 3) acute respiratory distress (ARD) set that is composed of 6 subsets (Alveolar macrophages, Monocytes, Neutrophils, Intermediate phase ARD, Late phase ARD and ARD cytokine storm). cache = ./cache/cord-336364-2ust3qoq.txt txt = ./txt/cord-336364-2ust3qoq.txt === reduce.pl bib === id = cord-336615-jfnj6l41 author = Wong, Sarah Sze Wah title = In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections date = 2014-01-22 pages = extension = .txt mime = text/plain words = 7875 sentences = 434 flesch = 54 summary = We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Second, the increased incidence of invasive candidiasis caused by non-albicans Candida (NAC) species, such as Candida glabrata, Candida tropicalis, Candida krusei or Candida parapsilosis, has been a major concern [13, 14] , because these infections are often associated with higher mortality and antifungal resistance than those caused by C. The antifungal activity of small molecules was assessed by disk diffusion and broth dilution assays (see below) using four groups of Candida isolates. cache = ./cache/cord-336615-jfnj6l41.txt txt = ./txt/cord-336615-jfnj6l41.txt === reduce.pl bib === id = cord-335859-k37jivp6 author = Wu, Daphne C. title = Predictors of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey date = 2020-10-21 pages = extension = .txt mime = text/plain words = 3112 sentences = 160 flesch = 52 summary = To understand the socio-demographic predictors of COVID symptoms, we conducted a logistic regression analysis where the outcome was self-reported symptoms suggestive of COVID infection which we defined in this study as the respondent reporting himself/herself and/or at least one member of the household having had a combination of fever (with or without hallucinations) and any of i) difficulty breathing/shortness of breath or ii) dry cough so severe that it disrupts sleep or iii) a loss of a sense of smell in the past month; and the explanatory variables were gender (male, female, or other), education level (high school and under, or some college/ university and higher), province, age, ethnicity (Indigenous, English and other European, or others), visible minority (defined as persons, other than Aboriginal peoples, who are nonwhite in race or colour) [6] , and number of household members. cache = ./cache/cord-335859-k37jivp6.txt txt = ./txt/cord-335859-k37jivp6.txt === reduce.pl bib === id = cord-336420-1a2u9p4t author = Söderman, Martina title = Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study date = 2016-06-16 pages = extension = .txt mime = text/plain words = 4200 sentences = 208 flesch = 46 summary = title: Frequent Respiratory Viral Infections in Children with Febrile Neutropenia A Prospective Follow-Up Study Advances in molecular methods have increased the sensitivity of viral diagnostics tests, with recent studies reporting the detection of respiratory viruses in the nasopharynx in 44-57% of childhood febrile neutropenia episodes using real-time polymerase chain reaction (PCR) [3] [4] [5] 12] . Viral nucleic acids were extracted from the NPA with a MagAttract Virus Mini M48 kit (Qiagen, Sollentuna, Sweden) and analyzed with in-house real-time PCRs for the following 16 viruses: adenovirus (HAdV); bocavirus (HBoV); coronaviruses NL63/OC43/229E/HKU1 (HCoV); enterovirus (EV); influenza virus A, including A(H1N1)pdm09 and B (Flu); metapneumovirus (HMPV); parainfluenza viruses 1-3 (PIV); respiratory syncytial virus (RSV) and rhinovirus (RV) [19] . These results support the theory holding that there is a causal relationship between respiratory viral infections and episodes of febrile neutropenia, but proving this theory will require more longitudinal studies with asymptomatic neutropenic control cohorts. cache = ./cache/cord-336420-1a2u9p4t.txt txt = ./txt/cord-336420-1a2u9p4t.txt === reduce.pl bib === id = cord-337795-khqx4t4q author = Pellecchia, Umberto title = Social Consequences of Ebola Containment Measures in Liberia date = 2015-12-09 pages = extension = .txt mime = text/plain words = 5120 sentences = 277 flesch = 50 summary = INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. To address these questions, this study was conducted to assess Liberian community perspectives on State-imposed Ebola public health and outbreak containment measures implemented in 2014 and 2015. The grids were organized according to three main themes: 1) general social perception of the epidemic and community's reactions; 2) funerary and burial practices before and during the epidemic, and opinions on cremation; and 3) health-seeking behaviours and perception of quarantine. Forced quarantine of asymptomatic contacts of positive cases was the main State-imposed measure that transformed social perceptions and practices. Cremation of bodies and forced quarantine, as ways to quickly reduce transmission of Ebola outbreak for the benefit of the larger public, produced social dynamics of resistance in the same population that they wished to protect. cache = ./cache/cord-337795-khqx4t4q.txt txt = ./txt/cord-337795-khqx4t4q.txt === reduce.pl bib === id = cord-335441-bj3me7p8 author = Jourdain, Elsa title = Influenza Virus in a Natural Host, the Mallard: Experimental Infection Data date = 2010-01-28 pages = extension = .txt mime = text/plain words = 6354 sentences = 311 flesch = 52 summary = Five of the six ducks excreted viral RNA in their feces on the first day post-inoculation (PI) and all samples (feces, cloacal and oral swabs) from all birds were positive on the second day PI (Figures 4 and S1 ). Intermittent and moderate (high ct-values) viral RNA shedding was detected for all birds in water, fecal or cloacal samples between day 1 and 7 after H7N7 re-inoculation ( Figure 4 ). Active H5 infection was confirmed only in one duck, by expression of H5-specific antibodies and detection of viral RNA in the various sample types (feces, water, oral and cloacal swabs) with a pattern similar to the H5-inoculated control bird. Eight 3-month-old male wild-type mallards (Anas platyrhynchos) of approximately the same body mass and size (measurement of the left wing, the right tarsus length and the distance from bill tip to back of the skull) were selected from a Swedish duck farm known from previous successive sampling to be free from IAV infection. cache = ./cache/cord-335441-bj3me7p8.txt txt = ./txt/cord-335441-bj3me7p8.txt === reduce.pl bib === id = cord-335880-m8gecsf0 author = Peci, Adriana title = Epidemiology of Enterovirus D68 in Ontario date = 2015-11-23 pages = extension = .txt mime = text/plain words = 4030 sentences = 218 flesch = 52 summary = In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data. Data for this study included specimens submitted for EV-D68 testing at PHOL from patients who presented with respiratory symptoms in different health care settings across Ontario, from September 1, 2014 to October 31, 2014. Percent positivity and descriptions of EV-D68 cases by timing of specimen collection, age, sex, setting, symptoms and local health unit of residence were analysed at the patient level. Bivariate and multivariate logistic regression analyses were performed at the patient level to compare cases and controls in terms of age, sex, settings, symptoms and timing of specimen collection. cache = ./cache/cord-335880-m8gecsf0.txt txt = ./txt/cord-335880-m8gecsf0.txt === reduce.pl bib === id = cord-330079-pdaowkop author = Xu, Lin title = Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China date = 2012-09-11 pages = extension = .txt mime = text/plain words = 4469 sentences = 205 flesch = 50 summary = To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. In our current study, we screened throat swab specimens from patients with acute respiratory tract infection symptoms for HBoV and other common respiratory viruses over a 12-month period using polymerase chain reaction (PCR) methods, and in addition, the molecular phylogeny and complete genome sequences of 2 HBoV strains were also analyzed. Of the 3460 samples collected from patients with respiratory tract infection symptoms and signs enrolled in the study during the period between March 2010 and February 2011, detection for 7 viruses, namely, Influenza, PIV, RSV, HMPV, HCoV, AdV and HBoV, showed that 1275 (36.8%) were found positive for one single virus and 112 (3.2%) were infected by more than one virus. cache = ./cache/cord-330079-pdaowkop.txt txt = ./txt/cord-330079-pdaowkop.txt === reduce.pl bib === id = cord-335505-s013j5ex author = Zhang, Chen title = Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China date = 2013-08-22 pages = extension = .txt mime = text/plain words = 3186 sentences = 173 flesch = 44 summary = BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. The RVP Fast assay simultaneously detects the following viruses: respiratory syncytial virus (RSV); influenza(IFV) A (H1, H3, and H5) and B viruses; parainfluenza viruse (PIV) 1, 2, 3, and 4; human metapneumovirus (hMPV); adenovirus(ADV); piconavirus(PIC) which includes enterovirus (EV) and rhinovirus (RV); human coronaviruse(HCoV) NL63, HKU1, 229E, and OC43; and human bocavirus(BoCA). To find the reason that causes severe infection, we performed complete comparison between VSARI patients and the SARI, including clinical signs, number of viral target, gender, and age(Table 3, Figure 2B ). To find the association between virus infection and clinical signs in SARI, binary logistic regression was performed between 4 commonly diagnosed respiratory abnormality, including anhelation, respiratory failure, heart failure and pleural effusion, and the viral target detected by xTAG® RVP FAST. cache = ./cache/cord-335505-s013j5ex.txt txt = ./txt/cord-335505-s013j5ex.txt === reduce.pl bib === id = cord-332922-2qjae0x7 author = Mbuvha, Rendani title = Bayesian inference of COVID-19 spreading rates in South Africa date = 2020-08-05 pages = extension = .txt mime = text/plain words = 3224 sentences = 169 flesch = 52 summary = In this work, we perform Bayesian parameter inference using Markov Chain Monte Carlo (MCMC) methods on the Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological models with time-varying spreading rates for South Africa. The results find two change points in the spreading rate of COVID-19 in South Africa as inferred from the confirmed cases. The second change point coincides with the start of a state-led mass screening and testing programme which has highlighted community-level disease spread that was not well represented in the initial largely traveller based and private laboratory dominated testing data. In this work we combine Bayesian inference with the compartmental SEIR and SIR models to infer time varying spreading rates that allow for quantification of the impact of government interventions in South Africa. SIR and SEIR model parameter inference was performed using confirmed cases data up to and including 20 April 2020 and MCMC samplers described in the methodology section. cache = ./cache/cord-332922-2qjae0x7.txt txt = ./txt/cord-332922-2qjae0x7.txt === reduce.pl bib === id = cord-336441-m6pur6td author = Wang, Changjian title = Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model date = 2019-02-11 pages = extension = .txt mime = text/plain words = 5186 sentences = 282 flesch = 45 summary = title: Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model Based on the apparent energy consumption data, a systematic and comprehensive city-level total carbon accounting approach was established and applied in Guangzhou, China. g. Stochastic impacts by regression on population, affluence, and technology (STIRPAT) model) are the most commonly applied methods for the scientific evaluation and quantitative analysis of factors influencing city-level carbon emissions, especially the Logarithmic Mean Divisia Index (LMDI) method based on the IDA framework. [51] performed a multi-sectoral decomposition analysis of city-level greenhouse gas emissions in Tianjin from 2001 to 2009, including the agricultural, industrial, transportation, commercial and other sectors, and the results showed that economic growth was the most important driver for emissions increments while energy efficiency was primarily responsible for emissions reductions. cache = ./cache/cord-336441-m6pur6td.txt txt = ./txt/cord-336441-m6pur6td.txt === reduce.pl bib === id = cord-335404-s48psqth author = Mukandavire, Zindoga title = Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios date = 2020-07-24 pages = extension = .txt mime = text/plain words = 3570 sentences = 183 flesch = 48 summary = We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83–3.33). Here, we adapt a susceptible-exposed-infected-removed (SEIR) compartmental model to quantify early transmissibility of COVID-19 in South Africa and explore the potential utility of a vaccine in containing the disease. Following a similar approach in [37] , we use a Markov Chain Monte Carlo (MCMC) within a Bayesian framework (in R FME package [38] ) to fit the model to the cumulative data of confirmed COVID-19 cases in South Africa and estimate the magnitude of the epidemic using the basic reproductive number and quantify required vaccines' attributes to stem similar outbreaks. cache = ./cache/cord-335404-s48psqth.txt txt = ./txt/cord-335404-s48psqth.txt === reduce.pl bib === id = cord-333248-5342lyeu author = Elenius, Varpu title = The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response date = 2017-02-24 pages = extension = .txt mime = text/plain words = 3309 sentences = 206 flesch = 45 summary = We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T celland innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. We studied how serum vitamins and antimicrobial peptide LL-37 levels and allergic and tonsillar diseases were associated with direct in vivo detection of respiratory viruses and T cell subset-related transcription factors, cytokines as well as type I, II and III interferons in tonsils. The associations of serum levels of vitamins and LL-37, allergy status and virus detection with intratonsillar cytokine and transcription factor expressions were analyzed using univariable and age-adjusted linear regression. This study provides new insights into connections between serum levels of vitamins A, D, and E and antimicrobial peptide LL-37 and several important outcomes: allergy, respiratory virus detection and tonsillar immune responses. cache = ./cache/cord-333248-5342lyeu.txt txt = ./txt/cord-333248-5342lyeu.txt === reduce.pl bib === id = cord-338067-vjyad10p author = Hao, Yan title = Prediction and analysis of Corona Virus Disease 2019 date = 2020-10-05 pages = extension = .txt mime = text/plain words = 4775 sentences = 258 flesch = 59 summary = In this study, the development trend analysis of the cumulative confirmed cases, cumulative deaths, and cumulative cured cases was conducted based on data from Wuhan, Hubei Province, China from January 23, 2020 to April 6, 2020 using an Elman neural network, long short-term memory (LSTM), and support vector machine (SVM). In the present study, three methods, namely, an Elman neural network, LSTM, and SVM are applied to predict and analyze COVID-19 data from January 23, 2020 to April 6, 2020 in Wuhan, Hubei Province, China, including cumulative confirmed cases, confirmed new cases, cumulative deaths, new deaths, and cumulative cured cases and new cured cases. Experimental results showed that the Elman neural network and SVM adopted in this study can accurately predict the development trend of COVID-19, whereas LSTM is more suitable for the prediction of cumulative confirmed cases. cache = ./cache/cord-338067-vjyad10p.txt txt = ./txt/cord-338067-vjyad10p.txt === reduce.pl bib === id = cord-333650-4towah1t author = Malmo, Jostein title = Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date = 2016-05-12 pages = extension = .txt mime = text/plain words = 4659 sentences = 250 flesch = 50 summary = Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . cache = ./cache/cord-333650-4towah1t.txt txt = ./txt/cord-333650-4towah1t.txt === reduce.pl bib === id = cord-339789-151d1j4n author = Hong, Hyokyoung G. title = Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic date = 2020-07-21 pages = extension = .txt mime = text/plain words = 3934 sentences = 286 flesch = 60 summary = title: Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic However, time-independent parameters in the classical models may not capture the dynamic transmission and removal processes, governed by virus containment strategies taken at various phases of the epidemic. We propose a Poisson model with time-dependent transmission and removal rates to account for possible random errors in reporting and estimate a time-dependent disease reproduction number, which may reflect the effectiveness of virus control strategies. To choose the optimal number of knots for each country when implementing the spline approach, we used 5-fold cross-validation by minimizing the combined mean squared error for the estimated infectious and removed cases. Our model accommodates possible random errors and estimates a timedependent disease reproduction number, R 0 ðtÞ, which can serve as a metric for timely evaluating the effects of health policies. cache = ./cache/cord-339789-151d1j4n.txt txt = ./txt/cord-339789-151d1j4n.txt === reduce.pl bib === id = cord-339026-eu11larc author = Ryals, Renee C. title = The effects of PEGylation on LNP based mRNA delivery to the eye date = 2020-10-29 pages = extension = .txt mime = text/plain words = 4786 sentences = 257 flesch = 46 summary = Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. Most intriguingly, these particles successfully transfect RPE, Müller glia, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. Since the subretinal injection places the LNPs in close proximity to the RPE, we utilized this method to understand how PEGylation and size may impact intracellular delivery ( In general, for all particles, luciferase activity in the eye was measurable at 4 hours post-injection, increased to a maximum level at 24 hours post-injection and decreased by 48 hours post-injection (Figs 2B and 3B). cache = ./cache/cord-339026-eu11larc.txt txt = ./txt/cord-339026-eu11larc.txt === reduce.pl bib === id = cord-336843-c0sr3six author = Gerritsen, M. G. title = Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography date = 2017-02-24 pages = extension = .txt mime = text/plain words = 4321 sentences = 239 flesch = 49 summary = title: Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. Two studies comparing LDCT to CXR in patients with persistent febrile neutropenia demonstrated an increased detection of pulmonary abnormalities. The diagnosis of possible IFD in the patient with a negative LDCT scan was based on abnormalities on HRCT made on day 4 of fever. We conducted a prospective study to evaluate whether pulmonary focus detection would improve using a LDCT scan instead of CXR on the first day of febrile neutropenia. [3] In a retrospective study 1083 adult SCT patients were evaluated, but in none of the 242 CXRs performed in asymptomatic patients with febrile neutropenia pulmonary abnormalities indicative of infection were detected. cache = ./cache/cord-336843-c0sr3six.txt txt = ./txt/cord-336843-c0sr3six.txt === reduce.pl bib === id = cord-339578-eg19rfvi author = Garcia-Garcia, Maria Luz title = Role of viral coinfections in asthma development date = 2017-12-05 pages = extension = .txt mime = text/plain words = 3651 sentences = 190 flesch = 47 summary = OBJECTIVE: Our aim was to compare the frequency of asthma development at 6–8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. CONCLUSIONS: Asthma at 6–8 years is more frequent and severe in those children previously hospitalized with viral coinfection-bronchiolitis compared with those with single infection. Of the 351 children previously admitted with bronchiolitis, with positive viral detection and current age between 6 and 8 years, 244 (52 coinfections and 192 single infections) could be located and agreed to participate in the study. In conclusion, asthma at the age of 6-8 is more frequent and severe in those children previously hospitalized with viral coinfection bronchiolitis compared with those with single infection. Moreover, viral coinfection, allergic rhinitis and older age at admission seem also to be strong independent risk factors for asthma development in children previously hospitalised because of bronchiolitis. cache = ./cache/cord-339578-eg19rfvi.txt txt = ./txt/cord-339578-eg19rfvi.txt === reduce.pl bib === id = cord-337585-kpghvb6u author = Moustaqim-Barrette, Amina title = Accessing Take-Home Naloxone in British Columbia and the role of community pharmacies: Results from the analysis of administrative data date = 2020-09-11 pages = extension = .txt mime = text/plain words = 4016 sentences = 191 flesch = 50 summary = Individuals not personally at risk of overdose had higher odds of collecting naloxone at a pharmacy site, compared to other community sites (including harm reduction supply distribution sites, peer led organizations, drop-in centers, and supportive housing sites) (Adjusted Odds Ratio (AOR): 2.69; 95% CI: 2.50–2.90). While those at highest risk of overdose may preferentially access naloxone through community sites, naloxone distribution through pharmacies has allowed the BC THN program to expand dramatically, increasing naloxone availability through longer opening hours on evenings and weekends. While analyses from the BCCDC shows that the BC THN program, combined with other harm reduction interventions, has averted thousands of opioid overdose deaths [20, 21] , there is still relatively little data in the published literature examining community reach and barriers to access of naloxone distribution programs in Canada. After evaluating data from 2018, our analysis also finds that individuals at risk of opioid overdose were significantly less likely to collect a naloxone kit at a pharmacy site compared to community-based sites. cache = ./cache/cord-337585-kpghvb6u.txt txt = ./txt/cord-337585-kpghvb6u.txt === reduce.pl bib === id = cord-339157-wj47xeqj author = Zhang, Chao title = Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease date = 2018-05-23 pages = extension = .txt mime = text/plain words = 3062 sentences = 174 flesch = 55 summary = RESULTS: The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. According to the "diagnosis and treatment guideline on hand-foot-and-mouth disease (2010)", patients younger than 60 months with severe symptoms including meningitis, pulmonary edema, and mild cases without any nervous system lesions or pulmonary edema were included in this study. The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls (P<0.001). The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls (P<0.001). In the present study, we found that the concentrations of Ang II and NA were increased in serum of HFMD cases with mild or severe symptoms. cache = ./cache/cord-339157-wj47xeqj.txt txt = ./txt/cord-339157-wj47xeqj.txt === reduce.pl bib === id = cord-338594-wft7yy6j author = Winkler, Michael title = Rhesus macaque IFITM3 gene polymorphisms and SIV infection date = 2017-03-03 pages = extension = .txt mime = text/plain words = 4633 sentences = 277 flesch = 48 summary = In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. Polymorphisms in several immune-relevant gene loci such as MHC or KIR are associated with the transmission and course of disease in SIV infected rhesus macaques and HIV-1 infected humans [36, 37] . Immune-related IFITM proteins have been established as important antiviral effectors of the interferon response, and a polymorphism in the human IFITM3 gene has been found to be associated with disease severity and progression in FLUAV and HIV-1 infection [27, 33] . Notably, all polymorphism in the coding region were silent and strong evidence for an association of rhIFITM3 polymorphisms with disease progression and viral load in SIV infected animals was not obtained. cache = ./cache/cord-338594-wft7yy6j.txt txt = ./txt/cord-338594-wft7yy6j.txt === reduce.pl bib === id = cord-335245-1eksm537 author = Pattyn, Els title = HyperISGylation of Old World Monkey ISG15 in Human Cells date = 2008-06-18 pages = extension = .txt mime = text/plain words = 7011 sentences = 419 flesch = 54 summary = Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Western blot analysis on total cell lysates containing b-ME confirmed ISGylation of UbcH10, H13 and H17 with AgmISG15 but not with HuISG15, as seen by a 15 kDa shift upon staining with anti-V5 Ab detecting the ectopic expressed UbcH proteins (Figure 3a ,b and Figure S2a ). Previous studies using Western blot analysis in HekT cells revealed Hu or MoISG15 conjugation to substrates such as UbcH13 only upon co-transfection of at least UbE1L -and generally also UbcH/M8or upon IFN stimulation. The effect of mutating HuISG15 residues situated near the predicted UbE1L interface and the different allelic variants on conjugation to UbcH proteins is shown in Figure 5a and S3a. As shown in Figure 5c , mutation of D133N and QIT31-33KIA in the HuISG15 N89D variant further enhanced its ISGylation in human HekT cells. cache = ./cache/cord-335245-1eksm537.txt txt = ./txt/cord-335245-1eksm537.txt === reduce.pl bib === id = cord-339327-4422s317 author = Norris, Susan L. title = An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks date = 2018-05-30 pages = extension = .txt mime = text/plain words = 3690 sentences = 169 flesch = 43 summary = For guidelines, the methods for development were incompletely reported; WHO's quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. For guidelines, the methods for development were incompletely reported; WHO's quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. WHO quality standards dictate that guidelines must address a critical public health problem, use transparent and explicit processes minimizing potential sources of bias such as conflicts of interest, include diverse perspectives in the guideline development group, reflect the current state of the evidence, and provide a clear link between the evidence and recommendations taking into consideration the balance of benefits and harms of interventions and other important considerations [2] . cache = ./cache/cord-339327-4422s317.txt txt = ./txt/cord-339327-4422s317.txt === reduce.pl bib === id = cord-334695-cjxlw1tu author = Kam, Yiu-Wing title = Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro date = 2009-11-17 pages = extension = .txt mime = text/plain words = 6404 sentences = 315 flesch = 43 summary = title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro We observed that SARS-CoV spike glycoprotein can be efficiently cleaved by several airway proteases and that this processing enhances entry of SARS-CoVpp. Furthermore, we have identified the putative cleavage sites of airway proteases and, by site-directed mutagenesis, have determined the role of specific amino acid residue for proteolytic processing of the envelope glycoprotein, and for SARS-CoVpp entry into human airway epithelial cells (16HBE) in vitro. In an effort to directly demonstrate that airway protease mediated virus entry enhancement is due to the presence of cleavage site on the SARS spike glycoprotein, 16HBE cells were pre-incubated with wild-type (SARS-CoVpp) or mutant (R667App) pseudotypes on ice, which allowed virus attachment but not entry. cache = ./cache/cord-334695-cjxlw1tu.txt txt = ./txt/cord-334695-cjxlw1tu.txt === reduce.pl bib === id = cord-337067-j8ebslif author = Mades, Andreas title = Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date = 2012-11-15 pages = extension = .txt mime = text/plain words = 8726 sentences = 459 flesch = 48 summary = The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. Similar results were obtained with cell lysates prepared with the denaturing detergent SDS (Fig. 1B) , indicating that the observed down-regulation of HBV.S by excess Sec63 was not merely due to changes in the solubility profile. To analyze whether an up-regulation of these ERdj proteins might also affect the level of a multi-spanning membrane protein, FLAG-tagged versions of ERdj1 and ERdj4 were cotransfected with HBV.S. FLAG-specific Western blotting confirmed the ectopic expression of ERdj1 and ERdj4 in 63 and 25 kDa forms, respectively, consistent with their theoretical molecular masses (Fig. 9) . cache = ./cache/cord-337067-j8ebslif.txt txt = ./txt/cord-337067-j8ebslif.txt === reduce.pl bib === id = cord-340027-6l55rcfm author = Mamode Khan, Naushad title = Studying the trend of the novel coronavirus series in Mauritius and its implications date = 2020-07-10 pages = extension = .txt mime = text/plain words = 3627 sentences = 198 flesch = 52 summary = This paper proposes an integer-valued time series model to analyze the series of COVID-19 cases in Mauritius wherein the corresponding innovation term accommodates for covariate specification. Based on the proposed COM-Poisson mixture models, we could predict the number of COVID-19 cases in Mauritius. The paper therefore proposes an integer-valued auto-regressive model (INAR(1)) with Conway-Maxwell Poisson (COM-Poisson) mixed innovation terms that can accommodate for covariate, random effect and serial auto-correlation specifications. The organization of the paper is as follows: In Section 2, material in terms of time series of COVID-19 in Mauritius and proposed methods principally the INAR(1) Process and the COM-Poisson mixture innovations have been provided. The results of this research revealed that several factors, the most significant being confinement measure, and least one being climatic conditions, affect the number of COVID-19 cases in Mauritius. cache = ./cache/cord-340027-6l55rcfm.txt txt = ./txt/cord-340027-6l55rcfm.txt === reduce.pl bib === id = cord-339724-roj8ksvc author = Lan, Jiaming title = Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen date = 2014-11-18 pages = extension = .txt mime = text/plain words = 5017 sentences = 249 flesch = 49 summary = title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. In this study, different adjuvants combination regimens including alum, IFA, CpG and poly(I:C) were compared in an effort to promote balance between Th1 and Th2 immune response to bystander rRBD antigen spanning residues 367-606 of MERS-CoV S in a murine model to develop an effective vaccine against MERS-CoV infection. The results indicated that rRBD protein combined with any adjuvant, including alum, IFA, CpG or poly(I:C), could induce a RBD-specific IgG antibody response in the majority of mice after the second immunisation. cache = ./cache/cord-339724-roj8ksvc.txt txt = ./txt/cord-339724-roj8ksvc.txt === reduce.pl bib === id = cord-340763-cxnu9g8y author = Grimm, Sebastian K. title = Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies date = 2015-02-17 pages = extension = .txt mime = text/plain words = 7822 sentences = 341 flesch = 45 summary = title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. The rationally designed d-SOSIP variant and a mutant with disrupted CD4 binding site (CD4bs)-specific Ab binding (d-SOSIP D368R) were displayed as Aga2 fusion proteins on yeast ( Fig. 2A ), and compared for display level and binding to a panel of HIV bnAbs together with the well-characterized and folded YU2 gp120 core [47] and an unrelated viral envelope protein (E2) derived from Hepatitis C virus (HCV E2) as positive and negative controls Fig. 2) . cache = ./cache/cord-340763-cxnu9g8y.txt txt = ./txt/cord-340763-cxnu9g8y.txt === reduce.pl bib === id = cord-337913-eu2gn4bl author = Stojanov, Ana title = Does Perceived Lack of Control Lead to Conspiracy Theory Beliefs? Findings from an online MTurk sample date = 2020-08-17 pages = extension = .txt mime = text/plain words = 7933 sentences = 414 flesch = 48 summary = Across six studies conducted online using MTurk samples, we observed no effect of control manipulations on conspiracy theory beliefs, while replicating previously reported correlational evidence of their association. Given the significance and potential consequences of widespread conspiracy beliefs [38, 39] , and the plausible but largely unsubstantiated role of control in their appeal, we here report three studies to test the effects of lack of control on conspiracy theory beliefs using a standard priming paradigm and a validated measure of conspiracy ideation, which reflects the belief that a powerful entity lies behind significant social or political events and that the conventional (official) truth is not the "real" truth. In a recent meta-analysis of experimental manipulations of control on conspiracy beliefs [68] conducted on 45 effect sizes across 23 studies (including those reported here), we found no moderating effect of sample type (MTurk vs. cache = ./cache/cord-337913-eu2gn4bl.txt txt = ./txt/cord-337913-eu2gn4bl.txt === reduce.pl bib === id = cord-337879-liqhbqxl author = Kriesel, John D. title = Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain date = 2012-03-08 pages = extension = .txt mime = text/plain words = 5060 sentences = 296 flesch = 54 summary = Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. Multiple sclerosis (MS) is a chronic demyelinating disease of unknown cause, which affects the brain and spinal cord of about 400,000 individuals in the U.S. A number of viral infections of the CNS can lead to demyelination, including distemper (dogs), measles (SSPE, humans), and influenza (humans). To enhance the detection of non-human sequences, RNA samples that passed the quality control step above were subjected to rRNA removal using the RiboMinus kit (Invitrogen Inc., Carlsbad, CA). One subject who died with primary-progressive MS had .1000 36 bp sequences detected that mapped to GBV-C virus (hepatitis G), a human flavivirus not known to cause any persistent disease and never before detected in human brain. cache = ./cache/cord-337879-liqhbqxl.txt txt = ./txt/cord-337879-liqhbqxl.txt === reduce.pl bib === id = cord-340195-425rd7ul author = Smith, Kristine M. title = Zoonotic Viruses Associated with Illegally Imported Wildlife Products date = 2012-01-10 pages = extension = .txt mime = text/plain words = 4427 sentences = 210 flesch = 48 summary = Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence. Our study is the first to establish surveillance for zoonotic viruses in wild animal products illegally imported into the United States in an effort to prevent the transmission of infectious agents from these shipments. To date, four groups of HTLV viruses found in humans are believed to have originated from corresponding STLV strains in NHP species (including mangabeys, baboons, and chimpanzees) via multiple transmission events [35] . In summary, our study establishes initial surveillance methodology to detect and identify zoonotic pathogens and species of origin of wildlife products entering the United States. cache = ./cache/cord-340195-425rd7ul.txt txt = ./txt/cord-340195-425rd7ul.txt === reduce.pl bib === id = cord-339920-dr5bvpm0 author = Soberman, Roy J. title = CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2 date = 2012-10-17 pages = extension = .txt mime = text/plain words = 7447 sentences = 406 flesch = 54 summary = We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1 2/2 macrophages showed a marked decrease in the generation of both IL-6 and CCL5 (Rantes) in response to stimulation by both Pam 2 CSK 4 and HSV-1, whereas no difference was observed in the generation of any cytokine/chemokine in response to the TLR4 ligand bacterial lipopolysaccharide (LPS). These results indicated that CD200R1 directly controls the inducible surface expression of TLR2 either directly or secondary to decreased viral replication and that it may play a role in the amplification of HSV-1 infection. The lack of difference in brain leukocyte scores, and in CCL2 (MCP-1), CCL5 (Rantes), and IL-6 levels indicated that CD200R1 2/2 mice had equivalent or modestly reduced brain inflammation, rather than an enhanced, inflammatory response to HSV-1 infection compared to CD200R1 +/+ mice (see above). cache = ./cache/cord-339920-dr5bvpm0.txt txt = ./txt/cord-339920-dr5bvpm0.txt === reduce.pl bib === id = cord-339392-2ocz784l author = Sharma, Kulbhushan title = Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation date = 2011-06-15 pages = extension = .txt mime = text/plain words = 6208 sentences = 375 flesch = 51 summary = BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. It is known that under stress conditions the expression level of Hsp40 is enhanced and its cellular localization changes from cytoplasmic to nuclear [38] , however its distribution in influenza virus infected cells was not studied. Taken together, these results suggest that during IAV infection, NP induces the dissociation of the P58 IPK -Hsp40 complex leading to an inhibition of PKR activation and downregulation of eIF2a phosphorylation. In case of influenza virus infection, viral NS1 protein is known to bind directly to PKR and inhibit its activation [20, 21] . cache = ./cache/cord-339392-2ocz784l.txt txt = ./txt/cord-339392-2ocz784l.txt === reduce.pl bib === id = cord-337630-ojhk5opy author = Tasic, Velibor title = Clinical and Functional Characterization of URAT1 Variants date = 2011-12-16 pages = extension = .txt mime = text/plain words = 5356 sentences = 313 flesch = 45 summary = reported that mutations in gene SLC22A12 encoding the URAT1 transporter were responsible for most cases of idiopathic renal hypouricaemia [3] . It is noteworthy that reports of idiopathic renal hypouricaemia secondary to mutations in uric acid transporters URAT1 and GLUT9 were initially reported from Japan, Korea and China [23] . Since the hypouricaemia was associated with an elevated FE urate , we undertook mutational analysis of SLC22A12 which revealed a heterozygous missense mutation, leading to amino acid change R434C. SLC22A12 encodes the protein URAT1 and loss of function mutations are responsible for majority of patients with idiopathic renal hypouricaemia. reported a W258X homozygous mutation in a 7 year old child, whose mother and brother were also heterozygous for W258X and had mild hypouricaemia and abnormally high FE urate , whilst his father who was also heterozygous for W258X, had a normal serum uric acid level of 4.6 mg/dL [23] . cache = ./cache/cord-337630-ojhk5opy.txt txt = ./txt/cord-337630-ojhk5opy.txt === reduce.pl bib === id = cord-341914-l2bomgji author = Flies, Andrew S. title = Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity date = 2015-10-07 pages = extension = .txt mime = text/plain words = 6626 sentences = 297 flesch = 44 summary = Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis. A more robust understanding of the effects of ecological variables such as pathogen exposure on immune function might be gained by studying immune function in non-traditional species, and assessing how basic immune defenses differ between wild and captive animals with similar genetic backgrounds. cache = ./cache/cord-341914-l2bomgji.txt txt = ./txt/cord-341914-l2bomgji.txt === reduce.pl bib === id = cord-339796-gccnvh0z author = Zhang, Si Min title = Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins date = 2015-07-31 pages = extension = .txt mime = text/plain words = 9073 sentences = 403 flesch = 45 summary = The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. Here we describe the roles of the Trp residues in the membrane-active MPER sequence in anti-HIV fusion inhibitor design and a surprising role in the biosynthesis of viral structural proteins. cache = ./cache/cord-339796-gccnvh0z.txt txt = ./txt/cord-339796-gccnvh0z.txt === reduce.pl bib === id = cord-340718-amfs4zay author = Zhu, Gengping title = Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus date = 2014-04-01 pages = extension = .txt mime = text/plain words = 2395 sentences = 103 flesch = 42 summary = CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Since the first case was reported, researchers focused on improving diagnosis, understanding location of origin, and methods of cure; however, little is known about the geographic potential of H7N9 or environmental correlates of its transmission, except Butler [3] and He and Chen [4] , who presented ideas based on lessons from the previous avian influenza threat (i.e. H5N1), and Shi [5] and Fang [6] , who mapped the spread potential of H7N9 using spatial regression method. Effective and predictive risk maps can provide a useful means by which to design targeted surveillance efforts [3] [4] [5] [6] , and ecological niche modeling approaches are offering novel views of the geography of potential for disease transmission [9, 18] . cache = ./cache/cord-340718-amfs4zay.txt txt = ./txt/cord-340718-amfs4zay.txt === reduce.pl bib === id = cord-340713-v5sdowb7 author = Bird, Jordan J. title = Country-level pandemic risk and preparedness classification based on COVID-19 data: A machine learning approach date = 2020-10-28 pages = extension = .txt mime = text/plain words = 5669 sentences = 260 flesch = 53 summary = The three four-class classification problems are then explored and benchmarked through leave-one-country-out cross validation to find the strongest model, producing a Stack of Gradient Boosting and Decision Tree algorithms for risk of transmission, a Stack of Support Vector Machine and Extra Trees for risk of mortality, and a Gradient Boosting algorithm for the risk of inability to test. The classification problem of risk is therefore formulated based on prior knowledge of the pandemic in terms of class only, but the attributes to attempt to classify them are purely country-level information regardless of number of cases, deaths and other coronavirus specific data. Country-level pandemic risk and preparedness classification based on COVID-19 data Fig 10 shows a comparison of other models that were explored. Country-level pandemic risk and preparedness classification based on COVID-19 data Table 1 shows the predicted class values for the best models applied to each of the respective risk classification problems. cache = ./cache/cord-340713-v5sdowb7.txt txt = ./txt/cord-340713-v5sdowb7.txt === reduce.pl bib === id = cord-340703-vtuy806l author = Cascio, Antonio title = Low bone mineral density in HIV-positive young Italians and migrants date = 2020-09-03 pages = extension = .txt mime = text/plain words = 4488 sentences = 230 flesch = 55 summary = We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Our study aims to emphasize the burden of bone health in naïve ARV HIV positive patients and compare the bone density of the native Italian population group (ItG) with that of HIV Migrants (MiG) upon arrival in Italy. Finally, in Table 3 , we report the logistic regression analysis between Low BMD variable (dichotomous) and the independent variables: Gender (dichotomous), BMI (continuous), Hydroxy-Vitamin D (continuous), CD4 (continuous), and Previous Fractures (dichotomous) for the total sample, ItG, and MiG. Our previous reports [13, 14] on the prevalence of Low-BMD in HIV mono-infected patients who underwent ARV therapy showed higher percentage rates of osteopenia (44.9%) and osteoporosis (20.9%) than an agerelated healthy Italian population (18%) [16] . cache = ./cache/cord-340703-vtuy806l.txt txt = ./txt/cord-340703-vtuy806l.txt === reduce.pl bib === id = cord-340656-ltd6ueoi author = Grant, Michael C. title = The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries date = 2020-06-23 pages = extension = .txt mime = text/plain words = 3435 sentences = 199 flesch = 48 summary = title: The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries Furthermore, with few included studies (30 in the largest and most recent [12] ), the range of symptoms were limited and the estimates of prevalence are likely to be upwardly biased because only unwell patients (largely those admitted to hospital) were tested in the early phase of the outbreak. We excluded case reports, articles which failed to disaggregate symptoms in adult and paediatric cohorts, studies of patients with prior respiratory infections (e.g. tuberculosis) or co-infections with other viruses (e.g. similar viruses SARS-CoV-1 or HCoV-EMC/2012, etc) and articles which we are unable to translate to English in a timely fashion. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms cache = ./cache/cord-340656-ltd6ueoi.txt txt = ./txt/cord-340656-ltd6ueoi.txt === reduce.pl bib === id = cord-340627-xyvzgkxl author = Ornaghi, Sara title = Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy date = 2020-09-15 pages = extension = .txt mime = text/plain words = 3804 sentences = 228 flesch = 51 summary = title: Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy Initially, a targeted SARS-CoV-2 screening approach triggered by a positive questionnaire and based on RT-PCR testing of nasopharyngeal swabs was used in women with hospital admission after accessing the Emergency Department. On April 8 th , we changed our policy and started testing all women for SARS-CoV-2 infection independent of the type of hospital admission and the questionnaire result, in agreement with a disposition of the Lombardy Region Health Care Authority. Our study investigated the accuracy of a comprehensive questionnaire thoroughly assessing obstetric patients upon hospital admission to identify cases suspected for SARS-CoV-2 infection. Our data show that thorough assessment of obstetric patients upon hospital admission by means of an exhaustive questionnaire is feasible and effective in discriminating women at low risk of SARS-CoV-2 infection in the context of both a targeted and a universal screening cache = ./cache/cord-340627-xyvzgkxl.txt txt = ./txt/cord-340627-xyvzgkxl.txt === reduce.pl bib === id = cord-340937-6mpob1nx author = Varshney, Mohit title = Initial psychological impact of COVID-19 and its correlates in Indian Community: An online (FEEL-COVID) survey date = 2020-05-29 pages = extension = .txt mime = text/plain words = 3662 sentences = 217 flesch = 51 summary = The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Event–revised (IES-R) scale. The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Eventrevised (IES-R) scale. The current study investigated the initial psychological impact of COVID-19 outbreak in Indian population. Despite the limitations, this study provides the first cross-sectional data on actual level of psychological impact among Indian community; and how mental health of people is affected during a pandemic of this nature. Our survey is one of the first mental health related data from India, during the initial phase of COVID-19 pandemic and indicated that a significant proportion of them have had a psychological impact during the crisis. cache = ./cache/cord-340937-6mpob1nx.txt txt = ./txt/cord-340937-6mpob1nx.txt === reduce.pl bib === id = cord-340766-aic570x8 author = Kim, Se Jin title = Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia date = 2015-04-15 pages = extension = .txt mime = text/plain words = 3631 sentences = 196 flesch = 41 summary = The present study describes in detail the clinical characteristics and favorable treatment outcomes of non-immunocompromised adults who had experienced severe AdV pneumonia and received early cidofovir administration. Only non-immunocompromised adult patients who fulfilled the criteria for severe community-acquired pneumonia, set out in the Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines [23] , and admitted to the intensive care unit with progressive respiratory failure, defined as a partial pressure of arterial oxygen (PaO 2 )/fraction of inspired oxygen (FiO 2 ) ratio of < 300 mmHg and/or tachypnea (respiration rate >30 breaths/min) [24] , were included in the analysis. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. cache = ./cache/cord-340766-aic570x8.txt txt = ./txt/cord-340766-aic570x8.txt === reduce.pl bib === id = cord-339869-euikj8fv author = Cebey-López, Miriam title = Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children? date = 2016-04-20 pages = extension = .txt mime = text/plain words = 3325 sentences = 201 flesch = 40 summary = However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory Introduction Molecular techniques including polymerase chain reaction (PCR) have increased the sensitivity of detection for common and emerging respiratory viruses, and often reveal the presence of more than one pathogen in respiratory patients. Our study aims to analyze the relationship between viral or bacterial co-infection detected by molecular methods, and the clinical phenotype of children admitted to hospital with lower tract acute respiratory infections (LT-ARI). PICU admission, disease severity according to different scales, need for respiratory support, and length of hospital stay followed a similar pattern in viral mono-versus co-infected children. cache = ./cache/cord-339869-euikj8fv.txt txt = ./txt/cord-339869-euikj8fv.txt === reduce.pl bib === id = cord-340387-ohkjheat author = Wynne, James W. title = Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date = 2013-01-07 pages = extension = .txt mime = text/plain words = 7004 sentences = 390 flesch = 52 summary = title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. Considering that in other mammalian species, immunoglobulins IgG, IgM and IgA are present in relatively high abundance in serum and tissues, we anticipated that bats would possess a similar immunoglobulin profile. IgG-depleted samples were fractionated by affinity chromatography on immobilised anti-Fab-specific antibodies adopting the same procedure as that described for immobilised Protein A and G except that the binding and washing buffer consisted of 0.3 M NaCl in 50 mM phosphate buffer, pH 7.4. Two major bands were detected by reducing SDS-PAGE in the eluate from both serum and plasma samples; a 66-70 kDa band representative of IgM H , and a 25 kDa band representative of immunoglobulin light chain ( Fig. 3A and 3B ). cache = ./cache/cord-340387-ohkjheat.txt txt = ./txt/cord-340387-ohkjheat.txt === reduce.pl bib === id = cord-342476-0rupk21u author = van Rijn, Anneloes L. title = The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease date = 2019-10-24 pages = extension = .txt mime = text/plain words = 4036 sentences = 220 flesch = 44 summary = The sensitivity, specificity and predictive values of mNGS were calculated based on 24 PCR positive and 1120 PCR negative target results of 88 samples and the normalized read counts (Table 5 ). The following markers were tested for potential associations with clinical severity of exacerbation (exacerbation severity, self-reported exacerbation severity), length of exacerbation and a decrease/increase in FEV 1 (control visit compared to baseline): mNGS pathogen positive versus negative exacerbation (qPCR targets), the number of normalized reads (log, cutoff of �5normalized reads) for the different target viruses (species level). The Shannon diversity scores for bacteriophages (normalized reads, cut-off of �5normalized reads) were comparable for COPD exacerbations of viral aetiology in PCR positive versus negative patients (Fig 5) . In this study, the respiratory virome in patients with COPD exacerbations was analysed with both mNGS and qPCR, and combined with clinical data. cache = ./cache/cord-342476-0rupk21u.txt txt = ./txt/cord-342476-0rupk21u.txt === reduce.pl bib === id = cord-341880-wxliz485 author = Mottaleb, Khondoker Abdul title = COVID-19 induced economic loss and ensuring food security for vulnerable groups: Policy implications from Bangladesh date = 2020-10-16 pages = extension = .txt mime = text/plain words = 7552 sentences = 365 flesch = 60 summary = This study examines the food security and welfare impacts of the COVID-19 induced lockdown on daily wage workers both in the farm and nonfarm sectors in Bangladesh. Then, applying simple econometric estimation processes, this study estimates the minimum compensation packages for the daily wage-based farm and nonfarm households of Bangladesh that ensure their minimum food security during the lockdown. The estimation suggests a common minimum support at US $ 1 per daily wage-based household in Bangladesh to ensure minimum food security during COVID-19 induced lockdown time. Using information of more than 50,000 respondents from the HIES 2016-17 dataset, this study, firstly quantified the economic loss due to the COVID-19 induced lockdown and suggested the minimum support package to ensure food security of the daily wage-based workers in Bangladesh. cache = ./cache/cord-341880-wxliz485.txt txt = ./txt/cord-341880-wxliz485.txt === reduce.pl bib === id = cord-343135-m0pdixw5 author = Marguet, Christophe title = In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses date = 2009-02-25 pages = extension = .txt mime = text/plain words = 3344 sentences = 182 flesch = 48 summary = BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The aim of this prospective study was to assess the clinical severity and viral etiology in infants hospitalized with a first episode of acute bronchiolitis during the epidemic season. In this study, the clinical severity of dual RSV/RV infection was comparable to that observed with RSV, but differed in a shorter duration of hospitalization in the coinfected infants. cache = ./cache/cord-343135-m0pdixw5.txt txt = ./txt/cord-343135-m0pdixw5.txt === reduce.pl bib === id = cord-342133-khrljehj author = Principi, Nicola title = Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease date = 2015-08-12 pages = extension = .txt mime = text/plain words = 5116 sentences = 243 flesch = 49 summary = To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). To evaluate the circulation of the different hBoV types and the possible relationships between viral load, virus genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children attending the emergency room of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection arising between November 1 and March 31 during 3 winters (2009-2010, 2011-2012, and 2013-2014) . Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children cache = ./cache/cord-342133-khrljehj.txt txt = ./txt/cord-342133-khrljehj.txt === reduce.pl bib === id = cord-341097-c96hm610 author = Mayer, Craig S. title = Analysis of data dictionary formats of HIV clinical trials date = 2020-10-05 pages = extension = .txt mime = text/plain words = 6899 sentences = 366 flesch = 57 summary = To facilitate aggregation across studies, we defined three types of data dictionary (data element, forms, and permissible values) and created a simple information model for each type. The presented study is limited to data dictionary analysis, although the motivation is to later analyze a large body of past HIV data elements to inform data-driven consensus on CDEs. This study is part of a larger research project titled 'Identification of Research Common Data Elements in HIV/AIDS using data science methods' [12] . We use the term Forms Data Dictionary (or forms dictionary in shorter form) to refer to a data dictionary that provides a full list of titles and descriptions of all Case Report Forms (CRFs) used in the study (or other relevant metadata for data element grouping). Use of categorical data elements in research is extremely common and, as stated earlier, most studies would be expected to provide a permissible value dictionary. cache = ./cache/cord-341097-c96hm610.txt txt = ./txt/cord-341097-c96hm610.txt === reduce.pl bib === id = cord-342519-tjr6dvtt author = Souza, Thiago Moreno L. title = H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis date = 2010-11-30 pages = extension = .txt mime = text/plain words = 5166 sentences = 293 flesch = 48 summary = The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. Because the analysis of this novel viral infection in cancer patients is an important component of the 2009 pandemics, we conducted a prospective cohort study aimed at evaluating the clinical course of influenza infection, the duration of viral shedding, H1N1pdm evolution and the emergence of antiviral resistance in hospitalized cancer patients with a severe H1N1pdm infection in a reference cancer center during the winter of 2009 in Brazil. Although prolonged influenza A shedding has been observed for a cancer patient infected with the H3N2 seasonal virus [15] , more detailed data on H1N1pdm secretion in severely ill cancer patients are required. cache = ./cache/cord-342519-tjr6dvtt.txt txt = ./txt/cord-342519-tjr6dvtt.txt === reduce.pl bib === id = cord-344782-ond1ziu5 author = Zhang, Jing title = Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi) date = 2018-10-24 pages = extension = .txt mime = text/plain words = 6003 sentences = 280 flesch = 49 summary = Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Following the detection of the novel virus, in November 2015 (about 6 months after the cessation of the outbreak) an intensive survey of the parts of the river where affected turtles had been detected [2] was undertaken by groups of biologists and ecologists and samples collected from a wide range of aquatic species and some terrestrial animals (n = 360) to establish the size of the remaining population and whether any other animals were carrying this virus. BRV, as a novel nidovirus, was isolated from tissues of diseased animals, very high levels of viral RNA were detected in tissues with marked pathological changes and in situ hybridisation assays demonstrated the presence of specific viral RNA in lesions in kidneys and eye tissue-two of the main affected organs. cache = ./cache/cord-344782-ond1ziu5.txt txt = ./txt/cord-344782-ond1ziu5.txt === reduce.pl bib === id = cord-343973-n5ogyxz7 author = Ip, Andrew title = Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—An observational study date = 2020-08-13 pages = extension = .txt mime = text/plain words = 4322 sentences = 239 flesch = 43 summary = In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Subsequently, an observational cohort study of 1376 hospitalized patients from a New York hospital using propensity modeling found no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32) [14] . A recently reported randomized Brazilian trial enrolling 504 hospitalized SARS-CoV-2 confirmed patients with mild-to-moderate disease (defined as not requiring significant supplemental oxygen support) found that a 7-day course of hydroxychloroquine either with azithromycin or alone did not result in better clinical outcomes as measured by a seven-level ordinal scale at 15 days [16] . In this observational cohort study we report our survival outcomes with hydroxychloroquine and tocilizumab among hospitalized patients with COVID-19. cache = ./cache/cord-343973-n5ogyxz7.txt txt = ./txt/cord-343973-n5ogyxz7.txt === reduce.pl bib === id = cord-344357-ocyaqs1y author = Fu, Yue-Qiang title = Effect of blood analysis and immune function on the prognosis of patients with COVID-19 date = 2020-10-30 pages = extension = .txt mime = text/plain words = 4482 sentences = 277 flesch = 58 summary = INTRODUCTION: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with Coronavirus Disease 2019 (COVID-19). The percentage of neutrophil count > 6.3×10 9 /L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10 9 /L was independently associated with mortality. The percentage of neutrophil count > 6.3×10 9 /L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10 9 /L was independently associated with mortality. Another study also indicated that COVID-19 patients in the death group had significantly lower lymphocyte count on admission than the recovered group [8] . Collected information included: age; gender; concomitant disease; symptoms; hemoglobin; platelet; leukocyte, neutrophil, and lymphocyte counts; CRP, CD3+, CD4+, CD8+, CD4/8, CD19+, and CD16+56+;IgG, IgM, IgA, IgE, C3, and C4 chest CT; alanine aminotransferase, creatinine; arterial blood gas; procalcitonin; and the result of the RT-PCR assay of SARS-CoV-2 RNA. cache = ./cache/cord-344357-ocyaqs1y.txt txt = ./txt/cord-344357-ocyaqs1y.txt === reduce.pl bib === id = cord-344839-r05p9h0e author = Majmundar, Monil title = Efficacy of corticosteroids in non-intensive care unit patients with COVID-19 pneumonia from the New York Metropolitan region date = 2020-09-09 pages = extension = .txt mime = text/plain words = 4072 sentences = 235 flesch = 44 summary = OBJECTIVE: The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). The results of our study showed that the administration of corticosteroids in patients admitted to the general medical ward with AHRF and a diagnosis of COVID-19 pneumonia was associated with a lower risk of developing the primary outcome composite of ICU transfer, intubation or death. In our analysis of hospitalized patients in the general ward with COVID-19 pneumonia complicated by acute hypoxic respiratory failure, early use of moderate dose systemic corticosteroid for the shorter duration was associated with a significantly lower rate of the primary outcomes of ICU transfer, intubation, or in-hospital death. cache = ./cache/cord-344839-r05p9h0e.txt txt = ./txt/cord-344839-r05p9h0e.txt === reduce.pl bib === id = cord-344870-tbgqulpu author = Lloyd-Smith, James O. title = Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases date = 2007-02-14 pages = extension = .txt mime = text/plain words = 5997 sentences = 290 flesch = 50 summary = METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. This study uses simulated data to assess the bias and precision of NB parameter estimates and the coverage accuracy of CIs for highly overdispersed datasets, addressing the challenges of small datasets as well as potential biases arising in the data collection process. In the epidemiological context that motivated this study, these values x i correspond to the numbers of secondary cases that were infected by n different infectious individuals, but similar data could arise from many other processes. cache = ./cache/cord-344870-tbgqulpu.txt txt = ./txt/cord-344870-tbgqulpu.txt === reduce.pl bib === id = cord-342730-b7y8mybg author = Dellagi, Koussay title = Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009 date = 2011-09-29 pages = extension = .txt mime = text/plain words = 5974 sentences = 283 flesch = 49 summary = In order to assess at the community level, the actual magnitude of the pH1N1/2009v pandemic and the extent of the herd immunity acquired after passage of the epidemic wave, a prospective population serosurvey was conducted in Reunion Island during the passage of the epidemic wave in the 2009 austral winter season (July-December 2009): prevalence of infection was assessed on a weekly basis and seroconversion rates were measured using paired sera. The CoPanFlu-RUN cohort was set up to conduct a prospective population-based study investigating the herd immunity induced by the 2009 pandemic influenza virus and identifying risk factors for pH1N1/2009v infection from paired sera collected in an entire community. Our study shows that a substantial proportion of Reunion Island's population had pre-existing immunity to 2009 pandemic influenza virus with the highest baseline-proxy seroprevalence rate observed among adults aged of 60 years or more. cache = ./cache/cord-342730-b7y8mybg.txt txt = ./txt/cord-342730-b7y8mybg.txt === reduce.pl bib === id = cord-342639-vf9n2vf9 author = Chang, Chung-ke title = Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date = 2013-05-23 pages = extension = .txt mime = text/plain words = 5386 sentences = 243 flesch = 42 summary = For disulfide trapping experiments, we chose mutation sites that would form disulfide linkages based on the crystal packing structures of the SARS-CoV N protein CTD ( Figure 1 ) [9] . Within the crystal asymmetric unit, the SARS-CoV N protein CTD packs as an octamer which stacks to form a helical arrangement with a continuous positively charged surface that could potentially allow the RNA to bind to it through electrostatic interactions ( Fig. 1 ) [9] . By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that SARS-CoV N protein is capable of transient oligomerization in solution through the CTD in the absence of nucleic acids. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA cache = ./cache/cord-342639-vf9n2vf9.txt txt = ./txt/cord-342639-vf9n2vf9.txt === reduce.pl bib === id = cord-345695-5vi9wibk author = Hicks, Lorin L. title = A statistical approach to white-nose syndrome surveillance monitoring using acoustic data date = 2020-10-22 pages = extension = .txt mime = text/plain words = 5489 sentences = 262 flesch = 48 summary = From these data, we developed site-specific prediction models for bat activity to account for seasonal and annual temperature variation prior to known occurrence of WNS. We propose this model-based method for future monitoring efforts that could be used to trigger targeted sampling of individual bats or hibernacula for WNS, in areas where traditional disease surveillance approaches are logistically difficult to implement or because of human-wildlife transmission concerns from COVID-19. We predicted that bat populations in the western U.S. would have low levels of activity during winter months, high levels of activity during the summer, and that acoustic monitoring could be used as an effective approach for disease surveillance in remote areas of the Intermountain West. The model was fit to data from all 41 sites to estimate among-site and among-year variation in activity, but we use the results to generate prediction intervals for four forest sites to depict how a landowner might implement this approach for WNS surveillance monitoring. cache = ./cache/cord-345695-5vi9wibk.txt txt = ./txt/cord-345695-5vi9wibk.txt === reduce.pl bib === id = cord-345717-ktajrf7d author = Monagin, Corina title = Serologic and behavioral risk survey of workers with wildlife contact in China date = 2018-04-03 pages = extension = .txt mime = text/plain words = 4585 sentences = 241 flesch = 45 summary = We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. The present study focuses on the potential for zoonotic viral transfer through contact with wildlife in Guangdong prefectures in China, and seeks to augment our understanding and identification of risky populations, occupations, and behaviors, as well as the perceptions of risk at these interfaces. We performed a serological survey and concurrent behavioral questionnaire of individuals with wildlife contact in Guangdong Province, China, in order to better characterize occupations and community-level behavioral risks that contribute to zoonotic transmission of various wildlife pathogens with pandemic potential. We targeted high-risk individuals, defined as individuals with high levels of exposure to wildlife (wild animal blood or bodily fluids)-primarily hunters, persons working in wet markets and restaurants that butcher wild game, who could be followed over a period of time. cache = ./cache/cord-345717-ktajrf7d.txt txt = ./txt/cord-345717-ktajrf7d.txt === reduce.pl bib === id = cord-346586-fxxceffl author = Razanajatovo, Norosoa Harline title = Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013 date = 2018-11-21 pages = extension = .txt mime = text/plain words = 4150 sentences = 213 flesch = 49 summary = CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Following the A/H1N1/2009 influenza pandemic that was associated with a high morbidity and an increased risk of mortality among particular groups [13] , a number of countries have strengthened vigilance for the surveillance of severe diseases and deaths in order to rapidly detect new viruses and to provide information in assessing the impact on the population and having operational preparedness plans. A meta-analysis of data from Africa reported that the incidence of RSV in lower acute respiratory infections that required hospitalization ranged from 10-18 per 1000 person year for infants and 3-9 per 1000 person year for children under 5 years of age [26] . cache = ./cache/cord-346586-fxxceffl.txt txt = ./txt/cord-346586-fxxceffl.txt === reduce.pl bib === id = cord-345019-i7zm9bt1 author = Al-Waleedi, Ali Ahmed title = The first 2 months of the SARS-CoV-2 epidemic in Yemen: Analysis of the surveillance data date = 2020-10-29 pages = extension = .txt mime = text/plain words = 4496 sentences = 236 flesch = 55 summary = A total of 268 individuals with confirmed SARS-CoV-2 infection were hospitalized (57%), among whom there were 95 in-hospital deaths, CONCLUSIONS: The surveillance strategy implemented in the first 2 months of the SARS CoV 2 in the southern and eastern governorates of Yemen, captured mainly severe cases. For early detection of SARS-CoV-2 in Yemen, as in other countries, a case definition, active surveillance, and contact tracing were required [10, 11] . The first 2 months after confirmation of the SARS-CoV-2 epidemic in Yemen was characterized by a 57% hospitalization rate in the southern and eastern parts of the country included in The First 2 Months of the SARS-CoV-2 Epidemic in Yemen our study, 63% of deaths occurring in individuals aged <60 years, confirmatory testing of <50% of the suspected cases, and majority of cases were not related to a defined chain of transmission. cache = ./cache/cord-345019-i7zm9bt1.txt txt = ./txt/cord-345019-i7zm9bt1.txt === reduce.pl bib === id = cord-344152-pb1e2w7s author = Kolatkar, Anand title = C-ME: A 3D Community-Based, Real-Time Collaboration Tool for Scientific Research and Training date = 2008-02-20 pages = extension = .txt mime = text/plain words = 5434 sentences = 258 flesch = 45 summary = Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members. For example, protein structure/activity data annotations and images may be kept in paper lab notebooks, manuscripts might be stored electronically in Portable Document Format (PDF), and molecular structure coordinate files may be stored on a hard disk to be viewed and analyzed in graphical molecular viewers, to name a few. Most recently we have developed the Collaborative Molecular Modeling Environment (C-ME), a new collaboratory system that integrates many of the key features available on Kinemage, MICE, iSee, and BioCoRE systems into one thin-client Windows application. cache = ./cache/cord-344152-pb1e2w7s.txt txt = ./txt/cord-344152-pb1e2w7s.txt === reduce.pl bib === id = cord-347465-yu6oj30v author = Kurskaya, Olga title = Viral etiology of acute respiratory infections in hospitalized children in Novosibirsk City, Russia (2013 – 2017) date = 2018-09-18 pages = extension = .txt mime = text/plain words = 3383 sentences = 194 flesch = 45 summary = METHODS: We tested nasal and throat swabs of 1560 children with upper or lower respiratory infection for main respiratory viruses (influenza viruses A and B, parainfluenza virus types 1–4, respiratory syncytial virus, metapneumovirus, four human coronaviruses, rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected 1128 (72.3%) samples were positive for at least one virus. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. In conclusion, in our study we investigated the etiological structure of acute respiratory viral infections in hospitalized children in Novosibirsk, Russia, and evaluated age and seasonal distribution of the various respiratory viruses. cache = ./cache/cord-347465-yu6oj30v.txt txt = ./txt/cord-347465-yu6oj30v.txt === reduce.pl bib === id = cord-348055-azlb1zy1 author = Patel, Mira C. title = Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus) date = 2016-11-04 pages = extension = .txt mime = text/plain words = 7758 sentences = 351 flesch = 50 summary = To determine effect of the EV-D68 infection on the induction of an inflammatory response, we focused on the lung tissue and measured the expression of cotton rat mRNA for several chemokines, Type I and Type II interferons (IFNs), cytokines, and select IFN-inducible genes following VANBT infection. As there are no current animal models for EV-D68 and information regarding relevant disease-related outcomes from human cases is limited, we herein characterized EV-D68 infection in cotton rats by measuring viral load and vRNA (negative or total) in either nose or lung tissues until 4 days p.i., assessing mRNA expression of various chemokines, IFNs, and proinflammatory cytokines, and lung histology. Although the replication cycle of VANBT appeared to be short-lived, its profile of viral titer in the nose over time (showing clear virus eclipse at 4 h, rising quickly and reaching a peak by 10 h p.i.), and their differences with the output virus obtained after infection with different strains demonstrate that VANBT replicates in upper respiratory tract of cotton rats. cache = ./cache/cord-348055-azlb1zy1.txt txt = ./txt/cord-348055-azlb1zy1.txt === reduce.pl bib === id = cord-346089-u31n0qxa author = McDade, Thomas W. title = High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay date = 2020-08-14 pages = extension = .txt mime = text/plain words = 2232 sentences = 140 flesch = 52 summary = title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). Serological testing for SARS-CoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection. In addition, we demonstrate the feasibility and utility of quantifying SARS-CoV-2 antibodies in self-collected DBS with results from a community-based sample enriched with health care workers. We have validated a DBS assay to facilitate large-scale serological testing of SARS-CoV-2 IgG antibodies, and results from our feasibility study document a high rate of household transmission. cache = ./cache/cord-346089-u31n0qxa.txt txt = ./txt/cord-346089-u31n0qxa.txt === reduce.pl bib === id = cord-346067-zly8p0y7 author = Ruiz-Irastorza, Guillermo title = Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data date = 2020-09-22 pages = extension = .txt mime = text/plain words = 4513 sentences = 221 flesch = 52 summary = title: Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data Our therapeutic protocol was updated on April 3 rd 2020, including the recommendation of MP for patients with COVID-19 pneumonia with altered/worsening inflammatory parameters (lymphopenia, thrombocytopenia, rising ferritin, D-dimers and or C-reactive protein) and clinical deterioration, particularly those showing impending respiratory failure with decreasing SpO2/FiO2 values. Other independent predictors of death included a previous diagnosis of arterial hypertension, the use of non-pulse glucocorticoids, a high-risk CURB65 category and SpO2/FiO2 at week 2 ( Table 2 ). Glucocorticoid use, however, should not be indiscriminate, but rather restricted to patients with laboratory evidence of inflammation and progressing respiratory compromise, and best used as short-course pulse therapy (125-250 mg/d of methyl-prednisolone during 3 days) administered during the second week after the onset of symptoms, where the hyperinflammatory reaction takes usually place. cache = ./cache/cord-346067-zly8p0y7.txt txt = ./txt/cord-346067-zly8p0y7.txt === reduce.pl bib === id = cord-346347-r4ork18p author = Borrion, Hervé title = Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China date = 2020-10-14 pages = extension = .txt mime = text/plain words = 7552 sentences = 358 flesch = 49 summary = There are reasons to believe that crime-related performance measures during a pandemic period, or other disasters, may not match the idealised resilience triangle, but rather resemble the dipper-shaped function depicted in Fig 2. Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China RD(n) provides a useful measure to monitor the operating level (%) of offenders. In the case where the crime level in this phase exceeds the pre-Disruptive Event (t DE ) level (μ 7 �μ 1 ), two sub-indicators can be used to measure the ecosystem's resilience during the recovery phase. Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China between τ − and τ + shows it took significantly longer for crime to drop than to return to its expected level. cache = ./cache/cord-346347-r4ork18p.txt txt = ./txt/cord-346347-r4ork18p.txt === reduce.pl bib === id = cord-346819-11fkgzaa author = Khan, Mohd Imran title = Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date = 2020-09-03 pages = extension = .txt mime = text/plain words = 4405 sentences = 291 flesch = 57 summary = title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . cache = ./cache/cord-346819-11fkgzaa.txt txt = ./txt/cord-346819-11fkgzaa.txt === reduce.pl bib === id = cord-348807-9xxc5hyl author = Cuomo, Raphael E. title = Sub-national longitudinal and geospatial analysis of COVID-19 tweets date = 2020-10-28 pages = extension = .txt mime = text/plain words = 3235 sentences = 143 flesch = 43 summary = METHODS: In an effort to better understand the impacts of COVID-19, we concurrently assessed the geospatial and longitudinal distributions of Twitter messages about COVID-19 which were posted between March 3rd and April 13th and compared these results with the number of confirmed cases reported for sub-national levels of the United States. This study suggests that, across subnational areas within the United States, there exists a highly variable threshold of perceived dangerousness and/or intrusiveness required to activate outbreak-related conversations on social media platforms such as Twitter, a finding that can inform future outbreak communication and health promotion strategies. Concurrent geospatial and longitudinal analyses also indicate that predominantly rural areas of the United States increased engagement in COVID-19 social media conversations at later stages of the study timeframe. This study is unique in that it uses Twitter data as a proxy measure for assessing the concurrent longitudinal and geospatial distributions of attention to COVID-19 across local and regional communities in the United States. cache = ./cache/cord-348807-9xxc5hyl.txt txt = ./txt/cord-348807-9xxc5hyl.txt === reduce.pl bib === id = cord-346314-o9fjpqaj author = Jarboui, Mohamed Ali title = Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date = 2012-11-15 pages = extension = .txt mime = text/plain words = 10004 sentences = 521 flesch = 36 summary = Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. Following the detailed annotation of the quantitative abundance changes in the nucleolar protein composition upon Tat expression, we focussed on the Tat-affected cellular complexes and signalling pathways associated with ribosome biogenesis, spliceosome, molecular chaperones, DNA replication and repair and metabolism and discuss their potential involvement in HIV-1 pathogenesis. In this study, we investigated the quantitative changes in the nucleolar proteome of Jurkat T cells constitutively expressing HIV-1 Tat (86aa) versus their Tat-negative counterpart, using stable isotope labelling with amino acids in cell culture (SILAC) technology, followed by ESI tandem mass spectrometry and implemented the experimental approach described in Figure 1A . cache = ./cache/cord-346314-o9fjpqaj.txt txt = ./txt/cord-346314-o9fjpqaj.txt === reduce.pl bib === id = cord-347014-88zmtky7 author = Esposito, Susanna title = Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia date = 2016-11-15 pages = extension = .txt mime = text/plain words = 5518 sentences = 247 flesch = 44 summary = STUDY DESIGN: This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. CONCLUSIONS: This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard. A global evaluation of the results of this study seemed to indicate that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels are unable to differentiate bacterial from viral diseases or to identify severe cases. cache = ./cache/cord-347014-88zmtky7.txt txt = ./txt/cord-347014-88zmtky7.txt === reduce.pl bib === id = cord-348243-e5tdb08v author = Schermer, Bernhard title = Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay date = 2020-11-02 pages = extension = .txt mime = text/plain words = 3958 sentences = 236 flesch = 56 summary = METHODS: To avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK). To allow for the comparison of different nucleic acid detection methods for SARS-CoV-2 we collected redundant material from nasopharyngeal swabs obtained for qPCR testing in clinical routine due to suspected COVID-19. We first tested two recently described assays for SARS-CoV-2 detection on isolated RNA from patient samples. In summary, our multiplex RT-LAMP protocol is a simple and sensitive way to detect SARS-CoV-2 RNA from clinical samples. Currently, a test based on our multiplexed RT-LAMP assay would-in contrast to a good specificity-most likely miss to identify those infected patients with very low amounts of viral RNA in the nose or throat and would not yet reach the sensitivity of the gold-standard qPCR assays. cache = ./cache/cord-348243-e5tdb08v.txt txt = ./txt/cord-348243-e5tdb08v.txt === reduce.pl bib === id = cord-346858-18q8rxzg author = Hossain, Md. Tanvir title = Social and electronic media exposure and generalized anxiety disorder among people during COVID-19 outbreak in Bangladesh: A preliminary observation date = 2020-09-11 pages = extension = .txt mime = text/plain words = 3462 sentences = 171 flesch = 51 summary = Classified as a pandemic by the World Health Organization, the novel Coronavirus Disease (COVID-19) has spread to Bangladesh since early March of 2020, and people are getting daily updates from the social and electronic media. For this cross-sectional study, data were collected from 880 participants by a self-administered online-based questionnaire relating personal characteristics, self-rate health (SRH), SME, and EME with anxiety. The mental health burden of the COVID-19 infected patients and the healthcare professionals, fearing the persisting social prejudice and stigma generated from 'overexposure' to media 'misinformation,' forced some people to commit suicide [22] [23] [24] . At present, the level of anxiety generated from the exposure to social and electronic media during COVID-19 pandemic is not known in Bangladesh, while some other countries have addressed the issue vigorously [13, 18, 36] . cache = ./cache/cord-346858-18q8rxzg.txt txt = ./txt/cord-346858-18q8rxzg.txt === reduce.pl bib === id = cord-347317-qcghtkk0 author = Russo, Lucia title = Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach date = 2020-10-30 pages = extension = .txt mime = text/plain words = 9776 sentences = 397 flesch = 51 summary = For the estimation of the day-zero of the outbreak in Lombardy, as well as of the "effective" per-day transmission rate for which no clinical data are available, we have used the proposed SEIIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March. Among the perplexing problems that mathematical models face when they are used to estimate epidemiological parameters and to forecast the evolution of the outbreak, two stand out: (a) the uncertainty regarding the day-zero of the outbreak, the knowledge of which is crucial to assess the stage and dynamics of the epidemic, especially during the first growth period, and (b) the uncertainty that characterizes the actual number of the asymptomatic infected cases in the total population (see e.g. cache = ./cache/cord-347317-qcghtkk0.txt txt = ./txt/cord-347317-qcghtkk0.txt === reduce.pl bib === id = cord-348499-7ll7sd3o author = Manderstedt, Eric title = Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients date = 2018-02-01 pages = extension = .txt mime = text/plain words = 5449 sentences = 262 flesch = 53 summary = von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. Additional studies of STXBP5 and STX2 [8] and CLEC4M [9, 10] have confirmed that single nucleotide variants (SNVs) in these genes are associated with the variation observed for plasma levels of VWF. CLEC4M also binds to VWF [9] and variants in this gene contribute to the variation in the VWF level observed both in normal individuals [4] and in type 1 VWD patients [9, 10] . The present study aimed to screen comprehensively for genetic variation in the CLEC4M gene in individuals from 106 unrelated type 1 VWD families by re-sequencing the gene region (excluding exon 4) and genotyping the polymorphic neck region (exon 4) of the gene. cache = ./cache/cord-348499-7ll7sd3o.txt txt = ./txt/cord-348499-7ll7sd3o.txt === reduce.pl bib === id = cord-349029-zyfop43z author = Dobrovolny, Hana M. title = Modeling the role of asymptomatics in infection spread with application to SARS-CoV-2 date = 2020-08-10 pages = extension = .txt mime = text/plain words = 4596 sentences = 233 flesch = 48 summary = In order to estimate how effective these strategies will be, we will need a better understanding of the role of asymptomatic individuals in SARS-CoV-2 spread and the effect the proportion and relative infectiousness of asymptomatics have on the time course of the epidemic. In this paper, we study a compartmental epidemic model that includes asymptomatic infections to determine the role that asymptomatic individuals might play in the spread of SARS-CoV-2. We apply our model to data from SARS-CoV-2 epidemics in California, Florida, New York, and Texas, finding that a large number of infections in these states are unreported and that relaxing social distancing measures too early will cause a rapid spike in infections driven in part by these hidden infections. For the SARS-CoV epidemics examined here, the model predicts that there are far more asymptomatic or unreported cases at the peak of the infection, suggesting that there might be widespread community transmission if stay-at-home orders are relaxed too early. cache = ./cache/cord-349029-zyfop43z.txt txt = ./txt/cord-349029-zyfop43z.txt === reduce.pl bib === id = cord-349217-vpih1wvs author = Petropoulos, Fotios title = Forecasting the novel coronavirus COVID-19 date = 2020-03-31 pages = extension = .txt mime = text/plain words = 3159 sentences = 185 flesch = 60 summary = Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. While all three data patterns show an exponential increase, the trends of both the confirmed cases and the deaths were reduced in the mid of February; a second exponential increase is observed in late February and March as a result of the increased number of cases in South Korea, Iran, and Europe. The mean estimate (point forecast) for the confirmed cases ten-days-ahead was 209 thousand with the 90% prediction intervals ranging from about 38 to 534 thousand cases. However, the estimated uncertainty by splitting the data is considerably lower, possibly since the confirmed cases outside Mainland China have significantly increased only recently. cache = ./cache/cord-349217-vpih1wvs.txt txt = ./txt/cord-349217-vpih1wvs.txt === reduce.pl bib === id = cord-350842-4m82l5t8 author = Xing, Jun title = Study of the mental health status of medical personnel dealing with new coronavirus pneumonia date = 2020-05-19 pages = extension = .txt mime = text/plain words = 3219 sentences = 150 flesch = 47 summary = Factors affecting the mental health and status of medical personnel based on their significance from high to low are: the degree of suspicion that they were infected when the novel coronavirusrelated symptoms occurred, the level of concern whether they and their family members have been infected, age, whether they have supported in affected areas in Hubei Province, designated hospitals, and other places for the novel coronavirus, and whether family members support them working on the front line (p < 0.05). The results of this study have shown that the factors affecting the mental health status of medical personnel based on the significance from high to low are: the degree of suspicion that they were infected when the novel coronavirus-related symptoms occurred, the level of concern whether they and their family members have been infected, age, whether they have supported in affected areas in Hubei Province, designated hospitals, and other places for the novel coronavirus, and whether their family members support them working on the front line. cache = ./cache/cord-350842-4m82l5t8.txt txt = ./txt/cord-350842-4m82l5t8.txt === reduce.pl bib === id = cord-349781-l93978vq author = Cong, Yu title = MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells date = 2018-03-22 pages = extension = .txt mime = text/plain words = 5653 sentences = 311 flesch = 51 summary = Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. However, MERS-CoV continued to propagate in immature MDDCs up to 8 days pi, demonstrating differential infection and replication capabilities in MDMs and immature MDDCs. To compare the ability of MERS-CoV to induce innate immune responses in three types of APCs, the release of cytokines and chemokines was measured from virus-or mock-infected cells. cache = ./cache/cord-349781-l93978vq.txt txt = ./txt/cord-349781-l93978vq.txt === reduce.pl bib === id = cord-349476-iac9fak3 author = Mao, Liang title = Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior date = 2011-10-17 pages = extension = .txt mime = text/plain words = 4662 sentences = 245 flesch = 43 summary = The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment. The control of influenza primarily involves applying health resources to affected people, known as control strategies, for example, medical treatment for infected individuals, closure of affected workplaces/schools, and travel restriction to affected communities [4] . Results from the influenza-only model indicate the effectiveness of control strategies without individual preventive behavior. Meanwhile, outcomes from the dual-diffusion model show the combined effectiveness of both control strategies and individual preventive behavior. These two modeled effectiveness are compared to a baseline epidemic scenario, which represents a worst situation of no control strategies and no preventive behavior. This research estimates the combined effectiveness of both control strategies and individual preventive behavior. cache = ./cache/cord-349476-iac9fak3.txt txt = ./txt/cord-349476-iac9fak3.txt === reduce.pl bib === id = cord-350443-ca5avyjf author = Zhang, Lei title = Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy date = 2012-02-16 pages = extension = .txt mime = text/plain words = 7958 sentences = 383 flesch = 49 summary = This study reviews trends in notifiable infectious diseases in China, in their historical context, discusses the current epidemiological state of these infections and their implications for disease surveillance and public health interventions. The total number of diagnosed and death cases were estimated by multiplying morbidity and mortality rates by the overall Chinese population in the study years. In 2008, the three most frequently reported disease types included viral hepatitis (38.3%), bacterial infections (33.3%) and STIs and HIV (9.8%), which account for 5.4, 4.8 and 1.4 million diagnosed cases respectively during the period 2005-2008 (Table 1) . Second, the rapid rise in the number of notified cases of STIs, especially HIV infection, and viral hepatitis in China is associated with growth of the sex industry, increasingly frequent risky sexual behaviours and an increasing number of sexual partners in the general Chinese population. cache = ./cache/cord-350443-ca5avyjf.txt txt = ./txt/cord-350443-ca5avyjf.txt === reduce.pl bib === id = cord-351868-w4d45fue author = Zuwała, Kaja title = The Nucleocapsid Protein of Human Coronavirus NL63 date = 2015-02-20 pages = extension = .txt mime = text/plain words = 6708 sentences = 421 flesch = 53 summary = Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. In order to test subcellular localization of the N protein in LLC-MK2 cells, the maxFP-Green-N/NL63-N encoding RNA was prepared based on the original plasmid. For EMSA assay 10 μg of RNA or DNA corresponding in sequence to the N-NL63 gene (prepared in the same manner as for the transfection of eukaryotic cells) was incubated in buffered solution (5 mM Tris, 50 mM NaCl, pH8.0) with 10 μg of the NTD or CTD for 30 minutes at room temperature. The constructs of NTD and CTD used in this study were designed based on literature data, HCoV-NL63 N protein amino acid sequence alignment with known homologs and on the comparative analysis of currently available crystal structures of these homologs. cache = ./cache/cord-351868-w4d45fue.txt txt = ./txt/cord-351868-w4d45fue.txt === reduce.pl bib === id = cord-349911-dx8wvqkm author = Dahl, Viktor title = Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013 date = 2015-09-23 pages = extension = .txt mime = text/plain words = 4092 sentences = 208 flesch = 49 summary = Ten pathogens in the highest priority group (Borrelia, calicivirus, Campylobacter, Echinococcus multilocularis, hepatitis C virus, HIV, respiratory syncytial virus, SARSand MERS coronavirus, tick-borne encephalitis virus and varicella-zoster virus) did not have any surveillance of typing results. The Public Health Agency of Sweden identified the need to use a structured method that takes relevant aspects into account in order to rationally prioritize between different pathogens when allocating resources for surveillance. The Robert Koch Institute invited ten senior external experts and ten internal experts and asked them to score the pathogens with -1, 0 or 1 for ten variables"Incidence", "Work and school absenteeism", "Health care utilization", "Chronicity of illness or sequelae", "Case fatality rate", "Proportion of events requiring public health actions", "Trend", "Public attention", "Prevention and Treatment possibilities") ( Table 1 ). We used a standardized procedure developed at the Robert Koch Institute to generate a list of pathogens prioritized for surveillance to be used by the Public Health Agency of Sweden. cache = ./cache/cord-349911-dx8wvqkm.txt txt = ./txt/cord-349911-dx8wvqkm.txt === reduce.pl bib === id = cord-351142-g20f6bxc author = Kiaghadi, Amin title = Assessing COVID-19 risk, vulnerability and infection prevalence in communities date = 2020-10-29 pages = extension = .txt mime = text/plain words = 6778 sentences = 313 flesch = 48 summary = A finer spatial resolution is important from a vulnerability and risk standpoint as demonstrated in a recent study that showed that the poorest neighborhoods in Houston, Texas, might be at a higher risk of hospitalization from COVID-19 [14] based on an analysis of the Centers for Disease Control (CDC) underlying risk factors for severe COVID-19 cases [4] that include: asthma, Chronic Obstructive Pulmonary Disease (COPD), heart disease, hypertension, diabetes, and a history of heart attacks or strokes. In this study, we develop a rigorous planning tool at the census tract level that examines influential determinants of vulnerability to COVID-19 in 5 broad categories (with 46 variables) that include: 1) access to medical services, 2) underlying medical conditions, 3) environmental exposures, 4) vulnerability to natural disasters and 5) sociodemographic, behavioral, and lifestyle factors. Fig 9A shows the normalized total number of confirmed COVID-19 cases as of August 16, 2020, in Harris County at the census tract level. cache = ./cache/cord-351142-g20f6bxc.txt txt = ./txt/cord-351142-g20f6bxc.txt === reduce.pl bib === id = cord-352200-i05h8csb author = Xu, Yi title = Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date = 2012-04-27 pages = extension = .txt mime = text/plain words = 5286 sentences = 278 flesch = 47 summary = title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. As a whole, 81388 distinct unigenes have been identified and the results indicated that SRBSDV infection can potentially perturb primary metabolism and the ubiquitin-proteasome pathway of WBPH and activate immune regulatory systems, such as RNA interfering, autophagy and antimicrobial peptide production. However, some unigenes were obtained only from viruliferous or non-viruliferous samples (data not shown) and we believe these differences may be caused by distinctions that arise from long-term ecological adaptation to virus infection. In addition, GO analysis also showed a similar distribution of gene functions for non-viruliferous and viruliferous WBPH (Figure 4 ), indicating that the number of genes expressed in each GO category was not significantly affected by SRBSDV infection. cache = ./cache/cord-352200-i05h8csb.txt txt = ./txt/cord-352200-i05h8csb.txt === reduce.pl bib === id = cord-351387-i0zamkpd author = Witte, Katrin title = The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date = 2015-09-25 pages = extension = .txt mime = text/plain words = 4360 sentences = 220 flesch = 49 summary = In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. In the first setting, PBMCs were stimulated with EPs 7630 (3 and 30 μg/ml), Escherichia coli 0127:B8 lipopolysaccharide (TLR4 ligand; 100 ng/ml; Sigma-Aldrich), polyinosinic-polycytidylic acid [poly (I:C); 10 μg/ml; Sigma-Aldrich], a cytokine mixture of IL-1β, IL-2 and IL-12 (10 ng/ml each; R&D systems), anti-CD3 (Orthoclone; Cilag) and anti-CD28 (R&D systems) monoclonal antibodies (1 μg/ml each), or were left without specific treatment (0.1% ethanol as solvent control) for 4 and 24 h, before cell culture supernatant was recovered for ELISA cytokine production analysis. Our data show that EPs 7630 strongly and dose-dependently induced the production of the pro-inflammatory cytokines TNF-α and IL-6 in human blood immune cells. cache = ./cache/cord-351387-i0zamkpd.txt txt = ./txt/cord-351387-i0zamkpd.txt === reduce.pl bib === id = cord-351185-3y3gou6v author = Buckles, Thomas C. title = Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating date = 2020-05-29 pages = extension = .txt mime = text/plain words = 10061 sentences = 465 flesch = 45 summary = However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). In contrast, ibuprofen and acetaminophen are classified as adaptive because rapid addition of either drug to polarized cells yields short-term collapse of the leading edge pseudopod and loss of the PIP 3 signal, followed by slow recovery. In contrast to the four therapeutic adaptive drugs, the two non-clinical control inhibitors wortmannin and Gö6976 are each known to directly inhibit key components of the leading edge positive feedback loop and rapid addition is observed herein to trigger long term collapse of the pseudopod with no detected recovery as previously observed [26, 30, [50] [51] [52] [53] [54] . cache = ./cache/cord-351185-3y3gou6v.txt txt = ./txt/cord-351185-3y3gou6v.txt === reduce.pl bib === id = cord-352222-zq9o66i4 author = Rajatonirina, Soatiana title = Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012 date = 2013-09-12 pages = extension = .txt mime = text/plain words = 4137 sentences = 245 flesch = 46 summary = BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. Our study aimed to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old hospitalised in one of the four main public hospitals in Antananarivo. In our study, Streptococcus pneumoniae was the most common bacterial pathogen as in other studies of hospitalised patients with acute respiratory illness, and Haemophilus influenzae type B was the next most frequent [16] [17] [18] [19] . cache = ./cache/cord-352222-zq9o66i4.txt txt = ./txt/cord-352222-zq9o66i4.txt === reduce.pl bib === id = cord-352403-4591ewsa author = Hartwig, Stacey M. title = Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection date = 2014-03-07 pages = extension = .txt mime = text/plain words = 3773 sentences = 194 flesch = 55 summary = In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. We have previously shown that intranasal MHV-1 infection of C3H/HeJ mice, which harbor a natural mutation in the gene that encodes toll-like receptor 4 (TLR4) [15, 16] , results in increased morbidity and mortality along with severe pulmonary disease as compared to the wild-type C3H/HeN mice [17] . We observed a significant (p,0.05) decrease in the total number of MHV-1-specific IFN-c-producing CD4 T cells in the BAL of CL-treated mice as compared to PBS controls ( Figure 4C ). We also observed a significant increase in the total number and frequency of Tregs following MHV-1 infection in both the airways and lung tissue of the CL-treated mice. cache = ./cache/cord-352403-4591ewsa.txt txt = ./txt/cord-352403-4591ewsa.txt === reduce.pl bib === id = cord-351990-aham72b9 author = Radin, Jennifer M. title = Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations date = 2014-12-30 pages = extension = .txt mime = text/plain words = 4511 sentences = 220 flesch = 43 summary = METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. This study aimed to describe characteristics associated with specific respiratory pathogens, as well as the etiology, seasonality, and coinfection rates among three US populations: military recruits, Department of Defense (DoD) beneficiaries, and civilians living near the US-Mexico border. Additionally, the following demographic and clinical signs and symptoms were collected from each FRI and SARI case: sex, age, study population, month of illness, pneumonia, sore throat, cough, nausea, shortness of breath, congestion, pink eye, body ache, headache, temperature, number of days of symptoms before seeking care, and date of seeking care. cache = ./cache/cord-351990-aham72b9.txt txt = ./txt/cord-351990-aham72b9.txt === reduce.pl bib === id = cord-351918-pu7i1jfe author = Baek, Yae Jee title = A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies date = 2020-10-26 pages = extension = .txt mime = text/plain words = 4902 sentences = 278 flesch = 51 summary = The effects of different intervention strategies such as front door screening, quarantine unit for newly admitted patients, early testing of suspected infected people, and personal protective equipment for both medical staff and visitors were evaluated. The model suggested that the early testing (within eight hours) of infected cases and monitoring the quarantine ward for newly hospitalized patients are effective measures for decreasing the incidence of COVID-19 within a hospital (81.3% and 70% decrease of number of incident cases, respectively, during 60 days). Setting the population vector η as the number of staff, and the stabilized number of inflow and outflow to each department for visitors, we construct the WAIFW matrix, W, by assuming that it is proportional to the contact rate matrix [8, 9] : The diagram for the SEIR (susceptible-exposed-infectious-recovered) model with compartments of doctor, nurse, patient, and caregiver. cache = ./cache/cord-351918-pu7i1jfe.txt txt = ./txt/cord-351918-pu7i1jfe.txt === reduce.pl bib === id = cord-351098-x729wpp7 author = Long, Rachel B. title = Characterizing trends in human-wildlife conflicts in the American Midwest using wildlife rehabilitation records date = 2020-09-11 pages = extension = .txt mime = text/plain words = 6361 sentences = 244 flesch = 37 summary = The purpose of this study was to examine the value of wildlife rehabilitation facility admissions records for informing understanding of local human-wildlife conflicts and wildlife disease trends by 1) identifying the top reasons for admission to this facility, 2) examining how occurrences as measured by admitted cases may fluctuate monthly and across taxa, and 3) analyzing trends in commonly admitted disease cases. To examine how human-wildlife conflict as measured by admissions to this facility may vary seasonally and across taxonomic groups, we assessed changes in mean cases admitted per month via Chi-squared tests. We further examined the top four identified specific causes of admission to the wildlife rehabilitation facility: orphaned, dog attacks, cat attacks, and vehicle strikes. Our study demonstrates the value of wildlife rehabilitation records for characterizing local human-wildlife conflicts and potentially select disease trends, as well as how occurrences may fluctuate seasonally and impact taxa differently. cache = ./cache/cord-351098-x729wpp7.txt txt = ./txt/cord-351098-x729wpp7.txt === reduce.pl bib === id = cord-352564-2j4pjjwk author = Dominguez, Samuel R. title = Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response date = 2013-07-24 pages = extension = .txt mime = text/plain words = 4449 sentences = 199 flesch = 46 summary = Because they are the natural target cells for respiratory virus infection, primary human respiratory epithelial cell cultures provide the ideal in vitro systems for investigation of cell factors required for growth of respiratory human viruses, for analysis of their interactions with viruses and their innate immune responses to infection, and for isolation and propagation of novel respiratory pathogens. Here we demonstrate that HCoV-HKU1 can infect and be serially propagated in primary human alveolar type II cells but not in alveolar type I-like cells or alveolar macrophages at the air-liquid interface. Titers of viral RNA in the wash from the apical surface of the cells were determined by qRT-PCR at the indicated time points, and HCoV-HKU1 Infection of Type II Alveolar Cells PLOS ONE | www.plosone.org cultures were fixed and immunolabeled with antibodies to the HCoV-HKU1 spike glycoprotein to identify infected cells. In summary, HCoV-HKU1 can infect, be serially propagated, and induce an anti-viral response in human alveolar type II cells maintained at an air-liquid interface. cache = ./cache/cord-352564-2j4pjjwk.txt txt = ./txt/cord-352564-2j4pjjwk.txt === reduce.pl bib === id = cord-353200-5csewb1k author = Jehi, Lara title = Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19 date = 2020-08-11 pages = extension = .txt mime = text/plain words = 4344 sentences = 226 flesch = 40 summary = OBJECTIVE: To characterize a large cohort of patients hospitalized with COVID-19, their outcomes, develop and validate a statistical model that allows individualized prediction of future hospitalization risk for a patient newly diagnosed with COVID-19. DESIGN: Retrospective cohort study of patients with COVID-19 applying a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to retain the most predictive features for hospitalization risk, followed by validation in a temporally distinct patient cohort. MEASUREMENTS: Demographic, clinical, social influencers of health, exposure risk, medical co-morbidities, vaccination history, presenting symptoms, medications, and laboratory values were collected on all patients, and considered in our model development. Hospitalization risk prediction and outcomes in COVID-19 PLOS ONE | https://doi.org/10.1371/journal.pone.0237419 August 11, 2020 2 / 15 ethical restrictions by the Cleveland clinic regulatory bodies including the institutional review Board and legal counsel. We also develop and validate a statistical model that can assist with individualized prediction of hospitalization risk for a patient with COVID-19. cache = ./cache/cord-353200-5csewb1k.txt txt = ./txt/cord-353200-5csewb1k.txt === reduce.pl bib === id = cord-350398-w75flrwv author = Sampath, Rangarajan title = Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry date = 2012-06-29 pages = extension = .txt mime = text/plain words = 11138 sentences = 581 flesch = 50 summary = Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry. In addition to detecting the threat organisms, the biothreat assay described here also detects virulence factors associated with three of the agents: Bacillus anthracis (pXO1 and pXO2), Yersinia pestis (pla and caf), and Vibrio cholera (ctx1). PCR primers were designed to conserved regions within the selected target genes such that the targeted threat agent was clearly identified and differentiated from its near-neighbor species ( Table 1) . In the biothreat assay, the Francisella biocluster is identified by two genus-specific primer pairs targeting the asd (BCT2328) and galE (BCT2332) genes ( Table 1) . cache = ./cache/cord-350398-w75flrwv.txt txt = ./txt/cord-350398-w75flrwv.txt === reduce.pl bib === id = cord-352511-gkm7i62s author = Yamada, Yoshiyuki title = Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells date = 2009-07-02 pages = extension = .txt mime = text/plain words = 5731 sentences = 317 flesch = 55 summary = title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins. In this study, we report that acquisition of the cell-cell fusion activity by point mutations in the spike (S) protein of avian coronavirus infectious bronchitis virus (IBV) plays a critical role in adaptation and/or selection of a variant that infects cultured cells. Sequence comparison of two S protein constructs, S(EP3) and S(CK), cloned from EP3 and CK-adapted IBV strains, respectively, showed amino acid substitutions at 31 positions (Fig. 1a) . cache = ./cache/cord-352511-gkm7i62s.txt txt = ./txt/cord-352511-gkm7i62s.txt === reduce.pl bib === id = cord-353866-0r1b44id author = Sun, Hongpeng title = Changes of Adult Population Health Status in China from 2003 to 2008 date = 2011-12-02 pages = extension = .txt mime = text/plain words = 3421 sentences = 185 flesch = 54 summary = Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. This study aimed to describe the male and female adult Chinese population health status in multiple dimensions, including overall morbidity, presence of illness in the last 2 weeks and chronic disease in the last 6 months, and healthy behavior as regards smoking, alcohol consumption, and physical activity, using data from the most recent National Health Services Surveys by the Chinese government in 2003 and 2008. However, overall Chinese adult population health status has not been improved due to short time and small proportion of residents performing frequent exercise; hence it seems that the prevalence and burden of chronic diseases will continue to grow. cache = ./cache/cord-353866-0r1b44id.txt txt = ./txt/cord-353866-0r1b44id.txt === reduce.pl bib === id = cord-352219-z245sb3s author = Tallam, Aravind title = Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date = 2016-02-12 pages = extension = .txt mime = text/plain words = 9117 sentences = 467 flesch = 43 summary = Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Putative transcriptional regulators of IRG1 were hypothesized from the resulting GRN and tested using siRNA-mediated gene silencing experiments in mouse and human macrophages under LPS stimulation. Although the human data were obtained from primary cells, while the mouse analysis was conducted using the macrophage cell line RAW264.7, it is tempting to speculate that the transcriptional machinery inducing IRG1 expression, with the exception of IRF1, is mostly species-specific, as highlighted by the different transcriptional regulators identified in the two species (Table 1) . cache = ./cache/cord-352219-z245sb3s.txt txt = ./txt/cord-352219-z245sb3s.txt === reduce.pl bib === id = cord-352522-qnvgg2e9 author = Langille, Morgan G. I. title = BioTorrents: A File Sharing Service for Scientific Data date = 2010-04-14 pages = extension = .txt mime = text/plain words = 2994 sentences = 158 flesch = 51 summary = In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. A BitTorrent software client (see Table 1 ) uses the data in the torrent file to contact the tracker and allow transferring of the data between computers containing either full or partial copies of the dataset. Information about each dataset on BioTorrents is supplied on a details page giving a description of the data, number of files, date added, user name of the person who created the dataset, and various other details including a link to the actual torrent file. As the number of datasets and users of BioTorrents increases, and to improve on transfer speeds on a geospatial scale (i.e. across countries and continents), we would encourage other institutions to automatically download and share all or some of the data on BioTorrents. cache = ./cache/cord-352522-qnvgg2e9.txt txt = ./txt/cord-352522-qnvgg2e9.txt === reduce.pl bib === id = cord-352720-z1cvjc2y author = Díaz-Corvillón, Pilar title = Routine screening for SARS CoV-2 in unselected pregnant women at delivery date = 2020-09-29 pages = extension = .txt mime = text/plain words = 4061 sentences = 244 flesch = 49 summary = While initial evidence suggests that pregnant women were not at increased risk for COVID-19, neither developed a more severe disease compared to non-pregnant adults [3, 4] , recent reports suggest increased rates of preterm birth [5] , pneumonia and intensive care unit admission [6] , and maternal mortality [6, 7] . The main objective of this study was to assess point-prevalence of SARS CoV-2 infection in unselected obstetrical population at the time of delivery and to describe the presentation and clinical evolution of confirmed cases. women were screened for COVID-19 clinical symptoms including fever, cough and shortness of breath by trained personnel, and RT-PCR for SARS CoV-2 (Allplex TM 2019-nCoV Assay [17] ) was performed by nasopharyngeal swab, unless a prior test with no more than 48 hours to admission was reported. cache = ./cache/cord-352720-z1cvjc2y.txt txt = ./txt/cord-352720-z1cvjc2y.txt === reduce.pl bib === id = cord-353245-es7b1rs0 author = Song, Deping title = Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013 date = 2015-03-19 pages = extension = .txt mime = text/plain words = 4259 sentences = 176 flesch = 55 summary = Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5'-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. Genetic characteristics were observed between the two groups: 1) compared to genome sequences of the members in G1, four insertions, 20803G, 20810CAGGGTGTCAA20820, 20830G, 21042AAT21044 and two deletions, 20842A, 21097CGTGAT21102, existed in the N-terminal domain (NTD) of the S protein in G 2 members; 2) the three field PEDV strains of JS2008, JS2008new and SD-M together with two attenuated PEDV strains, DR13 and vaccine_KC189944, were clustered into subgroup 1b. Notably, an amino acid substitution was found in the middle of one neutralizing epitope Phylogenetic trees based on the complete genome, aa sequences of structural proteins and ORF3 of PEDV strains. Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China cache = ./cache/cord-353245-es7b1rs0.txt txt = ./txt/cord-353245-es7b1rs0.txt === reduce.pl bib === id = cord-352447-bc1pf272 author = Nishida, Yu title = Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio date = 2020-10-26 pages = extension = .txt mime = text/plain words = 3481 sentences = 197 flesch = 47 summary = Despite conflicting results, the development of pouchitis in patients with UC, as reported in several studies, has been linked to various factors, including primary sclerosing cholangitis [2, 4] , other extraintestinal manifestations of inflammatory bowel disease [4, 8, 9] , young age at UC diagnosis [4] , preoperative terminal ileal inflammation [10, 11] , extensive colonic disease [10], presence of interleukin-1 receptor antagonist gene allele 2 [12] , total steroid dose of > 10000 mg [13] , use of infliximab [14] , neutrophil percentage of > 65% [13] , and presence of perinuclear antineutrophil cytoplasmic antibodies [15, 16] . Therefore, our study aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in patients with UC. Third, we were unable to evaluate the reported pouchitis predictive factors, such as extraintestinal manifestations of inflammatory bowel disease, preoperative terminal ileal inflammation, the presence of interleukin-1 receptor antagonist gene allele 2, total steroid dose of >10000 mg, or presence of perinuclear antineutrophil cytoplasmic antibodies owing to the retrospective design of the study. cache = ./cache/cord-352447-bc1pf272.txt txt = ./txt/cord-352447-bc1pf272.txt === reduce.pl bib === id = cord-353869-l53ms3q8 author = Friesen, Robert H. E. title = New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets date = 2010-02-08 pages = extension = .txt mime = text/plain words = 4680 sentences = 202 flesch = 44 summary = METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. Mean decline in body weight at the end of the experiment was 6.2% in the group of ferrets that received CR6261 4 hours after challenge ( Figure 2B) , which was significantly less (p = 0.025) than the 10.1% observed in control animals. These findings were in accordance with the observation that the mean lung weights of ferrets treated with CR6261 at 4 hours post challenge were lower compared to the control group (5.7 g versus 14.9 g, p,0.001; Figure 2F ). cache = ./cache/cord-353869-l53ms3q8.txt txt = ./txt/cord-353869-l53ms3q8.txt === reduce.pl bib === id = cord-356132-1nisyl5r author = Wang, Huiyao title = The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey date = 2020-05-14 pages = extension = .txt mime = text/plain words = 3022 sentences = 148 flesch = 43 summary = The population with younger age (F = 102.04), unmarried (t = 15.28), with history of visiting Wuhan in the past month (t = -40.86), with history of epidemics occurring in the community (t = -10.25), more concern with media reports (F = 21.84), perceived more impacts of the epidemic outbreak (changes over living situations, F = 331.71; emotional control, F = 1863.07; epidemic-related dreams, F = 1642.78) and negative coping style (t = 37.41) had higher level of psychological distress. The general mainland Chinese population with unmarried, history of visiting Wuhan in the past month, perceived more impacts of the epidemic and negative coping style had higher level of psychological distress in the early stages of COVID-19 epidemic. Unmarried, history of visiting Wuhan, more serious changes over living situations, more difficult of emotional control, higher frequency of epidemic-related dreams, and negative coping style in the general population showed higher level of psychological distress. cache = ./cache/cord-356132-1nisyl5r.txt txt = ./txt/cord-356132-1nisyl5r.txt === reduce.pl bib === id = cord-353253-kk2q71vg author = Itokawa, Kentaro title = Disentangling primer interactions improves SARS-CoV-2 genome sequencing by multiplex tiling PCR date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3327 sentences = 179 flesch = 52 summary = Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. In our experience, the low to zero depth for those two amplicons was the most frequent bottleneck for using the ARTIC primer set V1 to sequence all targeted genomic regions from samples with middle to low viral load (Ct > 27). The results indicated that preventing primer dimerformation is an effective measure to improve coverage bias in the ARTIC Network's SARS-CoV-2 genome sequencing protocol, and may be applicable to other PrimalSeq methods in general. The formation of primer-dimers is a major cause of coverage bias in the ARTIC Network's multiplex PCR protocol for SARS-CoV-2 genome sequencing. A proposal of an alternative primer for the ARTIC Network's multiplex PCR to improve coverage of SARS-CoV-2 genome sequencing (manuscript version 1) cache = ./cache/cord-353253-kk2q71vg.txt txt = ./txt/cord-353253-kk2q71vg.txt === reduce.pl bib === id = cord-355874-nz6eqcdb author = Wang, Le title = A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia date = 2016-09-14 pages = extension = .txt mime = text/plain words = 3067 sentences = 160 flesch = 54 summary = title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia In this study, we used the GeXP-based assay for simultaneous detection of 20 types/subtypes of viruses in 1699 nasopharyngeal specimens collected from hospitalized children with CAP. To evaluate the sensitivity of the GeXP assay, nucleic acid from all 20 target viruses and the internal control pcDNA3.1 (+) DNA were mixed to make the template pool. In the present study, we applied multiplex RT-PCR together with automated capillary electrophoresis, namely the GeXP-based assay, to detect virus in 1699 nasopharyngeal specimens from hospitalized children with CAP. We showed that the GeXP-based assay had high sensitivity and specificity for simultaneous detection of multiple viruses, and about 65% of cases tested were positive for virus. The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/ subtypes cache = ./cache/cord-355874-nz6eqcdb.txt txt = ./txt/cord-355874-nz6eqcdb.txt === reduce.pl bib === id = cord-353410-tbmtg88k author = Sharma, Shreela V. title = Using a rapid assessment methodology to identify and address immediate needs among low-income households with children during COVID-19 date = 2020-10-01 pages = extension = .txt mime = text/plain words = 3942 sentences = 205 flesch = 56 summary = Due to COVID-19-related school closures, states were under "shelter in place" orders, and Brighter Bites administered a rapid assessment survey to identify social needs among their families. While overall results of the qualitative thematic analysis for the n = 1048 participants are presented elsewhere (Sharma et al., under review) , a qualitative analysis of participant responses in the high-risk group revealed four major themes presented in Table 2 : fear of contracting COVID-19, disruption of employment status, financial hardship, and exacerbated food insecurity. Conducting a COVID-19 rapid response survey was a purposeful decision on part of Brighter Bites to identify those with highest need during this time of crisis and develop a framework to immediately address a variety of social needs among those in the "high risk" category. cache = ./cache/cord-353410-tbmtg88k.txt txt = ./txt/cord-353410-tbmtg88k.txt === reduce.pl bib === id = cord-354000-jxqskt4k author = Warren, Cody J. title = The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date = 2014-05-14 pages = extension = .txt mime = text/plain words = 4420 sentences = 265 flesch = 47 summary = Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. cache = ./cache/cord-354000-jxqskt4k.txt txt = ./txt/cord-354000-jxqskt4k.txt === reduce.pl bib === id = cord-356364-ipi81ce3 author = Ho, Bo-Lin title = Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease date = 2015-12-14 pages = extension = .txt mime = text/plain words = 5038 sentences = 277 flesch = 62 summary = In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. The colorimetry-based peptide substrate, TSAVLQ-para-nitroanilide (TQ6-pNA) (purity 95-99% by HPLC; GL Biochem Ltd, Shanghai, China), was used to measure the proteolytic activity of MERS-CoV M pro and its mutants throughout the course of the study as described previously [25, 28] . In addition, although the K d values of wild-type SARS-CoV M pro without or with substrates show no significant difference (Table 2) , it was possible to detect substrate-induced dimerization at a protein concentration of 1 μM by AEC [33] . Biochemical and AUC studies indicated that MERS-CoV M pro shows almost the same proteolytic activity as SARS-CoV M pro ; although it is a monomer in aqueous buffer and displays substrate-induced dimerization (Fig 6) . cache = ./cache/cord-356364-ipi81ce3.txt txt = ./txt/cord-356364-ipi81ce3.txt === reduce.pl bib === id = cord-354052-x4ckzw64 author = Li, Chunhua title = Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination date = 2013-08-02 pages = extension = .txt mime = text/plain words = 4932 sentences = 256 flesch = 53 summary = We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. All mPEDV infected cells stained positive both with the polyclonal MHV serum and with the monoclonal antibody directed against the PEDV nucleocapsid protein confirming the purity and the identity of the chimeric virus. Donor RNAs transcribed from the pPEDV and pPEDV-DORF3 transfer vectors were electroporated into mPEDV-infected L cells after which we were able to recover and purify the r-wtPEDV and PEDV-DORF3 viruses in VERO cells. Thus, the PEDV-DORF3/GFP and PEDV-DORF3/RLuc virus were preincubated with dilutions of serum obtained from an experimentally PEDV-infected pig and control serum, and the mixtures were subsequently added to VERO cells and incubated after which the GFP and Renilla luciferase expression was recorded at 9 and 6 hours p.i., respectively (Fig. 5D) . cache = ./cache/cord-354052-x4ckzw64.txt txt = ./txt/cord-354052-x4ckzw64.txt === reduce.pl bib === id = cord-354763-odzrco6q author = Drake, John M. title = Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore date = 2006-12-20 pages = extension = .txt mime = text/plain words = 5739 sentences = 283 flesch = 46 summary = We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. We also retrospectively explore the effect of societal learning during the 2003 outbreak of SARS in Singapore, using weekly data on the time between onset of symptoms and removal of infectious individuals. Finally, we discuss societal and epidemiological factors that might affect societal learning, we observe that a difficult task during the early stages of an outbreak is to estimate the learning rate and suggest that the rate estimated here might be used as prior information in future outbreaks, and we conclude by recommending rapid investment in research at the time of initial detection when actions taken to reduce disease spread can be most efficient and cost effective. cache = ./cache/cord-354763-odzrco6q.txt txt = ./txt/cord-354763-odzrco6q.txt === reduce.pl bib === id = cord-353596-8iqjugcx author = Bédubourg, Gabriel title = Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study date = 2017-07-17 pages = extension = .txt mime = text/plain words = 5603 sentences = 313 flesch = 53 summary = Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The objective of this paper is to evaluate the performance of 21 statistical methods applied to large simulated datasets for outbreak detection in weekly health surveillance. Table 2 presents averaged FPR, specificity, POD, POD1week, sensitivity, negative predictive value, positive predictive value and F 1 -measure for all 42 scenarios and all past and current outbreak amplitude and duration and for α = 0.01. cache = ./cache/cord-353596-8iqjugcx.txt txt = ./txt/cord-353596-8iqjugcx.txt === reduce.pl bib === id = cord-355259-779czzzx author = Yang, Xiaoyun title = A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus date = 2014-10-15 pages = extension = .txt mime = text/plain words = 6143 sentences = 324 flesch = 47 summary = Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract. To this purpose, we applied swine influenza virus to a model we previously set up using porcine respiratory mucus, pseudorabies virus (PRV) and single particle tracking (SPT) [20] . This does not only confirm the beneficial effect of neuraminidase on releasing SIV from respiratory mucus, but also highlights bidirectional synergistic interactions between influenza virus and bacterial infections. cache = ./cache/cord-355259-779czzzx.txt txt = ./txt/cord-355259-779czzzx.txt === reduce.pl bib === id = cord-354547-eomm1sl5 author = Wang, Jibin title = Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date = 2009-03-16 pages = extension = .txt mime = text/plain words = 6319 sentences = 295 flesch = 51 summary = title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding In this study, we report that interaction between coronavirus membrane protein (M) and actin with functional implication in facilitating virion assembly and budding. Similarly, analysis of cells expressing the M protein either on its own or together with the Myc-tagged actin by Western blot with anti-M polyclonal antibodies showed the detection of the full-length glycosylated (two upper bands) and unglycosylated (25 kDa) forms of the M protein (Fig. 2, lanes 5 and 6) . In cells transfected with both wild type and MD5 constructs with or without IBV infection, detection of similar amounts of M protein was observed (Fig. 5b, top two panels, lanes 1 and 2) , suggesting that both constructs were expressed at similar efficiencies. cache = ./cache/cord-354547-eomm1sl5.txt txt = ./txt/cord-354547-eomm1sl5.txt === reduce.pl bib === id = cord-353730-owcapg8h author = Dietrich, Jes title = Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01 date = 2014-06-23 pages = extension = .txt mime = text/plain words = 7885 sentences = 389 flesch = 53 summary = The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. Based on neutralization titers obtained from mice vaccinated with a range of doses from 30 DU (D-Units) to 0.1 DU (data not shown) we choose 20 DU as a full mouse dose and 2 DU as the dose formulated into the CAF01 adjuvant (indicated dose units in the all experiments correspond to polio virus type-1 D antigen units). Taken together, compared to IM administration a side by side ID+IM administration with a CAF01-adjuvanted vaccine followed by an IM administration did not negatively affect systemic immunity, measured by antibody binding and neutralization titers and T cell IFN-c secretion (Fig. 6) . cache = ./cache/cord-353730-owcapg8h.txt txt = ./txt/cord-353730-owcapg8h.txt ===== Reducing email addresses cord-268524-lr51ubz5 cord-312033-iarl77n0 cord-353200-5csewb1k Creating transaction Updating adr table ===== Reducing keywords cord-000013-pr9i9swk cord-000063-tex6bgab cord-000166-36bfeoqv cord-000050-tfcerilc cord-000079-533xlisc cord-000266-xwfptmmv cord-000131-ugbwvy6j cord-000006-104sqoxz cord-000008-3dgjv0x1 cord-000082-jy7j8sh0 cord-000269-v4jochbe cord-000574-7eflwyxk cord-000255-73nlxqgk cord-000540-bbjmcdo5 cord-000366-u4649rtx cord-000140-5kapn32k cord-000408-pt3b4yc7 cord-000224-2lz03oqb cord-000176-z76vjkxg cord-000077-d441jam3 cord-000460-h3owwjao cord-000588-3wok0n21 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score: 48 nouns: cells; virus; infection; study; patients; protein; data; cell; influenza; analysis; disease; time; expression; cases; number; results; viruses; studies; model; samples; control; proteins; health; mice; group; type; gene; infections; levels; population; risk; response; ml; detection; activity; age; sequence; days; children; effect; coronavirus; case; antibody; rate; treatment; sequences; system; role; level; factors verbs: using; shown; including; based; report; increased; find; associated; compared; identified; following; detected; infected; performed; observed; inducing; suggest; indicates; described; contains; provide; determine; binding; expressing; testing; obtained; confirmed; reduced; collected; required; caused; result; related; analyzed; considering; gave; develop; demonstrates; estimating; seen; known; assess; affect; represents; lead; measure; taken; making; according; predicting adjectives: viral; human; respiratory; high; different; specific; clinical; positive; higher; significant; severe; non; acute; anti; first; similar; infectious; immune; low; negative; total; important; new; lower; single; several; infected; molecular; social; large; present; previous; small; novel; early; possible; many; available; multiple; potential; cellular; public; common; primary; bacterial; covid-19; effective; antiviral; like; inflammatory adverbs: also; however; well; respectively; significantly; previously; therefore; highly; even; first; furthermore; recently; approximately; still; moreover; finally; less; directly; prior; together; least; especially; often; relatively; particularly; frequently; similarly; statistically; much; additionally; interestingly; specifically; rather; likely; subsequently; currently; mainly; alone; potentially; indeed; generally; commonly; strongly; almost; fully; briefly; clearly; later; now; overall pronouns: we; it; our; their; its; they; i; them; us; his; one; you; itself; themselves; her; he; my; your; she; me; him; ours; pregn; myself; yourself; imagej; mrnas; ifitm3; em; ourselves; nsp10; ns3/4a; apod; 9b; mg; interleukin-10; il-2rcc; herself; clustalx; stat1; oneself; cav-1b; ĝ; theirs; snoz40; s; rad5; p450s; mine; lc16m8 proper nouns: Fig; RNA; PCR; SARS; COVID-19; C; Table; T; China; IFN; RT; CoV-2; A; Health; CoV; S1; H1N1; mg; HIV; HIV-1; M; USA; PBS; HCV; B; S; HA; CD4; N; MERS; RSV; II; Influenza; NP; Figure; ELISA; H5N1; CD8; PLoS; HRV; sha; United; a1111111111; DNA; Coronavirus; University; D; Disease; E.; pH keywords: covid-19; sars; pcr; rna; cell; virus; patient; respiratory; protein; ifn; influenza; china; dna; infection; h1n1; case; study; rsv; health; model; hiv-1; hcv; bat; mers; hiv; h5n1; table; icu; cd8; cd4; vero; sequence; pneumonia; pedv; lps; gene; viral; usa; sari; sample; risk; ili; ibv; hrv; ebola; united; taiwan; peptide; outbreak; elisa one topic; one dimension: virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565067/ titles(s): HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection three topics; one dimension: study; virus; cells file(s): https://doi.org/10.1371/journal.pone.0239666, https://doi.org/10.1371/journal.pone.0134851, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733918/ titles(s): Why do people spread false information online? The effects of message and viewer characteristics on self-reported likelihood of sharing social media disinformation | Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins | TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection five topics; three dimensions: covid study health; cells virus cell; respiratory virus influenza; protein proteins using; infection virus mice file(s): https://doi.org/10.1371/journal.pone.0240878, https://www.ncbi.nlm.nih.gov/pubmed/22359682/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712091/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035654/, https://www.ncbi.nlm.nih.gov/pubmed/27556586/ titles(s): A social network model of COVID-19 | Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin | Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection | Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA | Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge Type: cord title: journal-plosOne-cord date: 2021-05-30 time: 15:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"PLoS One" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-000877-usz7pnvu author: Abdel-Moneim, Ahmed S. title: Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia date: 2013-01-30 words: 1826.0 sentences: 101.0 pages: flesch: 51.0 cache: ./cache/cord-000877-usz7pnvu.txt txt: ./txt/cord-000877-usz7pnvu.txt summary: title: Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV. Human bocavirus (HBoV) was first found in children with acute respiratory tract infections in 2005 [1] . The current study aims to screen the epidemiological status and molecular phylogeny of HBoV isolates prevailing in pediatric patients with respiratory infection in Saudi Arabia. The current study investigated the prevalence of HBoV in patients suffering from respiratory tract infections in Saudi Arabia. Furthermore, the phylogenetic analysis results of three selected sequences showed that the Saudi HBoV1 strains obtained from respiratory samples belonged to group I human bocaviruses (Fig. 1) . Detection of human bocavirus in Japanese children with lower respiratory tract infections Frequent detection of viral coinfection in children hospitalized with acute respiratory tract infection using a real-time polymerase chain reaction abstract: Human bocavirus (HBoV) was recently discovered in children with respiratory distress and/or diarrhea. To our knowledge, no previous study has reported the existence of bocavirus in Saudi Arabia. Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV. Real-time polymerase chain reaction was used as a sensitive method to detect the HBoV. Direct gene sequencing was used to determine the genotype of the detected virus isolates. HBoV was detected in 22.5% of the examined patients. The NP1 partial gene sequence from all patients showed that the circulated strains were related to HBoV-1 genotype. Most of HBoV infected patients showed evidence of mixed coinfection with other viral pathogens. The current study clearly demonstrated that genetically conserved HBoV1 circulates in Saudi Arabia. Interestingly, most of the HBoV1 infected cases were associated with high rates of co-infections with other viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559585/ doi: 10.1371/journal.pone.0055500 id: cord-004091-gex0zvoa author: Abdulkareem, Shaheen A. title: Risk perception and behavioral change during epidemics: Comparing models of individual and collective learning date: 2020-01-06 words: 8379.0 sentences: 432.0 pages: flesch: 50.0 cache: ./cache/cord-004091-gex0zvoa.txt txt: ./txt/cord-004091-gex0zvoa.txt summary: For this study, we ran eight ABMs to test various combinations of individual and group learning, using different information sources-with or without interactions among agents-as factors in the BNs. We investigate the extent to which the epidemic spreads, depending on these different learning approaches regarding risk perception and coping decisions. The empirically-driven BNs model a two-stage decision process of people facing a disease risk: learning to update risk perceptions (threat appraisal, BN1 in Fig 1) and making decisions about how to adapt their behavior during the epidemic (coping appraisal, BN2 in Fig 1) . To evaluate the impact of individual and social intelligence on agents'' learning processes regarding risk perception and coping appraisal and the resulting patterns of disease spread, we used four output measures: disease diffusion, risk perception, spatial patterns, and model performance. Finally, in M7, where household agents learned risk perception in decentralized groups and learned to cope individually, 2,911 infected cases were recorded (Table 3) . abstract: Modern societies are exposed to a myriad of risks ranging from disease to natural hazards and technological disruptions. Exploring how the awareness of risk spreads and how it triggers a diffusion of coping strategies is prominent in the research agenda of various domains. It requires a deep understanding of how individuals perceive risks and communicate about the effectiveness of protective measures, highlighting learning and social interaction as the core mechanisms driving such processes. Methodological approaches that range from purely physics-based diffusion models to data-driven environmental methods rely on agent-based modeling to accommodate context-dependent learning and social interactions in a diffusion process. Mixing agent-based modeling with data-driven machine learning has become popularity. However, little attention has been paid to the role of intelligent learning in risk appraisal and protective decisions, whether used in an individual or a collective process. The differences between collective learning and individual learning have not been sufficiently explored in diffusion modeling in general and in agent-based models of socio-environmental systems in particular. To address this research gap, we explored the implications of intelligent learning on the gradient from individual to collective learning, using an agent-based model enhanced by machine learning. Our simulation experiments showed that individual intelligent judgement about risks and the selection of coping strategies by groups with majority votes were outperformed by leader-based groups and even individuals deciding alone. Social interactions appeared essential for both individual learning and group learning. The choice of how to represent social learning in an agent-based model could be driven by existing cultural and social norms prevalent in a modeled society. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944362/ doi: 10.1371/journal.pone.0226483 id: cord-292475-jrl1fowa author: Abry, Patrice title: Spatial and temporal regularization to estimate COVID-19 reproduction number R(t): Promoting piecewise smoothness via convex optimization date: 2020-08-20 words: 7470.0 sentences: 386.0 pages: flesch: 53.0 cache: ./cache/cord-292475-jrl1fowa.txt txt: ./txt/cord-292475-jrl1fowa.txt summary: The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. In that spirit, the overarching goal of the present work is twofold: (1) proposing a new, more versatile framework for the estimation of R(t) within the semi-parametric model of [8, 10] , reformulating its estimation as an inverse problem whose functional is minimized by using non smooth proximal-based convex optimization; (2) inserting this approach in an extended multivariate framework, with applications to various complementary datasets corresponding to different geographical regions. abstract: Among the different indicators that quantify the spread of an epidemic such as the on-going COVID-19, stands first the reproduction number which measures how many people can be contaminated by an infected person. In order to permit the monitoring of the evolution of this number, a new estimation procedure is proposed here, assuming a well-accepted model for current incidence data, based on past observations. The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. The effectiveness of the approach is first supported by simulations, and two main applications to real COVID-19 data are then discussed. The first one refers to the comparative evolution of the reproduction number for a number of countries, while the second one focuses on French departments and their joint analysis, leading to dynamic maps revealing the temporal co-evolution of their reproduction numbers. url: https://www.ncbi.nlm.nih.gov/pubmed/32817697/ doi: 10.1371/journal.pone.0237901 id: cord-290773-kgb8r561 author: Ahn, Jong Gyun title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus date: 2018-07-03 words: 2594.0 sentences: 148.0 pages: flesch: 47.0 cache: ./cache/cord-290773-kgb8r561.txt txt: ./txt/cord-290773-kgb8r561.txt summary: title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus Therefore, in this study, we investigated the epidemiological, clinical, and virological characteristics of HRV infections in children with acute lower respiratory tract infections. This study demonstrates that HRV is an important cause of lower respiratory infection in young children that is associated with symptoms of respiratory distress, such as chest retraction and wheezing. In our study, there were no significant differences in the clinical features, laboratory data or NPA cytokine levels between HRV-A and -C infections. High prevalence of human rhinovirus C infection in Thai children with acute lower respiratory tract disease Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions Rhinovirus load and disease severity in children with lower respiratory tract infections abstract: The clinical profile of human rhinovirus (HRV) with regard to lower respiratory infections remains unclear. We analyzed the clinical features and cytokine responses of HRV isolates in children with respiratory infections. Quantitative analysis and genotyping of the HRV-positive samples from 601 nasopharyngeal aspirates (NPAs) were performed using VP4/VP2 sequencing. To compare T-helper1 (Th1) type (IFN-γ, TNF-α) and Th2 type (IL-4, IL-10) cytokine responses between HRV-A, B and C, the levels of the four cytokines were measured. The HRV-positive children had shorter fever duration (P = 0.018), and higher frequencies of chest retraction (P = 0.002) and wheezing (P = 0.022) than did the HRV-negative group. HRV-A was identified in 55 cases (58.5%), HRV-B in 8 (8.5%), and HRV-C in 31 (33.0%). There were no significant differences in the clinical data or NPA cytokines levels between patients with HRV-A and HRV-C infections. HRV is an important pathogen of the lower respiratory tract in young children. HRV-A and HRV-C are the dominant species that cause respiratory difficulty in young children. url: https://www.ncbi.nlm.nih.gov/pubmed/29969445/ doi: 10.1371/journal.pone.0198624 id: cord-001145-hc9ssruz author: Akazawa, Yuko title: Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis date: 2013-12-13 words: 6256.0 sentences: 407.0 pages: flesch: 52.0 cache: ./cache/cord-001145-hc9ssruz.txt txt: ./txt/cord-001145-hc9ssruz.txt summary: We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. pylori-positive gastric mucosa, as well as transcriptional up-regulation of Bim in AZ-521 cells treated with VacA plus NH 4 Cl. Since knockdown of PERK decreased VacA-mediated Bim mRNA expression, activation of Bim likely occurred downstream of ER stress. abstract: Vacuolating cytotoxin A (VacA) is one of the important virulence factors produced by H. pylori. VacA induces apoptotic cell death, which is potentiated by ammonia. VacA also causes cell death by mitochondrial damage, via signaling pathways that are not fully defined. Our aim was to determine whether endoplasmic reticulum (ER) stress is associated with VacA-induced mitochondrial dysfunction and apoptosis. We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. The effect of VacA on CHOP induction was significantly enhanced by co-incubation with ammonium chloride. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Knockdown of CHOP by siRNA resulted in inhibition of VacA-induced apoptosis. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. Activation of ER stress and up-regulation of BH3-only proteins were also observed in human H. pylori-infected gastric mucosa. Collectively, this study reveals a possible association between VacA-induced apoptosis in gastric epithelial cells, and activation of ER stress in H. pylori-positive gastric mucosa. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862672/ doi: 10.1371/journal.pone.0082322 id: cord-320466-l7017jis author: Akgun, Emel title: Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients date: 2020-10-20 words: 3722.0 sentences: 226.0 pages: flesch: 42.0 cache: ./cache/cord-320466-l7017jis.txt txt: ./txt/cord-320466-l7017jis.txt summary: Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified up-regulated proteins Myeloperoxidase, Myeloblastin, Neutrophil Elastase, Cathepsin G, and Azurocidin (MPO, PRTN3, ELANE, CTSG, and AZU1) in nasooropharyngeal swab samples are discussed to highlight the molecular mechanism changes in the site of infection. Pathway analysis of the significantly altered protein levels between COVID-19 positive and negative patients'' naso-oropharyngeal swab samples were analyzed using the STRING online database. In SARS-CoV-2 patients'' naso-oropharyngeal samples, we have identified azurophilic granule (AG) proteins like Myeloperoxidase (MPO), elastase (ELANE), cathepsin G (CTSG), azurocidin 1 (AZU1) and proteinase 3 (PRTN3) to be highly overexpressed. The alterations of various proteins in SARS-CoV-2 infected patients'' naso-oropharyngeal samples depict the molecular changes that govern the host antiviral defense system. abstract: COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 9 million people and caused the death of around 470,000 patients. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative naso-oropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis. url: https://doi.org/10.1371/journal.pone.0240012 doi: 10.1371/journal.pone.0240012 id: cord-317912-v2wovcqd author: Akmatov, Manas K. title: Equivalence of Self- and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens date: 2012-11-14 words: 3488.0 sentences: 176.0 pages: flesch: 57.0 cache: ./cache/cord-317912-v2wovcqd.txt txt: ./txt/cord-317912-v2wovcqd.txt summary: found similar detection rates for respiratory pathogens between self-and staffcollected midturbinate swabs when one staff-collected and one selfcollected swab were taken from opposite nostrils during the same visit to a campus health center [5] . In the study center, a trained staff member (A.G.) obtained a nasal swab (regular flocked swab, Copan, Brescia, Italy, product number 359C) from the participant''s left nostril and instructed him/her how to perform a self-swab. Sensitivity and specificity of self-collected swabs, obtained in the study center, to detect viral respiratory pathogens (compared to staff-collected swabs)*. The detection of a viral pathogen was independent of the amount of b-actin DNA in both staff-and self-swabs collected on day 1 (Fig. 4) . This prospective study comparing staff-and self-collected nasal swabs for the detection of ARI pathogens clearly demonstrated the validity of self-swabbing; specifically, self-swabbing was not inferior in terms of acceptance, satisfaction, sample adequacy, and viral detection rate. abstract: BACKGROUND: The need for the timely collection of diagnostic biosamples during symptomatic episodes represents a major obstacle to large-scale studies on acute respiratory infection (ARI) epidemiology. This may be circumvented by having the participants collect their own nasal swabs. We compared self- and staff-collected swabs in terms of swabbing quality and detection of viral respiratory pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study among employees of our institution during the ARI season 2010/2011 (December-March). Weekly emails were sent to the participants (n = 84), reminding them to come to the study center in case of new symptoms. The participants self-collected an anterior nasal swab from one nostril, and trained study personnel collected one from the other nostril. The participants self-collected another two swabs (one from each nostril) on a subsequent day. Human β-actin DNA concentration was determined in the swabs as a quality control. Viral respiratory pathogens were detected by multiplex RT-PCR (Seeplex RV15 kit, Seegene, Eschborn, Germany). Of 84 participants, 56 (67%) reported at least one ARI episode, 18 participants two, and one participant three. Self-swabbing was highly accepted by the participants. The amount of β-actin DNA per swab was higher in the self- than in the staff-collected swabs (p = 0.008). β-actin concentration was lower in the self-swabs collected on day 1 than in those collected on a subsequent day (p<0.0001). A respiratory viral pathogen was detected in 31% (23/75) of staff- and in 35% (26/75) of self-collected swabs (p = 0.36). With both approaches, the most frequently identified pathogens were human rhinoviruses A/B/C (12/75 swabs, 16%) and human coronavirus OC43 (4/75 swabs, 5%). There was almost perfect agreement between self- and staff-collected swabs in terms of pathogen detection (agreement = 93%, kappa = 0.85, p<0.0001). CONCLUSIONS/SIGNIFICANCE: Nasal self-swabbing for identification of viral ARI pathogens proved to be equivalent to staff-swabbing in this population in terms of acceptance and pathogen detection. url: https://doi.org/10.1371/journal.pone.0048508 doi: 10.1371/journal.pone.0048508 id: cord-345019-i7zm9bt1 author: Al-Waleedi, Ali Ahmed title: The first 2 months of the SARS-CoV-2 epidemic in Yemen: Analysis of the surveillance data date: 2020-10-29 words: 4496.0 sentences: 236.0 pages: flesch: 55.0 cache: ./cache/cord-345019-i7zm9bt1.txt txt: ./txt/cord-345019-i7zm9bt1.txt summary: A total of 268 individuals with confirmed SARS-CoV-2 infection were hospitalized (57%), among whom there were 95 in-hospital deaths, CONCLUSIONS: The surveillance strategy implemented in the first 2 months of the SARS CoV 2 in the southern and eastern governorates of Yemen, captured mainly severe cases. For early detection of SARS-CoV-2 in Yemen, as in other countries, a case definition, active surveillance, and contact tracing were required [10, 11] . The first 2 months after confirmation of the SARS-CoV-2 epidemic in Yemen was characterized by a 57% hospitalization rate in the southern and eastern parts of the country included in The First 2 Months of the SARS-CoV-2 Epidemic in Yemen our study, 63% of deaths occurring in individuals aged <60 years, confirmatory testing of <50% of the suspected cases, and majority of cases were not related to a defined chain of transmission. abstract: INTRODUCTION: Yemen was one of the last countries in the world to declare the first case of the pandemic, on 10 April 2020. Fear and concerns of catastrophic outcomes of the epidemic in Yemen were immediately raised, as the country is facing a complex humanitarian crisis. The purpose of this report is to describe the epidemiological situation in Yemen during the first 2 months of the SARS-CoV-2 epidemic. METHODS: We analyzed the epidemiological data from 18 February to 05 June 2020, including the 2 months before the confirmation of the first case. We included in our analysis the data from 10 out of 23 governorates of Yemen, located in southern and eastern part of the country. RESULTS: A total of 469 laboratory confirmed, 552 probable and 55 suspected cases with onset of symptoms between 18 February and 5 June 2020 were reported through the surveillance system. The median age among confirmed cases was 46 years (range: 1–90 years), and 75% of the confirmed cases were male. A total of 111 deaths were reported among those with confirmed infection. The mean age among those who died was 53 years (range: 14–88 years), with 63% of deaths (n = 70) occurring in individuals under the age 60 years. A total of 268 individuals with confirmed SARS-CoV-2 infection were hospitalized (57%), among whom there were 95 in-hospital deaths, CONCLUSIONS: The surveillance strategy implemented in the first 2 months of the SARS CoV 2 in the southern and eastern governorates of Yemen, captured mainly severe cases. The mild and moderate cases were not self-reported to the health facilities and surveillance system due to limited resources, stigma, and other barriers. The mortality appeared to be higher in individuals aged under 60 years, and most fatalities occurred in individuals who were in critical condition when they reached the health facilities. It is unclear whether the presence of other acute comorbidities contributed to the high death rate among SARS-CoV-2 cases. The findings only include the southern and eastern part of the country, which is home to 31% of the total population of Yemen, as the data from the northern part of the country was inaccessible for analysis. This makes our results not generalizable to the rest of the country. url: https://www.ncbi.nlm.nih.gov/pubmed/33119720/ doi: 10.1371/journal.pone.0241260 id: cord-001639-p9mbmfaq author: Alfonso-Morales, Abdulahi title: Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent date: 2015-05-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Infectious bursal disease (IBD) is a highly contagious and acute viral disease, which has caused high mortality rates in birds and considerable economic losses in different parts of the world for more than two decades and it still represents a considerable threat to poultry. The current study was designed to rigorously measure the reliability of a phylogenetic marker included into segment B. This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Sequences of the segment B gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank Database; Cuban sequences were obtained in the current work. A phylogenetic marker named B-marker was assessed by different phylogenetic principles such as saturation of substitution, phylogenetic noise and high consistency. This last parameter is based on the ability of B-marker to reconstruct the same topology as the complete segment B of the viral genome. From the results obtained from B-marker, demographic history for both main lineages of IBDV regarding segment B was performed by Bayesian skyline plot analysis. Phylogenetic analysis for both segments of IBDV genome was also performed, revealing the presence of a natural reassortant strain with segment A from vvIBDV strains and segment B from non-vvIBDV strains within Cuban IBDV population. CONCLUSIONS/SIGNIFICANCE: This study contributes to a better understanding of the emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the state-of-the-art methodology concerning phylogenetic reconstruction. This study also revealed the presence of a novel natural reassorted strain as possible manifest of change in the genetic structure and stability of the vvIBDV strains. Therefore, it highlights the need to obtain information about both genome segments of IBDV for molecular epidemiology studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422720/ doi: 10.1371/journal.pone.0125853 id: cord-268429-drejl99k author: Almberg, Emily S. title: A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community date: 2009-09-16 words: 7276.0 sentences: 349.0 pages: flesch: 52.0 cache: ./cache/cord-268429-drejl99k.txt txt: ./txt/cord-268429-drejl99k.txt summary: METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. Thus we sought to use long-term serological data to identify temporal, spatial, and demographic patterns of pathogen exposure among wolves, coyotes (Canis latrans), and foxes (Vulpes vulpes) in YNP. In summary, the constant high canid exposure to CPV, CAV-1, and CHV in YNP suggest that these pathogens are established in the wolf and coyote populations and that they are unlikely to be causing acute mortality in their hosts [50, 51] . abstract: BACKGROUND: Gray wolves (Canis lupus) were reintroduced into Yellowstone National Park (YNP) after a >70 year absence, and as part of recovery efforts, the population has been closely monitored. In 1999 and 2005, pup survival was significantly reduced, suggestive of disease outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. We found high, constant exposure to canine parvovirus (wolf seroprevalence: 100%; coyote: 94%), canine adenovirus-1 (wolf pups [0.5–0.9 yr]: 91%, adults [≥1 yr]: 96%; coyote juveniles [0.5–1.5 yrs]: 18%, adults [≥1.6 yrs]: 83%), and canine herpesvirus (wolf: 87%; coyote juveniles: 23%, young adults [1.6–4.9 yrs]: 51%, old adults [≥5 yrs]: 87%) suggesting that these pathogens were enzootic within YNP wolves and coyotes. An average of 50% of wolves exhibited exposure to the protozoan parasite, Neospora caninum, although individuals’ odds of exposure tended to increase with age and was temporally variable. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. The years of high wolf-pup mortality in 1999 and 2005 in the northern region of the park were correlated with peaks in CDV seroprevalence, suggesting that CDV contributed to the observed mortality. CONCLUSIONS/SIGNIFICANCE: Of the pathogens we examined, none appear to jeopardize the long-term population of canids in YNP. However, CDV appears capable of causing short-term population declines. Additional information on how and where CDV is maintained and the frequency with which future epizootics might be expected might be useful for future management of the Northern Rocky Mountain wolf population. url: https://doi.org/10.1371/journal.pone.0007042 doi: 10.1371/journal.pone.0007042 id: cord-294768-bs6thjw2 author: Alonso-Fernández, Alberto title: Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study date: 2020-08-25 words: 4652.0 sentences: 278.0 pages: flesch: 49.0 cache: ./cache/cord-294768-bs6thjw2.txt txt: ./txt/cord-294768-bs6thjw2.txt summary: title: Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion. [12] found, in a retrospective study in 184 intensive care unit (ICU) patients with severe COVID-19 pneumonia, a high prevalence of thrombotic complications and, by far, pulmonary embolism (PE) was the most frequent. Pulmonary embolism in COVID-19 pneumonia with high D-dimer values: A prospective study procoagulant (D-dimer) markers that correlated with the extend of the thromboembolic episode compared to those patients without PE. We included patients with D-dimer values higher than 1 μg/mL, which have been associated with disease severity and in-hospital mortality in patients with COVID-19 infection. Pulmonary embolism in COVID-19 pneumonia with high D-dimer values: A prospective study of our patients, allocated in the non-PE group, was not on enoxaparin prophylaxis during hospitalization. abstract: INTRODUCTION: Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile. D-dimer elevation is particularly frequent, and values higher than 1μg/mL have been associated with disease severity and in-hospital mortality. Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected. MATERIAL AND METHODS: Single-center prospective cohort study. Between April 6(th) and April 17(th) 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 μg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE. Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE. RESULTS: Thirty consecutive patients (11 women) were included. PE was diagnosed in 15 patients (50%). In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%). Patients with PE were significantly older (median age 67.0 (IQR 63.0–73.0) vs. 57.0 (IQR 48.0–69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group. D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients. D-dimer values correlated with the radiologic magnitude of PE (p<0.001). CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion. We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found. url: https://doi.org/10.1371/journal.pone.0238216 doi: 10.1371/journal.pone.0238216 id: cord-321855-7b1c2xdh author: Alshami, Alanoud title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date: 2020-10-30 words: 3380.0 sentences: 190.0 pages: flesch: 56.0 cache: ./cache/cord-321855-7b1c2xdh.txt txt: ./txt/cord-321855-7b1c2xdh.txt summary: title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. have examined 24 asymptomatic infected individuals with a history of close contact with SARS-COV-2 confirmed cases and found that only 20% of them developed symptoms. Our findings are in light with a recent study that reported a 59% prevalence of loss of taste and smell in a cohort of COVID-19 patients [15] . Sudden onset of loss of smell and taste were prevalent in our study and were key symptoms of mild disease. abstract: OBJECTIVES: In this study, we aimed to study the clinical presentations, and viral clearance of SARS-COV-2 positive quarantined individuals. DESIGN: Cross-sectional study. SETTING: Governmental- designated facility in the eastern province, Saudi Arabia. PARTICIPANTS: 128 laboratory-confirmed COVID-19 quarantined individuals who had a history of travel abroad in the last 14 days before the quarantine or were in direct contact with laboratory-confirmed cases. The study was from March 18th-till April 16th. PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. RESULTS: Sixty-nine of the 128 residents (54%) were completely asymptomatic until the end of the study. The remaining 59 residents (46%) had only mild symptoms. The most common symptom was a sudden loss of smell and taste, accounting for 47.5%. The median time to virus clearance was significantly different between the two groups. Symptomatic residents cleared the virus at a median of 17 days (95% CI, 12.4–21.6) from the first positive PCR vs. 11days (95% CI, 8.7–13.3) in the asymptomatic group (P = 0.011). False-negative test results occurred in 18.8% of the total residents and false-positive results in 3%. CONCLUSION: The prevalence of asymptomatic carriers among quarantined travelers and those identified by contact tracing is high in our study. Therefore, testing, tracing, and isolating travelers and contacts of laboratory-confirmed cases, regardless of symptoms, were very effective measures for early disease identification and containment. Loss of taste and smell were the most common presentations in our mild symptomatic residents and should be used as a screening tool for COVID-19. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. url: https://doi.org/10.1371/journal.pone.0241258 doi: 10.1371/journal.pone.0241258 id: cord-294912-xl0wzi16 author: Alteri, Claudia title: Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date: 2020-09-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32898153/ doi: 10.1371/journal.pone.0236311 id: cord-001571-drcfdv9z author: Alvarez, Julio title: Impact of Porcine Epidemic Diarrhea on Performance of Growing Pigs date: 2015-03-13 words: 3100.0 sentences: 133.0 pages: flesch: 60.0 cache: ./cache/cord-001571-drcfdv9z.txt txt: ./txt/cord-001571-drcfdv9z.txt summary: Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs'' performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014. Collected data included information on the site in which pigs were located, site production type (nursery or wean to finish (WF)), pig source (sow farm from which pigs originated), start and close period on each site, number of pigs per batch, mortality (defined by percentage of total pigs started), average daily gain (ADG), average daily feed intake (ADFI), feed conversion (FCR), and status of the sow farm from which pigs were weaned for PRRS and PED. abstract: The impact of porcine epidemic diarrhea virus (PEDv) infection on the US pork industry has mainly been attributed to the mortality that it causes in suckling piglets, and, consequently, much effort has been invested in the quantification of its effect in sow farms. However, no information on the performance of surviving pigs that were exposed to the PEDv as piglets is available. Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs’ performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014. Production records from the first batch of growing pigs weaned in infected flows after the PEDv outbreak (“infected batches”) were compared with those from pigs weaned within the previous 14 to 120 days (“control batches”). Performance records from infected and control batches, paired by flow, were compared using non-parametric paired tests. Mortality, ADG and FCR were significantly different in PEDv-positive (infected) compared with PEDv-negative (control) batches, with a mean increase of mortality and FCR of 11% and 0.5, respectively, and a decrease of ADG of 0.16 lb/day. Our results demonstrate a poorer performance of growing pigs weaned after a PEDv outbreak compared with those weaned within the previous 14-120 days, suggesting that in addition to the mortality induced by PEDv in suckling pigs, the disease also impairs the performance of surviving pig. These findings help to quantify the impact of PEDv infection in the US and, ultimately, contribute to efforts to quantify the cost-effectiveness of disease prevention and control measures. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359118/ doi: 10.1371/journal.pone.0120532 id: cord-311074-j3fw4dfc author: Alviset, Sophie title: Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study date: 2020-10-14 words: 4842.0 sentences: 254.0 pages: flesch: 49.0 cache: ./cache/cord-311074-j3fw4dfc.txt txt: ./txt/cord-311074-j3fw4dfc.txt summary: title: Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study From 27th March to 23rd April, consecutive patients who had respiratory failure or were unable to maintain an SpO2 > 90%, despite receiving 10–15 l/min of oxygen with a non-rebreather mask, were treated by continuous positive airway pressure (CPAP) unless the ICU physician judged that immediate intubation was indicated. The following baseline patient characteristics were retrieved from patient electronic medical record: sex, age, comorbidities, body mass index (BMI), withholding / withdrawal of lifesustaining therapies, associated COVID-19 therapies administered before the primary outcome under study occurred (antivirals, corticosteroids, immuno-modulating therapies, prone positioning), oxygen flow rate and SpO2 before and after starting CPAP treatment, duration of CPAP treatment, medical unit where CPAP treatment was performed, duration of invasive mechanical ventilation, SAPS2 score for patients admitted in ICU, driving pressure and P/F ratio on first day of mechanical ventilation. abstract: INTRODUCTION: Because of the COVID-19 pandemic, intensive care units (ICU) can be overwhelmed by the number of hypoxemic patients. MATERIAL AND METHODS: This single centre retrospective observational cohort study took place in a French hospital where the number of patients exceeded the ICU capacity despite an increase from 18 to 32 beds. Because of this, 59 (37%) of the 159 patients requiring ICU care were referred to other hospitals. From 27th March to 23rd April, consecutive patients who had respiratory failure or were unable to maintain an SpO2 > 90%, despite receiving 10–15 l/min of oxygen with a non-rebreather mask, were treated by continuous positive airway pressure (CPAP) unless the ICU physician judged that immediate intubation was indicated. We describe the characteristics, clinical course, and outcomes of these patients. The main outcome under study was CPAP discontinuation. RESULTS: CPAP was initiated in 49 patients and performed out of ICU in 41 (84%). Median age was 65 years (IQR = 54–71) and 36 (73%) were men. Median respiratory rate before CPAP was 36 (30–40) and median SpO2 was 92% (90–95) under 10 to 15 L/min oxygen flow. Median duration of CPAP was 3 days (IQR = 1–5). Reasons for discontinuation of CPAP were: intubation in 25 (51%), improvement in 16 (33%), poor tolerance in 6 (12%) and death in 2 (4%) patients. A decision not to intubate had been taken for 8 patients, including the 2 who died while on CPAP. Two patients underwent less than one hour CPAP for poor tolerance. In the end, 15 (38%) out of 39 evaluable patients recovered with only CPAP whereas 24 (62%) were intubated. CONCLUSIONS: CPAP is feasible in a non-ICU environment in the context of massive influx of patients. In our cohort up to 1/3 of the patients presenting with acute respiratory failure recovered without intubation. url: https://www.ncbi.nlm.nih.gov/pubmed/33052968/ doi: 10.1371/journal.pone.0240645 id: cord-287761-73qgx58i author: Aly, Mahmoud title: Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update date: 2017-10-13 words: 3389.0 sentences: 164.0 pages: flesch: 55.0 cache: ./cache/cord-287761-73qgx58i.txt txt: ./txt/cord-287761-73qgx58i.txt summary: Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. The emergence of MERS-CoV dates back to July 2012 when an elderly patient of age 60 years died from an acute pneumonia in Saudi Arabia, and a new coronavirus strain was isolated from his lung tissue [1] . With regard to viral origin and transmission, the first case of MERS-CoV infection did not relate it to any particular contact with animals before the disease onset; however, other studies did link it to Dromedary camels [5] [6] [7] [8] . abstract: The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections has become a global issue of dire concerns. MERS-CoV infections have been identified in many countries all over the world whereas high level occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly spreading across the geographical region of the Middle East, especially in the Arabian Peninsula, while some imported sporadic cases were reported from the Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV infections across the Gulf Corporation Council (GCC) countries still remains unclear. Therefore, the objective of the current study was to report the prevalence of MERS-CoV in the GCC countries and to also elucidate on its demographics in the Arabian Peninsula. To date, the World Health Organization (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since June 2012, involving 687 deaths in 27 different countries worldwide. Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. Our data comprise a total of 1550 cases (67.1% male and 32.9% female). The age-specific prevalence and distribution of MERS-CoV was as follow: <20 yrs (36 cases: 3.28%), 20–39 yrs (331 cases: 30.15%), 40–59 yrs (314 cases: 28.60%), and the highest-risk elderly group aged ≥60 yrs (417 cases: 37.98%). The case distribution among GCC countries was as follows: Saudi Arabia (1441 cases: 93%), Kuwait (4 cases: 0.3%), Bahrain (1 case: 0.1%), Oman (8 cases: 0.5%), Qatar (16 cases: 1.0%), and United Arab Emirates (80 cases: 5.2%). Thus, MERS-CoV was found to be more prevalent in Saudi Arabia especially in Riyadh, where 756 cases (52.4%) were the worst hit area of the country identified, followed by the western region Makkah where 298 cases (20.6%) were recorded. This prevalence update indicates that the Arabian Peninsula, particularly Saudi Arabia, is the hardest hit region regarding the emerging MERS-CoV infections worldwide. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. Given the continuum of emergence and the large magnitude of the disease in our region, more studies will be required to bolster capabilities for timely detection and effective control and prevention of MERS-CoV in our region. url: https://doi.org/10.1371/journal.pone.0183850 doi: 10.1371/journal.pone.0183850 id: cord-266797-uglsx7se author: Anastassopoulou, Cleo title: Data-based analysis, modelling and forecasting of the COVID-19 outbreak date: 2020-03-31 words: 5420.0 sentences: 235.0 pages: flesch: 55.0 cache: ./cache/cord-266797-uglsx7se.txt txt: ./txt/cord-266797-uglsx7se.txt summary: Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Based on the released data, we attempted to estimate the mean values of the main epidemiological parameters, i.e. the basic reproduction number R 0 , the case fatality (ĝ) and case recovery (b) ratios, along with their 90% confidence intervals. Then, as described above, we provide coarse estimations of the "effective" per day recovery and mortality rates of the SIRD model based on the reported data by solving the corresponding least squares problems. abstract: Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infectious-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R(0)), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R(0) as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ∼4.6, while the one computed under the second scenario was found to be ∼3.2. Thus, based on the SIRD simulations, the estimated average value of R(0) was found to be ∼2.6 based on confirmed cases and ∼2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with a lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around ∼0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February. url: https://www.ncbi.nlm.nih.gov/pubmed/32231374/ doi: 10.1371/journal.pone.0230405 id: cord-002305-qq73gr9y author: Anson, Marie title: Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool date: 2016-11-23 words: 5422.0 sentences: 248.0 pages: flesch: 51.0 cache: ./cache/cord-002305-qq73gr9y.txt txt: ./txt/cord-002305-qq73gr9y.txt summary: In conclusion, the adoptive cell transfer strategy allowed the development of a primary immune response with B cell activation and expansion, induction of AID expression, class switch recombination, antigen-specific IgM and IgG antibody production and germinal center formation. In this study we show that it is possible to fully reconstitute a primary response and the establishment of antibody memory in immune deficient mice after adoptive transfer of antigen-specific monoclonal B cells together with a population of monoclonal helper T cells. In contrast we showed that after adoptive transfer in immune deficient hosts antigen immunization induced B cell activation and expansion, induction of AID expression, class switch recombination, antigen-specific IgM and IgG antibody production, germinal center formation and the generation of two subsets of AID/YFP + IgM + IgGand AID/YFP + Ig-M -IgG + antigen-experienced B cell subsets able to persist in a lymphopenic environment by cell division mimicking responses obtained in intact non-Tg mice [4] . abstract: We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM(+)IgG(-) and IgM(-)IgG(+) antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM(-)IgG(+) cells responded by the production of antigen-specific IgG while the IgM(+) memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120830/ doi: 10.1371/journal.pone.0167003 id: cord-000809-9voqa1oy author: Archer, Brett N. title: Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa date: 2012-11-16 words: 3885.0 sentences: 208.0 pages: flesch: 50.0 cache: ./cache/cord-000809-9voqa1oy.txt txt: ./txt/cord-000809-9voqa1oy.txt summary: We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial R(t)) and the temporal variation of R(t). In this work we incorporate data collected on all laboratory-confirmed cases detected during the 2009 pH1N1 epidemic in South Africa with the aim of describing the transmissibility characteristics (initial R t and temporal variation of R t ) of the epidemic in the country and compare its dynamics with those observed in other countries in the same year. When estimating initial R t , we focus our analysis on the exponential growth phase of the epidemic in South Africa (i.e. the period from the first occurrence of five consecutive days with confirmed cases reported to the epidemic peak). abstract: BACKGROUND/OBJECTIVE: Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks. We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial R(t)) and the temporal variation of R(t). METHODS: We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value. We apply a likelihood-based method (method 1) for simultaneous estimation of initial R(t) and the SI; estimate initial R(t) from SI distributions established from prior field studies (method 2); and the Wallinga and Teunis method (method 3) to model the temporal variation of R(t). RESULTS: 12,360 confirmed pH1N1 cases were reported in the central registry. During the period of exponential growth of the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean R(t) of 1.47 (95% CI: 1.30–1.72) and mean SI of 2.78 days (95% CI: 1.80–3.75) (method 1). Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases. Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial R(t) of 1.43 (95% CI: 1.38–1.49) (method 2). The mean R(t) peaked at 2.91 (95% CI: 0.85–2.91) on June 21, as the epidemic commenced, and R(t)>1 was sustained until August 22 (method 3). CONCLUSIONS: Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa. Estimations using the likelihood-based method are in agreement with field findings. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500305/ doi: 10.1371/journal.pone.0049482 id: cord-002601-d8908t93 author: Arellano-Llamas, Rocío title: Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter seasons 2012-2014 date: 2017-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011–2012 winter season and finally, during the 2013–2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease. In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a clear variation of the virus in Mexico from the 2011–2014 season due to different markers and in accordance with previous reports. In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function. The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503254/ doi: 10.1371/journal.pone.0180419 id: cord-284501-5i0w74q4 author: Armesto, Maria title: The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity date: 2009-10-09 words: 7792.0 sentences: 322.0 pages: flesch: 54.0 cache: ./cache/cord-284501-5i0w74q4.txt txt: ./txt/cord-284501-5i0w74q4.txt summary: The IBV cDNA within pGPT-BeauR-Rep-M41-Struct-3UTR was introduced, by homologous recombination using the transient dominant selection (TDS) ( [25, 37] ), into the IBV Beaudette cDNA within the vaccinia virus genome in rVV-BeauR-Rep-DStruct containing Beau-R-derived sequence corresponding to the replicase gene followed by the first 376 nt of the S gene, part of the N gene and the 39-UTR (Fig. 1) . The samples were analysed for the presence of viable IBV by titration in TOCs or used for RNA extraction using the RNeasy method and analysed by RTThe M41-CK-derived cDNA, representing the M41 structural and accessory genes and the M41 39-UTR, within pGPT-BeauR-Rep-M41-Struct-3UTR was fused to the Beau-R replicase gene in the rVV by a homologous recombination event between the Beau-R replicase sequence common to both constructs. Analysis of the tracheal epithelial cells isolated from the infected chickens, for the presence of IBV by titration on TOCs, had indicated that either there was no Beau-R or rBeauR-Rep-M41-Struct-2 present or that the levels of both viruses were below detection. abstract: We have previously demonstrated that the replacement of the S gene from an avirulent strain (Beaudette) of infectious bronchitis virus (IBV) with an S gene from a virulent strain (M41) resulted in a recombinant virus (BeauR-M41(S)) with the in vitro cell tropism of the virulent virus but that was still avirulent. In order to investigate whether any of the other structural or accessory genes played a role in pathogenicity we have now replaced these from the Beaudette strain with those from M41. The recombinant IBV was in effect a chimaeric virus with the replicase gene derived from Beaudette and the rest of the genome from M41. This demonstrated that it is possible to exchange a large region of the IBV genome, approximately 8.4 kb, using our transient dominant selection method. Recovery of a viable recombinant IBV also demonstrated that it is possible to interchange a complete replicase gene as we had in effect replaced the M41 replicase gene with the Beaudette derived gene. Analysis of the chimaeric virus showed that it was avirulent indicating that none of the structural or accessory genes derived from a virulent isolate of IBV were able to restore virulence and that therefore, the loss of virulence associated with the Beaudette strain resides in the replicase gene. url: https://doi.org/10.1371/journal.pone.0007384 doi: 10.1371/journal.pone.0007384 id: cord-283976-jgae7r2q author: Armstrong, Melissa J. title: Research priorities of caregivers and individuals with dementia with Lewy bodies: An interview study date: 2020-10-07 words: 4111.0 sentences: 208.0 pages: flesch: 37.0 cache: ./cache/cord-283976-jgae7r2q.txt txt: ./txt/cord-283976-jgae7r2q.txt summary: BACKGROUND: Funding bodies are placing increased emphasis on patient and public involvement in research, but the research priorities of individuals and caregivers living with dementia with Lewy bodies (DLB) are unknown. Funding should be informed by the priorities of all relevant stakeholders and support research investigating causes, natural history, biomarkers, and treatment in addition to research targeting themes regarding living with disease (e.g. independence, quality of life, caregiving, and education). The study guide queried a variety of research categories and individuals with DLB and caregivers identified topics important for research in all of them-focusing on awareness, determining the cause of DLB, improving diagnosis, investigating what to expect and disease stages, DLB symptoms needing additional research, therapies to prevent, cure, or slow the progression of DLB, targeting daily function and quality of life, caregiving, and improving education. abstract: BACKGROUND: Funding bodies are placing increased emphasis on patient and public involvement in research, but the research priorities of individuals and caregivers living with dementia with Lewy bodies (DLB) are unknown. METHOD: Investigators conducted telephone interviews with individuals living with DLB and caregivers. Participants were recruited from a Lewy Body Dementia Association Research Center of Excellence. Interviews employed a semi-structured questionnaire querying research needs in different categories and then asking participants to select their top priorities. Investigators used a qualitative descriptive approach to analyze transcripts and identify themes. RESULTS: Twenty individuals with DLB and 25 caregivers participated. Seventeen from each group participated as part of a patient-caregiver dyad. Twenty-three of the caregivers were spouses, two were daughters. Individuals with DLB and caregivers identified research needs relating to focusing on awareness, determining the cause of DLB, improving diagnosis, and investigating what to expect/disease stages. Participants also highlighted DLB symptoms needing additional research, therapies to prevent, cure, or slow the progression of DLB, and research targeting daily function and quality of life, caregiving, and improving education. CONCLUSIONS: These findings support the research priorities defined in the National Institutes of Health dementia care summits in addition to ADRD priority-setting summits. Research is needed across all domains of DLB. Funding should be informed by the priorities of all relevant stakeholders and support research investigating causes, natural history, biomarkers, and treatment in addition to research targeting themes regarding living with disease (e.g. independence, quality of life, caregiving, and education). url: https://www.ncbi.nlm.nih.gov/pubmed/33027276/ doi: 10.1371/journal.pone.0239279 id: cord-002953-4rqoenhr author: Arruda, Andréia Gonçalves title: Time-series analysis for porcine reproductive and respiratory syndrome in the United States date: 2018-04-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Industry-driven voluntary disease control programs for swine diseases emerged in North America in the early 2000’s, and, since then, those programs have been used for monitoring diseases of economic importance to swine producers. One example of such initiatives is Dr. Morrison’s Swine Health Monitoring Project, a nation-wide monitoring program for swine diseases including the porcine reproductive and respiratory syndrome (PRRS). PRRS has been extensively reported as a seasonal disease in the U.S., with predictable peaks that start in fall and are extended through the winter season. However, formal time series analysis stratified by geographic region has never been conducted for this important disease across the U.S. The main objective of this study was to use approximately seven years of PRRS incidence data in breeding swine herds to conduct time-series analysis in order to describe the temporal patterns of PRRS outbreaks at the farm level for five major swine-producing states across the U.S. including the states of Minnesota, Iowa, North Carolina, Nebraska and Illinois. Data was aggregated retrospectively at the week level for the number of herds containing animals actively shedding PRRS virus. Basic descriptive statistics were conducted followed by autoregressive integrated moving average (ARIMA) modelling, conducted separately for each of the above-mentioned states. Results showed that there was a difference in the nature of PRRS seasonality among states. Of note, when comparing states, the typical seasonal pattern previously described for PRRS could only be detected for farms located in the states of Minnesota, North Carolina and Nebraska. For the other two states, seasonal peaks every six months were detected within a year. In conclusion, we showed that epidemic patterns are not homogeneous across the U.S, with major peaks of disease occurring through the year. These findings highlight the importance of coordinating alternative control strategies in different regions considering the prevailing epidemiological patterns. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882168/ doi: 10.1371/journal.pone.0195282 id: cord-336364-2ust3qoq author: Artigas, Laura title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date: 2020-10-02 words: 5858.0 sentences: 295.0 pages: flesch: 45.0 cache: ./cache/cord-336364-2ust3qoq.txt txt: ./txt/cord-336364-2ust3qoq.txt summary: title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm This has provided 3 sets of proteins related with the infection process: 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lungcells infection set, and 3) acute respiratory distress (ARD) set. According to the findings by GUILDify, we confirm the effect of the combination of pirfenidone and melatonin in the entry points of the SARS-CoV-2 infection, specifically the neighbours of furin and GRP-78, and some proteins associated with ARD. 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lung-cells infection set, and 3) acute respiratory distress (ARD) set that is composed of 6 subsets (Alveolar macrophages, Monocytes, Neutrophils, Intermediate phase ARD, Late phase ARD and ARD cytokine storm). abstract: From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications. url: https://doi.org/10.1371/journal.pone.0240149 doi: 10.1371/journal.pone.0240149 id: cord-002621-sq5iod1w author: Attia, Mohamed I. title: New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres date: 2017-07-25 words: 5948.0 sentences: 280.0 pages: flesch: 47.0 cache: ./cache/cord-002621-sq5iod1w.txt txt: ./txt/cord-002621-sq5iod1w.txt summary: Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC(50) values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC(50) value of 8.11 μM. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC(50) value less than 0.8 μM. The human lung cancer A549 cell line was incubated with various concentrations (0.8, 1.6, 3.13, 6.25, 12.5, 25 and 50 μM) of both free 7e and 7e-loaded microspheres to evaluate the anti-proliferative activity by assessing their effect on cell viability. Synthesis and anticancer activity of certain hydrazonoindolin-2-ones Fig 13B illustrates the obtained results when 7e-loaded microspheres were incubated with the human lung cancer cell lineA549for incubation periods and concentrations similar to that of the free 7e. abstract: The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC(50) values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC(50) value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC(50) value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC(50) value less than 0.8 μM. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526551/ doi: 10.1371/journal.pone.0181241 id: cord-001546-ndz3oarf author: Ayithan, Natarajan title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 words: 5128.0 sentences: 298.0 pages: flesch: 52.0 cache: ./cache/cord-001546-ndz3oarf.txt txt: ./txt/cord-001546-ndz3oarf.txt summary: Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. abstract: Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar(-/-) mice. Accordingly, EBOV infected Ifnar(-/-) mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342244/ doi: 10.1371/journal.pone.0118345 id: cord-257603-ov0b8yub author: Azlan, Arina Anis title: Public knowledge, attitudes and practices towards COVID-19: A cross-sectional study in Malaysia date: 2020-05-21 words: 4685.0 sentences: 256.0 pages: flesch: 54.0 cache: ./cache/cord-257603-ov0b8yub.txt txt: ./txt/cord-257603-ov0b8yub.txt summary: To measure practices, participants were asked yes/no questions on whether they had avoided going to crowded places such as weddings; wore a face mask when leaving home; and whether they practiced proper hand hygiene in the week before the movement control order (MCO). The first question asked whether or not they agreed that the COVID-19 situation would be successfully controlled; second, whether they thought Malaysia would be able to win its battle against the virus; and third, whether they thought the Malaysian government was handling the health crisis well [Fig 1] . Practices toward COVID-19 were measured using three questions enquiring on: 1) avoidance of crowded places, 2) wearing of face masks; and 3) practising proper hand hygiene in the week before the Movement Control Order (MCO) was implemented in Malaysia [Fig 2] . Public knowledge, attitudes and practices towards COVID-19 in Malaysia residents in the Eastern region and retirees were among the highest percentage of participants who had not practised good hand hygiene in the week before the MCO. abstract: In an effort to mitigate the outbreak of COVID-19, many countries have imposed drastic lockdown, movement control or shelter in place orders on their residents. The effectiveness of these mitigation measures is highly dependent on cooperation and compliance of all members of society. The knowledge, attitudes and practices people hold toward the disease play an integral role in determining a society’s readiness to accept behavioural change measures from health authorities. The aim of this study was to determine the knowledge levels, attitudes and practices toward COVID-19 among the Malaysian public. A cross-sectional online survey of 4,850 Malaysian residents was conducted between 27(th) March and 3(rd) April 2020. The survey instrument consisted of demographic characteristics, 13 items on knowledge, 3 items on attitudes and 3 items on practices, modified from a previously published questionnaire on COVID-19. Descriptive statistics, chi-square tests, t-tests and one-way analysis of variance (ANOVA) were conducted. The overall correct rate of the knowledge questionnaire was 80.5%. Most participants held positive attitudes toward the successful control of COVID-19 (83.1%), the ability of Malaysia to conquer the disease (95.9%) and the way the Malaysian government was handling the crisis (89.9%). Most participants were also taking precautions such as avoiding crowds (83.4%) and practising proper hand hygiene (87.8%) in the week before the movement control order started. However, the wearing of face masks was less common (51.2%). This survey is among the first to assess knowledge, attitudes and practice in response to the COVID-19 pandemic in Malaysia. The results highlight the importance of consistent messaging from health authorities and the government as well as the need for tailored health education programs to improve levels of knowledge, attitudes and practices. url: https://doi.org/10.1371/journal.pone.0233668 doi: 10.1371/journal.pone.0233668 id: cord-320091-2lrqubdl author: Badawi, Alaa title: Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis date: 2018-07-10 words: 8511.0 sentences: 411.0 pages: flesch: 46.0 cache: ./cache/cord-320091-2lrqubdl.txt txt: ./txt/cord-320091-2lrqubdl.txt summary: The objective of this study is to systematically review the existing literature on the prevalence of the most common non-communicable comorbidities related to the cluster of metabolic syndromes-associated diseases, such as diabetes mellitus, heart diseases, hypertension, asthma, stroke and obesity in flavivirus infections and to evaluate the difference of their prevalence in severe vs. Data extracted from the selected studies in duplicate by two reviewers and included the first author''s name, publication date, country, dates of recruitment, total sample size (divided to males and females), age estimates (from reported mean, median or the mid-point for age range of the highest subject frequency), procedures for case identification, type of flavivirus infection, severity of infection, prevalence of clinical manifestations (mild symptoms such as fever, headache, muscle pain, rash, and malaise together with severe symptoms as described below) and percentage of comorbidities including diabetes (both type I and type II, if mentioned), hypertension, heart diseases (due to the small sample size of individual conditions, we (Table 1) . abstract: BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases. url: https://doi.org/10.1371/journal.pone.0200200 doi: 10.1371/journal.pone.0200200 id: cord-351918-pu7i1jfe author: Baek, Yae Jee title: A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies date: 2020-10-26 words: 4902.0 sentences: 278.0 pages: flesch: 51.0 cache: ./cache/cord-351918-pu7i1jfe.txt txt: ./txt/cord-351918-pu7i1jfe.txt summary: The effects of different intervention strategies such as front door screening, quarantine unit for newly admitted patients, early testing of suspected infected people, and personal protective equipment for both medical staff and visitors were evaluated. The model suggested that the early testing (within eight hours) of infected cases and monitoring the quarantine ward for newly hospitalized patients are effective measures for decreasing the incidence of COVID-19 within a hospital (81.3% and 70% decrease of number of incident cases, respectively, during 60 days). Setting the population vector η as the number of staff, and the stabilized number of inflow and outflow to each department for visitors, we construct the WAIFW matrix, W, by assuming that it is proportional to the contact rate matrix [8, 9] : The diagram for the SEIR (susceptible-exposed-infectious-recovered) model with compartments of doctor, nurse, patient, and caregiver. abstract: Novel coronavirus (named SARS-CoV-2) can spread widely in confined settings including hospitals, cruise ships, prisons, and places of worship. In particular, a healthcare-associated outbreak could become the epicenter of coronavirus disease (COVID-19). This study aimed to evaluate the effects of different intervention strategies on the hospital outbreak within a tertiary hospital. A mathematical model was developed for the COVID-19 transmission within a 2500-bed tertiary hospital of South Korea. The SEIR (susceptible-exposed-infectious-recovered) model with a compartment of doctor, nurse, patient, and caregiver was constructed. The effects of different intervention strategies such as front door screening, quarantine unit for newly admitted patients, early testing of suspected infected people, and personal protective equipment for both medical staff and visitors were evaluated. The model suggested that the early testing (within eight hours) of infected cases and monitoring the quarantine ward for newly hospitalized patients are effective measures for decreasing the incidence of COVID-19 within a hospital (81.3% and 70% decrease of number of incident cases, respectively, during 60 days). Front door screening for detecting suspected cases had only 42% effectiveness. Screening for prohibiting the admission of COVID-19 patients was more effective than the measures for patients before emergency room or outpatient clinic. This model suggests that under the assumed conditions, some effective measures have a great influence on the incidence of COVID-19 within a hospital. The implementation of the preventive measures could reduce the size of a hospital outbreak. url: https://www.ncbi.nlm.nih.gov/pubmed/33104736/ doi: 10.1371/journal.pone.0241169 id: cord-289892-yh1lioyz author: Bai, Bingke title: Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells date: 2008-07-16 words: 5451.0 sentences: 300.0 pages: flesch: 55.0 cache: ./cache/cord-289892-yh1lioyz.txt txt: ./txt/cord-289892-yh1lioyz.txt summary: Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. In addition, because in vitro infection model of bat SL-CoV has not so far been established, we intended to use VLPs as an alternative to study the immune responses induced in DCs. Therefore, we compared the phenotypic and functional changes of immature DCs inoculated with BVLPs or with SARS CoV VLPs. The S-specific immune activation was further confirmed in mice using S DNA vaccines. Combining the flow cytometry results in Fig. 2 , it is reasonable to draw a conclusion that the structure of BVLPs, not LPS contamination, contributed to cytokine production in BVLPs-treated DCs. We previously constructed SARS CoV VLPs and investigated the humoral and cellular immune responses induced by SARS CoV VLPs in mice [29] . abstract: The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV. url: https://www.ncbi.nlm.nih.gov/pubmed/18628832/ doi: 10.1371/journal.pone.0002685 id: cord-295339-nzc47itk author: Baker, Marissa G. title: Estimating the burden of United States workers exposed to infection or disease: A key factor in containing risk of COVID-19 infection date: 2020-04-28 words: 3320.0 sentences: 139.0 pages: flesch: 41.0 cache: ./cache/cord-295339-nzc47itk.txt txt: ./txt/cord-295339-nzc47itk.txt summary: METHODS: To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. Given the proportion of the United States workforce exposed to disease or infection at work, this analysis also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve. To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. abstract: INTRODUCTION: With the global spread of COVID-19, there is a compelling public health interest in quantifying who is at increased risk of contracting disease. Occupational characteristics, such as interfacing with the public and being in close quarters with other workers, not only put workers at high risk for disease, but also make them a nexus of disease transmission to the community. This can further be exacerbated through presenteeism, the term used to describe the act of coming to work despite being symptomatic for disease. Quantifying the number of workers who are frequently exposed to infection and disease in the workplace, and understanding which occupational groups they represent, can help to prompt public health risk response and management for COVID-19 in the workplace, and subsequent infectious disease outbreaks. METHODS: To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. This allowed us to estimate the number of United States workers, across all occupations, exposed to disease or infection at work more than once a month. RESULTS: Based on our analyses, approximately 10% (14.4 M) of United States workers are employed in occupations where exposure to disease or infection occurs at least once per week. Approximately 18.4% (26.7 M) of all United States workers are employed in occupations where exposure to disease or infection occurs at least once per month. While the majority of exposed workers are employed in healthcare sectors, other occupational sectors also have high proportions of exposed workers. These include protective service occupations (e.g. police officers, correctional officers, firefighters), office and administrative support occupations (e.g. couriers and messengers, patient service representatives), education occupations (e.g. preschool and daycare teachers), community and social services occupations (community health workers, social workers, counselors), and even construction and extraction occupations (e.g. plumbers, septic tank installers, elevator repair). CONCLUSIONS: The large number of persons employed in occupations with frequent exposure to infection and disease underscore the importance of all workplaces developing risk response plans for COVID-19. Given the proportion of the United States workforce exposed to disease or infection at work, this analysis also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve. url: https://doi.org/10.1371/journal.pone.0232452 doi: 10.1371/journal.pone.0232452 id: cord-282202-q2q4vies author: Banerjee, Amitava title: Clinical academic research in the time of Corona: A simulation study in England and a call for action date: 2020-08-13 words: 4106.0 sentences: 229.0 pages: flesch: 46.0 cache: ./cache/cord-282202-q2q4vies.txt txt: ./txt/cord-282202-q2q4vies.txt summary: DESIGN: A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics). "Learning is difficult in the midst of an emergency" [7] , but our ability to deliver timely, high-impact clinical research, relevant to patients and populations, is critical across the academic spectrum [8] , from "bench to bedside to big data", whether basic biology, repurposed and novel therapeutic approaches, vaccines or modelling. Our aims were to: (i) model potential impact of the pandemic on clinical academic capacity in England relating to COVID-19; and (ii) develop evidence-based recommendations to inform the optimal scientific response to COVID-19. abstract: OBJECTIVES: We aimed to model the impact of coronavirus (COVID-19) on the clinical academic response in England, and to provide recommendations for COVID-related research. DESIGN: A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics). SETTING: Clinical academics in primary and secondary care in England. PARTICIPANTS: Equivalent of 3200 full-time clinical academics in England. INTERVENTIONS: Four policy approaches to COVID-19 with differing population infection rates: “Italy model” (6%), “mitigation” (10%), “relaxed mitigation” (40%) and “do-nothing” (80%) scenarios. Low and high strain on the health system (no clinical academics able to do research at 10% and 5% infection rate, respectively. MAIN OUTCOME MEASURES: Number of full-time clinical academics available to conduct clinical research during the pandemic in England. RESULTS: In the “Italy model”, “mitigation”, “relaxed mitigation” and “do-nothing” scenarios, from 5 March 2020 the duration (days) and peak infection rates (%) are 95(2.4%), 115(2.5%), 240(5.3%) and 240(16.7%) respectively. Near complete attrition of academia (87% reduction, <400 clinical academics) occurs 35 days after pandemic start for 11, 34, 62, 76 days respectively—with no clinical academics at all for 37 days in the “do-nothing” scenario. Restoration of normal academic workforce (80% of normal capacity) takes 11, 12, 30 and 26 weeks respectively. CONCLUSIONS: Pandemic COVID-19 crushes the science needed at system level. National policies mitigate, but the academic community needs to adapt. We highlight six key strategies: radical prioritisation (eg 3–4 research ideas per institution), deep resourcing, non-standard leadership (repurposing of key non-frontline teams), rationalisation (profoundly simple approaches), careful site selection (eg protected sites with large academic backup) and complete suspension of academic competition with collaborative approaches. url: https://doi.org/10.1371/journal.pone.0237298 doi: 10.1371/journal.pone.0237298 id: cord-258172-p54j4zzo author: Barker, Harlan title: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2 date: 2020-10-28 words: 8453.0 sentences: 409.0 pages: flesch: 48.0 cache: ./cache/cord-258172-p54j4zzo.txt txt: ./txt/cord-258172-p54j4zzo.txt summary: Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Analysis of ACE2 promoter regions was performed using the TFBSfootprinter tool (https:// github.com/thirtysix/TFBS_footprinting) which uses transcription-relevant data from several major databases to enhance prediction of putative TFBSs, including: all cell types aggregated and merged human ATAC-Seq data from ENCODE [43] , transcription start sites and expression data from FANTOM5 [44] , expression quantitative trail loci from GTEx [39] , TFBS metacluster data from GTRD [45] , TFBS binding profile data from JASPAR [46] , and sequence and conservation data from Ensembl [47] . abstract: The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung. url: https://www.ncbi.nlm.nih.gov/pubmed/33112891/ doi: 10.1371/journal.pone.0240647 id: cord-003498-4ct0ywnw author: Bdeir, Najat title: A system for production of defective interfering particles in the absence of infectious influenza A virus date: 2019-03-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396908/ doi: 10.1371/journal.pone.0212757 id: cord-289093-si8btsab author: Beard, Philippa M. title: A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference date: 2014-06-05 words: 6578.0 sentences: 310.0 pages: flesch: 49.0 cache: ./cache/cord-289093-si8btsab.txt txt: ./txt/cord-289093-si8btsab.txt summary: To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. The methodology in the previously published VACV screens varied considerably; Mercer et al [32] measured the growth of a thymidine-kinase-deficient VACV (strain Western Reserve) after only 8 h of infection, thereby identifying cellular proteins involved in the initial stages of virus replication but excluding analysis of viral spread. abstract: Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics. url: https://doi.org/10.1371/journal.pone.0098431 doi: 10.1371/journal.pone.0098431 id: cord-011857-brbqgbpz author: Beasley, Steven A. title: An Angelman syndrome substitution in the HECT E3 ubiquitin ligase C-terminal Lobe of E6AP affects protein stability and activity date: 2020-07-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by speech impairment, intellectual disability, ataxia, and epilepsy. AS is caused by mutations in the maternal copy of UBE3A located on chromosome 15q11-13. UBE3A codes for E6AP (E6 Associated Protein), a prominent member of the HECT (Homologous to E6AP C-Terminus) E3 ubiquitin ligase family. E6AP catalyzes the posttranslational attachment of ubiquitin via its HECT domain onto various intracellular target proteins to regulate DNA repair and cell cycle progression. The HECT domain consists of an N-lobe, required for E2~ubiquitin recruitment, while the C-lobe contains the conserved catalytic cysteine required for ubiquitin transfer. Previous genetic studies of AS patients have identified point mutations in UBE3A that result in amino acid substitutions or premature termination during translation. An AS transversion mutation (codon change from ATA to AAA) within the region of the gene that codes for the catalytic HECT domain of E6AP has been annotated (I827K), but the molecular basis for this loss of function substitution remained elusive. Here, we demonstrate that the I827K substitution destabilizes the 3D fold causing protein aggregation of the C-terminal lobe of E6AP using a combination of spectropolarimetry and nuclear magnetic resonance (NMR) spectroscopy. Our fluorescent ubiquitin activity assays with E6AP-I827K show decreased ubiquitin thiolester formation and ubiquitin discharge. Using 3D models in combination with our biochemical and biophysical results, we rationalize why the I827K disrupts E6AP-dependent ubiquitylation. This work provides new insight into the E6AP mechanism and how its malfunction can be linked to the AS phenotype. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343168/ doi: 10.1371/journal.pone.0235925 id: cord-000261-ip32y0j5 author: Becker, Pablo D. title: Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice date: 2010-10-04 words: 5816.0 sentences: 270.0 pages: flesch: 48.0 cache: ./cache/cord-000261-ip32y0j5.txt txt: ./txt/cord-000261-ip32y0j5.txt summary: Following immunization, human CD19 + B cells were sorted based on surface CD27 expression, as a marker of memory phenotype, and the isotype of surface Igs. The sorted B cell populations were immortalized in vitro by retroviral transduction with human B cell lymphoma (BCL)-6 and BCL-XL genes and antigen-specific B cell clones were established and characterized. The obtained results provided the proof-of-concept for the usefulness of this generic approach based on HIS mice combined with immortalization of human B cells for the rapid and inexpensive development of human mAbs against a wide range of antigens. Since HIS mice contained broad naïve B cell repertoires, we analyzed the induction of human antigen-specific B cell responses after immunization with commercially available human vaccines. So far, humanized mouse models based on the transplantation of human HSC only -i.e. without additional human tissues -share these limitations, and immunization strategies result in the limited generation of class-switched antigen-specific B cell responses [14, 31, 32] . abstract: BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949385/ doi: 10.1371/journal.pone.0013137 id: cord-000895-z5rdf0mi author: Belalov, Ilya S. title: Causes and Implications of Codon Usage Bias in RNA Viruses date: 2013-02-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Choice of synonymous codons depends on nucleotide/dinucleotide composition of the genome (termed mutational pressure) and relative abundance of tRNAs in a cell (translational pressure). Mutational pressure is commonly simplified to genomic GC content; however mononucleotide and dinucleotide frequencies in different genomes or mRNAs may vary significantly, especially in RNA viruses. A series of in silico shuffling algorithms were developed to account for these features and analyze the relative impact of mutational pressure components on codon usage bias in RNA viruses. Total GC content was a poor descriptor of viral genome composition and causes of codon usage bias. Genomic nucleotide content was the single most important factor of synonymous codon usage. Moreover, the choice between compatible amino acids (e.g., leucine and isoleucine) was strongly affected by genomic nucleotide composition. Dinucleotide composition at codon positions 2-3 had additional effect on codon usage. Together with mononucleotide composition bias, it could explain almost the entire codon usage bias in RNA viruses. On the other hand, strong dinucleotide content bias at codon position 3-1 found in some viruses had very little effect on codon usage. A hypothetical innate immunity sensor for CpG in RNA could partially explain the codon usage bias, but due to dependence of virus translation upon biased host translation machinery, experimental studies are required to further explore the source of dinucleotide bias in RNA viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581513/ doi: 10.1371/journal.pone.0056642 id: cord-303187-ny4qr2a2 author: Belo, Vinícius Silva title: Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil date: 2017-11-01 words: 7691.0 sentences: 410.0 pages: flesch: 44.0 cache: ./cache/cord-303187-ny4qr2a2.txt txt: ./txt/cord-303187-ny4qr2a2.txt summary: Despite the perceived need and usefulness of such parameter estimates and recommendations for the most appropriate approaches applicable under such study designs [30] , survival and recruitment estimates of free-ranging dogs had not been obtained using methods of capture and recapture. In this study, we present estimates of abundance, survival and recruitment rates, and the probabilities of capture of two free-roaming dog populations by means of analytical models for open populations, so far unexplored in previous studies. We estimated critical parameters (survival, recruitment and abundance) that describe the population dynamics of free-roaming dogs based on a capture and recapture study design and on models suitable for open populations. Our study demonstrated the increase in population size in both areas, the predominance and greater recruitment of males, the temporal variability in recruitment and in survival probabilities, the lack of effect of sterilization on population dynamics, the influence of abandon and of density-independent factors and a high demographic turnover. abstract: The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices. url: https://www.ncbi.nlm.nih.gov/pubmed/29091961/ doi: 10.1371/journal.pone.0187233 id: cord-000547-adfigzc1 author: Beniac, Daniel R. title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date: 2012-01-11 words: 7782.0 sentences: 392.0 pages: flesch: 51.0 cache: ./cache/cord-000547-adfigzc1.txt txt: ./txt/cord-000547-adfigzc1.txt summary: METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes ( Figure 5 ) to a resolution of 14 Å as measured by the Fourier Shell Correlation (FSC) 0.5 criterion. Analysis of 2090 distinct intact virions with a nucleocapsid from cryo-electron micrographs shows that the most common class length (53%) of virus particles is 982679 nm ( Figure 1A , Table S1 ). abstract: BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256159/ doi: 10.1371/journal.pone.0029608 id: cord-305274-mcsdem7y author: Beniac, Daniel R. title: Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion date: 2007-10-24 words: 5463.0 sentences: 254.0 pages: flesch: 51.0 cache: ./cache/cord-305274-mcsdem7y.txt txt: ./txt/cord-305274-mcsdem7y.txt summary: We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis. The structures of ACE2 bound to a fragment of the SARS spike containing the receptor-binding domain and the pre-and postfusion configurations of the fusion core heptad repeats of the spike have been solved to atomic resolution [2, 3, [24] [25] [26] . In addition, the atomic resolution structures of two neutralizing antibodies bound to the SARS spike receptor-binding domain have been solved [27, 28] showing that blocking of the receptor binding domain, preventing attachment of virions to cell-surface ACE2, is the likely mechanism of virus neutralization by these antibodies. abstract: The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis. url: https://www.ncbi.nlm.nih.gov/pubmed/17957264/ doi: 10.1371/journal.pone.0001082 id: cord-000638-ss1435el author: Beq, Stephanie title: Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date: 2012-04-16 words: 5142.0 sentences: 237.0 pages: flesch: 47.0 cache: ./cache/cord-000638-ss1435el.txt txt: ./txt/cord-000638-ss1435el.txt summary: The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. In contrast, Arizcorreta and colleagues showed that IFNa and ribavirin therapy induces a substantial reduction of circulating sjTRECs, in HIV/HCV co-infected patients, accompanied by sustained naïve CD4 + T-cell defect, suggesting thymic dysfunction [10] . While the number of RTEs was similar in HCV-infected patients at study entry and healthy individuals ( These data demonstrate that, as early as one month following treatment initiation, IFNa induces stronger alterations of naïve Tcell subsets, and more specifically in the RTE compartment than in any other T-cell subset, suggesting a specific effect on thymopoiesis. abstract: Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328332/ doi: 10.1371/journal.pone.0034326 id: cord-000248-zueoyesj author: Berretta, Regina title: Cancer Biomarker Discovery: The Entropic Hallmark date: 2010-08-18 words: 33594.0 sentences: 1678.0 pages: flesch: 43.0 cache: ./cache/cord-000248-zueoyesj.txt txt: ./txt/cord-000248-zueoyesj.txt summary: These authors cite, for example, ''''mitochondrial dysfunction'''' [5, 6] (including, but not limited to ''''glucose avidity'''' [7] and ''''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'''' [6, 8] , ''''altered glycolysis'''' [9] , ''''altered bioenergetic function of mitochondria'''' [10] ), ''''dysregulation of cell cycle and defective genome-integrity checkpoints'''' [11] , ''''aberrant DNA methylation'''' [12] (''''promoter hypermethylation of hallmark cancer genes'''' [13] and ''''CpG island hypermethylation and global genomic hypomethylation'''' [14] ), ''''shift in cellular metabolism'''' [15, 16, 17] , ''''regional hypoxia'''' [18] , ''''microenviroment acidosis'''' [19] , ''''abnormal microRNA regulation'''' [20, 21] , ''''aneuploidy'''' and ''''chromosome aberrations'''' [22, 23, 24, 25, 26] , ''''disruption of cellular junctions'''' [27] , ''''avoidance of the immune response'''' [28] , ''''pre-existing chronic inflammatory conditions'''' [29, 30] , ''''cancerrelated inflammation'''' [29] , ''''disabled autophagy'''' [28] , ''''impaired cellular senescence'''' [31] , ''''altered NF-kappaB signalling'''' [32] , ''''altered growth patterns, not altered growth per se'''' [33] , ''''disregulated DNA methylation and histone modifications'''' [34] , ''''tissue dedifferentiation'''' [35, 36] , and ''''somatically heritable molecular alterations'''' [37] . abstract: BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923618/ doi: 10.1371/journal.pone.0012262 id: cord-330537-xz0wt1sz author: Biermann, Olivia title: Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review date: 2020-10-28 words: 5668.0 sentences: 307.0 pages: flesch: 49.0 cache: ./cache/cord-330537-xz0wt1sz.txt txt: ./txt/cord-330537-xz0wt1sz.txt summary: title: Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review BACKGROUND: The World Health Organization (WHO) stresses the importance of active case-finding (ACF) for early detection of tuberculosis (TB), especially in the 30 high-burden countries that account for almost 90% of cases globally. OBJECTIVE: To describe the attitudes of National TB Programme (NTP) managers related to ACF policy development, implementation and scale-up in the 30 high-burden countries, and to review national TB strategic plans. Moreover, this study focuses on National TB Programme (NTP) managers, key stakeholders in developing and implementing ACF policies [13] . The study comprised a cross-sectional survey with NTP managers from 30 high TB burden countries, which included closed and open-ended questions designed to elicit quantitative and qualitative information, enhancing each other [15] . abstract: BACKGROUND: The World Health Organization (WHO) stresses the importance of active case-finding (ACF) for early detection of tuberculosis (TB), especially in the 30 high-burden countries that account for almost 90% of cases globally. OBJECTIVE: To describe the attitudes of National TB Programme (NTP) managers related to ACF policy development, implementation and scale-up in the 30 high-burden countries, and to review national TB strategic plans. METHODS: This was a mixed-methods study with an embedded design: A cross-sectional survey with NTP managers yielded quantitative and qualitative data. A review of national TB strategic plans complemented the results. All data were analyzed in parallel and merged in the interpretation of the findings. RESULTS: 23 of the 30 NTP managers (77%) participated in the survey and 22 (73%) national TB strategic plans were reviewed. NTP managers considered managers in districts and regions key stakeholders for both ACF policy development and implementation. Different types of evidence were used to inform ACF policy, while there was a particular demand for local evidence. The NSPs reflected the NTP managers’ unanimous agreement on the need for ACF scale-up, but not all included explicit aims and targets related to ACF. The NTP managers recognized that ACF may decrease health systems costs in the long-term, while acknowledging the risk for increased health system costs in the short-term. About 90% of the NTP managers declared that financial and human resources were currently lacking, while they also elaborated on strategies to overcome resource constraints. CONCLUSION: NTP managers stated that ACF should be scaled up but reported resource constraints. Strategies to increase resources exist but may not yet have been fully implemented, e.g. generating local evidence including from operational research for advocacy. Managers in districts and regions were identified as key stakeholders whose involvement could help improve ACF policy development, implementation and scale-up. url: https://www.ncbi.nlm.nih.gov/pubmed/33112890/ doi: 10.1371/journal.pone.0240696 id: cord-333955-bnzbppof author: Biesold, Susanne E. title: Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date: 2011-11-30 words: 5016.0 sentences: 275.0 pages: flesch: 51.0 cache: ./cache/cord-333955-bnzbppof.txt txt: ./txt/cord-333955-bnzbppof.txt summary: Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. Cells from Pteropus species have been shown to produce high amounts of interferon (IFN)-l after stimulation with the double-strand (ds)RNA analogue poly IC, and after infection with the bat-associated paramyxovirus, Tioman [13] . In accordance with the IFN mRNA induction, the highest equivalent amount of bioactive secreted IFN upon RVFV 13 virus infection and poly IC transfection was measured in EidNi/41.3 cells, followed by MEF and MA104 (Figure 3 ). Increases of infectious virus formation were about 1000-fold within 24 hpi, and specific infectivities, expressed as PFU per genome equivalent (PCR units), were highly comparable between cell cultures ( Figure 4C) . abstract: Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs. url: https://doi.org/10.1371/journal.pone.0028131 doi: 10.1371/journal.pone.0028131 id: cord-340713-v5sdowb7 author: Bird, Jordan J. title: Country-level pandemic risk and preparedness classification based on COVID-19 data: A machine learning approach date: 2020-10-28 words: 5669.0 sentences: 260.0 pages: flesch: 53.0 cache: ./cache/cord-340713-v5sdowb7.txt txt: ./txt/cord-340713-v5sdowb7.txt summary: The three four-class classification problems are then explored and benchmarked through leave-one-country-out cross validation to find the strongest model, producing a Stack of Gradient Boosting and Decision Tree algorithms for risk of transmission, a Stack of Support Vector Machine and Extra Trees for risk of mortality, and a Gradient Boosting algorithm for the risk of inability to test. The classification problem of risk is therefore formulated based on prior knowledge of the pandemic in terms of class only, but the attributes to attempt to classify them are purely country-level information regardless of number of cases, deaths and other coronavirus specific data. Country-level pandemic risk and preparedness classification based on COVID-19 data Fig 10 shows a comparison of other models that were explored. Country-level pandemic risk and preparedness classification based on COVID-19 data Table 1 shows the predicted class values for the best models applied to each of the respective risk classification problems. abstract: In this work we present a three-stage Machine Learning strategy to country-level risk classification based on countries that are reporting COVID-19 information. A K% binning discretisation (K = 25) is used to create four risk groups of countries based on the risk of transmission (coronavirus cases per million population), risk of mortality (coronavirus deaths per million population), and risk of inability to test (coronavirus tests per million population). The four risk groups produced by K% binning are labelled as ‘low’, ‘medium-low’, ‘medium-high’, and ‘high’. Coronavirus-related data are then removed and the attributes for prediction of the three types of risk are given as the geopolitical and demographic data describing each country. Thus, the calculation of class label is based on coronavirus data but the input attributes are country-level information regardless of coronavirus data. The three four-class classification problems are then explored and benchmarked through leave-one-country-out cross validation to find the strongest model, producing a Stack of Gradient Boosting and Decision Tree algorithms for risk of transmission, a Stack of Support Vector Machine and Extra Trees for risk of mortality, and a Gradient Boosting algorithm for the risk of inability to test. It is noted that high risk for inability to test is often coupled with low risks for transmission and mortality, therefore the risk of inability to test should be interpreted first, before consideration is given to the predicted transmission and mortality risks. Finally, the approach is applied to more recent risk levels to data from September 2020 and weaker results are noted due to the growth of international collaboration detracting useful knowledge from country-level attributes which suggests that similar machine learning approaches are more useful prior to situations later unfolding. url: https://doi.org/10.1371/journal.pone.0241332 doi: 10.1371/journal.pone.0241332 id: cord-012891-heqsfzkm author: Blanco Vázquez, Cristina title: Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity date: 2020-09-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bovine paratuberculosis (PTB) is a chronic granulomatous enteritis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), responsible for important economic losses in the dairy industry. Current diagnostic methods have low sensitivities for detection of latent forms of MAP infection, defined by focal granulomatous lesions and scarce humoral response or MAP presence. In contrast, patent infections correspond to multifocal and diffuse types of enteritis where there is increased antibody production, and substantial mycobacterial load. Our previous RNA-Seq analysis allowed the selection of five candidate biomarkers overexpressed in peripheral blood of MAP infected Holstein cows with focal (ABCA13 and MMP8) and diffuse (FAM84A, SPARC and DES) lesions vs. control animals with no detectable PTB-associated lesions in intestine and regional lymph nodes. The aim of the current study was to assess the PTB diagnostic potential of commercial ELISAs designed for the specific detection of these biomarkers. The ability of these ELISAs to identify animals with latent and/or patent forms of MAP infection was investigated using serum from naturally infected cattle (n = 88) and non-infected control animals (n = 67). ROC analysis revealed that the ABCA13-based ELISA showed the highest diagnostic accuracy for the detection of infected animals with focal lesions (AUC 0.837, sensitivity 79.25% and specificity 88.06%) and with any type of histological lesion (AUC 0.793, sensitivity 69.41% and specificity 86.57%) improving on the diagnostic performance of the popular IDEXX ELISA and other conventional diagnostic methods. SPARC and MMP8 showed the highest diagnostic accuracy for the detection of animals with multifocal (AUC 0.852) and diffuse lesions (AUC 0.831), respectively. In conclusion, our results suggest that quantification of ABCA13, SPARC and MMP8 by ELISA has the potential for implementation as a diagnostic tool to reliably identify MAP infection, greatly improving early detection of MAP latent infections when antibody responses and fecal shedding are undetectable using conventional diagnostic methods. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470414/ doi: 10.1371/journal.pone.0236336 id: cord-013099-j816c3tw author: Blease, Charlotte title: US primary care in 2029: A Delphi survey on the impact of machine learning date: 2020-10-08 words: 5698.0 sentences: 303.0 pages: flesch: 54.0 cache: ./cache/cord-013099-j816c3tw.txt txt: ./txt/cord-013099-j816c3tw.txt summary: To address this research gap, we designed a Delphi survey to explore leading health informaticians'' predictions about the impact of machine learning on primary care in the US in 2029. Acknowledging that heterogeneous panels have been shown to result in more accurate estimates [33] , and that what counts as an expert can be influenced by goals, values, and the manner in which knowledge is generated, we aimed to recruit diverse participants from across academia, healthcare, non-profit organizations, and industry; and to strive for panelists with a varied complementarity of interests within health informatics. In the first round, the Delphi survey requested demographic information; this was followed by 5 sections, with 7 open-ended questions, on the impact of machine learning on primary care by 2029 (see S1 Appendix; Table 1 We also included a final comment-box for feedback on the survey. abstract: OBJECTIVE: To solicit leading health informaticians’ predictions about the impact of AI/ML on primary care in the US in 2029. DESIGN: A three-round online modified Delphi poll. PARTICIPANTS: Twenty-nine leading health informaticians. METHODS: In September 2019, health informatics experts were selected by the research team, and invited to participate the Delphi poll. Participation in each round was anonymous, and panelists were given between 4–8 weeks to respond to each round. In Round 1 open-ended questions solicited forecasts on the impact of AI/ML on: (1) patient care, (2) access to care, (3) the primary care workforce, (4) technological breakthroughs, and (5) the long-future for primary care physicians. Responses were coded to produce itemized statements. In Round 2, participants were invited to rate their agreement with each item along 7-point Likert scales. Responses were analyzed for consensus which was set at a predetermined interquartile range of ≤ 1. In Round 3 items that did not reach consensus were redistributed. RESULTS: A total of 16 experts participated in Round 1 (16/29, 55%). Of these experts 13/16 (response rate, 81%), and 13/13 (response rate, 100%), responded to Rounds 2 and 3, respectively. As a result of developments in AI/ML by 2029 experts anticipated workplace changes including incursions into the disintermediation of physician expertise, and increased AI/ML training requirements for medical students. Informaticians also forecast that by 2029 AI/ML will increase diagnostic accuracy especially among those with limited access to experts, minorities and those with rare diseases. Expert panelists also predicted that AI/ML-tools would improve access to expert doctor knowledge. CONCLUSIONS: This study presents timely information on informaticians’ consensus views about the impact of AI/ML on US primary care in 2029. Preparation for the near-future of primary care will require improved levels of digital health literacy among patients and physicians. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544100/ doi: 10.1371/journal.pone.0239947 id: cord-003484-ylpa702c author: Blázquez, Elena title: Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma date: 2019-02-21 words: 6990.0 sentences: 352.0 pages: flesch: 53.0 cache: ./cache/cord-003484-ylpa702c.txt txt: ./txt/cord-003484-ylpa702c.txt summary: Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The objective of this study was to assess inactivation efficiency of the SurePure Turbulator UV-C irradiation system with selected swine enveloped viruses Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Swine influenza A virus (SIV) and Classical swine fever virus (CSFV) and non-enveloped viruses Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus 2 (PCV-2) and Senecavirus A (SVA) inoculated in liquid bovine or porcine plasma. abstract: The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383881/ doi: 10.1371/journal.pone.0212332 id: cord-001065-j4hvyyoi author: Boncristiani, Humberto F. title: In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera) date: 2013-09-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764161/ doi: 10.1371/journal.pone.0073429 id: cord-346347-r4ork18p author: Borrion, Hervé title: Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China date: 2020-10-14 words: 7552.0 sentences: 358.0 pages: flesch: 49.0 cache: ./cache/cord-346347-r4ork18p.txt txt: ./txt/cord-346347-r4ork18p.txt summary: There are reasons to believe that crime-related performance measures during a pandemic period, or other disasters, may not match the idealised resilience triangle, but rather resemble the dipper-shaped function depicted in Fig 2. Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China RD(n) provides a useful measure to monitor the operating level (%) of offenders. In the case where the crime level in this phase exceeds the pre-Disruptive Event (t DE ) level (μ 7 �μ 1 ), two sub-indicators can be used to measure the ecosystem''s resilience during the recovery phase. Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China between τ − and τ + shows it took significantly longer for crime to drop than to return to its expected level. abstract: This paper uses resilience as a lens through which to analyse disasters and other major threats to patterns of criminal behaviour. A set of indicators and mathematical models are introduced that aim to quantitatively describe changes in crime levels in comparison to what could otherwise be expected, and what might be expected by way of adaptation and subsequent resumption of those patterns. The validity of the proposed resilience assessment tool is demonstrated using commercial theft data from the COVID-19 pandemic period. A 64 per cent reduction in crime was found in the studied city (China) during an 83-day period, before daily crime levels bounced back to higher than expected values. The proposed resilience indicators are recommended as benchmarking instruments for evaluating and comparing the global impact of COVID-19 policies on crime and public safety. url: https://doi.org/10.1371/journal.pone.0240077 doi: 10.1371/journal.pone.0240077 id: cord-256424-t3dtabi4 author: Bousbia, Sabri title: Repertoire of Intensive Care Unit Pneumonia Microbiota date: 2012-02-28 words: 5641.0 sentences: 294.0 pages: flesch: 39.0 cache: ./cache/cord-256424-t3dtabi4.txt txt: ./txt/cord-256424-t3dtabi4.txt summary: Recently, the bacterial microbiota of patients with cystic fibrosis and ventilator-associated pneumonia (VAP) were studied using 16S rDNA gene amplification followed by clone libraries sequencing [9] [10] [11] . Bacterial microbiota as evaluated by 16S rDNA Molecular assays were positive for at least one bacterium for 129 out of 185 bronchoalveolar lavage (BAL) samples from patients with pneumonia as well as from 13 out of 25 from control individuals (p = 0.07). Fungal microbiota obtained from patients showed the presence of 22 different species belonging to 2 phyla (8 orders, 11 families and 12 genera) among which 6 phylotypes had not been previously identified in BAL fluids from pneumonia. Indeed, our study reveals that some pathogens that till now had been considered typical for ICU pneumonia, such as Pseudomonas aeruginosa and Streptococcus species, or viruses, such CMV and HSV, can be detected as commonly in controls as in patients (Fig. S1 and S2 ). abstract: Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls). Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77±2.93). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented. url: https://www.ncbi.nlm.nih.gov/pubmed/22389704/ doi: 10.1371/journal.pone.0032486 id: cord-293393-kbndie8e author: Braesch-Andersen, Sten title: ApoD Mediates Binding of HDL to LDL and to Growing T24 Carcinoma date: 2014-12-16 words: 6253.0 sentences: 386.0 pages: flesch: 60.0 cache: ./cache/cord-293393-kbndie8e.txt txt: ./txt/cord-293393-kbndie8e.txt summary: To investigate the presence of particles containing both apoD and apoB, we performed a dual-specific ELISA using the anti-apoD mAb D554 as a capture antibody and a biotinylated anti-apoB mAb, LDL20, for detection. To determine the importance of having intact lipoprotein particles, we repeated the dual-specific apoD/B ELISA in the presence of detergent, using anti-apoD-D544 as the capture mAb and anti-apoB-LDL20 as the detecting mAb. As seen in Fig. 4A , only small amounts of apoB bound to D544 when detergent was present, indicating that intact lipoprotein particles are needed for the apoD-LDL interaction. In agreement with this latter finding, apoD production was high in confluent, growth-arrested T24 cell cultures (2,5 million cells in 9 ml), but was not detectable in non-confluent proliferating Anti-apoD (D544) was used as the capture antibody and anti-apoB (LDL20-biotin) was used as the detection antibody in a detergent free dualspecific ELISA. abstract: Apolipoprotein (Apo) D is an important protein produced in many parts of the body. It is necessary for the development and repair of the brain and protection from oxidative stress. The purpose of this study was to investigate the extent to which apoD interacts with lipoproteins in human plasma. By using detergent-free ELISA, we show that immobilized monoclonal antibodies against apoD very efficiently bind to low density lipoprotein (LDL) from plasma; this binding is as equally efficient as binding to an anti-apoB monoclonal antibody. Adding detergent to the plasma inhibited the binding, suggesting that the binding is dependent on the presence of intact lipoprotein particles. Reversing the system by using immobilized anti-apoB revealed that the affinity of apoD for LDL is rather low, suggesting that multiple bindings are needed for a durable connection. Biosensor experiments using purified lipoproteins also showed that purified apoD and high density lipoprotein 3 (HDL3), a lipoprotein fraction rich in apoD, were both able to bind LDL very efficiently, indicating that the HDL3-LDL interaction may be a physiological consequence of the affinity of apoD for LDL. Furthermore, we found that apoD increases the binding of HDL to actively growing T24 bladder carcinoma cells but not to quiescent, contact-inhibited, confluent T24 cells. This result is especially intriguing given that the T24 supernatant only contained detectable levels of apoD after growth inhibition, raising the possibility that alternating the expression of apoD and a putative apoD-receptor could give direction to the flow of lipids. In the current paper, we conclude that apoD mediates binding of HDL to LDL and to growing T24 carcinomas, thereby highlighting the importance of apoD in lipid metabolism. url: https://doi.org/10.1371/journal.pone.0115180 doi: 10.1371/journal.pone.0115180 id: cord-001446-mpuovmeb author: Bratcher, Preston E. title: Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA date: 2014-11-03 words: 4873.0 sentences: 226.0 pages: flesch: 43.0 cache: ./cache/cord-001446-mpuovmeb.txt txt: ./txt/cord-001446-mpuovmeb.txt summary: Circulating levels of SP-D have been examined for their potential use as a biomarker in various diseases including dermatitis [2, 3] , acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] , periodontitis [14] , interstitial pulmonary fibrosis (IPF) [10, 12, [15] [16] [17] [18] [19] [20] [21] [22] [23] , chronic obstructive pulmonary disease (COPD) [15, [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] , emphysema [37] , cystic fibrosis (CF) [15, 38, 39] , coronary disease [40, 41] , sclerosis [42] [43] [44] [45] [46] , cancer [47, 48] , sarcoidosis [21, 49] , allergies [28, [50] [51] [52] , rheumatoid arthritis [53, 54] , and respiratory infections [18, [55] [56] [57] [58] [59] [60] . Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis abstract: BACKGROUND: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature. In order to determine the source of these variations, factors influencing the measurement by ELISA were explored. MATERIALS AND METHODS: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw. Recombinant SP-D was diluted into different matrices and used for a standard curve. Samples were analyzed by capture ELISA using one of two distinct detection antibodies. RESULTS: The type of matrix had some effects on detection of recombinant SP-D. The type of anticoagulant used and dilution factor had very little effect, except for in plasma collected in EDTA vacutainers. The extent of variation in published values seemed to be due to the ELISA configuration employed, and, in agreement with this, we found that by switching the detection antibody, there was a 50% decrease in the extrapolated SP-D value of serum and plasma samples. Storage of samples resulted in slight changes in measured SP-D levels. CONCLUSIONS: The ELISA configuration employed to measure circulating levels of SP-D has a significant effect on the extrapolated values. In both configurations tested, the use of EDTA as a coagulant resulted in inconsistent values, and we, therefore, suggest the avoidance of this anticoagulant when assaying for SP-D by ELISA. While the demonstrated effects of several factors on measurement of SP-D may not account for all the disparities amongst the previous studies, they stress that variations in methodologies for measuring the same protein can result in very inconsistent results. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218753/ doi: 10.1371/journal.pone.0111466 id: cord-297287-0i4nc353 author: Braun, Benjamin title: Simulating phase transitions and control measures for network epidemics caused by infections with presymptomatic, asymptomatic, and symptomatic stages date: 2020-09-10 words: 4005.0 sentences: 204.0 pages: flesch: 49.0 cache: ./cache/cord-297287-0i4nc353.txt txt: ./txt/cord-297287-0i4nc353.txt summary: Using agent-based simulations on small world networks, we observe phase transitions for epidemic spread related to: 1) Global social distancing with a fixed probability of adherence. Phase transitions and control measures for network epidemics self-isolate in response to one infected social contact) all the way up to 97% with low levels of any type of social distancing. Because our goal is to understand the behavior of phase transitions regarding total number of infections in our model, we conducted secondary simulations on a refined parameter space based on the results of our regression tree analysis. There is also a clear interaction between the social distance probability and viral shedding parameters and the resulting number of infected agents and the length of the epidemic. Social distancing controls in this model exhibit a phase transition regarding total number of infections, either when imposed globally or when based on individual response to infected contacts. abstract: We investigate phase transitions associated with three control methods for epidemics on small world networks. Motivated by the behavior of SARS-CoV-2, we construct a theoretical SIR model of a virus that exhibits presymptomatic, asymptomatic, and symptomatic stages in two possible pathways. Using agent-based simulations on small world networks, we observe phase transitions for epidemic spread related to: 1) Global social distancing with a fixed probability of adherence. 2) Individually initiated social isolation when a threshold number of contacts are infected. 3) Viral shedding rate. The primary driver of total number of infections is the viral shedding rate, with probability of social distancing being the next critical factor. Individually initiated social isolation was effective when initiated in response to a single infected contact. For each of these control measures, the total number of infections exhibits a sharp phase transition as the strength of the measure is varied. url: https://www.ncbi.nlm.nih.gov/pubmed/32911518/ doi: 10.1371/journal.pone.0238412 id: cord-267519-a0bcmjkn author: Bravi, Francesca title: Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date: 2020-06-24 words: 3303.0 sentences: 144.0 pages: flesch: 44.0 cache: ./cache/cord-267519-a0bcmjkn.txt txt: ./txt/cord-267519-a0bcmjkn.txt summary: AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5] [6] [7] [8] , and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and ACE inhibitors (more consistently on animals than in humans) [9] [10] [11] [12] [13] [14] [15] [16] , some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), thus the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17] [18] [19] . abstract: AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). METHODS AND RESULTS: All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50–1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40–2.23), diabetes (AOR: 1.52; 1.05–2.18), CVD (AOR: 1.88; 1.32–2.70) and COPD (AOR: 1.88; 1.11–3.20). Only gender, age and diabetes also predicted very severe/lethal disease. CONCLUSION: No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians. url: https://www.ncbi.nlm.nih.gov/pubmed/32579597/ doi: 10.1371/journal.pone.0235248 id: cord-000006-104sqoxz author: Bray, Daniel P. title: Composition and Function of Haemolymphatic Tissues in the European Common Shrew date: 2008-10-15 words: 5701.0 sentences: 259.0 pages: flesch: 46.0 cache: ./cache/cord-000006-104sqoxz.txt txt: ./txt/cord-000006-104sqoxz.txt summary: Here, we examined the unique haemolymphatic system of the European common shrew (Sorex araneus) to investigate the capacity of this short-lived mammal, restricted by a fast metabolism and extremely limited fat reserves, to defend against its unusually diverse parasite fauna, both as a young animal and an adult. We examined and compared the structure, composition and function of relevant haemolymphatic tissues including the pancreas of Aselli, in wild-caught common shrews of different ages pre and post maturation, and the extent and type of inflammatory reactions produced in response to naturally occurring parasitic infections. While some degree of lymphatic exhaustion was obvious in adult animals (perhaps as a result of age-related changes, or reduced investment in immunity as a consequence of breeding effort), there was also evidence of some degree of compensation, in the form of storage of plasma cells particularly in the pancreas of Aselli, possibly as a defence against previously encountered parasites. abstract: BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561066/ doi: 10.1371/journal.pone.0003413 id: cord-296635-8r3tm966 author: Breed, Andrew C. title: Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management date: 2011-12-14 words: 4573.0 sentences: 199.0 pages: flesch: 47.0 cache: ./cache/cord-296635-8r3tm966.txt txt: ./txt/cord-296635-8r3tm966.txt summary: title: Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. Hendra virus (HeV) and Nipah virus (NiV) are paramyxoviruses of the genus Henipavirus with pteropid bats (i.e. flying-foxes; Pteropus sp., Family Pteropodidae) being the primary wildlife reservoir [1] . Henipaviruses have the potential to infect a wide range of mammalian species, and Hendra virus has spread from flying-foxes to horses in Australia on at least 20 reported separate occasions (five involving horse-human transmission), most recently in 2011 [5, 6, 7] . [14] on the infection dynamics of HeV in the little red flying-fox, Pteropus scapulatus, in the Northern Territory of Australia suggested that viral transmission may be predominantly horizontal, with pregnancy and lactation suggested as risk factors for infection. abstract: This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses. url: https://doi.org/10.1371/journal.pone.0028816 doi: 10.1371/journal.pone.0028816 id: cord-296399-vvbjulm9 author: Brinkmann, Constantin title: The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date: 2017-12-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. url: https://www.ncbi.nlm.nih.gov/pubmed/29216247/ doi: 10.1371/journal.pone.0189073 id: cord-308261-hxlebas8 author: Broekhuis, Femke title: Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya date: 2019-04-03 words: 4771.0 sentences: 223.0 pages: flesch: 52.0 cache: ./cache/cord-308261-hxlebas8.txt txt: ./txt/cord-308261-hxlebas8.txt summary: title: Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya To determine the static interactions between male cheetahs we calculated their space use and the amount of overlap for each dyad to determine the possibility that individuals could encounter each other either directly or indirectly. In general, cheetahs were closer to the encounter location after a possible encounter compared to before for all four time lags, apart from individual M03 in Dyad 3 where the opposite trend was Intraspecific interactions among carnivores: A case study of male cheetahs observed, however none of the results were significant (S1 Table) . Using GPS collar data we documented static and dynamic interactions between male cheetahs in Kenya''s Maasai Mara and investigated the outcomes of these interactions in terms of movement behaviour and mortalities. abstract: Intraspecific interactions between individuals or groups of individuals of the same species are an important component of population dynamics. Interactions can be static, such as spatial overlap, or dynamic based on the interactions of movements, and can be mediated through communication, such as the deployment of scent marks. Interactions and their behavioural outcomes can be difficult to determine, especially for species that live at low densities. With the use of GPS collars we quantify both static and dynamic interactions between male cheetahs (Acinonyx jubatus) and the behavioural outcomes. The 99% home-ranges of males overlapped significantly while there was little overlap of the 50% home-ranges. Despite this overlap, male cheetahs rarely came into close proximity of one another, possibly because presence was communicated through frequent visits to marking posts. The minimum distance between individuals in a dyad ranged from 89m to 196m but the average proximity between individuals ranged from 17,145 ± 6,865m to 26,367 ± 11,288m. Possible interactions took place more frequently at night than by day and occurred mostly in the 50% home-range of one individual of a dyad or where cores of both individuals overlapped. After a possible encounter male cheetahs stayed in close proximity to each other for up to 6 hours, which could be the result of a territory defence strategy or the presence of a receptive female. We believe that one of the encounters between a singleton and a 5-male coalition resulted in the death of the singleton. Our results give new insights into cheetah interactions, which could help our understanding of ecological processes such as disease transmission. url: https://www.ncbi.nlm.nih.gov/pubmed/30943236/ doi: 10.1371/journal.pone.0213910 id: cord-326568-twv2i3fb author: Bruminhent, Jackrapong title: Clinical characteristics and risk factors for coronavirus disease 2019 (COVID-19) among patients under investigation in Thailand date: 2020-09-15 words: 4402.0 sentences: 245.0 pages: flesch: 48.0 cache: ./cache/cord-326568-twv2i3fb.txt txt: ./txt/cord-326568-twv2i3fb.txt summary: To manage coronavirus disease 2019 (COVID-19), a national health authority has implemented a case definition of patients under investigation (PUIs) to guide clinicians'' diagnoses. Multivariate analysis identified close contact with an index case (OR, 3.49; 95%CI, 1.49–8.15; P = 0.004), visiting high-risk places (OR, 1.92; 95%CI, 1.03–3.56; P = 0.039), productive cough (OR, 2.03; 95%CI, 1.05–3.92; P = 0.034), and no medical coverage (OR, 3.91; 95%CI, 1.35–11.32; P = 0.012) as independent risk factors for COVID-19 among the PUIs. The majority had favorable outcomes, though one (1.9%) died from severe pneumonia. Apart from close contact with an infected case and visiting high-risk places, we found that having no medical coverage and presenting with productive cough were predictors of being diagnosed with COVID-19 among PUIs. SARS-CoV-2 is an emerging respiratory virus that commonly causes no or mild respiratory tract infection and is occasionally complicated by severe pneumonia [1] . abstract: To manage coronavirus disease 2019 (COVID-19), a national health authority has implemented a case definition of patients under investigation (PUIs) to guide clinicians’ diagnoses. We aimed to determine characteristics among all PUIs and those with and without COVID-19. We retrospectively reviewed clinical characteristics and risk factors for laboratory-confirmed COVID-19 cases among PUIs at a tertiary care center in Bangkok, Thailand, between March 23 and April 7, 2020. Reverse transcription-polymerase chain reaction for SARS-CoV-2 RNA was performed. There were 405 evaluable PUIs; 157 (38.8%) were men, with a mean age ± SD of 36.2 ± 12.6 years. The majority (68.9%) reported no comorbidities. There were 53 (13.1%) confirmed COVID-19 cases. The most common symptoms among those were cough (73.6%), fever (58.5%), sore throat (39.6%), and muscle pain (37.4%). Among these patients, diagnoses were upper respiratory tract infection (69.8%), viral syndrome (15.1%), pneumonia (11.3%), and asymptomatic infection (3.8%). Multivariate analysis identified close contact with an index case (OR, 3.49; 95%CI, 1.49–8.15; P = 0.004), visiting high-risk places (OR, 1.92; 95%CI, 1.03–3.56; P = 0.039), productive cough (OR, 2.03; 95%CI, 1.05–3.92; P = 0.034), and no medical coverage (OR, 3.91; 95%CI, 1.35–11.32; P = 0.012) as independent risk factors for COVID-19 among the PUIs. The majority had favorable outcomes, though one (1.9%) died from severe pneumonia. COVID-19 was identified in 13% of PUIs defined per a national health authority’s case definition. History of contact with a COVID-19 patient, visiting a high-risk place, having no medical coverage, and productive cough may identify individuals at risk of COVID-19 in Thailand. url: https://www.ncbi.nlm.nih.gov/pubmed/32931517/ doi: 10.1371/journal.pone.0239250 id: cord-329999-flzqm3wh author: Buchanan, Tom title: Why do people spread false information online? The effects of message and viewer characteristics on self-reported likelihood of sharing social media disinformation date: 2020-10-07 words: 13812.0 sentences: 728.0 pages: flesch: 50.0 cache: ./cache/cord-329999-flzqm3wh.txt txt: ./txt/cord-329999-flzqm3wh.txt summary: Four studies (total N = 2,634) explored the effect of message attributes (authoritativeness of source, consensus indicators), viewer characteristics (digital literacy, personality, and demographic variables) and their interaction (consistency between message and recipient beliefs) on self-reported likelihood of spreading examples of disinformation. Descriptive statistics for participant characteristics (personality, conservatism, new media literacy and age) and their reactions to the stimuli (likelihood of sharing, belief the stories were likely to be true, and rating of likelihood that they had seen them before) are summarised in Table 2 . This evaluated the extent to which digital media literacy (NMLS), authority of the message source, consensus, belief in veracity of the messages, consistency with participant beliefs (operationalised as the total SECS conservatism scale score), age and personality (Extraversion, Conscientiousness, Agreeableness, Openness to Experience and Neuroticism), predicted self-rated likelihood of sharing the posts. abstract: Individuals who encounter false information on social media may actively spread it further, by sharing or otherwise engaging with it. Much of the spread of disinformation can thus be attributed to human action. Four studies (total N = 2,634) explored the effect of message attributes (authoritativeness of source, consensus indicators), viewer characteristics (digital literacy, personality, and demographic variables) and their interaction (consistency between message and recipient beliefs) on self-reported likelihood of spreading examples of disinformation. Participants also reported whether they had shared real-world disinformation in the past. Reported likelihood of sharing was not influenced by authoritativeness of the source of the material, nor indicators of how many other people had previously engaged with it. Participants’ level of digital literacy had little effect on their responses. The people reporting the greatest likelihood of sharing disinformation were those who thought it likely to be true, or who had pre-existing attitudes consistent with it. They were likely to have previous familiarity with the materials. Across the four studies, personality (lower Agreeableness and Conscientiousness, higher Extraversion and Neuroticism) and demographic variables (male gender, lower age and lower education) were weakly and inconsistently associated with self-reported likelihood of sharing. These findings have implications for strategies more or less likely to work in countering disinformation in social media. url: https://doi.org/10.1371/journal.pone.0239666 doi: 10.1371/journal.pone.0239666 id: cord-351185-3y3gou6v author: Buckles, Thomas C. title: Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating date: 2020-05-29 words: 10061.0 sentences: 465.0 pages: flesch: 45.0 cache: ./cache/cord-351185-3y3gou6v.txt txt: ./txt/cord-351185-3y3gou6v.txt summary: However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). In contrast, ibuprofen and acetaminophen are classified as adaptive because rapid addition of either drug to polarized cells yields short-term collapse of the leading edge pseudopod and loss of the PIP 3 signal, followed by slow recovery. In contrast to the four therapeutic adaptive drugs, the two non-clinical control inhibitors wortmannin and Gö6976 are each known to directly inhibit key components of the leading edge positive feedback loop and rapid addition is observed herein to trigger long term collapse of the pseudopod with no detected recovery as previously observed [26, 30, [50] [51] [52] [53] [54] . abstract: Leukocyte migration is controlled by a membrane-based chemosensory pathway on the leading edge pseudopod that guides cell movement up attractant gradients during the innate immune and inflammatory responses. This study employed single cell and population imaging to investigate drug-induced perturbations of leading edge pseudopod morphology in cultured, polarized RAW macrophages. The drugs tested included representative therapeutics (acetylsalicylic acid, diclofenac, ibuprofen, acetaminophen) as well as control drugs (PDGF, Gö6976, wortmannin). Notably, slow addition of any of the four therapeutics to cultured macrophages, mimicking the slowly increasing plasma concentration reported for standard oral dosage in patients, yielded no detectable change in pseudopod morphology. This finding is consistent with the well established clinical safety of these drugs. However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). The novel observation of adaptive exposures leads us to hypothesize that rapid addition of an adaptive drug overwhelms an intrinsic or extrinsic adaptation system yielding temporary collapse followed by adaptive recovery, while slow addition enables gradual adaptation to counteract the drug perturbation in real time. Overall, the results illustrate an approach that may help identify therapeutic drugs that temporarily inhibit the leading edge pseudopod during extreme inflammation events, and toxic drugs that yield long term inhibition of the pseudopod with negative consequences for innate immunity. Future studies are needed to elucidate the mechanisms of drug-induced pseudopod collapse, as well as the mechanisms of adaptation and recovery following some inhibitory drug exposures. url: https://doi.org/10.1371/journal.pone.0233012 doi: 10.1371/journal.pone.0233012 id: cord-324405-6uanhe2p author: Burke, Rachel M. title: Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States date: 2020-09-02 words: 6616.0 sentences: 242.0 pages: flesch: 41.0 cache: ./cache/cord-324405-6uanhe2p.txt txt: ./txt/cord-324405-6uanhe2p.txt summary: To interrupt transmission and facilitate early identification of secondary cases (i.e., transmissions of SARS-CoV-2 from the original travel-related case patient to a close contact), public health authorities at the state, county, and local levels, in consultation with subject-matter experts from the U.S. Centers for Disease Control and Prevention (CDC), mobilized rapidly to place the patients under appropriate isolation and identify contacts exposed to these patients. To understand the prevalence of asymptomatic or pre-symptomatic infection, a convenience sample of actively monitored close contacts was selected from whom to request respiratory (nasopharyngeal [NP] and oropharyngeal [OP]) samples outside of diagnostic specimen collection procedures (i.e., while contacts were asymptomatic or, in some cases, symptomatic with � 1 previous negative SARS-CoV-2 result); some sites were able to request at least one set of samples from all close contacts, but most sites targeted sample collection mainly to close contacts determined to have had high-risk exposures, such as household members and some healthcare personnel. abstract: Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4–38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19. url: https://doi.org/10.1371/journal.pone.0238342 doi: 10.1371/journal.pone.0238342 id: cord-001213-gxqufddb author: Butt, Azeem Mehmood title: Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses date: 2014-03-04 words: 7178.0 sentences: 371.0 pages: flesch: 54.0 cache: ./cache/cord-001213-gxqufddb.txt txt: ./txt/cord-001213-gxqufddb.txt summary: Therefore, from the similarity index analysis, we observed that selection pressure from hosts and vectors have contributed to shaping the molecular evolution of CHIKV at the respectively, on the formation of the overall codon usage patterns of CHIKV (Figure 2 ). Although, the nucleotide composition correlation analysis showed that codon usage in CHIKV genomes is mainly caused by compositional constraints or mutational pressure, we were interested to determine the possible influence of other factors, such as natural selection. However, in case of CHIKV genomes, variations in nucleotide base compositions were noted (Table 1 ), indicating that other factors, such as natural selection, could also influence overall synonymous codon usage bias. The RSCU values for all the coding sequences of CHIKV genomes were calculated to determine the characteristics of synonymous codon usage without the confounding influence of amino acid composition and the size of coding sequence of different gene samples, following a previously described method [18] . abstract: Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942501/ doi: 10.1371/journal.pone.0090905 id: cord-323133-gdg50omp author: Buzatto, G. P. title: The pathogens profile in children with otitis media with effusion and adenoid hypertrophy date: 2017-02-23 words: 4243.0 sentences: 209.0 pages: flesch: 45.0 cache: ./cache/cord-323133-gdg50omp.txt txt: ./txt/cord-323133-gdg50omp.txt summary: OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Therefore, the present study was carried out to compare the detection of common respiratory viruses and bacteria in adenoids and middle ear fluid in children with OME and in controls. In our study, we used a sensitive method to detect nucleic acid of a comprehensive panel of respiratory viruses and bacteria to compare the microbial colonization of adenoid and its correspondence in the middle ear in both OME children and controls. Concluding, in children with OME and adenoid hypertrophy we observed higher detection rates of potentially pathogenic bacteria, but not respiratory viruses, by real-time PCR in middle ear samples, as compared to control patients without adenoid hypertrophy. abstract: OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Specific DNA or RNA of 9 respiratory viruses (rhinovirus, influenza virus, picornavirus, syncytial respiratory virus, metapneumovirus, coronavirus, enterovirus, adenovirus and bocavirus) and 5 bacteria (S. pneumoniae, H. influenzae, M. catarrhalis, P. aeruginosa and S. aureus) were extracted and quantified by real-time PCR. RESULTS: 37 OME and 14 cochlear implant children were included in the study. At the adenoid, virus and bacteria were similarly detected in both OME and control patients. At the middle ear washes, however, a higher prevalence of bacteria was observed in patients with OME (p = 0.01). S. pneumoniae (p = 0.01) and M. catarrhalis (p = 0.022) were the bacteria responsible for this difference. Although total virus detection was not statistically different from controls at the middle ear washes (p = 0.065), adenovirus was detected in higher proportions in adenoid samples of OME patients than controls (p = 0.019). CONCLUSIONS: Despite both OME and control patients presented similar rates of viruses and bacteria at the adenoid, children with OME presented higher prevalence of S. pneumonia, M. catarrhalis in middle ear and adenovirus in adenoids when compared to controls. These findings could suggest that these pathogens could contribute to the fluid persistence in the middle ear. url: https://doi.org/10.1371/journal.pone.0171049 doi: 10.1371/journal.pone.0171049 id: cord-001909-yy9xp5ms author: Buß, O. title: Statistical Evaluation of HTS Assays for Enzymatic Hydrolysis of β-Keto Esters date: 2016-01-05 words: 6998.0 sentences: 414.0 pages: flesch: 49.0 cache: ./cache/cord-001909-yy9xp5ms.txt txt: ./txt/cord-001909-yy9xp5ms.txt summary: Two of the tested high throughput screening (HTS) assays depend on coupled enzymatic reactions which detect the alcohol released during ester hydrolysis by luminescence or absorption. The objective of this study is to select an HTS assay to screen for one enzyme for a two-step reaction cascade for the synthesis of β-amino acids. One assay relies on the change of the pH-value, the second is based on enzymatic oxidation of the released ethanol to acetic acid and the third, which we expected to be most sensitive, is based on the oxidation of ethanol to ethanal and hydrogen peroxide which is then converted by horseradish peroxidase (HRP) in a luminescence reaction. According to the other assays a positive control for the evaluation test contained only 2.0 mM ethanol without ester and hydrolase (see also subsection statistical analysis). abstract: β-keto esters are used as precursors for the synthesis of β-amino acids, which are building blocks for some classes of pharmaceuticals. Here we describe the comparison of screening procedures for hydrolases to be used for the hydrolysis of β-keto esters, the first step in the preparation of β-amino acids. Two of the tested high throughput screening (HTS) assays depend on coupled enzymatic reactions which detect the alcohol released during ester hydrolysis by luminescence or absorption. The third assay detects the pH shift due to acid formation using an indicator dye. To choose the most efficient approach for screening, we assessed these assays with different statistical methods—namely, the classical Z’-factor, standardized mean difference (SSMD), the Kolmogorov-Smirnov-test, and t-statistics. This revealed that all three assays are suitable for HTS, the pH assay performing best. Based on our data we discuss the explanatory power of different statistical measures. Finally, we successfully employed the pH assay to identify a very fast hydrolase in an enzyme-substrate screening. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711668/ doi: 10.1371/journal.pone.0146104 id: cord-000981-6vloa2w3 author: Bálint, Zoltán title: Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells date: 2013-06-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca(2+)) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca(2+) signaling in hPAECs by inhibiting the sarco-endoplasmic Ca(2+)-ATPase (SERCA) which is involved in the regulation of the intracellular Ca(2+) homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670875/ doi: 10.1371/journal.pone.0063776 id: cord-270681-6ayciihs author: Bálint, Ádám title: Comparative In Vivo Analysis of Recombinant Type II Feline Coronaviruses with Truncated and Completed ORF3 Region date: 2014-02-20 words: 4679.0 sentences: 230.0 pages: flesch: 49.0 cache: ./cache/cord-270681-6ayciihs.txt txt: ./txt/cord-270681-6ayciihs.txt summary: Our previous in vitro comparative study on a feline coronavirus (FCoV) pair, differing only in the intactness of their ORF3abc regions, showed that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II feline infectious peritonitis virus (FIPV). In the present study using the parent FIPV DF-2 strain and its recombinant derivates we aimed to collect in vivo data how the completed ORF3abc alters virulence, virus shedding, viremia, viral load of organs and humoral immune response against type II FCoV. Shedding of FIPV DF-2 and PBFIPV-DF-2 was detected from day 3 p.i. to euthanasia of the PIP diseased animals at very low and variable amounts of an average value close to the detection limit of the genomic qRT-PCR (1.9610 1 FCoV RNA copies per ml fecal extract) ( Fig. 1) with undetectable virus replication using the subgenomic qRT-PCR assay (data not shown). abstract: Our previous in vitro comparative study on a feline coronavirus (FCoV) pair, differing only in the intactness of their ORF3abc regions, showed that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II feline infectious peritonitis virus (FIPV). In the present study, we describe a challenge experiment with the same recombinant FCoVs in order to gain data on the in vivo characteristics on these viruses. While parent virus FIPV DF-2 developed feline infectious peritonitis in all the infected cats, its recombinant virus PBFIPV-DF-2, differing only in seven nucleotides, proved to be surprisingly low virulent, although caused an acute febrile episode similarly to the original FIPV DF-2. PBFIPV-DF-2 infection induced significantly lower virus neutralization titers than its parent virus, and lacked the second phase of viremia and development of fatal course of the disease. The recombinant PBFIPV-DF-2-R3i with completed ORF3abc gained biological properties that differentiate between the feline enteric coronavirus (FECV) and FIPV biotypes such as intensive replication in the gut, absence of viremia and weak or no serological response. Using reverse genetic approaches our study is the first experimental proof that ORF3abc is indeed responsible for the restriction of FECV replication to the intestine in vivo. url: https://doi.org/10.1371/journal.pone.0088758 doi: 10.1371/journal.pone.0088758 id: cord-353596-8iqjugcx author: Bédubourg, Gabriel title: Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study date: 2017-07-17 words: 5603.0 sentences: 313.0 pages: flesch: 53.0 cache: ./cache/cord-353596-8iqjugcx.txt txt: ./txt/cord-353596-8iqjugcx.txt summary: Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The objective of this paper is to evaluate the performance of 21 statistical methods applied to large simulated datasets for outbreak detection in weekly health surveillance. Table 2 presents averaged FPR, specificity, POD, POD1week, sensitivity, negative predictive value, positive predictive value and F 1 -measure for all 42 scenarios and all past and current outbreak amplitude and duration and for α = 0.01. abstract: The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances. url: https://www.ncbi.nlm.nih.gov/pubmed/28715489/ doi: 10.1371/journal.pone.0181227 id: cord-305547-e66o5j85 author: Bénet, Thomas title: Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study date: 2015-12-22 words: 4161.0 sentences: 227.0 pages: flesch: 43.0 cache: ./cache/cord-305547-e66o5j85.txt txt: ./txt/cord-305547-e66o5j85.txt summary: title: Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. The primary objective of this prospective case-control study was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children in Mali. pneumoniae, human metapneumovirus, RSV, and influenza A were the main microbial agents associated with pneumonia among children in Mali, independently of patient age, gender, period, and other pathogens. recently observed, in a pneumonia cases-control study implemented in hospitals of Utah, that detection respiratory syncytial virus, human metapneumovirus and influenza from nasopharyngeal or oropharyngeal sample of patients with pneumonia probably indicates an etiologic role [24] . abstract: BACKGROUND: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. METHODS: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. RESULTS: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). CONCLUSIONS: In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries. url: https://doi.org/10.1371/journal.pone.0145447 doi: 10.1371/journal.pone.0145447 id: cord-290539-8ak2tths author: Cagno, Valeria title: Novel broad spectrum virucidal molecules against enveloped viruses date: 2018-12-07 words: 5524.0 sentences: 276.0 pages: flesch: 51.0 cache: ./cache/cord-290539-8ak2tths.txt txt: ./txt/cord-290539-8ak2tths.txt summary: To further elucidate the mechanism of action we performed a virucidal assay in which 9d was incubated with the virus at 10 μM 5μM or 1μM concentration for different times (Fig 6A) or for 1h with serial dilutions of compound ( Fig 6B) ; subsequently, the mixture was titrated on cells and the viral titer was evaluated at dilutions at which the compound concentration was known not to be active in plaquing efficiency assays. The irreversibility of the mechanism was also tested with an assay in which the compound was incubated with the virus for 1h and subsequently the mixture has been diluted in drug free medium for additional 1, 2, 3 or 4 hours before the addition on cells (S2 Fig) . abstract: Viral infections are an important cause of death worldwide. Unfortunately, there is still a lack of antiviral drugs or vaccines for a large number of viruses, and this represents a remarkable challenge particularly for emerging and re-emerging viruses. For this reason, the identification of broad spectrum antiviral compounds provides a valuable opportunity for developing efficient antiviral therapies. Here we report on a class of rhodanine and thiobarbituric derivatives displaying a broad spectrum antiviral activity against seven different enveloped viruses including an HSV-2 acyclovir resistant strain with favorable selectivity indexes. Due to their selective action on enveloped viruses and to their lipid oxidation ability, we hypothesize a mechanism on the viral envelope that affects the fluidity of the lipid bilayer, thus compromising the efficiency of virus-cell fusion and preventing viral entry. url: https://doi.org/10.1371/journal.pone.0208333 doi: 10.1371/journal.pone.0208333 id: cord-003548-zuwt7gk5 author: Cai, Haiming title: Modulating the 3’ end-DNA and the fermentation process for enhanced production and biological activity of porcine interferon-gamma date: 2019-03-26 words: 6848.0 sentences: 447.0 pages: flesch: 56.0 cache: ./cache/cord-003548-zuwt7gk5.txt txt: ./txt/cord-003548-zuwt7gk5.txt summary: In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3'' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3'' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry. The expression of pIFN-γ protein was maximal when the concentration of DO in the substrate was 30%, especially for the recombinant Pichia pastoris with the optimized pIFN-γ gene and the 3'' signaling peptide mutation, which had significantly higher expression than that of the other treatment groups (p<0.05). abstract: Porcine gamma interferon is a cytokine produced by activated T cells and NK cells with broad-spectrum antiviral activity and immunomodulatory function. However, pIFN-γ is a secretory protein that has a short half-life in organisms and is easily inactivated, making it difficult to apply widely in clinics. Therefore, we tried to optimize the expression of pIFN-γ in Pichia pastoris to obtain a large amount of highly active, easily purified pIFN-γ protein in vitro. Through C-terminal sequence analysis, we found a signal sequence (EKREAEAE) that was easily enzymolysed by a signal peptide enzyme, resulting in degradation and inactivation of the pIFN-γ protein. In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. Our data also showed that the fermentation process could significantly improve productivity. A recombinant Pichia pastoris strain with the optimized pIFN-γ gene could obtain a high yield of pIFN-γ protein, up to 9536 mg/L, after staged incubation for 0–24 h at 28°C, pH 6.0, and 50% dissolved oxygen (DO), followed by incubation for 24–72 h at 25°C, pH 6.0 and 30% DO. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435167/ doi: 10.1371/journal.pone.0214319 id: cord-048339-nzh87aux author: Caley, Peter title: The Waiting Time for Inter-Country Spread of Pandemic Influenza date: 2007-01-03 words: 5739.0 sentences: 253.0 pages: flesch: 45.0 cache: ./cache/cord-048339-nzh87aux.txt txt: ./txt/cord-048339-nzh87aux.txt summary: On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. In this paper we demonstrate how the delay to importation of an epidemic of pandemic strain influenza may be quantified in terms of the growing infection incidence in the source region, traveler volumes, border screening measures, travel duration, inflight transmission and the delay until an infected arrival initiates a chain of transmission that gathers momentum. For example, if R = 1.5, and we reduce the number of intending travelers from 400 to 10 per day, implement 100% flight-based quarantining, implement compulsory mask wearing during travel and presentation at 6 hours following symptom onset then there is a substantial probability (0.74) that the pandemic strain will never be imported (assuming the epidemic is confined to the source country). abstract: BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764036/ doi: 10.1371/journal.pone.0000143 id: cord-305071-4ck8nd24 author: Calvo, Cristina title: Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses date: 2015-07-06 words: 3527.0 sentences: 205.0 pages: flesch: 49.0 cache: ./cache/cord-305071-4ck8nd24.txt txt: ./txt/cord-305071-4ck8nd24.txt summary: Human adenovirus (HAdV), a double-stranded DNA virus, causes a wide range of clinical syndromes and is a well-recognized agent of upper and lower respiratory infections in children [1, 2] . Although the literature on adenoviral infections in children is increasing, there are few prospective, long term studies, designed specifically to evaluate the role of HAdV in acute respiratory infections requiring hospitalization. Patients with influenza have fever more frequently (p = 0.028) and have a lower leukocytes count in blood (p<0.001), than children infected by HAdV. HAdV frequently (11% of cases) caused lengthy hospitalizations (more than 7 days) 21% of the single infections were diagnosed with pneumonia. Jin et al [13] , in China, describe similar findings, that children with RSV are younger than patients with HAdV, and have lower respiratory tract infections such as bronchiolitis and bronchitis more frequently. abstract: Human adenovirus (HAdV) cause upper and lower respiratory tract infections. However, there are few large prospective studies focused on HAdVs acute infections requiring hospitalization. From 2005 to 2013 a prospective study was conducted on children admitted with acute respiratory infections. Specimens of nasopharyngeal aspirate were taken for virological study by PCR and clinical data was recorded. HAdV specimens were genotyped. Frequency and clinical course of HAdV infections were compared with RSV, rhinovirus (RV), human bocavirus (HBoV) and influenza in the same population. HAdV was detected in 403 cases of 2371 confirmed viral infections (17.2%) , of which 154 were single virus infections (38%). We genotyped 154 HAdVs. The most frequent genotypes were HAdV-3 (24%), HAdV-6 (21%), and HAdV-5 (20%). A total of 262 children had fever (64.9%); 194 suffered hypoxia (48%), and 147 presented infiltrate in chest x-rays (36.4%). The most frequent diagnoses were recurrent wheezing or asthma (51.7%), bronchiolitis (18.3 %), and pneumonia (11.9%), and 46 (11.4%) episodes required prolonged hospitalization (>7 days) due to the severity. Adenovirus single infections were compared with single infections of 598 RSV, 494 RV, 83 influenza and 78 HBoV. Significant clinical differences were found between HAdV, RSV and RV infections. url: https://doi.org/10.1371/journal.pone.0132162 doi: 10.1371/journal.pone.0132162 id: cord-292237-45hi4iz2 author: Calvo-Pinilla, Eva title: Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the Alpha/Beta Interferon Receptor date: 2009-04-09 words: 4735.0 sentences: 251.0 pages: flesch: 53.0 cache: ./cache/cord-292237-45hi4iz2.txt txt: ./txt/cord-292237-45hi4iz2.txt summary: Furthermore, IFNAR((−/−)) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. All these data, and the presence of an otherwise intact immune system in these mice [20, 22] suggest that IFNAR (2/2) mice could be a good animal model to study BTV infections and to evaluate vaccine strategies against this virus. By contrast, IFNAR (2/2) mice were susceptible to BTV-4 infection (Fig. 1A) , showing disease symptoms characterized by ocular discharges and apathy starting at 48 h.p.i. Disease progression led to animal death within 60 h.p.i. The LD 50 value was obtained by i.v. inoculation with 10-fold dilutions of BTV-4, resulting in a LD 50 value of 10 2.6 PFU (Fig. 1B) . Infectious viral titers were analyzed in the blood of immunized and nonimmunized IFNAR (2/2) mice by plaque assay after intravenous infection with BTV-4 (Fig. 5C ). abstract: Bluetongue (BT) is a noncontagious, insect-transmitted disease of ruminants caused by the bluetongue virus (BTV). A laboratory animal model would greatly facilitate the studies of pathogenesis, immune response and vaccination against BTV. Herein, we show that adult mice deficient in type I IFN receptor (IFNAR((−/−))) are highly susceptible to BTV-4 and BTV-8 infection when the virus is administered intravenously. Disease was characterized by ocular discharges and apathy, starting at 48 hours post-infection and quickly leading to animal death within 60 hours of inoculation. Infectious virus was recovered from the spleen, lung, thymus, and lymph nodes indicating a systemic infection. In addition, a lymphoid depletion in spleen, and severe pneumonia were observed in the infected mice. Furthermore, IFNAR((−/−)) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. The data indicate that this mouse model may facilitate the study of BTV pathogenesis, and the development of new effective vaccines for BTV. url: https://doi.org/10.1371/journal.pone.0005171 doi: 10.1371/journal.pone.0005171 id: cord-000352-qzkpik3z author: Carvalho, Gabrielle title: Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation date: 2011-03-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation. Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown. Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation. METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells. siRNA-based knockdown of PALS1 hampered TCR-induced activation and optimal proliferation of lymphocyte. We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB. CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068181/ doi: 10.1371/journal.pone.0018159 id: cord-340703-vtuy806l author: Cascio, Antonio title: Low bone mineral density in HIV-positive young Italians and migrants date: 2020-09-03 words: 4488.0 sentences: 230.0 pages: flesch: 55.0 cache: ./cache/cord-340703-vtuy806l.txt txt: ./txt/cord-340703-vtuy806l.txt summary: We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Our study aims to emphasize the burden of bone health in naïve ARV HIV positive patients and compare the bone density of the native Italian population group (ItG) with that of HIV Migrants (MiG) upon arrival in Italy. Finally, in Table 3 , we report the logistic regression analysis between Low BMD variable (dichotomous) and the independent variables: Gender (dichotomous), BMI (continuous), Hydroxy-Vitamin D (continuous), CD4 (continuous), and Previous Fractures (dichotomous) for the total sample, ItG, and MiG. Our previous reports [13, 14] on the prevalence of Low-BMD in HIV mono-infected patients who underwent ARV therapy showed higher percentage rates of osteopenia (44.9%) and osteoporosis (20.9%) than an agerelated healthy Italian population (18%) [16] . abstract: BACKGROUND: Human immunodeficiency virus (HIV) infected individuals may have osteoporosis. We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. METHODS: We conducted a cross-sectional study on 83 HIV patients less than 50 years old. We used the dual-energy X-ray absorptiometry (DXA) within six months from the HIV diagnosis. Participants were categorized as having low BMD if the femoral neck or total lumbar spine Z-score was– 2 or less. RESULTS: MiG showed low BMD more often than ItG (37.5% vs.13.6%), especially for the female gender (16.7% vs. 0.0%). A low CD4 rate (<200 cells/μl) was most often detected in MiG than ItG. In particular, we found most often male Italians with abnormal CD4 than male migrants (67.8% vs. 33.3%) and vice versa for females (30.5% vs. 66.7%). We found an abnormal bone mineral density at the lumbar site. Low BMD at the lumbar site was more frequently observed in female migrants than female Italians. Both male and female migrants had a Z-score value significantly lower than male and female Italians, respectively. By logistic regression low vitamin-D level was positively correlated to low BMD in ItG only. All data were verified and validated using a triple code identifier. CONCLUSIONS: Both DXA and vitamin-D evaluation should be offered after the diagnosis of HIV infection. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Vitamin D levels and supplementation may be considered after HIV diagnosis independently of age to improve bone health. HIGHLIGHTS: This study evaluates the frequency of bone mineral density in HIV positive patients naive to antiretroviral therapy. It compares the density of the native Italian population with that of HIV Migrants upon arrival in Italy. The results show that HIV positive migrants, even if younger than 50 years of age, are at risk for osteoporosis, especially if they are female. url: https://doi.org/10.1371/journal.pone.0237984 doi: 10.1371/journal.pone.0237984 id: cord-048358-z5klydpi author: Catic, André title: Screen for ISG15-crossreactive Deubiquitinases date: 2007-07-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. RESULTS: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. CONCLUSIONS: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1919423/ doi: 10.1371/journal.pone.0000679 id: cord-281364-syg0wo77 author: Caì, Yíngyún title: CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection date: 2014-11-19 words: 3827.0 sentences: 178.0 pages: flesch: 49.0 cache: ./cache/cord-281364-syg0wo77.txt txt: ./txt/cord-281364-syg0wo77.txt summary: title: CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Finally, we demonstrate that persistent MERS-CoV infections can be established in permissive bat cell lines after sequential virus passage, leading to downregulation of natural CD26/DPP4 cellsurface expression. None of the four MERS-CoV-resistant cell lines tested in this study (PESU-B5L, R05T, R06E, and Tb1Lu) were recognized by anti-human CD26/DPP4 antibody in this assay, whereas all susceptible bat cells (EidNi/41.3, EpoNi/22.1, HypLu/45.1, HypNi/1.1, RoNi/7.1, and RoNi/7.2) tested positive for CD26/DPP4 expression (Figure 2 ). Our study confirms the role of CD26/DPP4 as receptor for two divergent MERS-CoV isolates and correlates its presence or absence on the surface of bat cells directly with bat cell susceptibility or resistance to productive MERS-CoV infection (Figures 2 and 3 ). abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors. url: https://www.ncbi.nlm.nih.gov/pubmed/25409519/ doi: 10.1371/journal.pone.0112060 id: cord-339869-euikj8fv author: Cebey-López, Miriam title: Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children? date: 2016-04-20 words: 3325.0 sentences: 201.0 pages: flesch: 40.0 cache: ./cache/cord-339869-euikj8fv.txt txt: ./txt/cord-339869-euikj8fv.txt summary: However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory Introduction Molecular techniques including polymerase chain reaction (PCR) have increased the sensitivity of detection for common and emerging respiratory viruses, and often reveal the presence of more than one pathogen in respiratory patients. Our study aims to analyze the relationship between viral or bacterial co-infection detected by molecular methods, and the clinical phenotype of children admitted to hospital with lower tract acute respiratory infections (LT-ARI). PICU admission, disease severity according to different scales, need for respiratory support, and length of hospital stay followed a similar pattern in viral mono-versus co-infected children. abstract: BACKGROUND: Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES: To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). METHODS: We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. RESULTS: 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. CONCLUSION: The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. url: https://www.ncbi.nlm.nih.gov/pubmed/27096199/ doi: 10.1371/journal.pone.0152481 id: cord-306135-pt4jsr6d author: Chan, Kamfai title: A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics date: 2016-02-12 words: 6292.0 sentences: 284.0 pages: flesch: 56.0 cache: ./cache/cord-306135-pt4jsr6d.txt txt: ./txt/cord-306135-pt4jsr6d.txt summary: Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. This thermos thermal cycler (TTC) uses a very simple design that performs PCR amplification based on the "archaic" method of hand-transferring reaction tubes through a series of water baths, minimizing the temperature ramping time needed for PCR tubes to reach thermal equilibrium (Fig 1) . The TTC RT-PCR was performed using protocols similar to the HIV test, with PCR tubes transferred between three thermoses (reverse transcription, denaturation, and annealing/extension) and an optional room-temperature water bath. The gel photo in Fig 3 shows that the TTC can produce multiplexed amplicons with the correct sizes and that the yield is similar to a three-step reaction performed in the commercial cycler with same number of PCR cycles. abstract: The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC’s ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC’s performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings. url: https://doi.org/10.1371/journal.pone.0149150 doi: 10.1371/journal.pone.0149150 id: cord-310438-744r7gc3 author: Chan, Ta-Chien title: The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly date: 2010-06-25 words: 5083.0 sentences: 226.0 pages: flesch: 40.0 cache: ./cache/cord-310438-744r7gc3.txt txt: ./txt/cord-310438-744r7gc3.txt summary: This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan''s influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. The aims of this study were: (1) to evaluate the effectiveness of matching or mismatching influenza vaccine strains on influenzaassociated mortality, (2) to assess whether public health improvements during the post-SARS period might have decreased elderly mortality, and (3) to investigate molecular variation among vaccine-mismatched influenza viruses that may be associated with increased excess influenza-associated mortality. Explanatory variables for the above three outcome measures include monthly meteorological parameters (monthly means of temperature and humidity), annual periodic cycle (i.e., sine/cosine function of seasonal periodicity), monthly virus isolation rates for different subtypes/types of influenza viruses [A (H3N2) or A (H1N1) or B], matching status of different vaccine strains for each subtype/type in each of the studied years, post-SARS effect, and linear temporal monthly trends. abstract: Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness. url: https://www.ncbi.nlm.nih.gov/pubmed/20592764/ doi: 10.1371/journal.pone.0011317 id: cord-000726-tonaaft2 author: Chang, Binggong title: Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems date: 2012-07-27 words: 4986.0 sentences: 239.0 pages: flesch: 50.0 cache: ./cache/cord-000726-tonaaft2.txt txt: ./txt/cord-000726-tonaaft2.txt summary: Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy). We compared the effect of individual PrP-specific monoclonal antibodies (Mabs) on the PrP C -PrP Sc conversion process using both an N2a/22L cell culture model and the test-tube PMCA system. To more completely explore the possible therapeutic effect of anti-PrP antibodies, and to establish another system to analyze the influence of Abs on the conversion process, we screened Mabs produced in our laboratory for their capacity to inhibit PrP Sc formation. abstract: PrP(Sc) is believed to serve as a template for the conversion of PrP(C) to the abnormal isoform. This process requires contact between the two proteins and implies that there may be critical contact sites that are important for conversion. We hypothesized that antibodies binding to either PrP(c)or PrP(Sc) would hinder or prevent the formation of the PrP(C)–PrP(Sc) complex and thus slow down or prevent the conversion process. Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). The two systems yielded similar results, in most cases, and demonstrate that PrP-specific monoclonal antibodies (Mabs) vary in their ability to inhibit the PrP(C)–PrP(Sc) conversion process. Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407222/ doi: 10.1371/journal.pone.0041626 id: cord-342639-vf9n2vf9 author: Chang, Chung-ke title: Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date: 2013-05-23 words: 5386.0 sentences: 243.0 pages: flesch: 42.0 cache: ./cache/cord-342639-vf9n2vf9.txt txt: ./txt/cord-342639-vf9n2vf9.txt summary: For disulfide trapping experiments, we chose mutation sites that would form disulfide linkages based on the crystal packing structures of the SARS-CoV N protein CTD ( Figure 1 ) [9] . Within the crystal asymmetric unit, the SARS-CoV N protein CTD packs as an octamer which stacks to form a helical arrangement with a continuous positively charged surface that could potentially allow the RNA to bind to it through electrostatic interactions ( Fig. 1 ) [9] . By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that SARS-CoV N protein is capable of transient oligomerization in solution through the CTD in the absence of nucleic acids. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA abstract: The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization. url: https://www.ncbi.nlm.nih.gov/pubmed/23717688/ doi: 10.1371/journal.pone.0065045 id: cord-000765-r7y1cqou author: Chang, Yu-Ming title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date: 2012-09-21 words: 5770.0 sentences: 317.0 pages: flesch: 54.0 cache: ./cache/cord-000765-r7y1cqou.txt txt: ./txt/cord-000765-r7y1cqou.txt summary: title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. IcaR DNA1 probe duplex of 1 mM was pre-incubated with 2 mM TcaR (dimer) at room temperature for 15 min before mixing with increasing concentration of GC33 ssDNA, followed by the same procedure as described in the legend to Figure 1B . In the EMSA analysis, 1 mM IcaR DNA1 probe duplex was pre-incubated with 1 mM GC33 ssDNA fragment for 15 min at room temperature before mixing with TcaR protein of increasing concentration. abstract: The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG). Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448645/ doi: 10.1371/journal.pone.0045665 id: cord-320938-f526k9q1 author: Chen, Hongjun title: Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses date: 2012-09-28 words: 8614.0 sentences: 455.0 pages: flesch: 60.0 cache: ./cache/cord-320938-f526k9q1.txt txt: ./txt/cord-320938-f526k9q1.txt summary: In order to determine whether a Flu PCR amplicon could be transfected into cells and be amplified by the influenza polymerase complex, a PCR product was produced encoding the GFP reporter gene in negative orientation flanked by the influenza segment 7 untranslated regions (UTRs) and further flanked by the human pol1 promoter and the mouse t1 termination signal, pol1EGFPt1 (Fig. 1A, Fig. S1A , Table S1 ). doi:10.1371/journal.pone.0046378.g001 Efficient influenza virus rescue using Flu PCR amplicons in either ''''1+7'''' or ''''2+6'''' modes The pol1HA pdm t1 or pol1HA D072 t1 HA PCR amplicons (Table 1) were co-transfected into co-cultured 293T/MDCK cells in a ''''1+7'''' mode along with 7 RG plasmids encoding the corresponding additional gene segments from the influenza A/Puerto Rico/ 8/1934 (H1N1) strain (PR8). abstract: Since 1999, plasmid-based reverse genetics (RG) systems have revolutionized the way influenza viruses are studied. However, it is not unusual to encounter cloning difficulties for one or more influenza genes while attempting to recover virus de novo. To overcome some of these shortcomings we sought to develop partial or full plasmid-free RG systems. The influenza gene of choice is assembled into a RG competent unit by virtue of overlapping PCR reactions containing a cDNA copy of the viral gene segment under the control of RNA polymerase I promoter (pol1) and termination (t1) signals – herein referred to as Flu PCR amplicons. Transfection of tissue culture cells with either HA or NA Flu PCR amplicons and 7 plasmids encoding the remaining influenza RG units, resulted in efficient virus rescue. Likewise, transfections including both HA and NA Flu PCR amplicons and 6 RG plasmids also resulted in efficient virus rescue. In addition, influenza viruses were recovered from a full set of Flu PCR amplicons without the use of plasmids. url: https://doi.org/10.1371/journal.pone.0046378 doi: 10.1371/journal.pone.0046378 id: cord-258243-2utl2mfl author: Chen, Jeng-Wen title: Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study date: 2018-05-29 words: 4350.0 sentences: 230.0 pages: flesch: 44.0 cache: ./cache/cord-258243-2utl2mfl.txt txt: ./txt/cord-258243-2utl2mfl.txt summary: We investigated the distribution of the three major categories of surgical indication according to sex, age group (<5 years, 5-11 years, 11-17 years, 18-40 years, and >40 years), hospital level (medical centers, regional hospitals, and local hospitals), and insured residence areas according to the NHI divisions (Taipei, Northern, Central, Southern, Kaoping, and Eastern). In the adult subgroup (Figs 2B and 3B) , the incidence and proportion of AT performed for RICI decreased from 46 (78%) in 1997 to 32 Table 3 indicates the number and percentage of the three categories of surgical indications according to sex, age groups, hospital level, and insured residence areas in the total study population. The trend in the AT rate and the proportion of surgical indications by the calendar year according to sex, age groups, hospital level, and insured residence areas in the total study population are shown in the supplemental data (S1 File). abstract: OBJECTIVE: Adenotonsillectomy (AT) is one of the most common surgical procedures performed in children and adults. We aim to assess the factors associated with changes in the incidence of and indications for AT using population-level data. STUDY DESIGN: This retrospective cohort study investigated patients who underwent AT between 1997 and 2010 by using data from the Taiwan National Health Insurance Research Database. We examined surgical rates and indications by the calendar year as well as age, sex, hospital level, and insured residence areas for the correlating factors. RESULTS: The average annual incidence rate of AT was 14.7 per 100,000 individuals during 1997–2010. Pediatric (<18 years) patients represented 48.2% of the total AT population. More than 99% of the patients underwent the AT procedures as an inpatient intervention. Longitudinal data demonstrated an increasing trend in the pediatric AT rates from 1997 (4.3/100,000) to 2010 (5.7/100,000) (p = 0.029). In the adult subgroup, a decreasing prevalence of infectious indications (p = 0.014) coincided with an increasing neoplastic indications (p = 0.001). In the pediatric subgroup, the prevalence of obstructive indications increased (p = 0.002). The logistic regression analyses indicated that the significant factors associated with the changing surgical indications for AT were the age in the adult subgroup and hospital level in the pediatric subgroup. CONCLUSIONS: This study revealed a low AT rate in Taiwan than that in other countries. Pediatric AT incidence increased during 1997–2010. Although a rising prevalence of obstructive and neoplastic indications was noted, infection remained the most common indications for AT. Age in the adult subgroup and hospital level in the pediatric subgroup were factors associated with the changing indications for AT. url: https://doi.org/10.1371/journal.pone.0193317 doi: 10.1371/journal.pone.0193317 id: cord-283604-fqc9jp0l author: Chen, Meng title: Adenoviruses Associated with Acute Respiratory Diseases Reported in Beijing from 2011 to 2013 date: 2015-03-27 words: 3060.0 sentences: 127.0 pages: flesch: 39.0 cache: ./cache/cord-283604-fqc9jp0l.txt txt: ./txt/cord-283604-fqc9jp0l.txt summary: To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination. The comparison results of the penton base, hexon, and fiber gene sequences between the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and the strains from the GenBank database indicated significant conservation and stability of the sequences within the genome across time and space. abstract: BACKGROUND: Adenovirus is one of the most common causes of viral acute respiratory infections. To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011. PRINCIPAL FINDINGS: Through the surveillance project, 4617 cases of respiratory infections were identified during 2011-2013. Throat swabs (pharynx and tonsil secretions) were collected from all the patients, and 15 different respiratory viruses were screened by multiplex one-step PCR method. 45 were identified as adenovirus-positive from sporadic and outbreak cases of respiratory infection by a multiplex one-step RT-PCR method, and a total of 21 adenovirus isolates were obtained. Five HAdV types among three species, including HAdV-3 (species HAdV-B), HAdV-4 (species HAdV-E), HAdV-7 (species HAdV-B), HAdV-55 (species HAdV-B), and an undefined HAdV type (species HAdV-C) were identified. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination. CONCLUSIONS: This study confirmed that at least 5 HAdV types including HAdV-3, HAdV-4, HAdV-7, HAdV-55 and an undefined HAdV type were co-circulating and were the causative agents of respiratory tract infections in recent years in Beijing. HAdV-3, HAdV-4, HAdV-7, and HAdV-55 showed the apparent stability of the genomes, while intraspecies recombination was identified in strain BJ04 and BJ09. The recombinants carrying penton base gene of HAdV-1 as well as hexon and fiber genes of HAdV-2 might be a novel type of HAdV worthy of further study. url: https://www.ncbi.nlm.nih.gov/pubmed/25816320/ doi: 10.1371/journal.pone.0121375 id: cord-001078-5m29nugu author: Chen, Xiaorong title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study date: 2013-09-17 words: 3930.0 sentences: 200.0 pages: flesch: 47.0 cache: ./cache/cord-001078-5m29nugu.txt txt: ./txt/cord-001078-5m29nugu.txt summary: title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection. Factors analyzed for possible correlation with clinical features and treatment outcomes in patients included 1) baseline characteristics of patients, such as age, sex, occupation, underlying conditions, exposure to poultry and/or wild birds in the past seven days, date of symptom onset and hospital admission, date of specimen collection, and date of positive diagnosis; 2) results from laboratory tests and imaging examinations; 3) treatment regimen including basic supporting therapy, antibiotic therapy, antiviral therapy, traditional Chinese medicine (TCM) therapy, and other therapies if applicable; and 4) current condition of patients including the length of stay in the hospital. abstract: OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection. METHODS: The clinical progress in 18 H7N9-infected patients was monitored and recorded. The clinical features of H7N9 infection were noted and factors associated with treatment outcomes were analyzed by univariate analyses. RESULTS: The average ages of patients in recovered and critical conditions were 67.0±10.83 years and 72.75±12.0 years, respectively. Renal insufficiency developed more frequently in critically ill patients (P = 0.023). The duration of traditional Chinese medicine (TCM) therapy was longer in recovered patients than in critically ill patients (P = 0.01). Laboratory tests showed that levels of C-reactive protein, serum creatinine, and myoglobin were significantly higher in critically ill patients than in recovered patients (P = 0.011, 0.04, and 0.016, respectively). Meanwhile, levels of all T cell subsets examined including total CD3(+), CD4(+), CD8(+), and CD45(+) T cells were lower in critically ill patients than in recovered patients (P = 0.033, 0.059, 0.015, and 0.039, respectively). Logistic regression analysis demonstrated that C-reactive protein level, myoglobin level and TCM therapy duration were likely associated with treatment outcomes of H7N9 infection (P = 0.032, 0.041 and 0.017, respectively). CONCLUSION: Elderly people may have increased risk for H7N9 virus infection. T cell-mediated responses play an important role in defense against the H7N9 virus. C-reactive protein level, myoglobin level and TCM duration may be associated with treatment outcomes of H7N9 infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775774/ doi: 10.1371/journal.pone.0073362 id: cord-001275-a9o2dvke author: Chen, Xue title: A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types date: 2014-05-06 words: 5558.0 sentences: 254.0 pages: flesch: 47.0 cache: ./cache/cord-001275-a9o2dvke.txt txt: ./txt/cord-001275-a9o2dvke.txt summary: title: A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. In this study, we showed for the first time that fusing HPV16 L2 aa 17-36 epitope repeats to a recombinant ligand for FccRs (designated L2R4, see Figure 1A -B) could significantly increase the immunogenicity of the L2 peptide and induce cross-neutralizing antibodies and protective immunity against a range of phylogenetically distant HPV types. abstract: Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%. Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization. Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits. Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011685/ doi: 10.1371/journal.pone.0095448 id: cord-302355-3se1wp8o author: Chen, Yi-Shiuan title: The conserved stem-loop II structure at the 3'' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA date: 2018-07-26 words: 6004.0 sentences: 292.0 pages: flesch: 53.0 cache: ./cache/cord-302355-3se1wp8o.txt txt: ./txt/cord-302355-3se1wp8o.txt summary: Although XRN1 digestion of a 3''-terminal 800-nt RNA could stall at a position to generate the sfRNA in vitro, we found that knocking out XRN1 had no effect on the accumulation of sfRNA in Japanese encephalitis virus (JEV) infected cells. Furthermore, the minus-strand templates covering the putative promoter region used for an in vitro RdRp assay gave rise to synthetic products, suggesting that the JEV sfRNA could be initially transcribed from the antigenome and may be further trimmed by XRN1 or other unidentified exoribonucleases. Although efficient RNA replication is required for the detection of any flaviviral RNAs despite which mechanism used for the sfRNA formation, our results were clearly different from the observations from WNV that BHK-21 cells transfected with replicon constructs containing various deletions had no effect on the accumulation of sfRNA when compared to the WT [8] . abstract: Flaviviruses accumulate abundant subgenomic RNA (sfRNA) in infected cells. It has been reported that sfRNA results from stalling of host 5’-to-3’ exoribonuclease XRN1 at the highly structured RNA of the 3’ untranslated region (UTR). Although XRN1 digestion of a 3’-terminal 800-nt RNA could stall at a position to generate the sfRNA in vitro, we found that knocking out XRN1 had no effect on the accumulation of sfRNA in Japanese encephalitis virus (JEV) infected cells. Mutagenesis studies revealed that the stemloop II (SLII) at the 3’ UTR is required for the accumulation of sfRNA. According to the results of an in vitro RNA-dependent RNA polymerase (RdRp) assay, the (-)10431-10566 RNA fragment, containing the putative promoter on the antigenome for the sfRNA transcription, binds to RdRp protein and exhibits a strong promoter activity. Taken together, our results indicate that the JEV sfRNA could be transcribed initially and then be trimmed by XRN1 or other unidentified exoribonucleases. url: https://doi.org/10.1371/journal.pone.0201250 doi: 10.1371/journal.pone.0201250 id: cord-282194-0sjmf1yn author: Cherak, Stephana J. title: Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review date: 2020-09-11 words: 5411.0 sentences: 276.0 pages: flesch: 42.0 cache: ./cache/cord-282194-0sjmf1yn.txt txt: ./txt/cord-282194-0sjmf1yn.txt summary: title: Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review The purpose of this scoping review was to summarize existing research on the impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit (ICU). For the purposes of this review, we defined: (1) a caregiver as any informal (i.e., non-clinical) person who regularly provides support to the patient and is in some way directly implicated in the patient''s care or directly affected by the patient''s health problem (e.g., family, friend); (2) social media as any form of electronic communication that allow users to share information and other content and create online communities; and (3) critically ill patients as any persons who are currently admitted to an intensive care unit (ICU) or had previously been admitted to an ICU. abstract: BACKGROUND: The use of social media in healthcare continues to evolve. The purpose of this scoping review was to summarize existing research on the impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit (ICU). METHODS: This review followed established scoping review methods, including an extensive a priori-defined search strategy implemented in the MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane CENTRAL Register of Controlled Trials databases to July 10, 2020. Primary research studies reporting on the use of social media by informal caregivers for critically ill patients were included. RESULTS: We identified 400 unique citations and thirty-one studies met the inclusion criteria. Nine were interventional trials–four randomized controlled trials (RCTs)–and a majority (n = 14) were conducted (i.e., data collected) between 2013 to 2015. Communication platforms (e.g., Text Messaging, Web Camera) were the most commonly used social media tool (n = 17), followed by social networking sites (e.g., Facebook, Instagram) (n = 6), and content communities (e.g., YouTube, SlideShare) (n = 5). Nine studies’ primary objective was caregiver satisfaction, followed by self-care (n = 6), and health literacy (n = 5). Nearly every study reported an outcome on usage feasibility (e.g., user attitudes, preferences, demographics) (n = 30), and twenty-three studies reported an outcome related to patient and caregiver satisfaction. Among the studies that assessed statistical significance (n = 18), 12 reported statistically significant positive effects of social media use. Overall, 16 of the 31 studies reported positive conclusions (e.g., increased knowledge, satisfaction, involvement) regarding the use of social media among informal caregivers for critically ill patients. CONCLUSIONS: Social media has potential benefits for caregivers of the critically ill. More robust and clinically relevant studies are required to identify effective social media strategies used among caregivers for the critically ill. url: https://www.ncbi.nlm.nih.gov/pubmed/32915848/ doi: 10.1371/journal.pone.0238803 id: cord-310790-3ikgmiof author: Cherrak, Sabri Ahmed title: Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies date: 2020-10-15 words: 3471.0 sentences: 226.0 pages: flesch: 50.0 cache: ./cache/cord-310790-3ikgmiof.txt txt: ./txt/cord-310790-3ikgmiof.txt summary: title: Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. The three compounds with highest affinity (Fig 2) for the active site are quercetin 3-rhamonoside, myricetin 3-rutinoside and rutin with binding energies of -9.7, -9,3 and -9.2 kcal.mol -1 respectively. Thirty eight flavonoids have been tested in this study by molecular docking against the active site of the SARS-CoV-2Mpro. Glycosylated flavonoids as SARS-CoV-2 Inhibitors: A molecular docking and simulation studies Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies abstract: A novel coronavirus responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, to test existing drugs as inhibitors of SARS-CoV-2 main protease is a good approach. Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules. The flavonoids chemical structures were downloaded from PubChem and protease structure 6LU7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. MD simulations were further performed to evaluate the dynamic behavior and stability of the protein in complex with the three best hits of docking experiments. Our results indicate that the rutin is a potential drug to inhibit the function of Chymotrypsin-like protease (3CL pro) of Coronavirus. url: https://www.ncbi.nlm.nih.gov/pubmed/33057452/ doi: 10.1371/journal.pone.0240653 id: cord-260653-5qwtvm9x author: Chikhlikar, Priya title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date: 2006-12-27 words: 6117.0 sentences: 278.0 pages: flesch: 49.0 cache: ./cache/cord-260653-5qwtvm9x.txt txt: ./txt/cord-260653-5qwtvm9x.txt summary: Thomas; Marques, Ernesto T.A. title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. This study demonstrates that Rhesus macaques immunized with a DNA plasmid vaccine-encoding gag as an hLAMP/gag chimera develops strong antigen-specific humoral responses as well as CD4 + and CD8 + T-cell responses. abstract: Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. ELISPOT analyses indicated that the average Gag-specific IFN-γ response elicited by the hLAMP/gag chimera was detectable after only two or three naked DNA immunizations in all five immunized macaques and reached an average of 1000 spot-forming cells (SFC)/10(6) PBMCs. High IFN-γ ELISPOT responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells play a major role in these responses. The T-cell responses of four of the macaques were also tested by use of ELISPOT to 12 overlapping 15-amino acids (aa) peptide pools containing ten peptides each, encompassing the complete Gag protein sequence. The two Mamu 08 immunized macaques responded to eight and twelve of the pools, the Mamu B01 to six, and the other macaque to five pools indicating that the hLAMP/gag DNA antigen formulation elicits a broad T-cell response against Gag. Additionally, there was a strong HIV-1-specific IgG response. The IgG antibody titers increased after each DNA injection, indicating a strong amnestic B-cell response, and were highly elevated in all the macaques after three immunizations. Moreover, the serum of each macaque recognized 13 of the 49 peptides of a 20-aa peptide library covering the complete Gag amino acid sequence. In addition, HIV-1-specific IgA antibodies were present in the plasma and external secretions, including nasal washes. These data support the findings of increased immunogenicity of genetic vaccines encoded as LAMP chimeras, including the response to DNA vaccines by non-human primates. url: https://www.ncbi.nlm.nih.gov/pubmed/17205139/ doi: 10.1371/journal.pone.0000135 id: cord-048353-hqc7u9w3 author: Chis Ster, Irina title: Transmission Parameters of the 2001 Foot and Mouth Epidemic in Great Britain date: 2007-06-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1876810/ doi: 10.1371/journal.pone.0000502 id: cord-305811-987dhnf7 author: Cho, Che-Pei title: Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins date: 2013-04-29 words: 5837.0 sentences: 301.0 pages: flesch: 49.0 cache: ./cache/cord-305811-987dhnf7.txt txt: ./txt/cord-305811-987dhnf7.txt summary: Because both 59CC-WT and 13363-13520 constructs share 27 identical nucleotides upstream of their slippery sites, the attenuation activity difference is not likely to be caused by an E-site flanking sequences effect [12, 13] but rather by the disruption of the two potential AU base pairs. We noticed a potential to form four extra base pairs between 59and 39-flanking sequences (GACG and CGUU, respectively) of the 6BPGC hairpin stem (and other deletion mutants) due to the existence of a 59 SalI cloning site (Fig. S1A ). The results (Fig. S1C ) indicate that the two potential base pairs involving E-site sequences are not the main cause of observed attenuation activity in 293T cell cultures. Furthermore, mutating two nucleotides (27 nucleotides upstream of the E site) to disrupt Watson-Crick base pairs in the lower hairpin stem dramatically impairs attenuation activity (Fig. 2) , indicating that attenuation is not caused by primary sequencemediated flanking-sequences effects [12, 13] . abstract: RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3′ direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) −1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate−1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for−1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing−1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study’s findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation. url: https://doi.org/10.1371/journal.pone.0062283 doi: 10.1371/journal.pone.0062283 id: cord-001280-skavefji author: Choi, Sang-Ho title: Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients date: 2014-05-13 words: 4136.0 sentences: 204.0 pages: flesch: 35.0 cache: ./cache/cord-001280-skavefji.txt txt: ./txt/cord-001280-skavefji.txt summary: This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. Exclusion criteria were as follows: (1) patients in whom the pathogen was not identified, (2) patients in whom BAL fluid analysis was impossible (due to severe neutropenia or clotting of specimen) or not performed, (3) patients with a mixed infection (identification of bacteria and virus), (4) patients who were treated with antimicrobial agents for more than 24 hours before bronchoscopic BAL, (5) patients with invasive pulmonary aspergillosis, (6) patients with mycobacterial infection, and (7) patients with Pneumocystis jirovecii pneumonia. Several authors of the current study previously investigated the diagnostic utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in BAL fluid of various patient populations with bilateral lung infiltrates. abstract: BACKGROUND: The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. METHODS: BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis. CONCLUSIONS: Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019586/ doi: 10.1371/journal.pone.0097346 id: cord-003244-abs3tc3r author: Chong, Ka Chun title: Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China date: 2018-10-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China. METHODS: We estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used. RESULTS: The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year. CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175510/ doi: 10.1371/journal.pone.0205339 id: cord-274268-0ucqp3uz author: Chorus, Caspar title: Diabolical dilemmas of COVID-19: An empirical study into Dutch society’s trade-offs between health impacts and other effects of the lockdown date: 2020-09-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We report and interpret preferences of a sample of the Dutch adult population for different strategies to end the so-called ‘intelligent lockdown’ which their government had put in place in response to the COVID-19 pandemic. Using a discrete choice experiment, we invited participants to make a series of choices between policy scenarios aimed at relaxing the lockdown, which were specified not in terms of their nature (e.g. whether or not to allow schools to re-open) but in terms of their effects along seven dimensions. These included health-related effects, but also impacts on the economy, education, and personal income. From the observed choices, we were able to infer the implicit trade-offs made by the Dutch between these policy effects. For example, we find that the average citizen, in order to avoid one fatality directly or indirectly related to COVID-19, is willing to accept a lasting lag in the educational performance of 18 children, or a lasting (>3 years) and substantial (>15%) reduction in net income of 77 households. We explore heterogeneity across individuals in terms of these trade-offs by means of latent class analysis. Our results suggest that most citizens are willing to trade-off health-related and other effects of the lockdown, implying a consequentialist ethical perspective. Somewhat surprisingly, we find that the elderly, known to be at relatively high risk of being affected by the virus, are relatively reluctant to sacrifice economic pain and educational disadvantages for the younger generation, to avoid fatalities. We also identify a so-called taboo trade-off aversion amongst a substantial share of our sample, being an aversion to accept morally problematic policies that simultaneously imply higher fatality numbers and lower taxes. We explain various ways in which our results can be of value to policy makers in the context of the COVID-19 and future pandemics. url: https://www.ncbi.nlm.nih.gov/pubmed/32936815/ doi: 10.1371/journal.pone.0238683 id: cord-003062-qm8kalyt author: Chowdhury, Fazle Rabbi title: The association between temperature, rainfall and humidity with common climate-sensitive infectious diseases in Bangladesh date: 2018-06-21 words: 4997.0 sentences: 274.0 pages: flesch: 50.0 cache: ./cache/cord-003062-qm8kalyt.txt txt: ./txt/cord-003062-qm8kalyt.txt summary: This observational study examined the association of temperature, humidity and rainfall with six common climate-sensitive infectious diseases in adults (malaria, diarrheal disease, enteric fever, encephalitis, pneumonia and bacterial meningitis) in northeastern Bangladesh. Unfortunately, very few studies on the relationship between various environmental variables and trends of infectious disease incidence have been performed so far in Bangladesh, although there are reports of some infections increasing sporadically in different regions of the country [17] [18] [19] . This study examined six infectious diseases based on clinical syndromes and laboratory support (malaria, enteric fever, encephalitis, diarrheal disease, pneumonia and meningitis) to offer a broader scope on the trend of these infectious diseases and their possible relation to climate change in Bangladesh. W.H.O reported dengue, viral encephalitis, diarrheal disease, enteric fever, pneumonia and meningitis as most sensitive to climate factors, and predicted a huge rise of cases in tropical countries [25] . abstract: Bangladesh is one of the world’s most vulnerable countries for climate change. This observational study examined the association of temperature, humidity and rainfall with six common climate-sensitive infectious diseases in adults (malaria, diarrheal disease, enteric fever, encephalitis, pneumonia and bacterial meningitis) in northeastern Bangladesh. Subjects admitted to the adult medicine ward of a tertiary referral hospital in Sylhet, Bangladesh from 2008 to 2012 with a diagnosis of one of the six chosen climate-sensitive infectious diseases were enrolled in the study. Climate-related data were collected from the Bangladesh Meteorological Institute. Disease incidence was then analyzed against mean temperature, humidity and average rainfall for the Sylhet region. Statistical significance was determined using Mann-Whitney test, Chi-square test and ANOVA testing. 5033 patients were enrolled (58% male, 42% female, ratio 1.3:1). All six diseases showed highly significant (p = 0.01) rises in incidence between the study years 2008 (540 cases) and 2012 (1330 cases), compared with no significant rise in overall all-cause hospital admissions in the same period (p = 0.19). The highest number of malaria (135), diarrhea (266) and pneumonia (371) cases occurred during the rainy season. On the other hand, the maximum number of enteric fever (408), encephalitis (183) and meningitis (151) cases occurred during autumn, which follows the rainy season. A positive (P = 0.01) correlation was observed between increased temperature and the incidence of malaria, enteric fever and diarrhea, and a negative correlation with encephalitis, meningitis and pneumonia. Higher humidity correlated (P = 0.01) with a higher number of cases of malaria and diarrhea, but inversely correlated with meningitis and encephalitis. Higher incidences of encephalitis and meningitis occurred while there was low rainfall. Incidences of diarrhea, malaria and enteric fever, increased with rainfall, and then gradually decreased. The findings support a relationship between weather patterns and disease incidence, and provide essential baseline data for future large prospective studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013221/ doi: 10.1371/journal.pone.0199579 id: cord-306958-8bx8kxxh author: Christensen, Sarah R. title: Political and personal reactions to COVID-19 during initial weeks of social distancing in the United States date: 2020-09-24 words: 4271.0 sentences: 223.0 pages: flesch: 45.0 cache: ./cache/cord-306958-8bx8kxxh.txt txt: ./txt/cord-306958-8bx8kxxh.txt summary: This study examines individual attitudes, behaviors, anxieties, mental health impacts, and knowledge early in the pandemic response, as well as those outcomes by sociodemographic characteristics and political ideology. Four items asked respondents to indicate agreement on a 7-point scale that "events related to COVID-19 had interrupted" their social life, home life, work or vocational life, and/or hurt their mental health. Chi-square, t, and F tests were used to examine the influence of demographic characteristics, political ideology, and mental health on attitudes, knowledge, anxieties, behavior change, and impact variables. Initial covariate selection included all variables that were significant (p <0.05) in bivariate tests, including: political ideology, bias score for consumed news media, attitudes toward global warming and vaccination, sex, race, poverty level, and education. In the adjusted logistic regression model ( Table 2 ) liberals had 5.7 (95%CI: 3.3-9.7) and moderates had 2.5 (95%CI 1.5-4.3) times the odds of responding that the government had not done enough in response to COVID-19 compared to conservatives. abstract: OBJECTIVE: To examine perceptions, behaviors, and impacts surrounding COVID-19 early in the pandemic response. MATERIALS AND METHODS: A cross-sectional survey of 1,030 U.S. adults was administered on March 31st, 2020. This survey examined attitudes toward media, government, and community responses to COVID-19 by political ideology and sociodemographic factors. Knowledge, anxieties, and impacts of COVID-19 were also assessed. RESULTS: Conservatives were more likely to report that COVID-19 was receiving too much media coverage and people were generally overreacting; liberals were more likely to report the government had not done enough in response to the pandemic. Females and those with lower income experienced more COVID-19 related economic anxieties. Those working and with children at home reported higher social, home, and work disruption. Social distancing behaviors were more common among liberals and were associated with increases in depressive symptoms. General knowledge about COVID-19 was widely exhibited across the sample, however, Black and Hispanic respondents were less likely to correctly answer questions about the availability of a vaccine and modes of transmission. CONCLUSIONS: Public health experts should consider the political climate in crafting messaging that appeals to the values of those across the political spectrum. Research on the COVID-19 pandemic should continue to monitor the effects of social distancing on mental health and among vulnerable populations. url: https://doi.org/10.1371/journal.pone.0239693 doi: 10.1371/journal.pone.0239693 id: cord-000786-ofpcgxce author: Chua, Brendon Y. title: Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses date: 2012-10-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam(2)Cys (E(8)Pam(2)Cys) to enhance the immunogenicity of VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a. While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an aluminium hydroxide-based adjuvant (Alum). Dramatically improved VLP and E2-specific antibody responses were observed in VLP+E(8)Pam(2)Cys vaccinated mice where up to 3 doses of non-adjuvanted or traditionally alum-adjuvanted VLPs was required to match the antibody titres obtained with a single dose of VLPs formulated with this lipopeptide. This result also correlated with significantly higher numbers of specific antibody secreting cells that was detected in the spleens of VLP+E(8)Pam(2)Cys vaccinated mice and greater ability of sera from these mice to neutralise the binding and uptake of VLPs by Huh7 cells. Moreover, vaccination of HLA-A2 transgenic mice with this formulation also induced better VLP-specific IFN-γ-mediated responses compared to non-adjuvanted VLPs but comparable levels to that achieved when coadministered with complete freund’s adjuvant. These results suggest overall that the immunogenicity of HCV VLPs can be significantly improved by the addition of this novel adjuvant by targeting their delivery to DCs and could therefore constitute a viable vaccine strategy for the treatment of HCV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472981/ doi: 10.1371/journal.pone.0047492 id: cord-286708-igu984oc author: Chua, Kaw Bing title: Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections date: 2008-11-25 words: 4359.0 sentences: 219.0 pages: flesch: 53.0 cache: ./cache/cord-286708-igu984oc.txt txt: ./txt/cord-286708-igu984oc.txt summary: Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Here, we report the discovery and characterization of Kampar virus (KamV), the fourth member in the NBV species group and its isolation from a human patient with fever and acute respiratory illness. Due to the similar CPE morphology ( Figure 1 ) and cell line susceptibility patterns between KamV and the recently discovered Melaka virus (MelV), which also causes acute respiratory diseases in humans [5] , immunofluorescent antibody testing was conducted to examine cross reactivity. abstract: First discovered in the early 1950s, reoviruses (respiratory enteric orphan viruses) were not associated with any known disease, and hence named orphan viruses. Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Serological studies indicated that Kampar virus was transmitted from the index case to at least one other individual and caused respiratory disease in the contact case. Sequence analysis of the four small class genome segments indicated that Kampar and Melaka viruses are closely related. This was confirmed by virus neutralization assay, showing an effective two-way cross neutralization, i.e., the serum against one virus was able to neutralize the other. Although the exact origin of Kampar virus is unknown, epidemiological tracing revealed that the house of the index case is surrounded by fruit trees frequently visited by fruit bats. There is a high probability that Kampar virus originated from bats and was transmitted to humans via bat droppings or contaminated fruits. The discovery of Kampar virus highlights the increasing trend of emergence of bat zoonotic viruses and the need to expand our understanding of bats as a source of many unknown viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/19030226/ doi: 10.1371/journal.pone.0003803 id: cord-003551-jzfl4xuk author: Ciejka, Justyna title: Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus date: 2019-03-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438514/ doi: 10.1371/journal.pone.0214646 id: cord-312367-24huwt3y author: Coelho, Camila title: Biochemical screening for SARS-CoV-2 main protease inhibitors date: 2020-10-06 words: 3351.0 sentences: 210.0 pages: flesch: 49.0 cache: ./cache/cord-312367-24huwt3y.txt txt: ./txt/cord-312367-24huwt3y.txt summary: As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 M(pro). As viral proteases, following polymerases, are the most prominent targets for antiviral drug design [9] , here we describe initial biochemical screenings with recombinant purified SARS-CoV-2 M pro performed in order to define possible candidates which could serve as lead compounds for the design of future COVID-19 therapies. In order to contribute to the ongoing worldwide research and development efforts to contain COVID-19, we cloned, expressed recombinantly in E.coli BL21(DE3) and purified an important drug target of SARS-CoV-2, its main protease (M pro ). From these obtained compounds, esculetin-4-carboxylic acid ethyl ester (IC 50 = 46 μM in M pro inhibition assays), a coumarin derivative and natural product, demonstrated an EC 50 of 112 μM (median toxic concentration TC 50 >800μM) in Vero-cell SARS-CoV assays [13] and MP576 (IC 50 = 2.5 μM), a quinolinecarboxylate, demonstrated an EC 50 of 7 μM (TC 50 >50μM) [15, 17] , thus validating the M pro biochemical screening approach for the development of SARS-CoV drugs. abstract: The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic represents a global challenge. SARS-CoV-2's ability to replicate in host cells relies on the action of its non-structural proteins, like its main protease (M(pro)). This cysteine protease acts by processing the viruses' precursor polyproteins. As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 M(pro). A fluorescent assay was used to identify inhibitors in a compound library containing known drugs, bioactive molecules and natural products. These screens led to the identification of 13 inhibitors with IC(50) values ranging from 0.2 μM to 23 μM. The screens confirmed several known SARS-CoV M(pro) inhibitors as inhibitors of SARS-CoV-2 M(pro), such as the organo-mercuric compounds thimerosal and phenylmercuric acetate. Benzophenone derivatives could also be identified among the most potent screening hits. Additionally, Evans blue, a sulfonic acid-containing dye, could be identified as an M(pro) inhibitor. The obtained compounds could be of interest as lead compounds for the development of future SARS-CoV-2 drugs. url: https://doi.org/10.1371/journal.pone.0240079 doi: 10.1371/journal.pone.0240079 id: cord-307540-dr5m9pfk author: Coelho, Flávio C. title: Assessing the spread of COVID-19 in Brazil: Mobility, morbidity and social vulnerability date: 2020-09-18 words: 3517.0 sentences: 201.0 pages: flesch: 52.0 cache: ./cache/cord-307540-dr5m9pfk.txt txt: ./txt/cord-307540-dr5m9pfk.txt summary: Probabilistic models were used to calculate the probability of COVID-19 spread from São Paulo and Rio de Janeiro, the initial hotspots, using mobility data from the pre-epidemic period, while multivariate cluster analysis of socio-economic indices was done to identify areas with similar social vulnerability. To identify regions with high geographical and social vulnerability, we proposed a classification scheme based on three main criteria: population mobility, socio-demographic-economic characteristics, and the available health care infrastructure in terms of hospital capacity. To assess the probability of COVID-19 spreading within Brazil, in the absence of mobility restrictions, we first calculated the effective distance (E f (i,j)) between micro-regions using the air travel data. We computed the effective distance, E f (i,j), between each micro-region and the two COVID-19''s hotspots, Rio de Janeiro and Sao Paulo. Mostly urban micro-regions, with above-average life expectancy, with comparatively less social inequality, less population living in extreme poverty, better access to water supply and sewage disposal services, higher education. abstract: Brazil detected community transmission of COVID-19 on March 13, 2020. In this study we identified which areas in the country were the most vulnerable for COVID-19, both in terms of the risk of arrival of cases, the risk of sustained transmission and their social vulnerability. Probabilistic models were used to calculate the probability of COVID-19 spread from São Paulo and Rio de Janeiro, the initial hotspots, using mobility data from the pre-epidemic period, while multivariate cluster analysis of socio-economic indices was done to identify areas with similar social vulnerability. The results consist of a series of maps of effective distance, outbreak probability, hospital capacity and social vulnerability. They show areas in the North and Northeast with high risk of COVID-19 outbreak that are also highly socially vulnerable. Later, these areas would be found the most severely affected. The maps produced were sent to health authorities to aid in their efforts to prioritize actions such as resource allocation to mitigate the effects of the pandemic. In the discussion, we address how predictions compared to the observed dynamics of the disease. url: https://doi.org/10.1371/journal.pone.0238214 doi: 10.1371/journal.pone.0238214 id: cord-001092-pkps5j8w author: Coleman, Ryan G. title: Ligand Pose and Orientational Sampling in Molecular Docking date: 2013-10-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys - Enhanced (DUD-E) benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20000 molecular orientations in the binding site (and so from about 1×10(10) to 4×10(10) to 1×10(11) to 2×10(11) to 5×10(11) mean atoms scored per target, since multiple conformations are sampled per orientation), the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787967/ doi: 10.1371/journal.pone.0075992 id: cord-289017-vwye3pk9 author: Comach, Guillermo title: Sentinel Surveillance of Influenza-Like Illness in Two Hospitals in Maracay, Venezuela: 2006–2010 date: 2012-09-11 words: 6262.0 sentences: 301.0 pages: flesch: 47.0 cache: ./cache/cord-289017-vwye3pk9.txt txt: ./txt/cord-289017-vwye3pk9.txt summary: CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Recent prospective studies, which utilized more sensitive methods for detecting respiratory viruses such as multiplex polymerase chain reaction (PCR), have similarly demonstrated that the highest rates of viral respiratory infection occur among children and the frequency of infection tends to decrease with age due to increasing acquired immunity [8] . On the other hand, the percentage of influenza viruses (not including pH1N1) detected in our study during a similar period of time, but in different years accounted for the significant differences found in both studies: a) the collection, preservation and further processing of respiratory samples, and b) the type of cells and IFA reagents used for virus isolation and identification. In contrast, a prospective study of ILI among Brazilian adults, which utilized viral isolation and RT-PCR testing on respiratory samples, detected rhinoviruses in 19.6% of patients [14] . abstract: BACKGROUND: Limited information exists on the epidemiology of acute febrile respiratory illnesses in tropical South American countries such as Venezuela. The objective of the present study was to examine the epidemiology of influenza-like illness (ILI) in two hospitals in Maracay, Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective surveillance study of persons with ILI who presented for care at two hospitals in Maracay, Venezuela, from October 2006 to December 2010. A respiratory specimen and clinical information were obtained from each participant. Viral isolation and identification with immunofluorescent antibodies and molecular methods were employed to detect respiratory viruses such as adenovirus, influenza A and B, parainfluenza, and respiratory sincytial virus, among others. There were 916 participants in the study (median age: 17 years; range: 1 month – 86 years). Viruses were identified in 143 (15.6%) subjects, and one participant was found to have a co-infection with more than one virus. Influenza viruses, including pandemic H1N1 2009, were the most frequently detected pathogens, accounting for 67.4% (97/144) of the viruses detected. Adenovirus (15/144), parainfluenza virus (13/144), and respiratory syncytial virus (11/144) were also important causes of ILI in this study. Pandemic H1N1 2009 virus became the most commonly isolated influenza virus during its initial appearance in 2009. Two waves of the pandemic were observed: the first which peaked in August 2009 and the second - higher than the preceding - that peaked in October 2009. In 2010, influenza A/H3N2 re-emerged as the most predominant respiratory virus detected. CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Pandemic H1N1 2009 influenza virus did not completely replace other circulating influenza viruses during its initial appearance in 2009. Seasonal influenza A/H3N2 was the most common influenza virus in the post-pandemic phase. url: https://www.ncbi.nlm.nih.gov/pubmed/22984519/ doi: 10.1371/journal.pone.0044511 id: cord-276372-q1fzxt3r author: Conde, Dalia A. title: Zoos through the Lens of the IUCN Red List: A Global Metapopulation Approach to Support Conservation Breeding Programs date: 2013-12-11 words: 4780.0 sentences: 225.0 pages: flesch: 48.0 cache: ./cache/cord-276372-q1fzxt3r.txt txt: ./txt/cord-276372-q1fzxt3r.txt summary: To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. To understand the complexity of maintaining CBPs of threatened species across the ISIS zoo network, we developed a second algorithm to find the optimal radial distance from any given zoo at which the probability of finding a metapopulation size of at least 50, 100 or 250 recruited living individuals was highest relative to that radial distance. As expected, the optimal distance radii and the number of zoos required to maximize the probability of reaching a given population increase with the metapopulation size threshold (.50, .100 and .250 individuals) ( Figure 3) . Therefore, for the zoo community, one of the main challenges of managing their threatened species in CBPs is the complexity of moving individuals across borders and the coordination of conservation efforts among zoos and other institutions at a global level. abstract: Given current extinction trends, the number of species requiring conservation breeding programs (CBPs) is likely to increase dramatically. To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. Our results show that 695 of the 3,955 (23%) terrestrial vertebrate species in ISIS zoos are threatened. Only two of the 59 taxonomic orders show a higher proportion of threatened species in ISIS zoos than would be expected if species were selected at random. In addition, for most taxa, the management of a zoo metapopulation of more than 250 individuals will require the coordination of a cluster of 11 to 24 ISIS zoos within a radius of 2,000 km. Thus, in the zoo network, the representation of species that may require CBPs is currently low and the spatial distribution of these zoo populations makes management difficult. Although the zoo community may have the will and the logistical potential to contribute to conservation actions, including CBPs, to do so will require greater collaboration between zoos and other institutions, alongside the development of international agreements that facilitate cross-border movement of zoo animals. To maximize the effectiveness of integrated conservation actions that include CBPs, it is fundamental that the non-zoo conservation community acknowledges and integrates the expertise and facilities of zoos where it can be helpful. url: https://doi.org/10.1371/journal.pone.0080311 doi: 10.1371/journal.pone.0080311 id: cord-349781-l93978vq author: Cong, Yu title: MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells date: 2018-03-22 words: 5653.0 sentences: 311.0 pages: flesch: 51.0 cache: ./cache/cord-349781-l93978vq.txt txt: ./txt/cord-349781-l93978vq.txt summary: Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. However, MERS-CoV continued to propagate in immature MDDCs up to 8 days pi, demonstrating differential infection and replication capabilities in MDMs and immature MDDCs. To compare the ability of MERS-CoV to induce innate immune responses in three types of APCs, the release of cytokines and chemokines was measured from virus-or mock-infected cells. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) presents an emerging threat to public health worldwide by causing severe respiratory disease in humans with high virulence and case fatality rate (about 35%) since 2012. Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. While chloroquine was not active in these primary cells, chlorpromazine showed strong anti-MERS-CoV activity, but it was associated with high cytotoxicity narrowing the potential window for drug utilization. Unlike in established cells, toremifene had marginal activity when tested in antigen presenting cells, with high apparent cytotoxicity, also limiting its potential as a therapeutic option. These results demonstrate the value of testing drugs in primary cells, in addition to established cell lines, before initiating preclinical or clinical studies for MERS treatment and the importance of carefully assessing cytotoxicity in drug screen assays. Furthermore, these studies also highlight the role of APCs in stimulating a robust protective immune response to MERS-CoV infection. url: https://doi.org/10.1371/journal.pone.0194868 doi: 10.1371/journal.pone.0194868 id: cord-000208-th0wddvc author: Cornelissen, Lisette A. H. M. title: A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 date: 2010-05-14 words: 5671.0 sentences: 290.0 pages: flesch: 49.0 cache: ./cache/cord-000208-th0wddvc.txt txt: ./txt/cord-000208-th0wddvc.txt summary: title: A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 Such HA trimers, expressed either in insect or mammalian cells, were indeed shown to elicit neutralizing antibodies [16] and to partially protect mice against HPAI H5N1 challenge infection [19] . In view of their promising potential we have evaluated recombinant soluble HA trimers in chickens and mice for their ability to induce protective immunity against infection with HPAI H5N1. Subsequently, vaccination with the sH5 3 preparation was shown to provide complete protection against challenge with HPAI H5N1 both in mice and in chickens, in the latter already after a single immunization. In the present study we evaluated the vaccine potential of a recombinant soluble H5 protein (sH5 3 ) to protect chickens and mice against a lethal infection with HPAI H5N1. A pseudotype baculovirusmediated vaccine confers protective immunity against lethal challenge with H5N1 avian influenza virus in mice and chickens abstract: BACKGROUND: The highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry. In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate. Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we evaluated the vaccine potential of recombinant soluble trimeric subtype 5 hemagglutinin (sH5(3)) produced in mammalian cells. The secreted, purified sH5(3) was biologically active as demonstrated by its binding to ligands in a sialic acid-dependent manner. It was shown to protect chickens, in a dose-dependent manner, against a lethal challenge with H5N1 after a single vaccination. Protected animals did not shed challenge virus as determined by a quantitative RT-PCR on RNA isolated from trachea and cloaca swabs. Also in mice, vaccination with sH5(3) provided complete protection against challenge with HPAI H5N1. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that sH5(3) constitutes an attractive vaccine antigen for protection of chickens and mammals against HPAI H5N1. As these recombinant soluble hemagglutinin preparations can be produced with high yields and with relatively short lead time, they enable a rapid response to circulating and potentially pandemic influenza viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871037/ doi: 10.1371/journal.pone.0010645 id: cord-000158-d08buwtu author: Corti, Davide title: Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals date: 2010-01-20 words: 8060.0 sentences: 343.0 pages: flesch: 44.0 cache: ./cache/cord-000158-d08buwtu.txt txt: ./txt/cord-000158-d08buwtu.txt summary: The 2G12 epitope is not present in the majority of clade C isolates [27] , but, of more concern, no 2G12-like activity has been detected in the sera of HIV-1 infected individuals [21, 22] , suggesting that this type of neutralizing antibody may not be generally amenable to elicitation by B cells. By using an improved memory B cell immortalization method [41] , combined with highthroughput parallel screening with a panel of recombinant Envbased antigens, we isolated a panel of 58 human mAbs which we have characterized with regard to epitope specificity and breadth of neutralization. The mAbs were purified and further characterized for binding specificity and neutralizing activity using an extended panel of recombinant Env proteins and pseudoviruses representative of several HIV-1 clades with diverse coreceptor usage, geographic origin and conformation. abstract: BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808385/ doi: 10.1371/journal.pone.0008805 id: cord-260647-7bjhobg7 author: Coudray-Meunier, Coralie title: A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System date: 2016-01-29 words: 5581.0 sentences: 278.0 pages: flesch: 48.0 cache: ./cache/cord-260647-7bjhobg7.txt txt: ./txt/cord-260647-7bjhobg7.txt summary: A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The aim of this study was to develop real time RT-PCR assays for detection of a total of 19 human enteric viruses (including 3 genogroupes of norovirus and 4 coronaviruses) and two control process viruses (mengovirus and murine norovirus) generally used for monitoring the recovery of viral foodstuff extraction methods. The sensitivity of conventional qPCR assays targeting 21 viral genomes was compared to the quantitative digital RT-PCR array and to the qualitative nanofluidic real-time PCR array performed on Fluidigm''s BioMark System. Similarly, by testing genomes from viruses in stools and RNA from virus production in cells, the limit of detection (LOD) as determined by RT-dPCR was respectively 1.5 to 3.4 log 10 and 1.6 to 2.1 log 10 lower than the expected copy numbers calculated via the standard curve by RT-qPCR. abstract: Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log(10). Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log(10). Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log(10) lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log(10). Conversely, sensitivity was only 0.30 log(10) better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health. url: https://www.ncbi.nlm.nih.gov/pubmed/26824897/ doi: 10.1371/journal.pone.0147832 id: cord-258366-fu9b446y author: Couto, Carla R. title: Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project date: 2012-02-06 words: 3287.0 sentences: 180.0 pages: flesch: 49.0 cache: ./cache/cord-258366-fu9b446y.txt txt: ./txt/cord-258366-fu9b446y.txt summary: At Hospital das Clinicas, University of Sã o Paulo School of Medical Sciences, a previous study showed a 34% compliance with influenza vaccination among HCWs. In the mentioned study, the main reasons for non-compliance were the perception of vaccine inefficacy and the fear of adverse reactions [4] . To diminish the arguments of fear of adverse events or perception of vaccine inefficacy, this prospective study was conducted to demonstrate to a subset of HCWs from our hospital, that severe adverse events following influenza vaccination are rare and the episodes of respiratory symptoms occurring in the first four months after vaccination are generally caused by other respiratory viruses and not by influenza virus. As expected, no severe adverse event was observed in the present study, and the events more frequently reported, such as headache, myalgia and malaise could be related to influenza vaccine itself as well as to other causes, given their unspecificity. abstract: The compliance with influenza vaccination is poor among health care workers (HCWs) due to misconceptions about safety and effectiveness of influenza vaccine. We proposed an educational prospective study to demonstrate to HCWs that influenza vaccine is safe and that other respiratory viruses (RV) are the cause of respiratory symptoms in the months following influenza vaccination. 398 HCWs were surveyed for adverse events (AE) occurring within 48 h of vaccination. AE were reported by 30% of the HCWs. No severe AE was observed. A subset of 337 HCWs was followed up during four months, twice a week, for the detection of respiratory symptoms. RV was diagnosed by direct immunofluorescent assay (DFA) and real time PCR in symptomatic HCWs. Influenza A was detected in five episodes of respiratory symptoms (5.3%) and other RV in 26 (27.9%) episodes. The incidence density of influenza and other RV was 4.3 and 10.8 episodes per 100 HCW-month, respectively. The educational nature of the present study may persuade HCWs to develop a more positive attitude to influenza vaccination. url: https://doi.org/10.1371/journal.pone.0030670 doi: 10.1371/journal.pone.0030670 id: cord-001142-puj74k7y author: Crescenzo-Chaigne, Bernadette title: The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression date: 2013-11-21 words: 3355.0 sentences: 183.0 pages: flesch: 55.0 cache: ./cache/cord-001142-puj74k7y.txt txt: ./txt/cord-001142-puj74k7y.txt summary: To investigate whether, or not, and how the complete NC regions of a given segment are involved in type specificity, we attempted to rescue, by reverse genetics, type A and C influenza viruses with chimeric non-coding sequences. The sole difference between 5''A/3''C(C5U) and wild-type 5''A/3''A viruses being the 3'' distal extremity of the NS segment suggested that the level of NS encoded proteins (i.e. NS1 or/and NS2/NEP) was affected at early stages of infection for this virus (5''A/3''C(C5U)). The major role of the proximal panhandle in type specificity that we identified and the hypothesized involvement of the distal panhandle in transcription need to be tested on the other (2 PFU/cell), viral vRNA and mRNA levels for each segment were evaluated by specific two-step RT-qPCRs previously described [23] . abstract: Exchange of the extremities of the NS segment of type A and C influenza viruses in reverse genetics systems was used to assess their putative role in type specificity. Restoration of each specific proximal panhandle was mandatory to allow the rescue of viruses with heterotypic extremities. Moreover, the transcription level of the modified segment seemed to be directly affected by the distal panhandle strength. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858493/ doi: 10.1371/journal.pone.0081550 id: cord-001420-b4zcvd04 author: Crescenzo-Chaigne, Bernadette title: Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation date: 2014-09-30 words: 6267.0 sentences: 296.0 pages: flesch: 56.0 cache: ./cache/cord-001420-b4zcvd04.txt txt: ./txt/cord-001420-b4zcvd04.txt summary: Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication. The sequence of both ends of each segment of each rescued virus was verified as described [9] , and no Influenza NP Non Coding Region Role in Translation PLOS ONE | www.plosone.org genetics, type A and type C viruses with one or both heterotypic ends. These data based on type A influenza virus NP segment showed that it is possible to obtain virus by reverse genetics when a homotypic proximal panhandle and a homotypic strength of the initial distal panhandle are maintained, and that the length of the 59 end plays an important role in the efficiency of rescue. abstract: Exchange of the non coding regions of the NP segment between type A and C influenza viruses was used to demonstrate the importance not only of the proximal panhandle, but also of the initial distal panhandle strength in type specificity. Both elements were found to be compulsory to rescue infectious virus by reverse genetics systems. Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182659/ doi: 10.1371/journal.pone.0109046 id: cord-000013-pr9i9swk author: Croyle, Maria A. title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice date: 2008-10-29 words: 6509.0 sentences: 272.0 pages: flesch: 37.0 cache: ./cache/cord-000013-pr9i9swk.txt txt: ./txt/cord-000013-pr9i9swk.txt summary: We have previously found that a single dose of a recombinant adenovirus expressing Ebola Zaire GP given by either the oral or the nasal route is capable of affording protection against lethal challenge in naïve mice and that mucosal immunization can stimulate a broad, prolonged T cell-mediated immune response in both the systemic and mucosal compartments [37] . In an effort to correlate markers of immunity with protection against Ebola infection after mucosal immunization, T and B cell specific immune responses against Ebola glycoprotein were analyzed in mice in the presence or absence of pre-existing immunity (PEI) to adenovirus 10 days after vaccination with a first generation adenovirus serotype 5 vector expressing the Zaire Ebola glycoprotein (Ad5-ZGP). A single intranasal dose of a recombinant Ad5 vaccine expressing the Zaire Ebola glycoprotein conferred 100% protection in both naïve mice and those with pre-existing immunity despite the fact that the strength of the immune response generated by this route of administration was quantitatively lower than that seen in animals vaccinated by intramuscular injection. abstract: Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups). The number of INF-γ+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by ∼25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569416/ doi: 10.1371/journal.pone.0003548 id: cord-254340-e1x0z3rh author: Cruz, Christian Joy Pattawi title: Exploring the young demographic profile of COVID-19 cases in Hong Kong: Evidence from migration and travel history data date: 2020-06-26 words: 4963.0 sentences: 227.0 pages: flesch: 59.0 cache: ./cache/cord-254340-e1x0z3rh.txt txt: ./txt/cord-254340-e1x0z3rh.txt summary: Using detailed case data from Hong Kong''s Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong''s high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Our study includes an examination of the age and sex distribution of the COVID-19 confirmed cases in Hong Kong and an exploration of how the different measures to combat this outbreak resulted in a relatively low number of cases and deaths. In this paper, we highlight the potential impact of the young profile of the confirmed cases on the total number of mortalities and the effect of early, aggressive policy measures including travel bans, enforced quarantines and contact-tracing imposed by the Hong Kong government as early as January 27, 2020 in containing the spread of the COVID-19. abstract: This paper investigates the profile of COVID-19 cases in Hong Kong, highlighting the unique age structure of confirmed cases compared to other territories. While the majority of cases in most territories around the world have fitted an older age profile, our analysis shows that positive cases in Hong Kong have been concentrated among younger age groups, with the largest incidence of cases reported in the 15–24 age group. This is despite the population’s rapidly aging structure and extremely high levels of population density. Using detailed case data from Hong Kong’s Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong’s high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Combined with community action and targeted and aggressive early policy measures taken to contain the virus, these factors may have contributed to the uniquely younger age structure of COVID-19 cases in the city. Consequently, this young profile of confirmed cases may have prevented fatalities in the territory. Recent research has highlighted the importance of a demographic approach to understanding COVID-19 transmission and fatality rates. The experience in Hong Kong shows that while an older population age structure may be important for understanding COVID-19 fatality, it is not a given. From a social science perspective at least, there is ‘no easy answer’ to why one area should experience COVID-19 differently from another. url: https://www.ncbi.nlm.nih.gov/pubmed/32589645/ doi: 10.1371/journal.pone.0235306 id: cord-326011-5rmhjbri author: Cui, Dawei title: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study date: 2016-11-01 words: 3508.0 sentences: 172.0 pages: flesch: 44.0 cache: ./cache/cord-326011-5rmhjbri.txt txt: ./txt/cord-326011-5rmhjbri.txt summary: title: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. Respiratory syncytial virus (RSV) is a leading cause of viral infection in children and older adults worldwide, particularly young children aged <5 years [1] . In this study, we aimed to evaluate the epidemiology, clinical characteristics and management of ALRIs caused by RSV infection among hospitalized patients of all age groups in eastern China between 2009 and 2013 in a hospital-based surveillance study. Clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants abstract: Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009–2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged ≥60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ≥38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact. url: https://www.ncbi.nlm.nih.gov/pubmed/27802292/ doi: 10.1371/journal.pone.0165437 id: cord-348807-9xxc5hyl author: Cuomo, Raphael E. title: Sub-national longitudinal and geospatial analysis of COVID-19 tweets date: 2020-10-28 words: 3235.0 sentences: 143.0 pages: flesch: 43.0 cache: ./cache/cord-348807-9xxc5hyl.txt txt: ./txt/cord-348807-9xxc5hyl.txt summary: METHODS: In an effort to better understand the impacts of COVID-19, we concurrently assessed the geospatial and longitudinal distributions of Twitter messages about COVID-19 which were posted between March 3rd and April 13th and compared these results with the number of confirmed cases reported for sub-national levels of the United States. This study suggests that, across subnational areas within the United States, there exists a highly variable threshold of perceived dangerousness and/or intrusiveness required to activate outbreak-related conversations on social media platforms such as Twitter, a finding that can inform future outbreak communication and health promotion strategies. Concurrent geospatial and longitudinal analyses also indicate that predominantly rural areas of the United States increased engagement in COVID-19 social media conversations at later stages of the study timeframe. This study is unique in that it uses Twitter data as a proxy measure for assessing the concurrent longitudinal and geospatial distributions of attention to COVID-19 across local and regional communities in the United States. abstract: OBJECTIVES: According to current reporting, the number of active coronavirus disease 2019 (COVID-19) infections is not evenly distributed, both spatially and temporally. Reported COVID-19 infections may not have properly conveyed the full extent of attention to the pandemic. Furthermore, infection metrics are unlikely to illustrate the full scope of negative consequences of the pandemic and its associated risk to communities. METHODS: In an effort to better understand the impacts of COVID-19, we concurrently assessed the geospatial and longitudinal distributions of Twitter messages about COVID-19 which were posted between March 3rd and April 13th and compared these results with the number of confirmed cases reported for sub-national levels of the United States. Geospatial hot spot analysis was also conducted to detect geographic areas that might be at elevated risk of spread based on both volume of tweets and number of reported cases. RESULTS: Statistically significant aberrations of high numbers of tweets were detected in approximately one-third of US states, most of which had relatively high proportions of rural inhabitants. Geospatial trends toward becoming hotspots for tweets related to COVID-19 were observed for specific rural states in the United States. DISCUSSION: Population-adjusted results indicate that rural areas in the U.S. may not have engaged with the COVID-19 topic until later stages of an outbreak. Future studies should explore how this dynamic can inform future outbreak communication and health promotion. url: https://doi.org/10.1371/journal.pone.0241330 doi: 10.1371/journal.pone.0241330 id: cord-289510-spmknns5 author: Curado, Evaldo M. F. title: A discrete-time-evolution model to forecast progress of Covid-19 outbreak date: 2020-10-29 words: 5920.0 sentences: 325.0 pages: flesch: 67.0 cache: ./cache/cord-289510-spmknns5.txt txt: ./txt/cord-289510-spmknns5.txt summary: Here, we present a model that can easily incorporate these available data sets and is based on discrete-time equations to forecast the number of confirmed cases by Covid-19 in any given country for the next 14 days. Among its strengths, the presented model: (i) presents low relative error rates, as tested in data from Brazil, South Korea and UK; (ii) provides easily interpretable results, specifically the predicted number of infected people in the next 14 days; (iii) presents results that are directly comparable across countries; and (iv) incorporates the average time related to the disease incubation period (asymptomatic phase) and the average time related to the symptomatic phase, both parameters adjustable according to the pandemics'' characteristics. With the intention to test the method and find good values for the parameters α and β, we considered our fictitious t f N ¼ 102-th day, so it is possible to compare the total number of infected people as provided by the original source (JHU) with the predicted data generated by the model. abstract: Here we present a discrete-time-evolution model with one day interval to forecast the propagation of Covid-19. The proposed model can be easily implemented with daily updated data sets of the pandemic publicly available by distinct online sources. It has only two adjustable parameters and it predicts the evolution of the total number of infected people in a country for the next 14 days if parameters do not change during the analyzed period. The model incorporates the main aspects of the disease such as the fact that there are asymptomatic and symptomatic phases (both capable of propagating the virus), and that these phases take almost two weeks before the infected person status evolves to the next (asymptomatic becomes symptomatic or symptomatic becomes either recovered or dead). A striking advantage of the model for its implementation by the health sector is that it gives directly the number of total infected people in each day (in thousands, tens of thousands or hundred of thousands). Here, the model is tested with data from Brazil, UK and South Korea, presenting low error rates on the prediction of the evolution of the disease in all analyzed countries. We hope this model may be a useful tool to estimate the propagation of the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/33119708/ doi: 10.1371/journal.pone.0241472 id: cord-293794-vudufao5 author: Cuthbertson, Leah title: Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children date: 2019-10-17 words: 4820.0 sentences: 255.0 pages: flesch: 48.0 cache: ./cache/cord-293794-vudufao5.txt txt: ./txt/cord-293794-vudufao5.txt summary: No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Using 16s rRNA gene sequencing of respiratory samples from children presenting to hospital with acute wheezing, this study aimed to examine whether the bacterial community in the airways of children with acute respiratory wheeze was altered compared with that of nonwheezing children. However, when the microbiota in children with bronchiolitis were compared to those closest in age there was a significant reduction in alpha diversity (richness; p = 0.01, Shannon-Weiner, p = 0.003, inverse Simpsons, p = 0.005) that was not associated with change in bacterial biomass (p = 0.874). When those with a diagnosis of bronchiolitis were compared to other cases that wheezed or age matched control subjects, significant differences in alpha and beta diversity were observed however this may have been driven by subjects with bronchiolitis being significantly younger than other groups of subjects. abstract: Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences. url: https://www.ncbi.nlm.nih.gov/pubmed/31622414/ doi: 10.1371/journal.pone.0223990 id: cord-000905-1rhlu59c author: Cyktor, Joshua C. title: Clonal Expansions of CD8(+) T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection date: 2013-03-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The exact role of CD8(+) T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8(+) T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+) T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+), Tim-3(+), CD122(+)). CD8(+) T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8(+) T cell depletion did not significantly alter Mtb burden. Further analysis revealed that pulmonary CD8(+) T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR) Vβ chain 8 (8.2, 8.3) or Vβ 14. Although Vβ8(+) CD8(+) T cells were responsible for the majority of IL-10 production, in vivo depletion of Vβ8(+) did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN-γ secreting profiles. Our data demonstrate that IL-10-secreting CD8(+) T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589362/ doi: 10.1371/journal.pone.0058612 id: cord-349911-dx8wvqkm author: Dahl, Viktor title: Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013 date: 2015-09-23 words: 4092.0 sentences: 208.0 pages: flesch: 49.0 cache: ./cache/cord-349911-dx8wvqkm.txt txt: ./txt/cord-349911-dx8wvqkm.txt summary: Ten pathogens in the highest priority group (Borrelia, calicivirus, Campylobacter, Echinococcus multilocularis, hepatitis C virus, HIV, respiratory syncytial virus, SARSand MERS coronavirus, tick-borne encephalitis virus and varicella-zoster virus) did not have any surveillance of typing results. The Public Health Agency of Sweden identified the need to use a structured method that takes relevant aspects into account in order to rationally prioritize between different pathogens when allocating resources for surveillance. The Robert Koch Institute invited ten senior external experts and ten internal experts and asked them to score the pathogens with -1, 0 or 1 for ten variables"Incidence", "Work and school absenteeism", "Health care utilization", "Chronicity of illness or sequelae", "Case fatality rate", "Proportion of events requiring public health actions", "Trend", "Public attention", "Prevention and Treatment possibilities") ( Table 1 ). We used a standardized procedure developed at the Robert Koch Institute to generate a list of pathogens prioritized for surveillance to be used by the Public Health Agency of Sweden. abstract: To establish strategic priorities for the Public Health Agency of Sweden we prioritized pathogens according to their public health relevance in Sweden in order to guide resource allocation. We then compared the outcome to ongoing surveillance. We used a modified prioritization method developed at the Robert Koch Institute in Germany. In a Delphi process experts scored pathogens according to ten variables. We ranked the pathogens according to the total score and divided them into four priority groups. We then compared the priority groups to self-reported time spent on surveillance by epidemiologists and ongoing programmes for surveillance through mandatory and/or voluntary notifications and for surveillance of typing results. 106 pathogens were scored. The result of the prioritization process was similar to the outcome of the prioritization in Germany. Common pathogens such as calicivirus and Influenza virus as well as blood-borne pathogens such as human immunodeficiency virus, hepatitis B and C virus, gastro-intestinal infections such as Campylobacter and Salmonella and vector-borne pathogens such as Borrelia were all in the highest priority group. 63% of time spent by epidemiologists on surveillance was spent on pathogens in the highest priority group and all pathogens in the highest priority group, except for Borrelia and varicella-zoster virus, were under surveillance through notifications. Ten pathogens in the highest priority group (Borrelia, calicivirus, Campylobacter, Echinococcus multilocularis, hepatitis C virus, HIV, respiratory syncytial virus, SARS- and MERS coronavirus, tick-borne encephalitis virus and varicella-zoster virus) did not have any surveillance of typing results. We will evaluate the possibilities of surveillance for the pathogens in the highest priority group where we currently do not have any ongoing surveillance and evaluate the need of surveillance for the pathogens from the low priority group where there is ongoing surveillance in order to focus our work on the pathogens with the highest relevance. url: https://doi.org/10.1371/journal.pone.0136353 doi: 10.1371/journal.pone.0136353 id: cord-260843-c97kctjz author: Dai, Lei title: Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake date: 2016-11-16 words: 4635.0 sentences: 255.0 pages: flesch: 46.0 cache: ./cache/cord-260843-c97kctjz.txt txt: ./txt/cord-260843-c97kctjz.txt summary: In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Therefore, in the study, we aimed to examine the in vitro effects of TGEV infection on glucose uptake and the expression of SGLT1 and GLUT2 in porcine intestinal columnar epithelial (IPEC-J2) cells, which have been shown to offer a practical model for studying TGEV infection [11, 12] . Together, these results indicate that EGFR and p-EGFR regulates glucose uptake in mock-infected IPEC-J2 cells by modulation of SGLT1 protein expression. Together, these results indicate that EGFR influences glucose uptake in TGEV-infected cells by promoting both SGLT1 and GLUT2 expression. abstract: Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes villus atrophy, followed by crypt hyperplasia, reduces the activities of intestinal digestive enzymes, and disrupts the absorption of intestinal nutrients. In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. In this study, we therefore sought to evaluate the effects of TGEV infection on glucose uptake and SGLT1 and GLUT2 expression. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Moreover, inhibition studies showed that EGFR modulated glucose uptake in control and TGEV infected cells. Finally, high glucose absorption was subsequently found to promote TGEV replication. url: https://www.ncbi.nlm.nih.gov/pubmed/27851758/ doi: 10.1371/journal.pone.0165585 id: cord-309981-4p3ybrn1 author: Dai, Ling-Ling title: Anxiety and depressive symptoms among COVID-19 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China date: 2020-08-28 words: 3554.0 sentences: 179.0 pages: flesch: 43.0 cache: ./cache/cord-309981-4p3ybrn1.txt txt: ./txt/cord-309981-4p3ybrn1.txt summary: From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. As with other infectious diseases, preliminary evidence suggests that COVID-19 also causes public panic and mental health stress; symptoms of anxiety and depression are common psychological reactions to the COVID-19 pandemic, and may be associated with sociodemographic factors and sleep quality [6] [7] [8] [9] . This cross-sectional study examined the prevalence of anxiety, depression, and poor sleep quality among 307 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China, 2 months after the start of the COVID-19 pandemic. In addition, using one-sample-tests, it was determined that both SAS (42.92±7.30) and SDS (39.77±10.11) scores of the participants of our study were higher than Chinese norms (SAS, 29.78±10.07, n = 1158; SDS, 33.46±8.55, n = 1340) (both P<0.001) [26] , indicating more severe levels of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang hospitals, compared with the general public. abstract: Fangcang shelter hospitals were established in China during the coronavirus disease 2019 (COVID-19) pandemic as a countermeasure to stop the spread of the disease. To our knowledge, no research has been conducted on mental health problems among patients in Fangcang shelter hospitals. This study aimed to determine the prevalence and major influencing factors of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang shelter hospitals. From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. Data were obtained with an online questionnaire. The questionnaire consisted of a set of items on demographic characteristics, a set of items on clinical characteristics, the Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Pittsburgh Sleep Quality Index. Three hundred seven COVID-19 patients who were admitted to Jianghan Fangcang Shelter Hospital participated in this study. The prevalence of anxiety and depressive symptoms were 18.6% and 13.4%, respectively. Poor sleep quality and having ≥ two current physical symptoms were independent risk factors for anxiety symptoms. Female sex, having a family member with confirmed COVID-19, and having ≥ two current physical symptoms were independent risk factors for depressive symptoms. Anxiety and depressive symptoms were found to be common among COVID-19 patients in Fangcang Shelter Hospital, with some patients being at high risk. url: https://www.ncbi.nlm.nih.gov/pubmed/32857826/ doi: 10.1371/journal.pone.0238416 id: cord-316319-m6uha1qn author: Daleno, Cristina title: Phylogenetic Analysis of Human Rhinovirus Isolates Collected from Otherwise Healthy Children with Community-Acquired Pneumonia during Five Successive Years date: 2013-11-19 words: 3942.0 sentences: 177.0 pages: flesch: 53.0 cache: ./cache/cord-316319-m6uha1qn.txt txt: ./txt/cord-316319-m6uha1qn.txt summary: In order to evaluate the circulation of the different human rhinovirus (HRV) species and genotypes in Italian children with radiographically confirmed community-acquired pneumonia (CAP), a nasopharyngeal swab was obtained from 643 children admitted to hospital because of CAP during five consecutive winter and early spring seasons (2007-2012). However, most of these studies were carried out in a single year and involved a relatively small number of patients, and only a few analysed specific LRTIs. Consequently, there are few data concerning the circulation of HRVs over a long period of time or the real role of the different species and genotypes in causing LRTIs. The aim of this study was to evaluate the circulation of the different HRV species and genotypes in Italian children with radiographically confirmed CAP during the winter and early spring of five consecutive years as this information could help to develop tailored strategies for the prevention and treatment of pediatric HRV infections. abstract: In order to evaluate the circulation of the different human rhinovirus (HRV) species and genotypes in Italian children with radiographically confirmed community-acquired pneumonia (CAP), a nasopharyngeal swab was obtained from 643 children admitted to hospital because of CAP during five consecutive winter and early spring seasons (2007-2012). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to identify HRV, and the HRV-positive samples were used for sequencing analysis and to reconstruct the phylogenetic tree. HRV was identified in 198 samples (42.2%), and the VP4/VP2 region was successfully amplified in 151 (76.3%). HRV-A was identified in 78 samples (51.6%), HRV-B in 14 (9.3%) and HRV-C in 59 (39.1%). Forty-seven (31.1%) of the children with HRV infection were aged <1 year, 71 (47.0%) were aged 1-3 years, and 33 (21.9%) were aged ≥4 years. Blast and phylogenetic analyses showed that the HRV strains were closely related to a total of 66 reference genotypes, corresponding to 29 HRV-A, 9 HRV-B and 28 HRV-C strains. Nucleotide variability was 37% between HRV-A and HRV-B, 37.3% between HRV-A and HRV-C, and 39.9% between HRV-B and HRV-C. A number of sequences clustered with known serotypes and, within these clusters, there were strains circulating during several seasons. The most frequently detected genotypes were HRV-A78 (n=17), HRV-A12 (n=9) and HRV-C2 (n=5). This study shows that, although it is mainly associated with HRV-A, pediatric CAP can also be diagnosed in subjects infected by HRV-C and, more rarely, by HRV-B. Moreover, a large number of genotypes may be involved in causing pediatric CAP and can be different from year to year. Although the prolonged circulation of the same genotypes can sometimes be associated with a number of CAP episodes in different years. url: https://doi.org/10.1371/journal.pone.0080614 doi: 10.1371/journal.pone.0080614 id: cord-002473-2kpxhzbe author: Das, Jayanta Kumar title: Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach date: 2017-03-31 words: 4613.0 sentences: 285.0 pages: flesch: 61.0 cache: ./cache/cord-002473-2kpxhzbe.txt txt: ./txt/cord-002473-2kpxhzbe.txt summary: Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. The primary protein sequence is read as consecutive order pairs serially from first amino acid to the end of sequence, and each order pair is nothing but a connected edge between the two nodes where nodes in the graph are involved with different chemical groups of amino acids. Our method of phylogenetic tree formation used the dissimilarity matrix which is obtained for every pair of sequence on the basis of chemical group specific score of amino acids. Based on the phylogenetic tree of five members, we find that the PpcA and PpcD, PpcB and PpcE are mostly closed with regards to the frequency of amino acids of respective eight chemical groups. abstract: Periplasmic c7 type cytochrome A (PpcA) protein is determined in Geobacter sulfurreducens along with its other four homologs (PpcB-E). From the crystal structure viewpoint the observation emerges that PpcA protein can bind with Deoxycholate (DXCA), while its other homologs do not. But it is yet to be established with certainty the reason behind this from primary protein sequence information. This study is primarily based on primary protein sequence analysis through the chemical basis of embedded amino acids. Firstly, we look for the chemical group specific score of amino acids. Along with this, we have developed a new methodology for the phylogenetic analysis based on chemical group dissimilarities of amino acids. This new methodology is applied to the cytochrome c7 family members and pinpoint how a particular sequence is differing with others. Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. Thirdly, we search for unique patterns as subsequences which are common among the group or specific individual member. In all the cases, we are able to show some distinct features of PpcA that emerges PpcA as an outstanding protein compared to its other homologs, resulting towards its binding with deoxycholate. Similarly, some notable features for the structurally dissimilar protein PpcD compared to the other homologs are also brought out. Further, the five members of cytochrome family being homolog proteins, they must have some common significant features which are also enumerated in this study. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376323/ doi: 10.1371/journal.pone.0175031 id: cord-002180-gsdk5x3e author: Davies, Colin title: Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest date: 2016-08-24 words: 4491.0 sentences: 223.0 pages: flesch: 52.0 cache: ./cache/cord-002180-gsdk5x3e.txt txt: ./txt/cord-002180-gsdk5x3e.txt summary: Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5. Several RNA viruses, including murine norovirus 1 (MNV-1) have been characterized to manipulate cell cycle progression at the G 1 /S restriction point, often creating favorable conditions for viral replication [14] [15] [16] [17] [18] [19] [20] [21] . The effect of NS5 on the host cell cycle was therefore determined by transfection of RAW-Blue cells with RNA transcripts, encoding individual viral genes, NS1-2 from MNV-1 was included as a negative control (Fig 1A) . Furthermore, the NS5(F123A) variant decreased cyclin A protein expression by 67% when compared to the mocktransfected population in a synonymous manner to NS5, strongly implying that the host eukaryotic initiation factor binding domain of NS5 does not play a role in its cell cycle manipulation (Fig 3D) . abstract: Murine norovirus-1 (MNV-1) is known to subvert host cell division inducing an accumulation of cells in the G(0)/G(1) phase, creating conditions where viral replication is favored. This study identified that NS5 (VPg), is capable of inducing cell cycle arrest in the absence of viral replication or other viral proteins in an analogous manner to MNV-1 infection. NS5 expression induced an accumulation of cells in the G(0)/G(1) phase in an asynchronous population by inhibiting progression at the G(1)/S restriction point. Furthermore, NS5 expression resulted in a down-regulation of cyclin A expression in asynchronous cells and inhibited cyclin A expression in cells progressing from G(1) to S phase. The activity of NS5 on the host cell cycle occurs through an uncharacterized function. Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5. To the best of our knowledge, this is the first report of a VPg protein manipulating the host cell cycle. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996510/ doi: 10.1371/journal.pone.0161582 id: cord-265812-1hcp36cw author: De Jong, Cornelis N. title: Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience date: 2017-10-26 words: 3168.0 sentences: 186.0 pages: flesch: 53.0 cache: ./cache/cord-265812-1hcp36cw.txt txt: ./txt/cord-265812-1hcp36cw.txt summary: W.; Van der Klift, Marjolein; Cornelissen, Jan J.; Broers, Annoek E. High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients. High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients [2, 3] . Studies evaluating second-line treatment with the anti-TFNα agent etanercept have shown promising results with overall response rates of 50-80% [8] [9] [10] . In conclusion, although second-line treatment of SR-aGVHD of the gut with etanercept was associated with a promising initial response rate, overall survival appeared very poor, mainly due to progression of GVHD and opportunistic infections. abstract: BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. METHODS: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. RESULTS: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5–267) for the entire group. Median overall survival was 99 days (range 47–267 days) for responders and 17 days (range 5–66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients. url: https://www.ncbi.nlm.nih.gov/pubmed/29073260/ doi: 10.1371/journal.pone.0187184 id: cord-269690-6r2bfydw author: De Lorenzo, Rebecca title: Residual clinical damage after COVID-19: A retrospective and prospective observational cohort study date: 2020-10-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Data on residual clinical damage after Coronavirus disease-2019 (COVID-19) are lacking. The aims of this study were to investigate whether COVID-19 leaves behind residual dysfunction, and identify patients who might benefit from post-discharge monitoring. All patients aged ≥18 years admitted to the Emergency Department (ED) for COVID-19, and evaluated at post-discharge follow-up between 7 April and 7 May, 2020, were enrolled. Primary outcome was need of follow-up, defined as the presence at follow-up of at least one among: respiratory rate (RR) >20 breaths/min, uncontrolled blood pressure (BP) requiring therapeutic change, moderate to very severe dyspnoea, malnutrition, or new-onset cognitive impairment, according to validated scores. Post-traumatic stress disorder (PTSD) served as secondary outcome. 185 patients were included. Median [interquartile range] time from hospital discharge to follow-up was 23 [20–29] days. 109 (58.9%) patients needed follow-up. At follow-up evaluation, 58 (31.3%) patients were dyspnoeic, 41 (22.2%) tachypnoeic, 10 (5.4%) malnourished, 106 (57.3%) at risk for malnutrition. Forty (21.6%) patients had uncontrolled BP requiring therapeutic change, and 47 (25.4%) new-onset cognitive impairment. PTSD was observed in 41 (22.2%) patients. At regression tree analysis, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO(2)/FiO(2)) and body mass index (BMI) at ED presentation, and age emerged as independent predictors of the need of follow-up. Patients with PaO(2)/FiO(2) <324 and BMI ≥33 Kg/m(2) had the highest odds to require follow-up. Among hospitalised patients, age ≥63 years, or age <63 plus non-invasive ventilation or diabetes identified those with the highest probability to need follow-up. PTSD was independently predicted by female gender and hospitalisation, the latter being protective (odds ratio, OR, 4.03, 95% confidence interval, CI, 1.76 to 9.47, p 0.0011; OR 0.37, 95% CI 0.14 to 0.92, p 0.033, respectively). COVID-19 leaves behind physical and psychological dysfunctions. Follow-up programmes should be implemented for selected patients. url: https://www.ncbi.nlm.nih.gov/pubmed/33052920/ doi: 10.1371/journal.pone.0239570 id: cord-001045-jm60nxc2 author: DeLisle, Sylvain title: Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy date: 2013-08-13 words: 4332.0 sentences: 209.0 pages: flesch: 45.0 cache: ./cache/cord-001045-jm60nxc2.txt txt: ./txt/cord-001045-jm60nxc2.txt summary: METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The ARI CDA flagged an outpatient visit if the provider assigned it an ARI-related International Disease Classification, 9 th Revision, Clinical Modification (ICD-9) diagnostic code OR issued a prescription for a cough remedy OR documented at least two symptoms from the above ARI case definition in his/her clinical note, as retrieved by computerized text analysis [10] . Discussion Automated text analyses of chest imaging reports improved the performance of EMR-based CDAs that included structured data elements and free-text search for ARI symptoms. abstract: BACKGROUND: Timely information about disease severity can be central to the detection and management of outbreaks of acute respiratory infections (ARI), including influenza. We asked if two resources: 1) free text, and 2) structured data from an electronic medical record (EMR) could complement each other to identify patients with pneumonia, an ARI severity landmark. METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The x-ray reports served as a reference to develop a text classifier using machine-learning software that did not require custom coding. To identify pneumonia cases, the classifier was combined with EMR-based structured data and with text analyses aimed at ARI symptoms in clinical notes. RESULTS: 370 reference cases with Possible Pneumonia and 250 with Pneumonia-in-Plan were identified. The x-ray report text classifier increased the positive predictive value of otherwise identical EMR-based case-detection algorithms by 20–70%, while retaining sensitivities of 58–75%. These performance gains were independent of the case definitions and of whether patients were admitted to the hospital or sent home. Text analyses seeking ARI symptoms in clinical notes did not add further value. CONCLUSION: Specialized software development is not required for automated text analyses to help identify pneumonia patients. These results begin to map an efficient, replicable strategy through which EMR data can be used to stratify ARI severity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742728/ doi: 10.1371/journal.pone.0070944 id: cord-303845-y6ws3u6x author: DeLisle, Sylvain title: Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections date: 2010-10-14 words: 5608.0 sentences: 246.0 pages: flesch: 44.0 cache: ./cache/cord-303845-y6ws3u6x.txt txt: ./txt/cord-303845-y6ws3u6x.txt summary: Several factors, some of which have already been mentioned, may limit the generalizability of our results: 1) factors related to the performance of our study at the VA health care system: a) the veterans study population is mostly male and excludes the pediatric population, a key target for ARI surveillance [44] ; b) veterans health care utilization may differ from that observed in uninsured or privately insured individuals; c) clinical practices, documentation and coding habits by VA practitioners may differ from those observed in solo or group practices or in health systems subject to different financial or quality-control incentives; 2) factors related to our study period: optimal CDAs could differ outside the respiratory infection season, or during periods of heightened apprehension for an influenza epidemic; 3) factors related to our iterative CDA development process, which may have over adapted CDAs to VA''s particular EMR implementation and to our sample dataset in particular, this despite our efforts to maintain a separation between development and validation data subsets; 4) factors related to our text mining approach: a) we did not employ a spell checker prior to applying the NegEx algorithm. abstract: BACKGROUND: The electronic medical record (EMR) contains a rich source of information that could be harnessed for epidemic surveillance. We asked if structured EMR data could be coupled with computerized processing of free-text clinical entries to enhance detection of acute respiratory infections (ARI). METHODOLOGY: A manual review of EMR records related to 15,377 outpatient visits uncovered 280 reference cases of ARI. We used logistic regression with backward elimination to determine which among candidate structured EMR parameters (diagnostic codes, vital signs and orders for tests, imaging and medications) contributed to the detection of those reference cases. We also developed a computerized free-text search to identify clinical notes documenting at least two non-negated ARI symptoms. We then used heuristics to build case-detection algorithms that best combined the retained structured EMR parameters with the results of the text analysis. PRINCIPAL FINDINGS: An adjusted grouping of diagnostic codes identified reference ARI patients with a sensitivity of 79%, a specificity of 96% and a positive predictive value (PPV) of 32%. Of the 21 additional structured clinical parameters considered, two contributed significantly to ARI detection: new prescriptions for cough remedies and elevations in body temperature to at least 38°C. Together with the diagnostic codes, these parameters increased detection sensitivity to 87%, but specificity and PPV declined to 95% and 25%, respectively. Adding text analysis increased sensitivity to 99%, but PPV dropped further to 14%. Algorithms that required satisfying both a query of structured EMR parameters as well as text analysis disclosed PPVs of 52–68% and retained sensitivities of 69–73%. CONCLUSION: Structured EMR parameters and free-text analyses can be combined into algorithms that can detect ARI cases with new levels of sensitivity or precision. These results highlight potential paths by which repurposed EMR information could facilitate the discovery of epidemics before they cause mass casualties. url: https://doi.org/10.1371/journal.pone.0013377 doi: 10.1371/journal.pone.0013377 id: cord-255384-tljyx6ua author: Decaro, Nicola title: Full-Genome Analysis of a Canine Pneumovirus Causing Acute Respiratory Disease in Dogs, Italy date: 2014-01-06 words: 4629.0 sentences: 243.0 pages: flesch: 55.0 cache: ./cache/cord-255384-tljyx6ua.txt txt: ./txt/cord-255384-tljyx6ua.txt summary: The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. In order to obtain new insights into the genetic diversity of CnPnV, the Italian prototype strain dog/Bari/100-12/ITA/2012 was submitted to RT-PCR amplification and subsequent sequence analysis of the full-length genome, using oligonucleotide retrieved from previous studies [13] [14] . When the analysis was restricted to the 8,600 and 8,598 nt available for reference CnPnV strains Brne17 and Ane4, respectively, that span from the very 39 end of the L gene to the 59end of the leader region (genome sense), an overall sequence identity of 96.5-96.6% was found against the canine strains. abstract: An outbreak of canine infectious respiratory disease (CIRD) associated to canine pneumovirus (CnPnV) infection is reported. The outbreak occurred in a shelter of the Apulia region and involved 37 out of 350 dogs that displayed cough and/or nasal discharge with no evidence of fever. The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. The present study represents a useful contribution to the knowledge of the pathogenic potential of CnPnV and its association with CIRD in dogs. Further studies will elucidate the pathogenicity and epidemiology of this novel pneumovirus, thus addressing the eventual need for specific vaccines. url: https://doi.org/10.1371/journal.pone.0085220 doi: 10.1371/journal.pone.0085220 id: cord-013263-xw611i8k author: Dederichs, Melina title: Students’ perspectives on interventions to reduce stress in medical school: A qualitative study date: 2020-10-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The mental health of medical students remains to be a matter of concern. Numerous setting-based and individual-based interventions for student mental health have been proposed in the literature. However, the student perspective on those interventions has been largely neglected. This study aims to explore how medical students perceive different interventions and if they desire any additional changes with regard to their studies. Eight focus groups with 71 participants were conducted at a large German medical school. Focus groups were recorded, transcribed and content-analyzed using MAXQDA 18. We found that medical students prefer setting-based interventions. Most proposed interventions were on a setting-based level. For instance, students asked for more information on the university’s psychosocial counseling services and for better information management regarding contact persons. Interventions proposed in the literature received mixed reactions: Several participants did not favour a pass/fail grading system. Students considered a peer-to-peer mentoring program for freshmen very helpful. Students had diverse attitudes towards Balint groups. They approved of several self-management courses, most of them being related to time or stress management. Interestingly, the most urgently wanted interventions appear to be rather easy to implement (e.g. a mentoring program). This study explored the medical student perspective on student mental health interventions. Additionally, our study illustrates the benefit and feasibility of involving students early on in the conception of interventions. Further research with a representative sample is needed to obtain broader information on the acceptance of the suggested interventions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561099/ doi: 10.1371/journal.pone.0240587 id: cord-342730-b7y8mybg author: Dellagi, Koussay title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009 date: 2011-09-29 words: 5974.0 sentences: 283.0 pages: flesch: 49.0 cache: ./cache/cord-342730-b7y8mybg.txt txt: ./txt/cord-342730-b7y8mybg.txt summary: In order to assess at the community level, the actual magnitude of the pH1N1/2009v pandemic and the extent of the herd immunity acquired after passage of the epidemic wave, a prospective population serosurvey was conducted in Reunion Island during the passage of the epidemic wave in the 2009 austral winter season (July-December 2009): prevalence of infection was assessed on a weekly basis and seroconversion rates were measured using paired sera. The CoPanFlu-RUN cohort was set up to conduct a prospective population-based study investigating the herd immunity induced by the 2009 pandemic influenza virus and identifying risk factors for pH1N1/2009v infection from paired sera collected in an entire community. Our study shows that a substantial proportion of Reunion Island''s population had pre-existing immunity to 2009 pandemic influenza virus with the highest baseline-proxy seroprevalence rate observed among adults aged of 60 years or more. abstract: BACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season. METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive. CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses. url: https://www.ncbi.nlm.nih.gov/pubmed/21980532/ doi: 10.1371/journal.pone.0025738 id: cord-003841-7uaj9hmx author: Desmonts de Lamache, D. title: Immuno-modulating properties of Tulathromycin in porcine monocyte-derived macrophages infected with porcine reproductive and respiratory syndrome virus date: 2019-08-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707645/ doi: 10.1371/journal.pone.0221560 id: cord-001447-oi7bkm4z author: Dhanasekaran, Sakthivel title: Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo date: 2014-11-04 words: 6012.0 sentences: 318.0 pages: flesch: 51.0 cache: ./cache/cord-001447-oi7bkm4z.txt txt: ./txt/cord-001447-oi7bkm4z.txt summary: We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Infection of peripheral blood mononuclear cells (PBMC) from four breeds of goats and water buffalo resulted in differential viral replication kinetics and inflammatory cytokine profile including IFNa, IFNc and TNFa with differential activation of TLR3 and TLR7. To determine whether the differential IFN and pro-inflammatory cytokine production between Kanni/Salem vs Barbari/ Tellicherry breeds of goats are dependent on single nucleotide polymorphisms (SNPs) in TLR genes, we examined the complete gene sequence of TLR7. abstract: Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219731/ doi: 10.1371/journal.pone.0111609 id: cord-308344-ao9z00t7 author: Diep, Nguyen Van title: Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation date: 2017-01-17 words: 4179.0 sentences: 193.0 pages: flesch: 52.0 cache: ./cache/cord-308344-ao9z00t7.txt txt: ./txt/cord-308344-ao9z00t7.txt summary: title: Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. In this study, variants with large deletions in the S gene were found in eight primary and nine recurrent outbreaks from 16 pig farms, and they mostly (94.1%) coexisted with PEDV strains with an intact S gene. Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene New porcine epidemic diarrhoea virus variant with a large deletion in the spike gene identified in domestic pigs abstract: Since late 2013, after an absence of seven years, outbreaks of porcine epidemic diarrhea virus (PEDV) infection have reemerged and swept rapidly across Japan, resulting in significant economic losses. In this study, we report the emergence, mixed infection, and genetic characterization of 15 novel field PEDV variants with large genomic deletions. The sizes of deletion varied between 582 nt (194 aa) and 648 nt (216 aa) at positions 28–714 (10–238) on the S gene (protein). Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. These variants were found in eight primary and nine recurrent outbreaks, and they might be associated with persistent PEDV infection in the farms. Full-length S and ORF3 genes of eight variants derived from 2 samples were characterized. This is the first report of mixed infections caused by various genotypes of PEDV and would be important for the studies of viral isolation, pathogenesis, and molecular epidemiology of the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/28095455/ doi: 10.1371/journal.pone.0170126 id: cord-309010-tmfm5u5h author: Dietert, Kristina title: Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia date: 2017-11-20 words: 7842.0 sentences: 414.0 pages: flesch: 34.0 cache: ./cache/cord-309010-tmfm5u5h.txt txt: ./txt/cord-309010-tmfm5u5h.txt summary: Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. Transnasal infection with MERS-CoV following adenoviral transduction of human DPP4 yielded an expansive, (Fig 7A) interstitial pneumonia with severe alveolar epithelial cell necrosis and infiltration of mainly macrophages, lymphocytes, and fewer neutrophils (Fig 7B) . Different mouse models of acute pneumonia differ widely, with an obvious strong dependence on pathogen-specific features of virulence and spread, route of infection, infectious dose and other factors. abstract: Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models. url: https://doi.org/10.1371/journal.pone.0188251 doi: 10.1371/journal.pone.0188251 id: cord-353730-owcapg8h author: Dietrich, Jes title: Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01 date: 2014-06-23 words: 7885.0 sentences: 389.0 pages: flesch: 53.0 cache: ./cache/cord-353730-owcapg8h.txt txt: ./txt/cord-353730-owcapg8h.txt summary: The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. Based on neutralization titers obtained from mice vaccinated with a range of doses from 30 DU (D-Units) to 0.1 DU (data not shown) we choose 20 DU as a full mouse dose and 2 DU as the dose formulated into the CAF01 adjuvant (indicated dose units in the all experiments correspond to polio virus type-1 D antigen units). Taken together, compared to IM administration a side by side ID+IM administration with a CAF01-adjuvanted vaccine followed by an IM administration did not negatively affect systemic immunity, measured by antibody binding and neutralization titers and T cell IFN-c secretion (Fig. 6) . abstract: The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority, and will be required to eradicate polio. In addition, such a vaccine constitutes the only realistic polio vaccine in the post-eradication era. One way to reduce the cost of a vaccine is to increase immunogenicity by use of adjuvants. The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. CAF01 also influenced the kinetics of both the cellular and humoral response against IPV to produce a faster, as well as a stronger, response, dominated by IgG2a, IgG2b, and IgG2c isotypes as well as IPV specific T cells secreting IFN-γ/IL-2. Finally, as intestinal immunity is also a priority of polio vaccines, we present a vaccine strategy based on simultaneous priming at an intradermal and an intramuscular site that generate intestinal immune responses against polio virus. Taken together, the IPV-CAF01 formulation constitutes a new promising vaccine against polio with the ability to generate strong humoral and cellular immunity against the polio virus. url: https://doi.org/10.1371/journal.pone.0100879 doi: 10.1371/journal.pone.0100879 id: cord-253056-765rs3e7 author: Dionne, Audrey title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection date: 2018-10-17 words: 3725.0 sentences: 208.0 pages: flesch: 45.0 cache: ./cache/cord-253056-765rs3e7.txt txt: ./txt/cord-253056-765rs3e7.txt summary: title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with concurrent infection had higher rates of IVIG resistance (19 (33%) versus 17 (18%) patients, p = 0.04), and higher temperature at 48 hours (Fig 1) . In this retrospective series, the presence of a concomitant infection was associated with a higher rate of resistance to IVIG treatment. In this study, patients with concomitant infection had a higher rate of resistance to IVIG treatment. abstract: INTRODUCTION: Kawasaki disease (KD) can be associated with concomitant viral or bacterial infections. Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. Although concomitant infection does not affect coronary outcome, it is unknown how it influences the response to IVIG treatment. METHODOLOGY: Retrospective cohort study between 2008 and 2016 in a tertiary pediatric university hospital, including 154 children, of which 59 (38%) had concomitant infection. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p = 0.04), and 48 hours after IVIG administration (111 vs 59 mg/L, p = 0.003). Nevertheless, there was no statistically significant difference in the prevalence of coronary complications (Z-score > 2.5) between children with and without concomitant infection (36% vs 39%, p = 0.68). CONCLUSION: Children with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment. This association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication. Accordingly, prospective studies to distinguish true IVIG resistance from infection induced persistent fever is warranted. url: https://www.ncbi.nlm.nih.gov/pubmed/30332473/ doi: 10.1371/journal.pone.0206001 id: cord-267973-uvz7kavu author: Do, Lien Anh Ha title: Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity date: 2016-08-08 words: 5921.0 sentences: 476.0 pages: flesch: 61.0 cache: ./cache/cord-267973-uvz7kavu.txt txt: ./txt/cord-267973-uvz7kavu.txt summary: title: Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. However, information on detailed clinical, epidemiological features and virological characteristics of RSV infections (e.g. disease burden, demographics, seasonal variations of RSV and other viral infections, circulating genotypes and subgroups, viral load) or on the frequency / impact of other respiratory viruses among Vietnamese children under two years old are limited [6] . Here, we aimed to describe the viral etiologies and the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a LRTI, focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. abstract: BACKGROUND: Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. METHODS: A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. RESULTS: Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. CONCLUSION: We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity. url: https://doi.org/10.1371/journal.pone.0160606 doi: 10.1371/journal.pone.0160606 id: cord-349029-zyfop43z author: Dobrovolny, Hana M. title: Modeling the role of asymptomatics in infection spread with application to SARS-CoV-2 date: 2020-08-10 words: 4596.0 sentences: 233.0 pages: flesch: 48.0 cache: ./cache/cord-349029-zyfop43z.txt txt: ./txt/cord-349029-zyfop43z.txt summary: In order to estimate how effective these strategies will be, we will need a better understanding of the role of asymptomatic individuals in SARS-CoV-2 spread and the effect the proportion and relative infectiousness of asymptomatics have on the time course of the epidemic. In this paper, we study a compartmental epidemic model that includes asymptomatic infections to determine the role that asymptomatic individuals might play in the spread of SARS-CoV-2. We apply our model to data from SARS-CoV-2 epidemics in California, Florida, New York, and Texas, finding that a large number of infections in these states are unreported and that relaxing social distancing measures too early will cause a rapid spike in infections driven in part by these hidden infections. For the SARS-CoV epidemics examined here, the model predicts that there are far more asymptomatic or unreported cases at the peak of the infection, suggesting that there might be widespread community transmission if stay-at-home orders are relaxed too early. abstract: SARS-CoV-2 started causing infections in humans in late 2019 and has spread rapidly around the world. While the number of symptomatically infected and severely ill people is high and has overwhelmed the medical systems of many countries, there is mounting evidence that some of the rapid spread of this virus has been driven by asymptomatic infections. In this study, we use a compartmental mathematical model of a viral epidemic that includes asymptomatic infection to examine the role of asymptomatic individuals in the spread of the infection. We apply the model to epidemics in California, Florida, New York, and Texas, finding that asymptomatic infections far outnumber reported symptomatic infections at the peak of the epidemic in all four states. The model suggests that relaxing of social distancing measures too quickly could lead to a rapid rise in the number of cases, driven in part by asymptomatic infections. url: https://doi.org/10.1371/journal.pone.0236976 doi: 10.1371/journal.pone.0236976 id: cord-308249-es948mux author: Dokuka, Sofia title: How academic achievement spreads: The role of distinct social networks in academic performance diffusion date: 2020-07-27 words: 5043.0 sentences: 297.0 pages: flesch: 48.0 cache: ./cache/cord-308249-es948mux.txt txt: ./txt/cord-308249-es948mux.txt summary: We examine the spread of academic achievements of first-year undergraduate students through friendship and study assistance networks, applying stochastic actor-oriented modeling. In this paper, we analyze the diffusion of academic performance across different types of student social networks. We analyze the spread of academic achievements within two different social networks of first-year undergraduate students. It was shown that achievements spread well within friendship networks, while other types of ties (e.g. online relationships) do not serve as channels for the performance transmission. In this paper, we examine the diffusion of academic achievements in two distinct social networks: friendship and study assistance. We analyze the longitudinal data on friendship and study assistance networks and GPA of a first-year student cohort of the Economics department in one of the leading Russian universities in 2013-2014 academic year. In this paper we explore the academic performance diffusion through two social networks of different natures: friendship and study assistance. abstract: Behavior diffusion through social networks is a key social process. It may be guided by various factors such as network topology, type of propagated behavior, and the strength of network connections. In this paper, we claim that the type of social interactions is also an important ingredient of behavioral diffusion. We examine the spread of academic achievements of first-year undergraduate students through friendship and study assistance networks, applying stochastic actor-oriented modeling. We show that informal social connections transmit performance while instrumental connections do not. The results highlight the importance of friendship in educational environments and contribute to debates on the behavior spread in social networks. url: https://doi.org/10.1371/journal.pone.0236737 doi: 10.1371/journal.pone.0236737 id: cord-352564-2j4pjjwk author: Dominguez, Samuel R. title: Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response date: 2013-07-24 words: 4449.0 sentences: 199.0 pages: flesch: 46.0 cache: ./cache/cord-352564-2j4pjjwk.txt txt: ./txt/cord-352564-2j4pjjwk.txt summary: Because they are the natural target cells for respiratory virus infection, primary human respiratory epithelial cell cultures provide the ideal in vitro systems for investigation of cell factors required for growth of respiratory human viruses, for analysis of their interactions with viruses and their innate immune responses to infection, and for isolation and propagation of novel respiratory pathogens. Here we demonstrate that HCoV-HKU1 can infect and be serially propagated in primary human alveolar type II cells but not in alveolar type I-like cells or alveolar macrophages at the air-liquid interface. Titers of viral RNA in the wash from the apical surface of the cells were determined by qRT-PCR at the indicated time points, and HCoV-HKU1 Infection of Type II Alveolar Cells PLOS ONE | www.plosone.org cultures were fixed and immunolabeled with antibodies to the HCoV-HKU1 spike glycoprotein to identify infected cells. In summary, HCoV-HKU1 can infect, be serially propagated, and induce an anti-viral response in human alveolar type II cells maintained at an air-liquid interface. abstract: Because they are the natural target for respiratory pathogens, primary human respiratory epithelial cells provide the ideal in vitro system for isolation and study of human respiratory viruses, which display a high degree of cell, tissue, and host specificity. Human coronavirus HKU1, first discovered in 2005, has a worldwide prevalence and is associated with both upper and lower respiratory tract disease in both children and adults. Research on HCoV-HKU1 has been difficult because of its inability to be cultured on continuous cell lines and only recently it was isolated from clinical specimens using primary human, ciliated airway epithelial cells. Here we demonstrate that HCoV-HKU1 can infect and be serially propagated in primary human alveolar type II cells at the air-liquid interface. We were not able to infect alveolar type I-like cells or alveolar macrophages. Type II alveolar cells infected with HCoV-HKU1 demonstrated formation of large syncytium. At 72 hours post inoculation, HCoV-HKU1 infection of type II cells induced increased levels of mRNAs encoding IL29,CXCL10, CCL5, and IL-6 with no significant increases in the levels of IFNβ. These studies demonstrate that type II cells are a target cell for HCoV-HKU1 infection in the lower respiratory tract, that type II alveolar cells are immune-competent in response to infection exhibiting a type III interferon and proinflammatory chemokine response, and that cell to cell spread may be a major factor for spread of infection. Furthermore, these studies demonstrate that human alveolar cells can be used to isolate and study novel human respiratory viruses that cause lower respiratory tract disease. url: https://www.ncbi.nlm.nih.gov/pubmed/23894604/ doi: 10.1371/journal.pone.0070129 id: cord-000959-nk2thkme author: Downer, Eric J. title: Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date: 2013-05-06 words: 5396.0 sentences: 268.0 pages: flesch: 48.0 cache: ./cache/cord-000959-nk2thkme.txt txt: ./txt/cord-000959-nk2thkme.txt summary: METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The purpose of the study was to compare the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and the response of these cells to LPS in samples prepared from the LP cohort and a cohort which we classified as IQ memory-consistent (high-performing, HP) individuals. P) TLR4 expression on CD11b + MDMs was increased in the LP group compared with the HP group (P,0.05) and this is also shown in the representative dot plots of TLR4 + cells ( and following LPS stimulation [6] , while pro-inflammatory cytokine [52] and chemokine [53, 54] levels are elevated in peripheral blood monocytes isolated from the elderly after LPS stimulation. abstract: BACKGROUND: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). RESULTS: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. INTERPRETATION: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646027/ doi: 10.1371/journal.pone.0063194 id: cord-354763-odzrco6q author: Drake, John M. title: Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore date: 2006-12-20 words: 5739.0 sentences: 283.0 pages: flesch: 46.0 cache: ./cache/cord-354763-odzrco6q.txt txt: ./txt/cord-354763-odzrco6q.txt summary: We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. We also retrospectively explore the effect of societal learning during the 2003 outbreak of SARS in Singapore, using weekly data on the time between onset of symptoms and removal of infectious individuals. Finally, we discuss societal and epidemiological factors that might affect societal learning, we observe that a difficult task during the early stages of an outbreak is to estimate the learning rate and suggest that the rate estimated here might be used as prior information in future outbreaks, and we conclude by recommending rapid investment in research at the time of initial detection when actions taken to reduce disease spread can be most efficient and cost effective. abstract: BACKGROUND: Rapid response to outbreaks of emerging infectious diseases is impeded by uncertain diagnoses and delayed communication. Understanding the effect of inefficient response is a potentially important contribution of epidemic theory. To develop this understanding we studied societal learning during emerging outbreaks wherein patient removal accelerates as information is gathered and disseminated. METHODS AND FINDINGS: We developed an extension of a standard outbreak model, the simple stochastic epidemic, which accounts for societal learning. We obtained expressions for the expected outbreak size and the distribution of epidemic duration. We found that rapid learning noticeably affects the final outbreak size even when learning exhibits diminishing returns (relaxation). As an example, we estimated the learning rate for the 2003 outbreak of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation during the first eight weeks of the outbreak was inconclusive. We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. By contrast, the expected outbreak size for societal learning twice as effective was 116 cases. CONCLUSION: These results show that the rate of societal learning can greatly affect the final size of disease outbreaks, justifying investment in early warning systems and attentiveness to disease outbreak by both government authorities and the public. We submit that the burden of emerging infections, including the risk of a global pandemic, could be efficiently reduced by improving procedures for rapid detection of outbreaks, alerting public health officials, and aggressively educating the public at the start of an outbreak. url: https://www.ncbi.nlm.nih.gov/pubmed/17183647/ doi: 10.1371/journal.pone.0000020 id: cord-268524-lr51ubz5 author: Droit-Volet, Sylvie title: Time and Covid-19 stress in the lockdown situation: Time free, «Dying» of boredom and sadness date: 2020-08-10 words: 5266.0 sentences: 262.0 pages: flesch: 56.0 cache: ./cache/cord-268524-lr51ubz5.txt txt: ./txt/cord-268524-lr51ubz5.txt summary: This time experience was not explained by the levels of perceived stress or anxiety, although these were considerable, but rather by the increase in boredom and sadness felt in the lockdown situation. The aim of the present study was thus to conduct a scale survey on a large sample of an as yet untested population-French people-in order to assess not only the perceived stress related to Covid-19 but also the emotions (happiness, boredom, arousal) felt during as compared to before the lockdown and their links to the subjective experience of time. There is thus a risk in this period of pandemic that the chronic stress related to Covid-19 and its corollaries (anxiety, fear of death) are particularly high and therefore impact the subjective experience of time by speeding up the perceived passage of time. abstract: A lockdown of people has been used as an efficient public health measure to fight against the exponential spread of the coronavirus disease (Covid-19) and allows the health system to manage the number of patients. The aim of this study (clinicaltrials.gov NCT 0430818) was to evaluate the impact of both perceived stress aroused by Covid-19 and of emotions triggered by the lockdown situation on the individual experience of time. A large sample of the French population responded to a survey on their experience of the passage of time during the lockdown compared to before the lockdown. The perceived stress resulting from Covid-19 and stress at work and home were also assessed, as were the emotions felt. The results showed that people have experienced a slowing down of time during the lockdown. This time experience was not explained by the levels of perceived stress or anxiety, although these were considerable, but rather by the increase in boredom and sadness felt in the lockdown situation. The increased anger and fear of death only explained a small part of variance in the time judgment. The conscious experience of time therefore reflected the psychological difficulties experienced during lockdown and was not related to their perceived level of stress or anxiety. url: https://doi.org/10.1371/journal.pone.0236465 doi: 10.1371/journal.pone.0236465 id: cord-259771-653opx0h author: Dwivedi, Varun title: Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs date: 2012-12-11 words: 5900.0 sentences: 290.0 pages: flesch: 45.0 cache: ./cache/cord-259771-653opx0h.txt txt: ./txt/cord-259771-653opx0h.txt summary: In a pre-challenge study, intranasal delivery of Nano-KAg resulted in induction of innate immune response at both mucosal and systemic sites, indicated by a significant increase in the frequency of NK cells, DCs, and cd T cells in the lung MNC ( Figure 2 , A-C); and cd T cells and DCs in the PBMC compared to K-Ag vaccinated pigs (Figure 2, H & I) . Lung homogenates of Nano-KAg immunized pigs contained significantly higher levels of virus specific IgA and IgG antibodies compared to unvaccinated and K-Ag vaccinated, MN184 challenged pigs (Figure 4, A & B) . The frequency of cd T cells and CD4 + (but not CD8 + ) T cells in the lungs of Nano-KAg vaccinated animals were significantly increased compared to K-Ag and unvaccinated, virus challenged pigs ( Figure 5 , D, E & F). abstract: Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV). We entrapped PLGA [poly (lactide-co-glycolides)] nanoparticles with killed PRRSV antigens (Nano-KAg) and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses. In a virulent heterologous PRRSV challenge study, Nano-KAg vaccine significantly reduced the lung pathology and viremia, and the viral load in the lungs. Immunologically, enhanced innate and adaptive immune cell population and associated cytokines with decreased secretion of immunosuppressive mediators were observed at both mucosal sites and blood. In summary, we demonstrated the benefits of intranasal delivery of nanoparticle-based viral vaccine in eliciting cross-protective immune response in pigs, a potential large animal model. url: https://www.ncbi.nlm.nih.gov/pubmed/23240064/ doi: 10.1371/journal.pone.0051794 id: cord-352720-z1cvjc2y author: Díaz-Corvillón, Pilar title: Routine screening for SARS CoV-2 in unselected pregnant women at delivery date: 2020-09-29 words: 4061.0 sentences: 244.0 pages: flesch: 49.0 cache: ./cache/cord-352720-z1cvjc2y.txt txt: ./txt/cord-352720-z1cvjc2y.txt summary: While initial evidence suggests that pregnant women were not at increased risk for COVID-19, neither developed a more severe disease compared to non-pregnant adults [3, 4] , recent reports suggest increased rates of preterm birth [5] , pneumonia and intensive care unit admission [6] , and maternal mortality [6, 7] . The main objective of this study was to assess point-prevalence of SARS CoV-2 infection in unselected obstetrical population at the time of delivery and to describe the presentation and clinical evolution of confirmed cases. women were screened for COVID-19 clinical symptoms including fever, cough and shortness of breath by trained personnel, and RT-PCR for SARS CoV-2 (Allplex TM 2019-nCoV Assay [17] ) was performed by nasopharyngeal swab, unless a prior test with no more than 48 hours to admission was reported. abstract: BACKGROUND: South America has become the epicenter of coronavirus pandemic. It seems that asymptomatic population may contribute importantly to the spread of the disease. Transmission from asymptomatic pregnant patients’ needs to be characterized in larger population cohorts and symptom assessment needs to be standardized. OBJECTIVE: To assess the prevalence of SARS CoV-2 infection in an unselected obstetrical population and to describe their presentation and clinical evolution. METHODS: A cross-sectional study was designed. Medical records of pregnant women admitted at the Obstetrics & Gynecology department of Clínica Dávila for labor & delivery, between April 27(th) and June 7(th), 2020 were reviewed. All patients were screened with RT-PCR for SARS CoV-2 at admission. After delivery, positive cases were inquired by the researchers for clinical symptoms presented before admission and clinical evolution. All neonates born from mothers with confirmed SARS CoV-2 were isolated and tested for SARS CoV-2 infection. RESULTS: A total of 586 patients were tested for SARS CoV-2 during the study period. Outcomes were obtained from 583 patients which were included in the study. Thirty-seven pregnant women had a positive test for SARS CoV-2 at admission. Cumulative prevalence of confirmed SARS CoV-2 infection was 6.35% (37/583) [CI 95%: 4.63–8.65]. From confirmed cases, 43.2% (16/37) were asymptomatic. From symptomatic patients 85.7% (18/21) had mild symptoms and evolved without complications and 14.3% (3/21) presented severe symptoms requiring admission to intensive care unit. Only 5.4% (2/37) of the neonates born to mothers with a positive test at admission had a positive RT-PCR for SARS CoV-2. CONCLUSION: In our study nearly half of pregnant patients with SARS CoV-2 were asymptomatic at the time of delivery. Universal screening, in endemic areas, is necessary for adequate patient isolation, prompt neonatal testing and targeted follow-up. url: https://www.ncbi.nlm.nih.gov/pubmed/32991621/ doi: 10.1371/journal.pone.0239887 id: cord-012967-w1oc0wdd author: Eberle, Jaelyn J. title: Using tooth enamel microstructure to identify mammalian fossils at an Eocene Arctic forest date: 2020-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lower Eocene (Wasatchian-aged) sediments of the Margaret Formation on Ellesmere Island in Canada’s High Arctic preserve evidence of a rainforest inhabited by alligators, turtles, and a diverse mammalian fauna. The mammalian fossils are fragmentary and often poorly preserved. Here, we offer an alternative method for their identification. Among the best preserved and extensive of the Eocene Arctic forests is the Strathcona Fiord Fossil Forest, which contains permineralized in situ tree stumps protruding from a prominent coal seam, but a paucity of vertebrate fossils. In 2010 and 2018, we recovered mammalian tooth fragments at the fossil forest, but they are so incomplete as to be undiagnostic by using their external morphology. We used a combination of light microscopy and SEM analysis to study the enamel microstructure of two tooth fragments from the fossil forest—NUFV2092B and 2092E. The results of our analysis indicate that NUFV2092B and 2092E have Coryphodon-enamel, which is characterized by vertical bodies that manifest as bands of nested chevrons or treelike structures visible in the tangential section under light microscopy. This enamel type is not found in other mammals known from the Arctic. Additionally, when studied under SEM, the enamel of NUFV2092B and 2092E has rounded prisms that open to one side and are surrounded by interprismatic matrix that is nearly parallel to the prisms, which also occurs in Coryphodon enamel, based on prior studies. The tooth fragments reported here, along with some poorly preserved bone fragments, thus far are the only documented vertebrate fossils from the Strathcona Fiord Fossil Forest. However, fossils of Coryphodon occur elsewhere in the Margaret Formation, so its presence at the fossil forest is not surprising. What is novel in our study is the way in which we identified the fossils using their enamel microstructure. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511010/ doi: 10.1371/journal.pone.0239073 id: cord-319706-2e9jrv0s author: Ebinger, Joseph E. title: Pre-existing traits associated with Covid-19 illness severity date: 2020-07-23 words: 4904.0 sentences: 219.0 pages: flesch: 40.0 cache: ./cache/cord-319706-2e9jrv0s.txt txt: ./txt/cord-319706-2e9jrv0s.txt summary: For all patients considered to have Covid-19, based on direct or documented laboratory test result and suggestive signs and/or symptoms, we obtained information from the electronic health record (EHR) and verified data for the following demographic and clinical characteristics: age at the time of diagnosis; sex; race; ethnicity; smoking status defined as current versus prior, never, or unknown; comorbidities, including obesity, as clinically assessed and documented by a provider with ICD-10 coding; and, chronic use of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) medications. For the primary outcome of illness severity, categorized by escalating levels of care (i.e., hospitalization, intensive care, intubation), the pre-existing characteristics that demonstrated statistical significance in age-and sex-adjusted models included older age, male sex, African American race, obesity, hypertension, diabetes mellitus, and the Elixhauser comorbidity score ( Table 2 ; Fig 3) . abstract: IMPORTANCE: Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear. OBJECTIVE: To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection. DESIGN: Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation. SETTING: A large, multihospital healthcare system in Southern California. PARTICIPANTS: All patients with confirmed Covid-19 infection (N = 442). RESULTS: Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P = 0.001), African American (OR 2.1, P = 0.011), obese (OR 2.0, P = 0.021), with diabetes mellitus (OR 1.8, P = 0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (P(interaction)<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P = 0.003) irrespective of age, race, or morbidity profile. CONCLUSIONS AND RELEVANCE: In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings. url: https://doi.org/10.1371/journal.pone.0236240 doi: 10.1371/journal.pone.0236240 id: cord-262345-hti1jjpn author: Eddy, Lucy H. title: The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review date: 2020-08-25 words: 8728.0 sentences: 470.0 pages: flesch: 50.0 cache: ./cache/cord-262345-hti1jjpn.txt txt: ./txt/cord-262345-hti1jjpn.txt summary: title: The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review METHODS: A pre-search of ''fundamental movement skills'' OR ''fundamental motor skills'' in seven online databases (PubMed, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, EBSCO SPORTDiscus, Ovid PsycINFO and Web of Science) identified 24 assessment tools for school-aged children that: (i) assess FMS; (ii) measure actual motor competence and (iii) evaluate performance on a standard battery of tasks. The psychometric properties of observational assessments of fundamental movement skills for school children correlations to evaluate the concurrent validity between the MOT 4-6 and the KTK, with results showing moderate correlations for children aged 5-6 (mean r = .63), as was hypothesised prior to testing (r >. abstract: BACKGROUND: Fundamental Movement Skills (FMS) play a critical role in ontogenesis. Many children have insufficient FMS, highlighting the need for universal screening in schools. There are many observational FMS assessment tools, but their psychometric properties are not readily accessible. A systematic review was therefore undertaken to compile evidence of the validity and reliability of observational FMS assessments, to evaluate their suitability for screening. METHODS: A pre-search of ‘fundamental movement skills’ OR ‘fundamental motor skills’ in seven online databases (PubMed, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, EBSCO SPORTDiscus, Ovid PsycINFO and Web of Science) identified 24 assessment tools for school-aged children that: (i) assess FMS; (ii) measure actual motor competence and (iii) evaluate performance on a standard battery of tasks. Studies were subsequently identified that: (a) used these tools; (b) quantified validity or reliability and (c) sampled school-aged children. Study quality was assessed using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklists. RESULTS: Ninety studies were included following the screening of 1863 articles. Twenty-one assessment tools had limited or no evidence to support their psychometric properties. The Test of Gross Motor Development (TGMD, n = 34) and the Movement Assessment Battery for Children (MABC, n = 37) were the most researched tools. Studies consistently reported good evidence for validity, reliability for the TGMD, whilst only 64% of studies reported similarly promising results for the MABC. Twelve studies found good evidence for the reliability and validity of the Bruininks-Oseretsky Test of Motor Proficiency but poor study quality appeared to inflate results. Considering all assessment tools, those with promising psychometric properties often measured limited aspects of validity/reliability, and/or had limited feasibility for large scale deployment in a school-setting. CONCLUSION: There is insufficient evidence to justify the use of any observational FMS assessment tools for universal screening in schools, in their current form. url: https://www.ncbi.nlm.nih.gov/pubmed/32841268/ doi: 10.1371/journal.pone.0237919 id: cord-000868-vnwpzsu8 author: Eissmann, Kristin title: HIV-1 Fusion Is Blocked through Binding of GB Virus C E2D Peptides to the HIV-1 gp41 Disulfide Loop date: 2013-01-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551756/ doi: 10.1371/journal.pone.0054452 id: cord-323330-ghwhgkdm author: Ekundayo, Temitope Cyrus title: A global bibliometric analysis of Plesiomonas-related research (1990 – 2017) date: 2018-11-29 words: 4900.0 sentences: 279.0 pages: flesch: 40.0 cache: ./cache/cord-323330-ghwhgkdm.txt txt: ./txt/cord-323330-ghwhgkdm.txt summary: Here, we carried out a bibliometric survey that aimed to examine publication trends in Plesiomonas-related research by time and place, international collaborative works, identify gaps and suggest directions for future research. The articles were evaluated in terms of annual and country-specific output, theme, domain clusters, international collaboration networks, citations, topical evolution related to keywords and co-occurrence networks, co-authorship, and funding. We used the search term "Plesiomonas shigelloides" to identify primary research articles published between 1990 and 2017. Health emergencies (e.g., outbreaks of infection) relating to emerging viral pathogens including Zika and Chikungunya viruses have driven the generation of new scientific knowledge, resulting in a significant increase in the number of research articles on these subjects [68] . The United States and Sweden dominated the list of top 20 countries most actively researching Plesiomonas in terms of numbers of articles and citations. abstract: Plesiomonas shigelloides is an emerging pathogen with damaging effects on human health such as gastroenteritis and extraintestinal infections. Here, we carried out a bibliometric survey that aimed to examine publication trends in Plesiomonas-related research by time and place, international collaborative works, identify gaps and suggest directions for future research. The search term “Plesiomonas shigelloides” was used to retrieve articles published between 1990 and 2017 from the Web of Science database. Only primary research articles were included in the analysis. A total of 155 articles were published within the survey period, with an average of 5.54±2.66 articles per year and an annual growth rate of −0.8%. Research output peaked in 2000 and 2006 (each accounting for 7.7% of the total). The United States ranked first in terms of numbers of articles (n = 29, 18.1%) and total citations (n = 451). Cameroon, Canada, Cuba, Switzerland and Turkey co-shared the 10(th) position each with 2 articles (1.3%). Research collaboration was low (collaboration index = 3. 32). In addition to Plesiomonas shigelloides (n = 82, 52.9%), the top Authors Keywords and research focus included lipopolysaccharide and nuclear magnetic resonance (n = 13, 8.4%). Diarrhea (n = 43, 27.7%), Aeromonas species (n = 41, 26.5%) and infections (n = 31, 20.0%) were also highly represented in Keywords-Plus. Authors’ collaborations and coupling networks formed two mega-clusters which nodes were shared solely by authors from high-income countries. The common conceptual framework in retrieved articles determined by K-means clustering revealed three clusters with sizes of 7, 16, and 29, representing research responses focused on extraintestinal and gastroenteritis, P. shigelloides lipopolysaccharide structure, and co-infections, respectively. Our bibliometric analysis revealed a global diminishing research in Plesiomonas; greater research outcomes from high-income countries compared to others and low collaboration with developing countries. url: https://doi.org/10.1371/journal.pone.0207655 doi: 10.1371/journal.pone.0207655 id: cord-302529-43pd2qsp author: El Moussi, Awatef title: Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia date: 2013-09-19 words: 3251.0 sentences: 163.0 pages: flesch: 45.0 cache: ./cache/cord-302529-43pd2qsp.txt txt: ./txt/cord-302529-43pd2qsp.txt summary: METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses'' infection during three seasons in Tunisia. A subset of sentinel primary care physicians participating in virological surveillance schemes in the community submits respiratory samples for virological testing from patients presenting in primary health care with an ILI, as well as all regional emergency centres and hospitals that take on surveillance of influenza from community, hospitalized and fatal cases. Phylogenetic analysis of the HA1 nucleotid sequence of 23 influenza A(H1N1)pdm09 viruses from mild, severe (patients hospitalized with severe pneumonia and severe acute respiratory syndrome) and fatal cases, shows that all viruses characterised in Tunisia during season 2009-2010 were outside the seven genetic groups described in the European Centre for Disease Prevention and Control (ECDC) report [19] . abstract: BACKGROUND: The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. OBJECTIVE: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. RESULTS: The 2008–09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010–11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). CONCLUSION: This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases. url: https://www.ncbi.nlm.nih.gov/pubmed/24069267/ doi: 10.1371/journal.pone.0074064 id: cord-312678-81gnmxbk author: Elayeh, Eman title: Before and after case reporting: A comparison of the knowledge, attitude and practices of the Jordanian population towards COVID-19 date: 2020-10-15 words: 5442.0 sentences: 266.0 pages: flesch: 52.0 cache: ./cache/cord-312678-81gnmxbk.txt txt: ./txt/cord-312678-81gnmxbk.txt summary: Our research group initiated a study to ascertain the knowledge, attitude and practices (KAP) of Jordanians toward COVID-19 prior to any initial case report in Jordan. Therefore, the initial aim of this study was to evaluate the overall knowledge, attitude and practices (KAP) of Jordanian citizens to the ongoing international situation regarding the emergence and pandemic nature of COVID-19. where N is the sample size, Zα: type one error = 1.96 when α = 5%; Zβ: type two error = 1.28 when β = 10%; Q = 1-P: expected non-prevalence; P = proportion in the population possessing the characteristic of interest (based on the estimate that 50% of the respondents knew general information about COVID-19, its routes of transmission and the main preventative measures), d = one-half of the desired interval of confidence, in this study d = 5%. abstract: Coronavirus disease- 2019 (COVID-19) is an emerging contagious infectious disease. It is pandemic and has affected more than 21 million people and resulted in more than 750,000 deaths worldwide (https://www.worldometers.info/coronavirus/#countries; 14/08/20). Our research group initiated a study to ascertain the knowledge, attitude and practices (KAP) of Jordanians toward COVID-19 prior to any initial case report in Jordan. This project was underway when the first Jordanian case was reported. We extended our study to identify how case reporting would alter public KAP towards COVID-19. This cross-sectional study randomly selected and recruited 2104 Jordanian adults. A four-section questionnaire was devised to address the sociodemographic characteristics of the subjects and their KAP toward COVID-19. The mean knowledge score for the study population was 15.9 ± 2.2 (out of the 20 knowledge questions), with 60.9% of the participants having good knowledge about COVID-19. Participants’ practices to prevent transmission of COVID-19 were adequate in more than 60% of participants. Most participants had positive attitudes regarding their role in preventing COVID-19 and many of the participants’ attitudes and practices changed to more appropriate ones after reporting the first case of COVID-19 in Jordan. The percentage of participants who trust the government in confronting COVID-19 increased significantly (p value < 0.001). However, one alarming and unexpected finding was that the prevention practice score of participants working in the medical field was similar to those from the general population. This may necessitate stricter training and guidelines for this group who will be in the frontline in combating the disease. Impact of this study: The data generated from this study shows that when cases of disease were reported, the public’s attitudes and practices improved in many aspects, and that confidence in the government to contain the disease was boosted. We believe that this study is important in allowing other, international governments to develop an understanding of public KAP during pandemic disease outbreaks. url: https://doi.org/10.1371/journal.pone.0240780 doi: 10.1371/journal.pone.0240780 id: cord-333248-5342lyeu author: Elenius, Varpu title: The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response date: 2017-02-24 words: 3309.0 sentences: 206.0 pages: flesch: 45.0 cache: ./cache/cord-333248-5342lyeu.txt txt: ./txt/cord-333248-5342lyeu.txt summary: We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T celland innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. We studied how serum vitamins and antimicrobial peptide LL-37 levels and allergic and tonsillar diseases were associated with direct in vivo detection of respiratory viruses and T cell subset-related transcription factors, cytokines as well as type I, II and III interferons in tonsils. The associations of serum levels of vitamins and LL-37, allergy status and virus detection with intratonsillar cytokine and transcription factor expressions were analyzed using univariable and age-adjusted linear regression. This study provides new insights into connections between serum levels of vitamins A, D, and E and antimicrobial peptide LL-37 and several important outcomes: allergy, respiratory virus detection and tonsillar immune responses. abstract: BACKGROUND: Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. METHODS: 110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR. RESULTS: The median age of the patients was 16 years (range 3–60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05). CONCLUSIONS: Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects. url: https://doi.org/10.1371/journal.pone.0172350 doi: 10.1371/journal.pone.0172350 id: cord-004017-gcmpatlb author: Errecaborde, Kaylee Myhre title: Factors that enable effective One Health collaborations - A scoping review of the literature date: 2019-12-04 words: 9215.0 sentences: 458.0 pages: flesch: 34.0 cache: ./cache/cord-004017-gcmpatlb.txt txt: ./txt/cord-004017-gcmpatlb.txt summary: The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment). In this study, a multidisciplinary team of researchers reviewed a broad scope of literature describing collaborative and multi-sectoral approaches to past health events to understand how such collaborations are commonly described and evaluated and to identify and synthesize enabling factors for One Health collaborations. Starting condition factors reported to enable collaboration at the network level included network structures, existing relationships, available resources in the face of a health event, and the political environment in place to support these efforts. abstract: Advocates for a One Health approach recognize that global health challenges require multidisciplinary collaborative efforts. While past publications have looked at interdisciplinary competency training for collaboration, few have identified the factors and conditions that enable operational One Health. Through a scoping review of the literature, a multidisciplinary team of researchers analyzed peer-reviewed publications describing multisectoral collaborations around infectious disease-related health events. The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment). The researchers also identified the stage of collaboration during which these factors were most critical, further organizing into starting condition or process-based factors. The research found that publications on multisectoral collaboration for health events do not uniformly report on successes or challenges of collaboration and rarely identify outputs or outcomes of the collaborative process. This paper proposes a common language and framework to enable more uniform reporting, implementation, and evaluation of future One Health collaborations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892547/ doi: 10.1371/journal.pone.0224660 id: cord-306278-c4q4la5c author: Esposito, Susanna title: Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014 date: 2016-04-05 words: 4660.0 sentences: 220.0 pages: flesch: 48.0 cache: ./cache/cord-306278-c4q4la5c.txt txt: ./txt/cord-306278-c4q4la5c.txt summary: To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. To evaluate the circulation of the different HAdV types and the possible relationship between viral load, viral genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children consecutively attending the Emergency Room of the Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection. However, further studies are needed to identify the potential pathogenetic role of the different species and types of HAdV and the importance of viral load in the severity of infection. abstract: To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain reaction; their nucleotides were sequenced, and they were tested for positive selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV. HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in association with one other virus in 25 (41.0%) cases and with two or more viruses in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial virus were the most common co-infecting viral agents and were found in 12 (19.7%) and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed were highly conserved. In comparison to HAdV-negative children, those infected with HAdV had a reduced frequency of lower respiratory tract involvement (36.1% vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 ± 7,737 vs 9,565 ± 3,211 cells/μL; p = 0.04), respectively, in children infected by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%) but difference did not reach statistical significant (p = 0.21). Children with high viral load were absent from child care attendance for a longer period of time (14.5 ± 7.5 vs 5.5 ± 3.2 days; p = 0.002) and had higher C reactive protein levels (41.3 ± 78.5 vs 5.4 ± 9.6 μg/dL; p = 0.03). This study has shown that HAdV infections are diagnosed more commonly than usually thought and that HAdVs are stable infectious agents that do not frequently cause severe diseases. A trend toward more complex disease in cases due to HAdV species C and in those with higher viral load was demonstrated. However, further studies are needed to clarify factors contributing to disease severity to understand how to develop adequate preventive and therapeutic measures. url: https://www.ncbi.nlm.nih.gov/pubmed/27045588/ doi: 10.1371/journal.pone.0152375 id: cord-347014-88zmtky7 author: Esposito, Susanna title: Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia date: 2016-11-15 words: 5518.0 sentences: 247.0 pages: flesch: 44.0 cache: ./cache/cord-347014-88zmtky7.txt txt: ./txt/cord-347014-88zmtky7.txt summary: STUDY DESIGN: This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. CONCLUSIONS: This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard. A global evaluation of the results of this study seemed to indicate that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels are unable to differentiate bacterial from viral diseases or to identify severe cases. abstract: STUDY DESIGN: This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels. METHODS: This prospective, multicenter study was carried out in the most important children’s hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease. RESULTS: CRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%). CONCLUSIONS: This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard. url: https://doi.org/10.1371/journal.pone.0163262 doi: 10.1371/journal.pone.0163262 id: cord-001120-fxd533b4 author: Everitt, Aaron R. title: Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model date: 2013-11-21 words: 4874.0 sentences: 252.0 pages: flesch: 47.0 cache: ./cache/cord-001120-fxd533b4.txt txt: ./txt/cord-001120-fxd533b4.txt summary: We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. Here we sought therefore to expand and define the role of Ifitm3 in pathogen restriction by assessing the susceptibility of Ifitm3-deficient (Ifitm3 -/-) mice to bacteria (Salmonella Typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis), a parasite (Plasmodium berghei) and a virus (respiratory syncytial virus, RSV) to determine the specificity of this crucial antimicrobial protein. Similarly, bacterial counts revealed no significant differences between wild type and Ifitm3 -/-mice; together showing that Ifitm3 does not play a role in resistance or susceptibility to Salmonella infection. The experimental challenge revealed there to be no significant difference in phenotype seen in Ifitm3 -/-mice compared with wild type littermate controls, with both showing susceptibility to ECM ( Figure 5A ). abstract: The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836756/ doi: 10.1371/journal.pone.0080723 id: cord-002426-5e1xn7kj author: Falcón-Lezama, Jorge Abelardo title: Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico date: 2017-02-22 words: 5944.0 sentences: 261.0 pages: flesch: 49.0 cache: ./cache/cord-002426-5e1xn7kj.txt txt: ./txt/cord-002426-5e1xn7kj.txt summary: MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority''s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Sample: 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with age older than 12, and residents in Axochiapan, Morelos State, México, were selected from the cohort "Peridomestic infection as determinant for Dengue virus transmission" [13] . abstract: INTRODUCTION: Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. RESULTS: Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321279/ doi: 10.1371/journal.pone.0172313 id: cord-268977-hcg2rrhl author: Feikin, Daniel R. title: Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007–2010 date: 2012-08-24 words: 6440.0 sentences: 402.0 pages: flesch: 53.0 cache: ./cache/cord-268977-hcg2rrhl.txt txt: ./txt/cord-268977-hcg2rrhl.txt summary: METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings. Compared with other regions, the mortality rate among older children and adults remains several-fold higher in sub-Saharan Africa, where acute respiratory infections (ARI) are a leading cause of this high mortality, as well as associated morbidity [1] . abstract: BACKGROUND: Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings. url: https://www.ncbi.nlm.nih.gov/pubmed/22937071/ doi: 10.1371/journal.pone.0043656 id: cord-000947-psguw47w author: Feng, Jianyu title: A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation date: 2013-04-24 words: 4685.0 sentences: 270.0 pages: flesch: 54.0 cache: ./cache/cord-000947-psguw47w.txt txt: ./txt/cord-000947-psguw47w.txt summary: We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. To elucidate why scFv-A4 had the chaperone-like function, we combined computer modeling and peptide array membrane technique to study the interactions between scFv-A4 and HCK. Firstly, bioinformatics software tools were used to predict the interacting sites between scFv-A4 and HCK and then the results were combined with the peptide array membrane experiment results to build the 3D models of the binding complex. In complex model-I, scFv-A4 exhibits chaperone-like function by assisting the folding of HCK and stabilizing the whole structure. In this study we combined computer modeling and the peptide array membrane method to investigate the interaction between scFv-A4 and HCK. abstract: A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634753/ doi: 10.1371/journal.pone.0062147 id: cord-294568-12eyo13f author: Fernandes-Matano, Larissa title: Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico date: 2017-05-03 words: 4930.0 sentences: 240.0 pages: flesch: 45.0 cache: ./cache/cord-294568-12eyo13f.txt txt: ./txt/cord-294568-12eyo13f.txt summary: Influenza viruses are one of the main causative agents of ARIs worldwide; however, many other respiratory viruses for which insufficient epidemiological information is available can also cause ARIs. Studies performed at the international level have frequently identified human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), influenza virus (flu), human mastadenovirus (HMdV), rhinovirus (RV), and enterovirus (EV) and less frequently identified human metapneumovirus (HMPV), primate bocaparvovirus (PBpV), and human coronavirus (HCoV) [12] . Therefore, the objective of this study was to determine the viral aetiology of these infections and to analyse the behaviour of non-influenza respiratory viruses in the Mexican population. The importance of the differential diagnosis of other respiratory viruses in samples with negative influenza results becomes apparent when we observe the prevalence of the three main viruses identified in this study as well as their associations with severe cases and deaths, especially in the child population. abstract: BACKGROUND: Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. METHODS: This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. RESULTS: The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of co-infection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age. CONCLUSION: In this study, we identified 13 non-influenza respiratory viruses that could occur in any season of the year. This study provides evidence for the prevalence and seasonality of a wide range of respiratory viruses that circulate in Mexico and constitute a risk for the population. Additionally, our data suggest that including these tests more widely in the diagnostic algorithm for influenza may reduce the use of unnecessary antibiotics, reduce the hospitalisation time, and enrich national epidemiological data with respect to the infections caused by these viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/28467515/ doi: 10.1371/journal.pone.0176298 id: cord-341914-l2bomgji author: Flies, Andrew S. title: Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity date: 2015-10-07 words: 6626.0 sentences: 297.0 pages: flesch: 44.0 cache: ./cache/cord-341914-l2bomgji.txt txt: ./txt/cord-341914-l2bomgji.txt summary: Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis. A more robust understanding of the effects of ecological variables such as pathogen exposure on immune function might be gained by studying immune function in non-traditional species, and assessing how basic immune defenses differ between wild and captive animals with similar genetic backgrounds. abstract: Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis. url: https://doi.org/10.1371/journal.pone.0137679 doi: 10.1371/journal.pone.0137679 id: cord-000425-isw6jeir author: Flori, Laurence title: Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date: 2011-07-29 words: 7831.0 sentences: 388.0 pages: flesch: 46.0 cache: ./cache/cord-000425-isw6jeir.txt txt: ./txt/cord-000425-isw6jeir.txt summary: A study on Yorkshire pigs selected for eight generations for high and low adaptive IR (HIR and LIR, respectively) on an index combining four standardized measures of specific antibodies and cellmediated IR, after stimulation with specific antigens (bacillus Calmette-Guérin and hen egg white lysozyme), has revealed that HIR and LIR animals differ in response to immunization and infection [2, 11, 12, 13, 14] . Finally, several significant QTLs for total leukocyte count ( [20, 21] ; Animal-QTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/index), mitogen-induced proliferation [20] , antibody response [20, 22] , cytokine production (IL10 and IFNc) [23] , complement activity [22] , and acute phase protein serum concentration [22] have been detected and mapped to different pig chromosomes. In this report, we present the results of a global genetic study, combining principal component analysis (PCA), and genetic parameter estimation applied to a large number of innate and adaptive ITs in a pig population vaccinated against Mycoplasma hyopneumoniae (M. abstract: BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs). Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment. METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.10.4) heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146468/ doi: 10.1371/journal.pone.0022717 id: cord-048364-yfn8sy1m author: Fraser, Christophe title: Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic date: 2007-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950082/ doi: 10.1371/journal.pone.0000758 id: cord-294645-yzh8h7zo author: Freeman, David W. title: Association between GDF15, poverty and mortality in urban middle-aged African American and white adults date: 2020-08-07 words: 4977.0 sentences: 221.0 pages: flesch: 43.0 cache: ./cache/cord-294645-yzh8h7zo.txt txt: ./txt/cord-294645-yzh8h7zo.txt summary: Multivariable adjusted Cox regression models were used to assess the association between log-transformed GDF15 (logGDF15) and 12-year mortality outcomes (all-cause, cardiovascularand cancer-specific outcomes) and interactions with sex, race and poverty status. The objectives of the present study were to assess the association between serum GDF15 and all-cause and cause-specific mortality, and to identify interactions between GDF15 and sex, race and poverty status in a large cohort of community-based middle-aged adults recruited from Baltimore, Maryland. In a community-dwelling cohort of younger urban adults (mean age 49.6) with diverse racial and socioeconomic status, we found that elevated serum GDF15 level was strongly associated with all-cause mortality, CVD-and cancer-specific mortality risk. Our findings of increased risk of mortality due to all-causes and CVD and elevated GDF15 levels in a diverse cohort are consistent with results of previous studies conducted in apparently healthy, community-dwelling adults [12-15, 17, 18] . abstract: Mortality disparities are influenced by race and poverty. There is limited information about whether poverty influences biologic markers of mortality risk. Emerging data suggests that growth differentiation factor 15 (GDF15) is associated with mortality; however, the interplay between GDF15, sociodemographic factors and mortality is not known. We sought to evaluate the interactions between GDF15 and sex, race and poverty status on mortality. Serum GDF15 was measured in 1036 African American and white middle-aged men and women above and below 125% of the Federal poverty status from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Multivariable adjusted Cox regression models were used to assess the association between log-transformed GDF15 (logGDF15) and 12-year mortality outcomes (all-cause, cardiovascular- and cancer-specific outcomes) and interactions with sex, race and poverty status. Likelihood ratio tests were used to assess significance of the interaction terms. Median GDF15 was 655.2 pg/mL (IQR = 575.1). During 12.2 years of follow-up, 331 died of which 94 cardiovascular- and 87 were cancer-specific deaths. One unit of increase in logGDF15 was associated with a hazard ratio for all-cause mortality, cardiovascular- and cancer-specific mortality of 2.26 (95% confidence interval [CI], 1.94–2.64), 2.74 (95%CI, 2.06–3.63) and 1.41 (95%CI, 1.00–2.00), respectively. There was an interaction between logGDF15 and poverty status on all-cause mortality (p<0.05). The GDF15×poverty status interaction term improved model calibration for all-cause mortality. Our study provides the first evidence that the effect of elevated GDF15 on all-cause mortality is modified by poverty status. url: https://www.ncbi.nlm.nih.gov/pubmed/32764826/ doi: 10.1371/journal.pone.0237059 id: cord-353869-l53ms3q8 author: Friesen, Robert H. E. title: New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets date: 2010-02-08 words: 4680.0 sentences: 202.0 pages: flesch: 44.0 cache: ./cache/cord-353869-l53ms3q8.txt txt: ./txt/cord-353869-l53ms3q8.txt summary: METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. Mean decline in body weight at the end of the experiment was 6.2% in the group of ferrets that received CR6261 4 hours after challenge ( Figure 2B) , which was significantly less (p = 0.025) than the 10.1% observed in control animals. These findings were in accordance with the observation that the mean lung weights of ferrets treated with CR6261 at 4 hours post challenge were lower compared to the control group (5.7 g versus 14.9 g, p,0.001; Figure 2F ). abstract: BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. url: https://www.ncbi.nlm.nih.gov/pubmed/20161706/ doi: 10.1371/journal.pone.0009106 id: cord-310466-0lbbiq7u author: Fu, Yang-chih title: Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan date: 2012-10-03 words: 4415.0 sentences: 204.0 pages: flesch: 49.0 cache: ./cache/cord-310466-0lbbiq7u.txt txt: ./txt/cord-310466-0lbbiq7u.txt summary: To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation, we collected contact diaries from a representative national sample in Taiwan and extracted realistic parameters for our simulation modeling of disease infections. Our diary-based survey in Taiwan emphasizes the rigorous requirements on both systematic probability sampling and in-person (face-to-face) household interviews to ensure proper inference to the population as a whole. abstract: Recent studies of infectious diseases have attempted to construct more realistic parameters of interpersonal contact patterns from diary-approach surveys. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. A representative sample of 1,943 contact diaries recorded a total of 24,265 wide-range, face-to-face interpersonal contacts during a 24-hour period. Nearly 70% of the contacts occurred outside of respondents' households. The most active age group was schoolchildren (ages 5–14), who averaged around 16–18 daily contacts, about 2–3 times as many as the least active age groups. We show how such parameters of contact patterns help modify a sophisticated national simulation system that has been used for years to model the spread of pandemic diseases in Taiwan. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection. url: https://www.ncbi.nlm.nih.gov/pubmed/23056193/ doi: 10.1371/journal.pone.0045113 id: cord-344357-ocyaqs1y author: Fu, Yue-Qiang title: Effect of blood analysis and immune function on the prognosis of patients with COVID-19 date: 2020-10-30 words: 4482.0 sentences: 277.0 pages: flesch: 58.0 cache: ./cache/cord-344357-ocyaqs1y.txt txt: ./txt/cord-344357-ocyaqs1y.txt summary: INTRODUCTION: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with Coronavirus Disease 2019 (COVID-19). The percentage of neutrophil count > 6.3×10 9 /L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10 9 /L was independently associated with mortality. The percentage of neutrophil count > 6.3×10 9 /L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10 9 /L was independently associated with mortality. Another study also indicated that COVID-19 patients in the death group had significantly lower lymphocyte count on admission than the recovered group [8] . Collected information included: age; gender; concomitant disease; symptoms; hemoglobin; platelet; leukocyte, neutrophil, and lymphocyte counts; CRP, CD3+, CD4+, CD8+, CD4/8, CD19+, and CD16+56+;IgG, IgM, IgA, IgE, C3, and C4 chest CT; alanine aminotransferase, creatinine; arterial blood gas; procalcitonin; and the result of the RT-PCR assay of SARS-CoV-2 RNA. abstract: INTRODUCTION: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with Coronavirus Disease 2019 (COVID-19). METHODS: Records were reviewed of 85 patients admitted with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital death. RESULTS: Fourteen patients died. The baseline leukocyte count, neutrophil count and hemoglobin was significantly higher in non-survivors compared with survivors, while the reverse was true of lymphocyte count, platelet, PaO(2)/FiO(2), CD3+ count and CD4+ count. The percentage of neutrophil count > 6.3×10(9)/L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10(9)/L was independently associated with mortality. However, there were not significant difference in IgG, IgM, IgA, C3, C4 and the percentage of IgE > 100 IU/ml between the death group and survival group. Areas under the receiver operating characteristic curves of the following at baseline could significantly predict mortality: leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts. CONCLUSIONS: For hospitalized patients with COVID-19, lymphocyte, CD3+ and CD4+ counts that marked decrease suggest a poor outcome. Admission neutrophil count > 6.3 ×10(9)/L is independently associated with mortality. At admission, leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts should receive added attention. url: https://www.ncbi.nlm.nih.gov/pubmed/33125396/ doi: 10.1371/journal.pone.0240751 id: cord-257077-cdnkk6ou author: Gabor, Kristin A. title: Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish date: 2013-07-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. Caveolae are integral to numerous signaling pathways and these membrane domains have been previously implicated in viral entry but not antiviral defense. This study shows, for the first time, the importance of spatio-temporal regulation of signaling receptors and the importance of the regulation of clustering for downstream signaling. A novel mechanism for virus evasion of host cell defenses is demonstrated through disruption of clusters of signaling molecules organized within caveolin-rich domains. Viral infection leads to a downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish type I interferon receptor (–R) subunit. Super-resolution microscopy has enabled the first single-molecule imaging of CRFB1 association with cav-1b-containing membrane domains. Strikingly, downregulation of Cav-1b, the major protein component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1 clusters led to a suppressed antiviral immune response both in vitro and in vivo, through abrogation of downstream signaling. This response strongly suggests that CRFB1 organization within cav-1b-containing membrane domains is critical for IFN-mediated antiviral defense and presents a previously undescribed antiviral evasion strategy to alter IFN signaling and the antiviral immune response. url: https://www.ncbi.nlm.nih.gov/pubmed/23874753/ doi: 10.1371/journal.pone.0068759 id: cord-311065-ie3gty6e author: Gaddi, Pamela J. title: IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection date: 2012-08-03 words: 6591.0 sentences: 328.0 pages: flesch: 46.0 cache: ./cache/cord-311065-ie3gty6e.txt txt: ./txt/cord-311065-ie3gty6e.txt summary: Further work has described a role for IL-10 in reducing systemic IFN-c production, CD4+ and CD8+ T cell cytokine responses and viral elimination in the spleen during MCMV infection [28] . The absence of IL-10 during acute MCMV infection results in elevated levels of systemic and local proinflammatory cytokines and chemokines, as well as increased inflammatory cell infiltration into infected livers. MCMV infection in the liver results in increased infiltration of NK cells, T cells and macrophages that contribute to viral clearance through cytokine and chemokine production [20, 23, 27, [38] [39] [40] . Virus-specific CD8+ T cells are recruited to the liver within 4 days of infection and control viral replication through release of cytotoxic molecules and production of cytokines such as IFN-c and TNF-a [18, [21] [22] [23] 26] . abstract: Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/22880122/ doi: 10.1371/journal.pone.0042850 id: cord-000265-llilwq1u author: Gao, Rongbao title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case date: 2010-10-12 words: 4896.0 sentences: 253.0 pages: flesch: 46.0 cache: ./cache/cord-000265-llilwq1u.txt txt: ./txt/cord-000265-llilwq1u.txt summary: Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Although H5N1 virus infection of humans is primarily one of the lower respiratory tract, more recent reports suggested that influenza A H5N1 may in rare, severe cases, disseminate beyond the lungs and infect brain [26, 27] , intestines [20, 27] and lymphoid tissues [27] , and result in extra-pulmonary clinical manifestations including encephalopathy or encephalitis [15, 28] . To better understand the pathogenesis of human H5N1 virus infection, and investigate the route of virus dissemination in vivo, we report on the use of different techniques to detect virus distribution and infection of 5 organ systems in a laboratory confirmed fatal human H5N1 virus infection, and analyze the relationship between viral load in tissues and host response. abstract: Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953511/ doi: 10.1371/journal.pone.0013315 id: cord-000554-p4ufea6x author: Gao, Wei title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date: 2012-01-18 words: 5516.0 sentences: 289.0 pages: flesch: 54.0 cache: ./cache/cord-000554-p4ufea6x.txt txt: ./txt/cord-000554-p4ufea6x.txt summary: title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus We have also observed cross-talk between MAP kinase and NFkB pathways, and our data indicate that MAP kinase ERK1/2 and JNK1/2 may impact the activation of NFkB through the induction of RIG-1, leading to IFN-b induction in H1N1pdm-infected swine macrophages. To understand the mechanism of proinflammatory cytokine and TNF family ligand induction in H1N1pdm-infected swine macrophages, we investigated how MAP kinases were activated and whether their signaling pathways were involved in the regulation of various cytokines and TNF family ligands in pig immune cells. To evaluate the role of MAP kinases in the regulation of proinflammatory cytokine responses in H1N1pdm-infected swine macrophages, we pre-treated 3D/4 cells with specific inhibitors for ERK1/2, p38, and JNK1/2 1 hr prior to infection. abstract: Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261190/ doi: 10.1371/journal.pone.0030328 id: cord-339578-eg19rfvi author: Garcia-Garcia, Maria Luz title: Role of viral coinfections in asthma development date: 2017-12-05 words: 3651.0 sentences: 190.0 pages: flesch: 47.0 cache: ./cache/cord-339578-eg19rfvi.txt txt: ./txt/cord-339578-eg19rfvi.txt summary: OBJECTIVE: Our aim was to compare the frequency of asthma development at 6–8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. CONCLUSIONS: Asthma at 6–8 years is more frequent and severe in those children previously hospitalized with viral coinfection-bronchiolitis compared with those with single infection. Of the 351 children previously admitted with bronchiolitis, with positive viral detection and current age between 6 and 8 years, 244 (52 coinfections and 192 single infections) could be located and agreed to participate in the study. In conclusion, asthma at the age of 6-8 is more frequent and severe in those children previously hospitalized with viral coinfection bronchiolitis compared with those with single infection. Moreover, viral coinfection, allergic rhinitis and older age at admission seem also to be strong independent risk factors for asthma development in children previously hospitalised because of bronchiolitis. abstract: BACKGROUND: Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections. OBJECTIVE: Our aim was to compare the frequency of asthma development at 6–8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. PATIENTS & METHODS: A cross-sectional study was performed in 244 children currently aged 6–8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction) and clinical data were prospectively taken during admission for bronchiolitis. RESULTS: Median current age at follow-up was 7.3 years (IQR: 6.7–8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented “wheezing in the last 12 months”, data that strongly correlate with current prevalence of asthma. “Dry cough at night” was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6–8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459–8.317, p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622–13.318, p<0.001), and viral coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542–7.386, p:0.01). CONCLUSIONS: Asthma at 6–8 years is more frequent and severe in those children previously hospitalized with viral coinfection-bronchiolitis compared with those with single infection. Allergic rhinitis and older age at admission seem also to be strong independent risk factors for asthma development in children previously hospitalised because of bronchiolitis. url: https://www.ncbi.nlm.nih.gov/pubmed/29206851/ doi: 10.1371/journal.pone.0189083 id: cord-278087-0nicp0eq author: García-García, María Luz title: Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study date: 2017-03-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. METHODS AND FINDINGS: A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children’s mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. CONCLUSIONS: HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections. url: https://doi.org/10.1371/journal.pone.0173504 doi: 10.1371/journal.pone.0173504 id: cord-267042-nvwnbp2j author: Gaspard, Philippe title: Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents date: 2019-09-24 words: 5624.0 sentences: 290.0 pages: flesch: 50.0 cache: ./cache/cord-267042-nvwnbp2j.txt txt: ./txt/cord-267042-nvwnbp2j.txt summary: This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). Our objective was to describe GE and RTI infection and all-cause lethality rates according to the individual characteristics of nursing home residents (sex, age, length of stay, autonomy status), and to identify specific susceptibility patterns related to these types of viral outbreaks in these facilities. In the present study, surveillance data obtained during GE and RTI outbreaks in nursing homes were used to construct stratified analyses and to identify specific infection and all-cause lethality rates according to the residents'' individual characteristics. abstract: BACKGROUND: Gastroenteritis (GE) and respiratory tract infection (RTI) outbreaks are a significant issue in nursing homes. This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. METHODS: Clinical and virological surveillance were conducted (2007 to 2018). Virus stratifications for the analysis were: outbreaks with positive norovirus or influenza identifications (respectively NoV+ or Flu+), episodes with no NoV or influenza identification or testing (respectively NoV- or Flu-). Associations between individual variables (sex, age, length of stay (LOS), autonomy status) and infection and lethality rates were tested with univariate and Mantel-Haenszel (MH) methods. RESULTS: 61 GE outbreaks and 76 RTI oubreaks (total 137 outbreaks) were recorded involving respectively 4309 and 5862 residents. In univariate analysis, higher infection rates and age were associated in NoV+, NoV-, and Flu+ contexts, and lower infection rates were associated with longer stays (NoV+ and NoV-). In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). In univariate analysis, lower autonomy status (NoV+, Flu+ and Flu-) and increased age (Flu+) were associated with higher lethality. In MH adjusted analysis, significant OR(age) adjusted for autonomy was: Flu+/ ≥86 years compared with <86 years, 1.97 (1.19–3.25) and OR(autonomy) adjusted for age for the more autonomous group (compared with the less autonomous group) was: Flu+, 0.41 (0.24–0.69); Flu-, 0.42 (0.20, 0.90). CONCLUSION: The residents of nursing homes are increasingly elderly and dependent. The specific infection and lethality risks according to these two factors indicate that surveillance and infection control measures are essential and of high priority. url: https://www.ncbi.nlm.nih.gov/pubmed/31550261/ doi: 10.1371/journal.pone.0222321 id: cord-336843-c0sr3six author: Gerritsen, M. G. title: Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography date: 2017-02-24 words: 4321.0 sentences: 239.0 pages: flesch: 49.0 cache: ./cache/cord-336843-c0sr3six.txt txt: ./txt/cord-336843-c0sr3six.txt summary: title: Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. Two studies comparing LDCT to CXR in patients with persistent febrile neutropenia demonstrated an increased detection of pulmonary abnormalities. The diagnosis of possible IFD in the patient with a negative LDCT scan was based on abnormalities on HRCT made on day 4 of fever. We conducted a prospective study to evaluate whether pulmonary focus detection would improve using a LDCT scan instead of CXR on the first day of febrile neutropenia. [3] In a retrospective study 1083 adult SCT patients were evaluated, but in none of the 242 CXRs performed in asymptomatic patients with febrile neutropenia pulmonary abnormalities indicative of infection were detected. abstract: We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose. url: https://doi.org/10.1371/journal.pone.0172256 doi: 10.1371/journal.pone.0172256 id: cord-000347-gdra8xhj author: Gibbons, Henry S. title: Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant date: 2011-03-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). RESULTS: Archival strains and two “present day” type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype. CONCLUSIONS: Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064580/ doi: 10.1371/journal.pone.0017836 id: cord-001716-lbtdex4p author: Gilca, Rodica title: Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015 date: 2015-07-22 words: 4070.0 sentences: 189.0 pages: flesch: 37.0 cache: ./cache/cord-001716-lbtdex4p.txt txt: ./txt/cord-001716-lbtdex4p.txt summary: Canada''s Sentinel Physician Surveillance Network (SPSN) measured vaccine effectiveness (VE) against medically-attended laboratory-confirmed outpatient A(H3N2) illness of -8% (95%CI:-50-23%) overall and 2% (95%CI:-49-36%) in non-elderly (<65-year-old) adults, indicating little or no vaccine protection even among individuals capable of mounting an effective immune response [2] . Although Canadian mid-season inpatient and outpatient VE findings for the 2014/15 season have been consistent with null vaccine effects (statistically non-significant and spanning zero) in both age groups, the CIRN finding of a lower and negative point estimate of VE against A(H3N2) hospitalization in the elderly, more closely broaching statistical significance, warrants further clarification. Multivariable analyses by logistic regression adjusted for age, underlying comorbidity placing individuals at higher risk of influenza-related complications [13] , interval between symptom onset and specimen collection (4 days, 5-7 days), hospital site, epidemic week based on hospital admission date (49-51, 52, 53 and 1-2), and primary residence (community, LTCF or other institutional/group setting). abstract: BACKGROUND: The 2014/15 influenza season in Canada was characterized by an early epidemic due to vaccine-mismatched influenza A(H3N2) viruses, disproportionately affecting elderly individuals ≥65-years-old. We assessed vaccine effectiveness (VE) against A(H3N2) hospitalization among elderly individuals during the peak weeks of the 2014/15 epidemic in Quebec, Canada. METHODS: Nasal specimens and clinical/epidemiological data were collected within 7 days of illness onset from elderly patients admitted with respiratory symptoms to one of four participating hospitals between November 30, 2014 and January 13, 2015. Cases tested RT-PCR positive for influenza A(H3N2) and controls tested negative for any influenza. VE was assessed by test-negative case-control design. RESULTS: There were 314 participants including 186 cases (62% vaccinated) and 128 controls (59% vaccinated) included in primary VE analysis. Median age was 81.5 years, two-thirds were admitted from the community and 91% had underlying comorbidity. Crude VE against A(H3N2) hospitalization was -17% (95%CI: -86% to 26%), decreasing to -23% (95%CI: -99 to 23%) with adjustment for age and comorbidity, and to -39% (95%CI: -142 to 20%) with additional adjustment for specimen collection interval, calendar time, type of residence and hospital. In sensitivity analyses, VE estimates were improved toward the null with restriction to participants admitted from the community (-2%; 95%CI: -105 to 49%) or with specimen collection ≤4 days since illness onset (- 8%; 95%CI: -104 to 43%) but further from the null with restriction to participants with comorbidity (-51%; 95%CI: -169 to 15%). CONCLUSION: The 2014/15 mismatched influenza vaccine provided elderly patients with no cross-protection against hospitalization with the A(H3N2) epidemic strain, reinforcing the need for adjunct protective measures among high-risk individuals and improved vaccine options. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511737/ doi: 10.1371/journal.pone.0132195 id: cord-291176-evb6yt0r author: Giorgi Rossi, Paolo title: Characteristics and outcomes of a cohort of COVID-19 patients in the Province of Reggio Emilia, Italy date: 2020-08-27 words: 4559.0 sentences: 213.0 pages: flesch: 46.0 cache: ./cache/cord-291176-evb6yt0r.txt txt: ./txt/cord-291176-evb6yt0r.txt summary: In this report, based on the cohort of all residents in the province of Reggio Emilia who were SARS-CoV-2-positive at nasal and pharyngeal swab and with symptoms (COVID-19 cases) since the inception of the epidemic, we describe patient characteristics and explore their role as putative prognostic factors in predicting the occurrence of hospital admission or death. We considered the following patient characteristics: age, sex, place of birth (Italy or abroad), time span (in days) from symptom onset to diagnosis/ hospitalization, and comorbidities, whose prognostic role was explored both singly (chronic obstructive pulmonary disease, arrhythmia, diabetes, coronary heart disease, heart failure, vascular diseases, obesity) and by computing the Charlson Comorbidity Index, which provides an overall measure of an individual patient''s complexity [12] . While in this study we focused on the risk of hospitalization and death in a cohort of COVID-19 patients diagnosed during the epidemic in Northern Italy, it also provided us with the opportunity to describe the pattern of distribution of the disease in the whole population. abstract: This is a population-based prospective cohort study on archive data describing the age- and sex-specific prevalence of COVID-19 and its prognostic factors. All 2653 symptomatic patients tested positive for SARS-CoV-2 from February 27 to April 2, 2020 in the Reggio Emilia province, Italy, were included. COVID-19 cumulative incidence, hospitalization and death rates, and adjusted hazard ratios (HR) with 95% confidence interval (95% CI) were calculated according to sociodemographic and clinical characteristics. Females had higher prevalence of infection than males below age 50 (2.61 vs. 1.84 ‰), but lower in older ages (16.49 vs. 20.86 ‰ over age 80). Case fatality rate reached 20.7% in cases with more than 4 weeks follow up. After adjusting for age and comorbidities, men had a higher risk of hospitalization (HR 1.4 95% CI 1.2 to 1.6) and of death (HR 1.6, 95% CI 1.2 to 2.1). Patients over age 80 compared to age < 50 had HR 7.1 (95% CI 5.4 to 9.3) and HR 27.8 (95% CI 12.5 to 61.7) for hospitalization and death, respectively. Immigrants had a higher risk of hospitalization (HR 1.3, 95% CI 0.99 to 1.81) than Italians and a similar risk of death. Risk of hospitalization and of death were higher in patients with heart failure, arrhythmia, dementia, coronary heart disease, diabetes, and hypertension, while COPD increased the risk of hospitalization (HR 1.9, 95% CI 1.4 to 2.5) but not of death (HR 1.1, 95% CI 0.7 to 1.7). Previous use of ACE inhibitors had no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34). Identified susceptible populations and fragile patients should be considered when setting priorities in public health planning and clinical decision making. url: https://doi.org/10.1371/journal.pone.0238281 doi: 10.1371/journal.pone.0238281 id: cord-316047-d9cpe9yl author: Gonzalez, T. title: Influence of COVID-19 confinement on students’ performance in higher education date: 2020-10-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This study analyzes the effects of COVID-19 confinement on the autonomous learning performance of students in higher education. Using a field experiment with 458 students from three different subjects at Universidad Autónoma de Madrid (Spain), we study the differences in assessments by dividing students into two groups. The first group (control) corresponds to academic years 2017/2018 and 2018/2019. The second group (experimental) corresponds to students from 2019/2020, which is the group of students that had their face-to-face activities interrupted because of the confinement. The results show that there is a significant positive effect of the COVID-19 confinement on students’ performance. This effect is also significant in activities that did not change their format when performed after the confinement. We find that this effect is significant both in subjects that increased the number of assessment activities and subjects that did not change the student workload. Additionally, an analysis of students’ learning strategies before confinement shows that students did not study on a continuous basis. Based on these results, we conclude that COVID-19 confinement changed students’ learning strategies to a more continuous habit, improving their efficiency. For these reasons, better scores in students’ assessment are expected due to COVID-19 confinement that can be explained by an improvement in their learning performance. url: https://doi.org/10.1371/journal.pone.0239490 doi: 10.1371/journal.pone.0239490 id: cord-277357-lpurk7pe author: González-González, Everardo title: Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection date: 2020-08-13 words: 3999.0 sentences: 211.0 pages: flesch: 49.0 cache: ./cache/cord-277357-lpurk7pe.txt txt: ./txt/cord-277357-lpurk7pe.txt summary: title: Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection containing the amplification products of each one of three experiments, where the three different sets of primers (namely N1, N2, and N3) were used to amplify the same range of concentrations of template. Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection others), we observe differences in the performance of each primer pair. abstract: The coronavirus disease 2019 (COVID-19) pandemic has crudely demonstrated the need for massive and rapid diagnostics. By the first week of July, more than 10,000,000 positive cases of COVID-19 have been reported worldwide, although this number could be greatly underestimated. In the case of an epidemic emergency, the first line of response should be based on commercially available and validated resources. Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. We used the miniPCR to detect and amplify SARS-CoV-2 DNA sequences using the sets of initiators recommended by the World Health Organization (WHO) for targeting three different regions that encode for the N protein. Prior to amplification, samples were combined with a DNA intercalating reagent (i.e., EvaGreen Dye). Sample fluorescence after amplification was then read using a commercial 96-well plate reader. This straightforward method allows the detection and amplification of SARS-CoV-2 nucleic acids in the range of ~625 to 2×10(5) DNA copies. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for COVID-19 pandemic testing, particularly in underdeveloped regions where RT-QPCR instrument availability may be limited. The portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for deployment in point-of-care SARS-CoV-2 detection efforts during pandemics. url: https://www.ncbi.nlm.nih.gov/pubmed/32790779/ doi: 10.1371/journal.pone.0237418 id: cord-324091-nljd2ok1 author: Gordon, Jennifer L. title: The psychological impact of fertility treatment suspensions during the COVID-19 pandemic date: 2020-09-18 words: 4497.0 sentences: 263.0 pages: flesch: 49.0 cache: ./cache/cord-324091-nljd2ok1.txt txt: ./txt/cord-324091-nljd2ok1.txt summary: PURPOSE: To examine the psychological impact of fertility treatment suspensions resulting from the COVID-19 pandemic and to clarify psychosocial predictors of better or worse mental health. Participants completed a battery of questionnaires assessing depressive symptoms, perceived mental health impact, and change in quality of life related to treatment suspensions. Table 2 depicts the correlation between three personality traits (trait optimism, defensive pessimism, and intolerance of uncertainty) that were considered potentially relevant under the current circumstances, in relation to the overall change in quality of life and the mental health impact attributed to fertility treatment suspensions. The psychological impact of fertility treatment suspensions during the COVID-19 pandemic the final subscales are as follows: 1) avoidance, α = 0.82, 2) active coping, α = 0.71, 3) finding meaning, α = 0.72, 4) defensive pessimism, α = 0.66, 5) optimism, α = 0.80, 6) seek social support, α = 0.77, and 7) behavioural engagement, α = 0.67. abstract: PURPOSE: To examine the psychological impact of fertility treatment suspensions resulting from the COVID-19 pandemic and to clarify psychosocial predictors of better or worse mental health. METHODS: 92 women from Canada and the United States (ages 20–45 years) whose fertility treatments had been cancelled were recruited via social media. Participants completed a battery of questionnaires assessing depressive symptoms, perceived mental health impact, and change in quality of life related to treatment suspensions. Potential predictors of psychological outcomes were also examined, including several personality traits, aspects of social support, illness cognitions, and coping strategies. RESULTS: 52% of respondents endorsed clinical levels of depressive symptoms. On a 7-point scale, participants endorsed a significant decline in overall quality of life (M(SD) = -1.3(1.3), p < .0001) as well as a significant decline in mental health related to treatment suspensions on a scale from -5 to +5 (M(SD) = -2.1(2.1), p < .001). Several psychosocial variables were found to positively influence these outcomes: lower levels of defensive pessimism (r = -.25, p < .05), greater infertility acceptance (r = .51, p < .0001), better quality social support (r = .31, p < .01), more social support seeking (r = .35, p < .001) and less avoidance of infertility reminders (r = -.23, p = .029). CONCLUSION: Fertility treatment suspensions have had a considerable negative impact on women’s mental health and quality of life. However, these findings point to several protective psychosocial factors that can be fostered in the future to help women cope. url: https://doi.org/10.1371/journal.pone.0239253 doi: 10.1371/journal.pone.0239253 id: cord-000478-88wo4xen author: Gowen, Brian B. title: Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date: 2011-10-24 words: 4407.0 sentences: 221.0 pages: flesch: 49.0 cache: ./cache/cord-000478-88wo4xen.txt txt: ./txt/cord-000478-88wo4xen.txt summary: Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. Interestingly, the 10 7 and 10 8 pfu DEF201 groups presented with little to no day-7 virus burden in the serum, liver, or spleen, while the 10 6 group developed viral titers that were comparable to the rAd EV and placebo controls ( Figure 2B-D) . This may not be the case with hamsters treated with DEF201 24 h prior to challenge since most had no detectable virus titers in spleen, liver, or serum on day 7 of PICV infection ( Figure 2B-D) . Animals were treated i.n. with a single dose 10 8 pfu of DEF201, the rAd EV control virus, or PBS placebo 7 or 14 days prior to PICV infection. abstract: Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200317/ doi: 10.1371/journal.pone.0026072 id: cord-340656-ltd6ueoi author: Grant, Michael C. title: The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries date: 2020-06-23 words: 3435.0 sentences: 199.0 pages: flesch: 48.0 cache: ./cache/cord-340656-ltd6ueoi.txt txt: ./txt/cord-340656-ltd6ueoi.txt summary: title: The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries Furthermore, with few included studies (30 in the largest and most recent [12] ), the range of symptoms were limited and the estimates of prevalence are likely to be upwardly biased because only unwell patients (largely those admitted to hospital) were tested in the early phase of the outbreak. We excluded case reports, articles which failed to disaggregate symptoms in adult and paediatric cohorts, studies of patients with prior respiratory infections (e.g. tuberculosis) or co-infections with other viruses (e.g. similar viruses SARS-CoV-1 or HCoV-EMC/2012, etc) and articles which we are unable to translate to English in a timely fashion. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms abstract: BACKGROUND: To limit the spread of SARS-CoV-2, an evidence-based understanding of the symptoms is critical to inform guidelines for quarantining and testing. The most common features are purported to be fever and a new persistent cough, although the global prevalence of these symptoms remains unclear. The aim of this systematic review is to determine the prevalence of symptoms associated with COVID-19 worldwide. METHODS: We searched PubMed, Embase, CINAHL, AMED, medRxiv and bioRxiv on 5(th) April 2020 for studies of adults (>16 years) with laboratory test confirmed COVID-19. No language or publication status restrictions were applied. Data were independently extracted by two review authors into standardised forms. All datapoints were independently checked by three other review authors. A random-effects model for pooling of binomial data was applied to estimate the prevalence of symptoms, subgrouping estimates by country. I(2) was used to assess inter-study heterogeneity. RESULTS: Of 851 unique citations, 148 articles were included which comprised 24,410 adults with confirmed COVID-19 from 9 countries. The most prevalent symptoms were fever (78% [95% CI 75%-81%]; 138 studies, 21,701 patients; I(2) 94%), a cough (57% [95% CI 54%-60%]; 138 studies, 21,682 patients; I(2) 94%) and fatigue (31% [95% CI 27%-35%]; 78 studies, 13,385 patients; I(2) 95%). Overall, 19% of hospitalised patients required non-invasive ventilation (44 studies, 6,513 patients), 17% required intensive care (33 studies, 7504 patients), 9% required invasive ventilation (45 studies, 6933 patients) and 2% required extra-corporeal membrane oxygenation (12 studies, 1,486 patients). The mortality rate was 7% (73 studies, 10,402 patients). CONCLUSIONS: We confirm that fever and cough are the most prevalent symptoms of adults infected by SARS-CoV-2. However, there is a large proportion of infected adults which symptoms-alone do not identify. url: https://doi.org/10.1371/journal.pone.0234765 doi: 10.1371/journal.pone.0234765 id: cord-002957-gw2cow0d author: Gray, Darren W. title: DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles date: 2018-04-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886402/ doi: 10.1371/journal.pone.0194488 id: cord-262846-1mhimfsf author: Gray, Nicholas title: Is “no test is better than a bad test”? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19 date: 2020-10-21 words: 6023.0 sentences: 337.0 pages: flesch: 55.0 cache: ./cache/cord-262846-1mhimfsf.txt txt: ./txt/cord-262846-1mhimfsf.txt summary: This strategy would involve detecting those who have successfully overcome the virus, and are likely to have some level of immunity (or at least reduced susceptibility to more serious illness if they are infected again), so are relatively safe to relax their personal lockdown measures. To explore the effect of imperfect testing on the disease dynamics when strategies testing regimes are employed to relax lockdown measures, three new classes were added to the model. implement quarantine in their model but do not incorporate the effects on the dynamics from imperfect testing, nor do they consider how the quality and scale of an available test affect the spread of a disease. Wide-scale screening for antibodies in the general population promises significant scientific value, and targeted antibody testing is likely to have value for reducing risks to NHS and care-sector staff, and other key workers who will need to have close contact with COVID-19 sufferers. abstract: Testing is viewed as a critical aspect of any strategy to tackle epidemics. Much of the dialogue around testing has concentrated on how countries can scale up capacity, but the uncertainty in testing has not received nearly as much attention beyond asking if a test is accurate enough to be used. Even for highly accurate tests, false positives and false negatives will accumulate as mass testing strategies are employed under pressure, and these misdiagnoses could have major implications on the ability of governments to suppress the virus. The present analysis uses a modified SIR model to understand the implication and magnitude of misdiagnosis in the context of ending lockdown measures. The results indicate that increased testing capacity alone will not provide a solution to lockdown measures. The progression of the epidemic and peak infections is shown to depend heavily on test characteristics, test targeting, and prevalence of the infection. Antibody based immunity passports are rejected as a solution to ending lockdown, as they can put the population at risk if poorly targeted. Similarly, mass screening for active viral infection may only be beneficial if it can be sufficiently well targeted, otherwise reliance on this approach for protection of the population can again put them at risk. A well targeted active viral test combined with a slow release rate is a viable strategy for continuous suppression of the virus. url: https://doi.org/10.1371/journal.pone.0240775 doi: 10.1371/journal.pone.0240775 id: cord-000501-qz68gtd4 author: Greatorex, Jane S. title: Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control date: 2011-11-22 words: 4311.0 sentences: 194.0 pages: flesch: 47.0 cache: ./cache/cord-000501-qz68gtd4.txt txt: ./txt/cord-000501-qz68gtd4.txt summary: METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. The potential for transmission of influenza by indirect contact (i.e. via fomites) is linked to the ability of virus to survive in transmissible titres on commonly touched surfaces; however few data exist on this subject. We evaluate the survival of influenza A (H1N1) viruses deliberately applied to a range of commonly touched household and workplace surfaces, using RT-PCR for genome detection and culture methods to determine viability. Our data are consistent with recent findings from a study of environmental deposition of pandemic H1N1 virus in the homes of infected patients, involving our laboratory, when almost 10% of tested surfaces yielded viable virus [15] . abstract: BACKGROUND: The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. CONCLUSIONS/SIGNIFICANCE: The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222642/ doi: 10.1371/journal.pone.0027932 id: cord-285546-5tjhdczt author: Green, Manfred S. title: The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries date: 2020-10-21 words: 2390.0 sentences: 142.0 pages: flesch: 64.0 cache: ./cache/cord-285546-5tjhdczt.txt txt: ./txt/cord-285546-5tjhdczt.txt summary: title: The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries BACKGROUND: Crude case-fatality rates (CFRs) for COVID-19 vary widely between countries. We examined how the age distribution of the cases is responsible for the COVID-19 CFR differences between countries. METHODS: COVID-19 cases and deaths, by ten-year age-groups, were available from the reports of seven countries. The age-adjusted CFRs were computed by the direct method, using the combined number of cases in all seven countries in each age group as the standard population. CONCLUSIONS: The age structure of the cases explains much of differences in the crude CFRs between countries and adjusting for age substantially reduces this variation. The age-specific number of cases, number of deaths and the crude CFRs by country are given in Table 1 . abstract: BACKGROUND: Crude case-fatality rates (CFRs) for COVID-19 vary widely between countries. There are serious limitations in the CFRs when making comparisons. We examined how the age distribution of the cases is responsible for the COVID-19 CFR differences between countries. METHODS: COVID-19 cases and deaths, by ten-year age-groups, were available from the reports of seven countries. The overall and age-specific CFRs were computed for each country. The age-adjusted CFRs were computed by the direct method, using the combined number of cases in all seven countries in each age group as the standard population. A meta-analytic approach was used to obtain pooled age-specific CFRs. FINDINGS: The crude overall CFRs varied between 0.82% and 14.2% in the seven countries and the variation in the age-specific CFRs were much smaller. There was wide variation in the age distribution of the cases between countries. The ratio of the crude CFR for the country with the highest CFR to that with the lowest (6.28) was much lower for the age-adjusted CFRs rates (2.57). CONCLUSIONS: The age structure of the cases explains much of differences in the crude CFRs between countries and adjusting for age substantially reduces this variation. Other factors such as the definition of cases, coding of deaths and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. At the very least, age-specific and age-adjusted CFRs should be used for comparisons. url: https://doi.org/10.1371/journal.pone.0241031 doi: 10.1371/journal.pone.0241031 id: cord-294372-pec1886j author: Greene, Dina N. title: Decreasing median age of COVID-19 cases in the United States—Changing epidemiology or changing surveillance? date: 2020-10-15 words: 1698.0 sentences: 103.0 pages: flesch: 60.0 cache: ./cache/cord-294372-pec1886j.txt txt: ./txt/cord-294372-pec1886j.txt summary: Result distributions by age and positivity were compared between early period (March-April 2020) and late periods (June-July 2020) of the COVID-19 pandemic. Overall, this suggests that observed age-related trends are driven by changes in testing patterns rather than true changes in the epidemiology of SARS-CoV-2 infection. In the United States, surveillance data suggest that mean age of infected patients is decreasing compared to the early stages of the COVID-19 pandemic. We used SARS-CoV-2 testing data from a national reference laboratory to characterize the age distribution of detected cases between March and July of 2020. Surveillance data in the United States have shown a trend toward decreasing age among persons with laboratory-confirmed SARS-CoV-2 infection. This study found a similar pattern among patients tested by a national reference laboratory, with the median age among patients testing positive being five years lower in June and early July compared to March and April. abstract: BACKGROUND: Understanding and monitoring the demographics of SARS-CoV-2 infection can inform strategies for prevention. Surveillance monitoring has suggested that the age distribution of people infected with SARS-CoV-2 has changed since the pandemic began, but no formal analysis has been performed. METHODS: Retrospective review of SARS-CoV-2 molecular testing results from a national reference laboratory was performed. Result distributions by age and positivity were compared between early period (March-April 2020) and late periods (June-July 2020) of the COVID-19 pandemic. Additionally, a sub-analysis compared changing age distributions between inpatients and outpatients. RESULTS: There were 277,601 test results of which 19320 (7.0%) were positive. The median age of infected people declined over time (p < 0.0005). In March-April, the median age of positive people was 40.8 years (Interquartile range (IQR): 29.0–54.1). In June-July, the median age of positive people was 35.8 years (IQR: 24.0–50.2). The positivity rate of patients under 50 increased from 6.0 to 10.6 percent and the positivity rate for those over 50 decreased from 6.3 to 5.0 percent between the early and late periods. The trend was only observed for outpatient populations. CONCLUSIONS: We confirm that there is a trend toward decreasing age among persons with laboratory-confirmed SARS-CoV-2 infection, but that these trends seem to be specific to the outpatient population. Overall, this suggests that observed age-related trends are driven by changes in testing patterns rather than true changes in the epidemiology of SARS-CoV-2 infection. This calls for caution in interpretation of routine surveillance data until testing patterns stabilize. url: https://doi.org/10.1371/journal.pone.0240783 doi: 10.1371/journal.pone.0240783 id: cord-280846-bbv6f5gf author: Greninger, Alexander L. title: A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America date: 2010-10-18 words: 8023.0 sentences: 327.0 pages: flesch: 44.0 cache: ./cache/cord-280846-bbv6f5gf.txt txt: ./txt/cord-280846-bbv6f5gf.txt summary: To determine whether a pan-viral microarray assay was capable of identifying novel 2009 H1N1 in the absence of a priori sequence information, we used the Virochip to comprehensively screen for viruses in 29 nasopharyngeal swab samples from individuals with influenza-like illness. To further characterize the metagenomics of 2009 H1N1 infection in humans, we labeled the 17 influenza samples positive for 2009 H1N1 by Virochip with distinct molecular barcodes and analyzed them by paired-end deep sequencing on three lanes of an Illumina Genome Analyzer IIx. After trimming reads to remove barcodes and exclude low-complexity or primer sequences, 11,427,212 high-quality 60-bp sequence reads were subjected to an iterative BLASTN analysis pipeline (Fig. 1B) . After stratifying by originating location and corresponding method of sample processing (pre-DNase and/or post-DNase treatment), the percentage of total reads aligning to influenza was linearly correlated with calculated viral titers by realtime quantitative RT-PCR for sites in the United States (California) and Canada but not in Mexico (Fig. 5A ). abstract: Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings. url: https://doi.org/10.1371/journal.pone.0013381 doi: 10.1371/journal.pone.0013381 id: cord-340763-cxnu9g8y author: Grimm, Sebastian K. title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies date: 2015-02-17 words: 7822.0 sentences: 341.0 pages: flesch: 45.0 cache: ./cache/cord-340763-cxnu9g8y.txt txt: ./txt/cord-340763-cxnu9g8y.txt summary: title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. The rationally designed d-SOSIP variant and a mutant with disrupted CD4 binding site (CD4bs)-specific Ab binding (d-SOSIP D368R) were displayed as Aga2 fusion proteins on yeast ( Fig. 2A ), and compared for display level and binding to a panel of HIV bnAbs together with the well-characterized and folded YU2 gp120 core [47] and an unrelated viral envelope protein (E2) derived from Hepatitis C virus (HCV E2) as positive and negative controls Fig. 2) . abstract: Design of an envelope-based immunogen capable of inducing a broadly neutralizing antibody response is thought to be key to the development of a protective HIV-1 vaccine. However, the broad diversity of viral variants and a limited ability to produce native envelope have hampered such design efforts. Here we describe adaptation of the yeast display system and use of a combinatorial protein engineering approach to permit directed evolution of HIV envelope variants. Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. We report for the first time the display of a designed SOSIP gp140 on yeast, and the in vitro evolution of derivatives with greatly improved expression and binding to conformation-dependent antibodies. These efforts represent an initial and critical step toward the ability to rapidly engineer HIV-1 envelope immunogens via directed evolution. url: https://doi.org/10.1371/journal.pone.0117227 doi: 10.1371/journal.pone.0117227 id: cord-333522-zsdymkjd author: Gruse, Jeannine title: Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits date: 2016-01-11 words: 7010.0 sentences: 333.0 pages: flesch: 46.0 cache: ./cache/cord-333522-zsdymkjd.txt txt: ./txt/cord-333522-zsdymkjd.txt summary: Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Basal blood samples were taken before the morning feeding on days 1, 2, 4 and 7 from the jugular vein using evacuated tubes containing either potassium-EDTA (1.2-2 mg/mL EDTA) for analyses of plasma metabolites, insulin, glucagon, immunoglobulins and acute-phase proteins or Li-heparin (12-30 IU heparin) for the determination of the cortisol and flavonol concentrations and the antioxidative status in the plasma. Feed intake, body temperature, heart and respiratory rate and plasma concentrations of metabolites, hormones, flavonols and markers of antioxidative status were analyzed by repeated measurement ANOVA using the MIXED procedure of SAS/STAT software and a model with the fixed factors diet, quercetin and day of life (repeated variable) and all interactions between the fixed factors. abstract: Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply. url: https://www.ncbi.nlm.nih.gov/pubmed/26752173/ doi: 10.1371/journal.pone.0146932 id: cord-319675-mwy3t1ny author: Gu, Li title: Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia date: 2016-08-17 words: 3081.0 sentences: 164.0 pages: flesch: 56.0 cache: ./cache/cord-319675-mwy3t1ny.txt txt: ./txt/cord-319675-mwy3t1ny.txt summary: At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). Our results suggest that a higher initial viral load (10 8 copy/ml) in the respiratory tract samples on day 5-7 after disease onset is a predictor for fatal clinical outcome. In one case, as shown in Fig 2, even though the patient presented with a higher viral load (10 8.32 copies / ml) in tracheal aspiration, which may be associated fatal outcome, his clinical manifestation recovered gradually with a downward trend in the viral load in respiratory tract and whole blood samples. A higher initial viral load (10 8 copy/ml) in the respiratory tract on day 5-7 after disease onset and sustained viremia for 2 weeks or more may be associated with fatal clinical outcomes. abstract: The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes. url: https://doi.org/10.1371/journal.pone.0160777 doi: 10.1371/journal.pone.0160777 id: cord-322827-h33su548 author: Guan, Lili title: Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives date: 2015-04-07 words: 5056.0 sentences: 232.0 pages: flesch: 50.0 cache: ./cache/cord-322827-h33su548.txt txt: ./txt/cord-322827-h33su548.txt summary: BACKGROUND: In 2005, China implemented a demonstration program known as "686" to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. This program has contributed to improving care for patients with severe mental disorders, including schizophrenia, psychosis, bipolar disorder and schizoaffective disorder, through increasing access to treatment and integrating hospital and community services designed to provide continuity of evidence-based care and to address patients'' rights. Patients with severe mental disorders were followed-up about their medication adherence, mental health status, social functioning and family burden in 2009 and 2012 to investigate the changes over time following the unlocking efforts. The finding that more than 92% of those unlocked and entered into continuous treatment by the 686 Program remained free of restraints by 2012 demonstrates the feasibility of improving the human rights of persons with severe mental illness by increasing access to mental health care in the community [22] , even with limited societal resources. abstract: BACKGROUND: In 2005, China implemented a demonstration program known as “686” to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. As part of the 686 Program, teams “unlocked” and provided continuous mental health care to people with severe mental disorders who were found in restraints and largely untreated in their family homes. We implemented a nation-wide two-stage follow-up study to measure the effectiveness and sustainability of the “unlocking and treatment” intervention and its impact on the well-being of patients’ families. METHODS: 266 patients unlocked from 2005 in “686” demonstration sites across China were recruited in Stage One of the study in 2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study). Outcome measures included the patient medication adherence and social functioning, family burden ratings, and relocking rate. We utilized pre-post tests to analyze the changes over time following the unlocking efforts. RESULTS: 96% of patients were diagnosed with schizophrenia. Prior to unlocking, their total time locked ranged from two weeks to 28 years, with 32% having been locked multiple times. The number of persons regularly taking medicines increased from one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post tests showed sustained improvement in patient social functioning and significant reductions in family burden. Over 92% of patients remained free of restraints in 2012. CONCLUSION: Practice-based evidence from our study suggests an important model for protecting the human rights of people with mental disorders and keeping them free of restraints can be achieved by providing accessible, community based mental health services with continuity of care. China’s “686” Program can inform similar efforts in low-resource settings where community locking of patients is practiced. url: https://doi.org/10.1371/journal.pone.0121425 doi: 10.1371/journal.pone.0121425 id: cord-000237-mticfoic author: Guan, Xuhua title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008 date: 2010-07-23 words: 5405.0 sentences: 266.0 pages: flesch: 51.0 cache: ./cache/cord-000237-mticfoic.txt txt: ./txt/cord-000237-mticfoic.txt summary: We conducted a systematic review of the Chinese-and Englishlanguage literature in order to describe pneumonia incidence and mortality in China, evaluate the quality of published studies, and identify gaps in the literature that can be addressed through surveillance and epidemiologic research projects in the future. Based on published recommendations for measuring quality of epidemiologic studies of pneumonia [15] , we assessed quality using the following six criteria: (1) geographic location was reported, (2) study was conducted for a period of at least one year or multiples of one year to account for seasonal factors, (3) site of case detection or surveillance location was reported, (4) age and population size of cohort of at least 50 cases were reported, (5) quality assurance and monitoring methods were employed to assure that data was complete and high quality, and (6) a clearly defined case definition (e.g., not based solely on clinical diagnosis) was used and reported. In children aged ,5 years, the highest mortality rates were reported by four studies that were each conducted in multiple regions throughout mainland China (9.55±14.40 deaths from pneumonia per 1,000 live births; Table S3 ) [21, 23, 38, 48] . abstract: BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06–0.27 episodes per person-year and mortality ranged from 184–1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas. CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909231/ doi: 10.1371/journal.pone.0011721 id: cord-255588-nh34lgdh author: Guo, Fang title: RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response date: 2012-10-03 words: 4776.0 sentences: 268.0 pages: flesch: 51.0 cache: ./cache/cord-255588-nh34lgdh.txt txt: ./txt/cord-255588-nh34lgdh.txt summary: Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 (''2''-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. In order to discover compounds with the expected pharmacological property, we set out to establish reporter cell lines for high throughput screening of small molecules that selectively enhance TLR3 ligand-induced IFN-b gene expression, but do not affect NFkB activation, which is a central player in the induction of proinflammatory cytokines, but plays a less prominent role in type I IFN gene expression [25] . abstract: Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 (‘2’-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy. url: https://www.ncbi.nlm.nih.gov/pubmed/23056170/ doi: 10.1371/journal.pone.0042583 id: cord-272971-9luzvzsu author: Guo, Hainan title: Hong Kong Hospital Authority resource efficiency evaluation: Via a novel DEA-Malmquist model and Tobit regression model date: 2017-09-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Hospital Authority (HA) is a statutory body managing all the public hospitals and institutes in Hong Kong (HK). In recent decades, Hong Kong Hospital Authority (HKHA) has been making efforts to improve the healthcare services, but there still exist some problems like unfair resource allocation and poor management, as reported by the Hong Kong medical legislative committee. One critical consequence of these problems is low healthcare efficiency of hospitals, leading to low satisfaction among patients. Moreover, HKHA also suffers from the conflict between limited resource and growing demand. An effective evaluation of HA is important for resource planning and healthcare decision making. In this paper, we propose a two-phase method to evaluate HA efficiency for reducing healthcare expenditure and improving healthcare service. Specifically, in Phase I, we measure the HKHA efficiency changes from 2000 to 2013 by applying a novel DEA-Malmquist index with undesirable factors. In Phase II, we further explore the impact of some exogenous factors (e.g., population density) on HKHA efficiency by Tobit regression model. Empirical results show that there are significant differences between the efficiencies of different hospitals and clusters. In particular, it is found that the public hospital serving in a richer district has a relatively lower efficiency. To a certain extent, this reflects the socioeconomic reality in HK that people with better economic condition prefers receiving higher quality service from the private hospitals. url: https://doi.org/10.1371/journal.pone.0184211 doi: 10.1371/journal.pone.0184211 id: cord-001734-bbeznd3r author: Gupta, Garvita title: NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics date: 2015-08-10 words: 9729.0 sentences: 418.0 pages: flesch: 53.0 cache: ./cache/cord-001734-bbeznd3r.txt txt: ./txt/cord-001734-bbeznd3r.txt summary: Taken together, CD and NMR results define the 172-residue NS3pro domain to be an intrinsically disordered protein which is lacking of both stable secondary and tertiary structures in the absence of the NS2B cofactor [22, [31] [32] [33] [34] [35] [36] . On the other hand, only a small set of broad peaks could be detected in its HSQC spectrum (Fig 4B) , indicating that the NS3B (1-130) in the LMPC micelle undergoes significant conformational exchanges on μs-ms time scale, or/and dynamic aggregation, which thus prevents from further high-resolution NMR studies. Interestingly, although NMR characterization deciphers that the NS3pro domains have different dynamics on the μs-ms time scale in the contexts of being complexed with NS (48-100) in buffer and with NS2B (1-130) in the LMPC micelle, they have very similar enzymatic activities. abstract: Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530887/ doi: 10.1371/journal.pone.0134823 id: cord-303034-w72oeoxq author: Haischer, Michael H. title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic date: 2020-10-15 words: 4429.0 sentences: 216.0 pages: flesch: 55.0 cache: ./cache/cord-303034-w72oeoxq.txt txt: ./txt/cord-303034-w72oeoxq.txt summary: To understand the demographics of mask wearers and resistors, and the impact of mandates on mask-wearing behavior, we observed shoppers (n = 9935) entering retail stores during periods of June, July, and August 2020. Wearing a mask in public is currently a controversial and politicized issue in the United States, even with case evidence from other countries that face coverings help to control the spread of coronavirus disease 2019 (COVID-19) [1] . To facilitate greater understanding and reliable experimental data on whether gender, age, location, and the presence of mask mandates influence mask wearing in the United States, we conducted a direct observational study at retail stores in Wisconsin. It is not surprising that our June data showed that older individuals wear masks more than middle-age and young people because older adults are at higher risk for more severe cases of COVID-19. abstract: Masks are an effective tool in combatting the spread of COVID-19, but some people still resist wearing them and mask-wearing behavior has not been experimentally studied in the United States. To understand the demographics of mask wearers and resistors, and the impact of mandates on mask-wearing behavior, we observed shoppers (n = 9935) entering retail stores during periods of June, July, and August 2020. Approximately 41% of the June sample wore a mask. At that time, the odds of an individual wearing a mask increased significantly with age and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Mask mandates enacted in late July and August increased mask-wearing compliance to over 90% in all groups, but a small percentage of resistors remained. Thus, gender, age, and location factor into whether shoppers in the United States wear a mask or face covering voluntarily. Additionally, mask mandates are necessary to increase mask wearing among the public to a level required to mitigate the spread of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33057375/ doi: 10.1371/journal.pone.0240785 id: cord-338067-vjyad10p author: Hao, Yan title: Prediction and analysis of Corona Virus Disease 2019 date: 2020-10-05 words: 4775.0 sentences: 258.0 pages: flesch: 59.0 cache: ./cache/cord-338067-vjyad10p.txt txt: ./txt/cord-338067-vjyad10p.txt summary: In this study, the development trend analysis of the cumulative confirmed cases, cumulative deaths, and cumulative cured cases was conducted based on data from Wuhan, Hubei Province, China from January 23, 2020 to April 6, 2020 using an Elman neural network, long short-term memory (LSTM), and support vector machine (SVM). In the present study, three methods, namely, an Elman neural network, LSTM, and SVM are applied to predict and analyze COVID-19 data from January 23, 2020 to April 6, 2020 in Wuhan, Hubei Province, China, including cumulative confirmed cases, confirmed new cases, cumulative deaths, new deaths, and cumulative cured cases and new cured cases. Experimental results showed that the Elman neural network and SVM adopted in this study can accurately predict the development trend of COVID-19, whereas LSTM is more suitable for the prediction of cumulative confirmed cases. abstract: The outbreak of Corona Virus Disease 2019 (COVID-19) in Wuhan has significantly impacted the economy and society globally. Countries are in a strict state of prevention and control of this pandemic. In this study, the development trend analysis of the cumulative confirmed cases, cumulative deaths, and cumulative cured cases was conducted based on data from Wuhan, Hubei Province, China from January 23, 2020 to April 6, 2020 using an Elman neural network, long short-term memory (LSTM), and support vector machine (SVM). A SVM with fuzzy granulation was used to predict the growth range of confirmed new cases, new deaths, and new cured cases. The experimental results showed that the Elman neural network and SVM used in this study can predict the development trend of cumulative confirmed cases, deaths, and cured cases, whereas LSTM is more suitable for the prediction of the cumulative confirmed cases. The SVM with fuzzy granulation can successfully predict the growth range of confirmed new cases and new cured cases, although the average predicted values are slightly large. Currently, the United States is the epicenter of the COVID-19 pandemic. We also used data modeling from the United States to further verify the validity of the proposed models. url: https://doi.org/10.1371/journal.pone.0239960 doi: 10.1371/journal.pone.0239960 id: cord-322414-dpx191xh author: Harke, Nina N. title: To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic date: 2020-09-15 words: 3778.0 sentences: 168.0 pages: flesch: 43.0 cache: ./cache/cord-322414-dpx191xh.txt txt: ./txt/cord-322414-dpx191xh.txt summary: MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16(th)-22(nd) and April 20(th)-26(th) 2020. The complete survey (S1 File) included detailed queries on numbers of available hospital beds and operating room (OR) capacity, staff members, surgical caseloads with subcategorization of surgeries at three different time points: week 1) baseline week that portrays the numbers of a regular/representative week before the outbreak of COVID-19, week 2) March 16 th to 22 nd 2020 which represent the first week after the lockdown in Germany (confirmed cases in Germany on March 16 th 2020: 6,012 with 13 deaths) and week 3) April 20 th to 26 th (confirmed cases in Germany on April 20 th 2020: 141,672; 4,404 deaths and approximately 91,500 recovered) [1] . abstract: INTRODUCTION: After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16(th)-22(nd) and April 20(th)-26(th) 2020. The results were evaluated using descriptive analyses. RESULTS: 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers–however, the number of COVID-19 patients and urologists did not reach double digits. CONCLUSION: The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low. url: https://doi.org/10.1371/journal.pone.0239027 doi: 10.1371/journal.pone.0239027 id: cord-352403-4591ewsa author: Hartwig, Stacey M. title: Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection date: 2014-03-07 words: 3773.0 sentences: 194.0 pages: flesch: 55.0 cache: ./cache/cord-352403-4591ewsa.txt txt: ./txt/cord-352403-4591ewsa.txt summary: In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. We have previously shown that intranasal MHV-1 infection of C3H/HeJ mice, which harbor a natural mutation in the gene that encodes toll-like receptor 4 (TLR4) [15, 16] , results in increased morbidity and mortality along with severe pulmonary disease as compared to the wild-type C3H/HeN mice [17] . We observed a significant (p,0.05) decrease in the total number of MHV-1-specific IFN-c-producing CD4 T cells in the BAL of CL-treated mice as compared to PBS controls ( Figure 4C ). We also observed a significant increase in the total number and frequency of Tregs following MHV-1 infection in both the airways and lung tissue of the CL-treated mice. abstract: Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality. url: https://doi.org/10.1371/journal.pone.0090720 doi: 10.1371/journal.pone.0090720 id: cord-278123-mq56em3z author: Hasan, Mohammad Rubayet title: Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA date: 2020-07-24 words: 3924.0 sentences: 259.0 pages: flesch: 58.0 cache: ./cache/cord-278123-mq56em3z.txt txt: ./txt/cord-278123-mq56em3z.txt summary: Nasopharyngeal specimens positive for SARS-CoV-2 and other coronaviruses collected in universal viral transport (UVT) medium were pre-processed by several commercial and laboratory-developed methods and tested by RT-qPCR assays without RNA extraction using different RT-qPCR master mixes. Standard approach for detection of SARS-CoV-2 RNA from nasopharyngeal specimens in our laboratory involves extraction of total nucleic acids from specimens in an IVD-labeled, automated extraction platform followed by RT-qPCR, based on one of the assays (Table 1) suggested by World Health Organization (WHO) [11] . Based on these results, the optimal pre-treatment and reaction conditions for the direct approach were: i) transfer and dilute (4-fold) 10 μl of NPFS specimen in NFW; ii) incubate at 65˚C for 10 min; and iii) test 8 μl of heat lysed specimen in a 20 μl reaction using TaqPath™ 1-Step RT-qPCR Master Mix. The analytical sensitivity of the direct RT-qPCR assay using specimens prepared in this manner was determined by serially diluting a specimen positive for SARS-CoV-2 with a negative specimen as a diluent. abstract: To circumvent the limited availability of RNA extraction reagents, we aimed to develop a protocol for direct RT-qPCR to detect SARS-CoV-2 in nasopharyngeal swabs without RNA extraction. Nasopharyngeal specimens positive for SARS-CoV-2 and other coronaviruses collected in universal viral transport (UVT) medium were pre-processed by several commercial and laboratory-developed methods and tested by RT-qPCR assays without RNA extraction using different RT-qPCR master mixes. The results were compared to that of standard approach that involves RNA extraction. Incubation of specimens at 65°C for 10 minutes along with the use of TaqPath(™) 1-Step RT-qPCR Master Mix provides higher analytical sensitivity for detection of SARS-CoV-2 RNA than many other conditions tested. The optimized direct RT-qPCR approach demonstrated a limit of detection of 6.6x10(3) copy/ml and high reproducibility (co-efficient of variation = 1.2%). In 132 nasopharyngeal specimens submitted for SARS-CoV-2 testing, the sensitivity, specificity and accuracy of our optimized approach were 95%, 99% and 98.5%, respectively, with reference to the standard approach. Also, the RT-qPCR C(T) values obtained by the two methods were positively correlated (Pearson correlation coefficient r = 0.6971, p = 0.0013). The rate of PCR inhibition by the direct approach was 8% compared to 9% by the standard approach. Our simple approach to detect SARS-CoV-2 RNA by direct RT-qPCR may help laboratories continue testing for the virus despite reagent shortages or expand their testing capacity in resource limited settings. url: https://doi.org/10.1371/journal.pone.0236564 doi: 10.1371/journal.pone.0236564 id: cord-282303-idh7io9v author: Hassan, Md. Zakiul title: Contamination of hospital surfaces with respiratory pathogens in Bangladesh date: 2019-10-28 words: 4158.0 sentences: 203.0 pages: flesch: 39.0 cache: ./cache/cord-282303-idh7io9v.txt txt: ./txt/cord-282303-idh7io9v.txt summary: With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. Respiratory viral and bacterial pathogens, including Staphylococcus aureus, Streptococcus pyogenes, influenza viruses, respiratory syncytial virus, adenovirus, rhinoviruses and novel coronavirus strains, can survive on hospital surfaces for days, weeks or even months. This study identified that hospital surfaces in these Bangladeshi hospitals, were frequently contaminated with respiratory pathogens and pose a potential threat for fomite-borne transmission of respiratory infections to patients, healthcare workers and family caregivers. abstract: With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. In this study, we aimed to identify if surfaces near hospitalized patients with respiratory infections were contaminated with respiratory pathogens and to identify which surfaces were most commonly contaminated. Between September-November 2013, we collected respiratory (nasopharyngeal and oropharyngeal) swabs from patients hospitalized with respiratory illness in adult medicine and paediatric medicine wards at two public tertiary care hospitals in Bangladesh. We collected surface swabs from up to five surfaces near each case-patient including: the wall, bed rail, bed sheet, clinical file, and multipurpose towel used for care giving purposes. We tested swabs using real-time multiplex PCR for 19 viral and 12 bacterial pathogens. Case-patients with at least one pathogen detected had corresponding surface swabs tested for those same pathogens. Of 104 patients tested, 79 had a laboratory-confirmed respiratory pathogen. Of the 287 swabs collected from surfaces near these patients, 133 (46%) had evidence of contamination with at least one pathogen. The most commonly contaminated surfaces were the bed sheet and the towel. Sixty-two percent of patients with a laboratory-confirmed respiratory pathgen (49/79) had detectable viral or bacterial nucleic acid on at least one surface. Klebsiella pneumoniae was the most frequently detected pathogen on both respiratory swabs (32%, 33/104) and on surfaces near patients positive for this organism (97%, 32/33). Surfaces near patients hospitalized with respiratory infections were frequently contaminated by pathogens, with Klebsiella pneumoniae being most common, highlighting the potential for transmission of respiratory pathogens via surfaces. Efforts to introduce routine cleaning in wards may be a feasible strategy to improve infection control, given that severe space constraints prohibit cohorting patients with respiratory illness. url: https://doi.org/10.1371/journal.pone.0224065 doi: 10.1371/journal.pone.0224065 id: cord-302962-qw6s1t7j author: Hause, Ben M. title: Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease date: 2015-03-19 words: 4948.0 sentences: 280.0 pages: flesch: 56.0 cache: ./cache/cord-302962-qw6s1t7j.txt txt: ./txt/cord-302962-qw6s1t7j.txt summary: Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations. The PCR assay specificity was confirmed using bovine rhinitis virus positive samples as determined by metagenomic sequencing as well as with cultures of common BRDC pathogens BVDV, BHV-1, BRSV, BCV, Mannheimia haemolytica, Histophilus somni, Pasteurella multocida and Mycoplasma bovis. As metagenomic sequencing of a nasal swab from a calf with acute respiratory disease identified concurrent infection with two bovine rhinitis virus species, we designed a 5''-nuclease reverse transcription PCR (rtPCR) assay targeting the conserved 3D polymerase gene to investigate the incidence of BRV in BRDC diagnostic submissions. abstract: Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5’-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations. url: https://doi.org/10.1371/journal.pone.0121998 doi: 10.1371/journal.pone.0121998 id: cord-001039-qocuprwb author: Hayasaka, Daisuke title: TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection date: 2013-08-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733918/ doi: 10.1371/journal.pone.0071643 id: cord-255013-njpuc475 author: He, Xiaocui title: Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses date: 2014-10-08 words: 4516.0 sentences: 263.0 pages: flesch: 54.0 cache: ./cache/cord-255013-njpuc475.txt txt: ./txt/cord-255013-njpuc475.txt summary: The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. myotis cell lines present a valuable in vitro model to study the interactions between lyssaviruses and their natural host, and to shed light on the mechanisms of resistance in bat''s central nervous system (CNS). To further evaluate the cell line models for study of the different susceptibility between MmBr and other cell lines, mRNA expressions of PRRs and IFN induced genes were investigated in MmTo and MmBr after RABV infection (MOI 0.01 to 1.0). The increased expression of dsRNA receptor TLR3 and IFN induced genes ISG56, ISG43, Mx1 and IFIT3 after stimulation with poly I:C mimicking a viral infection indicates that these cell lines can be used as effective in vitro models to study the bat''s innate immune responses to virus infection [32, 44] . abstract: Bats are found to be the natural reservoirs for many emerging viruses. In most cases, severe clinical signs caused by such virus infections are normally not seen in bats. This indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. Due to the strict protection of European bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. Here, we report about the establishment and functional characterization of Myotis myotis derived cell lines from different tissues: brain (MmBr), tonsil (MmTo), peritoneal cavity (MmPca), nasal epithelium (MmNep) and nervus olfactorius (MmNol) after immortalization by SV 40 large T antigen. The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. Performed experiments indicated varying susceptibility to lyssavirus infection with MmBr being considerably less susceptible than the other cell lines. Further investigation demonstrated a strong activation of interferon mediated antiviral response in MmBr contributing to its resistance. The pattern recognition receptors: RIG-I and MDA5 were highly up-regulated during rabies virus infection in MmBr, suggesting their involvement in promotion of antiviral responses. The presence of CD14 and CD68 in MmBr suggested MmBr cells are microglia-like cells which play a key role in host defense against infections in the central nervous system (CNS). Thus the expression pattern of MmBr combined with the observed limitation of lyssavirus replication underpin a protective mechanism of the CNS controlling the lyssavirus infection. Overall, the established cell lines are important tools to analyze antiviral innate immunity in M. myotis against neurotropic virus infections and present a valuable tool for a broad spectrum of future investigations in cellular biology of M. myotis. url: https://www.ncbi.nlm.nih.gov/pubmed/25295526/ doi: 10.1371/journal.pone.0109795 id: cord-002100-dt5zvebj author: He, Yonghua title: Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date: 2016-06-17 words: 6795.0 sentences: 336.0 pages: flesch: 45.0 cache: ./cache/cord-002100-dt5zvebj.txt txt: ./txt/cord-002100-dt5zvebj.txt summary: Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. Epidermal growth factor protein from humans was produced in soybean seeds by constructing a plant gene expression cassette that involved a synthetic codon optimized EGF nucleotide sequence (protein sequence from Genbank accession CCQ43157). To assess the bioactivity of soybean-produced hEGF, samples were prepared from both ShEGF transgenic soybean lines and nontransgenic controls that were used to stimulate HeLa cells to induce EGFR internalization, degradation and phosphorylation. In contrast, samples prepared from control nontransgenic soybeans exhibited no apparent bioactivity showing the degradation and phosphorylation of EGFR is the result of EGF binding of either commercial rhEGF added to the media or from the hEGF produced by the transgenic soybeans. abstract: Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912142/ doi: 10.1371/journal.pone.0157034 id: cord-000182-ni6iyzdn author: He, Zhisong title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date: 2010-03-11 words: 6037.0 sentences: 305.0 pages: flesch: 46.0 cache: ./cache/cord-000182-ni6iyzdn.txt txt: ./txt/cord-000182-ni6iyzdn.txt summary: title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou''s pseudo amino acid composition: an approach from discrete wavelet transform abstract: BACKGROUND: Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836373/ doi: 10.1371/journal.pone.0009603 id: cord-000540-bbjmcdo5 author: Hellard, Eléonore title: True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses date: 2012-01-03 words: 7597.0 sentences: 397.0 pages: flesch: 45.0 cache: ./cache/cord-000540-bbjmcdo5.txt txt: ./txt/cord-000540-bbjmcdo5.txt summary: By combining logistic regressions and chi-square tests, we are able to calculate the expected frequencies of co-infected individuals if parasites are independent considering their risk factors, and to compare them to the observed ones. The corrected chi-square approach is based on the idea that the coefficients of the logistic regression of the two viruses can be used to estimate the number of seronegative, single-and double-seropositive individuals expected if the two pathogens are independent. The two approaches (corrected chi-square and logistic regression) were used for the analysis of the interactions between four cat viruses ( Table 2) . Correcting for all risk factors, no pair of viruses involving the Feline Immunodeficiency Virus (FIV-FHV, FIV-FCV, FIV-FPV) was significantly associated. Table S1 Corrected chi-square tests and logistic regressions to search for feline viruses'' interactions using subsets randomly sampled in cat data such that the N F / n ratio takes various values. abstract: BACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these “false interactions”, methods accounting for parasite risk factors must be used. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed “the corrected chi-square.” Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250451/ doi: 10.1371/journal.pone.0029618 id: cord-300859-nqklx0vn author: Henderson, Kelley C. title: Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection date: 2015-06-29 words: 8223.0 sentences: 331.0 pages: flesch: 41.0 cache: ./cache/cord-300859-nqklx0vn.txt txt: ./txt/cord-300859-nqklx0vn.txt summary: title: Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection pneumoniae with statistically significant specificity and sensitivity in simulated and true clinical throat swab samples, and the ability to distinguish between reference strains of the two main genotypes of M. pneumoniae clinical isolates from globally diverse origins and distinguished these from a panel of 12 other human commensal and pathogenic mycoplasma species with 100% cross-validated statistical accuracy. A total of n = 390 pre-processed NA-SERS spectra collected from both substrates were included in the model, consisting of 20 nanorod substrate background spectra, 20 growth medium control spectra, 25 M129 spectra, 25 FH spectra, and 10 spectra per additional clinical isolate. pneumoniae strains from all 12 other human Mollicutes species and the growth medium control with 100% cross-validated sensitivity and specificity (Fig 3A-3C ). abstract: Mycoplasma pneumoniae is a cell wall-less bacterial pathogen of the human respiratory tract that accounts for > 20% of all community-acquired pneumonia (CAP). At present the most effective means for detection and strain-typing is quantitative polymerase chain reaction (qPCR), which can exhibit excellent sensitivity and specificity but requires separate tests for detection and genotyping, lacks standardization between available tests and between labs, and has limited practicality for widespread, point-of-care use. We have developed and previously described a silver nanorod array-surface enhanced Raman Spectroscopy (NA-SERS) biosensing platform capable of detecting M. pneumoniae with statistically significant specificity and sensitivity in simulated and true clinical throat swab samples, and the ability to distinguish between reference strains of the two main genotypes of M. pneumoniae. Furthermore, we have established a qualitative lower endpoint of detection for NA-SERS of < 1 genome equivalent (cell/μl) and a quantitative multivariate detection limit of 5.3 ± 1 cells/μl. Here we demonstrate using partial least squares- discriminatory analysis (PLS-DA) of sample spectra that NA-SERS correctly identified M. pneumoniae clinical isolates from globally diverse origins and distinguished these from a panel of 12 other human commensal and pathogenic mycoplasma species with 100% cross-validated statistical accuracy. Furthermore, PLS-DA correctly classified by strain type all 30 clinical isolates with 96% cross-validated accuracy for type 1 strains, 98% cross-validated accuracy for type 2 strains, and 90% cross-validated accuracy for type 2V strains. url: https://www.ncbi.nlm.nih.gov/pubmed/26121242/ doi: 10.1371/journal.pone.0131831 id: cord-002044-9xgt3tf4 author: Hendiger, Jacek title: Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms date: 2016-05-12 words: 4537.0 sentences: 238.0 pages: flesch: 56.0 cache: ./cache/cord-002044-9xgt3tf4.txt txt: ./txt/cord-002044-9xgt3tf4.txt summary: This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. In health care facilities, this way of ventilation system operation is utilized in both the Airborne Infection Isolation and Protective Environment Rooms, however, the key difference is the required direction of airflow between the room and the adjacent space, such as a corridor, which determines the application of negative or positive pressure in the protected room, respectively. The research described in the available literature, concerning migration of air between rooms in the conditions of pressure difference was conducted using tracer gases, CFD simulations and smoke visualization. The tests were made with dense smoke visualization in order to investigate the relation between the value of pressure difference, door swing and migration level of heavy contaminants between the rooms. abstract: This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. The analysis was based on airflow visualization made with cold smoke, which simulated the heavy contaminants. The test room was pressurized to a specific level and then the door was opened to observe the trail of the smoke plume in the plane of the door. The door was opened in both directions: to the positively and negatively pressurized room. This study focuses on the visualization of smoke plume discharge and an uncertainty analysis is not applicable. Unlike other studies which focus on the analysis of pressure difference, the present study looks at the contaminants which are heavier than air and on “pumping out” the contaminants by means of door swing. Setting the proper level of pressure difference between the contaminated room and the neighbouring rooms can prove instrumental in ensuring protection against toxic contaminants migration. This study helped to establish the threshold of pressure difference necessary to reduce migration of heavy contaminants to neighbouring rooms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865048/ doi: 10.1371/journal.pone.0155159 id: cord-002811-5hrydciz author: Hercik, Christine title: A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania date: 2017-12-29 words: 6511.0 sentences: 310.0 pages: flesch: 42.0 cache: ./cache/cord-002811-5hrydciz.txt txt: ./txt/cord-002811-5hrydciz.txt summary: Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. The objective of this hospital-based syndromic surveillance study was to examine exposure and epidemiologic associations with detection of bloodstream and respiratory agents among patients presenting to clinical settings with acute febrile illness (AFI) in Kilombero, Tanzania. Given the high frequency of detection of Plasmodium, we further examined detection status across three diagnostic platforms, and conducted a non-parametric tests Kruskal-Wallis test to compare mean C t values, as determined by qPCR, for patients grouped within each level of parasite intensity (1+, 2+, 3+, or 4+), as determined by blood smear. Clinical and epidemiologic correlates of agents detected among at least 10% of our patient population were evaluated using an agent-specific filtered multivariate logistic regression approach to determine statistically significant factors among test-positive participants against a test-negative control group. abstract: INTRODUCTION: In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment. METHODS: We conducted a year-long exploratory study of fever syndrome among patients ≥ 1 year if age, presenting to clinical settings with an axillary temperature of ≥37.5°C and symptomatic onset of ≤5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. RESULTS: From 15 September 2014–13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) ≥15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, Plasmodium was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium. Linear regression of fully-adjusted mean cycle threshold (C(t)) values for Plasmodium also identified statistically significant lower mean C(t) values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4). CONCLUSIONS: This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean C(t) values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747442/ doi: 10.1371/journal.pone.0189712 id: cord-345695-5vi9wibk author: Hicks, Lorin L. title: A statistical approach to white-nose syndrome surveillance monitoring using acoustic data date: 2020-10-22 words: 5489.0 sentences: 262.0 pages: flesch: 48.0 cache: ./cache/cord-345695-5vi9wibk.txt txt: ./txt/cord-345695-5vi9wibk.txt summary: From these data, we developed site-specific prediction models for bat activity to account for seasonal and annual temperature variation prior to known occurrence of WNS. We propose this model-based method for future monitoring efforts that could be used to trigger targeted sampling of individual bats or hibernacula for WNS, in areas where traditional disease surveillance approaches are logistically difficult to implement or because of human-wildlife transmission concerns from COVID-19. We predicted that bat populations in the western U.S. would have low levels of activity during winter months, high levels of activity during the summer, and that acoustic monitoring could be used as an effective approach for disease surveillance in remote areas of the Intermountain West. The model was fit to data from all 41 sites to estimate among-site and among-year variation in activity, but we use the results to generate prediction intervals for four forest sites to depict how a landowner might implement this approach for WNS surveillance monitoring. abstract: Traditional pathogen surveillance methods for white-nose syndrome (WNS), the most serious threat to hibernating North American bats, focus on fungal presence where large congregations of hibernating bats occur. However, in the western USA, WNS-susceptible bat species rarely assemble in large numbers and known winter roosts are uncommon features. WNS increases arousal frequency and activity of infected bats during hibernation. Our objective was to explore the effectiveness of acoustic monitoring as a surveillance tool for WNS. We propose a non-invasive approach to model pre-WNS baseline activity rates for comparison with future acoustic data after WNS is suspected to occur. We investigated relationships among bat activity, ambient temperatures, and season prior to presence of WNS across forested sites of Montana, USA where WNS was not known to occur. We used acoustic monitors to collect bat activity and ambient temperature data year-round on 41 sites, 2011–2019. We detected a diverse bat community across managed (n = 4) and unmanaged (n = 37) forest sites and recorded over 5.37 million passes from bats, including 13 identified species. Bats were active year-round, but positive associations between average of the nightly temperatures by month and bat activity were strongest in spring and fall. From these data, we developed site-specific prediction models for bat activity to account for seasonal and annual temperature variation prior to known occurrence of WNS. These prediction models can be used to monitor changes in bat activity that may signal potential presence of WNS, such as greater than expected activity in winter, or less than expected activity during summer. We propose this model-based method for future monitoring efforts that could be used to trigger targeted sampling of individual bats or hibernacula for WNS, in areas where traditional disease surveillance approaches are logistically difficult to implement or because of human-wildlife transmission concerns from COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33091068/ doi: 10.1371/journal.pone.0241052 id: cord-000725-rafwlw0t author: Hindinger, Claudia title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 words: 5114.0 sentences: 243.0 pages: flesch: 37.0 cache: ./cache/cord-000725-rafwlw0t.txt txt: ./txt/cord-000725-rafwlw0t.txt summary: Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). abstract: Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407093/ doi: 10.1371/journal.pone.0042088 id: cord-002023-7zd5zhbz author: Hiremath, Jagadish title: Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs date: 2016-04-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836704/ doi: 10.1371/journal.pone.0151922 id: cord-356364-ipi81ce3 author: Ho, Bo-Lin title: Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease date: 2015-12-14 words: 5038.0 sentences: 277.0 pages: flesch: 62.0 cache: ./cache/cord-356364-ipi81ce3.txt txt: ./txt/cord-356364-ipi81ce3.txt summary: In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. The colorimetry-based peptide substrate, TSAVLQ-para-nitroanilide (TQ6-pNA) (purity 95-99% by HPLC; GL Biochem Ltd, Shanghai, China), was used to measure the proteolytic activity of MERS-CoV M pro and its mutants throughout the course of the study as described previously [25, 28] . In addition, although the K d values of wild-type SARS-CoV M pro without or with substrates show no significant difference (Table 2) , it was possible to detect substrate-induced dimerization at a protein concentration of 1 μM by AEC [33] . Biochemical and AUC studies indicated that MERS-CoV M pro shows almost the same proteolytic activity as SARS-CoV M pro ; although it is a monomer in aqueous buffer and displays substrate-induced dimerization (Fig 6) . abstract: BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family. url: https://doi.org/10.1371/journal.pone.0144865 doi: 10.1371/journal.pone.0144865 id: cord-285749-0ejhd9nw author: Hoffmann, Markus title: The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells date: 2016-03-30 words: 6025.0 sentences: 329.0 pages: flesch: 49.0 cache: ./cache/cord-285749-0ejhd9nw.txt txt: ./txt/cord-285749-0ejhd9nw.txt summary: Generation of VSV pseudotypes (VSVpp) was performed as follows: HEK-293T cells were transfected by calcium-phosphate precipitation with expression plasmids encoding viral surface proteins, VSV-G (positive control) , NiV-F/G, FLUAV-HA and/or NA and bat-FLUAV-HAL and/or NAL, or empty plasmid (pCAGGS) as negative control. In order to investigate the potential of human TTSPs to proteolytically activate batFLUAV-HAL for host cell entry, we additionally cotransfected the cells with expression plasmids for TMPRSS2, DESC-1 or MSPL. Notably, three bat cell lines (EidNi/41, HypNi/1.1 and EpoNi/22.1) were susceptible to entry of pseudotypes bearing HAL and NAL of batFLUAV (Fig 2B) , demonstrating that surface glycoproteins of batFLUAV can mediate cellular entry. To assess proteolytic activation of HA/HAL proteins, vesicular stomatitis virus-based pseudotypes (VSVpp) were produced in cells transfected to express the indicated type II transmembrane serine proteases (B) or different amounts of TMPRSS2 (C). abstract: New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin. url: https://doi.org/10.1371/journal.pone.0152134 doi: 10.1371/journal.pone.0152134 id: cord-000346-9b6yz3f4 author: Holder, Benjamin P. title: Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model date: 2011-03-24 words: 7494.0 sentences: 323.0 pages: flesch: 49.0 cache: ./cache/cord-000346-9b6yz3f4.txt txt: ./txt/cord-000346-9b6yz3f4.txt summary: In order to obtain two complementary views of the infection kinetics for the A/Brisbane/59/2007 WT and H275Y mutant strains, virus growth over time was observed in two different in vitro systems: the viral plaque assay and the multiple-cycle viral yield assay. We are left then with two experimental measures -the viral titer growth rate and the plaque velocity -whose values may depend on three unknown infection kinetics parameters: the infecting time, t inf ; the latent infection period, t L ; and the infectious lifespan of a cell, t I . To demonstrate this concept using the A/ Brisbane/59/2007 (H1N1) WT and H275Y mutant strains, we have plotted the experimentally-measured values of plaque velocity and viral titer growth rate as functions of the infecting time and latent infection period, using the model dependence determined above ( Figure 6 ). abstract: In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008–2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1–3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063785/ doi: 10.1371/journal.pone.0014767 id: cord-013334-cptu0k7s author: Holst-Hansen, Joachim A. title: Does the size of rewards influence performance in cognitively demanding tasks? date: 2020-10-21 words: 6101.0 sentences: 326.0 pages: flesch: 55.0 cache: ./cache/cord-013334-cptu0k7s.txt txt: ./txt/cord-013334-cptu0k7s.txt summary: Empirical studies in sports settings show that athletes generally perform worse when the stakes are higher, while a range of lab studies involving cognitively demanding tasks have led to diverging results, supporting positive, negative and null-effects of higher (vs. Third, if the given task can''t be solved more efficiently than the level of performance a low monetary incentive allows, a higher stake can''t have an additional positive effect due to a ceiling effect [3] . Studies that have asked participants to solve various forms of cognitively demanding tasks have led to ambiguous findings; some studies find a positive effect on performance of higher stakes compared to lower [6, 16, 17] , some find a negative effect [5, 18] while others find no clear effect when comparing high vs. In order to further investigate how the reward size might influence behavior, we also assess if self-reported measures of effort [6] , intrinsic motivation [7] and focus [5] vary depending on the reward structure the participants have been exposed to. abstract: Classic micro-economic and psychology theories propose different implications of monetary incentives on performance. Empirical studies in sports settings show that athletes generally perform worse when the stakes are higher, while a range of lab studies involving cognitively demanding tasks have led to diverging results, supporting positive, negative and null-effects of higher (vs. lower) stakes. In order to further investigate this issue, we present a pre-registered, randomized, controlled trial of 149 participants solving both anagrams and math addition tasks. We do not find a statistically significant effect of the size of the reward on neither performance, self-reported effort nor intrinsic motivation. We propose that future studies should contrast the potential impact of rewards on different kinds of task, e.g. compare tasks that solely require cognitive effort vs. tasks that require motor skills, as in sports. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577432/ doi: 10.1371/journal.pone.0240291 id: cord-012889-dtil5xeo author: Holzer, Joshua title: The effect of copartisan justice ministers on human rights in presidential democracies date: 2020-09-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A body of literature suggests that states with independent courts are more likely to protect human rights. A recent article challenges this notion by arguing that when both the president and his or her justice minister share the same party—i.e., they are copartisans—that state is less likely to protect human rights, as justice ministers may value their loyalty to the president over their duty to enforce court decisions. In this article, I estimate government respect for human rights accounting for both copartisan justice ministers and an independent judiciary. In the end, I find copartisan justice ministers to be negatively associated with high government respect for human rights, even after controlling for judicial independence. Many constitutions already seek to ensure an independent judiciary, but if copartisan justice ministers increase the likelihood that governments repress, then perhaps constitutional engineers should also consider options that would reduce the likelihood that both the president and his or her justice minister share the same party. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467281/ doi: 10.1371/journal.pone.0234938 id: cord-339789-151d1j4n author: Hong, Hyokyoung G. title: Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic date: 2020-07-21 words: 3934.0 sentences: 286.0 pages: flesch: 60.0 cache: ./cache/cord-339789-151d1j4n.txt txt: ./txt/cord-339789-151d1j4n.txt summary: title: Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic However, time-independent parameters in the classical models may not capture the dynamic transmission and removal processes, governed by virus containment strategies taken at various phases of the epidemic. We propose a Poisson model with time-dependent transmission and removal rates to account for possible random errors in reporting and estimate a time-dependent disease reproduction number, which may reflect the effectiveness of virus control strategies. To choose the optimal number of knots for each country when implementing the spline approach, we used 5-fold cross-validation by minimizing the combined mean squared error for the estimated infectious and removed cases. Our model accommodates possible random errors and estimates a timedependent disease reproduction number, R 0 ðtÞ, which can serve as a metric for timely evaluating the effects of health policies. abstract: The coronavirus pandemic has rapidly evolved into an unprecedented crisis. The susceptible-infectious-removed (SIR) model and its variants have been used for modeling the pandemic. However, time-independent parameters in the classical models may not capture the dynamic transmission and removal processes, governed by virus containment strategies taken at various phases of the epidemic. Moreover, few models account for possible inaccuracies of the reported cases. We propose a Poisson model with time-dependent transmission and removal rates to account for possible random errors in reporting and estimate a time-dependent disease reproduction number, which may reflect the effectiveness of virus control strategies. We apply our method to study the pandemic in several severely impacted countries, and analyze and forecast the evolving spread of the coronavirus. We have developed an interactive web application to facilitate readers’ use of our method. url: https://arxiv.org/pdf/2004.05730v3.pdf doi: 10.1371/journal.pone.0236464 id: cord-000979-cav9n18w author: Hoppe, Sebastian title: Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni date: 2013-05-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Campylobacter jejuni remains one of the major gut pathogens of our time. Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool. Antibody-based detection presents a suitable means to identify pathogenic bacteria. However, the knowledge about immunodominant targets is limited. Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens. The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination. We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before. After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA. Subsequently, seven proteins were selected for epitope mapping. For cj0669 and cj0920c linear epitopes were identified. For cj0669, specificity assays revealed a specific linear epitope site. Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody. The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni. The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings. Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers. Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667084/ doi: 10.1371/journal.pone.0065837 id: cord-001435-ebl8yc92 author: Hoppe, Sebastian title: Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date: 2014-10-21 words: 9619.0 sentences: 545.0 pages: flesch: 50.0 cache: ./cache/cord-001435-ebl8yc92.txt txt: ./txt/cord-001435-ebl8yc92.txt summary: Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. Incubation with antibodies reactive to either of those two bacterial species resulted in signal intensities in the neighbourhood of the negative control independent of sequence alterations, see Figure 11 . In contrast, the other two proteins displaying linear epitopes, KPN_00363 and KPN_00459, indicated some specificity with the antibodies tested and two linear consensus sequences could be derived, GAVVALSTTFA and GIAFGAVELFD, respectively. abstract: The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205017/ doi: 10.1371/journal.pone.0110703 id: cord-346858-18q8rxzg author: Hossain, Md. Tanvir title: Social and electronic media exposure and generalized anxiety disorder among people during COVID-19 outbreak in Bangladesh: A preliminary observation date: 2020-09-11 words: 3462.0 sentences: 171.0 pages: flesch: 51.0 cache: ./cache/cord-346858-18q8rxzg.txt txt: ./txt/cord-346858-18q8rxzg.txt summary: Classified as a pandemic by the World Health Organization, the novel Coronavirus Disease (COVID-19) has spread to Bangladesh since early March of 2020, and people are getting daily updates from the social and electronic media. For this cross-sectional study, data were collected from 880 participants by a self-administered online-based questionnaire relating personal characteristics, self-rate health (SRH), SME, and EME with anxiety. The mental health burden of the COVID-19 infected patients and the healthcare professionals, fearing the persisting social prejudice and stigma generated from ''overexposure'' to media ''misinformation,'' forced some people to commit suicide [22] [23] [24] . At present, the level of anxiety generated from the exposure to social and electronic media during COVID-19 pandemic is not known in Bangladesh, while some other countries have addressed the issue vigorously [13, 18, 36] . abstract: Classified as a pandemic by the World Health Organization, the novel Coronavirus Disease (COVID-19) has spread to Bangladesh since early March of 2020, and people are getting daily updates from the social and electronic media. We aimed at assessing the prevalence of anxiety among Bangladeshi people during the pandemic in connection with social media exposure (SME) and electronic media exposure (EME). For this cross-sectional study, data were collected from 880 participants by a self-administered online-based questionnaire relating personal characteristics, self-rate health (SRH), SME, and EME with anxiety. Findings show that around half of the surveyed population experienced a spike of anxiety (49.1%) during the pandemic, ten times higher than the national anxiety rate in 2019. The participants with an increased SME of over four hours per day experienced a higher level of anxiety than individuals with < = 2 hours exposure to social media. Similarly, the anxiety was higher among people with fair/bad SRH compared to individuals with excellent SRH. It is highly recommended to develop active surveillance and effective monitoring systems to reduce the spread of misinformation from both social and electronic media to improve the state of mental health conditions during the pandemic. url: https://doi.org/10.1371/journal.pone.0238974 doi: 10.1371/journal.pone.0238974 id: cord-296550-wkmnfph3 author: Hossain, Mohammad Anwar title: Knowledge, attitudes, and fear of COVID-19 during the Rapid Rise Period in Bangladesh date: 2020-09-24 words: 4576.0 sentences: 239.0 pages: flesch: 53.0 cache: ./cache/cord-296550-wkmnfph3.txt txt: ./txt/cord-296550-wkmnfph3.txt summary: The study aims to determine the level of Knowledge, Attitude, and Practice (KAP) related to COVID-19 preventive health habits and perception of fear towards COVID-19 in subjects living in Bangladesh. The study objectives were to determine the level of knowledge, attitudes, and practices related to COVID-19 preventive health habits and the underlying fear of COVID-19 in the Bangladeshi population and how they are affected by socio-demographic factors. The KAP section of the questionnaire related to a total of 12 score knowledge questions on COVID-19, categorical answers to attitudes towards the control of the pandemic, and practices of wearing masks and avoiding public gatherings. This study is similar to one study in China that found a significant relationship between knowledge and age and knowledge and educational level, with males reporting higher levels of knowledge than females regarding COVID-19 symptoms, precautions, and health advisory practices [16] . However, in our study, subjects living in Bangladesh reported similar knowledge for both males and females regarding COVID-19 symptoms, precautions, and health advisory practices. abstract: The study aims to determine the level of Knowledge, Attitude, and Practice (KAP) related to COVID-19 preventive health habits and perception of fear towards COVID-19 in subjects living in Bangladesh. Design: Prospective, cross-sectional survey of (n = 2157) male and female subjects, 13–88 years of age, living in Bangladesh. Methods: Ethical approval and trial registration were obtained before the commencement of the study. Subjects who volunteered to participate and signed the informed consent were enrolled in the study and completed the structured questionnaire on KAP and Fear of COVID-19 scale (FCV-19S). Results: Twenty-eight percent (28.69%) of subjects reported one or more COVID-19 symptoms, and 21.4% of subjects reported one or more co-morbidities. Knowledge scores were slightly higher in males (8.75± 1.58) than females (8.66± 1.70). Knowledge was significantly correlated with age (p < .005), an education level (p < .001), attitude (p < .001), and urban location (p < .001). Knowledge scores showed an inverse correlation with fear scores (p < .001). Eighty-three percent (83.7%) of subjects with COVID-19 symptoms reported wearing a mask in public, and 75.4% of subjects reported staying away from crowded places. Subjects with one or more symptoms reported higher fear compared to subjects without (18.73± 4.6; 18.45± 5.1). Conclusion: Bangladeshis reported a high prevalence of self-isolation, positive preventive health behaviors related to COVID-19, and moderate to high fear levels. Higher knowledge and Practice were found in males, higher education levels, older age, and urban location. Fear of COVID-19 was more prevalent in female and elderly subjects. A positive attitude was reported for the majority of subjects, reflecting the belief that COVID-19 was controllable and containable. url: https://www.ncbi.nlm.nih.gov/pubmed/32970769/ doi: 10.1371/journal.pone.0239646 id: cord-000255-73nlxqgk author: Hosseini, Parviez title: Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread date: 2010-09-15 words: 4022.0 sentences: 184.0 pages: flesch: 50.0 cache: ./cache/cord-000255-73nlxqgk.txt txt: ./txt/cord-000255-73nlxqgk.txt summary: CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Of all the models evaluated, a multivariate model with three predictors, (1) total country-level healthcare spending per capita, (2) estimated passenger volume arriving from Mexico via direct flights (direct flight capacity), and (3) passenger volume from Mexico via indirect, or two-leg, flights (indirect flight capacity), provided the best fit to the data using AIC, as detailed under Methods (Table 1 , DAIC = 0, overall x 2 = 54.33 on 5 degrees of freedom, p-value,0.0001). We validated the model by determining how well a model fit to data up until May 8th predicted reporting dates for fourteen countries where the disease was detected between May 9 th and May 19 th (Supplemental Online Figure S2 ). abstract: BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939898/ doi: 10.1371/journal.pone.0012763 id: cord-321705-6a7avlro author: Hou, Tianya title: Social support and mental health among health care workers during Coronavirus Disease 2019 outbreak: A moderated mediation model date: 2020-05-29 words: 5372.0 sentences: 281.0 pages: flesch: 46.0 cache: ./cache/cord-321705-6a7avlro.txt txt: ./txt/cord-321705-6a7avlro.txt summary: The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Thus, the present research employed a sample of Chinese health care workers during COVID-19 outbreak to explore a conceptual model in which, on the one hand, resilience mediated the association between social support and mental health; On the other hand, the indirect relationships between social support and mental health via resilience were moderated by age group. Considering the present study was to compare the indirect effect of social support on mental health via resilience between the young and middle-aged heath care workers, participants aged 50 or over were excluded. abstract: PURPOSES: During the outbreak of Coronavirus Disease 2019 (COVID-19) all over the world, the mental health conditions of health care workers are of great importance to ensure the efficiency of rescue operations. The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Structural equation modeling (SEM) was used to examine the mediation effect of resilience on the relation between social support and mental health, whereas moderated mediation analysis was performed by Hayes PROCESS macro. RESULTS: The findings showed that resilience could partially mediate the effect of social support on mental health among health care workers. Age group moderated the indirect relationship between social support and mental health via resilience. Specifically, compared with younger health care workers, the association between resilience and mental health would be attenuated in the middle-aged workers. CONCLUSIONS: The results add knowledge to previous literature by uncovering the underlying mechanisms between social support and mental health. The present study has profound implications for mental health services for health care workers during the peak period of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32470007/ doi: 10.1371/journal.pone.0233831 id: cord-000695-g5sum116 author: Hou, Yanxia title: Prediction and Identification of T Cell Epitopes in the H5N1 Influenza Virus Nucleoprotein in Chicken date: 2012-06-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: T cell epitopes can be used for the accurate monitoring of avian influenza virus (AIV) immune responses and the rational design of vaccines. No T cell epitopes have been previously identified in the H5N1 AIV virus nucleoprotein (NP) in chickens. For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. H5N1 AIV NP was computationally parsed into octapeptides or nonapeptides according to the peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes. Seventy-five peptide sequences were modelled and their MHC class I molecule-binding abilities were analysed by molecular docking. Twenty-five peptides (Ten for B4, six for B12, two for B15, and seven for B19) were predicted to be potential T cell epitopes in chicken. Nine of these peptides and one unrelated peptide were manually synthesized and their T cell responses were tested in vitro. Spleen lymphocytes were collected from SPF chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and they were stimulated using the synthesized peptides. The secretion of chicken IFN-γ and the proliferation of CD8(+) T cells were tested using an ELISA kit and flow cytometry, respectively. The significant secretion of chicken IFN-γ and proliferation of CD8(+) T lymphocytes increased by 13.7% and 11.9% were monitored in cells stimulated with peptides NP(89–97) and NP(198–206), respectively. The results indicate that peptides NP(89–97) (PKKTGGPIY) and NP(198–206) (KRGINDRNF) are NP T cell epitopes in chicken of certain haplotypes. The method used in this investigation is applicable to predicting T cell epitopes for other antigens in chicken, while this study also extends our understanding of the mechanisms of the immune response to AIV in chicken. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3379973/ doi: 10.1371/journal.pone.0039344 id: cord-262759-ec2c25q3 author: Hsieh, Yi-Ting title: Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus date: 2013-11-04 words: 4838.0 sentences: 223.0 pages: flesch: 40.0 cache: ./cache/cord-262759-ec2c25q3.txt txt: ./txt/cord-262759-ec2c25q3.txt summary: The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. We hypothesized that G6PD-deficient cells are less tolerant to oxidative stress upon bacterial infection, leading to the accumulation of more intracellular ROS when compared to the control scramble cells. To determine whether the reduced ROS accumulation and apoptotic activity, particularly in G6PD-deficient cells, was due to deceased αhemolysin expression upon VRSA infection in the presence of vancomycin, the production of intracellular ROS and cell apoptosis when the α-hemolysin inhibitor Oroxylin A was added to the media was quantified by flow cytometry. Our results presented here indicate that expression of active caspase-9, as well as the downstream caspase-3, was much higher in G6PD-deficient cells than in control scramble cells upon VRSA infection, suggesting that mitochondrial dysfunction may be the major cause of the increase in cell apoptosis (Figure 4) . abstract: Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells. url: https://www.ncbi.nlm.nih.gov/pubmed/24223971/ doi: 10.1371/journal.pone.0079566 id: cord-000536-0mn1gbll author: Hu, Le-Le title: Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions date: 2011-12-29 words: 5134.0 sentences: 265.0 pages: flesch: 48.0 cache: ./cache/cord-000536-0mn1gbll.txt txt: ./txt/cord-000536-0mn1gbll.txt summary: In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. In this study, we proposed a multi-target model based on chemical-chemical interactions for predicting the metabolic pathways where compounds participate in. Listed in Table 2 are the accuracies by each of the 11 prediction orders for the 3,137 compounds about their involvement in the 11 metabolic pathway classes using the 5-fold crossvalidation test. abstract: Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248422/ doi: 10.1371/journal.pone.0029491 id: cord-294591-793ywpcd author: Hu, Xiaoyun title: Self-Reported Use of Personal Protective Equipment among Chinese Critical Care Clinicians during 2009 H1N1 Influenza Pandemic date: 2012-09-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Critically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs), representing significant risk of nosocomial transmission to critical care clinicians and other patients. Despite a large body of literature and guidelines recommending infection control practices, numerous barriers have been identified in ICUs, leading to poor compliance to the use of personal protective equipment (PPE). The use of PPE among critical care clinicians has not been extensively evaluated, especially during the pandemic influenza. This study examined the knowledge, attitudes, and self-reported behaviors, and barriers to compliance with the use of PPE among ICU healthcare workers (HCWs) during the pandemic influenza. METHODOLOGY/PRINCIPAL FINDINGS: A survey instrument consisting of 36 questions was developed and mailed to all HCWs in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty-six percent of respondents reported having received training program of pandemic influenza before they cared for H1N1 patients, while 77% reported to have adequate knowledge of self and patient protection. Only 18% of respondents were able to correctly identify all components of PPE, and 55% reported high compliance (>80%) with PPE use during patient care. In multivariate analysis, vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use, organizational factors such as availability of PPE in ICU, and patient information of influenza precautions, as well as reprimand for noncompliance by the supervisors were associated with high compliance, whereas negative attitudes towards PPE use and violation of PPE use were independent predictors of low compliance. CONCLUSION/SIGNIFICANCE: Knowledge and self-reported compliance to recommended PPE use among Chinese critical care clinicians is suboptimal. The perceived barriers should be addressed in order to close the significant gap between perception and knowledge or behavior. url: https://www.ncbi.nlm.nih.gov/pubmed/22957101/ doi: 10.1371/journal.pone.0044723 id: cord-321834-n5w88l23 author: Huang, Cheng-Yang title: Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases date: 2015-05-19 words: 5231.0 sentences: 297.0 pages: flesch: 47.0 cache: ./cache/cord-321834-n5w88l23.txt txt: ./txt/cord-321834-n5w88l23.txt summary: Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. In this study, we investigated the effects of the substrates and inhibitors of allantoinase and dihydroorotase, including the flavonols myricetin, quercetin, kaempferol, and galangin, on inhibiting the catalytic activity of a putative dihydropyrimidinase from P. Although dihydromyricetin and myricetin were docked Inhibition of Dihydropyrimidinase by Flavonoids into the active site pocket of dihydropyrimidinase, their binding modes differed. In this study, we showed that dihydromyricetin, a flavonol, significantly inhibited the catalytic activities of dihydropyrimidinase toward both the natural substrate dihydrouracil and xenobiotic substrate 5-propyl-hydantoin (Fig 3) . For example, as shown in Fig 3, the inhibitory effect of kaempferol on the activity of dihydropyrimidinase was significant only with dihydrouracil as a substrate (with IC 50 value of 50 ± 2 μM), but not with 5-propyl-hydantoin. abstract: Dihydropyrimidinase is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. These metalloenzymes possess very similar active sites and may use a similar mechanism for catalysis. However, whether the substrates and inhibitors of other cyclic amidohydrolases can inhibit dihydropyrimidinase remains unclear. This study investigated the inhibition of dihydropyrimidinase by flavonoids and substrates of other cyclic amidohydrolases. Allantoin, dihydroorotate, 5-hydantoin acetic acid, acetohydroxamate, orotic acid, and 3-amino-1,2,4-triazole could slightly inhibit dihydropyrimidinase, and the IC(50) values of these compounds were within the millimolar range. The inhibition of dihydropyrimidinase by flavonoids, such as myricetin, quercetin, kaempferol, galangin, dihydromyricetin, and myricitrin, was also investigated. Some of these compounds are known as inhibitors of allantoinase and dihydroorotase. Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. The results from the Lineweaver−Burk plot indicated that dihydromyricetin was a competitive inhibitor. Results from fluorescence quenching analysis indicated that dihydromyricetin could form a stable complex with dihydropyrimidinase with the K (d) value of 22.6 μM. A structural study using PatchDock showed that dihydromyricetin was docked in the active site pocket of dihydropyrimidinase, which was consistent with the findings from kinetic and fluorescence studies. This study was the first to demonstrate that naturally occurring product dihydromyricetin inhibited dihydropyrimidinase, even more than the substrate analogs (>3 orders of magnitude). These flavonols, particularly myricetin, may serve as drug leads and dirty drugs (for multiple targets) for designing compounds that target several cyclic amidohydrolases. url: https://www.ncbi.nlm.nih.gov/pubmed/25993634/ doi: 10.1371/journal.pone.0127634 id: cord-001898-ntqyjqqk author: Huang, Chih-Wei title: Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date: 2016-01-05 words: 6578.0 sentences: 337.0 pages: flesch: 47.0 cache: ./cache/cord-001898-ntqyjqqk.txt txt: ./txt/cord-001898-ntqyjqqk.txt summary: The changes in tryptophan fluorescence were Dilution of monomeric K315A mutant protein denatured in 5 M GdmCl resulted in refolding to a similar conformation as the original monomeric state (Fig 5A and 5B) . Since refolding of partly unfolded monomeric mutant δ-crystallin resulted in a conformation with high exposure of hydrophobic regions, the occurrence of protein aggregation in the process was determined using light scattering measurement. An increase in fluorescence intensity resulting from binding of ThT with the aggregates over time was observed following dilution of 0.84 and 3 M GdmCl denatured monomeric mutant δ-crystallin into buffer (Fig 6B) . The unique stable conformation from unfolding of K315A mutant protein in the presence of urea suggests that the interactions provided by this residue at the interfaces may play a critical role in stabilization of the quaternary structure of δ-crystallin. abstract: δ-Crystallin is the major structural protein in avian eye lenses and is homologous to the urea cycle enzyme argininosuccinate lyase. This protein is structurally assembled as double dimers. Lys-315 is the only residue which is arranged symmetrically at the diagonal subunit interfaces to interact with each other. This study found that wild-type protein had both dimers and monomers present in 2–4 M urea whilst only monomers of the K315A mutant were observed under the same conditions, as judged by sedimentation velocity analysis. The assembly of monomeric K315A mutant was reversible in contrast to wild-type protein. Molecular dynamics simulations showed that the dissociation of primary dimers is prior to the diagonal dimers in wild-type protein. These results suggest the critical role of Lys-315 in stabilization of the diagonal dimer structure. Guanidinium hydrochloride (GdmCl) denatured wild-type or K315A mutant protein did not fold into functional protein. However, the urea dissociated monomers of K315A mutant protein in GdmCl were reversible folding through a multiple steps mechanism as measured by tryptophan and ANS fluorescence. Two partly unfolded intermediates were detected in the pathway. Refolding of the intermediates resulted in a conformation with greater amounts of hydrophobic regions exposed which was prone to the formation of protein aggregates. The formation of aggregates was not prevented by the addition of α-crystallin. These results highlight that the conformational status of the monomers is critical for determining whether reversible oligomerization or aggregate formation occurs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701392/ doi: 10.1371/journal.pone.0145957 id: cord-000984-64p3wpav author: Huang, Shang-Hui title: Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin date: 2013-06-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities. We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. We narrowed down the active site of CRT to residues 150–230, the activity of which also depends on dimerization. By contrast, rCRT/18-197 is almost completely inactive. When rCRT/18-412 is fractionated into oligomers and monomers by gel filtration, the oligomers maintain most of their immunological activities in terms of activating macrophages in vitro and inducing specific antibodies in vivo, while the monomers were much less active by comparison. Additionally, rCRT/18-412 oligomers are much better than monomers in binding to, and uptake by, macrophages. Inhibition of macrophage endocytosis partially blocks the stimulatory effect of rCRT/18-412. We conclude that the immunologically active site of CRT maps between residues 198–230 and that soluble CRT could acquire potent immuno-pathological activities in microenvironments favoring its oligomerization. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677884/ doi: 10.1371/journal.pone.0064951 id: cord-000082-jy7j8sh0 author: Huang, Ting title: Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection date: 2009-07-27 words: 6190.0 sentences: 271.0 pages: flesch: 57.0 cache: ./cache/cord-000082-jy7j8sh0.txt txt: ./txt/cord-000082-jy7j8sh0.txt summary: Most surprisingly, 20 of the 34 strains classified as HRV-C by comparative analysis of VP4/P2 sequences ( Table 2) were related more closely to HRV-A strains when their 59UTRs were analyzed, and showed incongruent clustering in phylogenetic trees (Figs. When sequencing the VP4/VP2 region of the HRV genome, several recent studies have identified new strains of viruses from children and adults with ARI, asthma, or otitis, which are clustered differently from HRV-A and HRV-B, and have been classified into a novel HRV-C species [7, 8, 17, 18, 19, 20, 21, 25, 26, 27, 28] . In our study, we identified 34 HRVs (51.5%) that clustered differently from HRV-A and HRV-B in a phylogenetic tree that was established on the basis of VP4/VP2 sequences, which were related to recent strains classified in the novel HRV-C species (Fig. 1, Table 2 ). abstract: BACKGROUND: Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. METHODOLOGY/FINDINGS: We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. CONCLUSION: Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712091/ doi: 10.1371/journal.pone.0006355 id: cord-287739-58fth3xl author: Huang, Yhu-Chering title: Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign date: 2011-08-12 words: 3821.0 sentences: 188.0 pages: flesch: 42.0 cache: ./cache/cord-287739-58fth3xl.txt txt: ./txt/cord-287739-58fth3xl.txt summary: CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important pathogens of bacteremia in the intensive care units (ICU). To reduce and control healthcare-associated infections (HAIs) caused by MRSA, a ''''search and destroy'''' strategy, which first detects the patients with MRSA colonization and then decolonizes the MRSA with certain antimicrobial agents, was recently proposed and implemented in some hospitals of different countries, with inconsistent effects [12] [13] [14] [15] [16] . Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units abstract: BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA. METHODOLOGY/PRINCIPAL FINDINGS: To control MRSA spread in our NICUs, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since January 2000, augmentation of aseptic care over the insertion site of central venous catheter since July 2001, introduction of alcohol-based handrubs since April 2003, surveillance culture for MRSA and cohort care for the colonized patients between March 2003 and February 2004, and surveillance culture with subsequent decolonization of MRSA between August 2005 and July 2006. After implementation of these measures, MRSA healthcare-associated infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream infection reduced from 40 cases in 1999 to only one case in 2006. Compared to those obtained during the period of surveillance culture without decolonization, both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs. 12%, p<0.001) decreased significantly during the period of surveillance and decolonization. Molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between 1998 and 2005, almost disappeared in 2006, while the community clones increased significantly in 2006–2007. CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs. url: https://www.ncbi.nlm.nih.gov/pubmed/21857979/ doi: 10.1371/journal.pone.0023001 id: cord-001843-ceatyj3o author: Huang, Yong title: Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay date: 2015-11-06 words: 5184.0 sentences: 231.0 pages: flesch: 50.0 cache: ./cache/cord-001843-ceatyj3o.txt txt: ./txt/cord-001843-ceatyj3o.txt summary: PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. The duplex UNDP-PCR assay is suitable for simultaneous detection of RNA and DNA viruses in early viral infection, providing an effective approach for diagnosis of swine diseases. The duplex UNDP-PCR assay developed in this study provided a useful tool for simultaneous detection of RNA (TGEV) and DNA viruses (PCV2) without the need for viral nucleic acid extraction, purification and reverse transcription. abstract: Mixed infection of multiple viruses is common in modern intensive pig rearing. However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level. In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system. PCV2 and TGEV are selected as representatives of the two different types of viruses. PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently. The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays. No cross-reaction was observed with other viruses. The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636378/ doi: 10.1371/journal.pone.0141545 id: cord-293946-4bquxdqa author: Huong, Nguyen Quynh title: Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014 date: 2020-08-10 words: 6229.0 sentences: 292.0 pages: flesch: 51.0 cache: ./cache/cord-293946-4bquxdqa.txt txt: ./txt/cord-293946-4bquxdqa.txt summary: In this study we investigated the presence and diversity of coronavirus sequences in the field rat trade distribution chain, wildlife farms specializing in raising rodents for human consumption, and bat guano "farms" and roosts near human dwellings to better understand the natural hosts of coronaviruses and the risk for these interfaces to facilitate spillover into humans. Out of 70 sites, coronavirus positives were detected at 58 including 100% (24/24) of live rat trade sites, 60.7% (17/28) of rodent wildlife farm sites, 94.1% (16/17) of bat guano farm sites, and at the one natural pteropid bat roost. Significant findings of this study are the high proportion of coronavirus positive wildlife (bats and rodents) and the increasing proportion of positives found along the rat trade supply chain from sub-interfaces close to the capture site (rat traders) to restaurants. abstract: Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013–2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were also detected in rodents on the majority of wildlife farms sampled (60.7%, 17/28). These coronaviruses were found in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are raised on wildlife farms for human consumption as food. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces on wildlife farms. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people. url: https://www.ncbi.nlm.nih.gov/pubmed/32776964/ doi: 10.1371/journal.pone.0237129 id: cord-000079-533xlisc author: Huszthy, Peter C. title: Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy date: 2009-07-20 words: 5427.0 sentences: 268.0 pages: flesch: 45.0 cache: ./cache/cord-000079-533xlisc.txt txt: ./txt/cord-000079-533xlisc.txt summary: Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. Furthermore, we showed a significant therapeutic effect of LCMV-GP pseudotyped lentiviral vectors in the cell-line based 9L rat glioma model using the suicide gene HSV-1-tk. In the presented work, we showed that both, VSV-G and LCMV-GP pseudotyped lentiviruses efficiently transduced human glioma cells in vitro and in vivo, whereas gammaretroviral transduction was inefficient. When analyzed at higher magnification, both LCMV-GP and VSV-G pseudotyped lentiviral vectors showed efficient transgene delivery to nestin-positive tumor cells in solid ( Figure 3B ,E) and invasive tumor areas ( Figure 3C ,F). abstract: BACKGROUND: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model. METHODOLOGY/PRINCIPAL FINDINGS: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors. Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo. Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect. CONCLUSIONS/SIGNIFICANCE: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients. The inefficient gene delivery by gammaretroviral vectors is in line with the results obtained in clinical therapy for GBM and thus confirms the high reproducibility of the invasive glioma animal model for translational research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707627/ doi: 10.1371/journal.pone.0006314 id: cord-298679-w0yp4u19 author: Iftimie, Simona title: Risk factors associated with mortality in hospitalized patients with SARS-CoV-2 infection. A prospective, longitudinal, unicenter study in Reus, Spain date: 2020-09-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Spain is one of the countries that has suffered the most from the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain that causes coronavirus disease 2019 (COVID-19). However, there is a lack of information on the characteristics of this disease in the Spanish population. The objective of this study has been to characterize our patients from an epidemiological point of view and to identify the risk factors associated with mortality in our geographical area. We performed a prospective, longitudinal study on 188 hospitalized cases of SARS-Cov-2 infection in Hospital Universitari de Sant Joan, in Reus, Spain, admitted between 15(th) March 2020 and 30(th) April 2020. We recorded demographic data, signs and symptoms and comorbidities. We also calculated the Charlson and McCabe indices. A total of 43 deaths occurred during the study period. Deceased patients were older than the survivors (77.7 ± 13.1 vs. 62.8 ± 18.4 years; p < 0.001). Logistic regression analyses showed that fever, pneumonia, acute respiratory distress syndrome, diabetes mellitus and cancer were the variables that showed independent and statistically significant associations with mortality. The Charlson index was more efficient than the McCabe index in discriminating between deceased and survivors. This is one of the first studies to describe the factors associated with mortality in patients infected with SARS-CoV-2 in Spain, and one of the few in the Mediterranean area. We identified the main factors independently associated with mortality in our population. Further studies are needed to complete and confirm our findings. url: https://doi.org/10.1371/journal.pone.0234452 doi: 10.1371/journal.pone.0234452 id: cord-275058-61eof7y8 author: Inoue, Hiroyasu title: The propagation of economic impacts through supply chains: The case of a mega-city lockdown to prevent the spread of COVID-19 date: 2020-09-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This study quantifies the economic effect of a possible lockdown of Tokyo to prevent the spread of COVID-19. The negative effect of such a lockdown may propagate to other regions through supply chains because of supply and demand shortages. Applying an agent-based model to the actual supply chains of nearly 1.6 million firms in Japan, we simulate what would happen to production activities outside Tokyo if production activities that are not essential to citizens’ survival in Tokyo were shut down for a certain period. We find that if Tokyo were locked down for a month, the indirect effect on other regions would be twice as large as the direct effect on Tokyo, leading to a total production loss of 27 trillion yen in Japan or 5.2% of the country’s annual GDP. Although the production that would be shut down in Tokyo accounts for 21% of the total production in Japan, the lockdown would result in an 86% reduction of the daily production in Japan after one month. url: https://doi.org/10.1371/journal.pone.0239251 doi: 10.1371/journal.pone.0239251 id: cord-343973-n5ogyxz7 author: Ip, Andrew title: Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—An observational study date: 2020-08-13 words: 4322.0 sentences: 239.0 pages: flesch: 43.0 cache: ./cache/cord-343973-n5ogyxz7.txt txt: ./txt/cord-343973-n5ogyxz7.txt summary: In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Subsequently, an observational cohort study of 1376 hospitalized patients from a New York hospital using propensity modeling found no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32) [14] . A recently reported randomized Brazilian trial enrolling 504 hospitalized SARS-CoV-2 confirmed patients with mild-to-moderate disease (defined as not requiring significant supplemental oxygen support) found that a 7-day course of hydroxychloroquine either with azithromycin or alone did not result in better clinical outcomes as measured by a seven-level ordinal scale at 15 days [16] . In this observational cohort study we report our survival outcomes with hydroxychloroquine and tocilizumab among hospitalized patients with COVID-19. abstract: Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80–1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83–1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75–1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57–1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993 url: https://doi.org/10.1371/journal.pone.0237693 doi: 10.1371/journal.pone.0237693 id: cord-317779-j67vb7f3 author: Irizarry, Kristopher J. L. title: RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date: 2017-08-28 words: 9733.0 sentences: 443.0 pages: flesch: 42.0 cache: ./cache/cord-317779-j67vb7f3.txt txt: ./txt/cord-317779-j67vb7f3.txt summary: Our experimental design leveraged an initial 6 day window for monocytes to differentiate into macrophages, which was followed by IFNγ stimulation between 1 and 24 h to further characterize subsequent RNA gene expression and the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages The t-3 day time point, representing 3 days of differentiation in cell culture, exhibited the greatest expression of genes with a total of 11,429 expressed in both B19 and B2 birds while just 4068 genes lacked evidence of expression in both haplotypes. Overall, the gene enrichment analysis of the RNA sequence data provides a cellular-level picture of the specific biological processes that occur over time following activation of monocyte-derived macrophages. abstract: Discovering genetic biomarkers associated with disease resistance and enhanced immunity is critical to developing advanced strategies for controlling viral and bacterial infections in different species. Macrophages, important cells of innate immunity, are directly involved in cellular interactions with pathogens, the release of cytokines activating other immune cells and antigen presentation to cells of the adaptive immune response. IFNγ is a potent activator of macrophages and increased production has been associated with disease resistance in several species. This study characterizes the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages.A large-scale RNA sequencing approach was employed to sequence the RNA of purified macrophages from each haplotype group (B2 vs. B19) during differentiation and after stimulation. Our results demonstrate that a large number of genes exhibit divergent expression between B2 and B19 haplotype cells both prior and after stimulation. These differences in gene expression appear to be regulated by complex epigenetic mechanisms that need further investigation. url: https://www.ncbi.nlm.nih.gov/pubmed/28846708/ doi: 10.1371/journal.pone.0179391 id: cord-252795-x66zqmgv author: Islam, Md. Akhtarul title: Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey date: 2020-08-26 words: 4011.0 sentences: 214.0 pages: flesch: 47.0 cache: ./cache/cord-252795-x66zqmgv.txt txt: ./txt/cord-252795-x66zqmgv.txt summary: title: Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey Following the detection of first COVID-19 case on March 8, 2020 [6] , Bangladesh like many other countries put the lockdown strategy into effect on March 26, 2020 , to ensure ''social distance'' through ''home quarantine'' to curb the ''spread'' among its population [7] [8] [9] , since a precise treatment or vaccine for the infected and people at risk are yet to achieved by the global health community [10, 11] . The ongoing COVID-19 pandemic is creating a psycho-emotional chaotic situation as countries have been reporting a sharp rise of mental health problems, including anxiety, depression, stress, sleep disorder as well as fear, among its citizens [15] [16] [17] [18] [19] , that eventually increased the substance use [15] and sometimes suicidal behavior [20] [21] [22] . Researchers in China observed that the greater exposure to ''misinformation'' through social media are more likely contributing to the development of anxiety, depression, and other mental health problems among its population of different socioeconomic background [23] [24] [25] [26] . abstract: The purpose of this study was to investigate the prevalence of depression and anxiety among Bangladeshi university students during the COVID-19 pandemic. It also aimed at identifying the determinants of depression and anxiety. A total of 476 university students living in Bangladesh participated in this cross-sectional web-based survey. A standardized e-questionnaire was generated using the Google Form, and the link was shared through social media—Facebook. The information was analyzed in three consecutive levels, such as univariate, bivariate, and multivariate analysis. Students were experiencing heightened depression and anxiety. Around 15% of the students reportedly had moderately severe depression, whereas 18.1% were severely suffering from anxiety. The binary logistic regression suggests that older students have greater depression (OR = 2.886, 95% CI = 0.961–8.669). It is also evident that students who provided private tuition in the pre-pandemic period had depression (OR = 1.199, 95% CI = 0.736–1.952). It is expected that both the government and universities could work together to fix the academic delays and financial problems to reduce depression and anxiety among university students. url: https://doi.org/10.1371/journal.pone.0238162 doi: 10.1371/journal.pone.0238162 id: cord-013265-qrfi6e5c author: Isono, Toshihito title: Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model date: 2020-10-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S. pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S. pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S. pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S. pneumoniae in the BALF and the concentration of S. pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561173/ doi: 10.1371/journal.pone.0240329 id: cord-353253-kk2q71vg author: Itokawa, Kentaro title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by multiplex tiling PCR date: 2020-09-18 words: 3327.0 sentences: 179.0 pages: flesch: 52.0 cache: ./cache/cord-353253-kk2q71vg.txt txt: ./txt/cord-353253-kk2q71vg.txt summary: Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. In our experience, the low to zero depth for those two amplicons was the most frequent bottleneck for using the ARTIC primer set V1 to sequence all targeted genomic regions from samples with middle to low viral load (Ct > 27). The results indicated that preventing primer dimerformation is an effective measure to improve coverage bias in the ARTIC Network''s SARS-CoV-2 genome sequencing protocol, and may be applicable to other PrimalSeq methods in general. The formation of primer-dimers is a major cause of coverage bias in the ARTIC Network''s multiplex PCR protocol for SARS-CoV-2 genome sequencing. A proposal of an alternative primer for the ARTIC Network''s multiplex PCR to improve coverage of SARS-CoV-2 genome sequencing (manuscript version 1) abstract: Since December 2019, the coronavirus disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2 has rapidly spread to almost every nation in the world. Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. The ARTIC primer set amplifies 98 amplicons, which are separated only in two PCRs, across a nearly entire viral genome. The original primer set and protocol showed a fairly small amplification bias when clinical samples with relatively high viral loads were used. However, as sample’s viral load become low, rapid decrease in abundances of several amplicons were seen. In this report, we will show that dimer formations between some primers are the major cause of coverage bias in the multiplex PCR. Based on this, we propose 12 alternative primers in total in the ARTIC primer set that were predicted to be involved in 14 primer interactions. The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network’s original (V1) and modified (V3) primer set. url: https://doi.org/10.1371/journal.pone.0239403 doi: 10.1371/journal.pone.0239403 id: cord-304616-k92fa15l author: Izes, Aaron M. title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date: 2020-08-05 words: 4208.0 sentences: 234.0 pages: flesch: 50.0 cache: ./cache/cord-304616-k92fa15l.txt txt: ./txt/cord-304616-k92fa15l.txt summary: title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. Consequently, the aim of this study was two-fold: first, to develop and validate a high pressure liquid chromatography (HPLC) method to detect mefloquine in feline plasma, and second, to determine the in vitro plasma protein binding of mefloquine in both clinically normal and FIP-affected cats. Here, although a significant difference was found between the plasma protein binding of mefloquine in clinically normal and FIP-affected cats, due to the unknown biological variability of the assay, it is likely that this difference is equivocal. This study has validated an accurate and reliable assay to detect mefloquine in feline plasma and demonstrated that mefloquine is highly plasma protein bound in both clinically normal and FIP-affected cats. abstract: The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay’s lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%). url: https://doi.org/10.1371/journal.pone.0236754 doi: 10.1371/journal.pone.0236754 id: cord-328627-cf8f71dr author: Jando, Julia title: Expression and regulation of the neutral amino acid transporter B(0)AT1 in rat small intestine date: 2017-09-15 words: 8971.0 sentences: 389.0 pages: flesch: 50.0 cache: ./cache/cord-328627-cf8f71dr.txt txt: ./txt/cord-328627-cf8f71dr.txt summary: Protein abundance of B 0 AT1, ACE2 and CD13 along the small intestine was measured by Western blotting performed on brush-border membrane vesicles (bbmv) prepared from duodenum, proximal-, middle-and distal jejunum as well as ileum and quantified relative to the microvilli cytoskeletal protein β-actin,. Additionally, rats fed different diets (NP, HP and AA) were euthanized 3 h after light-onset (ZT3) or 3 h after light-offset The three proteins tested in these bbmv showed a clearly increasing expression level in distal direction along the small intestine, as shown for distal versus proximal jejunum at both time points (Fig 1C, right panels) . This suggested the possibility that rats on a HP or AA diet may have expressed more functional B 0 AT1 along the small intestine and performed a more efficient absorption of neutral amino acids like L-isoleucine. abstract: Absorption of neutral amino acids across the luminal membrane of intestinal enterocytes is mediated by the broad neutral amino acid transporter B(0)AT1 (SLC6A19). Its intestinal expression depends on co-expression of the membrane-anchored peptidase angiotensin converting enzyme 2 (ACE2) and is additionally enhanced by aminopeptidase N (CD13). We investigated in this study the expression of B(0)AT1 and its auxiliary peptidases as well as its transport function along the rat small intestine. Additionally, we tested its possible short- and long-term regulation by dietary proteins and amino acids. We showed by immunofluorescence that B(0)AT1, ACE2 and CD13 co-localize on the luminal membrane of small intestinal villi and by Western blotting that their protein expression increases in distal direction. Furthermore, we observed an elevated transport activity of the neutral amino acid L-isoleucine during the nocturnal active phase compared to the inactive one. Gastric emptying was delayed by intragastric application of an amino acid cocktail but we observed no acute dietary regulation of B(0)AT1 protein expression and L-isoleucine transport. Investigation of the chronic dietary regulation of B(0)AT1, ACE2 and CD13 by different diets revealed an increased B(0)AT1 protein expression under amino acid-supplemented diet in the proximal section but not in the distal one and for ACE2 protein expression a reverse localization of the effect. Dietary regulation for CD13 protein expression was not as distinct as for the two other proteins. Ring uptake experiments showed a tendency for increased L-isoleucine uptake under amino acid-supplemented diet and in vivo L-isoleucine absorption was more efficient under high protein and amino acid-supplemented diet. Additionally, plasma levels of branched-chain amino acids were elevated under high protein and amino acid diet. Taken together, our experiments did not reveal an acute amino acid-induced regulation of B(0)AT1 but revealed a chronic dietary adaptation mainly restricted to the proximal segment of the small intestine. url: https://www.ncbi.nlm.nih.gov/pubmed/28915252/ doi: 10.1371/journal.pone.0184845 id: cord-001251-forh7lw4 author: Jank, Johanna M. title: The Domain-Specific and Temperature-Dependent Protein Misfolding Phenotype of Variant Medium-Chain acyl-CoA Dehydrogenase date: 2014-04-09 words: 7785.0 sentences: 553.0 pages: flesch: 51.0 cache: ./cache/cord-001251-forh7lw4.txt txt: ./txt/cord-001251-forh7lw4.txt summary: Here we established a comprehensive experimental setup to analyze the structural consequences of eight ACADM missense mutations (p.Ala52Val, p.Tyr67His, p.Tyr158His, p.Arg206Cys, p.Asp266Gly, p.Lys329Glu, p.Arg334Lys, p.Arg413Ser) identified after newborn screening and linked the corresponding protein misfolding phenotype to the site of side-chain replacement with respect to the domain. In a previous study, we provided first experimental evidence for the impact of eight additional ACADM mutations identified in NBS on MCAD structure and function and all of these were clearly associated with conformational derangement and decreased protein stability [16] . Moreover, we summarized and quantified the structural data and visualized the molecular protein misfolding phenotype of the variant MCAD proteins in a 3D plot comparing them to the wild-type, to p.Lys329Glu, the classical severe mutation, and to p.Tyr67His, discussed to be a mild mutation. To visualize results from experiments investigating thermal stability, kinetic stability, and conformation of MCAD wild-type and variants, we combined data and developed relative scores assessing the severity of mutation-induced changes. abstract: The implementation of expanded newborn screening programs reduced mortality and morbidity in medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by mutations in the ACADM gene. However, the disease is still potentially fatal. Missense induced MCADD is a protein misfolding disease with a molecular loss-of-function phenotype. Here we established a comprehensive experimental setup to analyze the structural consequences of eight ACADM missense mutations (p.Ala52Val, p.Tyr67His, p.Tyr158His, p.Arg206Cys, p.Asp266Gly, p.Lys329Glu, p.Arg334Lys, p.Arg413Ser) identified after newborn screening and linked the corresponding protein misfolding phenotype to the site of side-chain replacement with respect to the domain. With fever being the crucial risk factor for metabolic decompensation of patients with MCADD, special emphasis was put on the analysis of structural and functional derangements related to thermal stress. Based on protein conformation, thermal stability and kinetic stability, the molecular phenotype in MCADD depends on the structural region that is affected by missense-induced conformational changes with the central β-domain being particularly prone to structural derangement and destabilization. Since systematic classification of conformational derangements induced by ACADM mutations may be a helpful tool in assessing the clinical risk of patients, we scored the misfolding phenotype of the variants in comparison to p.Lys329Glu (K304E), the classical severe mutation, and p.Tyr67His (Y42H), discussed to be mild. Experiments assessing the impact of thermal stress revealed that mutations in the ACADM gene lower the temperature threshold at which MCAD loss-of-function occurs. Consequently, increased temperature as it occurs during intercurrent infections, significantly increases the risk of further conformational derangement and loss of function of the MCAD enzyme explaining the life-threatening clinical courses observed during fever episodes. Early and aggressive antipyretic treatment thus may be life-saving in patients suffering from MCADD. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981736/ doi: 10.1371/journal.pone.0093852 id: cord-299852-t0mqe7yy author: Janssen, Loes H. C. title: Does the COVID-19 pandemic impact parents’ and adolescents’ well-being? An EMA-study on daily affect and parenting date: 2020-10-16 words: 8570.0 sentences: 476.0 pages: flesch: 51.0 cache: ./cache/cord-299852-t0mqe7yy.txt txt: ./txt/cord-299852-t0mqe7yy.txt summary: In this ecological momentary assessment study, we investigated if the COVID-19 pandemic affected positive and negative affect of parents and adolescents and parenting behaviors (warmth and criticism). However, Intolerance of uncertainty, nor any pandemic related characteristics (i.e. living surface, income, relatives with COVID-19, hours of working at home, helping children with school and contact with COVID-19 patients at work) were linked to the increase of parents'' negative affect during COVID-19. In addition, we asked parents and adolescents about daily difficulties and helpful activities during the COVID-19 pandemic that possibly influenced their affect in positive and negative ways. During the COVID-19 pandemic, the most reported daily difficulties across the 14 days of EMA for parents were (1) missing social contact with friends (14.6%), (2) concerns about the coronavirus in general (13.5%), (3) irritations with family members (12.8%), (4) worrying about health of others (8.3%), and (5) coronavirus-related news items (8.0%). abstract: Due to the COVID- 19 outbreak in the Netherlands (March 2020) and the associated social distancing measures, families were enforced to stay at home as much as possible. Adolescents and their families may be particularly affected by this enforced proximity, as adolescents strive to become more independent. Yet, whether these measures impact emotional well-being in families with adolescents has not been examined. In this ecological momentary assessment study, we investigated if the COVID-19 pandemic affected positive and negative affect of parents and adolescents and parenting behaviors (warmth and criticism). Additionally, we examined possible explanations for the hypothesized changes in affect and parenting. To do so, we compared daily reports on affect and parenting that were gathered during two periods of 14 consecutive days, once before the COVID-19 pandemic (2018–2019) and once during the COVID-19 pandemic. Multilevel analyses showed that only parents’ negative affect increased as compared to the period before the pandemic, whereas this was not the case for adolescents’ negative affect, positive affect and parenting behaviors (from both the adolescent and parent perspective). In general, intolerance of uncertainty was linked to adolescents’ and parents’ negative affect and adolescents’ positive affect. However, Intolerance of uncertainty, nor any pandemic related characteristics (i.e. living surface, income, relatives with COVID-19, hours of working at home, helping children with school and contact with COVID-19 patients at work) were linked to the increase of parents’ negative affect during COVID-19. It can be concluded that on average, our sample (consisting of relatively healthy parents and adolescents) seems to deal fairly well with the circumstances. The substantial heterogeneity in the data however, also suggest that whether or not parents and adolescents experience (emotional) problems can vary from household to household. Implications for researchers, mental health care professionals and policy makers are discussed. url: https://doi.org/10.1371/journal.pone.0240962 doi: 10.1371/journal.pone.0240962 id: cord-346314-o9fjpqaj author: Jarboui, Mohamed Ali title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date: 2012-11-15 words: 10004.0 sentences: 521.0 pages: flesch: 36.0 cache: ./cache/cord-346314-o9fjpqaj.txt txt: ./txt/cord-346314-o9fjpqaj.txt summary: Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. Following the detailed annotation of the quantitative abundance changes in the nucleolar protein composition upon Tat expression, we focussed on the Tat-affected cellular complexes and signalling pathways associated with ribosome biogenesis, spliceosome, molecular chaperones, DNA replication and repair and metabolism and discuss their potential involvement in HIV-1 pathogenesis. In this study, we investigated the quantitative changes in the nucleolar proteome of Jurkat T cells constitutively expressing HIV-1 Tat (86aa) versus their Tat-negative counterpart, using stable isotope labelling with amino acids in cell culture (SILAC) technology, followed by ESI tandem mass spectrometry and implemented the experimental approach described in Figure 1A . abstract: The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins collectively participate in interconnected networks converging to adapt the nucleolus dynamic activities, which favor host biosynthetic activities and may contribute to create a cellular environment supporting robust HIV-1 production. url: https://www.ncbi.nlm.nih.gov/pubmed/23166591/ doi: 10.1371/journal.pone.0048702 id: cord-353200-5csewb1k author: Jehi, Lara title: Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19 date: 2020-08-11 words: 4344.0 sentences: 226.0 pages: flesch: 40.0 cache: ./cache/cord-353200-5csewb1k.txt txt: ./txt/cord-353200-5csewb1k.txt summary: OBJECTIVE: To characterize a large cohort of patients hospitalized with COVID-19, their outcomes, develop and validate a statistical model that allows individualized prediction of future hospitalization risk for a patient newly diagnosed with COVID-19. DESIGN: Retrospective cohort study of patients with COVID-19 applying a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to retain the most predictive features for hospitalization risk, followed by validation in a temporally distinct patient cohort. MEASUREMENTS: Demographic, clinical, social influencers of health, exposure risk, medical co-morbidities, vaccination history, presenting symptoms, medications, and laboratory values were collected on all patients, and considered in our model development. Hospitalization risk prediction and outcomes in COVID-19 PLOS ONE | https://doi.org/10.1371/journal.pone.0237419 August 11, 2020 2 / 15 ethical restrictions by the Cleveland clinic regulatory bodies including the institutional review Board and legal counsel. We also develop and validate a statistical model that can assist with individualized prediction of hospitalization risk for a patient with COVID-19. abstract: BACKGROUND: Coronavirus Disease 2019 is a pandemic that is straining healthcare resources, mainly hospital beds. Multiple risk factors of disease progression requiring hospitalization have been identified, but medical decision-making remains complex. OBJECTIVE: To characterize a large cohort of patients hospitalized with COVID-19, their outcomes, develop and validate a statistical model that allows individualized prediction of future hospitalization risk for a patient newly diagnosed with COVID-19. DESIGN: Retrospective cohort study of patients with COVID-19 applying a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to retain the most predictive features for hospitalization risk, followed by validation in a temporally distinct patient cohort. The final model was displayed as a nomogram and programmed into an online risk calculator. SETTING: One healthcare system in Ohio and Florida. PARTICIPANTS: All patients infected with SARS-CoV-2 between March 8, 2020 and June 5, 2020. Those tested before May 1 were included in the development cohort, while those tested May 1 and later comprised the validation cohort. MEASUREMENTS: Demographic, clinical, social influencers of health, exposure risk, medical co-morbidities, vaccination history, presenting symptoms, medications, and laboratory values were collected on all patients, and considered in our model development. RESULTS: 4,536 patients tested positive for SARS-CoV-2 during the study period. Of those, 958 (21.1%) required hospitalization. By day 3 of hospitalization, 24% of patients were transferred to the intensive care unit, and around half of the remaining patients were discharged home. Ten patients died. Hospitalization risk was increased with older age, black race, male sex, former smoking history, diabetes, hypertension, chronic lung disease, poor socioeconomic status, shortness of breath, diarrhea, and certain medications (NSAIDs, immunosuppressive treatment). Hospitalization risk was reduced with prior flu vaccination. Model discrimination was excellent with an area under the curve of 0.900 (95% confidence interval of 0.886–0.914) in the development cohort, and 0.813 (0.786, 0.839) in the validation cohort. The scaled Brier score was 42.6% (95% CI 37.8%, 47.4%) in the development cohort and 25.6% (19.9%, 31.3%) in the validation cohort. Calibration was very good. The online risk calculator is freely available and found at https://riskcalc.org/COVID19Hospitalization/. LIMITATION: Retrospective cohort design. CONCLUSION: Our study crystallizes published risk factors of COVID-19 progression, but also provides new data on the role of social influencers of health, race, and influenza vaccination. In a context of a pandemic and limited healthcare resources, individualized outcome prediction through this nomogram or online risk calculator can facilitate complex medical decision-making. url: https://www.ncbi.nlm.nih.gov/pubmed/32780765/ doi: 10.1371/journal.pone.0237419 id: cord-001117-llb4f74a author: Ji, Wen-Jie title: Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments date: 2013-11-19 words: 4964.0 sentences: 257.0 pages: flesch: 34.0 cache: ./cache/cord-001117-llb4f74a.txt txt: ./txt/cord-001117-llb4f74a.txt summary: Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. Based on current evidence, we speculated that pharmacological inhibition of MR with clinically approved drug, may regulate lung macrophage phenotype switching, as well as their progenitors, bone marrow-derived circulating monocytes, and may confer novel therapeutic potential in a murine model of bleomycin-induced acute pulmonary injury and fibrosis. abstract: BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834272/ doi: 10.1371/journal.pone.0081090 id: cord-288440-w7g2agaf author: Jia, Rui title: The C-Terminal Sequence of IFITM1 Regulates Its Anti-HIV-1 Activity date: 2015-03-04 words: 4902.0 sentences: 276.0 pages: flesch: 53.0 cache: ./cache/cord-288440-w7g2agaf.txt txt: ./txt/cord-288440-w7g2agaf.txt summary: This inhibition appears to be specific to HIV-1, since neither the WT IFITM1 nor its C-terminal truncations affected entry that was mediated by the G protein of vesicular stomatitis virus (VSV) ( Fig. 2A and 2B) . Removing the last 9 or 14 amino acids from C-terminal sequence re-localized the majority of IFITM1 to the cell periphery (Fig. 3A) , indicating that these C-terminus truncated IFITM1 mutants are mostly positioned at the plasma membrane where HIV-1 entry occurs. We recently reported that HIV-1 BH10 became resistant to IFITM1 restriction in the spread infection through acquiring mutations in viral Env and Vpu proteins that together enhance the virus transmission between cells [27] . One possible scenario is that HIV-1 Env protein may modulate virus sensitivity to human IFITM1 restriction by virtue of its ability to mediate and regulate virus cell-to-cell transmission. abstract: The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1(NL4-3)) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1(NL4-3) is profoundly inhibited by an IFITM1 mutant, known as Δ(117–125), which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117–125) mutant diminishes HIV-1(NL4-3) entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117–125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117–125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization. url: https://www.ncbi.nlm.nih.gov/pubmed/25738301/ doi: 10.1371/journal.pone.0118794 id: cord-319256-7pyinx1a author: Jin, Xin title: The values of coagulation function in COVID-19 patients date: 2020-10-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVE: To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. METHODS: We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). RESULT: The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What’s more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. CONCLUSION: Most COVID-19 patients with inordinate coagulation systems, dynamic monitoring of coagulation parameters might be a key in the control of COVID-19 death. url: https://www.ncbi.nlm.nih.gov/pubmed/33119703/ doi: 10.1371/journal.pone.0241329 id: cord-311941-0dpm35dd author: Jones, Bryony A. title: Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study date: 2013-12-02 words: 5745.0 sentences: 253.0 pages: flesch: 56.0 cache: ./cache/cord-311941-0dpm35dd.txt txt: ./txt/cord-311941-0dpm35dd.txt summary: Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A case had 18 times the odds of being born to a dam that was PregSurevaccinated rather than unvaccinated compared with a control, if the dam was first lactation and the calf did not receive colostrum from other cows, adjusting for type of milk fed (amOR 17.8; ci. A case had 3 times the odds of having been fed raw milk only from its dam rather than other types of milk (with or without dams milk) compared with a control (amOR 3.4; ci 1.6, 7.5; p = 0.002) when adjusting for dam PregSure-vaccination, lactation number and source of colostrum. Case control study to investigate risk factors for bovine neonatal pancytopenia (BNP) in young calves in southern Germany abstract: Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others. url: https://doi.org/10.1371/journal.pone.0080619 doi: 10.1371/journal.pone.0080619 id: cord-000131-ugbwvy6j author: Jones, James Holland title: Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1) date: 2009-12-03 words: 4322.0 sentences: 216.0 pages: flesch: 48.0 cache: ./cache/cord-000131-ugbwvy6j.txt txt: ./txt/cord-000131-ugbwvy6j.txt summary: Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the outbreak during the first few days of widespread media coverage (April 29 -May 5, 2009) of the emergence of novel swine-origin Influenza A(H1N1). To evaluate the hypothesis that respondents'' affective state (subjective anxiety, fatalism about infection) predicts protective measures, we include in the model demographic (age, gender), epidemiological (household size, number of contacts, survey day), and media (source of information on the outbreak) conditioning variables. While our sampling design is subject to many of the usual criticisms of internet-based surveys and is not necessarily representative of the general population, the unparalleled immediacy, longitudinal nature, and the large number of respondents it contains make our data set unique and scientifically important for the study of the spread of information and distribution of risk perception and behavioral change during the most uncertain time (i.e. the initial phase) of an epidemic of a virus novel to the human population. abstract: BACKGROUND: Since late April, 2009, a novel influenza virus A (H1N1), generally referred to as the “swine flu,” has spread around the globe and infected hundreds of thousands of people. During the first few days after the initial outbreak in Mexico, extensive media coverage together with a high degree of uncertainty about the transmissibility and mortality rate associated with the virus caused widespread concern in the population. The spread of an infectious disease can be strongly influenced by behavioral changes (e.g., social distancing) during the early phase of an epidemic, but data on risk perception and behavioral response to a novel virus is usually collected with a substantial delay or after an epidemic has run its course. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the Influenza A(H1N1) outbreak during the first few days of widespread media coverage (April 28 - May 5, 2009). We find that after an initially high level of concern, levels of anxiety waned along with the perception of the virus as an immediate threat. Overall, our data provide evidence that emotional status mediates behavioral response. Intriguingly, principal component analysis revealed strong clustering of anxiety about swine flu, bird flu and terrorism. All three of these threats receive a great deal of media attention and their fundamental uncertainty is likely to generate an inordinate amount of fear vis-a-vis their actual threat. CONCLUSIONS/SIGNIFICANCE: Our results suggest that respondents' behavior varies in predictable ways. Of particular interest, we find that affective variables, such as self-reported anxiety over the epidemic, mediate the likelihood that respondents will engage in protective behavior. Understanding how protective behavior such as social distancing varies and the specific factors that mediate it may help with the design of epidemic control strategies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779851/ doi: 10.1371/journal.pone.0008032 id: cord-000719-o7ttiu97 author: Jonsson, Colleen B. title: Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus date: 2012-07-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [(18)F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18)F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7–7.0). By days 2 and 3, consolidation (CT) and inflammation ([(18)F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0–7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18)F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman’s ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401186/ doi: 10.1371/journal.pone.0040094 id: cord-335441-bj3me7p8 author: Jourdain, Elsa title: Influenza Virus in a Natural Host, the Mallard: Experimental Infection Data date: 2010-01-28 words: 6354.0 sentences: 311.0 pages: flesch: 52.0 cache: ./cache/cord-335441-bj3me7p8.txt txt: ./txt/cord-335441-bj3me7p8.txt summary: Five of the six ducks excreted viral RNA in their feces on the first day post-inoculation (PI) and all samples (feces, cloacal and oral swabs) from all birds were positive on the second day PI (Figures 4 and S1 ). Intermittent and moderate (high ct-values) viral RNA shedding was detected for all birds in water, fecal or cloacal samples between day 1 and 7 after H7N7 re-inoculation ( Figure 4 ). Active H5 infection was confirmed only in one duck, by expression of H5-specific antibodies and detection of viral RNA in the various sample types (feces, water, oral and cloacal swabs) with a pattern similar to the H5-inoculated control bird. Eight 3-month-old male wild-type mallards (Anas platyrhynchos) of approximately the same body mass and size (measurement of the left wing, the right tarsus length and the distance from bill tip to back of the skull) were selected from a Swedish duck farm known from previous successive sampling to be free from IAV infection. abstract: Wild waterfowl, particularly dabbling ducks such as mallards (Anas platyrhynchos), are considered the main reservoir of low-pathogenic avian influenza viruses (LPAIVs). They carry viruses that may evolve and become highly pathogenic for poultry or zoonotic. Understanding the ecology of LPAIVs in these natural hosts is therefore essential. We assessed the clinical response, viral shedding and antibody production of juvenile mallards after intra-esophageal inoculation of two LPAIV subtypes previously isolated from wild congeners. Six ducks, equipped with data loggers that continually monitored body temperature, heart rate and activity, were successively inoculated with an H7N7 LPAI isolate (day 0), the same H7N7 isolate again (day 21) and an H5N2 LPAI isolate (day 35). After the first H7N7 inoculation, the ducks remained alert with no modification of heart rate or activity. However, body temperature transiently increased in four individuals, suggesting that LPAIV strains may have minor clinical effects on their natural hosts. The excretion patterns observed after both re-inoculations differed strongly from those observed after the primary H7N7 inoculation, suggesting that not only homosubtypic but also heterosubtypic immunity exist. Our study suggests that LPAI infection has minor clinically measurable effects on mallards and that mallard ducks are able to mount immunological responses protective against heterologous infections. Because the transmission dynamics of LPAIVs in wild populations is greatly influenced by individual susceptibility and herd immunity, these findings are of high importance. Our study also shows the relevance of using telemetry to monitor disease in animals. url: https://doi.org/10.1371/journal.pone.0008935 doi: 10.1371/journal.pone.0008935 id: cord-003602-wtestt8i author: Jung, Eunok title: Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy date: 2019-04-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476530/ doi: 10.1371/journal.pone.0215547 id: cord-304993-t4rua95e author: Jung, Kwonil title: The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals date: 2012-07-23 words: 7069.0 sentences: 369.0 pages: flesch: 50.0 cache: ./cache/cord-304993-t4rua95e.txt txt: ./txt/cord-304993-t4rua95e.txt summary: At 12 hours after treatment with 80 mM simvastatin, LDLR gene expression levels in IPEC-J2 cells were significantly increased compared to 0 to 20 mM treated groups (Fig. 1B) . Simvastatin Impaired TLR3-mediated Induction of IFN-a in Macrophages or Dendritic Cells, Possibly Due to Lowered Expression of TLR3 after Treatment Our in vivo data showing enhanced early infectivity of HuNoV suggested potential subversion of innate immunity related to simvasatin treatment. Oral treatment of Gn pigs with natural human IFN-a (nhIFN-a) [300 international unit (IU)/ kg/day] reduced or curtailed virus shedding in treated animals during the treatment period (PID 1 to 4), compared to untreated animals ( Fig. 7A-C) . In conclusion, simvastatin treatment increased HuNoV infectivity in the Gn pig model, possibly due to its inhibitory effect on innate immunity as well as its cholesterol lowering effect as reported previously [20] . abstract: The lack of an animal model for human norovirus (HuNoV) has hindered the development of therapeutic strategies. This study demonstrated that a commonly used cholesterol-lowering statin medication, simvastatin, which increases HuNoV replication in an in vitro replicon system, also enhances HuNoV infectivity in the gnotobiotic (Gn) pig model. In contrast, oral treatment with interferon (IFN)-α reduces HuNoV infectivity. Young piglets, all with A or H1 histo-blood group antigens on enterocytes, were treated orally with 8 mg/kg/day of simvastatin; 5 days later, the pigs were inoculated orally with a GII.4 HuNoV (HS194/2009/US strain) and then treated with simvastatin for 5 more days. Simvastatin induced significantly earlier onset and longer duration of HuNoV fecal shedding in treated pigs, frequently with higher fecal viral titers. Simvastatin impaired poly (I:C)-induced IFN-α expression in macrophages or dendritic cells, possibly due to lowered toll-like receptor (TLR) 3 expression; however, the mechanisms were not related to interferon regulatory factor 3 or nuclear factor kappa B signaling pathway. Thus, the enhanced, earlier infectivity of HuNoV in simvastatin-treated pigs coincided with the inhibitory effect of simvastatin on innate immunity. In contrast to the increased HuNoV shedding that simvastatin induced, viral shedding during the treatment period was reduced or curtailed in the HuNoV-inoculated pigs pre-treated/treated with human IFN-α. Our findings are the first to indicate that IFN-α has potential as antiviral therapy against HuNoV. Based on these intriguing and novel findings using the Gn pig model, we confirmed that HuNoV infectivity is altered by treatment with simvastatin or IFN-α. Collectively, these findings indicate that Gn pigs are a useful model to test immunomodulators or efficacy of antivirals against HuNoV. url: https://www.ncbi.nlm.nih.gov/pubmed/22911825/ doi: 10.1371/journal.pone.0041619 id: cord-048367-yya6w976 author: Jónsson, Stefán R. title: The Restriction of Zoonotic PERV Transmission by Human APOBEC3G date: 2007-09-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1963317/ doi: 10.1371/journal.pone.0000893 id: cord-001263-hqxiyxfj author: Kam, Yiu-Wing title: Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development date: 2014-04-22 words: 5676.0 sentences: 282.0 pages: flesch: 46.0 cache: ./cache/cord-001263-hqxiyxfj.txt txt: ./txt/cord-001263-hqxiyxfj.txt summary: title: Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development In addition to the anti-E2 glycoprotein responses, we also identified new linear B-cell epitopes that were recognized by anti-CHIKV antibodies from CHIKV-infected macaques. Results showed two structural proteins (Capsid protein and E2 glycoprotein) and three nonstructural proteins (nsP1, nsP3 and nsP4 proteins) contained linear epitopes that were recognized by macaque anti-CHIKV antibodies. Here, E2EP3 is one of the major B-cell linear epitopes recognized by antibodies from the sera of all CHIKV-infected macaques during the early phase of disease (amino acids 2800-2818, Table 1 ). Infection of macaques with the LR2006-OPY1 isolate, which encodes K 252 in the E2 glycoprotein, strongly induced anti-CHIKV antibodies against a particular linear B-cell epitope (amino acids 3025-3066) at 16 dpi. abstract: Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995782/ doi: 10.1371/journal.pone.0095647 id: cord-334695-cjxlw1tu author: Kam, Yiu-Wing title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro date: 2009-11-17 words: 6404.0 sentences: 315.0 pages: flesch: 43.0 cache: ./cache/cord-334695-cjxlw1tu.txt txt: ./txt/cord-334695-cjxlw1tu.txt summary: title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro We observed that SARS-CoV spike glycoprotein can be efficiently cleaved by several airway proteases and that this processing enhances entry of SARS-CoVpp. Furthermore, we have identified the putative cleavage sites of airway proteases and, by site-directed mutagenesis, have determined the role of specific amino acid residue for proteolytic processing of the envelope glycoprotein, and for SARS-CoVpp entry into human airway epithelial cells (16HBE) in vitro. In an effort to directly demonstrate that airway protease mediated virus entry enhancement is due to the presence of cleavage site on the SARS spike glycoprotein, 16HBE cells were pre-incubated with wild-type (SARS-CoVpp) or mutant (R667App) pseudotypes on ice, which allowed virus attachment but not entry. abstract: BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike) of the severe acute respiratory syndrome coronavirus (SARS-CoV) to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: Purified triSpike proteins were readily cleaved in vitro by three different airway proteases: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC) and amino acid sequencing analyses identified two arginine residues (R667 and R797) as potential protease cleavage site(s). The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A). Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV. url: https://www.ncbi.nlm.nih.gov/pubmed/19924243/ doi: 10.1371/journal.pone.0007870 id: cord-324359-88vy3dre author: Kamara, Foday Mamoud title: How villagers in central Sierra Leone understand infection risks under threat of Covid-19 date: 2020-06-24 words: 2949.0 sentences: 163.0 pages: flesch: 59.0 cache: ./cache/cord-324359-88vy3dre.txt txt: ./txt/cord-324359-88vy3dre.txt summary: We undertook fieldwork in two villages in central Sierra Leone to gain insight into how rural people faced with Covid-19 assess epidemic infection risks. Asked to explain their choices 48% of players cited information on infection risks modelled by the game and 31% stated that their choices reflected awareness of the need for personal action and respect for local regulations. The data relate to rural populations in Sierra Leone exposed both to Ebola Virus Disease (EVD) in 2014-15 and now to Covid-19 in 2020. Three kinds of responses (Table 5 , 89% of all remarks) dominated comments after people made choices in the game-need for rules governing e.g. quarantine, comments on personal capacities to prevent or avoid infection (often made in the context of justifying a choice for disease "mango"), and comments about the relative risks to be inferred from "reading the stones" (i.e. recognition of a pattern in the way the stones were cast, as in divination practices). abstract: BACKGROUND: Concern has been expressed over how well Africa is prepared to cope with the pandemic of Covid-19. Will rural populations with low levels of education know how to apply community-based infection control? We undertook fieldwork in two villages in central Sierra Leone to gain insight into how rural people faced with Covid-19 assess epidemic infection risks. METHODS: Two communities were selected based on prior contrasted exposure to Ebola Virus Disease–one with substantial number of cases and the other having resisted infection through strong community sequestration measures. We assessed understanding of infection risks via an experimental game. This asked players to express a preference for one of two diseases, one resembling Ebola with lower risk of infection and the other resembling Covid-19 with lower risk of death. Players were not told the identity of the diseases. RESULTS: In total 107 adult villagers played the game (58% women). Half (52%) preferred the disease model with lower risk of infection, 29% preferred the model with lower risk of death, while 21% saw the combined risk of infection and death as being equivalent. Differences in reactions between the two locations were small despite different experiences of Ebola. Asked to explain their choices 48% of players cited information on infection risks modelled by the game and 31% stated that their choices reflected awareness of the need for personal action and respect for local regulations. We concluded that villagers thoughtfully assess disease risks and that some are good intuitive statisticians. CONCLUSIONS: Results suggest rural people in Sierra Leone retain the lessons of experience from the Ebola outbreak of 2014–15 and will be able to apply these lessons to a new infectious disease for which have no prior practical experience. Our expectation is that rural populations will understand Covid-19 control measures, thus reducing need for draconian enforcement. url: https://www.ncbi.nlm.nih.gov/pubmed/32579602/ doi: 10.1371/journal.pone.0235108 id: cord-251979-j3mme15e author: Kandeel, Amr title: Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014 date: 2016-09-08 words: 4716.0 sentences: 272.0 pages: flesch: 43.0 cache: ./cache/cord-251979-j3mme15e.txt txt: ./txt/cord-251979-j3mme15e.txt summary: METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. The aims of this study were to (1) assess the proportion of SARI cases having influenza infection in Egypt; (2) examine the types and subtypes of detected influenza viruses in Egypt; (3) compare demographic and clinical characteristics of influenza-positive SARI cases to those of influenza-negative SARI cases in Egypt; (4) quantify influenza deaths and assess influenza mortality risk factors in Egypt; and (5) establish a defined period of influenza seasonality in Egypt. The odds of death among influenza-positive cases were modeled with logistic regression using different explanatory variables (age group: pediatric <15 years old versus adult 15 years old; sex: male versus female; days from symptom onset to hospitalization: 0-2 versus 3-4 versus 5; chronic conditions: at least one versus none; and influenza type: A versus B). abstract: BACKGROUND: Influenza typically comprises a substantial portion of acute respiratory infections, a leading cause of mortality worldwide. However, influenza epidemiology data are lacking in Egypt. We describe seven years of Egypt’s influenza hospitalizations from a multi-site influenza surveillance system. METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. Standardized demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, and influenza A specimens subtyped. RESULTS: From November 2007–November 2014, 2,936/17,441 (17%) SARI cases were influenza-positive. Influenza-positive patients were more likely to be older, female, pregnant, and have chronic condition(s) (all p<0.05). Among them, 53 (2%) died, and death was associated with older age, five or more days from symptom onset to hospitalization, chronic condition(s), and influenza A (all p<0.05). An annual seasonal influenza pattern occurred from July–June. Each season, the proportion of the season’s influenza-positive cases peaked during November–May (19–41%). CONCLUSIONS: In Egypt, influenza causes considerable morbidity and mortality and influenza SARI hospitalization patterns mirror those of the Northern Hemisphere. Additional assessment of influenza epidemiology in Egypt may better guide disease control activities and vaccine policy. url: https://doi.org/10.1371/journal.pone.0161301 doi: 10.1371/journal.pone.0161301 id: cord-263978-jk82bk1a author: Karaivanov, Alexander title: A social network model of COVID-19 date: 2020-10-29 words: 11398.0 sentences: 576.0 pages: flesch: 57.0 cache: ./cache/cord-263978-jk82bk1a.txt txt: ./txt/cord-263978-jk82bk1a.txt summary: The proposed network-augmented (NSIR) model allows the evaluation, via simulations, of (i) health and economic policies and outcomes for all or subset of the population: lockdown/distancing, herd immunity, testing, contact tracing; (ii) behavioral responses and/or imposing or lifting policies at specific times or conditional on observed states. I construct and compute a dynamic social network-based model of the COVID-19 epidemic and use it to evaluate a range of simulated health and economic policies-herd immunity, distancing, lockdown, testing, quarantine, and contact tracing. While helpful for simplifying the dynamics and computing outcomes, this population-level random matching assumption abstracts from important elements of realism and locality: (i) people are more likely to interact with members of their social network, broadly defined (e.g., family, work, or distance based); (ii) health and economic policies targeting disease mitigation, as well as individual behavioral responses, can affect the rate of viral transmission via a person''s network of contacts vs. abstract: I construct a dynamic social-network model of the COVID-19 epidemic which embeds the SIR epidemiological model onto a graph of person-to-person interactions. The standard SIR framework assumes uniform mixing of infectious persons in the population. This abstracts from important elements of realism and locality: (i) people are more likely to interact with members of their social networks and (ii) health and economic policies can affect differentially the rate of viral transmission via a person’s social network vs. the population as a whole. The proposed network-augmented (NSIR) model allows the evaluation, via simulations, of (i) health and economic policies and outcomes for all or subset of the population: lockdown/distancing, herd immunity, testing, contact tracing; (ii) behavioral responses and/or imposing or lifting policies at specific times or conditional on observed states. I find that viral transmission over a network-connected population can proceed slower and reach lower peak than transmission via uniform mixing. Network connections introduce uncertainty and path dependence in the epidemic dynamics, with a significant role for bridge links and superspreaders. Testing and contact tracing are more effective in the network model. If lifted early, distancing policies mostly shift the infection peak into the future, with associated economic costs. Delayed or intermittent interventions or endogenous behavioral responses generate a multi-peaked infection curve, a form of ‘curve flattening’, but may have costlier economic consequences by prolonging the epidemic duration. url: https://doi.org/10.1371/journal.pone.0240878 doi: 10.1371/journal.pone.0240878 id: cord-267307-kyh0xsrp author: Kasting, Monica L. title: Public perceptions of the effectiveness of recommended non-pharmaceutical intervention behaviors to mitigate the spread of SARS-CoV-2 date: 2020-11-04 words: 4343.0 sentences: 230.0 pages: flesch: 54.0 cache: ./cache/cord-267307-kyh0xsrp.txt txt: ./txt/cord-267307-kyh0xsrp.txt summary: Public health efforts should focus on increasing perceived severity and threat of SARS-CoV-2-related disease, while promoting NPI as effective in reducing threat. A six-item measure was used to assess participants'' perceptions of the effectiveness of NPIs to prevent SARS-CoV-2 infection and spread. Three of the six items measured the perceived effectiveness of preventing yourself from spreading COVID-19 to others and included: 1) wearing a mask anytime you leave the house to go out in public, 2) practicing social distancing by leaving at least six feet between you and other people (this does not include people you live with), and 3) covering your mouth when you cough. Any variable that was significant at p<0.01 in bivariate comparisons was included in an adjusted logistic regression model with the binary lower/ higher perceived effectiveness of COVID-19 prevention measures as the outcome. abstract: BACKGROUND: The COVID-19 pandemic is an unprecedented public health threat, both in scope and response. With no vaccine available, the public is advised to practice non-pharmaceutical interventions (NPI) including social distancing, mask-wearing, and washing hands. However, little is known about public perceptions of the effectiveness of these measures, and high perceived effectiveness is likely to be critical in order to achieve widespread adoption of NPI. METHODS: In May 2020, we conducted a cross-sectional survey among U.S. adults (N = 3,474). The primary outcome was a six-item measure assessing perceived effectiveness of recommended behaviors to prevent SARS-CoV-2 infection from 1 (not at all effective) to 5 (extremely effective). The sample was divided into “higher” and “lower” perceived effectiveness groups. Covariates included demographics, healthcare characteristics, and health beliefs. Variables that were significant at p<0.01 in bivariate analyses were entered into a multivariable logistic regression and a best-fit model was created using a cutoff of p<0.01 to stay in the model. RESULTS: Mean age was 45.5 years and most participants were non-Hispanic White (63%) and female (52.4%). The high perceived effectiveness group was slightly larger than the low perceived effectiveness group (52.7% vs. 47.3%). Almost all health belief variables were significant in the best-fit regression model. COVID-19-related worry (aOR = 1.82; 95% CI = 1.64–2.02), and perceived threat to physical health (aOR = 1.32; 95% CI = 1.20–1.45) were positively associated with perceived effectiveness while perceived severity of COVID-19 (0.84; 95% CI = 0.73–0.96) and perceived likelihood of infection (0.85; 95% CI = 0.77–0.94) switched directions in the adjusted model and were negatively associated with perceived effectiveness. CONCLUSIONS: This research indicates people generally believe NPI are effective, but there was variability based on health beliefs and there are mixed rates of engagement in these behaviors. Public health efforts should focus on increasing perceived severity and threat of SARS-CoV-2-related disease, while promoting NPI as effective in reducing threat. url: https://doi.org/10.1371/journal.pone.0241662 doi: 10.1371/journal.pone.0241662 id: cord-012387-1ogcxd7b author: Kaufman, Aaron R. title: The political consequences of opioid overdoses date: 2020-08-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The United States suffered a dramatic and well-documented increase in drug-related deaths from 2000 to 2018, primarily driven by prescription and non-prescription opioids, and concentrated in white and working-class areas. A growing body of research focuses on the causes, both medical and social, of this opioid crisis, but little work as yet on its larger ramifications. Using novel public records of accidental opioid deaths linked to behavioral political outcomes, we present causal analyses showing that opioid overdoses have significant political ramifications. Those close to opioid victims vote at lower rates than those less affected by the crisis, even compared to demographically-similar friends and family of other unexpected deaths. Moreover, among those friends and family affected by opioids, Republicans are 25% more likely to defect from the party than the statewide average Republican, while Democrats are no more likely to defect; Independents are moderately more likely to register as Democrats. These results illustrate an important research design for inferring the effects of tragic events and speak to the broad social and political consequences of what is becoming the largest public health crisis in modern United States history. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402477/ doi: 10.1371/journal.pone.0236815 id: cord-003507-22ylifqo author: Kelly, J. Daniel title: Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018 date: 2019-03-07 words: 4481.0 sentences: 246.0 pages: flesch: 53.0 cache: ./cache/cord-003507-22ylifqo.txt txt: ./txt/cord-003507-22ylifqo.txt summary: As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. We modeled Ebola virus transmission using a stochastic branching process model, parameterized by transmission rates estimated from the dynamics of prior EVD outbreaks, and conditioned on agreement with reported case counts from the 2018 EVD outbreak to date. abstract: As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405095/ doi: 10.1371/journal.pone.0213190 id: cord-010368-plpghewn author: Kenmoe, Sebastien title: Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies date: 2020-04-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: INTRODUCTION: Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. METHODS: We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. RESULTS: We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7–2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4–1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9–1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3–2.7]), food (OR = 0.8, [95% CI = 0.3–2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6–2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0–4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1–2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7–16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1–8.5]), or furred animals (OR = 0.6, [95% CI = 0.5–0.9]). CONCLUSION: These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182231/ doi: 10.1371/journal.pone.0231816 id: cord-318696-jheb2fnn author: Kesic, Matthew J. title: Exposure to Ozone Modulates Human Airway Protease/Antiprotease Balance Contributing to Increased Influenza A Infection date: 2012-04-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA) is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI). Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs) to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility. url: https://doi.org/10.1371/journal.pone.0035108 doi: 10.1371/journal.pone.0035108 id: cord-001982-arczqdza author: Khajah, Maitham A. title: Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis date: 2016-03-10 words: 6218.0 sentences: 313.0 pages: flesch: 56.0 cache: ./cache/cord-001982-arczqdza.txt txt: ./txt/cord-001982-arczqdza.txt summary: It is thought that the beneficial effects of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on blood pressure control and in delaying/inhibiting the cardiac remodeling process is through increasing serum levels of Ang1-7 [9] [10] [11] [12] . A seven fold decrease in the plasma level of Ang 1-7 was demonstrated in DSS treated mice compared to untreated (UT) group at day 7 post colitis induction (Fig 1A) . The level of phosphorylated forms of three key signaling intermediates, ERK1/2 (Fig 8) , p38 MAPK (Fig 9) and Akt (Fig 10) , were measured by immunofluorescence in sections from resected colon tissue of untreated mice or mice treated with DSS (for 7 days) plus daily Ang 1-7 or saline (vehicle) treatment. abstract: BACKGROUND: There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. METHODS: The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. RESULTS: Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. CONCLUSION: Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786309/ doi: 10.1371/journal.pone.0150861 id: cord-346819-11fkgzaa author: Khan, Mohd Imran title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 words: 4405.0 sentences: 291.0 pages: flesch: 57.0 cache: ./cache/cord-346819-11fkgzaa.txt txt: ./txt/cord-346819-11fkgzaa.txt summary: title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . abstract: A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds great potential in further scientific research towards the design of potential vaccine candidates/small molecular inhibitor against COVID19. url: https://www.ncbi.nlm.nih.gov/pubmed/32881907/ doi: 10.1371/journal.pone.0238344 id: cord-351142-g20f6bxc author: Kiaghadi, Amin title: Assessing COVID-19 risk, vulnerability and infection prevalence in communities date: 2020-10-29 words: 6778.0 sentences: 313.0 pages: flesch: 48.0 cache: ./cache/cord-351142-g20f6bxc.txt txt: ./txt/cord-351142-g20f6bxc.txt summary: A finer spatial resolution is important from a vulnerability and risk standpoint as demonstrated in a recent study that showed that the poorest neighborhoods in Houston, Texas, might be at a higher risk of hospitalization from COVID-19 [14] based on an analysis of the Centers for Disease Control (CDC) underlying risk factors for severe COVID-19 cases [4] that include: asthma, Chronic Obstructive Pulmonary Disease (COPD), heart disease, hypertension, diabetes, and a history of heart attacks or strokes. In this study, we develop a rigorous planning tool at the census tract level that examines influential determinants of vulnerability to COVID-19 in 5 broad categories (with 46 variables) that include: 1) access to medical services, 2) underlying medical conditions, 3) environmental exposures, 4) vulnerability to natural disasters and 5) sociodemographic, behavioral, and lifestyle factors. Fig 9A shows the normalized total number of confirmed COVID-19 cases as of August 16, 2020, in Harris County at the census tract level. abstract: BACKGROUND: The spread of coronavirus in the United States with nearly five and half million confirmed cases and over 170,000 deaths has strained public health and health care systems. While many have focused on clinical outcomes, less attention has been paid to vulnerability and risk of infection. In this study, we developed a planning tool that examines factors that affect vulnerability to COVID-19. METHODS: Across 46 variables, we defined five broad categories: 1) access to medical services, 2) underlying health conditions, 3) environmental exposures, 4) vulnerability to natural disasters, and 5) sociodemographic, behavioral, and lifestyle factors. The developed tool was validated by comparing the estimated overall vulnerability with the real-time reported normalized confirmed cases of COVID-19. ANALYSIS: A principal component analysis was undertaken to reduce the dimensions. In order to identify vulnerable census tracts, we conducted rank-based exceedance and K-means cluster analyses. RESULTS: All of the 5 vulnerability categories, as well as the overall vulnerability, showed significant (P-values <<0.05) and relatively strong correlations (0.203<ρ<0.57) with the normalized confirmed cases of COVID-19 at the census tract level. Our study showed a total of 722,357 (~17% of the County population) people, including 171,403 between the ages of 45–65 (~4% of County’s population), and 76,719 seniors (~2% of County population), are at a higher risk based on the aforementioned categories. The exceedance and K-means cluster analysis demonstrated that census tracts in the northeastern, eastern, southeastern and northwestern regions of the County are at highest risk. CONCLUSION: Policymakers can use this planning tool to identify neighborhoods at high risk for becoming hot spots; efficiently match community resources with needs, and ensure that the most vulnerable have access to equipment, personnel, and medical interventions. url: https://www.ncbi.nlm.nih.gov/pubmed/33119721/ doi: 10.1371/journal.pone.0241166 id: cord-302200-9gekjgr0 author: Kilich, Eliz title: Factors that influence vaccination decision-making among pregnant women: A systematic review and meta-analysis date: 2020-07-09 words: 6662.0 sentences: 345.0 pages: flesch: 38.0 cache: ./cache/cord-302200-9gekjgr0.txt txt: ./txt/cord-302200-9gekjgr0.txt summary: Previous reviews have established a narrative of evidence that suggests a broad range of factors (vaccine cost, accessibility, maternal knowledge, social influences, context, healthcare professional (HCP) recommendation and the perception of risks and benefits) all contribute to vaccine uptake. Thus, we performed a systematic review and meta-analysis of qualitative and quantitative literature to provide comprehensive evidence on the magnitude of effect that factors influence maternal vaccination decisions globally with the aim to inform policy makers, public health strategists and researchers involved in designing vaccine interventions to increase uptake. For seasonal influenza, the data is inconclusive since women who believed that the disease could be harmful to their pregnancy or baby had four-times greater odds of being vaccinated than those who did not (OR 3.70, 95% CI 1.37-9.94) yet there was no evidence to suggest belief in the risk of the disease generally (OR 1.56, 95% CI 0.88-2.76) or its ability to result in hospitalisation (OR 0.57, 95% CI 0.22-1.45) were related to vaccine uptake. abstract: BACKGROUND: The most important factor influencing maternal vaccination uptake is healthcare professional (HCP) recommendation. However, where data are available, one-third of pregnant women remain unvaccinated despite receiving a recommendation. Therefore, it is essential to understand the significance of other factors and distinguish between vaccines administered routinely and during outbreaks. This is the first systematic review and meta-analysis (PROSPERO: CRD 42019118299) to examine the strength of the relationships between identified factors and maternal vaccination uptake. METHODS: We searched MEDLINE, Embase Classic & Embase, PsycINFO, CINAHL Plus, Web of Science, IBSS, LILACS, AfricaWideInfo, IMEMR, and Global Health databases for studies reporting factors that influence maternal vaccination. We used random-effects models to calculate pooled odds ratios (OR) of being vaccinated by vaccine type. FINDINGS: We screened 17,236 articles and identified 120 studies from 30 countries for inclusion. Of these, 49 studies were eligible for meta-analysis. The odds of receiving a pertussis or influenza vaccination were ten to twelve-times higher among pregnant women who received a recommendation from HCPs. During the 2009 influenza pandemic an HCP recommendation increased the odds of antenatal H1N1 vaccine uptake six times (OR 6.76, 95% CI 3.12–14.64, I(2) = 92.00%). Believing there was potential for vaccine-induced harm had a negative influence on seasonal (OR 0.22, 95% CI 0.11–0.44 I(2) = 84.00%) and pandemic influenza vaccine uptake (OR 0.16, 95% CI 0.09–0.29, I(2) = 89.48%), reducing the odds of being vaccinated five-fold. Combined with our qualitative analysis the relationship between the belief in substantial disease risk and maternal seasonal and pandemic influenza vaccination uptake was limited. CONCLUSIONS: The effect of an HCP recommendation during an outbreak, whilst still powerful, may be muted by other factors. This requires further research, particularly when vaccines are novel. Public health campaigns which centre on the protectiveness and safety of a maternal vaccine rather than disease threat alone may prove beneficial. url: https://doi.org/10.1371/journal.pone.0234827 doi: 10.1371/journal.pone.0234827 id: cord-260572-vd65ygtm author: Kim, Curi title: Comparison of Nasopharyngeal and Oropharyngeal Swabs for the Diagnosis of Eight Respiratory Viruses by Real-Time Reverse Transcription-PCR Assays date: 2011-06-30 words: 3515.0 sentences: 173.0 pages: flesch: 52.0 cache: ./cache/cord-260572-vd65ygtm.txt txt: ./txt/cord-260572-vd65ygtm.txt summary: BACKGROUND: Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach. To evaluate the comparative yields of NP and OP swabs in detecting key respiratory viruses by real-time RT-PCR (qRT-PCR), we conducted a prospective study using paired NP and OP specimens from patients at two respiratory disease surveillance sites in Kenya. NP and OP specimens from each patient were separately tested by singleplex qRT-PCR for eight viral pathogens: adenovirus, influenza A virus, influenza B virus, human metapneumovirus (hMPV), parainfluenza viruses (PIV) 1-3, and respiratory syncytial virus (RSV). abstract: BACKGROUND: Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. METHODS: We collected paired NP and OP swabs separately from pediatric and adult patients with influenza-like illness or severe acute respiratory illness at two respiratory surveillance sites in Kenya. The specimens were tested for eight respiratory viruses by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Positivity for a specific virus was defined as detection of viral nucleic acid in either swab. RESULTS: Of 2,331 paired NP/OP specimens, 1,402 (60.1%) were positive for at least one virus, and 393 (16.9%) were positive for more than one virus. Overall, OP swabs were significantly more sensitive than NP swabs for adenovirus (72.4% vs. 57.6%, p<0.01) and 2009 pandemic influenza A (H1N1) virus (91.2% vs. 70.4%, p<0.01). NP specimens were more sensitive for influenza B virus (83.3% vs. 61.5%, p = 0.02), parainfluenza virus 2 (85.7%, vs. 39.3%, p<0.01), and parainfluenza virus 3 (83.9% vs. 67.4%, p<0.01). The two methods did not differ significantly for human metapneumovirus, influenza A (H3N2) virus, parainfluenza virus 1, or respiratory syncytial virus. CONCLUSIONS: The sensitivities were variable among the eight viruses tested; neither specimen was consistently more effective than the other. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach. url: https://doi.org/10.1371/journal.pone.0021610 doi: 10.1371/journal.pone.0021610 id: cord-002913-k5b6abyk author: Kim, Ha Kyun title: Asymmetric expression level of clock genes in left vs. right nasal mucosa in humans with and without allergies and in rats: Circadian characteristics and possible contribution to nasal cycle date: 2018-03-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1. Physiological function of nasal mucosa exhibits rhythmic variability to a day-night environmental cycle. Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa. The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats. In human and rat nasal mucosa, the levels of these genes are asymmetrically expressed in nasal mucosa derived from right and left cavities in normal controls, allergic patients, and rat. In human nasal mucosa, the expression levels of these genes were higher in the decongested side than the congested mucosa. In rat nasal mucosa, these clock genes are expressed in a rhythmic circadian manner under the regular light/dark cycles. The expression levels of MUC5AC, a key mucin genes produced in superficial epithelium, are higher in decongested side than that congested side in human nasal mucosa. In rat nasal mucosa, MUC5AC levels showed a circadian rhythm which was associated with different expression levels in nasal mucosa derived from the right and left nasal cavities. Taken together with these results, the present study shows that the clock genes such as PER1, PER2, CLOCK, and BMAL1 are present in human and rat nasal mucosa, and suggest that these clock genes may control the pathophysiological function of nasal mucosa as circadian oscillators and affect the maintenance of the nasal cycle. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849312/ doi: 10.1371/journal.pone.0194018 id: cord-001007-645zegcv author: Kim, Hak title: Identification of Recombinant Human Rhinovirus A and C in Circulating Strains from Upper and Lower Respiratory Infections date: 2013-06-27 words: 4060.0 sentences: 189.0 pages: flesch: 48.0 cache: ./cache/cord-001007-645zegcv.txt txt: ./txt/cord-001007-645zegcv.txt summary: This study analyzed parts of the viral genes spanning the 5′ noncoding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples. This study aimed to understand and characterize the various recombination events between 5'' NCR and VP4/VP2 region of field strains of HRV including species A, B and C, using 105 HRVs identified from two distinctive laboratory surveillance systems, the Acute Respiratory Infectious Network (ARINET) and Severe Lower Respiratory Tract Infections (SLRI) surveillances undertaken from October 2008 to March 2009. In conclusion, this study is the first report describing intraand interspecies genomic recombination in circulating HRV-A and -C isolated from patients with acute or severe respiratory illness and these results will assist in investigating the causes of the diversity and evolution of HRVs arising through recombination events. abstract: Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI). Enteroviruses are genetically highly variable, and recombination between serotypes is known to be a major contribution to their diversity. Recently it was reported that recombination events in HRVs cause the diversity of HRV-C. This study analyzed parts of the viral genes spanning the 5′ non- coding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples. When analyzing parts of the 5′NCR and VP4/VP2 encoding sequences, we found intra- and interspecies recombinants in field strains of HRV-A and -C. Nineteen cases of recombination events (18.1%) were found among 105 field strains. For HRV-A, there were five cases (4.8%) of intraspecies recombination events and three cases (2.8%) of interspecies recombination events. For HRV-C, there were four cases (3.8%) of intraspecies recombination events and seven cases (6.7%) of interspecies recombination events. Recombination events were significantly more frequently observed in the ARINET samples (18 cases) than in the SLRI samples (1 case; P< 0.0001). The recombination breakpoints were located in nucleotides (nt) 472–554, which comprise stem-loop 5 in the internal ribosomal entry site (IRES), based on the HRV-B 35 sequence (accession no. FJ445187). Our findings regarding genomic recombination in circulating HRV-A and -C strains suggest that recombination might play a role in HRV fitness and could be a possible determinant of disease severity caused by various HRV infections in patients with ARI. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695095/ doi: 10.1371/journal.pone.0068081 id: cord-340766-aic570x8 author: Kim, Se Jin title: Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia date: 2015-04-15 words: 3631.0 sentences: 196.0 pages: flesch: 41.0 cache: ./cache/cord-340766-aic570x8.txt txt: ./txt/cord-340766-aic570x8.txt summary: The present study describes in detail the clinical characteristics and favorable treatment outcomes of non-immunocompromised adults who had experienced severe AdV pneumonia and received early cidofovir administration. Only non-immunocompromised adult patients who fulfilled the criteria for severe community-acquired pneumonia, set out in the Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines [23] , and admitted to the intensive care unit with progressive respiratory failure, defined as a partial pressure of arterial oxygen (PaO 2 )/fraction of inspired oxygen (FiO 2 ) ratio of < 300 mmHg and/or tachypnea (respiration rate >30 breaths/min) [24] , were included in the analysis. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. abstract: The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/25875735/ doi: 10.1371/journal.pone.0122642 id: cord-254825-c5d0wul9 author: Kim, Sei Won title: Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience date: 2020-08-14 words: 3554.0 sentences: 205.0 pages: flesch: 49.0 cache: ./cache/cord-254825-c5d0wul9.txt txt: ./txt/cord-254825-c5d0wul9.txt summary: In this study, we retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing, contact history, and presence of respiratory symptoms in a single center with a healthcare-associated COVID-19 outbreak. We reviewed the history of patients to assess whether they visited China or other high-risk countries within two weeks prior to the outbreak of healthcare-associated COVID-19, or if they came into contact with confirmed COVID-19 cases. After SARS-CoV-2 infection was confirmed, the Seoul city government announced the closure of the hospital on February 21, 2020, to prevent a healthcare-associated outbreak. After the hospital staff member responsible for transporting patients was confirmed as the first COVID-19 case, people with contact history, fever, or respiratory symptoms were tested for SARS-CoV-2 infection with RT-PCR (Fig 2) . After the first case was reported, epidemiologists from KCDC and the infection control unit of our hospital reviewed electronic medical charts, CCTV, and personal movements to identify individuals with potential contact with confirmed COVID-19 patients. abstract: BACKGROUND: Our hospital experienced the first healthcare-associated COVID-19 outbreak in Seoul at the time the first COVID-19 cases were confirmed in Korea. The first confirmed COVID-19 patient was a hospital personnel who was in charge of transferring patients inside our hospital. To contain the virus spread, we shutdown our hospital, and tested all inpatients, medical staff members, and employees. METHODS: We retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing according to the contact history, occupation, and presence of respiratory symptoms. Closed-circuit television (CCTV) was reviewed in the presence of an epidemiologist to identify individuals who came into contact with confirmed COVID-19 patients. RESULTS: A total of 3,091 respiratory samples from 2,924 individuals were obtained. Among 2,924 individuals, two inpatients, and one caregiver tested positive (positivity rate, 0.1%). Although all confirmed cases were linked to a general ward designated for pulmonology patients, no medical staff members, medical support personnel, or employees working at the same ward were infected. Contact with confirmed COVID-19 cases was frequent among inpatients and medical support personnel. The most common contact area was the general ward for pulmonology patients and medical support areas, including clinical and imaging examination rooms. Finally, the total number of hospital-associated infections was 14, consisting of four diagnosed at our hospital and ten diagnosed outside the hospital. CONCLUSIONS: The robust control of the COVID-19 outbreak further minimized the transmission of SARS-CoV-2 in the hospital and local communities. However, there was also a debate over the appropriate period of hospital shutdown and testing of all hospital staff and patients. Future studies are required to refine and establish the in-hospital quarantine and de-isolation guidelines based on the epidemiological and clinical settings. url: https://doi.org/10.1371/journal.pone.0237692 doi: 10.1371/journal.pone.0237692 id: cord-001088-dugsh7mp author: Kim, So-Hee title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection date: 2013-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza vaccines that target the highly variable surface glycoproteins hemagglutinin and neuraminidase cause inconvenience of having vaccination every year. For this reason, development of universal vaccines targeting conserved viral components is needed. In this study, we generated recombinant adenovirus (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus, designated rAd/NP. BALB/c mice were immunized intranasally or sublingually with rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as well as homologous influenza viruses. We found that intranasal immunization of rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell responses toward immunodominant K(d)-restricted NP(147-155) epitope than sublingual immunization. Importantly, only single intranasal but not sublingual immunization of rAd/NP provides potent protection against both homologous and heterologous influenza virus challenges. These results suggest that recombinant rAd/NP could be a universal vaccine candidate for mucosal administration against influenza virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783479/ doi: 10.1371/journal.pone.0075460 id: cord-001014-8yrpcl94 author: Kitagawa, Hiroshi title: Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis date: 2013-07-03 words: 4451.0 sentences: 288.0 pages: flesch: 57.0 cache: ./cache/cord-001014-8yrpcl94.txt txt: ./txt/cord-001014-8yrpcl94.txt summary: title: Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. Expression of IL-4 mRNA was significantly decreased in the ear skin of intra-nasally rhPIV2/Ag85B treatment group compared to that of PBS treated mice (Fig. 4A) . mRNA expressions of TNF-a and MIP-2 were significantly decreased in both of intra-nasally and subcutaneously rhPIV2/Ag85B treated groups compared with PBS or vector treated group (Fig. 4E, F) . Ag85B is a conserved protein in mycobacterial species and can elicit a strong Th1-type immune Expressions of IL-4, TNF-a and MIP2-a mRNA were significantly decreased in the ear skin treated with intranasally rhPIV2/Ag85B treated group compared to those of control groups. abstract: Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701015/ doi: 10.1371/journal.pone.0066614 id: cord-254313-g2oc32dm author: Klink, Thomas title: Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons date: 2020-04-30 words: 4499.0 sentences: 215.0 pages: flesch: 49.0 cache: ./cache/cord-254313-g2oc32dm.txt txt: ./txt/cord-254313-g2oc32dm.txt summary: Several studies, including at least nine in the Eastern Mediterranean region, have been published since 2011 using the SARI case definition as inclusion criteria to report a combination of clinical characteristics, risk factors, viral burden, or outcomes in adult and pediatric populations for flu and other respiratory viruses [5] [6] [7] [8] [9] [10] [11] [12] [13] . Only a handful of studies have evaluated the effectiveness of the criteria by including both SARI-positive and SARI-negative patients, allowing them to calculate the diagnostic accuracy of the criteria for detecting flu and respiratory syncytial virus (RSV) [14] [15] [16] [17] [18] [19] . The age distribution differences likely explain these discrepancies as our cohort consists only of children under two years, and the SARI criteria were the least sensitive (15.9%) and most specific (80.5%) for detecting flu in our patients under three months, who make up 45.4% of our study population. abstract: OBJECTIVE: The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort. MATERIALS AND METHODS: The data for this study comes from a prospective acute respiratory surveillance study of hospitalized children <2 years in Amman, Jordan from March 16, 2010 to March 31, 2013. Participants were recruited if they had a fever and/or respiratory symptoms. Nasal and throat swabs were obtained and tested by real-time RT-PCR for eleven viruses. Subjects meeting SARI criteria were determined post-hoc. Sensitivity, specificity, positive predictive value, and negative predictive value of the SARI case definition for detecting ten different viruses were calculated and results were stratified by age. RESULTS: Of the 3,175 patients enrolled, 3,164 were eligible for this study, with a median age of 3.5 months, 60.4% male, and 82% virus-positive (44% RSV and 3.8% flu). The sensitivity and specificity of the SARI criteria for detecting virus-positive patients were 44% and 77.9%, respectively. Sensitivity of SARI criteria for any virus was lowest in children <3 months at 22.4%. Removing fever as a criterion improved the sensitivity by 65.3% for detecting RSV in children <3 months; whereas when cough was removed, the sensitivity improved by 45.5% for detecting flu in same age group. CONCLUSIONS: The SARI criteria have poor sensitivity for detecting RSV, flu, and other respiratory viruses—particularly in children <3 months. Researchers and policy makers should use caution if using the criteria to estimate burden of disease in children. url: https://doi.org/10.1371/journal.pone.0232188 doi: 10.1371/journal.pone.0232188 id: cord-286837-j2sqs20q author: Koetsier, Antonie title: Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics? date: 2013-12-31 words: 4526.0 sentences: 210.0 pages: flesch: 49.0 cache: ./cache/cord-286837-j2sqs20q.txt txt: ./txt/cord-286837-j2sqs20q.txt summary: METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In the season 2009/2010 as well as in the season 2010/2011, ILI incidence as measured by GP sentinel practices, reached the epidemic threshold of 5.1 consultations per 10.000 enlisted patients at a time when already more than 100 patients had been hospitalized, with several ICU admissions and deaths from laboratory confirmed Influenza (National Institute for Public Health and the Environment, unpublished surveillance data). In our study we built three additive Poisson GEE regression models with ICU data to predict the incidence of ILI patients, thereby detecting influenza epidemics and aimed at detecting opportunities for enhancing the current national surveillance method. abstract: OBJECTIVES: Severe influenza can lead to Intensive Care Unit (ICU) admission. We explored whether ICU data reflect influenza like illness (ILI) activity in the general population, and whether ICU respiratory infections can predict influenza epidemics. METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In addition, ICU data of the first three years was used to build three regression models to predict the start and end of influenza epidemics in the years thereafter, one to three weeks ahead. The predicted start and end of influenza epidemics were compared with observed start and end of such epidemics according to the incidence of ILI. RESULTS: Peaks in respiratory ICU admissions lasted longer than peaks in ILI incidence rates. Increases in ICU admissions occurred on average two days earlier compared to ILI. Predicting influenza epidemics one, two, or three weeks ahead yielded positive predictive values ranging from 0.52 to 0.78, and sensitivities from 0.34 to 0.51. CONCLUSIONS: ICU data was associated with ILI activity, with increases in ICU data often occurring earlier and for a longer time period. However, in the Netherlands, predicting influenza epidemics in the general population using ICU data was imprecise, with low positive predictive values and sensitivities. url: https://www.ncbi.nlm.nih.gov/pubmed/24391837/ doi: 10.1371/journal.pone.0083854 id: cord-344152-pb1e2w7s author: Kolatkar, Anand title: C-ME: A 3D Community-Based, Real-Time Collaboration Tool for Scientific Research and Training date: 2008-02-20 words: 5434.0 sentences: 258.0 pages: flesch: 45.0 cache: ./cache/cord-344152-pb1e2w7s.txt txt: ./txt/cord-344152-pb1e2w7s.txt summary: Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members. For example, protein structure/activity data annotations and images may be kept in paper lab notebooks, manuscripts might be stored electronically in Portable Document Format (PDF), and molecular structure coordinate files may be stored on a hard disk to be viewed and analyzed in graphical molecular viewers, to name a few. Most recently we have developed the Collaborative Molecular Modeling Environment (C-ME), a new collaboratory system that integrates many of the key features available on Kinemage, MICE, iSee, and BioCoRE systems into one thin-client Windows application. abstract: The need for effective collaboration tools is growing as multidisciplinary proteome-wide projects and distributed research teams become more common. The resulting data is often quite disparate, stored in separate locations, and not contextually related. Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. C-ME stores the information in industry-standard databases that are immediately accessible by appropriate permission within the computer network directory service or anonymously across the internet through the C-ME application or through a web browser. The system addresses two important aspects of collaboration: context and information management. C-ME allows a researcher to use a 3-D atomic structure model or a 2-D image as a contextual basis on which to attach and share annotations to specific atoms or molecules or to specific regions of a 2-D image. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members. url: https://doi.org/10.1371/journal.pone.0001621 doi: 10.1371/journal.pone.0001621 id: cord-329223-f84gjxm1 author: Kouokam, Joseph Calvin title: Investigation of Griffithsin''s Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate date: 2011-08-02 words: 8837.0 sentences: 382.0 pages: flesch: 47.0 cache: ./cache/cord-329223-f84gjxm1.txt txt: ./txt/cord-329223-f84gjxm1.txt summary: In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. When freshly-isolated PBMC were pre-incubated for 24 hrs with GRFT at various concentrations, washed and then infected with HIV-1 R5 strain BaL (without adding new compound), GRFT inhibited viral replication for 9 days of cell culture (Fig. 2) . In addition, the numbers of CD4 2 /CD25 + cells were elevated when PBMC were cultured in presence of PHA or ConA compared to their PBS and GRFT counterpart (Fig. 6 , left panel and data not shown). The heat map shown in Fig. 9A indicates that cells exposed for 24 hours to GRFT Lec-(1 and 8 mM), and low concentrations of GRFT (0.1 mM ) and CV-N (0.05 mM) showed comparable gene expression profiles to those that were incubated in presence of PBS alone. abstract: Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin. url: https://doi.org/10.1371/journal.pone.0022635 doi: 10.1371/journal.pone.0022635 id: cord-321624-z2mntwef author: Kowitdamrong, Ekasit title: Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date: 2020-10-09 words: 3382.0 sentences: 184.0 pages: flesch: 57.0 cache: ./cache/cord-321624-z2mntwef.txt txt: ./txt/cord-321624-z2mntwef.txt summary: AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. The objective of this study was to investigate the response of IgA and IgG antibodies to SARS--CoV-2 in serial blood samples collected from a population of Thai patients with confirmed COVID-19, and the association of these responses with the severity of the illness. The second subgroup included 49 plasma samples collected from May 1 to May 31, 2020, from patients under investigation (PUI) for COVID-19 with RT-PCR results that were negative for SARS-CoV-2. In the present study, 30% of COVID-19 patients developed positive IgA antibodies very early, within 3 days after the onset of symptoms. In the present study, 20% of the patients with mild symptoms did not develop any IgG antibodies specific to COVID-19, even after 2 weeks after the onset of symptoms. abstract: BACKGROUND: A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination. AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. METHODS: Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed. RESULTS: A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8–93.6) and 84.8% (95% CI: 76.2–91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003). CONCLUSION: The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection. url: https://www.ncbi.nlm.nih.gov/pubmed/33035234/ doi: 10.1371/journal.pone.0240502 id: cord-319538-bawzonq1 author: Krause, Martin title: Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients date: 2020-09-18 words: 2565.0 sentences: 138.0 pages: flesch: 35.0 cache: ./cache/cord-319538-bawzonq1.txt txt: ./txt/cord-319538-bawzonq1.txt summary: Based on observational studies from the epicenters of the pandemic in Wuhan, China, the Lombardy region in Italy, and the New York City area in the United States, a significant portion of patients diagnosed with coronavirus disease 2019 (COVID19) were admitted to the intensive care unit (ICU) for ventilatory support: Between 17%-24% of hospitalized patients and up to 72% of patients admitted to the ICU have required invasive mechanical ventilation [2] [3] [4] [5] . We aimed to identify if plasma procalcitonin levels on admission are associated with the duration of mechanical ventilation (primary outcome), 28-day mortality, and time to intubation (secondary outcomes) in a cohort of COVID-19 patients requiring mechanical ventilation. In the univariate analysis of our observational cohort study, procalcitonin levels >0.1 ng/ml on admission were associated with prolonged mechanical ventilation in critically ill COVID-19 patients. abstract: BACKGROUND: Patients diagnosed with COVID-19 frequently require mechanical ventilation. Knowledge of laboratory tests associated with the prolonged need for mechanical ventilation may guide resource allocation. We hypothesized that an elevated plasma procalcitonin level (>0.1 ng/ml) would be associated with the duration of invasive mechanical ventilation. METHODS: Patients diagnosed with COVID-19, who were admitted to any of our health system’s hospitals between March 9(th)-April 20(th), 2020 and required invasive mechanical ventilation, were eligible for this observational cohort study. Demographics, comorbidities, components of the Sequential Organ Failure Assessment score, and procalcitonin levels on admission were obtained from the electronic health record. The primary outcome was the duration of mechanical ventilation; secondary outcomes included 28-day mortality and time to intubation. Outcomes were assessed within the first 28 days of admission. Baseline demographics and comorbidities were summarized by descriptive statistics. Univariate comparisons were made using Pearson’s chi-square test for binary outcomes and Mann-Whitney U test for continuous outcomes. A multiple linear regression was fitted to assess the association between procalcitonin levels and the duration of mechanical ventilation. RESULTS: Patients with an initial procalcitonin level >0.1 ng/ml required a significantly longer duration of mechanical ventilation than patients with a level of ≤0.1 ng/ml (p = 0.021) in the univariate analysis. There was no significant difference in 28-day mortality or time to intubation between the two groups. After adjusted analysis using multivariable linear regression, the duration of mechanical ventilation was, on average, 5.6 (p = 0.016) days longer in patients with an initial procalcitonin level >0.1 ng/ml. CONCLUSION: In this cohort of 93 mechanically ventilated COVID-19 patients, we found an association between an initial plasma procalcitonin level >0.1 ng/ml and the duration of mechanical ventilation. These findings may help to identify patients at risk for prolonged mechanical ventilation upon admission. url: https://www.ncbi.nlm.nih.gov/pubmed/32946466/ doi: 10.1371/journal.pone.0239174 id: cord-337879-liqhbqxl author: Kriesel, John D. title: Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain date: 2012-03-08 words: 5060.0 sentences: 296.0 pages: flesch: 54.0 cache: ./cache/cord-337879-liqhbqxl.txt txt: ./txt/cord-337879-liqhbqxl.txt summary: Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. Multiple sclerosis (MS) is a chronic demyelinating disease of unknown cause, which affects the brain and spinal cord of about 400,000 individuals in the U.S. A number of viral infections of the CNS can lead to demyelination, including distemper (dogs), measles (SSPE, humans), and influenza (humans). To enhance the detection of non-human sequences, RNA samples that passed the quality control step above were subjected to rRNA removal using the RiboMinus kit (Invitrogen Inc., Carlsbad, CA). One subject who died with primary-progressive MS had .1000 36 bp sequences detected that mapped to GBV-C virus (hepatitis G), a human flavivirus not known to cause any persistent disease and never before detected in human brain. abstract: Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1–2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a “hit”. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4–10 million sequences (“reads”) each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here. url: https://doi.org/10.1371/journal.pone.0031886 doi: 10.1371/journal.pone.0031886 id: cord-325113-sou8xyld author: Kuiper, Johannes W. P. title: Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification date: 2020-11-02 words: 4973.0 sentences: 241.0 pages: flesch: 51.0 cache: ./cache/cord-325113-sou8xyld.txt txt: ./txt/cord-325113-sou8xyld.txt summary: The use of unprocessed swap samples is enabled by employing a heat-stable RNAand DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. A RNA-and DNA-reading heat-stable polymerase reverse transcribes and amplifies viral RNA Evidence of an acute SARS-CoV-2 infection depends on the detection of viral RNA species in patient samples, which necessitates reverse transcription of RNA followed by PCR amplification of the resulting DNA. To evaluate the potential of the high-temperature RT-PCR protocol using Volvano3G for the detection of viral RNAs in patient material, we assessed the presence of SARS-CoV-2 in RNA isolated from a small cohort of COVID-19 suspected cases. Interestingly, for most positive samples detected by the high-temperature RT-PCR with Volcano3G, the cq-values were lower compared to the standard RT-PCR (Fig 3C and 3D) , indicating that the detection of SARS-CoV-2 from unprocessed patient material is not limited by the sensitivity of this direct approach. abstract: SARS-CoV-2 is spreading globally with unprecedented consequences for modern societies. The early detection of infected individuals is a pre-requisite to contain the virus. Currently, purification of RNA from patient samples followed by RT-PCR is the gold standard to assess the presence of this single-strand RNA virus. However, these procedures are time consuming, require continuous supply of specialized reagents, and are prohibitively expensive in resource-poor settings. Here, we report an improved nucleic-acid-based approach to detect SARS-CoV-2 with the ability to detect as little as five viral genome equivalents. The approach delivers results without the need to purify RNA, reduces handling steps, minimizes costs, and allows evaluation by non-specialized equipment. The use of unprocessed swap samples is enabled by employing a heat-stable RNA- and DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. As results are obtained within 2 hours and can be read-out by a hand-held LED-screen, this novel protocol will be of particular importance for large-scale virus surveillance in economically constrained settings. url: https://doi.org/10.1371/journal.pone.0241740 doi: 10.1371/journal.pone.0241740 id: cord-000556-uu1oz2ei author: Kumar, Ranjit title: RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336” date: 2012-01-20 words: 4407.0 sentences: 235.0 pages: flesch: 46.0 cache: ./cache/cord-000556-uu1oz2ei.txt txt: ./txt/cord-000556-uu1oz2ei.txt summary: Whole genome transcriptome analysis is a complementary method to identify "novel" genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. Therefore, genome structural annotation or the identification and demarcation of boundaries of functional elements in a genome (e.g., genes, non-coding RNAs, proteins, and regulatory elements) are critical elements in infectious disease systems biology. Whole genome transcriptome studies (such as whole genome tiling arrays [13, 14, 15] and high throughput sequencing [16, 17] ) are complementary experimental approaches for bacterial genome annotation and can identify ''''novel'''' genes, gene boundaries, regulatory regions, intergenic regions, and operon structures. We compared the RNA-Seq based transcriptome map with the available genome annotation to identify expressed, novel, and intergenic regions in the genome. The single nucleotide resolution map helped uncover the structure and complexity of this pathogen''s transcriptome and led to the identification of novel, small RNAs and protein coding genes as well as gene co-expression. abstract: Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis. Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs). Whole genome transcriptome analysis is a complementary method to identify “novel” genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis. In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method. The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies. We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation. The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome. When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome). This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262788/ doi: 10.1371/journal.pone.0029435 id: cord-278099-ypov9ha3 author: Kumar, Surender title: Molecular characterization of a novel cryptic virus infecting pigeonpea plants date: 2017-08-03 words: 11403.0 sentences: 622.0 pages: flesch: 55.0 cache: ./cache/cord-278099-ypov9ha3.txt txt: ./txt/cord-278099-ypov9ha3.txt summary: The four dsRNAs eluted from the agarose gel were purified and have been used as templates for RT-PCR amplification employed in SISPA to generate fulllength cDNAs. It is of interest to examine if ArCV-1 RNA dependent RNA polymerase (RdRp) structurally resembles the known RdRp of the dsRNA bacteriophage Փ-6, reovirus, or with other viruses like calciviruses and picornaviruses [12] [13] [14] [15] [16] . We report here the results of elaborated computer-assisted analysis of ArCV-1 replicase which revealed the presence of conserved sequence motifs (A to G) present in the fingers and palm subdomains of the polymerase that are shared in most of the RdRps. Interestingly, ArCV-1 replicase has more structural resemblances with several members of ssRNA (+) mono-partite Picornaviruses (viral replication by primer-dependent initiation), than the de novo dsRNA bacteriophage Փ-6 and reovirus polymerases. Possible functions of the residues of the A to G motifs described for identical RdRps was conserved with respect to the ArCV-1 3Dpol structure and was discussed in structural analysis of ArCVTable 1 ) and the 3'' terminus contained the sequence "GCA CCCATATTC". abstract: A new member of the genus Deltapartitivirus was identified containing three dsRNAs with an estimated size of 1.71, 1.49 and 1.43 kb. The dsRNAs were extracted from symptomless pigeonpea [Cajanus cajan (L.) Millspaugh] plants cv. Erra Kandulu. This new virus with 4.64 kb genome was tentatively named Arhar cryptic virus-1 (ArCV-1). The genomic RNAs were amplified and characterized by sequence independent single primer amplification. The dsRNAs shared a highly conserved 16 nt 5’ non-coding region (5’-GATAATGATCCAAGGA-3’). The largest dsRNA (dsRNA-1) was identified as the viral RNA dependent RNA polymerase (replicase), predicted to encode a putative 55.34 kDa protein (P1). The two other smaller dsRNAs (dsRNA-2 and dsRNA-3) predicted to encode for putative capsid proteins of 38.50kDa (P2) and 38.51kDa (P3), respectively. Phylogenetic analysis indicated that ArCV-1 formed a clade together with Fragaria chiloensis cryptic virus, Rosa multiflora cryptic virus and Rose cryptic virus-1, indicating that ArCV-1 could be a new member of the genus Deltapartitivirus. ArCV-1 3D(pol) structure revealed several interesting features. The 3D(pol) in its full-length shares structural similarities with members of the family Caliciviridaeand family Picornaviridae. In addition, fourth dsRNA molecule (dsRNA-2A), not related to ArCV-1 genome, was found in the same plant tissue. The dsRNA-2A (1.6 kb) encodes a protein (P4), with a predicted size of 44.5 kDa. P4 shares similarity with coat protein genes of several cryptic viruses, in particular the bipartite cryptic viruses including Raphanus sativus cryptic virus-3. This is the first report of occurrence of a cryptic virus in pigeonpea plants. url: https://doi.org/10.1371/journal.pone.0181829 doi: 10.1371/journal.pone.0181829 id: cord-001865-ji83zmy7 author: Kuroda, Kengo title: Immortalization of Fetal Bovine Colon Epithelial Cells by Expression of Human Cyclin D1, Mutant Cyclin Dependent Kinase 4, and Telomerase Reverse Transcriptase: An In Vitro Model for Bacterial Infection date: 2015-12-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cattle are the economically important animals in human society. They are essential for the production of livestock products such as milk and meats. The production efficiency of livestock products is negatively impacted by infection with zoonotic pathogens. To prevent and control infectious diseases, it is important to understand the interaction between cattle tissue and pathogenic bacteria. In this study, we established an in vitro infection model of an immortalized bovine colon-derived epithelial cell line by transducing the cells with lentiviral vectors containing genes encoding cell cycle regulators cyclin D1, mutant cyclin dependent kinase 4 (CDK4), and human telomerase reverse transcriptase (TERT). The established cell line showed continuous cell proliferation, expression of epithelial markers, and an intact karyotype, indicating that the cells maintained their original nature as colon-derived epithelium. Furthermore, we exposed the established cell line to two strains of Salmonella enterica and EHEC. Interestingly, S. Typhimurium showed higher affinity for the established cell line and invaded the cytoplasm than S. Enteritidis. Quantitative RT-PCR revealed that gene expression of Toll-like receptor 1 (TLR1), TLR 2 and TLR 3, whereas TLR 4, 5 and 6 were not detectable in established cells. Our established immortalized colon-derived epithelial cell should be a useful tool for studies evaluating the molecular mechanisms underlying bacterial infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666463/ doi: 10.1371/journal.pone.0143473 id: cord-347465-yu6oj30v author: Kurskaya, Olga title: Viral etiology of acute respiratory infections in hospitalized children in Novosibirsk City, Russia (2013 – 2017) date: 2018-09-18 words: 3383.0 sentences: 194.0 pages: flesch: 45.0 cache: ./cache/cord-347465-yu6oj30v.txt txt: ./txt/cord-347465-yu6oj30v.txt summary: METHODS: We tested nasal and throat swabs of 1560 children with upper or lower respiratory infection for main respiratory viruses (influenza viruses A and B, parainfluenza virus types 1–4, respiratory syncytial virus, metapneumovirus, four human coronaviruses, rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected 1128 (72.3%) samples were positive for at least one virus. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. In conclusion, in our study we investigated the etiological structure of acute respiratory viral infections in hospitalized children in Novosibirsk, Russia, and evaluated age and seasonal distribution of the various respiratory viruses. abstract: BACKGROUND: Acute respiratory infections (ARIs) cause a considerable morbidity and mortality worldwide especially in children. However, there are few studies of the etiological structure of ARIs in Russia. In this work, we analyzed the etiology of ARIs in children (0–15 years old) admitted to Novosibirsk Children’s Municipal Clinical Hospital in 2013–2017. METHODS: We tested nasal and throat swabs of 1560 children with upper or lower respiratory infection for main respiratory viruses (influenza viruses A and B, parainfluenza virus types 1–4, respiratory syncytial virus, metapneumovirus, four human coronaviruses, rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected 1128 (72.3%) samples were positive for at least one virus. The most frequently detected pathogens were respiratory syncytial virus (358/1560, 23.0%), influenza virus (344/1560, 22.1%), and rhinovirus (235/1560, 15.1%). Viral co-infections were found in 163 out of the 1128 (14.5%) positive samples. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. CONCLUSIONS: We evaluated the distribution of respiratory viruses in children with ARIs and showed the prevalence of respiratory syncytial virus and influenza virus in the etiological structure of infections. This study is important for the improvement and optimization of diagnostic tactics, control and prevention of the respiratory viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/30226876/ doi: 10.1371/journal.pone.0200117 id: cord-298078-uqrwq5qk author: Kwak, Hoyun title: Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus date: 2011-08-30 words: 5346.0 sentences: 318.0 pages: flesch: 56.0 cache: ./cache/cord-298078-uqrwq5qk.txt txt: ./txt/cord-298078-uqrwq5qk.txt summary: The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs. Ribosomal frameshifing is a recoding process of translation where a specific messenger RNA (mRNA)-mediated signal directs a ribosome to shift its reading frame and to continue in the new frame. To search for cellular proteins that directly interacted with IBV pseudoknot RNA, a RNA pull down assay was performed in the presence of cell extracts (Figure 2A ). Through the RNA-immunoprecipitation assay, we showed that ANXA2 specifically interacted with wild-type IBV pseudoknot RNA but not with mutant IBV RNA in LNCaP and HEK293T cells ( Figure 3C and 3D). To test how ANXA2 regulates the frameshifting efficiency of IBV pseudoknot RNA, we first overexpressed ANXA2 protein in the presence of the reporters and measured the luciferase activities. abstract: Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs. url: https://doi.org/10.1371/journal.pone.0024067 doi: 10.1371/journal.pone.0024067 id: cord-267566-gdjl0qmu author: Kweon, Oh Joo title: Antibody kinetics and serologic profiles of SARS-CoV-2 infection using two serologic assays date: 2020-10-22 words: 3599.0 sentences: 232.0 pages: flesch: 51.0 cache: ./cache/cord-267566-gdjl0qmu.txt txt: ./txt/cord-267566-gdjl0qmu.txt summary: This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays. METHODS: A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI(™) Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA). The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI(™) Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results. abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging threat worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays. METHODS: A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI(™) Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA). RESULTS: With both assays, IgM and IgG rapidly increased after 7 days post symptom onset (PSO). IgM antibody levels reached a peak at 15–35 d PSO and gradually decreased. IgG levels gradually increased and remained at similar levels after 22–35 d. The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI(™) Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results. CONCLUSIONS: The antibody kinetics against SARS-CoV-2 are similar to common findings of acute viral infectious diseases. Antibody testing is useful for ruling out SARS-CoV-2 infection after 14 d PSO, detecting past infection, and epidemiologic surveys. url: https://www.ncbi.nlm.nih.gov/pubmed/33091042/ doi: 10.1371/journal.pone.0240395 id: cord-307934-84zfabti author: Lai, Chao-Kuen title: Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date: 2014-06-06 words: 8211.0 sentences: 465.0 pages: flesch: 55.0 cache: ./cache/cord-307934-84zfabti.txt txt: ./txt/cord-307934-84zfabti.txt summary: Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. Both NS5A and Core proteins are found to be closely associated with and co-transported along the microtubules from the perinuclear region of cells via the LDs and endosomes to the plasma membrane. (A) The HCV-infected cells (at day 10 p.i.) were labeled with antibodies specific for Core protein (red) and NS5A (green) (upper row) or NS4B (green) (lower row). abstract: Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) serves dual functions in viral RNA replication and virus assembly. Here, we demonstrate that HCV replication complex along with NS5A and Core protein was transported to the lipid droplet (LD) through microtubules, and NS5A-Core complexes were then transported from LD through early-to-late endosomes to the plasma membrane via microtubules. Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Furthermore, exosomal markers CD63 and CD81 were also detected in the low-density fractions, but not in the high-density fractions. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. url: https://www.ncbi.nlm.nih.gov/pubmed/24905011/ doi: 10.1371/journal.pone.0099022 id: cord-261908-olcuq6tm author: Lai, Ka-Man title: Propagation of Respiratory Aerosols by the Vuvuzela date: 2011-05-23 words: 3983.0 sentences: 199.0 pages: flesch: 53.0 cache: ./cache/cord-261908-olcuq6tm.txt txt: ./txt/cord-261908-olcuq6tm.txt summary: The fate of the droplet nuclei on inhalation also depends on their size; particles greater than five microns are likely to remain in the upper airways but smaller particles are more likely to deposit in the alveoli and so may transmit infections of the lower respiratory tract such as tuberculosis [22, 23] . The large number of aerosols emitted by the vuvuzela raises the possibility that, if used by persons with an infection of the respiratory tract, they could act a conduit for the spread of infectious particles. To obtain the desired trumpet sound when blowing the vuvuzela air is forced through the lips into the opening of the instrument which may serve to create further aerosols, or alter the size of droplets produced elsewhere in the respiratory tract. Exhale duration, peak air velocity, particle concentration and mean particle diameter recorded during playing the vuvuzela and shouting by four male and four female volunteers. abstract: Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658×10(3) per litre for the vuvuzela and 3.7×10(3) per litre for shouting, representing a mean log(10) difference of 2.20 (95% CI: 2.03,2.36; p<0.001). The majority (>97%) of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas) have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others. url: https://doi.org/10.1371/journal.pone.0020086 doi: 10.1371/journal.pone.0020086 id: cord-305393-96mrxt8a author: Lai, Yvonne title: Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date: 2011-10-10 words: 9604.0 sentences: 587.0 pages: flesch: 60.0 cache: ./cache/cord-305393-96mrxt8a.txt txt: ./txt/cord-305393-96mrxt8a.txt summary: Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. Transfection of two plasmids, one containing an interferon stimulated response element (ISRE) promoter-driven firefly luciferase and a second encoding a constitutively expressed Renilla luciferase allow the analysis of TLR3 activation by different RNAs. HEK 293T cells expressing WT TLR3 responded to poly(I:C) (1-2 mg/ml), better than viral dsRNAs (1-2 mg/ml) purified from Reovirus and BPEV (Fig. 1B) . abstract: Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs) from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV) were also potent enhancers of TLR3 signaling by poly(I:C) or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. url: https://doi.org/10.1371/journal.pone.0025837 doi: 10.1371/journal.pone.0025837 id: cord-291360-z19ri377 author: Lan, Fan-Yun title: COVID-19 symptoms predictive of healthcare workers’ SARS-CoV-2 PCR results date: 2020-06-26 words: 4339.0 sentences: 251.0 pages: flesch: 52.0 cache: ./cache/cord-291360-z19ri377.txt txt: ./txt/cord-291360-z19ri377.txt summary: Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8–99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. Therefore, we investigated the presenting symptoms most predictive of positive/negative SARS-CoV-2 RT-PCR results among HCWs. Since March 9, 2020, the occupational health service of a Massachusetts community healthcare system has implemented a staff "hotline" system to maintain a viable/healthy workforce and operational continuity during the pandemic. The clinical COVID-19 attack rate during the study period was calculated as: (the number of initial positive SARS-CoV-2 assays + the number of false negatives) divided by the system''s estimated total HCW population (n = 4600). abstract: BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9—April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10–3.64), which increased to 2.61 (95% CI: 1.50–4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature ≥ 37.5°C (3.49 (95% CI: 1.95–6.21)), and those with myalgias (1.83 (95% CI: 1.04–3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95–17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8–99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays. url: https://doi.org/10.1371/journal.pone.0235460 doi: 10.1371/journal.pone.0235460 id: cord-339724-roj8ksvc author: Lan, Jiaming title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen date: 2014-11-18 words: 5017.0 sentences: 249.0 pages: flesch: 49.0 cache: ./cache/cord-339724-roj8ksvc.txt txt: ./txt/cord-339724-roj8ksvc.txt summary: title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. In this study, different adjuvants combination regimens including alum, IFA, CpG and poly(I:C) were compared in an effort to promote balance between Th1 and Th2 immune response to bystander rRBD antigen spanning residues 367-606 of MERS-CoV S in a murine model to develop an effective vaccine against MERS-CoV infection. The results indicated that rRBD protein combined with any adjuvant, including alum, IFA, CpG or poly(I:C), could induce a RBD-specific IgG antibody response in the majority of mice after the second immunisation. abstract: The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses. url: https://doi.org/10.1371/journal.pone.0112602 doi: 10.1371/journal.pone.0112602 id: cord-255351-vp19ydce author: Lanata, Claudio F. title: Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review date: 2013-09-04 words: 5451.0 sentences: 221.0 pages: flesch: 48.0 cache: ./cache/cord-255351-vp19ydce.txt txt: ./txt/cord-255351-vp19ydce.txt summary: We present the results of a systematic literature review of studies of diarrhea etiology in hospitalized children and use these results to estimate the global burden of diarrhea mortality by pathogen for children under 5 years of age for 2011. From 22 643 citations identified in the electronic search, 1 003 articles were selected for further evaluation (Fig. 1) ; 840 articles were excluded because they had one or more of the exclusion criteria (About 35% because they were not longitudinal studies or inappropriate laboratory methods were used, 31% because no data was given for children ,5 years of age, 23% for studies that lasted less than 12 months of duration, and the rest because data were reported after rotavirus vaccine introduction, duplicate publications or reporting results on a pathogen not included in our list). abstract: Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children <5 years of age hospitalized with diarrhea. We included 2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO. We excluded studies conducted during diarrhea outbreaks that did not discriminate between inpatient and outpatient cases, reporting nosocomial infections, those conducted in special populations, not done with adequate methods, and rotavirus studies in countries where the rotavirus vaccine was used. Age-adjusted median proportions for each pathogen were calculated and applied to 712 000 deaths due to diarrhea in children under 5 years for 2011, assuming that those observed among children hospitalized for diarrhea represent those causing child diarrhea deaths. 163 articles and WHO studies done in 31 countries were selected representing 286 inpatient studies. Studies seeking only one pathogen found higher proportions for some pathogens than studies seeking multiple pathogens (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5–13 pathogens, p<0·0001). The percentage of episodes for which no pathogen could be identified was estimated to be 34%; the total of all age-adjusted percentages for pathogens and no-pathogen cases was 138%. Adjusting all proportions, including unknowns, to add to 100%, we estimated that rotavirus caused 197 000 [Uncertainty range (UR) 110 000–295 000], enteropathogenic E. coli 79 000 (UR 31 000–146 000), calicivirus 71 000 (UR 39 000–113 000), and enterotoxigenic E. coli 42 000 (UR 20 000–76 000) deaths. Rotavirus, calicivirus, enteropathogenic and enterotoxigenic E. coli cause more than half of all diarrheal deaths in children <5 years in the world. url: https://doi.org/10.1371/journal.pone.0072788 doi: 10.1371/journal.pone.0072788 id: cord-352522-qnvgg2e9 author: Langille, Morgan G. I. title: BioTorrents: A File Sharing Service for Scientific Data date: 2010-04-14 words: 2994.0 sentences: 158.0 pages: flesch: 51.0 cache: ./cache/cord-352522-qnvgg2e9.txt txt: ./txt/cord-352522-qnvgg2e9.txt summary: In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. A BitTorrent software client (see Table 1 ) uses the data in the torrent file to contact the tracker and allow transferring of the data between computers containing either full or partial copies of the dataset. Information about each dataset on BioTorrents is supplied on a details page giving a description of the data, number of files, date added, user name of the person who created the dataset, and various other details including a link to the actual torrent file. As the number of datasets and users of BioTorrents increases, and to improve on transfer speeds on a geospatial scale (i.e. across countries and continents), we would encourage other institutions to automatically download and share all or some of the data on BioTorrents. abstract: The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net. url: https://www.ncbi.nlm.nih.gov/pubmed/20418944/ doi: 10.1371/journal.pone.0010071 id: cord-001249-awn9ayy6 author: Lasecka, Lidia title: The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space date: 2014-04-08 words: 9953.0 sentences: 453.0 pages: flesch: 50.0 cache: ./cache/cord-001249-awn9ayy6.txt txt: ./txt/cord-001249-awn9ayy6.txt summary: ERp57 while the structure of the ER, ERGIC and Golgi remains unchanged Two isolates of NSDV have been previously described by us [29] : a multiple-times passaged isolate of NSDV from Uganda, which appeared attenuated upon infection of a susceptible animal, and an isolate of GV from India which had been passaged a limited number of times in mouse brain or BHK21 clone 13 cells and which caused haemorrhagic gastroenteritis in sheep upon experimental inoculation. No change to the cellular distribution of calnexin was observed (Figure 2 j-l), indicating that, despite the disappearance of PDI and ERp57, the overall structure of the ER remains unchanged in NSDV-infected cells. Another flavivirus, Dengue virus (DENV) (which, like NSDV, can cause a haemorrhagic fever), increased surface levels of PDI in infected endothelial cells [86] . In this study we have demonstrated that NSDV induces the redistribution of soluble ER oxidoreductases, specifically PDI and ERp57, in infected cells, and that the viral PreGn glycoprotein appears to be involved in this process. abstract: Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979861/ doi: 10.1371/journal.pone.0094656 id: cord-295293-ickp2n47 author: Latsuzbaia, Ardashel title: Evolving social contact patterns during the COVID-19 crisis in Luxembourg date: 2020-08-06 words: 2976.0 sentences: 153.0 pages: flesch: 52.0 cache: ./cache/cord-295293-ickp2n47.txt txt: ./txt/cord-295293-ickp2n47.txt summary: While the number of social contacts was substantially lower during the lockdown by more than 80% compared to the pre-pandemic period, we observed a more recent 121% increase during the post lockdown period showing an increased potential for COVID-19 spread. We repeatedly conducted an internet survey to follow up the impact of the local government interventions on social contact patterns in Luxembourg shortly after the lockdown was implemented due to the rapid local spread of the COVID-19. The average number of contacts reported by Luxembourg residents in a study before the pandemic was 17.5 [4] , suggesting that contacts during lockdown had decreased by 81.7%. Our study suggests that the strict physical distancing measures implemented in Luxembourg had a substantial and immediate impact on social mixing patterns resulting in a large reduction of the average number of contacts per day. In conclusion, our stud shows that physical distance measures resulted in significant reduction in social contacts and therefore decreased the spread of COVID-19 in Luxembourg. abstract: We conducted an internet survey using Survey Monkey over six weeks to evaluate the impact of the government interventions on social contact patterns in Luxembourg. Participants were recruited via the science.lu website on March 25, April 2, April 16, May 1 during lockdown, and June 12 and June 25 after the lockdown to provide an estimate of their number of contacts within the previous 24 hours. During the lockdown, a total of 5,644 survey participants with a mean age of 44.2 years reported 18,118 contacts (mean = 3.2, IQR 1–4). The average number of contacts per day increased by 24% from 2.9 to 3.6 over the lockdown period. The average number of contacts decreased with age: 4.2 (IQR 2–5) for participants below 25 years and 1.7 (IQR 1–2) for participants above 64 years. Residents of Portuguese nationality reported a higher number of contacts (mean = 4.3, IQR 2–5) than Luxembourgish (mean = 3.5, IQR 2–4) or other foreign residents, respectively. After lockdown, 1,119 participants reported 7,974 contacts with 7.1 (IQR 3–9) contacts per day on average, of which 61.7% (4,917/7,974) occurred without a facemask (mean = 4.9, IQR 2–6). While the number of social contacts was substantially lower during the lockdown by more than 80% compared to the pre-pandemic period, we observed a more recent 121% increase during the post lockdown period showing an increased potential for COVID-19 spread. Monitoring social contacts is an important indicator to estimate the possible impact of government interventions on social contacts and the COVID-19 spread in the coming months. url: https://www.ncbi.nlm.nih.gov/pubmed/32760114/ doi: 10.1371/journal.pone.0237128 id: cord-000937-8vk89i4h author: Law, John title: Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool date: 2013-04-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control). RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found. The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C). Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH. After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified. These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database. Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses. The presence of this novel circovirus was confirmed by PCR. BLASTx also identified many polypeptides resembling nucleo-cytoplasmic large DNA viruses (NCLDV) proteins. We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms. This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein. Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629200/ doi: 10.1371/journal.pone.0060595 id: cord-290034-4b0mshqa author: Le, Yen H. title: Virus detections among patients with severe acute respiratory illness, Northern Vietnam date: 2020-05-12 words: 2833.0 sentences: 145.0 pages: flesch: 43.0 cache: ./cache/cord-290034-4b0mshqa.txt txt: ./txt/cord-290034-4b0mshqa.txt summary: To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. There was one case of co-infection with enterovirus and coronavirus 229E including a female military hospital patient 28 years of age. Additionally, our results display enterovirus, adenovirus and coronavirus infections among the SARI cases, suggesting that cities in northern Vietnam could benefit also from local surveillance of non-influenza respiratory viruses. abstract: Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2–3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7–22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics. url: https://doi.org/10.1371/journal.pone.0233117 doi: 10.1371/journal.pone.0233117 id: cord-289305-mfjyjjer author: Lee, Min Hye title: A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control date: 2020-03-10 words: 7550.0 sentences: 417.0 pages: flesch: 47.0 cache: ./cache/cord-289305-mfjyjjer.txt txt: ./txt/cord-289305-mfjyjjer.txt summary: title: A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control Three studies on gastrointestinal infection, in which adherence to hand hygiene among HCWs was crucial to prevent its spread, reported control measures including stringent hand hygiene practice and reinforcement of standard precautions [23, 27, 31] . The study on the RSV and HMPV outbreak reported various measures including active surveillance, isolation, contact precaution, antiviral prophylaxis for residents and work restriction for ill staff to control respiratory pathogen transmission [50] . This update for understanding outbreaks in LTCFs by reviewing recent studies indicates that staff members and residents are still at risk for contagious disease outbreaks including influenza, gastroenteritis, and GAS infection. Influenza outbreak control practices and the effectiveness of interventions in long-term care facilities: a systematic review abstract: BACKGROUND: The unique characteristics of long-term care facilities (LTCFs) including host factors and living conditions contribute to the spread of contagious pathogens. Control measures are essential to interrupt the transmission and to manage outbreaks effectively. AIM: The aim of this systematic review was to verify the causes and problems contributing to transmission and to identify control measures during outbreaks in LTCFs. METHODS: Four electronic databases were searched for articles published from 2007 to 2018. Articles written in English reporting outbreaks in LTCFs were included. The quality of the studies was assessed using the risk-of-bias assessment tool for nonrandomized studies. FINDINGS: A total of 37 studies were included in the qualitative synthesis. The most commonly reported single pathogen was influenza virus, followed by group A streptococcus (GAS). Of the studies that identified the cause, about half of them noted outbreaks transmitted via person-to-person. Suboptimal infection control practice including inadequate decontamination and poor hand hygiene was the most frequently raised issue propagating transmission. Especially, lapses in specific care procedures were linked with outbreaks of GAS and hepatitis B and C viruses. About 60% of the included studies reported affected cases among staff, but only a few studies implemented work restriction during outbreaks. CONCLUSIONS: This review indicates that the violation of basic infection control practice could be a major role in introducing and facilitating the spread of contagious diseases in LTCFs. It shows the need to promote compliance with basic practices of infection control to prevent outbreaks in LTCFs. url: https://www.ncbi.nlm.nih.gov/pubmed/32155208/ doi: 10.1371/journal.pone.0229911 id: cord-286613-cmtsu73g author: Lee, Sung Woo title: Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation date: 2015-10-15 words: 3601.0 sentences: 203.0 pages: flesch: 57.0 cache: ./cache/cord-286613-cmtsu73g.txt txt: ./txt/cord-286613-cmtsu73g.txt summary: title: Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The cut-off values of SAPS2, serum sodium level, and ECMO pump speed for in-hospital mortality were a score of 69.5, 147.6 mmol/L, and 2.19 x 10 3 rpm, respectively (Table 3) . We showed that AKI, especially stage 3 AKI, was a significant risk factor for in-hospital mortality in patients receiving ECMO support. In conclusion, AKI is a significant risk factor for in-hospital mortality in patients receiving ECMO support. abstract: BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality. METHODS: Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality. RESULTS: Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI. url: https://www.ncbi.nlm.nih.gov/pubmed/26469793/ doi: 10.1371/journal.pone.0140674 id: cord-252347-vnn4135b author: Lee, Wai-Ming title: A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants date: 2007-10-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious. METHODS AND FINDINGS: To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12–35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group (“C”). None of these new strains could be cultured in traditional cell lines. CONCLUSIONS: By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group. url: https://www.ncbi.nlm.nih.gov/pubmed/17912345/ doi: 10.1371/journal.pone.0000966 id: cord-292396-8w06oc5i author: Leger, Thomas title: Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score date: 2020-11-03 words: 3373.0 sentences: 209.0 pages: flesch: 57.0 cache: ./cache/cord-292396-8w06oc5i.txt txt: ./txt/cord-292396-8w06oc5i.txt summary: OBJECTIVES: The purpose is to assess the ability of low-dose CT (LDCT) to determine lung involvement in SARS-CoV-2 pneumonia and to describe a COVID19-LDCT severity score. The objective is to evaluate the ability of (LDCT) to analyze well-known imaging abnormalities as well as to establish a COVID19-LDCT score reflecting disease severity and correlate it with clinical risk scores to allow better selection and follow-up of patients. For each patient, the following clinical parameters were recorded: age, sex, date of first symptoms, date of chest CT scan, delay between the first symptom and chest CT scan, fever, cough, dyspnea, diarrhea, myalgia, rhinorrhea, abnormalities at lung auscultation, temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, and oxygen needed. The main findings of the presented work are that 1) LDCT scans can depict the typical features of SARS-CoV-2 pneumonia with limited irradiation; and 2) the COVID19-LDCT score is correlated with the NEWS used routinely to assess disease severity and patient prognosis. abstract: OBJECTIVES: The purpose is to assess the ability of low-dose CT (LDCT) to determine lung involvement in SARS-CoV-2 pneumonia and to describe a COVID19-LDCT severity score. MATERIALS AND METHODS: Patients with SARS-CoV-2 infection confirmed by RT-PCR were retrospectively analysed. Clinical data, the National Early Warning Score (NEWS) and imaging features were recorded. Lung features included ground-glass opacities (GGO), areas of consolidation and crazy paving patterns. The COVID19-LDCT score was calculated by summing the score of each segment from 0 (no involvement) to 10 (severe impairment). Univariate analysis was performed to explore predictive factor of high COVID19-LDCT score. The nonparametric Mann-Whitney test was used to compare groups and a Spearman correlation used with p<0.05 for significance. RESULTS: Eighty patients with positive RT-PCR were analysed. The mean age was 55 years ± 16, with 42 males (53%). The most frequent symptoms were fever (60/80, 75%) and cough (59/80, 74%), the mean NEWS was 1.7±2.3. All LDCT could be analysed and 23/80 (28%) were normal. The major imaging finding was GGOs in 56 cases (67%). The COVID19-LDCT score (mean value = 19±29) was correlated with NEWS (r = 0.48, p<0.0001). No symptoms were risk factor to have pulmonary involvement. Univariate analysis shown that dyspnea, high respiratory rate, hypertension and diabetes are associated to a COVID19-LDCT score superior to 50. CONCLUSIONS: COVID19-LDCT score did correlate with NEWS. It was significantly different in the clinical low-risk and high-risk groups. Further work is needed to validate the COVID19-LDCT score against patient prognosis. url: https://doi.org/10.1371/journal.pone.0241407 doi: 10.1371/journal.pone.0241407 id: cord-001011-vjxmrmfc author: Lei, Daoxiong title: Hepatic Deficiency of COP9 Signalosome Subunit 8 Induces Ubiquitin-Proteasome System Impairment and Bim-Mediated Apoptosis in Murine Livers date: 2013-07-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The COP9 signalosome (CSN), an evolutionally highly conserved protein complex composed of 8 unique subunits (CSN1 through CSN8) in higher eukaryotes, is purported to modulate protein degradation mediated by the ubiquitin-proteasome system (UPS) but this has not been demonstrated in a critical mitotic parenchymal organ of vertebrates. Hepatocyte-specific knockout of the Cops8 gene (HS-Csn8KO) was shown to cause massive hepatocyte apoptosis and liver malfunction but the underlying mechanism remains unclear. Here, we report that Csn8/CSN exerts profound impacts on hepatic UPS function and is critical to the stability of the pro-apoptotic protein Bim. Significant decreases in CIS (cytokine-inducible Src homology 2 domain-containing protein), a Bim receptor of a cullin2-based ubiquitin ligase, were found to co-exist with a marked increase of Bim proteins. Csn8 deficiency also significantly decreased 19S proteasome subunit Rpt5 and markedly increased high molecular weight neddylated and ubiquitinated proteins. The use of a surrogate UPS substrate further reveals severe impairment of UPS-mediated proteolysis in HS-Csn8KO livers. Inclusion body-like materials were accumulated in Csn8 deficient hepatocytes. In addition to Bim, massive hepatocyte apoptosis in HS-Csn8KO livers is also associated with elevated expression of other members of the Bcl2 family, including pro-apoptotic Bax as well as anti-apoptotic Bcl2 and Bcl-XL. Increased interaction between Bcl2 and Bim, but not between Bcl2 and Bax, was detected. Hence, it is concluded that hepatic CSN8 deficiency impairs the UPS in the liver and the resultant Bim upregulation likely plays an important role in triggering hepatocyte apoptosis via sequestering Bcl2 away from Bax. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698095/ doi: 10.1371/journal.pone.0067793 id: cord-310396-jitao9k0 author: Lei, Yu title: MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins date: 2009-03-07 words: 6031.0 sentences: 325.0 pages: flesch: 46.0 cache: ./cache/cord-310396-jitao9k0.txt txt: ./txt/cord-310396-jitao9k0.txt summary: The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. Currently, there are no reports of viral proteins targeting MAVS for inhibition of virus-induced cell death responses. In this report, we describe a novel function of MAVS in mediating virus-induced apoptosis, and identify viral proteins as inhibitors of this response. In addition, the involvement of proteins on IFN axis in virusinduced host cell apoptosis has been implicated in another previous report, in which MAVS has been shown to be critical for reovirus-triggered caspase-3/7 activation in HEK293T cells [46] , however, the study did not evaluate whether MAVS mediates virus-induced apoptosis and what roles type 1 IFNs play in MAVS-mediated apoptosis. abstract: BACKGROUND: Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. PRINCIPAL FINDINGS: We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS(−/−) fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. SIGNIFICANCE: This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response. url: https://doi.org/10.1371/journal.pone.0005466 doi: 10.1371/journal.pone.0005466 id: cord-297835-ukrz8tlv author: Leith, Douglas J. title: Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram date: 2020-09-30 words: 5591.0 sentences: 264.0 pages: flesch: 58.0 cache: ./cache/cord-297835-ukrz8tlv.txt txt: ./txt/cord-297835-ukrz8tlv.txt summary: title: Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram Contact tracing apps based on the Google/Apple Exposure Notification (GAEN) API [4] are currently being rolled out across Europe, with apps already deployed in Italy, Switzerland and Germany. We observe that changing the people holding a pair of handsets, with the location of the handsets otherwise remaining unchanged, can cause variations of ±10dB in the attenuation level reported by the GAEN API. To provide baseline data on the radio propagation environment we also used the standard Android Bluetooth LE scanner API to collect measurements of RSSI as the distance was varied between two Google Pixel 2 handsets placed at a height of approximately 0.5m (about the same height as the tram seating) in the centre aisle of the tram carriage. abstract: We report on the results of a Covid-19 contact tracing app measurement study carried out on a standard design of European commuter tram. Our measurements indicate that in the tram there is little correlation between Bluetooth received signal strength and distance between handsets. We applied the detection rules used by the Italian, Swiss and German apps to our measurement data and also characterised the impact on performance of changes in the parameters used in these detection rules. We find that the Swiss and German detection rules trigger no exposure notifications on our data, while the Italian detection rule generates a true positive rate of 50% and a false positive rate of 50%. Our analysis indicates that the performance of such detection rules is similar to that of triggering notifications by randomly selecting from the participants in our experiments, regardless of proximity. url: https://www.ncbi.nlm.nih.gov/pubmed/32997724/ doi: 10.1371/journal.pone.0239943 id: cord-001129-gi2kswai author: Lemos de Matos, Ana title: Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals date: 2013-11-27 words: 6978.0 sentences: 342.0 pages: flesch: 47.0 cache: ./cache/cord-001129-gi2kswai.txt txt: ./txt/cord-001129-gi2kswai.txt summary: Because viruses are responsible for a great number of severe and lethal diseases, together with the important role that RLRs play in mammalian innate immune system, we expect that RIG-I, MDA5 and LGP2 genes may have been under intense selective pressures in all mammals. Evidence for positive selection on mammalian orthologous for RIG-I ( Figure S7 ), MDA5 ( Figure S8 ) and LGP2 ( Figure S9 ) genes was detected using PAML package [54, 55] site-specific models M1a versus M2a and M7 versus M8. (C) Positively-selected codons are exhibited in the table and numbered according to the mammalian LGP2 deduced protein sequences alignment ( Figure S6 downstream RIG-I and MDA5 signaling, which implies functional constraints, the observed variability across species can be perceived as a great structural plasticity for mammalian CARDs. The helicase domain in the RLR family is generally described as exhibiting affinity for dsRNA [78] . abstract: The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842351/ doi: 10.1371/journal.pone.0081864 id: cord-291104-6chpmgry author: Leung, Danny T. M. title: Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients date: 2016-08-05 words: 6269.0 sentences: 313.0 pages: flesch: 58.0 cache: ./cache/cord-291104-6chpmgry.txt txt: ./txt/cord-291104-6chpmgry.txt summary: The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients'' plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. Similar results were found when the serum of these individuals was examined: the cancer patients (424 +/-121 ng/ mL) had significantly (P = 0.0002) higher levels of OPN than healthy subjects (314 +/-98 ng/ mL) (Fig 5B) , the assay sensitivity and specificity being 18% and 97%, respectively. The finding that the mAb 446 inhibition ELISA and the commercial OPN kit could not detect elevated OPN levels in the cancer patients suggested the possibility that the OPN present could be fragmented i.e. the target sites for the antibodies used in these assays could be missing, whereas, by virtue of the design of the mAb 659-based assay, the thrombin-sensitive site must be present. abstract: We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients’ plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions. url: https://doi.org/10.1371/journal.pone.0160412 doi: 10.1371/journal.pone.0160412 id: cord-354052-x4ckzw64 author: Li, Chunhua title: Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination date: 2013-08-02 words: 4932.0 sentences: 256.0 pages: flesch: 53.0 cache: ./cache/cord-354052-x4ckzw64.txt txt: ./txt/cord-354052-x4ckzw64.txt summary: We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. All mPEDV infected cells stained positive both with the polyclonal MHV serum and with the monoclonal antibody directed against the PEDV nucleocapsid protein confirming the purity and the identity of the chimeric virus. Donor RNAs transcribed from the pPEDV and pPEDV-DORF3 transfer vectors were electroporated into mPEDV-infected L cells after which we were able to recover and purify the r-wtPEDV and PEDV-DORF3 viruses in VERO cells. Thus, the PEDV-DORF3/GFP and PEDV-DORF3/RLuc virus were preincubated with dilutions of serum obtained from an experimentally PEDV-infected pig and control serum, and the mixtures were subsequently added to VERO cells and incubated after which the GFP and Renilla luciferase expression was recorded at 9 and 6 hours p.i., respectively (Fig. 5D) . abstract: Porcine epidemic diarrhea virus (PEDV) causes severe economic losses in the swine industry in China and other Asian countries. Infection usually leads to an acute, often lethal diarrhea in piglets. Despite the impact of the disease, no system is yet available to manipulate the viral genome which has severely hampered research on this virus until today. We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. Using this system, we deleted the ORF3 gene entirely from the viral genome and showed that the ORF3 protein is not essential for replication of the virus in vitro. In addition, we inserted heterologous genes (i.e. the GFP and Renilla luciferase genes) at two positions in the viral genome, either as an extra expression cassette or as a replacement for the ORF3 gene. We demonstrated the expression of both GFP and Renilla luciferase as well as the application of these viruses by establishing a convenient and rapid virus neutralization assay. The new PEDV reverse genetics system will enable functional studies of the structural proteins and the accessory ORF3 protein and will allow the rational design and development of next generation PEDV vaccines. url: https://doi.org/10.1371/journal.pone.0069997 doi: 10.1371/journal.pone.0069997 id: cord-011798-uss38ped author: Li, Guowei title: Intellectual capital and the efficiency of SMEs in the transition economy China; Do financial resources strengthen the routes? date: 2020-07-02 words: 8759.0 sentences: 490.0 pages: flesch: 38.0 cache: ./cache/cord-011798-uss38ped.txt txt: ./txt/cord-011798-uss38ped.txt summary: Despite the bourgeoning literature, studies have not yet unleashed the influence of each dimension of intellectual capital; human capital, structural capital and customer capital on SMEs'' efficiency with financial resources as a moderator. A survey method was used and collected evidence from 264 Chinese SMEs. The findings exhibit that human capital directly enhances SMEs'' efficiency but the presence of financial resources as a moderator weakens the influence. This research recommends that owners and managers of SMEs need to use their financial resources complementary with structural and customer capital while human capital should be used exclusively. Studies have also discussed the role of intellectual capital (IC) (human capital, customer capital and structural capital) in firm competitive advantage and performance in emerging and developed economies [12, 13] Also, studies have assessed the direct and indirect influence of IC on performance [14] [15] [16] . abstract: Intellectual capital has been grabbed the attention of researchers due to its momentous role in sustainable competitive advantage and organizational success. There is a growing catalog of related assessments, publications and reviews that display the direct and indirect role of intellectual capital in business success and profitability. Despite the bourgeoning literature, studies have not yet unleashed the influence of each dimension of intellectual capital; human capital, structural capital and customer capital on SMEs' efficiency with financial resources as a moderator. The present study fills the gap and assesses if financial resources strengthen the paths between the dimensions of intellectual capital and SMEs' efficiency. A survey method was used and collected evidence from 264 Chinese SMEs. The findings exhibit that human capital directly enhances SMEs' efficiency but the presence of financial resources as a moderator weakens the influence. However, social capital and customer capital do not directly improve SMEs' efficiency but financial resources reinforce the paths social and customer capital and SMEs efficiency. This research recommends that owners and managers of SMEs need to use their financial resources complementary with structural and customer capital while human capital should be used exclusively. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332020/ doi: 10.1371/journal.pone.0235462 id: cord-278018-3qemb0x3 author: Li, Li title: Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy date: 2011-08-22 words: 5980.0 sentences: 332.0 pages: flesch: 57.0 cache: ./cache/cord-278018-3qemb0x3.txt txt: ./txt/cord-278018-3qemb0x3.txt summary: In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. The phenotypic and functional analysis of CD69-expressing cells strongly suggested that CD69 could be a useful marker for the identification or enrichment of antigen specific Th1 cells at local sites following MTB infection. However, following stimulation with MTB-specific peptides of ESAT-6/CFP-10, CD4 + CD69 + T cells from the same patients expressed high levels of IFN-c, IL-2 and TNF-a (data not shown). However, following stimulation with MTB-specific peptides of ESAT-6/ CFP-10, CD4 + CD69 + T cells from the same patients with tuberculous pleurisy expressed high levels of IFN-c, IL-2 and TNF-a, indicating that the response was MTB-specific. abstract: Th1 cell-mediated immune responses at the site of active infection are important to restrict the growth of M.tuberculosis (MTB) and for the spontaneous resolution of patients with tuberculous pleurisy (TBP). In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. CD4(+)CD69(+) T cells expressed T-bet and IL-12Rβ2. After stimulation with MTB-specific antigens, CD4(+)CD69(+) T cells expressed significantly higher levels of IFN-γ, IL-2 and TNF-α than CD4(+)CD69(−) T cells, demonstrating that CD4(+)CD69(+) T cells were MTB-specific Th1 cells. In addition, CD4(+)CD69(+) T cells were mostly polyfunctional Th1 cells that simultaneously produced IFN-γ, IL-2, TNF-α and displayed an effector or effector memory phenotype (CD45RA(−)CCR7(−)CD62L(−)CD27(−)). Moreover, the percentages of CD4(+)CD69(+) T cells were significantly and positively correlated with polyfunctional T cells. Interestingly, sorted CD4(+)CD69(+) but not CD4(+)CD69(−) fractions by flow cytometry produced IFN-γ, IL-2 and TNF-α that were significantly regulated by CD4(+)CD25(+) Treg cells. Taken together, based on the expression of CD69, we found a direct quantitative and qualitative method to detect and evaluate the in vivo generated MTB-specific polyfunctional CD4(+) T cells in PFCs from patients with TBP. This method can be used for the potential diagnosis and enrichment or isolation of MTB-specific Th1 cells in the investigations. url: https://doi.org/10.1371/journal.pone.0023700 doi: 10.1371/journal.pone.0023700 id: cord-273764-itu39mln author: Li, Taisheng title: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus date: 2006-12-20 words: 2660.0 sentences: 120.0 pages: flesch: 49.0 cache: ./cache/cord-273764-itu39mln.txt txt: ./txt/cord-273764-itu39mln.txt summary: In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. As show in Fig. 1 , recovered patients clearly experienced two distinct phases of cell restoration in the peripheral blood; an initial rapid phase for all the cell populations studied in the first 3 months after the onset of symptoms followed by a significant slower phase during the subsequent months. To study the sequential changes in CTL responses against SARS-CoV, we used ELISPOT-based technique to quantify the number of INF-c releasing cells in the peripheral blood against peptide pools covering the entire N protein derived from the Urbani strain [3] . We have shown for the first time that recovered patients have persistent and robust binding as well as neutralizing antibody and CTL responses throughout the study period with a moderate decline one year after the onset of symptoms. abstract: Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/17183651/ doi: 10.1371/journal.pone.0000024 id: cord-284016-zb6cv8ik author: Li, Wei title: Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection date: 2008-04-16 words: 4188.0 sentences: 258.0 pages: flesch: 48.0 cache: ./cache/cord-284016-zb6cv8ik.txt txt: ./txt/cord-284016-zb6cv8ik.txt summary: Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. It has been reported that influenza virus can activate the expression of COX-2 in cell culture systems [26] and that dsRNA can induce the production of COX-2, followed by PGE 2 release [5] . To identify the viral components which play important roles in IV-stimulated pro-inflammatory factors COX-2 and IL-32 expression, we screened all ten proteins of influenza virus: HA, NA, NP, NS1, NS2, M1, M2, PA, PB1, PB2 and poly(IC) (to mimic viral replicative intermediate dsRNA) by luciferase assays. Both influenza A virus infection and poly(IC)+IFN-c treatment in A549 human lung epithelial cells were able to induce COX-2/ IL-32 mRNA and protein expression as well as PGE 2 and IL-32 accumulation in the cell culture supernatants. abstract: BACKGROUND: Interleukin (IL)-32 is a recently described pro-inflammatory cytokine that has been reported to be induced by bacteria treatment in culture cells. Little is known about IL-32 production by exogenous pathogens infection in human individuals. METHODS AND FINDINGS: In this study, we found that IL-32 level was increased by 58.2% in the serum samples from a cohort of 108 patients infected by influenza A virus comparing to that of 115 healthy individuals. Another pro-inflammatory factor cyclooxygenase (COX)-2-associated prostaglandin E2 was also upregulated by 2.7-fold. Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. Interestingly, we found that COX-2-associate PGE(2) production activated by influenza virus infection was significantly suppressed by over-expression of IL-32 but increased by IL-32-specific siRNA, suggesting there was a feedback mechanism between IL-32 and COX-2. CONCLUSIONS: IL-32 is induced by influenza A virus infection via COX-2 in the inflammatory cascade. Our results provide that IL-32 is a potential target for anti-inflammatory medicine screening. url: https://doi.org/10.1371/journal.pone.0001985 doi: 10.1371/journal.pone.0001985 id: cord-001383-hww0watl author: Li, Wenchao title: Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats date: 2014-08-12 words: 6541.0 sentences: 291.0 pages: flesch: 48.0 cache: ./cache/cord-001383-hww0watl.txt txt: ./txt/cord-001383-hww0watl.txt summary: title: Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, we found that the major structural genes of PPRV can be efficiently expressed in recombinant baculovirus-infected Sf21 insect cells and that these genes can then support the production of PPRV VLPs. The expression of M protein was necessary and sufficient for the formation of VLPs (data not shown); the additional expression of the H or F glycoproteins allowed formation of budding particles with the typical morphology and size of PPRV and related paramyxoviruses. abstract: Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact. For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed morphology similar to that of the native virus particles. Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation. Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential “differentiating infected from vaccinated animals” (DIVA) vaccine candidates for the surveillance and eradication of PPR. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130610/ doi: 10.1371/journal.pone.0104791 id: cord-264880-0tmd9knh author: Li, Zhao title: Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date: 2016-04-13 words: 5347.0 sentences: 260.0 pages: flesch: 46.0 cache: ./cache/cord-264880-0tmd9knh.txt txt: ./txt/cord-264880-0tmd9knh.txt summary: We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. To avoid thermal cycling, different isothermal amplification methods have been developed that rapidly amplify nucleic acids to detectable levels at a single temperature [42, 43] , such as loop-mediated amplification (LAMP) [44] , rolling circle amplification (RCA) [45] , helicasedependent amplification (HDA) [46] , nucleic acid sequence-based amplification (NASBA) [47] , recombinase polymerase amplification (RPA) [48] , transcription-mediated amplification (TMA) [49] , multiple displacement amplification (MDA) [50] , and strand-displacement amplification (SDA) [51] . Finally, we sealed the PWA chip in a homemade copper chamber filled with oil and successfully performed real-time dRPA on an isothermal incubation setup for the absolute quantification of serial dilutions of a Listeria monocytogenes gDNA stock solution. abstract: Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings. url: https://doi.org/10.1371/journal.pone.0153359 doi: 10.1371/journal.pone.0153359 id: cord-308480-t2vukbwp author: Liang, Zhongjie title: Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant date: 2011-08-24 words: 4279.0 sentences: 206.0 pages: flesch: 48.0 cache: ./cache/cord-308480-t2vukbwp.txt txt: ./txt/cord-308480-t2vukbwp.txt summary: In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. Taking two typical antibiotics, imipenem and carbapenem as example, the docked complex structures revealed that although the antibiotics adopted diverse conformations in the active site, the lactam motifs were positioned in the same orientation by coordinating with zinc ions tightly ( Figure 2C ), which suggested that the catalytic mechanisms were highly conserved among B1 subclass enzymes, as shown in Figure 3 . To gain the structural insight into the mechanism of the potent hydrolysis of NDM-1, the intermolecular interactions of three models of NDM-1, VIM-2 and FEZ-1 in complex with antibiotics meropenem were compared and analyzed in details ( Figure 4A -C). abstract: The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat. In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model. At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies. url: https://doi.org/10.1371/journal.pone.0023606 doi: 10.1371/journal.pone.0023606 id: cord-000266-xwfptmmv author: Liao, Qiuyan title: Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study date: 2010-10-12 words: 7129.0 sentences: 356.0 pages: flesch: 44.0 cache: ./cache/cord-000266-xwfptmmv.txt txt: ./txt/cord-000266-xwfptmmv.txt summary: METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. We report on a theoretical model that incorporated elements of influenza causal knowledge, perceived self-efficacy and also social and affective influences ( Figure 1 ) because these latter variables have been less frequently studied in combination, but have theoretical and logical support for their potential importance in the context of RIDs. We tested this model against data collected in the early phase of the influenza A/H1N1 pandemic (Table S1 ) to examine how levels of trust in formal and informal sources of risk/prevention information associated with hand washing and social distancing. abstract: BACKGROUND: Whether information sources influence health protective behaviours during influenza pandemics or other emerging infectious disease epidemics is uncertain. METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. PRINCIPAL FINDINGS: Trust in formal (government/media) information about influenza was associated with greater reported understanding of A/H1N1 cause (β = 0.36) and A/H1N1 prevention self-efficacy (β = 0.25), which in turn were associated with more hand hygiene (β = 0.19 and β = 0.23, respectively). Trust in informal (interpersonal) information was negatively associated with perceived personal A/H1N1 susceptibility (β = −0.21), which was negatively associated with perceived self-efficacy (β = −0.42) but positively associated with influenza worry (β = 0.44). Trust in informal information was positively associated with influenza worry (β = 0.16) which was in turn associated with greater social distancing (β = 0.36). Multigroup comparisons showed gender differences regarding paths from trust in formal information to understanding of A/H1N1 cause, trust in informal information to understanding of A/H1N1 cause, and understanding of A/H1N1 cause to perceived self-efficacy. CONCLUSIONS/SIGNIFICANCE: Trust in government/media information was more strongly associated with greater self-efficacy and handwashing, whereas trust in informal information was strongly associated with perceived health threat and avoidance behaviour. Risk communication should consider the effect of gender differences. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953514/ doi: 10.1371/journal.pone.0013350 id: cord-000336-57es391o author: Liao, Qiuyan title: Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study date: 2011-03-11 words: 7649.0 sentences: 383.0 pages: flesch: 39.0 cache: ./cache/cord-000336-57es391o.txt txt: ./txt/cord-000336-57es391o.txt summary: Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). The model proposed that attitudes towards vaccination (perceived benefits of pH1N1 vaccination and concerns regarding possible adverse effects of pH1N1 vaccination), perceived social pressures from significant others and other people around regarding pH1N1 vaccination (social norms regarding pH1N1 vaccination), perceived self-efficacy in taking vaccination (perceived self-efficacy), anticipated regret for not taking the pH1N1 vaccination (anticipated regret) and seasonal influenza vaccination history would predict vaccination intention, which in turn predicts vaccination planning and future vaccination uptake; anticipated regret and perceived self-efficacy could also predict vaccination status directly; finally, vaccination planning was proposed to bridge the intention-behavior gap and predict vaccination status directly ( Figure 3 ). abstract: BACKGROUND: Vaccination was a core component for mitigating the 2009 influenza pandemic (pH1N1). However, a vaccination program's efficacy largely depends on population compliance. We examined general population decision-making for pH1N1 vaccination using a modified Theory of Planned Behaviour (TBP). METHODOLOGY: We conducted a longitudinal study, collecting data before and after the introduction of pH1N1 vaccine in Hong Kong. Structural equation modeling (SEM) tested if a modified TPB had explanatory utility for vaccine uptake among adults. PRINCIPAL FINDINGS: Among 896 subjects who completed both the baseline and the follow-up surveys, 7% (67/896) reported being “likely/very likely/certain” to be vaccinated (intent) but two months later only 0.8% (7/896) reported having received pH1N1 vaccination. Perception of low risk from pH1N1 (60%) and concerns regarding adverse effects of the vaccine (37%) were primary justifications for avoiding pH1N1 vaccination. Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). Social norm (β = 0.70), anticipated regret (β = 0.19) and vaccination intention (β = 0.31) were positively associated with, and accounted for 70% of variance in vaccination planning, which, in turn subsequently predicted self-reported vaccination uptake (β = 0.36) accounting for 36% of variance in reported vaccination behaviour. CONCLUSIONS/SIGNIFICANCE: Perceived low risk from pH1N1 and perceived high risk from pH1N1 vaccine inhibited pH1N1 vaccine uptake. Both the TPB and the additional components contributed to intended vaccination uptake but social norms and anticipated regret predominantly associated with vaccination intention and planning. Vaccination planning is a more significant proximal determinant of uptake of pH1N1 vaccine than is intention. Intention alone is an unreliable predictor of future vaccine uptake. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055876/ doi: 10.1371/journal.pone.0017713 id: cord-333413-8buawes0 author: Liebing, J. title: Health status of free-ranging ring-necked pheasant chicks (Phasianus colchicus) in North-Western Germany date: 2020-06-16 words: 5556.0 sentences: 306.0 pages: flesch: 51.0 cache: ./cache/cord-333413-8buawes0.txt txt: ./txt/cord-333413-8buawes0.txt summary: Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. In 2014 and 2015, the Institute for Terrestrial and Aquatic Wildlife Research (ITAW), University of Veterinary Medicine Hannover, Foundation, Hannover and the Wildlife Research Institute, State Office for Nature, Environment and Consumer Protection of North Rhine-Westphalia caught free-living Ring-necked Pheasant chicks from Lower Saxony (Cuxhaven, Grafschaft Bentheim, Emsland, Osnabrück, Vechta), North Rhine-Westphalia (Coesfeld, Warendorf) and Schleswig-Holstein (Dithmarschen) to assess the health state by means of pathological, microbiological, virological, parasitological and toxicological investigations. abstract: Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. Contributing factors to the ongoing negative trend, such as the effects of pesticides, diseases, predation, increase in traffic and reduced fallow periods, are currently being controversially discussed. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. The pheasant chicks were divided into three age groups to detect differences in their development and physical constitution. In addition, pathomorphological, parasitological, virological, bacteriological and toxicological investigations were performed. The younger chicks were emaciated, while the older chicks were of moderate to good nutritional status. However, the latter age group was limited to a maximum of three chicks per hen, while the youngest age class comprised up to ten chicks. The majority of chicks suffered from dermatitis of the periocular and caudal region of the head (57–94%) of unknown origin. In addition, intestinal enteritis (100%), pneumonia (26%), hepatitis (24%), perineuritis (6%), tracheitis (24%), muscle degeneration (1%) and myositis (1%) were found. In 78% of the cases, various Mycoplasma spp. were isolated. Mycoplasma gallisepticum (MG) was not detected using an MG-specific PCR. Parasitic infections included Philopteridae (55%), Coccidia (48%), Heterakis/Ascaridia spp. (8%) and Syngamus trachea (13%). A total of 8% of the chicks were Avian metapneumovirus (AMPV) positive using RT-PCR, 16% positive for infectious bronchitis virus (IBV) using RT-PCR, and 2% positive for haemorrhagic enteritis virus (HEV) using PCR. All samples tested for avian encephalomyelitis virus (AEV), infectious bursal disease virus (IBDV) or infectious laryngotracheitis virus (ILTV) were negative. The pool samples of the ten chicks were negative for all acid, alkaline-free and derivative substances, while two out of three samples tested were positive for the herbicide glyphosate. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. Theses impacts may have played a major role in the decline in pheasant populations. url: https://www.ncbi.nlm.nih.gov/pubmed/32544211/ doi: 10.1371/journal.pone.0234044 id: cord-001537-i34vmfpp author: Lima, Francisco Esmaile de Sales title: Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date: 2015-02-17 words: 3874.0 sentences: 195.0 pages: flesch: 53.0 cache: ./cache/cord-001537-i34vmfpp.txt txt: ./txt/cord-001537-i34vmfpp.txt summary: The predicted protein sequences encoded by ORF2 (cap) and ORF1 (rep) of BatCV I-VI genomes were used for phylogenetic analysis with representative and recently discovered circoviruses/cycloviruses; Pepper golden mosaic virus was used as outgroup, as they are somewhat related to other members in the Circoviridae family (Fig. 3A, 3B and 3C ). The phylogenetic analysis constructed based on the alignments of the complete REP and CAP protein confirms that BatCV POA/II and VI cluster into the genus Cyclovirus along with the Chinese cycloviruses sequences clade detected in bat feces [18] and sharing less than 65% of identity at the CAP/REP amino acid level. BatCV POA I and V had a low amino acid identity with CAP (<20%) and REP (<10%) sequences of two other sequences detected in bat feces in this study with known circoviruses/cycloviruses (Table 2) . abstract: Circoviruses are highly prevalent porcine and avian pathogens. In recent years, novel circular ssDNA genomes have recently been detected in a variety of fecal and environmental samples using deep sequencing approaches. In this study the identification of genomes of novel circoviruses and cycloviruses in feces of insectivorous bats is reported. Pan-reactive primers were used targeting the conserved rep region of circoviruses and cycloviruses to screen DNA bat fecal samples. Using this approach, partial rep sequences were detected which formed five phylogenetic groups distributed among the Circovirus and the recently proposed Cyclovirus genera of the Circoviridae. Further analysis using inverse PCR and Sanger sequencing led to the characterization of four new putative members of the family Circoviridae with genome size ranging from 1,608 to 1,790 nt, two inversely arranged ORFs, and canonical nonamer sequences atop a stem loop. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331541/ doi: 10.1371/journal.pone.0118070 id: cord-334218-bkjfy66e author: Lin, Jung-Da title: Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak date: 2016-01-15 words: 3619.0 sentences: 176.0 pages: flesch: 57.0 cache: ./cache/cord-334218-bkjfy66e.txt txt: ./txt/cord-334218-bkjfy66e.txt summary: title: Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak The objectives of the present study were to investigate the effects between a 1-year period before and after PEDV outbreak on a sow''s reproductive traits on a commercial pig farm in Taiwan. The average number of mated females, average parity of farrowed sows, number of matings, number of farrowings, FR, RR, number of abortions, LMFY, percentage of sows mated by 7 days after weaning, WFSI, FI, NPDs, replacement rates of sows and sow culling rates of preand post-PEDV outbreak periods were compared using a Mann-Whitney test. In the present study, we compared the productivity index of gilts and sows between 1 year pre-and post-PEDV outbreak in a Taiwanese breeding herd. Impact of porcine epidemic diarrhea virus infection at different periods of pregnancy on subsequent reproductive performance in gilts and sows abstract: Porcine epidemic diarrhea virus (PEDV) is an important pathogen that has a significant economic impact on the swine industry by imposing a high rate of mortality in suckling piglets. However, limited information on the productivity values of gilts and sows infected with PEDV is available. Here, we evaluate the productivity index in gilts and sows during the 1-year period before (19 January 2013 to 18 January 2014) and after (19 January 2014 to 18 January 2015) a PEDV outbreak from a 2000-sow breeding herd in Taiwan. The farrowing rate (FR), return rate (RR), total pigs born per litter (TB), pigs born alive per litter (BA), weaning pigs per litter (WPL), pre-weaning mortality, percentage of sows mated by 7 days after weaning, weaning to first service interval (WFSI), mated female nonproductive days (NPDs), replacement rate of sows and sow culling rate were compared using productive records. The FR (-9.6%), RR (+9.8%), TB (-1.6), BA (-1.1), WPL (-1.1), sows mated by 7 days after weaning (-6.9%), WFSI (+0.8 days), NPDs (+6.9 days) and sow culling rate (+7.2%) were significantly different between the 1-year pre-PEDV outbreak period and the post-PEDV outbreak period. Impacts of the PEDV infection on the reproductive performance were more severe in pregnant gilts than in sows. In conclusion, these findings indicate that the outbreak of PEDV caused an increase in the rate of NPDs in breeding herds. url: https://doi.org/10.1371/journal.pone.0147316 doi: 10.1371/journal.pone.0147316 id: cord-301180-ndiwmnv0 author: Lin, Min-Hsuan title: Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking date: 2012-12-10 words: 5161.0 sentences: 233.0 pages: flesch: 39.0 cache: ./cache/cord-301180-ndiwmnv0.txt txt: ./txt/cord-301180-ndiwmnv0.txt summary: Importantly, treatment of Myc-Rev and Nullbasic-mCherry expressing cells with LMB resulted in the complete restoration of Myc-Rev nucleolar accumulation (Fig. 3, row 6) , suggesting that Nullbasic requires functional CRM1 to mislocalize Rev most likely by an indirect interaction. While expression of Nullbasic-mCherry alone had no apparent effect on the nucleolar localization of either protein (Fig. 6 , rows 2 and 5), coexpression of Nullbasic-mCherry with Myc-Rev induced relocalization of C23 but not fibrillarin from the nucleolus to the nucleoplasm, in a manner concomitant with the redistribution of Myc-Rev (Fig. 6, rows 3 and 6 , respectively). CRM1 is a cellular receptor that recognizes and binds to the leucine-rich NES domain of Rev, an interaction which facilitates the egress of Rev/viral mRNA complexes through nuclear pores [3, 4, 42] and is readily visualized in cells as a colocalization in the nucleolus (Fig. 3, row 2 ). abstract: Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation. url: https://www.ncbi.nlm.nih.gov/pubmed/23251541/ doi: 10.1371/journal.pone.0051466 id: cord-001123-n2e4s7bu author: Lin, Yue-Zhi title: The Soluble Form of the EIAV Receptor Encoded by an Alternative Splicing Variant Inhibits EIAV Infection of Target Cells date: 2013-11-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838338/ doi: 10.1371/journal.pone.0079299 id: cord-256326-3ebcuzd6 author: Liotta, Giuseppe title: Is social connectedness a risk factor for the spreading of COVID-19 among older adults? The Italian paradox date: 2020-05-21 words: 2364.0 sentences: 114.0 pages: flesch: 57.0 cache: ./cache/cord-256326-3ebcuzd6.txt txt: ./txt/cord-256326-3ebcuzd6.txt summary: We analyzed several variables to test this hypothesis, such as the percentage of infected patients aged >80 years, available nursing home beds, COVID-19 incidence rate, and the number of days from when the number of positive tests exceeded 50 (epidemic maturity). While there is a very clear association between the case fatality rate and age demographics (Italy has the second oldest population worldwide and has the highest ageing index in Europe [4] with a value of 168.9), we wanted to test the hypothesis that the supposed closeness between younger and older generations in Italian families may have played a major role in the pandemic spread. Additionally, we explored the relationship between the proportion of infected patients aged >80 years and social connectedness indicators, such as the percentage of family comprising one members and household size [5] . abstract: Italy was one of the first European countries affected by the new coronavirus (COVID-19) pandemic, with over 105,000 infected people and close to 13,000 deaths, until March 31(st). The pandemic has hit especially hard because of the country's demographic structure, with a high percentage of older adults. The authors explore the possibility, recently aired in some studies, of extensive intergenerational contact as a possible determinant of the severity of the pandemic among the older Italian adults. We analyzed several variables to test this hypothesis, such as the percentage of infected patients aged >80 years, available nursing home beds, COVID-19 incidence rate, and the number of days from when the number of positive tests exceeded 50 (epidemic maturity). We also included in the analysis mean household size and percentage of households comprising one person, in the region. Paradoxically, the results are opposite of what was previously reported. The pandemic was more severe in regions with higher family fragmentation and increased availability of residential health facilities. url: https://www.ncbi.nlm.nih.gov/pubmed/32437377/ doi: 10.1371/journal.pone.0233329 id: cord-001199-9khx93c0 author: Liu, Fengchen title: Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model date: 2014-02-06 words: 6871.0 sentences: 300.0 pages: flesch: 48.0 cache: ./cache/cord-001199-9khx93c0.txt txt: ./txt/cord-001199-9khx93c0.txt summary: Changes in household structure and the proportion of children in the population as a result of the one-child policy could have more effects on the AR, and the difference in AR could be as high as 60% under a scenario of very high immunity loss rate per year ( Figures 5(A) ). For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average annual attack rates over 10 years (2015 to 2024) between two policies. For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average annual attack rates over 10 years (2015 to 2024) between two policies. For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average secondary attack rates over 10 years (2015 to 2024) between two policies. abstract: BACKGROUND: China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission? METHODS AND FINDINGS: To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, −0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy. CONCLUSIONS: This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916292/ doi: 10.1371/journal.pone.0084961 id: cord-292537-9ra4r6v6 author: Liu, Fenglin title: Predicting and analyzing the COVID-19 epidemic in China: Based on SEIRD, LSTM and GWR models date: 2020-08-27 words: 5662.0 sentences: 259.0 pages: flesch: 52.0 cache: ./cache/cord-292537-9ra4r6v6.txt txt: ./txt/cord-292537-9ra4r6v6.txt summary: For the study of infectious diseases like COVID-19, SARS, and Ebola, most of the literature used descriptive research or model methods to assess indicators and analyze the effect of interventions, such as combining migration data to evaluate the potential infection rate [18, 19] , understanding the impact of factors like environmental temperature and vaccines that might be potentially linked to the diseases [20, 21] , using basic and time-varying reproduction number (R 0 & R t ) to estimate changeable transmission dynamics of epidemic conditions [22] [23] [24] [25] [26] [27] , calculating and predicting the fatal risk to display any stage of outbreak [28] [29] [30] , or providing suggestions and interventions from risk management and other related aspects based on the results of modeling tools or historical lessons [31] [32] [33] [34] [35] [36] [37] [38] [39] . abstract: In December 2019, the novel coronavirus pneumonia (COVID-19) occurred in Wuhan, Hubei Province, China. The epidemic quickly broke out and spread throughout the country. Now it becomes a pandemic that affects the whole world. In this study, three models were used to fit and predict the epidemic situation in China: a modified SEIRD (Susceptible-Exposed-Infected-Recovered-Dead) dynamic model, a neural network method LSTM (Long Short-Term Memory), and a GWR (Geographically Weighted Regression) model reflecting spatial heterogeneity. Overall, all the three models performed well with great accuracy. The dynamic SEIRD prediction APE (absolute percent error) of China had been ≤ 1.0% since Mid-February. The LSTM model showed comparable accuracy. The GWR model took into account the influence of geographical differences, with R(2) = 99.98% in fitting and 97.95% in prediction. Wilcoxon test showed that none of the three models outperformed the other two at the significance level of 0.05. The parametric analysis of the infectious rate and recovery rate demonstrated that China's national policies had effectively slowed down the spread of the epidemic. Furthermore, the models in this study provided a wide range of implications for other countries to predict the short-term and long-term trend of COVID-19, and to evaluate the intensity and effect of their interventions. url: https://www.ncbi.nlm.nih.gov/pubmed/32853285/ doi: 10.1371/journal.pone.0238280 id: cord-317058-anvmj4li author: Liu, Xinkui title: Analysis of clinical features and early warning signs in patients with severe COVID-19: A retrospective cohort study date: 2020-06-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019. Although previous studies have described the clinical aspects of COVID-19, few studies have focused on the early detection of severe COVID-19. Therefore, this study aimed to identify the predictors of severe COVID-19 and to compare clinical features between patients with severe COVID-19 and those with less severe COVID-19. Patients admitted to designated hospital in the Henan Province of China who were either discharged or died prior to February 15, 2020 were enrolled retrospectively. Additionally, patients who underwent at least one of the following treatments were assigned to the severe group: continuous renal replacement therapy, high-flow oxygen absorption, noninvasive and invasive mechanical ventilation, or extracorporeal membrane oxygenation. The remaining patients were assigned to the non-severe group. Demographic information, initial symptoms, and first visit examination results were collected from the electronic medical records and compared between the groups. Multivariate logistic regression analysis was performed to determine the predictors of severe COVID-19. A receiver operating characteristic curve was used to identify a threshold for each predictor. Altogether,104 patients were enrolled in our study with 30 and 74 patients in the severe and non-severe groups, respectively. Multivariate logistic analysis indicated that patients aged ≥63 years (odds ratio = 41.0; 95% CI: 2.8, 592.4), with an absolute lymphocyte value of ≤1.02×10(9)/L (odds ratio = 6.1; 95% CI = 1.5, 25.2) and a C-reactive protein level of ≥65.08mg/L (odds ratio = 8.9; 95% CI = 1.0, 74.2) were at a higher risk of severe illness. Thus, our results could be helpful in the early detection of patients at risk for severe illness, enabling the implementation of effective interventions and likely lowering the morbidity of COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32589691/ doi: 10.1371/journal.pone.0235459 id: cord-000574-7eflwyxk author: Liu, Yanli title: Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20 date: 2012-02-07 words: 3919.0 sentences: 216.0 pages: flesch: 52.0 cache: ./cache/cord-000574-7eflwyxk.txt txt: ./txt/cord-000574-7eflwyxk.txt summary: The non-conservative N-terminal domain of the protein phosphatase1 (PP1), with 1-8 residues deleted, showed higher sensitivity to three substrates and influenced the structure and properties of PP1 [10] , whereas the truncation of the Cterminal region improved the thermal stability of endo-bglucanase from Bacillus subtilis JA18 [11] . The TIM barrel domain, which is one of the most common catalytic domains, is adopted by about 10% of the enzymes; thus, sequence modification inside or outside the domain to improve the enzymatic property and determine the catalytic mechanism was reported in many studies. In the present research, Atgus and the partial sequence [Atgus(-3t)] without Cterminal non-conservative sequence behind the TIM barrel domain were amplified in order to investigate effects of nonconservative sequence on enzymatic property. Based on the same hydrolyzing mode, relatively higher thermal stability, and especially the enhanced affinity and catalytic efficiency for GL, deletion of the non-conservative sequence behind the TIM barrel domain was a successful evolution of AtGUS. abstract: We cloned the β-glucuronidase gene (AtGUS) from Aspergillus terreus Li-20 encoding 657 amino acids (aa), which can transform glycyrrhizin into glycyrrhetinic acid monoglucuronide (GAMG) and glycyrrhetinic acid (GA). Based on sequence alignment, the C-terminal non-conservative sequence showed low identity with those of other species; thus, the partial sequence AtGUS(-3t) (1–592 aa) was amplified to determine the effects of the non-conservative sequence on the enzymatic properties. AtGUS and AtGUS(-3t) were expressed in E. coli BL21, producing AtGUS-E and AtGUS(-3t)-E, respectively. At the similar optimum temperature (55°C) and pH (AtGUS-E, 6.6; AtGUS(-3t)-E, 7.0) conditions, the thermal stability of AtGUS(-3t)-E was enhanced at 65°C, and the metal ions Co(2+), Ca(2+) and Ni(2+) showed opposite effects on AtGUS-E and AtGUS(-3t)-E, respectively. Furthermore, Km of AtGUS(-3t)-E (1.95 mM) was just nearly one-seventh that of AtGUS-E (12.9 mM), whereas the catalytic efficiency of AtGUS(-3t)-E was 3.2 fold higher than that of AtGUS-E (7.16 vs. 2.24 mM s(−1)), revealing that the truncation of non-conservative sequence can significantly improve the catalytic efficiency of AtGUS. Conformational analysis illustrated significant difference in the secondary structure between AtGUS-E and AtGUS(-3t)-E by circular dichroism (CD). The results showed that the truncation of the non-conservative sequence could preferably alter and influence the stability and catalytic efficiency of enzyme. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274521/ doi: 10.1371/journal.pone.0030998 id: cord-001363-irysq6pf author: Liu, Zhenjiang title: SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects date: 2014-07-23 words: 5113.0 sentences: 271.0 pages: flesch: 49.0 cache: ./cache/cord-001363-irysq6pf.txt txt: ./txt/cord-001363-irysq6pf.txt summary: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a breakthrough in clinical proteomics, and can detect different protein expression patterns of body fluid and tissue specimens between patients and healthy subjects, and its rapid development provides an alternative tool to search for biomarkers. The purpose of this pilot study was to preliminarily explore the differential protein expression pattern between NTD case mothers and normal control mothers using SELDI-TOF-MS protein profiling and Classification and Regression Tree (CART) analysis, in order to differentiate pregnancies complicated by the presence of an NTD-affected fetus from healthy controls. Analysis of amniotic fluid samples from mothers of NTDaffected fetuses and normal control mothers revealed two major, differentially expressed proteins at 14700 and 13776 Da used in the classification pattern to generate 3 terminal nodes (Fig. 7) . However, when we analyzed the data, we found that only four protein/peptide biomarkers, 4188, 6451, 11744 and 23425 Da, were detected in all serum, urine and amniotic fluid samples. abstract: Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108413/ doi: 10.1371/journal.pone.0103276 id: cord-267644-guzn0peq author: Livadiotis, George title: Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19 date: 2020-05-29 words: 6525.0 sentences: 326.0 pages: flesch: 54.0 cache: ./cache/cord-267644-guzn0peq.txt txt: ./txt/cord-267644-guzn0peq.txt summary: We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. First, we derive the exponential growth rates of the infected cases characterizing each examined region of US and Italy; then, we plot these values against the environmental temperatures of each region, and perform the corresponding statistical analysis. abstract: We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. The critical temperature, which eliminates the exponential growth, and thus the COVID-19 spread in US regions, is estimated to be T(C) = 86.1 ± 4.3 F(0). url: https://www.ncbi.nlm.nih.gov/pubmed/32469989/ doi: 10.1371/journal.pone.0233875 id: cord-344870-tbgqulpu author: Lloyd-Smith, James O. title: Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases date: 2007-02-14 words: 5997.0 sentences: 290.0 pages: flesch: 50.0 cache: ./cache/cord-344870-tbgqulpu.txt txt: ./txt/cord-344870-tbgqulpu.txt summary: METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. This study uses simulated data to assess the bias and precision of NB parameter estimates and the coverage accuracy of CIs for highly overdispersed datasets, addressing the challenges of small datasets as well as potential biases arising in the data collection process. In the epidemiological context that motivated this study, these values x i correspond to the numbers of secondary cases that were infected by n different infectious individuals, but similar data could arise from many other processes. abstract: BACKGROUND: The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k≥1), and the accuracy of confidence intervals estimated for k is typically not explored. METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. CONCLUSIONS: Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets. url: https://www.ncbi.nlm.nih.gov/pubmed/17299582/ doi: 10.1371/journal.pone.0000180 id: cord-351098-x729wpp7 author: Long, Rachel B. title: Characterizing trends in human-wildlife conflicts in the American Midwest using wildlife rehabilitation records date: 2020-09-11 words: 6361.0 sentences: 244.0 pages: flesch: 37.0 cache: ./cache/cord-351098-x729wpp7.txt txt: ./txt/cord-351098-x729wpp7.txt summary: The purpose of this study was to examine the value of wildlife rehabilitation facility admissions records for informing understanding of local human-wildlife conflicts and wildlife disease trends by 1) identifying the top reasons for admission to this facility, 2) examining how occurrences as measured by admitted cases may fluctuate monthly and across taxa, and 3) analyzing trends in commonly admitted disease cases. To examine how human-wildlife conflict as measured by admissions to this facility may vary seasonally and across taxonomic groups, we assessed changes in mean cases admitted per month via Chi-squared tests. We further examined the top four identified specific causes of admission to the wildlife rehabilitation facility: orphaned, dog attacks, cat attacks, and vehicle strikes. Our study demonstrates the value of wildlife rehabilitation records for characterizing local human-wildlife conflicts and potentially select disease trends, as well as how occurrences may fluctuate seasonally and impact taxa differently. abstract: Human-wildlife conflict is difficult to measure, but the analysis of records from wildlife rehabilitation facilities has shown potential as a technique for characterizing human impacts on wildlife. To examine the value of wildlife rehabilitation records for characterizing local human-wildlife conflicts and prevalence of select wildlife diseases, we reviewed 45,668 records representing over 280 species admitted to a wildlife rehabilitation facility over a 10-year period (2005–2014). We identified the most frequently recorded causes of admission for commonly admitted species, and evaluated how causes of admission may vary across taxa throughout the year. Our analyses support the value of wildlife rehabilitation facility data for characterizing some pressures from human-wildlife conflict and select disease trends for certain taxa, as well as utility for informing topics to emphasize in local conservation education efforts. For example, orphaned neonatal wildlife accounted for the largest proportion of admissions to this facility, and highlights a opportunity for conservation education regarding when wildlife is truly orphaned and requires professional intervention. Additionally, domestic dog attack cases accounted for a proportion of admissions comparable to that of domestic cat attacks, demonstrating a need for the conversation surrounding the impact of domestic pets on local wildlife to expand to include dogs in addition to cats. url: https://doi.org/10.1371/journal.pone.0238805 doi: 10.1371/journal.pone.0238805 id: cord-277548-hgmmtew3 author: Lou, Emil title: Perspectives of cancer patients and their health during the COVID-19 pandemic date: 2020-10-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: INTRODUCTION: The immunosuppressive nature of some cancers and many cancer-directed treatments may increase the risk of infection with and severe sequelae from Coronavirus Disease 2019 (COVID-19). The objective of this study was to compare concerns about COVID-19 among individuals undergoing cancer treatment to those with a history of cancer not currently receiving therapy and to those without a cancer history. METHODS: We conducted a cross-sectional anonymous online survey study of adults currently residing in the United States. Participants were recruited over a one-week period (April 3–11, 2020) using promoted advertisements on Facebook and Twitter. Groups were compared using chi-squared tests, Fisher’s exact tests, and t-tests. RESULTS: 543 respondents from 47 states provided information on their cancer history and were included in analyses. Participants receiving active treatment reported greater concern about infection from the SARS-CoV-2 coronavirus (p<0.001), higher levels of family distress caused by the COVID-19 pandemic (p = 0.004), and greater concern that the general public does not adequately understand the seriousness of COVID-19 (p = 0.04). Those with metastatic disease were more likely to indicate that COVID-19 had negatively affected their cancer care compared to patients with non-metastatic cancer (50.8% vs. 31.0%; p = 0.02). The most commonly reported treatment modifications included chemotherapy delays. CONCLUSIONS: Patients undergoing active treatment for cancer were most concerned about the short-term effects of the COVID-19 pandemic on the logistics as well as potential efficacy of ongoing cancer treatment, longer term effects, and overarching societal concerns that the population at large is not as concerned about the public health implications of SARS-CoV-2 infection. url: https://doi.org/10.1371/journal.pone.0241741 doi: 10.1371/journal.pone.0241741 id: cord-276763-x3dqi0ym author: Lowery-North, Douglas W. title: Measuring Social Contacts in the Emergency Department date: 2013-08-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Infectious individuals in an emergency department (ED) bring substantial risks of cross infection. Data about the complex social and spatial structure of interpersonal contacts in the ED will aid construction of biologically plausible transmission risk models that can guide cross infection control. METHODS AND FINDINGS: We sought to determine the number and duration of contacts among patients and staff in a large, busy ED. This prospective study was conducted between 1 July 2009 and 30 June 2010. Two 12-hour shifts per week were randomly selected for study. The study was conducted in the ED of an urban hospital. There were 81 shifts in the planned random sample of 104 (78%) with usable contact data, during which there were 9183 patient encounters. Of these, 6062 (66%) were approached to participate, of which 4732 (78%) agreed. Over the course of the year, 88 staff members participated (84%). A radiofrequency identification (RFID) system was installed and the ED divided into 89 distinct zones structured so copresence of two individuals in any zone implied a very high probability of contact <1 meter apart in space. During study observation periods, patients and staff were given RFID tags to wear. Contact events were recorded. These were further broken down with respect to the nature of the contacts, i.e., patient with patient, patient with staff, and staff with staff. 293,171 contact events were recorded, with a median of 22 contact events and 9 contacts with distinct individuals per participant per shift. Staff-staff interactions were more numerous and longer than patient-patient or patient-staff interactions. CONCLUSIONS: We used RFID to quantify contacts between patients and staff in a busy ED. These results are useful for studies of the spread of infections. By understanding contact patterns most important in potential transmission, more effective prevention strategies may be implemented. url: https://www.ncbi.nlm.nih.gov/pubmed/23990915/ doi: 10.1371/journal.pone.0070854 id: cord-284275-bqo203pf author: Lu, Roujian title: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays date: 2012-06-15 words: 2978.0 sentences: 165.0 pages: flesch: 52.0 cache: ./cache/cord-284275-bqo203pf.txt txt: ./txt/cord-284275-bqo203pf.txt summary: title: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. In our retrospective study, a 16.0% detection rate for HCoVs infection was found in adults with URTI; 229E was the most common infection (9.8% of all cases), followed by OC43 (4.3%), HKU1 (1.6%) and NL63 (1.1%). abstract: BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs) are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV) and human bocavirus (HBoV). 157 of the 981 (16.0%) nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%), OC43 (42 cases, 4.3%), HKU1 (16 cases, 1.6%) and NL63 (11 cases, 1.1%). HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003), and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03). 48 of 157(30.57%) HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu) A were the most common viruses detected (more than 35%) in HCoV co-infections. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China. url: https://www.ncbi.nlm.nih.gov/pubmed/22719912/ doi: 10.1371/journal.pone.0038638 id: cord-289873-6hivjqof author: Lu, Rui title: Patients with mild and general COVID-19 should be negative for at least 3 consecutive nucleic acid tests before discharged date: 2020-10-02 words: 1693.0 sentences: 80.0 pages: flesch: 51.0 cache: ./cache/cord-289873-6hivjqof.txt txt: ./txt/cord-289873-6hivjqof.txt summary: The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests of these patients was 21 days. Thus, we suggested that the patient should be negative for at least 3 consecutive nucleic acid tests before discharge, and the test time should be no earlier than the 23rd day since the onset of the disease. According to the latest COVID-19 clinical diagnosis and treatment guideline [3] , patients who meet the following four criteria can be discharged: (1) the body temperature has returned to normal for more than 3 days; (2) the respiratory symptoms have improved significantly; (3) the pulmonary imaging examination shows that the acute exudative lesions have improved significantly, (4) two consecutive negative nucleic acid test for respiratory specimens such as sputum and nasopharyngeal swabs (sampling interval at least 24 hours). The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests in 845 patients with COVID-19 was 21 days (range: 1-56 days). abstract: Given the global spread of coronavirus disease (COVID-19), strict discharge standard is of great significance for the prevention and control of the epidemic, thus, the purpose of this study is to formulate more strict and scientific discharge standards. A total of 845 patients with mild and general COVID-19 who were considered to be discharged from hospital were included in this study. The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests of these patients was 21 days. 223 of the 845 patients were tested again after two consecutive negative nucleic acid tests and 17.49% of the patients were positive. Moreover, 82.51% (184 of 223) of these patients experienced negative results from three consecutive nucleic acid tests, the median time from the onset of COVID-19 to the occurrence of three consecutive negative nucleic acid tests was 23 days (range: 3–56 days), and 38 of which were further tested after three consecutive negative nucleic acid tests, while about 5.26% (2 of 38) patients showed positive nucleic acid test results. Thus, we suggested that the patient should be negative for at least 3 consecutive nucleic acid tests before discharge, and the test time should be no earlier than the 23rd day since the onset of the disease. url: https://doi.org/10.1371/journal.pone.0240081 doi: 10.1371/journal.pone.0240081 id: cord-000408-pt3b4yc7 author: Lu, Sydney X. title: Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation date: 2011-07-06 words: 5433.0 sentences: 262.0 pages: flesch: 48.0 cache: ./cache/cord-000408-pt3b4yc7.txt txt: ./txt/cord-000408-pt3b4yc7.txt summary: The accelerated early mortality of Ceacam1 2/2 allo-BMT recipients, together with increased accumulation of donor T cells in GI tract and mesenteric lymph nodes, but decreased numbers peripheral lymph nodes ( Figure 3C ), led us to ask whether Ceacam1 had differential effects in regulating GVHD target organ damage for various target organs and tissues. We analyzed donor WT and Ceacam1 2/2 alloactivated splenic T cells on day 14 after allo-BMT for trafficking molecules, and found that Ceacam1 2/2 CD8 + CD44 + CD62L 2 effector T cells expressed higher levels of integrin b 7 subunit and the gut homing integrin a 4 b 7 ( Figure 5A) , which is important for intestinal GVHD [31, 32, 33] . Ceacam12/2 CD4 effector T cells had similar integrin b 7 subunit expression, yet also accumulated in greater numbers in the gut ( Figure 3A) , suggesting that regulation of target organ damage by Ceacam1 is very likely to involve multiple additional mechanisms beyond trafficking molecule expression. abstract: BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(−/−) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(−/−) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(−/−) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(−/−) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(−/−) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130781/ doi: 10.1371/journal.pone.0021611 id: cord-319190-esjfhztp author: Lu, Xi title: In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus date: 2013-07-02 words: 3288.0 sentences: 185.0 pages: flesch: 45.0 cache: ./cache/cord-319190-esjfhztp.txt txt: ./txt/cord-319190-esjfhztp.txt summary: title: In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. In this study, we examined the in vitro activity of SNH and its potential for synergy when combined with antibiotics against a collection of hospital-associated MRSA (HA-MRSA) isolates recovered from various clinical samples in recent years. This study evaluated activity of SNH against MRSA and its potential for synergistic effect when combined with antibiotics. SNH in combination with OXA exhibited synergistic effect for all the five MRSA strains tested in time-kill analysis. abstract: BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA. url: https://www.ncbi.nlm.nih.gov/pubmed/23844154/ doi: 10.1371/journal.pone.0068053 id: cord-309194-jtouafgd author: Lu, Xiao title: Lung ultrasound score in establishing the timing of intubation in COVID-19 interstitial pneumonia: A preliminary retrospective observational study date: 2020-09-03 words: 3668.0 sentences: 191.0 pages: flesch: 46.0 cache: ./cache/cord-309194-jtouafgd.txt txt: ./txt/cord-309194-jtouafgd.txt summary: PURPOSE: To investigate the role of lung ultrasound score (LUS) in assessing intubation timing for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Lung ultrasound was performed on days 1, 2, 3, 5, and 7 after patients were admitted to the ICU; if the patient was intubated, LUS determination was performed before intubation within 24 h (T1) and on days 1, 2, 5, and 7 after intubation (T2, T3, T4, and T5, respectively).The goal of this study was to evaluate the severity of lung aeration loss in intubated and non-intubated patients with SARS-CoV-2 pneumonia by ultrasound at different time points within one week. Few studies have addressed the timing of intubation for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia due to the high mortality of patients treated with invasive ventilation. The patient''s gender, age, body mass index (BMI index), sequential organ failure assessment (SOFA score), and 28-day mortality rate were recorded; and the evolution of respiratory parameters between the two groups on time point T1 (lung ultrasound performed before intubation within 24 h) were also recorded. abstract: PURPOSE: To investigate the role of lung ultrasound score (LUS) in assessing intubation timing for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. MATERIALS AND METHODS: Seventy-two patients with critical coronavirus disease 2019 (COVID-19) were admitted to a makeshift intensive care unit (ICU). All patients underwent bedside lung ultrasonography one to two times per day. The patients were either intubated, treated with noninvasive ventilation (NIV), or given high-flow nasal cannula (HFNC) after a discussion with the multidisciplinary group after their conditions worsened. Bedside lung ultrasound was performed daily after intubation, and patients received mechanical ventilation. Lung ultrasound was performed on days 1, 2, 3, 5, and 7 after patients were admitted to the ICU; if the patient was intubated, LUS determination was performed before intubation within 24 h (T1) and on days 1, 2, 5, and 7 after intubation (T2, T3, T4, and T5, respectively).The goal of this study was to evaluate the severity of lung aeration loss in intubated and non-intubated patients with SARS-CoV-2 pneumonia by ultrasound at different time points within one week. RESULTS: A total of 16 patients were included in this study, including nine who were intubated and mechanically ventilated and seven patients without intubation. The number of elderly individuals in the intubated group was higher than in the non-intubated group (P < 0.05). In addition, there were more male than female patients in both groups. Patient characteristics (BMI, SOFA, and PaO(2)/FiO(2) value) were similar between the two groups (P > 0.05). The 28-day mortality rate of intubated patients was higher than that of non-intubated patients; six patients in the intubated group and two patients in the non-intubated group died. Nine intubated patients showed changes in LUS within seven days (n = 9). The mean LUS within 24 h before intubation was 12.8 ± 1.3. LUS was significantly higher on T1 than on T5 (P <0.05), and did not significantly differ from T1 to T4. Comparing LUS between intubated and non-intubated patients on T1 showed that the LUS of intubated patients was significantly higher than that of non-intubated patients (P <0.05). Between the two patient groups, oxygenation index was 140.1 ± 7.7 vs. 137.8 ± 5.9 on T1, and the respiratory rate of the two groups was 26 ± 5 vs. 28 ± 4 breaths/min. Neither oxygenation index nor RR significantly differed between the two groups. CONCLUSION: LUS may be an effective tool for assessing intubation timing in critically ill patients with Covid-19 interstitial pneumonia. url: https://www.ncbi.nlm.nih.gov/pubmed/32881950/ doi: 10.1371/journal.pone.0238679 id: cord-252838-av7ducrk author: Lucchi, Naomi W. title: Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria date: 2010-10-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. METHODOLOGY AND SIGNIFICANT FINDINGS: Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. CONCLUSION: This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs. url: https://doi.org/10.1371/journal.pone.0013733 doi: 10.1371/journal.pone.0013733 id: cord-311288-6ttux2uu author: Luo, Chen title: What triggers online help-seeking retransmission during the COVID-19 period? Empirical evidence from Chinese social media date: 2020-11-03 words: 6202.0 sentences: 385.0 pages: flesch: 43.0 cache: ./cache/cord-311288-6ttux2uu.txt txt: ./txt/cord-311288-6ttux2uu.txt summary: We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion of help-seeking messages. For example, harness the social media posts to predict infected case counts and inform timely responses under the infoveillance or infodemiology framework [3, 4] ; analyze the help-seeking posts to identify the characteristics of COVID-19 patients [5] ; More retransmission means more users receiving the message, thus increasing the chance of getting help. There is plenty of research providing conceptual references, such as the depth of self-disclosure [16, 28] , different types of support messages [16, 29] , physical and emotional proximity to the target [30] , the social capital stock of the help seeker [22] . Enlightened by existing experience, we will summarize the impelling factors of help-seeking information diffusion into five dimensions: completeness, proximity, support typology, disease severity, emotion, and elaborate them in the following sections. abstract: The past nine months witnessed COVID-19's fast-spreading at the global level. Limited by medical resources shortage and uneven facilities distribution, online help-seeking becomes an essential approach to cope with public health emergencies for many ordinaries. This study explores the driving forces behind the retransmission of online help-seeking posts. We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion of help-seeking messages. A quantitative content analysis was conducted with a probability sample consisting of 727 posts. The results illustrate the importance of individual information completeness, high proximity, instrumental support seeking. This study also demonstrates slight inconformity with the severity principle but stresses the power of anger in help-seeking messages dissemination. As one of the first online help-seeking diffusion analyses in the COVID-19 period, our research provides a reference for constructing compelling and effective help-seeking posts during a particular period. It also reveals further possibilities for harnessing social media’s power to promote reciprocal and cooperative actions as a response to this deepening global concern. url: https://doi.org/10.1371/journal.pone.0241465 doi: 10.1371/journal.pone.0241465 id: cord-312033-iarl77n0 author: López Barreda, Rodrigo title: Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile date: 2020-10-08 words: 4058.0 sentences: 235.0 pages: flesch: 51.0 cache: ./cache/cord-312033-iarl77n0.txt txt: ./txt/cord-312033-iarl77n0.txt summary: The objective of this study was to assess the quality of life and psychological wellbeing of adults with congenital heart disease (CHD) in Chile, and to identify other associated factors. They completed a questionnaire, which included a quality of life assessment tool (the Medical Outcome Study 36-Item Short Form Health Survey), a number of psychological scales (the General Health Questionnaire, the Basic Psychological Needs Scales and the Beck Hopelessness Scale), a socioeconomic survey, and some clinical data. The primary aim of this study was to assess the QoL and psychological wellbeing of a population of adults suffering from CHD in Chile. Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile general population [5, 11, 38] . abstract: The objective of this study was to assess the quality of life and psychological wellbeing of adults with congenital heart disease (CHD) in Chile, and to identify other associated factors. The study enrolled 68 patients aged between 18 and 72 (median 29), 35 being females. They completed a questionnaire, which included a quality of life assessment tool (the Medical Outcome Study 36-Item Short Form Health Survey), a number of psychological scales (the General Health Questionnaire, the Basic Psychological Needs Scales and the Beck Hopelessness Scale), a socioeconomic survey, and some clinical data. CHD patients reported worse scores in those scales assessing physical dimensions of quality of life (physical function (70.5), physical role functioning (64), vitality (65.3)), and general quality of life (58.6), than in emotional or social dimensions. Female gender was associated with lower scores in physical function (59.12 versus 82.66; p<0.01) and physical role functioning (53.68 versus 75; p<0.05); poverty was associated with worse results in physical function (61.92 versus 82.96; p<0.01), role physical (53.21 versus 79.63; p<0.01), vitality (60.89 versus 71.67; p<0.05), social role functioning (70.19 versus 82.87; p<0.05) and bodily pain (65.77 versus 81.2; p<0.05). Furthermore, we found that psychological scales had an association with quality of life, but clinical variables did not show significant correlations to any dimension. Poverty has an impact on the quality of life of CHD patients. This population only has a decrease in the quality of life physical dimensions, suggesting that quality of life depends on many different factors. url: https://doi.org/10.1371/journal.pone.0240383 doi: 10.1371/journal.pone.0240383 id: cord-321438-llnqzkqt author: Ma, Ruili title: Proteome Profile of Swine Testicular Cells Infected with Porcine Transmissible Gastroenteritis Coronavirus date: 2014-10-21 words: 7110.0 sentences: 310.0 pages: flesch: 43.0 cache: ./cache/cord-321438-llnqzkqt.txt txt: ./txt/cord-321438-llnqzkqt.txt summary: The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV)-infected swine testicular (ST) cells in order to determine potential virus-host interactions. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Moreover, at the later time point, 64 hpi, our GO term analysis also indicated that a significant number of the differentially expressed proteins were related to cellular stress (p = 8.18E-4), generation of precursor metabolites and energy (p = 2.74E-3), cell motility (p = 6.71E-3), protein complex assembly (p = 4.69E-2), growth (p = 3.87E-2), developmental maturation (p = 1.53E-2), and immune system processes (p = 4.67E-2) ( Table 2) . Prior to proteomic analysis, we determined which time points to investigate following infection by observing the morphological changes and analyzing viral gene expression dynamics in the TGEV infected cells. abstract: The interactions occurring between a virus and a host cell during a viral infection are complex. The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV)-infected swine testicular (ST) cells in order to determine potential virus-host interactions. A proteomic approach using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography-tandem mass spectrometry identification was conducted on the TGEV-infected ST cells. The results showed that the 4-plex iTRAQ-based quantitative approach identified 4,112 proteins, 146 of which showed significant changes in expression 48 h after infection. At 64 h post infection, 219 of these proteins showed significant change, further indicating that a larger number of proteomic changes appear to occur during the later stages of infection. Gene ontology analysis of the altered proteins showed enrichment in multiple biological processes, including cell adhesion, response to stress, generation of precursor metabolites and energy, cell motility, protein complex assembly, growth, developmental maturation, immune system process, extracellular matrix organization, locomotion, cell-cell signaling, neurological system process, and cell junction organization. Changes in the expression levels of transforming growth factor beta 1 (TGF-β1), caspase-8, and heat shock protein 90 alpha (HSP90α) were also verified by western blot analysis. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Therefore, this study provides a solid foundation for further investigation, and will likely help us to better understand the mechanisms of TGEV infection and pathogenesis. url: https://doi.org/10.1371/journal.pone.0110647 doi: 10.1371/journal.pone.0110647 id: cord-296487-m4xba78g author: MacIntyre, Chandini Raina title: Health system capacity in Sydney, Australia in the event of a biological attack with smallpox date: 2019-06-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions. url: https://doi.org/10.1371/journal.pone.0217704 doi: 10.1371/journal.pone.0217704 id: cord-000180-howix091 author: MacLeod, Iain J. title: Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry date: 2010-03-05 words: 6788.0 sentences: 316.0 pages: flesch: 49.0 cache: ./cache/cord-000180-howix091.txt txt: ./txt/cord-000180-howix091.txt summary: By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. As induction of the NF-kB reporter construct occurred within one hour of inoculation with DgH virions and peaked at around two-and-a-half hours post-inoculation, then the transcripts previHFFs were stimulated with 1000 particles/cell of DgB, DgD or DgH HSV-1 for six hours and a cDNA microarray corresponding to targets of 19 signalling pathways was used to detect changes in cellular gene expression when compared to mock-infected. Real-time PCR confirmed that changes in transcription associated with the NF-kB, JAK/STAT, JAK/Src and PI3K pathways were modulated as a result of virion binding, all of which required gD on the envelope surface To demonstrate that signalling occurred at physiologically relevant multiplicities of infection, HFFs were inoculated with either 1000, 100, 10 or 1 particles per cell of entry-defective HSV-1. abstract: The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon. By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD. Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection. Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction. The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832691/ doi: 10.1371/journal.pone.0009560 id: cord-003125-iptisi1m author: Machablishvili, Ann title: Overview of three influenza seasons in Georgia, 2014–2017 date: 2018-07-27 words: 3714.0 sentences: 196.0 pages: flesch: 48.0 cache: ./cache/cord-003125-iptisi1m.txt txt: ./txt/cord-003125-iptisi1m.txt summary: We aimed to present Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) surveillance data and characterize influenza viruses circulating in the country over three influenza seasons. The objectives were to: (1) define periods of influenza activity in Georgia; (2) assess the proportions of influenza infections among ILI and SARI cases; (3) determine most affected age groups; (4) describe epidemiological characteristics of influenza-associated fatal cases; and (5) determine antigenic and genetic profiles of influenza viruses circulating in the country. Influenza virus detection rates among hospitalized patients were highest, almost equally, in the age groups 30-64 years (55%, OR = 3.48, CI 2.58-4.69, p<0.001) and 15-29 years (53%, OR = 3.03, CI 2.14-4.28, p<0.001) ( Table 1) Among 1,997 sampled SARI cases, only 25 were vaccinated against influenza; of these, three tested positive for A/H1N1pdm09 and three for A/H3N2. abstract: BACKGROUND: Influenza epidemiological and virologic data from Georgia are limited. We aimed to present Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) surveillance data and characterize influenza viruses circulating in the country over three influenza seasons. METHODS: We analyzed sentinel site ILI and SARI data for the 2014–2017 seasons in Georgia. Patients’ samples were screened by real-time RT-PCR and influenza viruses isolated were characterized antigenically by haemagglutination inhibition assay and genetically by sequencing of HA and NA genes. RESULTS: 32% (397/1248) of ILI and 29% (581/1997) of SARI patients tested were positive for influenza viruses. In 2014–2015 the median week of influenza detection was week 7/2015 with B/Yamagata lineage viruses dominating (79%); in 2015–2016—week 5/2016 was the median with A/H1N1pdm09 viruses prevailing (83%); and in 2016–2017 a bimodal distribution of influenza activity was observed—the first wave was caused by A/H3N2 (55%) with median week 51/2016 and the second by B/Victoria lineage viruses (45%) with median week 9/2017. For ILI, influenza virus detection was highest in children aged 5–14 years while for SARI patients most were aged >15 years and 27 (4.6%) of 581 SARI cases died during the three seasons. Persons aged 30–64 years had the highest risk of fatal outcome, notably those infected with A/H1N1pdm09 (OR 11.41, CI 3.94–33.04, p<0.001). A/H1N1pdm09 viruses analyzed by gene sequencing fell into genetic groups 6B and 6B.1; A/H3N2 viruses belonged to genetic subclades 3C.3b, 3C.3a, 3C.2a and 3C.2a1; B/Yamagata lineage viruses were of clade 3 and B/Victoria lineage viruses fell in clade1A. CONCLUSION: In Georgia influenza virus activity occurred mainly from December through March in all seasons, with varying peak weeks and predominating viruses. Around one third of ILI/ SARI cases were associated with influenza caused by antigenically and genetically distinct influenza viruses over the course of the three seasons. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063423/ doi: 10.1371/journal.pone.0201207 id: cord-337067-j8ebslif author: Mades, Andreas title: Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date: 2012-11-15 words: 8726.0 sentences: 459.0 pages: flesch: 48.0 cache: ./cache/cord-337067-j8ebslif.txt txt: ./txt/cord-337067-j8ebslif.txt summary: The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. Similar results were obtained with cell lysates prepared with the denaturing detergent SDS (Fig. 1B) , indicating that the observed down-regulation of HBV.S by excess Sec63 was not merely due to changes in the solubility profile. To analyze whether an up-regulation of these ERdj proteins might also affect the level of a multi-spanning membrane protein, FLAG-tagged versions of ERdj1 and ERdj4 were cotransfected with HBV.S. FLAG-specific Western blotting confirmed the ectopic expression of ERdj1 and ERdj4 in 63 and 25 kDa forms, respectively, consistent with their theoretical molecular masses (Fig. 9) . abstract: The Sec61 translocon of the endoplasmic reticulum (ER) membrane forms an aqueous pore, allowing polypeptides to be transferred across or integrated into membranes. Protein translocation into the ER can occur co- and posttranslationally. In yeast, posttranslational translocation involves the heptameric translocase complex including its Sec62p and Sec63p subunits. The mammalian ER membrane contains orthologs of yeast Sec62p and Sec63p, but their function is poorly understood. Here, we analyzed the effects of excess and deficit Sec63 on various ER cargoes using human cell culture systems. The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. Consistent with this, the knock-down of Sec63 increases the steady-state pools of polytopic ER proteins, suggesting a substrate-specific and regulatory function of Sec63 in ER import. Overexpressed Sec63 exerts its down-regulating activity on polytopic protein levels independent of its Sec62-interacting motif, indicating that it may not act in conjunction with Sec62 in human cells. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. A J domain-specific mutation of Sec63, proposed to weaken its interaction with the ER resident BiP chaperone, reduces the down-regulating capacity of excess Sec63, suggesting an involvement of BiP in this process. Together, these results suggest that Sec63 may perform a substrate-selective quantity control function during cotranslational ER import. url: https://doi.org/10.1371/journal.pone.0049243 doi: 10.1371/journal.pone.0049243 id: cord-287784-f7usy52w author: Maestre, Ana M. title: Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells date: 2011-06-15 words: 8981.0 sentences: 395.0 pages: flesch: 45.0 cache: ./cache/cord-287784-f7usy52w.txt txt: ./txt/cord-287784-f7usy52w.txt summary: Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We did not observe any CPE on the cells treated with UV-inactivated virus (data not shown), and neither of the two caspase substrates was processed in these cells (Fig. 5B) , suggesting that BEV apoptosis triggering is dependent upon viral replication. As a whole, these results indicate that although both cell death receptor and mitochondrial pathways are implicated in the BEV induction of apoptosis, the mitochondrial pathway could be secondarily activated by caspase-8-mediated cleavage of Bid. To further ascertain the involvement of the mitochondrial pathway in BEV-induced apoptosis we analyzed the cellular distribution of cytochrome c at different times postinfection. abstract: Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/21698249/ doi: 10.1371/journal.pone.0020972 id: cord-317244-4su5on6s author: Maganga, Gael D. title: Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity date: 2014-12-31 words: 3476.0 sentences: 191.0 pages: flesch: 50.0 cache: ./cache/cord-317244-4su5on6s.txt txt: ./txt/cord-317244-4su5on6s.txt summary: In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. To further investigate the presence of the virus in bat populations, a strain-specific real-time RT-PCR assay (primers: GB09-478-F, 59-GGCGGCTCTTAAAAGT-GAATG-39; GB09-478-R, 59-GCGGGGTCAAATTGGTCAT-39; probe: GB09-478-P, 59-TCCAGCACAAACATATCCGAGAAGGCTAG-39) was designed within the initial PCR fragment and was used to test total RNA extracted from mixed liver and spleen samples from each of all the other bat species. In order to determine the organ distribution of this virus in infected bats, total RNA was extracted from heart, liver, spleen, kidney, lung, intestine and brain samples from all 14 real-time RT-PCR-positive bats, as described previously, and screened, using the same strain-specific real-time RT-PCR assay shown above. abstract: Bats are known to harbor multiple paramyxoviruses. Despite the creation of two new genera, Aquaparamyxovirus and Ferlavirus, to accommodate this increasing diversity, several recently isolated or characterized viruses remain unclassified beyond the subfamily level. In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. Phylogenetically, BelPV is related to J virus and Beilong virus (BeiPV), two other unclassified paramyxoviruses isolated from rodents. In the diseased BelPV-infected C. afra individual, high viral load was detected in the heart, and the lesions were consistent with those reported in wild rodents and mice experimentally infected by J virus. BelPV was not detected in other tested bat species sharing the same roosting sites and living in very close proximity with C. afra in the two caves sampled, suggesting that this virus may be host-specific for C. afra. The mode of transmission of this paramyxovirus in bat populations remains to be discovered. url: https://doi.org/10.1371/journal.pone.0115588 doi: 10.1371/journal.pone.0115588 id: cord-344839-r05p9h0e author: Majmundar, Monil title: Efficacy of corticosteroids in non-intensive care unit patients with COVID-19 pneumonia from the New York Metropolitan region date: 2020-09-09 words: 4072.0 sentences: 235.0 pages: flesch: 44.0 cache: ./cache/cord-344839-r05p9h0e.txt txt: ./txt/cord-344839-r05p9h0e.txt summary: OBJECTIVE: The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). The results of our study showed that the administration of corticosteroids in patients admitted to the general medical ward with AHRF and a diagnosis of COVID-19 pneumonia was associated with a lower risk of developing the primary outcome composite of ICU transfer, intubation or death. In our analysis of hospitalized patients in the general ward with COVID-19 pneumonia complicated by acute hypoxic respiratory failure, early use of moderate dose systemic corticosteroid for the shorter duration was associated with a significantly lower rate of the primary outcomes of ICU transfer, intubation, or in-hospital death. abstract: INTRODUCTION: The role of systemic corticosteroid as a therapeutic agent for patients with COVID-19 pneumonia is controversial. OBJECTIVE: The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). METHODS: This was a single-center retrospective cohort study, from 16(th) March, 2020 to 30(th) April, 2020; final follow-up on 10(th) May, 2020. 265 patients consecutively admitted to the non-ICU wards with laboratory-confirmed COVID-19 pneumonia were screened for inclusion. 205 patients who developed AHRF (SpO(2)/FiO(2) ≤ 440 or PaO(2)/FiO(2) ≤ 300) were only included in the final study. Direct admission to the Intensive care unit (ICU), patients developing composite primary outcome within 24 hours of admission, and patients who never became hypoxic during their stay in the hospital were excluded. Patients were divided into two cohorts based on corticosteroid. The primary outcome was a composite of ICU transfer, intubation, or in-hospital mortality. Secondary outcomes were ICU transfer, intubation, in-hospital mortality, discharge, length of stay, and daily trend of SpO(2)/FiO(2) (SF) ratio from the index date. Cox-proportional hazard regression was implemented to analyze the time to event outcomes. RESULT: Among 205 patients, 60 (29.27%) were treated with corticosteroid. The mean age was ~57 years, and ~75% were men. Thirteen patients (22.41%) developed a primary composite outcome in the corticosteroid cohort vs. 54 (37.5%) patients in the non-corticosteroid cohort (P = 0.039). The adjusted hazard ratio (HR) for the development of the composite primary outcome was 0.15 (95% CI, 0.07–0.33; P <0.001). The adjusted hazard ratio for ICU transfer was 0.16 (95% CI, 0.07 to 0.34; P < 0.001), intubation was 0.31 (95% CI, 0.14 to 0.70; P– 0.005), death was 0.53 (95% CI, 0.22 to 1.31; P– 0.172), composite of death or intubation was 0.31 (95% CI, 0.15 to 0.66; P– 0.002) and discharge was 3.65 (95% CI, 2.20 to 6.06; P<0.001). The corticosteroid cohort had increasing SpO(2)/FiO(2) over time compared to the non-corticosteroid cohort who experience decreasing SpO(2)/FiO(2) over time. CONCLUSION: Among non-ICU patients hospitalized with COVID-19 pneumonia complicated by AHRF, treatment with corticosteroid was associated with a significantly lower risk of the primary composite outcome of ICU transfer, intubation, or in-hospital death, composite of intubation or death and individual components of the primary outcome. url: https://www.ncbi.nlm.nih.gov/pubmed/32903258/ doi: 10.1371/journal.pone.0238827 id: cord-295352-b8kztgt8 author: Maksimowski, Nicholas title: Kidney ACE2 expression: Implications for chronic kidney disease date: 2020-10-30 words: 3517.0 sentences: 212.0 pages: flesch: 54.0 cache: ./cache/cord-295352-b8kztgt8.txt txt: ./txt/cord-295352-b8kztgt8.txt summary: Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. Tubulointerstitial and glomerular median-centered log2 mRNA expression of ACE2 or TMPRSS2 from renal biopsy samples were compared in CKD and HLD, as well as in male and female subgroups. Mean values for ACE2 mRNA expression in both the tubulointerstitial and glomerular compartments were similar in all of the disease categories represented in the CKD cohort (S1 Fig) . abstract: Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. Together, tissue expression of ACE2 and TMPRSS2 may determine infection. Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. Accordingly, we obtained renal tubulointerstitial and glomerular microarray expression data and clinical variables from healthy living donors (HLD) and patients with CKD from the European Renal cDNA Bank. ACE2 expression was similar in the tubulointerstitium of the two groups, but greater in females than males in HLD (P = 0.005) and CKD (P < 0.0001). ACE2 expression was lower in glomeruli of CKD patients compared to HLD (P = 0.0002) and lower in males than females. TMPRSS2 expression was similar in the tubulointerstitium but lower in glomeruli of CKD patients compared to HLD (P < 0.0001). There was a strong relationship between ACE2 and TMPRSS2 expression in the glomerulus (r = 0.51, P < 0.0001). In CKD, there was a relationship between tubulointerstitial ACE2 expression and estimated glomerular filtration rate (r = 0.36, P < 0.0001) and age (r = -0.17, P = 0.03), but no relationship with BMI. There were no relationships between TMPRSS2 expression and clinical variables. Genes involved in inflammation (CCL2, IL6, and TNF) and fibrosis (COL1A1, TGFB1, and FN1) were inversely correlated with ACE2 expression. In summary, kidney expression of ACE2 and TMPRSS2 differs in HLD and CKD. ACE2 is related to sex and eGFR. ACE2 is also associated with expression of genes implicated in inflammation and fibrosis. url: https://www.ncbi.nlm.nih.gov/pubmed/33125431/ doi: 10.1371/journal.pone.0241534 id: cord-001083-vy1nxax2 author: Malagnac, Fabienne title: Rab-GDI Complex Dissociation Factor Expressed through Translational Frameshifting in Filamentous Ascomycetes date: 2013-09-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In the model fungus Podospora anserina, the PaYIP3 gene encoding the orthologue of the Saccharomyces cerevisiae YIP3 Rab-GDI complex dissociation factor expresses two polypeptides, one of which, the long form, is produced through a programmed translation frameshift. Inactivation of PaYIP3 results in slightly delayed growth associated with modification in repartition of fruiting body on the thallus, along with reduced ascospore production on wood. Long and short forms of PaYIP3 are expressed in the mycelium, while only the short form appears expressed in the maturing fruiting body (perithecium). The frameshift has been conserved over the evolution of the Pezizomycotina, lasting for over 400 million years, suggesting that it has an important role in the wild. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777964/ doi: 10.1371/journal.pone.0073772 id: cord-333650-4towah1t author: Malmo, Jostein title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date: 2016-05-12 words: 4659.0 sentences: 250.0 pages: flesch: 50.0 cache: ./cache/cord-333650-4towah1t.txt txt: ./txt/cord-333650-4towah1t.txt summary: Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . abstract: Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children. url: https://doi.org/10.1371/journal.pone.0155484 doi: 10.1371/journal.pone.0155484 id: cord-340027-6l55rcfm author: Mamode Khan, Naushad title: Studying the trend of the novel coronavirus series in Mauritius and its implications date: 2020-07-10 words: 3627.0 sentences: 198.0 pages: flesch: 52.0 cache: ./cache/cord-340027-6l55rcfm.txt txt: ./txt/cord-340027-6l55rcfm.txt summary: This paper proposes an integer-valued time series model to analyze the series of COVID-19 cases in Mauritius wherein the corresponding innovation term accommodates for covariate specification. Based on the proposed COM-Poisson mixture models, we could predict the number of COVID-19 cases in Mauritius. The paper therefore proposes an integer-valued auto-regressive model (INAR(1)) with Conway-Maxwell Poisson (COM-Poisson) mixed innovation terms that can accommodate for covariate, random effect and serial auto-correlation specifications. The organization of the paper is as follows: In Section 2, material in terms of time series of COVID-19 in Mauritius and proposed methods principally the INAR(1) Process and the COM-Poisson mixture innovations have been provided. The results of this research revealed that several factors, the most significant being confinement measure, and least one being climatic conditions, affect the number of COVID-19 cases in Mauritius. abstract: Mauritius stands as one of the few countries in the world to have controlled the current pandemic, the novel coronavirus 2019 (COVID-19) to a significant extent in a relatively short lapse of time. Owing to uncertainties and crisis amid the pandemic, as an emergency announcement, the World Health Organization (WHO) solicits the help of health authorities, especially, researchers to conduct in-depth research on the evolution and treatment of COVID-19. This paper proposes an integer-valued time series model to analyze the series of COVID-19 cases in Mauritius wherein the corresponding innovation term accommodates for covariate specification. In this set-up, sanitary curfew followed by sanitization and sensitization campaigns, time factor and safe shopping guidelines have been tested as the most significant variables, unlike climatic conditions. The over-dispersion estimates and the serial auto-correlation parameter are also statistically significant. This study also confirms the presence of some unobservable effects like the pathological genesis of the novel coronavirus and environmental factors which contribute to rapid propagation of the zoonotic virus in the community. Based on the proposed COM-Poisson mixture models, we could predict the number of COVID-19 cases in Mauritius. The forecasting results provide satisfactory mean squared errors. Such findings will subsequently encourage the policymakers to implement strict precautionary measures in terms of constant upgrading of the current health care and wellness system and re-enforcement of sanitary obligations. url: https://doi.org/10.1371/journal.pone.0235730 doi: 10.1371/journal.pone.0235730 id: cord-348499-7ll7sd3o author: Manderstedt, Eric title: Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients date: 2018-02-01 words: 5449.0 sentences: 262.0 pages: flesch: 53.0 cache: ./cache/cord-348499-7ll7sd3o.txt txt: ./txt/cord-348499-7ll7sd3o.txt summary: von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. Additional studies of STXBP5 and STX2 [8] and CLEC4M [9, 10] have confirmed that single nucleotide variants (SNVs) in these genes are associated with the variation observed for plasma levels of VWF. CLEC4M also binds to VWF [9] and variants in this gene contribute to the variation in the VWF level observed both in normal individuals [4] and in type 1 VWD patients [9, 10] . The present study aimed to screen comprehensively for genetic variation in the CLEC4M gene in individuals from 106 unrelated type 1 VWD families by re-sequencing the gene region (excluding exon 4) and genotyping the polymorphic neck region (exon 4) of the gene. abstract: von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. This study aims to screen comprehensively for CLEC4M variants and investigate their association with type 1 VWD in the Swedish population. In order to screen for CLEC4M variants, the CLEC4M gene region was re-sequenced and the polymorphic neck region was genotyped in 106 type 1 VWD patients from unrelated type 1 VWD families. Single nucleotide variants (SNV) and variable number tandem repeat (VNTR) allele and genotype frequencies were then compared with 294 individuals from the 1000Genomes project and 436 Swedish control individuals. Re-sequencing identified a total of 42 SNVs. Rare variants showed no accumulation in type 1 VWD patients and are not thought to contribute substantially to type 1 VWD. The only missense mutation (rs2277998, NP_001138379.1:p.Asp224Asn) had a higher frequency in type 1 VWD patients than in controls (4.9%). The VNTR genotypes 57 and 67 were observed at higher frequencies than expected in type 1 VWD patients (6.4% and 6.2%) and showed an increase in patients compared with controls (7.4% and 3.1%). Strong linkage disequilibrium in the CLEC4M region makes it difficult to distinguish between the effect of the missense mutation and the VNTR genotypes. In conclusion, heterozygous VNTR genotypes 57 and 67 of CLEC4M were highly enriched and are the most likely mechanism through which CLEC4M contributes to disease in the Swedish type 1 VWD population. url: https://doi.org/10.1371/journal.pone.0192024 doi: 10.1371/journal.pone.0192024 id: cord-349476-iac9fak3 author: Mao, Liang title: Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior date: 2011-10-17 words: 4662.0 sentences: 245.0 pages: flesch: 43.0 cache: ./cache/cord-349476-iac9fak3.txt txt: ./txt/cord-349476-iac9fak3.txt summary: The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment. The control of influenza primarily involves applying health resources to affected people, known as control strategies, for example, medical treatment for infected individuals, closure of affected workplaces/schools, and travel restriction to affected communities [4] . Results from the influenza-only model indicate the effectiveness of control strategies without individual preventive behavior. Meanwhile, outcomes from the dual-diffusion model show the combined effectiveness of both control strategies and individual preventive behavior. These two modeled effectiveness are compared to a baseline epidemic scenario, which represents a worst situation of no control strategies and no preventive behavior. This research estimates the combined effectiveness of both control strategies and individual preventive behavior. abstract: Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment. url: https://doi.org/10.1371/journal.pone.0024706 doi: 10.1371/journal.pone.0024706 id: cord-001421-6t5puo6p author: Marfà, Santiago title: Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date: 2014-10-02 words: 5057.0 sentences: 229.0 pages: flesch: 46.0 cache: ./cache/cord-001421-6t5puo6p.txt txt: ./txt/cord-001421-6t5puo6p.txt summary: The serum proteomic profile and routine liver and renal function tests were initially analyzed in a training set of 10 HCV-RNA recurrent LT patients 6 months post LT that showed a fibrosis stage F$1 at 1 year after LT. HVPG was assessed in 53 of these patients and the average value was of 5.560.8 mm Hg. All the serum samples showed a quite similar expression pattern and coincidences included both the different peptide fragments detected and the signal intensity of these fragments (Data S4). All serum samples included in the test set showed an intensity m/z 5905 peak well below the values found in both healthy subjects and non recurrent HCV patients. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. abstract: Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183580/ doi: 10.1371/journal.pone.0109254 id: cord-343135-m0pdixw5 author: Marguet, Christophe title: In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses date: 2009-02-25 words: 3344.0 sentences: 182.0 pages: flesch: 48.0 cache: ./cache/cord-343135-m0pdixw5.txt txt: ./txt/cord-343135-m0pdixw5.txt summary: BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The aim of this prospective study was to assess the clinical severity and viral etiology in infants hospitalized with a first episode of acute bronchiolitis during the epidemic season. In this study, the clinical severity of dual RSV/RV infection was comparable to that observed with RSV, but differed in a shorter duration of hospitalization in the coinfected infants. abstract: BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO(2)% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization. CONCLUSION: This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity. url: https://www.ncbi.nlm.nih.gov/pubmed/19240806/ doi: 10.1371/journal.pone.0004596 id: cord-012461-v8d91fdo author: Marnissi, Boutheina title: Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus date: 2020-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Aptamers are short single-stranded DNA (ssDNA), RNA or synthetic XNA molecules, which are used as a class of affinity binders recognizing target molecules with a very high affinity and specificity. The aim of this study was to generate and characterize ssDNA aptamers for the detection of Newcastle disease virus (NDV). These aptamers were selected using systematic evolution of ligands by exponential enrichment (SELEX) in combination with quantitative high-throughput DNA sequencing. After three rounds of selections, a highly enriched ssDNA pool was sequenced, and the results were analyzed using FASTAptamer Toolkit. Sequencing reads were sorted by copy numbers and clustered into groups, according to their sequence homology. Top aptameric sequences were used to develop a sandwich enzymatic linked aptamer assay (ELAA) for rapid and sensitive detection of NDV in farm samples. The selected aptamers have an affinity within the nanomolar range, and a high specificity with no cross-reactivity towards other avian viruses. Following optimization of the sandwich ELAA method, the results demonstrated that both selected aptamers Apt_NDV01 and Apt_NDV03 with dissociation constant values of 31 nM and 78.1 nM, respectively, showed the highest specificity and affinity for NDV detection. The ELAA results were verified by quantitative real-time PCR, demonstrating strong concordance, and showing outstanding accuracy for detection of NDV in field sample. In summary, combination of SELEX with high-throughput DNA sequencing allowed rapid screening and selection of aptamers. The selected aptamers allowed recognition of NDV with high affinities. This is the first report that uses a validated sandwich ELAA for rapid and specific detection of NDV in poultry samples. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425888/ doi: 10.1371/journal.pone.0237253 id: cord-260432-imslfm4l author: Marshall, Jenika D. title: THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation date: 2020-05-21 words: 5851.0 sentences: 287.0 pages: flesch: 47.0 cache: ./cache/cord-260432-imslfm4l.txt txt: ./txt/cord-260432-imslfm4l.txt summary: Thus, we hypothesized that one or more specific fatty acids that exist within the total FFA component of lipoprotein hydrolysis products that are generated by LPL impair cholesterol efflux through the activation of Akt. To test this hypothesis, using THP-1 macrophages, we examined the activation of Akt in response to various FFA mixtures that contain the concentrations of FFA species that we previously reported to be found within LPL hydrolysis products from total lipoproteins [16] . Lastly, we examined the molecular species of phosphoinositides (PIPx) of THP-1 macrophages treated with palmitoleate, to determine if there were changes to select PIPx species that may contribute to a preferential activation of Akt. We previously showed using antibody arrays that the hydrolysis products liberated by LPL from total lipoproteins (ρ<1.21 g/ml), as well as the reconstituted total FFA component matching that liberated by LPL at a physiological concentration of 0.68 mM, significantly increased the phosphorylation of Akt after 30 minutes within THP-1 macrophages [16] . abstract: Lipoprotein lipase (LPL) is upregulated in atherosclerotic lesions and it may promote the progression of atherosclerosis, but the mechanisms behind this process are not completely understood. We previously showed that the phosphorylation of Akt within THP-1 macrophages is increased in response to the lipid hydrolysis products generated by LPL from total lipoproteins. Notably, the free fatty acid (FFA) component was responsible for this effect. In the present study, we aimed to reveal more detail as to how the FFA component may affect Akt signalling. We show that the phosphorylation of Akt within THP-1 macrophages increases with total FFA concentration and that phosphorylation is elevated up to 18 hours. We further show that specifically the palmitoleate component of the total FFA affects Akt phosphorylation. This is tied with changes to the levels of select molecular species of phosphoinositides. We further show that the total FFA component, and specifically palmitoleate, reduces apolipoprotein A-I-mediated cholesterol efflux, and that the reduction can be reversed in the presence of the Akt inhibitor MK-2206. Overall, our data support a negative role for the FFA component of lipoprotein hydrolysis products generated by LPL, by impairing macrophage cholesterol efflux via Akt activation. url: https://www.ncbi.nlm.nih.gov/pubmed/32437392/ doi: 10.1371/journal.pone.0233180 id: cord-288502-qqg41daz author: Martini, Katharina title: Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019 date: 2020-10-05 words: 3613.0 sentences: 207.0 pages: flesch: 47.0 cache: ./cache/cord-288502-qqg41daz.txt txt: ./txt/cord-288502-qqg41daz.txt summary: BACKGROUND: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension. Therefore, the purpose of the study was to investigate possible typical parenchymal lung changes resembling patterns of infarct pneumonia or OP as surrogate for microscopic thromboembolic events in COVID-19 patients. Our hypothesis is further strengthened by the higher presence of CT signs for pulmonary artery hypertension and right heart failure in patients undergoing CT-PA or with CT patterns resembling infarct pneumonia. However, our COVID-19 cohort showed lung changes resembling those of infarct pneumonia and OP as well as CT-signs of pulmonary-artery hypertension. abstract: BACKGROUND: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events. METHODS: Real-time polymerase-chain-reaction (RT-PCR)-confirmed COVID-19 patients undergoing chest-CT (non-enhanced, enhanced, pulmonary-angiography [CT-PA]) from March-April 2020 were retrospectively included (COVID-19-cohort). As control-groups served 175 patients from 2020 (cohort-2020) and 157 patients from 2019 (cohort-2019) undergoing CT-PA for pulmonary embolism (PE) during the respective time frame at our institution. Two independent readers assessed for presence and location of PE in all three cohorts. In COVID-19 patients additionally parenchymal changes typical of COVID-19 pneumonia, infarct pneumonia and OP were assessed. Inter-reader agreement and prevalence of PE in different cohorts were calculated. RESULTS: From 68 COVID-19 patients (42 female [61.8%], median age 59 years [range 32–89]) undergoing chest-CT 38 obtained CT-PA. Inter-reader-agreement was good (k = 0.781). On CT-PA, 13.2% of COVID-19 patients presented with PE whereas in the control-groups prevalence of PE was 9.1% and 8.9%, respectively (p = 0.452). Up to 50% of COVID-19 patients showed changes typical for OP. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA. CONCLUSION: Despite the reported hypercoagulability in critically ill patients with COVID-19, we did not encounter higher prevalence of PE in our patient cohort compared to the control cohorts. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension. url: https://www.ncbi.nlm.nih.gov/pubmed/33017451/ doi: 10.1371/journal.pone.0240078 id: cord-003404-eqgc8v7y author: May, Win Lai title: Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children date: 2019-01-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency may affect the clinical presentation of dengue due to the altered redox state in immune cells. We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. A cross-sectional study was conducted among paediatric patients aged 2–13 years with dengue in Yankin Children Hospital, Myanmar. One hundred and ninety-six patients positive for dengue infection, as determined via PCR or ELISA, were enrolled. Dengue severity was determined according to the 2009 WHO classification guidelines. Spectrophotometric assays determined G6PD levels. The adjusted median G6PD value of males in the study population was used to define various cut-off points according to the WHO classification guidelines. G6PD genotyping for Mahidol, Kaiping and Mediterranean mutations was performed for 128 out of 196 samples by real-time multiplex PCR. 51 of 196 (26.0%) patients had severe dengue. The prevalence of G6PD phenotype deficiency (< 60% activity) in paediatric patients was 14.8% (29/196), specifically, 13.6% (14/103) in males and 16.2% (15/93) in females. Severe deficiency (< 10% activity) accounted for 7.1% (14/196) of our cohort, occurring 11.7% (12/103) in males and 2.2% (2/93) in females. Among 128 samples genotyped, the G6PD gene mutations were detected in 19.5% (25/128) of patients, with 20.3% (13/ 64) in males and 18.8% (12/64) in females. The G6PD Mahidol mutation was 96.0% (24/25) while the G6PD Kaiping mutation was 4.0% (1/25). Severe dengue was not associated with G6PD enzyme deficiency or presence of the G6PD gene mutation. Thus, no association between G6PD deficiency and dengue severity could be detected. Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001 url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314580/ doi: 10.1371/journal.pone.0209204 id: cord-341097-c96hm610 author: Mayer, Craig S. title: Analysis of data dictionary formats of HIV clinical trials date: 2020-10-05 words: 6899.0 sentences: 366.0 pages: flesch: 57.0 cache: ./cache/cord-341097-c96hm610.txt txt: ./txt/cord-341097-c96hm610.txt summary: To facilitate aggregation across studies, we defined three types of data dictionary (data element, forms, and permissible values) and created a simple information model for each type. The presented study is limited to data dictionary analysis, although the motivation is to later analyze a large body of past HIV data elements to inform data-driven consensus on CDEs. This study is part of a larger research project titled ''Identification of Research Common Data Elements in HIV/AIDS using data science methods'' [12] . We use the term Forms Data Dictionary (or forms dictionary in shorter form) to refer to a data dictionary that provides a full list of titles and descriptions of all Case Report Forms (CRFs) used in the study (or other relevant metadata for data element grouping). Use of categorical data elements in research is extremely common and, as stated earlier, most studies would be expected to provide a permissible value dictionary. abstract: BACKGROUND: Efforts to define research Common Data Elements try to harmonize data collection across clinical studies. OBJECTIVE: Our goal was to analyze the quality and usability of data dictionaries of HIV studies. METHODS: For the clinical domain of HIV, we searched data sharing platforms and acquired a set of 18 HIV related studies from which we analyzed 26 328 data elements. We identified existing standards for creating a data dictionary and reviewed their use. To facilitate aggregation across studies, we defined three types of data dictionary (data element, forms, and permissible values) and created a simple information model for each type. RESULTS: An average study had 427 data elements (ranging from 46 elements to 9 945 elements). In terms of data type, 48.6% of data elements were string, 47.8% were numeric, 3.0% were date and 0.6% were date-time. No study in our sample explicitly declared a data element as a categorical variable and rather considered them either strings or numeric. Only for 61% of studies were we able to obtain permissible values. The majority of studies used CSV files to share a data dictionary while 22% of the studies used a non-computable, PDF format. All studies grouped their data elements. The average number of groups or forms per study was 24 (ranging between 2 and 124 groups/forms). An accurate and well formatted data dictionary facilitates error-free secondary analysis and can help with data de-identification. CONCLUSION: We saw features of data dictionaries that made them difficult to use and understand. This included multiple data dictionary files or non-machine-readable documents, data elements included in data but not in the dictionary or missing data types or descriptions. Building on experience with aggregating data elements across a large set of studies, we created a set of recommendations (called CONSIDER statement) that can guide optimal data sharing of future studies. url: https://doi.org/10.1371/journal.pone.0240047 doi: 10.1371/journal.pone.0240047 id: cord-332922-2qjae0x7 author: Mbuvha, Rendani title: Bayesian inference of COVID-19 spreading rates in South Africa date: 2020-08-05 words: 3224.0 sentences: 169.0 pages: flesch: 52.0 cache: ./cache/cord-332922-2qjae0x7.txt txt: ./txt/cord-332922-2qjae0x7.txt summary: In this work, we perform Bayesian parameter inference using Markov Chain Monte Carlo (MCMC) methods on the Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological models with time-varying spreading rates for South Africa. The results find two change points in the spreading rate of COVID-19 in South Africa as inferred from the confirmed cases. The second change point coincides with the start of a state-led mass screening and testing programme which has highlighted community-level disease spread that was not well represented in the initial largely traveller based and private laboratory dominated testing data. In this work we combine Bayesian inference with the compartmental SEIR and SIR models to infer time varying spreading rates that allow for quantification of the impact of government interventions in South Africa. SIR and SEIR model parameter inference was performed using confirmed cases data up to and including 20 April 2020 and MCMC samplers described in the methodology section. abstract: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for performing accurate inference with limited data. Fundamental to the design of rapid state responses is the ability to perform epidemiological model parameter inference for localised trajectory predictions. In this work, we perform Bayesian parameter inference using Markov Chain Monte Carlo (MCMC) methods on the Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological models with time-varying spreading rates for South Africa. The results find two change points in the spreading rate of COVID-19 in South Africa as inferred from the confirmed cases. The first change point coincides with state enactment of a travel ban and the resultant containment of imported infections. The second change point coincides with the start of a state-led mass screening and testing programme which has highlighted community-level disease spread that was not well represented in the initial largely traveller based and private laboratory dominated testing data. The results further suggest that due to the likely effect of the national lockdown, community level transmissions are slower than the original imported case driven spread of the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32756608/ doi: 10.1371/journal.pone.0237126 id: cord-273343-als886fe author: McClenahan, Shasta D. title: Discovery of a Bovine Enterovirus in Alpaca date: 2013-08-12 words: 4596.0 sentences: 214.0 pages: flesch: 51.0 cache: ./cache/cord-273343-als886fe.txt txt: ./txt/cord-273343-als886fe.txt summary: A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Analysis of the full polyprotein and the individual capsid, 2A protease, 3C protease, and polymerase proteins of the alpaca-infecting virus relative to sequences of other representative enteroviruses from bovine EV-E (BEV-A serotypes 1-4) and EV-F (BEV-B serotypes 1-4), and sequences from three unclassified EV-F viruses [16] , two from bovine sources (AY724744 and AY724745) [20] , and one from a capped langur (JX538037) [21] , possum, porcine (PEV), and human (HEV) hosts. abstract: A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. Genomic sequence data of the alpaca isolate was obtained and compared with sequences of known viruses. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Because bovine enteroviruses have not been previously reported in U.S. alpaca, we suspect that this type of infection is fairly rare, and in this case appeared not to spread beyond the original outbreak. The capsid sequence of the detected virus had greatest homology to Enterovirus F type 1 (indicating that the virus should be considered a member of serotype 1), but the virus had greater homology in 2A protease sequence to type 3, suggesting that it may have been a recombinant. Identifying pathogens that infect a new host species for the first time can be challenging. As the disease in a new host species may be quite different from that in the original or natural host, the pathogen may not be suspected based on the clinical presentation, delaying diagnosis. Although this virus replicated in MDBK cells, existing standard culture and molecular methods could not identify it. In this case, a highly sensitive generic PCR-based pathogen-detection method was used to identify this pathogen. url: https://doi.org/10.1371/journal.pone.0068777 doi: 10.1371/journal.pone.0068777 id: cord-346089-u31n0qxa author: McDade, Thomas W. title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay date: 2020-08-14 words: 2232.0 sentences: 140.0 pages: flesch: 52.0 cache: ./cache/cord-346089-u31n0qxa.txt txt: ./txt/cord-346089-u31n0qxa.txt summary: title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). Serological testing for SARS-CoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection. In addition, we demonstrate the feasibility and utility of quantifying SARS-CoV-2 antibodies in self-collected DBS with results from a community-based sample enriched with health care workers. We have validated a DBS assay to facilitate large-scale serological testing of SARS-CoV-2 IgG antibodies, and results from our feasibility study document a high rate of household transmission. abstract: OBJECTIVE: Serological testing is needed to investigate the extent of transmission of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). We describe assay performance and demonstrate its utility for remote sampling with results from a community-based study. METHODS: An ELISA to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members. RESULTS: Among 30 individuals sharing a household with a virus-confirmed case of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies to the receptor binding domain. CONCLUSION: DBS ELISA provides a minimally-invasive alternative to venous blood collection. Early analysis suggests a high rate of transmission among household members. High rates of seroconversion were also noted following recovery from infection. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection. url: https://doi.org/10.1371/journal.pone.0237833 doi: 10.1371/journal.pone.0237833 id: cord-315531-2gc2dc46 author: McGarvey, Peter B. title: Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date: 2009-09-25 words: 7016.0 sentences: 335.0 pages: flesch: 39.0 cache: ./cache/cord-315531-2gc2dc46.txt txt: ./txt/cord-315531-2gc2dc46.txt summary: (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods. Here we describe in detail a protein-centric approach for systems integration of such a large and heterogeneous set of data from the NIAID Biodefense Proteomics program, and present scientific case studies to illustrate its application to facilitate the basic understanding of pathogen-host interactions and for the identification of potential candidates for therapeutic or diagnostic targets. abstract: The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification. url: https://www.ncbi.nlm.nih.gov/pubmed/19779614/ doi: 10.1371/journal.pone.0007162 id: cord-001387-2g9dc5z4 author: McIntyre, K. Marie title: A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe date: 2014-08-19 words: 4582.0 sentences: 215.0 pages: flesch: 40.0 cache: ./cache/cord-001387-2g9dc5z4.txt txt: ./txt/cord-001387-2g9dc5z4.txt summary: By coupling the H-index method with the EID2, the primary aim of this study was to establish priority lists of human and domestic animal pathogens (including zoonoses) present in Europe. Its potential as a quantitative One Health indicator (i.e. a single measure applicable to both human and animal diseases) was investigated by comparing scores for human-only, zoonotic, and animal-only pathogen groups, including emerging status as this would likely drive research impact. We investigated its value as a proxy for animal disease impact by comparing domestic animal pathogen H-indices with other measures of impact including presence on the OIE list [10] , and inclusion in DISCONTOOLS [11] . The study establishes priority lists of human and domestic animal pathogens (including zoonoses) present in Europe, using the H-index as a proxy measure for impact. abstract: Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138073/ doi: 10.1371/journal.pone.0103529 id: cord-319921-uxtydu60 author: Meli, Marina L. title: Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus) date: 2009-03-09 words: 5506.0 sentences: 259.0 pages: flesch: 48.0 cache: ./cache/cord-319921-uxtydu60.txt txt: ./txt/cord-319921-uxtydu60.txt summary: METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. Furthermore, the presence of feline leukemia virus (FeLV) provirus was recently reported in six samples originating from both the Doñ ana and Sierra Morena areas in southern Spain between 1994 and 2003 [29] . Thus, in the present study, we report on the prevalence of the aforementioned pathogens and we describe a dramatic FeLV epidemic, which most likely led to the death of 6 Iberian lynxes within a 6-months period in 2007, its possible origin, and its relationship to other infectious agents. However, endogenous FeLV sequences related to those of domestic cats are apparently not present in Iberian lynxes: only 5 of the 77 lynxes tested displayed weak signals by quantitative realtime PCR, which is not compatible with presence of enFeLV sequences. abstract: BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained. url: https://doi.org/10.1371/journal.pone.0004744 doi: 10.1371/journal.pone.0004744 id: cord-002141-9mxi4dzi author: Memczak, Henry title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding date: 2016-07-14 words: 8780.0 sentences: 476.0 pages: flesch: 51.0 cache: ./cache/cord-002141-9mxi4dzi.txt txt: ./txt/cord-002141-9mxi4dzi.txt summary: title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding We used complementary experimental and theoretical approaches to select HA binding VH-CDR peptides and to improve their potential to inhibit binding, and finally, infection of cells by influenza A virus. Contribution to the total binding free energy change of every amino acid of PeB GF binding to HA of Aichi H3N2 obtained by MD-simulations is shown in Fig 2B. Our aim was to obtain peptide inhibitors that recognize the conserved region of the sialic acid binding pocket of HA with a broader specificity to cover several influenza virus strains. The three CDRs of the VH-chain of antibody HC19 against hemagglutinin of influenza virus Aichi H3N2 were used as templates to design peptides being a potential inhibitor of virus binding to host cells. As a consequence, the hemagglutination inhibition efficiency may not necessarily be stronger against Aichi H3N2, even though the peptide was derived from an antibody binding to this influenza strain. abstract: Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944999/ doi: 10.1371/journal.pone.0159074 id: cord-001958-2gt3fwpy author: Meseda, Clement A. title: Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines date: 2016-02-19 words: 8161.0 sentences: 361.0 pages: flesch: 43.0 cache: ./cache/cord-001958-2gt3fwpy.txt txt: ./txt/cord-001958-2gt3fwpy.txt summary: Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. In the work described here, we demonstrate in mouse models that percutaneous inoculation of MVA elicited protective immune responses against lethal intranasal challenge with the Western Reserve (WR) strain of vaccinia virus, and at low doses of MVA, lower morbidity was recorded in mice that were vaccinated via the percutaneous route than in those immunized via the intramuscular or subcutaneous routes. In a preliminary experiment to investigate the utility of the percutaneous route for the delivery of MVA, we observed that MVA delivered by tail scarification, while statistically insignificant (p = 0.298), elicited a higher vaccinia-specific IgG response and protection in mice than the same dose (10 6 pfu) delivered by the intramuscular route (S1 Fig) . abstract: The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760941/ doi: 10.1371/journal.pone.0149364 id: cord-286065-x0g67pnb author: Metzgar, David title: The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood date: 2016-07-06 words: 5925.0 sentences: 240.0 pages: flesch: 38.0 cache: ./cache/cord-286065-x0g67pnb.txt txt: ./txt/cord-286065-x0g67pnb.txt summary: We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. During the clinical sample study, performed following the sterility and personal protective equipment recommendations of the manufacturer, 61 negative controls were tested and yielded no Other reportable organisms excluding potential contaminants (n = 550) 0 0 0 207 A These 11 culture-negative, IRIDICA BAC BSI Assay-positive detections were supported by later organism-specific ID data which identified the same species as agents of infection (as noted on the subjects'' charts). The broad-spectrum nature of the IRIDICA BAC BSI Assay primers, paired with a signal analysis method capable of sensitive and specific detection and identification of one or more species signatures in samples with high background levels of human DNA, make it uniquely suited as a molecular test for bacterial and Candida DNA in blood samples. abstract: Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. Disclaimer: The IRIDICA BAC BSI Assay is not available in the United States. url: https://www.ncbi.nlm.nih.gov/pubmed/27384540/ doi: 10.1371/journal.pone.0158186 id: cord-289285-aof7xy13 author: Michaelis, Martin title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression date: 2011-05-17 words: 4282.0 sentences: 270.0 pages: flesch: 42.0 cache: ./cache/cord-289285-aof7xy13.txt txt: ./txt/cord-289285-aof7xy13.txt summary: title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Glycyrrhizin 200 mg/ml (the maximum tested concentration) did not affect A549 cell viability (data not shown) but clearly decreased CPE formation in A549 cells infected with the H5N1 influenza strain A/Thailand/1(Kan-1)/04 at MOIs of 0.01, 0.1 or 1 ( Figure 1A ). Here, we show that glycyrrhizin inhibits the replication of highly pathogenic H5N1 influenza A virus, H5N1-induced apoptosis, and H5N1-induced expression of pro-inflammatory cytokines in lung-derived A549 cells. abstract: Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease. url: https://www.ncbi.nlm.nih.gov/pubmed/21611183/ doi: 10.1371/journal.pone.0019705 id: cord-291417-p49ukyhx author: Mikulska, Malgorzata title: Tocilizumab and steroid treatment in patients with COVID-19 pneumonia date: 2020-08-20 words: 4441.0 sentences: 219.0 pages: flesch: 44.0 cache: ./cache/cord-291417-p49ukyhx.txt txt: ./txt/cord-291417-p49ukyhx.txt summary: METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. We hypothesized that outcomes such as no need for intubation and survival of patients with severe COVID-19 pneumonia in whom tocilizumab and/or methylprednisolone were administered in addition to standard of care (SOC) could be better than in those who received only SOC. In this observational study in non-intubated patients with mainly severe COVID-19 pneumonia, the early addition of tocilizumab and/or methylprednisolone to SOC resulted in adjusted failure-free survival of 86.5% and 80.8% at day 14 and 30, which was, respectively, 10.7% and 16.7% higher than in SOC patients. abstract: INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24(th), also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HR(OW)). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30–100) and median PaO(2)/FiO(2) 200 mmHg (IQR 133–289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8–86.7) vs. 64.1% (95%CI, 51.3–74.0), HR(OW) 0.48, 95%CI, 0.23–0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7–92.6) vs. 71.9% (95%CI, 46–73), HR(OW) 0.41, 95%CI: 0.19–0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia. url: https://doi.org/10.1371/journal.pone.0237831 doi: 10.1371/journal.pone.0237831 id: cord-327199-ggomuomb author: Moerdyk-Schauwecker, Megan title: Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date: 2014-08-08 words: 6425.0 sentences: 288.0 pages: flesch: 43.0 cache: ./cache/cord-327199-ggomuomb.txt txt: ./txt/cord-327199-ggomuomb.txt summary: In another example, the presence of host complement control proteins such as CD46, CD55 and CD59 in the viral envelope has been shown to protect against antibody dependent complement mediated virus lysis in several viruses including human T cell leukemia/ lymphoma virus type I [16] , human cytomegalovirus [16] , hepatitis C virus [17] , HIV-1 [18, 19] , extracellular enveloped vaccinia virus [20] , simian virus 5 [21] and mumps virus [21] . As discussed in the previous section, proteins not associated with the interior of the virion, including proteins embedded in the host derived viral envelope, can be identified by their absence in ProK treated samples or by a size shift upon ProK treatment. While many of the proteins identified in VSV virions appear to be associated with viral assembly, budding or the host-derived viral envelope, they may also have additional functions that affect virus replication. abstract: Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact (“whole”) virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV. url: https://www.ncbi.nlm.nih.gov/pubmed/25105980/ doi: 10.1371/journal.pone.0104688 id: cord-001253-3jnkki5z author: Mohammad, Fahim title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data date: 2014-04-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Laboratory testing is the single highest-volume medical activity, making it useful to ask how well one can anticipate whether a given test result will be high, low, or within the reference interval (“normal”). We analyzed 10 years of electronic health records—a total of 69.4 million blood tests—to see how well standard rule-mining techniques can anticipate test results based on patient age and gender, recent diagnoses, and recent laboratory test results. We evaluated rules according to their positive and negative predictive value (PPV and NPV) and area under the receiver-operator characteristic curve (ROC AUCs). Using a stringent cutoff of PPV and/or NPV≥0.95, standard techniques yield few rules for sendout tests but several for in-house tests, mostly for repeat laboratory tests that are part of the complete blood count and basic metabolic panel. Most rules were clinically and pathophysiologically plausible, and several seemed clinically useful for informing pre-test probability of a given result. But overall, rules were unlikely to be able to function as a general substitute for actually ordering a test. Improving laboratory utilization will likely require different input data and/or alternative methods. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986061/ doi: 10.1371/journal.pone.0092199 id: cord-345717-ktajrf7d author: Monagin, Corina title: Serologic and behavioral risk survey of workers with wildlife contact in China date: 2018-04-03 words: 4585.0 sentences: 241.0 pages: flesch: 45.0 cache: ./cache/cord-345717-ktajrf7d.txt txt: ./txt/cord-345717-ktajrf7d.txt summary: We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. The present study focuses on the potential for zoonotic viral transfer through contact with wildlife in Guangdong prefectures in China, and seeks to augment our understanding and identification of risky populations, occupations, and behaviors, as well as the perceptions of risk at these interfaces. We performed a serological survey and concurrent behavioral questionnaire of individuals with wildlife contact in Guangdong Province, China, in order to better characterize occupations and community-level behavioral risks that contribute to zoonotic transmission of various wildlife pathogens with pandemic potential. We targeted high-risk individuals, defined as individuals with high levels of exposure to wildlife (wild animal blood or bodily fluids)-primarily hunters, persons working in wet markets and restaurants that butcher wild game, who could be followed over a period of time. abstract: We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals. 1,312 individuals were enrolled in the study. Contact with a wide range of wildlife species was reported in both occupational and occasional contexts. The overall proportion of individuals seropositive to any of the tested wildlife pathogens was approximately 4.0%. However, persons employed as butchers demonstrated a seropositivity of 9.0% to at least one pathogen of interest. By contrast, individuals working as hunters had lower rates of seropositivity. Among the study population, a number of other behaviors showed correlation with seropositivity, including contact with particular wildlife species such as field rats. These results demonstrate the need to further explore zoonotic risks of particular activities regarding wildlife contact, and to better understand risks of persons working as butchers with wildlife species. url: https://doi.org/10.1371/journal.pone.0194647 doi: 10.1371/journal.pone.0194647 id: cord-000642-mkwpuav6 author: Moreira, Rebeca title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date: 2012-04-19 words: 6848.0 sentences: 372.0 pages: flesch: 45.0 cache: ./cache/cord-000642-mkwpuav6.txt txt: ./txt/cord-000642-mkwpuav6.txt summary: title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. Moreover, a few transcripts encoded by genes putatively involved in the clam immune response against Perkinsus olseni have been reported by cDNA library sequencing [18] . philippinarum transcriptome and another four bivalve species sequences were analyzed by comparative genomics (Crassostrea gigas of the family Ostreidae, Bathymodiolus azoricus and Mytilus galloprovincialis of the family Mytilidae and Laternula elliptica of the family Laternulidae). abstract: BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp. The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully. The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present. CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system. Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334963/ doi: 10.1371/journal.pone.0035009 id: cord-002560-pue5q5wp author: Moreno, Paloma S. title: Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics date: 2017-06-01 words: 5137.0 sentences: 265.0 pages: flesch: 50.0 cache: ./cache/cord-002560-pue5q5wp.txt txt: ./txt/cord-002560-pue5q5wp.txt summary: Recently, due to the advent of molecular enrichment protocols, high throughput sequencing and new metagenomic analytical methods we are now able to explore, identify and characterise viruses from different biological and environmental samples with a greater capacity [2, [5] [6] [7] [8] [9] [10] [11] In studies of human faeces, the virome has been shown to include viruses that infect eukaryotic organisms and viruses that infect prokaryotes (bacteriophages) [2, 5, [12] [13] [14] [15] [16] [17] [18] . Another eukaryotic viral family found in one healthy dog sample was Parvoviridae, genetic analysis of the 3 contigs/singletons showed a coverage of approximately 3.5% of the complete genome of canine parvovirus reference sequence (NC_001539), or 9.3% of the polyprotetin Ns1-Ns2. Nucleic acids from a single faecal sample from a dog with acute diarrhoea (DD1), which had 18 contigs/singletons of canine astrovirus (after tBLASTx analysis) was used to determine the complete genome sequence. abstract: The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453527/ doi: 10.1371/journal.pone.0178433 id: cord-310678-33c3mp1o author: Morgantini, Luca A. title: Factors contributing to healthcare professional burnout during the COVID-19 pandemic: A rapid turnaround global survey date: 2020-09-03 words: 3491.0 sentences: 214.0 pages: flesch: 54.0 cache: ./cache/cord-310678-33c3mp1o.txt txt: ./txt/cord-310678-33c3mp1o.txt summary: INTERPRETATION: Burnout is present at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, and support for family, PPE, and mental health resources. assessed 376 Italian HCPs who interacted with COVID-19 infected patients for their reported burnout, psychosomatic symptoms and self-perceived general health, finding in their study population high emotional burnout, physical symptoms, and work-related pressure [7] . Across all countries (Fig 2) , in the multivariable regression analysis, reported burnout was associated with work impacting household activities (RR = 1�57, 95% CI = 1�39-1�78, P<0�001), feeling pushed beyond training (RR = 1�32, 95% CI = 1�20-1�47, P<0�001), exposure to COVID-19 patients (RR = 1�18, 95% CI = 1�05-1�32, P = 0�005), and making life prioritizing decisions due to supply shortages (RR = 1�16, 95% CI = 1�02-1�31, P = 0�03). abstract: BACKGROUND: Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload and stress. Understanding HCPs’ risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. METHODS: To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs’ self-assessment of burnout, indicated by a single item measure of emotional exhaustion, and other experiences and attitudes associated with working during the COVID-19 pandemic. FINDINGS: A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR = 1·57, 95% CI = 1·39–1·78, P<0·001), feeling pushed beyond training (RR = 1·32, 95% CI = 1·20–1·47, P<0·001), exposure to COVID-19 patients (RR = 1·18, 95% CI = 1·05–1·32, P = 0·005), and making life prioritizing decisions (RR = 1·16, 95% CI = 1·02–1·31, P = 0·03). Adequate personal protective equipment (PPE) was protective against burnout (RR = 0·88, 95% CI = 0·79–0·97, P = 0·01). Burnout was higher in high-income countries (HICs) compared to low- and middle-income countries (LMICs) (RR = 1·18; 95% CI = 1·02–1·36, P = 0·018). INTERPRETATION: Burnout is present at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, and support for family, PPE, and mental health resources. url: https://www.ncbi.nlm.nih.gov/pubmed/32881887/ doi: 10.1371/journal.pone.0238217 id: cord-295201-u2dola34 author: Morimoto, Konosuke title: The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study date: 2015-03-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society. METHODS: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. RESULTS: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). CONCLUSIONS: A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society. url: https://www.ncbi.nlm.nih.gov/pubmed/25822890/ doi: 10.1371/journal.pone.0122247 id: cord-328633-c31xsyeo author: Moser, Michael J. title: Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date: 2012-06-04 words: 7868.0 sentences: 441.0 pages: flesch: 54.0 cache: ./cache/cord-328633-c31xsyeo.txt txt: ./txt/cord-328633-c31xsyeo.txt summary: Most RT-PCR protocols rely on two DNA polymerase (Pol) enzymes; a retroviral reverse transcriptase (RT) to copy RNA into cDNA and a thermostable DNA Pol to amplify the target sequence. Despite their wide use and general reliability, existing twoenzyme RT-PCR systems have several documented performance problems attributed to deficiencies inherent in retroviral RTs: 1) poor reagent stability, 2) low fidelity, 3) frequent rearrangements during cDNA synthesis, 4) secondary enzymatic activities (i.e. RNase H and strand switching), 5) bias for specific primers and templates, and 6) inhibition of PCR Pol enzymes [3, 4, 5, 6, 7] . We describe the discovery and biochemical attributes of one of these, 3173 Pol, its inherent RT activity and its incorporation into a single-enzyme PyroScriptH 2X RT-PCR Master Mix. The sensitivity, specificity and overall performance of this mix were compared to available one-and two-enzyme systems using a control MS2 RNA bacteriophage template, the clinically-relevant influenza A RNA and commonly used reference mRNA transcripts. abstract: Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics. url: https://doi.org/10.1371/journal.pone.0038371 doi: 10.1371/journal.pone.0038371 id: cord-341880-wxliz485 author: Mottaleb, Khondoker Abdul title: COVID-19 induced economic loss and ensuring food security for vulnerable groups: Policy implications from Bangladesh date: 2020-10-16 words: 7552.0 sentences: 365.0 pages: flesch: 60.0 cache: ./cache/cord-341880-wxliz485.txt txt: ./txt/cord-341880-wxliz485.txt summary: This study examines the food security and welfare impacts of the COVID-19 induced lockdown on daily wage workers both in the farm and nonfarm sectors in Bangladesh. Then, applying simple econometric estimation processes, this study estimates the minimum compensation packages for the daily wage-based farm and nonfarm households of Bangladesh that ensure their minimum food security during the lockdown. The estimation suggests a common minimum support at US $ 1 per daily wage-based household in Bangladesh to ensure minimum food security during COVID-19 induced lockdown time. Using information of more than 50,000 respondents from the HIES 2016-17 dataset, this study, firstly quantified the economic loss due to the COVID-19 induced lockdown and suggested the minimum support package to ensure food security of the daily wage-based workers in Bangladesh. abstract: At present nearly half of the world’s population is under some form of government restriction to curb the spread of COVID-19, an extremely contagious disease. In Bangladesh, in the wake of five deaths and 48 infections from COVID-19, between March 24 and May 30, 2020, the government imposed a nationwide lockdown. While this lockdown restricted the spread of COVID-19, in the absence of effective support, it can generate severe food and nutrition insecurity for daily wage-based workers. Of the 61 million employed labor force in Bangladesh, nearly 35% of them are paid on a daily basis. This study examines the food security and welfare impacts of the COVID-19 induced lockdown on daily wage workers both in the farm and nonfarm sectors in Bangladesh. Using information from more than 50,000 respondents complied with the 2016–17 Household Income and Expenditure Survey (HIES) in Bangladesh, this study estimates daily wage rates as Bangladesh Taka (BDT) 272.2 in the farm sector and BDT 361.5 in the nonfarm sector. Using the estimated daily wage earnings, this study estimates that a one-day complete lockdown generates a US$64.2 million equivalent economic loss only considering the wage loss of the daily wage workers. After estimating the daily per capita food expenditure separately for farm and nonfarm households, this study estimates a minimum compensation package for the daily wage-based farm and nonfarm households around the US $ 1 per day per household to ensure minimum food security for the daily wage-based worker households. url: https://www.ncbi.nlm.nih.gov/pubmed/33064771/ doi: 10.1371/journal.pone.0240709 id: cord-337585-kpghvb6u author: Moustaqim-Barrette, Amina title: Accessing Take-Home Naloxone in British Columbia and the role of community pharmacies: Results from the analysis of administrative data date: 2020-09-11 words: 4016.0 sentences: 191.0 pages: flesch: 50.0 cache: ./cache/cord-337585-kpghvb6u.txt txt: ./txt/cord-337585-kpghvb6u.txt summary: Individuals not personally at risk of overdose had higher odds of collecting naloxone at a pharmacy site, compared to other community sites (including harm reduction supply distribution sites, peer led organizations, drop-in centers, and supportive housing sites) (Adjusted Odds Ratio (AOR): 2.69; 95% CI: 2.50–2.90). While those at highest risk of overdose may preferentially access naloxone through community sites, naloxone distribution through pharmacies has allowed the BC THN program to expand dramatically, increasing naloxone availability through longer opening hours on evenings and weekends. While analyses from the BCCDC shows that the BC THN program, combined with other harm reduction interventions, has averted thousands of opioid overdose deaths [20, 21] , there is still relatively little data in the published literature examining community reach and barriers to access of naloxone distribution programs in Canada. After evaluating data from 2018, our analysis also finds that individuals at risk of opioid overdose were significantly less likely to collect a naloxone kit at a pharmacy site compared to community-based sites. abstract: INTRODUCTION: British Columbia’s (BC) Take-Home Naloxone (THN) program provides naloxone to bystanders for use in cases of suspected opioid overdose. This study seeks to provide trends and analysis from the provincial BC THN program since inception in 2012 to the end of 2018. MATERIALS AND METHODS: BC THN shipment and distribution records from 2012–2018 were retrieved. Frequency distributions were used to describe characteristics of individuals accessing the program. To evaluate correlates of distribution after the addition of hundreds of pharmacy distribution sites, an analytic sample was limited to records from 2018, and multivariate logistic regression was used to evaluate correlates of collecting naloxone at a pharmacy site. RESULTS: Since program inception to the end of 2018, there were 398,167 naloxone kits shipped to distribution sites, 149,999 kits reported distributed, and 40,903 kits reported used to reverse an overdose in BC. There was a significant increasing trend in the number of naloxone kits used to reverse an overdose over time (p<0.01), and more than 90% of kits that were reported used were distributed to persons at risk of an overdose. Individuals not personally at risk of overdose had higher odds of collecting naloxone at a pharmacy site, compared to other community sites (including harm reduction supply distribution sites, peer led organizations, drop-in centers, and supportive housing sites) (Adjusted Odds Ratio (AOR): 2.69; 95% CI: 2.50–2.90). CONCLUSIONS: This study documents thousands of opioid overdose reversals facilitated through the BC THN program. While those at highest risk of overdose may preferentially access naloxone through community sites, naloxone distribution through pharmacies has allowed the BC THN program to expand dramatically, increasing naloxone availability through longer opening hours on evenings and weekends. and in rural and remote regions. A diversity of naloxone distribution sites and strategies is crucial to prevent rising opioid overdose deaths. url: https://doi.org/10.1371/journal.pone.0238618 doi: 10.1371/journal.pone.0238618 id: cord-335404-s48psqth author: Mukandavire, Zindoga title: Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios date: 2020-07-24 words: 3570.0 sentences: 183.0 pages: flesch: 48.0 cache: ./cache/cord-335404-s48psqth.txt txt: ./txt/cord-335404-s48psqth.txt summary: We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83–3.33). Here, we adapt a susceptible-exposed-infected-removed (SEIR) compartmental model to quantify early transmissibility of COVID-19 in South Africa and explore the potential utility of a vaccine in containing the disease. Following a similar approach in [37] , we use a Markov Chain Monte Carlo (MCMC) within a Bayesian framework (in R FME package [38] ) to fit the model to the cumulative data of confirmed COVID-19 cases in South Africa and estimate the magnitude of the epidemic using the basic reproductive number and quantify required vaccines'' attributes to stem similar outbreaks. abstract: The emergence and fast global spread of COVID-19 has presented one of the greatest public health challenges in modern times with no proven cure or vaccine. Africa is still early in this epidemic, therefore the extent of disease severity is not yet clear. We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. We also estimated the percentage reduction in effective contacts due to the social distancing measures implemented. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83–3.33). A vaccine with 70% efficacy had the capacity to contain COVID-19 outbreak but at very higher vaccination coverage 94.44% (95% Crl 92.44–99.92%) with a vaccine of 100% efficacy requiring 66.10% (95% Crl 64.72–69.95%) coverage. Social distancing measures put in place have so far reduced the number of social contacts by 80.31% (95% Crl 79.76–80.85%). These findings suggest that a highly efficacious vaccine would have been required to contain COVID-19 in South Africa. Therefore, the current social distancing measures to reduce contacts will remain key in controlling the infection in the absence of vaccines and other therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/32706790/ doi: 10.1371/journal.pone.0236003 id: cord-294592-zwvr57a0 author: Mukherjee, Moumita title: Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV-2 date: 2020-08-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV-2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5’ and 3’ untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon. METHODS: To have an idea of the global changes in 5’ and 3’-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV-2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by ‘RBPmap’ and ‘RNA22 v2’ respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue. RESULTS: We identified 28 unique variants in SARS-CoV-2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5’-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3’UTR among most of the continents. Furthermore, we found that despite the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs. CONCLUSION: Our results, shows for the first time in SARS-Cov-2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future. url: https://www.ncbi.nlm.nih.gov/pubmed/32780783/ doi: 10.1371/journal.pone.0237559 id: cord-001707-piyo00yg author: Murray, Jillian title: Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology date: 2015-07-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009–2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the national number of cases. The percent of SARI cases that tested positive for influenza ranged from 7–17% depending on age group, year, province and HIV status. In 2010, there were an estimated 21,555 total severe influenza cases in HIV-uninfected individuals and 13,876 in HIV-infected individuals. In 2011, there were an estimated 29,892 total severe influenza cases in HIV-uninfected individuals and 17,289 in HIV-infected individuals. The incidence of influenza-associated SARI was highest in children <5 years and was higher in HIV-infected than HIV-uninfected persons in all age groups. Influenza virus was associated with a substantial amount of severe disease, especially in young children and HIV-infected populations in South Africa. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496064/ doi: 10.1371/journal.pone.0132078 id: cord-294023-knaxr7t0 author: Murri, Rita title: Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy date: 2020-09-03 words: 2073.0 sentences: 115.0 pages: flesch: 51.0 cache: ./cache/cord-294023-knaxr7t0.txt txt: ./txt/cord-294023-knaxr7t0.txt summary: title: Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy Seventy percent (n = 261) of respondents reported that their use of social media to find medical information increased during the current pandemic (Fig 1) . In terms of COVID-19 medical practice, information coming from social media were considered "enough" or "much" or "very much" useful by 82.9% (n = 306) of the sample. To the question "During the last week, do you think that information shared on social media had an impact on your clinical practice for patients with COVID?" 28.7% (n = 106) answered "enough" and 47.1% (n = 174) "much" or "very much". Our survey shows that, at the time of COVID pandemic, many clinicians react to their urgent need for updates by seeking information through unconventional sources instead of academic journals publications. abstract: In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources that are parallel to academic journals. Aim of this work is to investigate the extent of this phenomenon. We administered an anonymous online cross-sectional survey to 645 Italian clinicians. Target of the survey were all medical figures potentially involved in the management of COVID-19 cases. 369 questionnaires were returned. 19.5% (n = 72) of respondents were younger than 30 years-old; 49,3% (n = 182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n = 42) in Intensive Care Unit and 7.4% (n = 27) were general practitioner. 70% (n = 261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties. Given the urgent need for scientific update during the present pandemic, these findings may help understanding how clinicians access new evidences and implement them in their daily practice. url: https://doi.org/10.1371/journal.pone.0238414 doi: 10.1371/journal.pone.0238414 id: cord-001964-iy6qzq58 author: Muñoz-González, Sara title: Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar date: 2016-02-26 words: 6933.0 sentences: 319.0 pages: flesch: 48.0 cache: ./cache/cord-001964-iy6qzq58.txt txt: ./txt/cord-001964-iy6qzq58.txt summary: The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Interestingly, the RNA of the vaccinal C-strain was undetectable by specific RT-PCR [8] in any of the samples analysed after vaccination, including blood, nasal and rectal swabs, or organs throughout the experiment, suggesting a phenomenon of homologous interference, also known as superinfection exclusion (SIE), between the high viral load generated by the primary persistent infection and the CSFV vaccine strain. abstract: Two groups with three wild boars each were used: Group A (animals 1 to 3) served as the control, and Group B (animals 4 to 6) was postnatally persistently infected with the Cat01 strain of CSFV (primary virus). The animals, six weeks old and clinically healthy, were inoculated with the virulent strain Margarita (secondary virus). For exclusive detection of the Margarita strain, a specific qRT-PCR assay was designed, which proved not to have cross-reactivity with the Cat01 strain. The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Furthermore, the data analysis of the Margarita qRT-PCR, by means of calculated ΔCt values, supported that PBMCs from persistently infected animals were substantially protected from superinfection after in vitro inoculation with the Margarita virus strain, while this virus was able to infect naive PBMCs efficiently. In parallel, IFN-α values were undetectable in the sera from animals in Group B after inoculation with the CSFV Margarita strain. Furthermore, these animals were unable to elicit adaptive humoral (no E2-specific or neutralising antibodies) or cellular immune responses (in terms of IFN-γ-producing cells) after inoculation with the second virus. Finally, a sequence analysis could not detect CSFV Margarita RNA in the samples tested from Group B. Our results suggested that the SIE phenomenon might be involved in the evolution and phylogeny of the virus, as well as in CSFV control by vaccination. To the best of our knowledge, this study was one of the first showing efficient suppression of superinfection in animals, especially in the absence of IFN-α, which might be associated with the lack of innate immune mechanisms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768946/ doi: 10.1371/journal.pone.0149469 id: cord-333208-tibtngy8 author: Muñoz-Moreno, Raquel title: Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date: 2016-04-26 words: 5867.0 sentences: 311.0 pages: flesch: 45.0 cache: ./cache/cord-333208-tibtngy8.txt txt: ./txt/cord-333208-tibtngy8.txt summary: The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. Thus, our goal in the current work was to test whether the IFITM family of proteins affected early entry steps of ASFV infection in Vero cell cultures using the cell-adapted Ba71V isolate. Confocal microscopy experiments revealed that, IFITM1 was mainly distributed at the plasma membrane and to a lesser extent in perinuclear compartments, resembling endosomal structures (Fig 3C, lower left panel) , while endogenous IFITM1 was barely detected in Vero cells containing the empty vector (Fig 3C, upper left panel) . abstract: The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. url: https://doi.org/10.1371/journal.pone.0154366 doi: 10.1371/journal.pone.0154366 id: cord-002398-0a3okta0 author: Myllykoski, Matti title: Structural aspects of nucleotide ligand binding by a bacterial 2H phosphoesterase date: 2017-01-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The 2H phosphoesterase family contains enzymes with two His-X-Ser/Thr motifs in the active site. 2H enzymes are found in all kingdoms of life, sharing little sequence identity despite the conserved overall fold and active site. For many 2H enzymes, the physiological function is unknown. Here, we studied the structure of the 2H family member LigT from Escherichia coli both in the apo form and complexed with different active-site ligands, including ATP, 2′-AMP, 3′-AMP, phosphate, and NADP(+). Comparisons to the well-characterized vertebrate myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) highlight specific features of the catalytic cycle and substrate recognition in both enzymes. The role played by the helix α7, unique to CNPases within the 2H family, is apparently taken over by Arg130 in the bacterial enzyme. Other residues and loops lining the active site groove are likely to be important for RNA substrate binding. We visualized conformational changes related to ligand binding, as well as the position of the nucleophilic water molecule. We also present a low-resolution model of E. coli LigT bound to tRNA in solution, and provide a model for RNA binding by LigT, involving flexible loops lining the active site cavity. Taken together, our results both aid in understanding the common features of 2H family enzymes and help highlight the distinct features in the 2H family members, which must result in different reaction mechanisms. Unique aspects in different 2H family members can be observed in ligand recognition and binding, and in the coordination of the nucleophilic water molecule and the reactive phosphate moiety. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283653/ doi: 10.1371/journal.pone.0170355 id: cord-289555-1z4vbldd author: Mühldorfer, Kristin title: Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates date: 2011-12-28 words: 5764.0 sentences: 303.0 pages: flesch: 44.0 cache: ./cache/cord-289555-1z4vbldd.txt txt: ./txt/cord-289555-1z4vbldd.txt summary: Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats. In this study, we provide new data on infectious diseases in European bat species, considering factors likely to affect the susceptibility of bats to infectious agents including effects of seasonality, individual and species-specific heterogeneities, and possible intra-and inter-species transmission dynamics. Comparative bacteriologic and histo-pathologic analysis identified 22 different bacterial species that were clearly associated with pathological lesions and/or systemic infection, found in 17% (n = 73) of bats investigated bacteriologically ( Table 5) . abstract: BACKGROUND: Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date. METHODOLOGY/PRINCIPAL FINDINGS: Between 2002 and 2009, 486 deceased bats of 19 European species (family Vespertilionidae) were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats. url: https://www.ncbi.nlm.nih.gov/pubmed/22216354/ doi: 10.1371/journal.pone.0029773 id: cord-272445-0xauff51 author: Naaber, Paul title: Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data date: 2020-10-27 words: 2751.0 sentences: 150.0 pages: flesch: 50.0 cache: ./cache/cord-272445-0xauff51.txt txt: ./txt/cord-272445-0xauff51.txt summary: title: Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data The specificity and sensitivity of SARS-CoV-2 antibody tests are known to vary and very few studies have addressed the performance of these tests in COVID-19 patient groups at different time points. We here compared the sensitivity and specificity of seven commercial (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor) and two in-house LIPS assays (LIPS N and LIPS S-RBD) IgG/total Ab tests in serum samples from 97 COVID-19 patients and 100 controls, and correlated the results with the patients'' clinical data and the time-point the test was performed. Our study aimed to compare the performance characteristics of seven commercial and two in-house IgG/total Ab tests, which analyze the reactivity to several target proteins, and to correlate the results with the patients'' clinical data (with different symptoms score and age), and time from disease onset. abstract: SARS-CoV-2 antibody tests are available in various formats, detecting different viral target proteins and antibody subclasses. The specificity and sensitivity of SARS-CoV-2 antibody tests are known to vary and very few studies have addressed the performance of these tests in COVID-19 patient groups at different time points. We here compared the sensitivity and specificity of seven commercial (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor) and two in-house LIPS assays (LIPS N and LIPS S-RBD) IgG/total Ab tests in serum samples from 97 COVID-19 patients and 100 controls, and correlated the results with the patients’ clinical data and the time-point the test was performed. We found a remarkable variation in the sensitivity of antibody tests with the following performance: LIPS N (91.8%), Epitope (85.6%), Abbott and in-house LIPS S-RBD (both 84.5%), Roche (83.5%), Euroimmun (82.5%), DiaSorin (81.4%), SNIBE (70.1%), and Biosensor (64.9%). The overall agreement between the tests was between 71–95%, whereas the specificity of all tests was within 98–100%. The correlation with patients’ clinical symptoms score ranged from strongest in LIPS N (ρ = 0.41; p<0.001) to nonsignificant in LIPS S-RBD. Furthermore, the time of testing since symptom onset had an impact on the sensitivity of some tests. Our study highlights the importance to consider clinical symptoms, time of testing, and using more than one viral antigen in SARS-CoV-2 antibody testing. Our results suggest that some antibody tests are more sensitive for the detection of antibodies in early stage and asymptomatic patients, which may explain the contradictory results of previous studies and should be taken into consideration in clinical practice and epidemiological studies. url: https://www.ncbi.nlm.nih.gov/pubmed/33108380/ doi: 10.1371/journal.pone.0237548 id: cord-000720-5b936n3g author: Nannyonga, Betty title: The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks date: 2012-07-24 words: 4405.0 sentences: 250.0 pages: flesch: 57.0 cache: ./cache/cord-000720-5b936n3g.txt txt: ./txt/cord-000720-5b936n3g.txt summary: The models designed are fit to data from the Kitgum outbreak, to estimate the basic reproduction number and to relate them to the level of contamination of the environment. Susceptible individuals without bore hole access become infected with the Hepatitis E virus at a rate bc, where b is the transmission rate of HEV from the contaminated environment c, to the human. To estimate model parameters and determine the critical level of control needed to eradicate the epidemic, the model described by the equations in (7) is fit to the data collected during the Kitgum outbreak ( Figure 1 ) During the invasion phase of HEV, the prevalence is approximately Under the above assumption, equations (7) are rewritten to incorporate the malaria dynamics in equation (11) where j is a parameter that models change the increase (or decrease) in susceptibility to Hepatitis E of malaria infected individuals [12] . abstract: Rapidly spreading infectious diseases are a serious risk to public health. The dynamics and the factors causing outbreaks of these diseases can be better understood using mathematical models, which are fit to data. Here we investigate the dynamics of a Hepatitis E outbreak in the Kitgum region of northern Uganda during 2007 to 2009. First, we use the data to determine that [Image: see text] is approximately 2.25 for the outbreak. Secondly, we use a model to estimate that the critical level of latrine and bore hole coverages needed to eradicate the epidemic is at least [Image: see text] and [Image: see text] respectively. Lastly, we further investigate the relationship between the co-infection factor for malaria and Hepatitis E on the value of [Image: see text] for Hepatitis E. Taken together, these results provide us with a better understanding of the dynamics and possible causes of Hepatitis E outbreaks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404073/ doi: 10.1371/journal.pone.0041135 id: cord-001983-zo9yngfc author: Napp, S. title: Understanding Spatio-Temporal Variability in the Reproduction Ratio of the Bluetongue (BTV-1) Epidemic in Southern Spain (Andalusia) in 2007 Using Epidemic Trees date: 2016-03-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Andalusia (Southern Spain) is considered one of the main routes of introduction of bluetongue virus (BTV) into Europe, evidenced by a devastating epidemic caused by BTV-1 in 2007. Understanding the pattern and the drivers of BTV-1 spread in Andalusia is critical for effective detection and control of future epidemics. A long-standing metric for quantifying the behaviour of infectious diseases is the case-reproduction ratio (R(t)), defined as the average number of secondary cases arising from a single infected case at time t (for t>0). Here we apply a method using epidemic trees to estimate the between-herd case reproduction ratio directly from epidemic data allowing the spatial and temporal variability in transmission to be described. We then relate this variability to predictors describing the hosts, vectors and the environment to better understand why the epidemic spread more quickly in some regions or periods. The R(t) value for the BTV-1 epidemic in Andalusia peaked in July at 4.6, at the start of the epidemic, then decreased to 2.2 by August, dropped below 1 by September (0.8), and by October it had decreased to 0.02. BTV spread was the consequence of both local transmission within established disease foci and BTV expansion to distant new areas (i.e. new foci), which resulted in a high variability in BTV transmission, not only among different areas, but particularly through time, which suggests that general control measures applied at broad spatial scales are unlikely to be effective. This high variability through time was probably due to the impact of temperature on BTV transmission, as evidenced by a reduction in the value of R(t) by 0.0041 for every unit increase (day) in the extrinsic incubation period (EIP), which is itself directly dependent on temperature. Moreover, within the range of values at which BTV-1 transmission occurred in Andalusia (20.6°C to 29.5°C) there was a positive correlation between temperature and R(t) values, although the relationship was not linear, probably as a result of the complex relationship between temperature and the different parameters affecting BTV transmission. R(t) values for BTV-1 in Andalusia fell below the threshold of 1 when temperatures dropped below 21°C, a much higher threshold than that reported in other BTV outbreaks, such as the BTV-8 epidemic in Northern Europe. This divergence may be explained by differences in the adaptation to temperature of the main vectors of the BTV-1 epidemic in Andalusia (Culicoides imicola) compared those of the BTV-8 epidemic in Northern Europe (Culicoides obsoletus). Importantly, we found that BTV transmission (R(t) value) increased significantly in areas with higher densities of sheep. Our analysis also established that control of BTV-1 in Andalusia was complicated by the simultaneous establishment of several distant foci at the start of the epidemic, which may have been caused by several independent introductions of infected vectors from the North of Africa. We discuss the implications of these findings for BTV surveillance and control in this region of Europe. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786328/ doi: 10.1371/journal.pone.0151151 id: cord-000143-2xvd5ogf author: Napthine, Sawsan title: Expression of the VP2 Protein of Murine Norovirus by a Translation Termination-Reinitiation Strategy date: 2009-12-22 words: 6886.0 sentences: 300.0 pages: flesch: 50.0 cache: ./cache/cord-000143-2xvd5ogf.txt txt: ./txt/cord-000143-2xvd5ogf.txt summary: In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity. Recent studies of termination-reinitiation in the expression of the orthomyxovirus influenza BM2 protein have revealed a requirement for a shorter stretch of mRNA (45 nt) upstream of the stop-start window, but nevertheless, the RNA contains a similar TURBS Motif 1 [19] . Whilst in principle, reinitiation of translation of the MNV 49.7 VP2fluc ORF, following termination, could occur at the next available AUG, this is located 54 amino acids from the natural stop-start signal and initiation here would produce a substantially shorter product that would have been detectable by SDS-PAGE. abstract: BACKGROUND: Expression of the minor virion structural protein VP2 of the calicivirus murine norovirus (MNV) is believed to occur by the unusual mechanism of termination codon-dependent reinitiation of translation. In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity. Consistent with this, the VP2 start codon (AUG) of MNV overlaps the stop codon of the upstream VP1 ORF (UAA) in the pentanucleotide UAA UG. PRINCIPAL FINDINGS: Here, we confirm that MNV VP2 expression is regulated by termination-reinitiation and define the mRNA sequence requirements. Efficient reintiation is dependent upon 43 nt of RNA immediately upstream of the UAA UG site. Chemical and enzymatic probing revealed that the RNA in this region is not highly structured and includes an essential stretch of bases complementary to 18S rRNA helix 26 (Motif 1). The relative position of Motif 1 with respect to the UAA UG site impacts upon the efficiency of the process. Termination-reinitiation in MNV was also found to be relatively insensitive to the initiation inhibitor edeine. CONCLUSIONS: The termination-reinitiation signal of MNV most closely resembles that of influenza BM2. Similar to other viruses that use this strategy, base-pairing between mRNA and rRNA is likely to play a role in tethering the 40S subunit to the mRNA following termination at the VP1 stop codon. Our data also indicate that accurate recognition of the VP2 ORF AUG is not a pre-requisite for efficient reinitiation of translation in this system. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793014/ doi: 10.1371/journal.pone.0008390 id: cord-002705-ntokyoai author: Nasir, Nazrila Hairin title: Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study date: 2017-10-04 words: 4464.0 sentences: 229.0 pages: flesch: 56.0 cache: ./cache/cord-002705-ntokyoai.txt txt: ./txt/cord-002705-ntokyoai.txt summary: However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. A non-randomized controlled study was conducted in Taiwan comparing the effects of oral rehydration with intravenous fluid replacement in adult patients with non-shock dengue haemorrhagic fever [7] . Most importantly, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. Thus, this pilot randomized controlled study aimed to assess the feasibility of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. abstract: INTRODUCTION: Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. METHODS: This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 10(9)/L). Both groups received a dengue home care card. The intervention group received the fluid chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. FINDINGS: Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. CONCLUSION: This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients. A randomized controlled trial with larger sample size is needed to determine this conclusively. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN25394628 http://www.isrctn.com/ISRCTN25394628 url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627892/ doi: 10.1371/journal.pone.0183544 id: cord-000721-leedutqo author: Nawaz, Sameena title: Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK date: 2012-07-24 words: 3199.0 sentences: 162.0 pages: flesch: 50.0 cache: ./cache/cord-000721-leedutqo.txt txt: ./txt/cord-000721-leedutqo.txt summary: Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). The prevalence of HBoV-2 in children in the UK was significantly lower than that reported in a study in Australia, in which HBoV-2 was detected in 17.2% and 8.1% of the cases and controls, respectively [22] . Human bocavirus in children hospitalized for acute gastroenteritis: a case-control study abstract: Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, a significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays. HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls. In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). A significant proportion of HBoV positives could not be typed using the type specific assays, 67% of the total positives, and this was most likely due to low viral loads being present in the samples. However, the distribution of the untyped HBoV strains was no different between cases and controls. In conclusion, HBoVs, including HBoV-2 do not appear to be a significant cause of gastroenteritis in the UK population. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404102/ doi: 10.1371/journal.pone.0041346 id: cord-307036-n44yml79 author: Ng, Oi-Wing title: Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody date: 2014-07-14 words: 8528.0 sentences: 392.0 pages: flesch: 57.0 cache: ./cache/cord-307036-n44yml79.txt txt: ./txt/cord-307036-n44yml79.txt summary: Next, to determine if mAb 1A9 exhibits cross-neutralizing activity, S-pseudotyped virus particles, or S-pps, carrying the human SARS-CoV S or the various RBD-modified chimeric S of civet SARS-CoV SZ3 strain and bat SL-CoV Rp3 and Rf1 strains were generated and used to infect CHO-ACE2 cells in the absence or presence of different concentrations (100, 150 and 200 mg/ml) of mAb 1A9. Wild-type S, substitution S mutants, namely D1128A, N1056K, and that containing both D1128A and N1056K, were then expressed in 293 FT cells and Western Blot analysis was performed to determine the effects of these mutations on the binding of the S protein to mAb 1A9. (A) S-pp expressing S protein of humans SARS-CoV HKU39849, civet SARS-CoV SZ3, bat SL-CoV Rp3 and Rf1 and (B) S-pp containing wild-type or mutant D1128A, N1056K or D1128A/ N1056K S were generated and used to infect CHO-ACE2 cells at equal amount (as quantitated using P24 ELISA). abstract: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus. url: https://www.ncbi.nlm.nih.gov/pubmed/25019613/ doi: 10.1371/journal.pone.0102415 id: cord-001601-tsuz3j40 author: Ngan, Luong Thi My title: Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses date: 2015-04-10 words: 6157.0 sentences: 328.0 pages: flesch: 53.0 cache: ./cache/cord-001601-tsuz3j40.txt txt: ./txt/cord-001601-tsuz3j40.txt summary: An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. In the presence of 100 μg/mL PA or 20 μg/mL PGG in MRC5 cell cultures infected with HRV-2, the RNA replication levels were reduced by 30.1 and 14.3 fold, respectively, compared to the levels in the cell cultures without the compounds (Fig 4A) . abstract: Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3–>8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393083/ doi: 10.1371/journal.pone.0121629 id: cord-000176-z76vjkxg author: Nguyen, Jack T. title: Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro date: 2010-02-22 words: 7331.0 sentences: 295.0 pages: flesch: 45.0 cache: ./cache/cord-000176-z76vjkxg.txt txt: ./txt/cord-000176-z76vjkxg.txt summary: Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadineand oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. In an earlier study, we explored the in vitro antiviral activity and synergy of single, double, and triple combinations of amantadine, ribavirin and oseltamivir against a panel of influenza A viruses that were susceptible to these drugs [10] . Statistical analysis of the variability across all replicates from the six experiments for each virus revealed that amantadine made a significant contribution to the synergy of the TCAD regimen at concentrations 0.1 mg/mL and 0.32 mg/mL and above against CA05 and CA10, respectively, compared to the double combination of ribavirin/oseltamivir carboxylate without amantadine ( Figure 1B ). abstract: The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21(st) century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI). To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825274/ doi: 10.1371/journal.pone.0009332 id: cord-282668-bs634hti author: Niang, Mbayame Ndiaye title: Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses date: 2017-03-22 words: 4623.0 sentences: 243.0 pages: flesch: 47.0 cache: ./cache/cord-282668-bs634hti.txt txt: ./txt/cord-282668-bs634hti.txt summary: In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenzalike Illness cases. From January 2012 to December 2015 we collected specimens (nasal-pharyngeal and oral-pharyngeal swabs) and surveillance data for influenza and other viral respiratory pathogens from outpatients presenting with influenza-like-illness (ILI) at different sentinel sites in Senegal. So the circulation of such HAdV genome types in Senegal emphasizes the need to reinforce HAdV surveillance, especially in hospitalized patients, by including HAdV genome detection and genotyping in the documentation of severe respiratory infections. Molecular epidemiology of human adenovirus isolated from children hospitalized with acute respiratory infection in São Paulo, Brazil abstract: BACKGROUND: Human adenoviruses (HAdVs) are highly contagious pathogens that are associated with a wide spectrum of human illnesses involving the respiratory tract. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. METHODOLOGY AND RESULTS: From January 2012 to December 2015 swabs were collected from consenting ILI outpatients. Adenoviral detection is performed by rRT-PCR with the Anyplex(™) II RV16 Detection kit (Seegene) and molecular characterization was performed using a partial hexon gene sequence. 6381 samples were collected. More than half of patients (51.7%; 3297/6381) were children of ≤ 5 years. 1967 (30.8%) were positive for HAdV with 1561 (79.4%) found in co-infection with at least one another respiratory virus. The most common co-detections were with influenza viruses (53.1%; 1045/1967), rhinoviruses (30%; 591/1967), enteroviruses (18.5%; 364/1967) and RSV (13.5%; 266/1967). Children under 5 were the most infected group (62.2%; 1224/1967; p <0.05). We noted that HAdV was detected throughout the year at a high level with detection peaks of different amplitudes without any clear seasonality. Phylogenetic analysis revealed species HAdV-C in majority, species HAdV-B and one HAdV- 4 genome type. The 9 HAdV-B species like strains from Senegal grouped with genome types HAdV-7, HAdV-55 and HAdV-11 as shown by a phylogenetic branch with a high bootstrap value of (88%). CONCLUSION: In conclusion, the results of the present study suggest strong year-round HAdV activity in Senegal, especially in children up to 5 years of age. Molecular studies revealed that the dominant species in circulation in patients with ILI appears to be HAdV-C and HAdV-B species. The circulation of though HAdV-7 and HAdV-55 genome types is of note as these serotypes are recognized causes of more severe and even fatal acute respiratory infections. url: https://doi.org/10.1371/journal.pone.0174287 doi: 10.1371/journal.pone.0174287 id: cord-000322-8ctsa9sd author: Ninove, Laetitia title: RNA and DNA Bacteriophages as Molecular Diagnosis Controls in Clinical Virology: A Comprehensive Study of More than 45,000 Routine PCR Tests date: 2011-02-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs). In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure. Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis. This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis. Various technical formats for using phages as ICs were optimised and validated. Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses. The frequency of inefficient detection of ICs was analyzed according to the nature of the sample. Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%). The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology. It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs. The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036576/ doi: 10.1371/journal.pone.0016142 id: cord-001432-d4zavkcn author: Nishida, Yoriko title: Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry date: 2014-10-16 words: 5268.0 sentences: 306.0 pages: flesch: 48.0 cache: ./cache/cord-001432-d4zavkcn.txt txt: ./txt/cord-001432-d4zavkcn.txt summary: PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Actin-related protein 3 (ACTR3) was over-expressed in the cytoplasm and nucleus of MNCs infiltrated to the islets in FT1DM-affected pancreas tissue. Signal transducer and activator of transcription 1-alpha/beta (STAT1) was highly expressed in islet endocrine cells and MNCs in FT1DM tissue ( Figure 2Q, R) . abstract: BACKGROUND: There are no reports of proteomic analyses of inflamed islets in type 1 diabetes. PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. RESULTS: Thirty-eight proteins were identified solely in FT1DM islets, most of which have not been previously linked to type 1 diabetes. Five protein-protein interacting clusters were identified, and the cellular localization of selected proteins was validated immunohistochemically. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Angiogenic (thymidine phosphorylase (TYMP)) and anti-angiogenic (tryptophan-tRNA ligase (WARS)) factors were identified in migrating CD8(+) T cells and CD68(+) macrophages. Proteins related to virus replication and cell proliferation, including probable ATP-dependent RNA helicase DEAD box helicase 5 (DDX5) and heterogeneous nuclear ribonucleoprotein H (HNRNPH1), were identified. The anti-apoptotic protein T-complex protein 1 subunit epsilon (CCT5), the anti-oxidative enzyme 6-phosphogluconate dehydrogenase (PDG), and the anti-viral and anti-apoptotic proteins serpin B6 (SERPINB6) and heat shock 70 kDa protein1-like (HSPA1L), were identified in FT1DM-affected islet cells. CONCLUSION: The identified FT1DM-characterizing proteins include those involved in aggressive beta cell destruction through massive immune cell migration and proteins involved in angiogenesis and islet vasculature bleeding, cell repair, and anti-inflammatory processes. Several target proteins for future type 1 diabetes interventions were identified. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199548/ doi: 10.1371/journal.pone.0107664 id: cord-352447-bc1pf272 author: Nishida, Yu title: Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio date: 2020-10-26 words: 3481.0 sentences: 197.0 pages: flesch: 47.0 cache: ./cache/cord-352447-bc1pf272.txt txt: ./txt/cord-352447-bc1pf272.txt summary: Despite conflicting results, the development of pouchitis in patients with UC, as reported in several studies, has been linked to various factors, including primary sclerosing cholangitis [2, 4] , other extraintestinal manifestations of inflammatory bowel disease [4, 8, 9] , young age at UC diagnosis [4] , preoperative terminal ileal inflammation [10, 11] , extensive colonic disease [10], presence of interleukin-1 receptor antagonist gene allele 2 [12] , total steroid dose of > 10000 mg [13] , use of infliximab [14] , neutrophil percentage of > 65% [13] , and presence of perinuclear antineutrophil cytoplasmic antibodies [15, 16] . Therefore, our study aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in patients with UC. Third, we were unable to evaluate the reported pouchitis predictive factors, such as extraintestinal manifestations of inflammatory bowel disease, preoperative terminal ileal inflammation, the presence of interleukin-1 receptor antagonist gene allele 2, total steroid dose of >10000 mg, or presence of perinuclear antineutrophil cytoplasmic antibodies owing to the retrospective design of the study. abstract: OBJECTIVES: Pouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients. MATERIALS AND METHODS: UC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment weighting (IPTW). RESULTS: Forty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7–47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01–1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31–9.89; P = 0.01). CONCLUSIONS: NLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice. url: https://www.ncbi.nlm.nih.gov/pubmed/33104762/ doi: 10.1371/journal.pone.0241322 id: cord-263453-7v4y02j6 author: Nishiura, Hiroshi title: Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic date: 2009-08-31 words: 5350.0 sentences: 231.0 pages: flesch: 55.0 cache: ./cache/cord-263453-7v4y02j6.txt txt: ./txt/cord-263453-7v4y02j6.txt summary: We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Nevertheless, a much-used crude estimate of the cCFR, i.e. the ratio of the cumulative number of deaths to cases at calendar time t, tends to yield a biased (and mostly underestimated) cCFR due to the time-delay from onset to death [8] ; similar estimates of such a biased cCFR for severe acute respiratory syndrome (SARS) have shown how such estimates can vary substantially as an epidemic progresses, stabilizing only in the later stages of the outbreak [8, 9] . doi:10.1371/journal.pone.0006852.g003 Figure 6 shows the time course of biased cCFR estimates in the USA and Canada based on the reporting date of confirmed cases and deaths to the World Health Organization. abstract: BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16–4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public. url: https://doi.org/10.1371/journal.pone.0006852 doi: 10.1371/journal.pone.0006852 id: cord-001748-7e8px4vx author: Nobach, Daniel title: Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews date: 2015-08-27 words: 4873.0 sentences: 249.0 pages: flesch: 47.0 cache: ./cache/cord-001748-7e8px4vx.txt txt: ./txt/cord-001748-7e8px4vx.txt summary: The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). In animals caught in 2013 (group 1: female #2, male #5, female #6), after an adaption phase of one month, samples of saliva, lacrimal fluid, skin surface, urine and excrements from the BoDV-1-infected shrews were taken weekly over a period of 4 weeks as necessary veterinary care. The five other shrews did not exhibit any evidence for BoDV-1-infection, neither infectious virus nor viral RNA was detected at any time point investigated. Current data from living shrews provide reliable evidence that natural BoDV-1-infection in these animals is indeed clinically inconspicuous over a long time period as already previously assumed [15, 18] despite persistent infection with shedding of infectious virus via various sites. Distribution of Borna Disease Virus Antigen and RNA in Tissues of naturally infected Bicolored White-Toothed Shrews, Crocidura leucodon, supporting their role as Reservoir Host Species abstract: BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed. The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white-toothed shrews were trapped and revealed to be naturally infected with BoDV-1. All shrews were monitored in captivity in a long-term study over a time period up to 600 days that differed between the individual shrews. Interestingly, all six animals showed an asymptomatic course of infection despite virus shedding via various routes indicating a highly adapted host-pathogen interaction. Infectious virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal fluid and faeces, both during the first 8 weeks of the investigation period and for long time shedding after more than 250 days in captivity. CONCLUSIONS: The various ways of shedding ensure successful virus maintenance in the reservoir population but also transmission to accidental hosts such as horses and sheep. Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host and pathogen factors responsible for persistent viral co-existence in reservoir species while maintaining their physiological integrity despite high viral load in many organ systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552160/ doi: 10.1371/journal.pone.0137018 id: cord-306466-y4yg42p8 author: Nofal, Ahmed Maged title: Who complies with COVID-19 transmission mitigation behavioral guidelines? date: 2020-10-08 words: 5717.0 sentences: 292.0 pages: flesch: 36.0 cache: ./cache/cord-306466-y4yg42p8.txt txt: ./txt/cord-306466-y4yg42p8.txt summary: Particularly, we examine if major personality traits (i.e. conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability) [12] , yield differences in the tendency of people to comply with 21 implemented COVID-19 transmission mitigation behavioral guidelines (see S1 Appendix). However, there has been no work examining the influence of personality traits, such as the big five (i.e. conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability) on the tendency of people to comply with COVID-19 transmission mitigation behavioral guidelines. Connecting literatures of emotional responses to COVID-19 messages, and personalized/tailored communication, we believe that this research not only supports prior work in highlighting the importance of pro-social messages, but also the importance of knowing the specific personality traits that may make individuals less likely to comply with COVID-19 transmission mitigation behavioral guidelines. First, drawing from research on persuasive mass communication [e.g., 19] , we aim to demonstrate if personality traits, specifically, conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability, relate to the tendency of people to comply with COVID-19 transmission mitigation behavioral guidelines. abstract: During the past 6 months, the world has lost almost 950,000 lives because of the outbreak of COVID-19, with more than 31 million individuals diagnosed with COVID-19 worldwide. In response, lockdowns, and various other policies have been implemented. Unfortunately, many individuals are violating those policies and governments have been urging people to comply with the behavioral guidelines. In this paper, we argue that personality traits need to be considered to understand and encourage more effective public compliance with COVID 19 transmission mitigation behavioral guidelines. Using a sample of 8,548 individuals from Japan, we show that certain personality traits are related to the tendency to comply with COVID-19 transmission mitigation behavioral guidelines. We emphasize the importance of understanding why people respond differently to the same authority’s messages and provide actionable insights for government policy makers and those who implement policies. url: https://doi.org/10.1371/journal.pone.0240396 doi: 10.1371/journal.pone.0240396 id: cord-339327-4422s317 author: Norris, Susan L. title: An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks date: 2018-05-30 words: 3690.0 sentences: 169.0 pages: flesch: 43.0 cache: ./cache/cord-339327-4422s317.txt txt: ./txt/cord-339327-4422s317.txt summary: For guidelines, the methods for development were incompletely reported; WHO''s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. For guidelines, the methods for development were incompletely reported; WHO''s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. WHO quality standards dictate that guidelines must address a critical public health problem, use transparent and explicit processes minimizing potential sources of bias such as conflicts of interest, include diverse perspectives in the guideline development group, reflect the current state of the evidence, and provide a clear link between the evidence and recommendations taking into consideration the balance of benefits and harms of interventions and other important considerations [2] . abstract: BACKGROUND: The production of high-quality guidelines in response to public health emergencies poses challenges for the World Health Organization (WHO). The urgent need for guidance and the paucity of structured scientific data on emerging diseases hinder the formulation of evidence-informed recommendations using standard methods and procedures. OBJECTIVES: In the context of the response to recent public health emergencies, this project aimed to describe the information products produced by WHO and assess the quality and trustworthiness of a subset of these products classified as guidelines. METHODS: We selected four recent infectious disease emergencies: outbreaks of avian influenza A—H1N1 virus (2009) and H7N9 virus (2013), Middle East respiratory syndrome coronavirus (MERS-CoV) (2013), and Ebola virus disease (EVD) (2014 to 2016). We analyzed the development and publication processes and evaluated the quality of emergency guidelines using AGREE-II. RESULTS: We included 175 information products of which 87 were guidelines. These products demonstrated variable adherence to WHO publication requirements including the listing of external contributors, management of declarations of interest, and entry into WHO’s public database of publications. For guidelines, the methods for development were incompletely reported; WHO’s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. CONCLUSIONS: Our study suggests that WHO guidelines produced in the context of a public health emergency can be improved upon, helping to assure the trustworthiness and utility of WHO information products in future emergencies. url: https://doi.org/10.1371/journal.pone.0198125 doi: 10.1371/journal.pone.0198125 id: cord-257217-f9sdt7ax author: Nunes, Marta C. title: Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children date: 2014-02-03 words: 4629.0 sentences: 215.0 pages: flesch: 43.0 cache: ./cache/cord-257217-f9sdt7ax.txt txt: ./txt/cord-257217-f9sdt7ax.txt summary: We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. The aim of this study was to identify the prevalence of hBoV, hRV, WUPyV, KIPyV, CoV-OC43, CoV-NL63, CoV-HKU1 and CoV-229E among HIV-infected and -uninfected children who were hospitalized for LRTI using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Very few viral aetiology studies have been conducted in Africa: in a Mozambican study of virus-associated acute respiratory infections (ARI) in infants with an estimated 3-5% HIV prevalence, the most frequently detected viruses were hRV (26%), influenza (15%) and adenovirus (14%) [27] . abstract: BACKGROUND: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. RESULTS: At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and –uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than –uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV–uninfected children). CONCLUSIONS: We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI. url: https://doi.org/10.1371/journal.pone.0086448 doi: 10.1371/journal.pone.0086448 id: cord-003024-17f1evh3 author: Nunes, Márcio Roberto Teixeira title: Revalidation and genetic characterization of new members of Group C (Orthobunyavirus genus, Peribunyaviridae family) isolated in the Americas date: 2018-05-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Group C serogroup includes members of the Orthobunyavirus genus (family Peribunyaviridae) and comprises 15 arboviruses that can be associated with febrile illness in humans. Although previous studies described the genome characterization of Group C orthobunyavirus, there is a gap in genomic information about the other viruses in this group. Therefore, in this study, complete genomes of members of Group C serogroup were sequenced or re-sequenced and used for genetic characterization, as well as to understand their phylogenetic and evolutionary aspects. Thus, our study reported the genomes of three new members in Group C virus (Apeu strain BeAn848, Itaqui strain BeAn12797 and Nepuyo strain BeAn10709), as well as re-sequencing of original strains of five members: Caraparu (strain BeAn3994), Madrid (strain BT4075), Murucutu (strain BeAn974), Oriboca (strain BeAn17), and Marituba (strain BeAn15). These viruses presented a typical genomic organization related to members of the Orthobunyavirus genus. Interestingly, all viruses of this serogroup showed an open reading frame (ORF) that encodes the putative nonstructural NSs protein that precedes the nucleoprotein ORF, an unprecedented fact in Group C virus. Also, we confirmed the presence of natural reassortment events. This study expands the genomic information of Group C viruses, as well as revalidates the genomic organization of viruses that were previously reported. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967719/ doi: 10.1371/journal.pone.0197294 id: cord-263464-fdosch11 author: Nuvey, Francis Sena title: Evaluation of the sentinel surveillance system for influenza-like illnesses in the Greater Accra region, Ghana, 2018 date: 2019-03-14 words: 4094.0 sentences: 227.0 pages: flesch: 47.0 cache: ./cache/cord-263464-fdosch11.txt txt: ./txt/cord-263464-fdosch11.txt summary: We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system''s attributes and its performance on set objectives. In collaboration with the Ghana Health Service (GHS) and the Ministry of Defense (MOD), it currently operates sentinel surveillance for influenza in 27 sites across all regions in Ghana with support from the U.S. Naval Medical Research Unit No. 3 (NAMRU-3), Centers for Disease Control and Prevention (CDC) and WHO [8] . We found that data on patients meeting the ILI case definition (S2 Table) from the sentinel sites are collected together with nasopharyngeal or oropharyngeal specimen. Our study provides evidence, that the ILI sentinel surveillance system in the Greater Accra Region (GAR), Ghana, is only partially meeting its objectives because it did not have thresholds for alerting the health system and does not perform antiviral resistance testing. abstract: BACKGROUND: Influenza-like Illness (ILI) is a medical diagnosis of possible influenza or another respiratory illness with a common set of symptoms. The deaths of four schoolchildren, during a pandemic influenza outbreak in December 2017 in Ghana, raised doubts about the ILI surveillance system’s performance. We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system’s attributes and its performance on set objectives. METHODS: CDC guidelines were used to evaluate the data of the ILI surveillance system between 2013 and 2017. We interviewed the surveillance personnel on the system’s description and operation. Additionally, routinely entered ILI data from the National Influenza Center provided by the six sentinel sites in Accra was extracted. We sampled and reviewed 120 ILI case-investigation forms from these sites. Surveillance activities were examined on system’s performance indicators, each being scored on a scale of 1 to 3 (poorest to best performance). RESULTS: All population and age groups were under ILI surveillance over the period evaluated. Overall, 2948 suspected case-patients, including 392 (13.3%) children under-five were reported, with 219 being positive for influenza virus (Predictive value positive = 7.4%). The predominant influenza subtype was H3N2, recorded in 90 (41.1%) of positive case-patients. The system only met two out of its four objectives. None of the six sentinel sites consistently met their annual 260 suspected case-detection quota. Samples reached the laboratory on average 48 hours after collection and results were disseminated within 7 days. Of 120 case-investigation forms sampled, 91 (76.3%) were completely filled in. CONCLUSIONS: The ILI surveillance system in the Greater Accra region is only partially meeting its objectives. While it is found to be sensitive, representative and timely, the data quality was sub-optimal. We recommend the determination of thresholds for alert and outbreak detection and ensuring that sentinel sites meet their weekly case-detection targets. url: https://doi.org/10.1371/journal.pone.0213627 doi: 10.1371/journal.pone.0213627 id: cord-329468-vjsurl60 author: Okino, Cintia Hiromi title: Early immune responses and development of pathogenesis of avian infectious bronchitis viruses with different virulence profiles date: 2017-02-15 words: 5853.0 sentences: 261.0 pages: flesch: 48.0 cache: ./cache/cord-329468-vjsurl60.txt txt: ./txt/cord-329468-vjsurl60.txt summary: This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken. In this study, we found a suppressive effect on expression of some early innate and adaptive cell-mediated immune genes in the primary site of virus replication (trachea) from chickens infected with one of the tested IBV isolates (B). abstract: Avian infectious bronchitis virus (IBV) primarily replicates in epithelial cells of the upper respiratory tract of chickens, inducing both morphological and immune modulatory changes. However, the association between the local immune responses induced by IBV and the mechanisms of pathogenesis has not yet been completely elucidated. This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. We detected a suppressive effect on the early activation of TLR7 pathway, followed by lower expression levels of inflammatory related genes induced by challenge with the IBV B isolate when compared to the challenge with to the IBV A isolate. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. Increased viral load and a higher percentage of birds with relevant lesions were observed in both tracheal and renal samples from chickens exposed to challenge with IBV B isolate. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken. url: https://www.ncbi.nlm.nih.gov/pubmed/28199419/ doi: 10.1371/journal.pone.0172275 id: cord-002222-rgqwm3vb author: Olarte-Castillo, Ximena A. title: Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study date: 2016-09-23 words: 7544.0 sentences: 339.0 pages: flesch: 46.0 cache: ./cache/cord-002222-rgqwm3vb.txt txt: ./txt/cord-002222-rgqwm3vb.txt summary: By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. A total of 20 partial RdRp gene sequences (16 from spotted hyenas, 3 from African lions and 1 from bat-eared foxes) were obtained and used for the phylogenetic analysis, together with publically available sequence data from 25 representatives of all sapovirus genogroups, divergent unclassified sapoviruses, and other genera in the Caliciviridae family, including Norovirus and Vesivirus. abstract: The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035092/ doi: 10.1371/journal.pone.0163548 id: cord-340627-xyvzgkxl author: Ornaghi, Sara title: Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy date: 2020-09-15 words: 3804.0 sentences: 228.0 pages: flesch: 51.0 cache: ./cache/cord-340627-xyvzgkxl.txt txt: ./txt/cord-340627-xyvzgkxl.txt summary: title: Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy Initially, a targeted SARS-CoV-2 screening approach triggered by a positive questionnaire and based on RT-PCR testing of nasopharyngeal swabs was used in women with hospital admission after accessing the Emergency Department. On April 8 th , we changed our policy and started testing all women for SARS-CoV-2 infection independent of the type of hospital admission and the questionnaire result, in agreement with a disposition of the Lombardy Region Health Care Authority. Our study investigated the accuracy of a comprehensive questionnaire thoroughly assessing obstetric patients upon hospital admission to identify cases suspected for SARS-CoV-2 infection. Our data show that thorough assessment of obstetric patients upon hospital admission by means of an exhaustive questionnaire is feasible and effective in discriminating women at low risk of SARS-CoV-2 infection in the context of both a targeted and a universal screening abstract: OBJECTIVES: 1. To assess the performance of an extended questionnaire in identifying cases of SARS-CoV-2 infection among obstetric patients. 2. To evaluate the rate of infection among healthcare workers involved in women’s care. STUDY DESIGN: A prospective cohort study of obstetric patients admitted to MBBM Foundation and Buzzi Hospital (Lombardy, Northern Italy) from March 16(th) to May 22(nd), 2020. Women were screened on admission by a questionnaire investigating major and minor symptoms of infection and high-risk contacts in the last 14 days. SARS-CoV-2 assessment was performed by RT-PCR on nasopharyngeal swabs. Till April 7(th), a targeted SARS-CoV-2 testing triggered by a positive questionnaire was used; from April 8(th), a universal testing approach was implemented. RESULTS: There were 1,177 women screened by the questionnaire, which yielded a positive result in 130 (11.0%) cases. SARS-CoV-2 RT-PCR was performed in 865 (73.5%) patients, identifying 51 (5.9%) infections. During the first period, there were 29 infected mothers, 4 (13.8%) of whom had a negative questionnaire. After universal testing implementation, there were 22 (3%, 95% CI 1.94% - 4.04%) infected mothers, 13 (59.1%) of whom had a negative questionnaire; rate of infection among asymptomatic women was 1.9%. Six of the 17 SARS-CoV-2-positive women with a negative questionnaire reported symptoms more than 14 but within 30 days before admission. Isolated olfactory or taste disorders were identified in 15.7% of infected patients. Rate of infection among healthcare workers was 5.8%. CONCLUSIONS: An exhaustive triage questionnaire can effectively discriminate women at low risk of SARS-CoV-2 infection in the context of a targeted and a universal viral testing approach. In 15.7% of infected women, correct classification as a suspected case of infection was due to investigation of olfactory and taste disorders. Extension of the assessed time-frame to 30 days may be worth considering to increase the questionnaire’s performance. url: https://www.ncbi.nlm.nih.gov/pubmed/32931524/ doi: 10.1371/journal.pone.0239173 id: cord-277306-r8jki3x4 author: Osborne, Christina title: Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans date: 2011-05-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted. url: https://doi.org/10.1371/journal.pone.0019156 doi: 10.1371/journal.pone.0019156 id: cord-001359-c1uom5f7 author: Oslund, Karen L. title: Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells date: 2014-07-17 words: 4567.0 sentences: 290.0 pages: flesch: 53.0 cache: ./cache/cord-001359-c1uom5f7.txt txt: ./txt/cord-001359-c1uom5f7.txt summary: In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level. In this study, we demonstrate synergistic induction of CXCL10 in well differentiated primary human bronchial epithelial (HBE) cells following influenza virus infection and the treatment with IFN c. As shown in Fig. 1A , well differentiated HBE cells demonstrated significant synergistic induction of CXCL10 mRNA following infection with the MEM influenza virus and treatment with IFN c. These results demonstrate that influenza virus in combination with IFN c synergistically induce CXCL10 mRNA and protein production from primary human airway epithelial cells. abstract: Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA) both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR) signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn’t affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102466/ doi: 10.1371/journal.pone.0100978 id: cord-312002-4qhvljpv author: Pacheco-Barrios, Kevin title: COVID-19 pandemic and Farr’s law: A global comparison and prediction of outbreak acceleration and deceleration rates date: 2020-09-17 words: 5434.0 sentences: 252.0 pages: flesch: 56.0 cache: ./cache/cord-312002-4qhvljpv.txt txt: ./txt/cord-312002-4qhvljpv.txt summary: However, a 150-year old epidemics law promulgated by William Farr might be useful as a simple arithmetical model (percent increase [R1] and acceleration [R2] of new cases and deaths) to provide a first sight of the epidemic behavior and to detect regions with high predicted dynamics. In this study, we will model COVID-19 current data (until April 10, 2020) of new confirmed cases and deaths, from 210 countries as to test the assumptions of the 1840 Farr''s law, to describe the epidemic dynamics, and also to make predictions to identify areas with high dynamic and suggest preparation and actions of health system in those regions. abstract: The COVID-19 outbreak has forced most of the global population to lock-down and has put in check the health services all over the world. Current predictive models are complex, region-dependent, and might not be generalized to other countries. However, a 150-year old epidemics law promulgated by William Farr might be useful as a simple arithmetical model (percent increase [R1] and acceleration [R2] of new cases and deaths) to provide a first sight of the epidemic behavior and to detect regions with high predicted dynamics. Thus, this study tested Farr’s Law assumptions by modeling COVID-19 data of new cases and deaths. COVID-19 data until April 10, 2020, was extracted from available countries, including income, urban index, and population characteristics. Farr’s law first (R(1)) and second ratio (R(2)) were calculated. We constructed epidemic curves and predictive models for the available countries and performed ecological correlation analysis between R(1) and R(2) with demographic data. We extracted data from 210 countries, and it was possible to estimate the ratios of 170 of them. Around 42·94% of the countries were in an initial acceleration phase, while 23·5% already crossed the peak. We predicted a reduction close to zero with wide confidence intervals for 56 countries until June 10 (high-income countries from Asia and Oceania, with strict political actions). There was a significant association between high R(1) of deaths and high urban index. Farr’s law seems to be a useful model to give an overview of COVID-19 pandemic dynamics. The countries with high dynamics are from Africa and Latin America. Thus, this is a call to urgently prioritize actions in those countries to intensify surveillance, to re-allocate resources, and to build healthcare capacities based on multi-nation collaboration to limit onward transmission and to reduce the future impact on these regions in an eventual second wave. url: https://www.ncbi.nlm.nih.gov/pubmed/32941485/ doi: 10.1371/journal.pone.0239175 id: cord-001460-eo2bxxbq author: Padhi, Siladitya title: Atomistic Detailed Mechanism and Weak Cation-Conducting Activity of HIV-1 Vpu Revealed by Free Energy Calculations date: 2014-11-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The viral protein U (Vpu) encoded by HIV-1 has been shown to assist in the detachment of virion particles from infected cells. Vpu forms cation-specific ion channels in host cells, and has been proposed as a potential drug target. An understanding of the mechanism of ion transport through Vpu is desirable, but remains limited because of the unavailability of an experimental structure of the channel. Using a structure of the pentameric form of Vpu – modeled and validated based on available experimental data – umbrella sampling molecular dynamics simulations (cumulative simulation time of more than 0.4 µs) were employed to elucidate the energetics and the molecular mechanism of ion transport in Vpu. Free energy profiles corresponding to the permeation of Na(+) and K(+) were found to be similar to each other indicating lack of ion selection, consistent with previous experimental studies. The Ser23 residue is shown to enhance ion transport via two mechanisms: creating a weak binding site, and increasing the effective hydrophilic length of the channel, both of which have previously been hypothesized in experiments. A two-dimensional free energy landscape has been computed to model multiple ion permeation, based on which a mechanism for ion conduction is proposed. It is shown that only one ion can pass through the channel at a time. This, along with a stretch of hydrophobic residues in the transmembrane domain of Vpu, explains the slow kinetics of ion conduction. The results are consistent with previous conductance studies that showed Vpu to be a weakly conducting ion channel. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231112/ doi: 10.1371/journal.pone.0112983 id: cord-013333-7jx4t0ol author: Palloni, Alberto title: Impacts of the 1918 flu on survivors' nutritional status: A double quasi-natural experiment date: 2020-10-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Robust empirical evidence supports the idea that embryonic and, more generally, intrauterine disruptions induced by the 1918-flu pandemic had long-term consequences on adult health status and other conditions. In this paper we assess the 1918-flu long-term effects not just of in utero exposure but also during infancy and early childhood. A unique set of events that took place in Puerto Rico during 1918–1919 generated conditions of a “double quasi-natural experiment”. We exploit these conditions to empirically identify effects of exposure to the 1918 flu pandemic and those of the devastation left by an earthquake-tsunami that struck the island in 1918. Because the earthquake-tsunami affected mostly the Western coast of the island whereas early (in utero and postnatal) exposure to the flu was restricted to those born in the interval 1917–1920, we use geographic variation to identify the effects of the quake and timing of birth variation to identify those of the flu. We benefit from availability of information on markers of nutritional status in a nationally representative sample of individuals aged 75 and older in 2002. We make two contributions. First, unlike most fetal-origins research that singles out early nutritional status as a determinant of adult health, we hypothesize that the 1918 flu damaged the nutritional status of adult survivors who, at the time of the flu, were in utero or infants. Second, we target markers of nutritional status largely set when the adult survivors were infants and young children. Estimates of effects of the pandemic are quite large mostly among females and those who were exposed to the earthquake-tsunami. Impacts of the flu in areas less affected by the earthquake are smaller but do vary by area flu severity. These findings constitute empirical evidence supporting the conjecture that effects of the 1918 flu and/or the earthquake are associated not just with disruption experienced during the fetal period but also postnatally. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575088/ doi: 10.1371/journal.pone.0232805 id: cord-310947-aqau2n7q author: Pan, Ji''An title: Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date: 2008-10-01 words: 6821.0 sentences: 302.0 pages: flesch: 43.0 cache: ./cache/cord-310947-aqau2n7q.txt txt: ./txt/cord-310947-aqau2n7q.txt summary: In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. However, the viral protein interaction maps have been generated until now only for a limited number of viruses, including T7 bacteriophage [1] , vaccinia virus [2] , potato virus A [3] , pea seed-borne mosaic virus [3] , wheat steak mosaic virus [4] , hepatitis C virus [5, 6] , porcine teschovirus [7] , Kaposi sarcoma-associated herpesvirus [8] , and very recently severe acute respiratory syndrome coronavirus (SARS-CoV) [9, 10] . abstract: Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/18827877/ doi: 10.1371/journal.pone.0003299 id: cord-003270-vu9b5a14 author: Panahi, Heidar Ali title: A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins date: 2018-10-24 words: 7005.0 sentences: 377.0 pages: flesch: 50.0 cache: ./cache/cord-003270-vu9b5a14.txt txt: ./txt/cord-003270-vu9b5a14.txt summary: In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens'' analyses were carried out successively by different tools. For the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and for the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens analyses were considered. In this study, the binding ability of the first step selected peptides to human and mouse MHC molecules, was analyzed by CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock/) server. In cancer immunotherapy, the CTL-mediated responses play the central role in eradication of malignant cells, and the binding of epitopes to MHC-I molecules is an essential step for antigen presentation to CTLs. Thus, in this study, predicted epitopes were primarily selected by their MHC-I binding and processing scores. abstract: Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues. A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide. Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them. Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response. Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers. Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study. For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes. In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools. Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach. These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers. Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200245/ doi: 10.1371/journal.pone.0205933 id: cord-279259-eu80ccm6 author: Pandey, Aseem title: Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine date: 2012-03-14 words: 4876.0 sentences: 249.0 pages: flesch: 47.0 cache: ./cache/cord-279259-eu80ccm6.txt txt: ./txt/cord-279259-eu80ccm6.txt summary: The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. To determine the level of vector immunity that can be tolerated without significantly affecting the vaccine efficacy, we primed groups of mice with varying doses of wild type (WT) HAd5 via intranasal (i.n.) or intramuscular (i.m.) route of inoculation to generate different levels of HAd5-neutralizing antibody titers. Further increase in the level of vector-specific neutralizing antibody titer to 3040 by i.m. priming with HAd5 only provided partial protection even in the groups receiving a high vaccine dose. abstract: The prevalence of preexisting immunity to adenoviruses in the majority of the human population might adversely impact the development of adaptive immune responses against adenovirus vector-based vaccines. To address this issue, we primed BALB/c mice either intranasally (i.n.) or intramuscularly (i.m.) with varying doses of wild type (WT) human adenovirus subtype 5 (HAd5). Following the development of immunity against HAd5, we immunized animals via the i.n. or i.m. route of inoculation with a HAd vector (HAd-HA-NP) expressing the hemagglutinin (HA) and nucleoprotein (NP) of A/Vietnam/1203/04 (H5N1) influenza virus. The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. A further increase in the priming dose to 10(9) p.f.u. allowed only partial protection. These results suggest possible strategies to overcome the variable levels of human immunity against adenoviruses, leading to better utilization of HAd vector-based vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/22432020/ doi: 10.1371/journal.pone.0033428 id: cord-270408-4qqyb8sd author: Pane, Masdalina title: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings date: 2013-08-21 words: 3456.0 sentences: 182.0 pages: flesch: 52.0 cache: ./cache/cord-270408-4qqyb8sd.txt txt: ./txt/cord-270408-4qqyb8sd.txt summary: title: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. In the last two decades, the mortality rate of Indonesian pilgrims, excluding years in which disasters such as stampedes occurred, fluctuated between 200-380 deaths per 100,000 persons during the ten-week Hajj period [5] . The cause of death based on this verbal autopsy method was then recorded in the database and compared to that reported by the hospital or flight doctor death certificate. A greater proportion of deaths were attributed to cardiovascular disease by the flight doctor or hospital death certificate (66%) compared to the cause of death ascertained using the verbal autopsy method (49%, p<0.001). Based on both the death certificates and verbal autopsy categories, cardiovascular disease was the leading cause of Indonesian pilgrim mortality in 2008. abstract: BACKGROUND: Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. METHODS: Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy. RESULTS: In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p<0.001). Significantly more deaths had ill-defined cause based on verbal autopsy method (p<0.001). CONCLUSIONS: Despite pre-departure health screening and other medical services, Indonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting. url: https://doi.org/10.1371/journal.pone.0073243 doi: 10.1371/journal.pone.0073243 id: cord-316703-8kxx3034 author: Parera, Mariona title: Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date: 2012-08-01 words: 4193.0 sentences: 220.0 pages: flesch: 52.0 cache: ./cache/cord-316703-8kxx3034.txt txt: ./txt/cord-316703-8kxx3034.txt summary: The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The target specificity for the MAVS and TRIF cleavage sites was tested by coexpressing them with CHV or HCV NS3/4A protease constructs. coli cells coexpressing the lambda cI repressor with either MAVS or TRIF cleavage site and a CHV NS3/4A construct, lambda phage replicated up to 2,000-fold more efficiently than in cells expressing a CHV protease variant that included a substitution in catalytic residue S139 ( Fig. 3A and 3B). In this study, we tested the ability of CHV NS3/4A protease to specifically cleave the human adaptor proteins MAVS and TRIF. Canine orthologs of human MAVS and TRIF differ in sequence at the cleavage site processed by HCV NS3/4A protease; therefore, they were not tested in this study. abstract: Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV. url: https://www.ncbi.nlm.nih.gov/pubmed/22870331/ doi: 10.1371/journal.pone.0042481 id: cord-261410-kb91eagd author: Park, Ji Young title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel date: 2017-01-23 words: 3504.0 sentences: 205.0 pages: flesch: 43.0 cache: ./cache/cord-261410-kb91eagd.txt txt: ./txt/cord-261410-kb91eagd.txt summary: The clinical features of respiratory adenoviral infection among military personnel were described previously; however, HAdV pneumonia in immunocompetent individuals and risk factors of disease progression to severe pneumonia or acute respiratory failure have not been well studied. All military trainees or active duty members, but not officers, were eligible for enrollment if they were !18 years old and had been admitted to the study hospital for pneumonia, defined by acute respiratory symptoms (fever, cough, sputum, dyspnea, and pleuritic chest pain) and pulmonary infiltrates on chest X-rays or computed tomography (CT) scans. Most HAdV pneumonia patients were basic military trainees or personnel who had recently completed training; active duty service personnel were not usually affected, even during outbreak peaks. Our results show that an outbreak of HAdV pneumonia occurred in Korean military training centers and indicate that emergent-type HAdV-55 infections might have caused the outbreak. abstract: BACKGROUND: The number of pneumonia patients increased suddenly in Korean military hospitals in late December 2014, indicating the urgent need for an epidemic outbreak investigation. METHODS: We conducted a prospective study of pneumonia etiology among immunocompetent young adults admitted to Daejeon Armed Forces hospital. Patient blood and sputum samples were subjected to conventional culture, serology, and polymerase chain reaction tests for respiratory viruses and atypical pathogens. RESULTS: From January to May 2015, we enrolled 191 (189 male) adults with pneumonia; the mean age was 20.1 ± 1.3 years. Five patients had severe pneumonia, and one died. Pathogenic human adenoviruses were most common (HAdV, 153/191 [80.1%]), indicating a HAdV pneumonia outbreak. Genotyping of 35 isolates indicated that 34 matched HAdV-55 and one matched HAdV-2. HAdV pneumonia infected recruit trainees most frequently. High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia. Only 12% of HAdV pneumonia patients displayed leukocytosis, whereas febrile leukopenia (62.7%) and thrombocytopenia (41%) were commonly observed. HAdV pneumonia patient chest CT scans displayed ground glass opacity (with or without septal thickness) with consolidation in 50.0% of patients. CONCLUSIONS: An outbreak of HAdV respiratory infection occurred at the Korean military training center. HAdV pneumonia exhibited specific laboratory and clinical features, and although most patients were cured without complication, some progressed to respiratory failure and fatality. Therefore, HAdV vaccine should be provided to military trainees in Korea. url: https://www.ncbi.nlm.nih.gov/pubmed/28114362/ doi: 10.1371/journal.pone.0170592 id: cord-001254-y2knt8g0 author: Parkhomenko, Taisiya A. title: Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis date: 2014-04-15 words: 6739.0 sentences: 325.0 pages: flesch: 50.0 cache: ./cache/cord-001254-y2knt8g0.txt txt: ./txt/cord-001254-y2knt8g0.txt summary: Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Finally, the relative concentration of total anti-DNA Abs correlated with the relative specific IgG DNase activity better in the sera (CC = +0.51; columns 6 and 12) than in CSF (CC = + 0.11; columns 5 and 11) (Tables 2 and 3 ). abstract: It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988009/ doi: 10.1371/journal.pone.0093001 id: cord-318008-4s9eoae3 author: Parsons Leigh, Jeanna title: A national cross-sectional survey of public perceptions of the COVID-19 pandemic: Self-reported beliefs, knowledge, and behaviors date: 2020-10-23 words: 5682.0 sentences: 268.0 pages: flesch: 48.0 cache: ./cache/cord-318008-4s9eoae3.txt txt: ./txt/cord-318008-4s9eoae3.txt summary: We assessed self-reported public perceptions related to COVID-19 including, beliefs (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) to understand perspectives in Canada and to inform future public health initiatives. We conducted a national survey of adults residing in Canada to gain a better understanding of public perceptions in several important domains-beliefs (e.g. severity of pandemic, concerns, impact on health), knowledge acquisition (e.g. sources, topics), and behaviors (e.g. isolation and physical distancing)-related to the COVID-19 pandemic. Our study provides a national cross-sectional description of public perceptions, knowledge and behaviors related to COVID-19 in the context of the evolving pandemic, adding to survey data published early in the outbreak [16] [17] [18] . In our survey, respondents from Ontario and Québec reported the least amount of trust in Canadian government and news sources and these were also the same provinces with the highest number of confirmed COVID-19 cases in Canada (32% and 51%, respectively). abstract: INTRODUCTION: Efforts to mitigate the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing Corona Virus Disease-19 (COVID-19) have largely relied on broad compliance with public health recommendations yet navigating the high volume of evolving information can be challenging. We assessed self-reported public perceptions related to COVID-19 including, beliefs (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) to understand perspectives in Canada and to inform future public health initiatives. METHODS: We administered a national online survey aiming to obtain responses from 2000 adults in Canada. Respondent sampling was stratified by age, sex, and region. We used descriptive statistics to summarize responses and tested for regional differences using chi-squared tests, followed by weighted logistic regression. RESULTS: We collected 1,996 eligible questionnaires between April 26(th) and May 1(st), 2020. One-fifth (20%) of respondents knew someone diagnosed with COVID-19, but few had tested positive themselves (0.6%). Negative impacts of pandemic conditions were evidenced in several areas, including concerns about healthcare (e.g. sufficient equipment, 52%), pandemic stress (45%), and worsening social (49%) and mental/emotional (39%) health. Most respondents (88%) felt they had good to excellent knowledge of virus transmission, and predominantly accessed (74%) and trusted (60%) Canadian news television, newspapers/magazines, or non-government news websites for COVID-19 information. We found high compliance with distancing measures (80% reported self-isolating or always physical distancing). We identified associations between region and self-reported beliefs, knowledge, and behaviors related to COVID-19. DISCUSSION: We found that information about COVID-19 is largely acquired through domestic news sources, which may explain high self-reported compliance with prevention measures. The results highlight the broader impact of a pandemic on the general public’s overall health and wellbeing, outside of personal infection. The study findings should be used to inform public health communications during COVID-19 and future pandemics. url: https://doi.org/10.1371/journal.pone.0241259 doi: 10.1371/journal.pone.0241259 id: cord-311531-wezrs7gc author: Parčina, Marijo title: Multicenter evaluation of the QIAstat Respiratory Panel—A new rapid highly multiplexed PCR based assay for diagnosis of acute respiratory tract infections date: 2020-03-12 words: 3584.0 sentences: 179.0 pages: flesch: 48.0 cache: ./cache/cord-311531-wezrs7gc.txt txt: ./txt/cord-311531-wezrs7gc.txt summary: The QIAstat Respiratory Panel(®) assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. The FilmArray RP is a multiplex sample-to-answer PCR panel that tests for 20 viral and bacterial pathogens on nasopharyngeal swabs in UTM at a time. Before resolution by discrepancy testing, QIAstat RP and FilmArray RP agreed on the detection of 376 pathogens in the 445 samples (Table 3) . After resolution by discrepancy testing on the Allplex RP, a total of 402 pathogen results were considered as true positive (Table 4) , of which QIAstat RP detected 394, for an overall PPA of 98.0% (95%CI 96.0%-99.1%). abstract: Acute respiratory tract infections (ARTI), including the common cold, pharyngitis, sinusitis, otitis media, bronchiolitis and pneumonia are the most common diagnoses among patients seeking medical care in western countries, and account for most antibiotic prescriptions. While a confirmed and fast ARTI diagnosis is key for antibiotic prescribing, empiric antimicrobial treatment remains common, because viral symptoms are often clinically similar and difficult to distinguish from those caused by bacteria. As a result, inappropriate antibiotic prescriptions are high and in certain settings likely higher than the commonly estimated 30%. The QIAstat Respiratory Panel(®) assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. We describe the first multicenter study of 445 respiratory samples, collected through the 2016–2017 and 2018 respiratory seasons, with performance compared against BioFire FilmArray RP v1.7 and discrepancy testing by Seegene Allplex RP. The QIAstat RP demonstrated a positive percentage of agreement of 98.0% (95% CI: 96.0–99.1%) and a negative percentage agreement of 99.8% (95% CI: 99.6–99.9%). With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship may potentially be achieved. url: https://doi.org/10.1371/journal.pone.0230183 doi: 10.1371/journal.pone.0230183 id: cord-048477-ze511t38 author: Patel, Mahomed S. title: General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries date: 2008-05-28 words: 6918.0 sentences: 343.0 pages: flesch: 41.0 cache: ./cache/cord-048477-ze511t38.txt txt: ./txt/cord-048477-ze511t38.txt summary: The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. Although there is little evidence linking specific preparedness activities to effective system-wide responses to pandemic influenza [5, 6] , change management theories point to a need for dynamic partnerships between general practices and other ambulatory care services, hospitals and public health departments [10] . We aimed to develop a framework that will facilitate systematic planning for the general practice response to pandemic influenza and used it to appraise coverage of key elements in publicly available pandemic plans from Australia, England, USA, New Zealand and Canada. This calls for coordination across general practices and other ambulatory care services to ensure primary health care needs within the community are effectively monitored and addressed; with hospitals to avoid/delay hospitalisation and facilitate early discharge; and with public health units to share responsibilities for contact tracing, monitoring and treating people in home isolation or quarantine, dispensing of anti-viral medications, and participation in mass immunisations against pandemic strains of the virus (when these become available). abstract: BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386973/ doi: 10.1371/journal.pone.0002269 id: cord-348055-azlb1zy1 author: Patel, Mira C. title: Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus) date: 2016-11-04 words: 7758.0 sentences: 351.0 pages: flesch: 50.0 cache: ./cache/cord-348055-azlb1zy1.txt txt: ./txt/cord-348055-azlb1zy1.txt summary: To determine effect of the EV-D68 infection on the induction of an inflammatory response, we focused on the lung tissue and measured the expression of cotton rat mRNA for several chemokines, Type I and Type II interferons (IFNs), cytokines, and select IFN-inducible genes following VANBT infection. As there are no current animal models for EV-D68 and information regarding relevant disease-related outcomes from human cases is limited, we herein characterized EV-D68 infection in cotton rats by measuring viral load and vRNA (negative or total) in either nose or lung tissues until 4 days p.i., assessing mRNA expression of various chemokines, IFNs, and proinflammatory cytokines, and lung histology. Although the replication cycle of VANBT appeared to be short-lived, its profile of viral titer in the nose over time (showing clear virus eclipse at 4 h, rising quickly and reaching a peak by 10 h p.i.), and their differences with the output virus obtained after infection with different strains demonstrate that VANBT replicates in upper respiratory tract of cotton rats. abstract: In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus). Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49), along with the historical prototype Fermon strain (ATCC), to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA) upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines against EV-D68 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/27814404/ doi: 10.1371/journal.pone.0166336 id: cord-335245-1eksm537 author: Pattyn, Els title: HyperISGylation of Old World Monkey ISG15 in Human Cells date: 2008-06-18 words: 7011.0 sentences: 419.0 pages: flesch: 54.0 cache: ./cache/cord-335245-1eksm537.txt txt: ./txt/cord-335245-1eksm537.txt summary: Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Western blot analysis on total cell lysates containing b-ME confirmed ISGylation of UbcH10, H13 and H17 with AgmISG15 but not with HuISG15, as seen by a 15 kDa shift upon staining with anti-V5 Ab detecting the ectopic expressed UbcH proteins (Figure 3a ,b and Figure S2a ). Previous studies using Western blot analysis in HekT cells revealed Hu or MoISG15 conjugation to substrates such as UbcH13 only upon co-transfection of at least UbE1L -and generally also UbcH/M8or upon IFN stimulation. The effect of mutating HuISG15 residues situated near the predicted UbE1L interface and the different allelic variants on conjugation to UbcH proteins is shown in Figure 5a and S3a. As shown in Figure 5c , mutation of D133N and QIT31-33KIA in the HuISG15 N89D variant further enhanced its ISGylation in human HekT cells. abstract: BACKGROUND: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. PRINCIPAL FINDINGS: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. CONCLUSIONS: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator. url: https://www.ncbi.nlm.nih.gov/pubmed/18560560/ doi: 10.1371/journal.pone.0002427 id: cord-270683-982eqtog author: Pavel, Shaikh Terkis Islam title: Isolation and characterization of severe acute respiratory syndrome coronavirus 2 in Turkey date: 2020-09-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with severe respiratory illness emerged in Wuhan, China, in late 2019. The virus has been able to spread promptly across all continents in the world. The current pandemic has posed a great threat to public health concern and safety. Currently, there are no specific treatments or licensed vaccines available for COVID-19. We isolated SARS-CoV-2 from the nasopharyngeal sample of a patient in Turkey with confirmed COVID-19. We determined that the Vero E6 and MA-104 cell lines are suitable for supporting SARS-CoV-2 that supports viral replication, development of cytopathic effect (CPE) and subsequent cell death. Phylogenetic analyses of the whole genome sequences showed that the hCoV-19/Turkey/ERAGEM-001/2020 strain clustered with the strains primarily from Australia, Canada, England, Iran and Kuwait and that the cases in the nearby clusters were reported to have travel history to Iran and to share the common unique nucleotide substitutions. url: https://doi.org/10.1371/journal.pone.0238614 doi: 10.1371/journal.pone.0238614 id: cord-303490-rixuuytu author: Pazos, Michael A. title: Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice date: 2012-07-05 words: 6624.0 sentences: 385.0 pages: flesch: 43.0 cache: ./cache/cord-303490-rixuuytu.txt txt: ./txt/cord-303490-rixuuytu.txt summary: These data suggest that despite significant morbidity associated with fetal gestation, pregnant mice have an impaired ability to control influenza virus infection in both lethal and nonlethal models. We did not observe any significant differences in the absolute number of cells infiltrating lung tissue during infection with X31 in pregnant ( Figure 5A ) or E2-treated mice (data not shown). In order to determine whether emigration from the lung was impaired, we investigated the number of dendritic cells in the draining mediastinal lymph node at key time points of infection and found no significant differences between pregnant mice and their non-pregnant controls ( Figure 5B ), or between E2-pelleted mice and their placebo controls (data not shown). We found strongly reduced levels of CD86 expression on CD11c+ cells at critical early time points after infection in both pregnancy ( Figure 5C ) and estrogen-treatment ( Figure 5D ), suggesting a deficiency in proper DC maturation. abstract: Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype. url: https://doi.org/10.1371/journal.pone.0040502 doi: 10.1371/journal.pone.0040502 id: cord-013356-y6vceq2x author: Peace, Angela title: Orchard layout and plant traits influence fruit yield more strongly than pollinator behaviour and density in a dioecious crop date: 2020-10-23 words: 5864.0 sentences: 313.0 pages: flesch: 57.0 cache: ./cache/cord-013356-y6vceq2x.txt txt: ./txt/cord-013356-y6vceq2x.txt summary: The predictive model provides strategies for improving crop management, such as choosing cultivars which have their peak bloom on the same day, increasing the number of flowers with approximately 70% female flowers in the orchard, and placing enough hives to maintain more than 6 bees per 1000 flowers to optimize yield. We expected that male-female kiwifruit flower ratio and pollinator density will influence fruit yield, along with various parameters of pollinator behavior. The model explicitly tracks pollinators (parameterized here based on data from honey bees), with varying pollen loads as they preferentially visit male and female flowers, as well as A major model output measure is the predicted yield, which is defined as the number of female flowers per ha that became fully pollinated fruit. The model includes preference parameters for pollinators to remain on the type of flower they are visiting, based again on data from honey bee observations. abstract: Mutualistic plant-pollinator interactions are critical for the functioning of both non-managed and agricultural systems. Mathematical models of plant-pollinator interactions can help understand key determinants in pollination success. However, most previous models have not addressed pollinator behavior and plant biology combined. Information generated from such a model can inform optimal design of crop orchards and effective utilization of managed pollinators like western honey bees (Apis mellifera), and help generate hypotheses about the effects of management practices and cultivar selection. We expect that the number of honey bees per flower and male to female flower ratio will influence fruit yield. To test the relative importance of these effects, both singly and simultaneously, we utilized a delay differential equation model combined with Latin hypercube sampling for sensitivity analysis. Empirical data obtained from historical records and collected in kiwifruit (Actinidia chinensis) orchards in New Zealand were used to parameterize the model. We found that, at realistic bee densities, the optimal orchard had 65-75% female flowers, and the most benefit was gained from the first 6-8 bees/1000 flowers, with diminishing returns thereafter. While bee density significantly impacted fruit production, plant-based parameters-flower density and male:female flower ratio-were the most influential. The predictive model provides strategies for improving crop management, such as choosing cultivars which have their peak bloom on the same day, increasing the number of flowers with approximately 70% female flowers in the orchard, and placing enough hives to maintain more than 6 bees per 1000 flowers to optimize yield. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584186/ doi: 10.1371/journal.pone.0231120 id: cord-335880-m8gecsf0 author: Peci, Adriana title: Epidemiology of Enterovirus D68 in Ontario date: 2015-11-23 words: 4030.0 sentences: 218.0 pages: flesch: 52.0 cache: ./cache/cord-335880-m8gecsf0.txt txt: ./txt/cord-335880-m8gecsf0.txt summary: In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data. Data for this study included specimens submitted for EV-D68 testing at PHOL from patients who presented with respiratory symptoms in different health care settings across Ontario, from September 1, 2014 to October 31, 2014. Percent positivity and descriptions of EV-D68 cases by timing of specimen collection, age, sex, setting, symptoms and local health unit of residence were analysed at the patient level. Bivariate and multivariate logistic regression analyses were performed at the patient level to compare cases and controls in terms of age, sex, settings, symptoms and timing of specimen collection. abstract: In August 2014, children’s hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5–9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data. url: https://www.ncbi.nlm.nih.gov/pubmed/26599365/ doi: 10.1371/journal.pone.0142841 id: cord-337795-khqx4t4q author: Pellecchia, Umberto title: Social Consequences of Ebola Containment Measures in Liberia date: 2015-12-09 words: 5120.0 sentences: 277.0 pages: flesch: 50.0 cache: ./cache/cord-337795-khqx4t4q.txt txt: ./txt/cord-337795-khqx4t4q.txt summary: INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. To address these questions, this study was conducted to assess Liberian community perspectives on State-imposed Ebola public health and outbreak containment measures implemented in 2014 and 2015. The grids were organized according to three main themes: 1) general social perception of the epidemic and community''s reactions; 2) funerary and burial practices before and during the epidemic, and opinions on cremation; and 3) health-seeking behaviours and perception of quarantine. Forced quarantine of asymptomatic contacts of positive cases was the main State-imposed measure that transformed social perceptions and practices. Cremation of bodies and forced quarantine, as ways to quickly reduce transmission of Ebola outbreak for the benefit of the larger public, produced social dynamics of resistance in the same population that they wished to protect. abstract: INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. Enforced by State-related actors, these were promoted as the only method to curtail transmissions as soon as possible. However, as with other harsh measures witnessed by Liberian citizens, in many cases those measures elicited uncontrolled negative reactions within the communities (stigma; fear) that produced, in some cases, the opposite effect of that intended. METHODOLOGY: The research has been conducted in two phases, for a total of 8 weeks. Ethnography of local practices was carried out in 7 neighbourhoods in Monrovia and 5 villages in Grand Cape Mount County in Liberia. 45 Focus Group Discussions (432 participants) and 30 semi-structured interviews sustained the observing participation. Randomly selected people from different social layers were targeted. The principal investigator worked with the help of two local assistants. Perceptions and practices were both analysed. RESULTS: Participants stressed how cremation perpetuated the social breakdown that started with the isolation for the sickness. Socio-economical divides were created by inequitable management of the dead: those who could bribe the burial teams obtained a burial in a private cemetery or the use of Funeral Homes. Conversely, those in economic disadvantage were forced to send their dead for cremation. State-enforced quarantine, with a mandatory prohibition of movement, raised condemnation, strengthened stigmatization and created serious socio-economic distress. Food was distributed intermittently and some houses shared latrines with non-quarantined neighbours. Escapes were also recorded. Study participants narrated how they adopted local measures of containment, through local task forces and socially-rooted control of outsiders. They also stressed how information that was not spread built up rumours and suspicion. CONCLUSIONS: Populations experiencing an epidemic feel a high degree of social insecurity, in addition to the health hazards. Vertical and coercive measures increase mistrust and fear, producing a counter-productive effect in the containment of the epidemic. On the other hand, local communities show a will to be engaged and a high degree of flexibility in participating to the epidemic response. Efforts in the direction of awareness and community involvement could prove to be better strategy to control the epidemic and root the response on social participation. url: https://doi.org/10.1371/journal.pone.0143036 doi: 10.1371/journal.pone.0143036 id: cord-318845-w7q5o8wc author: Pendell, Dustin L. title: Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility date: 2015-06-26 words: 8168.0 sentences: 409.0 pages: flesch: 48.0 cache: ./cache/cord-318845-w7q5o8wc.txt txt: ./txt/cord-318845-w7q5o8wc.txt summary: This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. To assess the economic impacts of unintentional FMDv releases from NBAF, we follow [4, 7, [21] [22] to link supply shocks from an animal disease spread model with a multi-commodity, multi-market partial equilibrium model. To determine the total economic impact for a scenario, the changes in producer returns to capital and management and consumer welfare, government indemnification and non-indemnification expenditures, and the costs to the non-agricultural regional sector were summed together. Because the duration of the FMD outbreaks and number of animals culled and vaccinated are similar to the aerosol scenarios, the total economic impacts of the transference release scenarios are similar to impacts of an aerosol release, including the distribution of impacts by production types across time. abstract: This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. Using an economic framework that estimates the impacts to agricultural firms and consumers, quantifies costs to non-agricultural activities in the epidemiologically impacted region, and assesses costs of response to the government, we find the distribution of economic impacts to be very significant. Furthermore, agricultural firms and consumers bear most of the impacts followed by the government and the regional non-agricultural firms. url: https://www.ncbi.nlm.nih.gov/pubmed/26114546/ doi: 10.1371/journal.pone.0129134 id: cord-003712-mafz21no author: Perez Vidakovics, Maria Laura A. title: Junín virus induces autophagy in human A549 cells date: 2019-06-19 words: 6151.0 sentences: 333.0 pages: flesch: 47.0 cache: ./cache/cord-003712-mafz21no.txt txt: ./txt/cord-003712-mafz21no.txt summary: We found that JUNV infection induces an increment of the LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cells and the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosome formation. Either with the early autophagy inhibitor (3-MA) or the late inhibitor (BAF), the treatment pre or post-infection resulted in reduced expression of N and lower viral titre as compared to JUNV-infected cells that received no treatment (NT) (Fig 4B-4D) . In parallel, experiments performed adding Rap post-infection resulted in a similar increase in viral yields of JUNV, which indicates that the activation of autophagy benefits both viral entry/uncoating and later steps as assembling and viral budding (Fig 4) . When compared to control cells, an increase in the number of mCherry puncta following rapamycin treatment was observed, indicating promoted autophagy and fusion between autophagosomes and acidic compartments (Fig 5C) . abstract: Autophagy, a highly regulated degradative process that promotes cellular homeostasis, is increasingly recognised as a fundamental component of the cellular response against viral infection. In this study, we investigated the role of autophagy during Junín virus (JUNV) multiplication using human A549 cells. We found that JUNV infection induces an increment of the LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cells and the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosome formation. JUNV infection also induced the degradation of the autophagy receptor p62, suggesting that complete autophagic flux was triggered. In addition, we showed that inhibition of autophagy with bafilomycin A1 or 3-methyladenine significantly reduces viral multiplication. Moreover, viral yield was increased when autophagy was induced using rapamycin. Furthermore, JUNV infection induced the colocalisation of p62, ATG16, RAB5, RAB7A and LAMP1 with the autophagosomal LC3 protein. That suggests that phagosomes undergo the maturation process during viral infection. Finally, we demonstrated that siRNA experiments targeting essential autophagy genes (ATG5, ATG7 and Beclin 1) reduce viral protein synthesis and viral yield. Overall, our results indicate that JUNV activates host autophagy machinery enhancing its multiplication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583977/ doi: 10.1371/journal.pone.0218730 id: cord-000837-rdpsxb4n author: Perez-Pepe, Marcelo title: BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis date: 2012-12-20 words: 7079.0 sentences: 366.0 pages: flesch: 50.0 cache: ./cache/cord-000837-rdpsxb4n.txt txt: ./txt/cord-000837-rdpsxb4n.txt summary: title: BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins. To assess the suitability of BUHO for the analysis of additional cell structures, we investigated several examples of cytoplasmic foci stained with different strategies, including SGs and PBs in mammalian and insect cells, and synapses and Smaug 1-mRNA silencing foci (S-foci) in primary neurons. Moreover, as expected given that SGs and PBs are morphologically similar, we found that prototype SGs were useful to identify PBs. To test the performance of BUHO in analyzing distances between objects, we focused on the presence of synaptic mRNA silencing foci at the synapse surroundings. With minor modifications, we have successfully applied it for processing images of different magnification and resolution of synapses, SGs, PBs and similar foci in mammalian and Drosophila cell lines as well as in primary cultured neurons. abstract: The spontaneous and reversible formation of foci and filaments that contain proteins involved in different metabolic processes is common in both the nucleus and the cytoplasm. Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins. SGs and PBs are highly dynamic and they form upon stress and dissolve thus releasing the repressed mRNAs according to changes in cell physiology. In addition, aggregates containing abnormal proteins are frequent in neurodegenerative disorders. In spite of the growing relevance of these supramolecular aggregates to diverse cellular functions a reliable automated tool for their systematic analysis is lacking. Here we report a MATLAB Script termed BUHO for the high-throughput image analysis of cellular foci. We used BUHO to assess the number, size and distribution of distinct objects with minimal deviation from manually obtained parameters. BUHO successfully addressed the induction of both SGs and PBs in mammalian and insect cells exposed to different stress stimuli. We also used BUHO to assess the dynamics of specific mRNA-silencing foci termed Smaug 1 foci (S-foci) in primary neurons upon synaptic stimulation. Finally, we used BUHO to analyze the role of candidate genes on SG formation in an RNAi-based experiment. We found that FAK56D, GCN2 and PP1 govern SG formation. The role of PP1 is conserved in mammalian cells as judged by the effect of the PP1 inhibitor salubrinal, and involves dephosphorylation of the translation factor eIF2α. All these experiments were analyzed manually and by BUHO and the results differed in less than 5% of the average value. The automated analysis by this user-friendly method will allow high-throughput image processing in short times by providing a robust, flexible and reliable alternative to the laborious and sometimes unfeasible visual scrutiny. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527446/ doi: 10.1371/journal.pone.0051495 id: cord-349217-vpih1wvs author: Petropoulos, Fotios title: Forecasting the novel coronavirus COVID-19 date: 2020-03-31 words: 3159.0 sentences: 185.0 pages: flesch: 60.0 cache: ./cache/cord-349217-vpih1wvs.txt txt: ./txt/cord-349217-vpih1wvs.txt summary: Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. While all three data patterns show an exponential increase, the trends of both the confirmed cases and the deaths were reduced in the mid of February; a second exponential increase is observed in late February and March as a result of the increased number of cases in South Korea, Iran, and Europe. The mean estimate (point forecast) for the confirmed cases ten-days-ahead was 209 thousand with the 90% prediction intervals ranging from about 38 to 534 thousand cases. However, the estimated uncertainty by splitting the data is considerably lower, possibly since the confirmed cases outside Mainland China have significantly increased only recently. abstract: What will be the global impact of the novel coronavirus (COVID-19)? Answering this question requires accurate forecasting the spread of confirmed cases as well as analysis of the number of deaths and recoveries. Forecasting, however, requires ample historical data. At the same time, no prediction is certain as the future rarely repeats itself in the same way as the past. Moreover, forecasts are influenced by the reliability of the data, vested interests, and what variables are being predicted. Also, psychological factors play a significant role in how people perceive and react to the danger from the disease and the fear that it may affect them personally. This paper introduces an objective approach to predicting the continuation of the COVID-19 using a simple, but powerful method to do so. Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. The risks are far from symmetric as underestimating its spread like a pandemic and not doing enough to contain it is much more severe than overspending and being over careful when it will not be needed. This paper describes the timeline of a live forecasting exercise with massive potential implications for planning and decision making and provides objective forecasts for the confirmed cases of COVID-19. url: https://doi.org/10.1371/journal.pone.0231236 doi: 10.1371/journal.pone.0231236 id: cord-000866-dr2uow4m author: Picard-Jean, Frédéric title: The Immunosuppressive Agent Mizoribine Monophosphate Is an Inhibitor of the Human RNA Capping Enzyme date: 2013-01-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Mizoribine monophosphate (MZP) is a specific inhibitor of the cellular inosine-5′-monophosphate dehydrogenase (IMPDH), the enzyme catalyzing the rate-limiting step of de novo guanine nucleotide biosynthesis. MZP is a highly potent antagonistic inhibitor of IMPDH that blocks the proliferation of T and B lymphocytes that use the de novo pathway of guanine nucleotide synthesis almost exclusively. In the present study, we investigated the ability of MZP to directly inhibit the human RNA capping enzyme (HCE), a protein harboring both RNA 5′-triphosphatase and RNA guanylyltransferase activities. HCE is involved in the synthesis of the cap structure found at the 5′ end of eukaryotic mRNAs, which is critical for the splicing of the cap-proximal intron, the transport of mRNAs from the nucleus to the cytoplasm, and for both the stability and translation of mRNAs. Our biochemical studies provide the first insight that MZP can inhibit the formation of the RNA cap structure catalyzed by HCE. In the presence of MZP, the RNA 5′-triphosphatase activity appears to be relatively unaffected while the RNA guanylyltransferase activity is inhibited, indicating that the RNA guanylyltransferase activity is the main target of MZP inhibition. Kinetic studies reveal that MZP is a non-competitive inhibitor that likely targets an allosteric site on HCE. Mizoribine also impairs mRNA capping in living cells, which could account for the global mechanism of action of this therapeutic agent. Together, our study clearly demonstrates that mizoribine monophosphate inhibits the human RNA guanylyltransferase in vitro and impair mRNA capping in cellulo. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547949/ doi: 10.1371/journal.pone.0054621 id: cord-280386-a8qr7nl6 author: Pires, Sara M. title: Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food date: 2015-12-03 words: 5931.0 sentences: 252.0 pages: flesch: 45.0 cache: ./cache/cord-280386-a8qr7nl6.txt txt: ./txt/cord-280386-a8qr7nl6.txt summary: The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. To identify and prioritize targeted interventions to reduce the public health impact of foodborne diseases, public health policy makers and other stakeholders need aetiology-specific regional and global estimates of the incidence and mortality of diarrhoeal diseases caused by pathogens that are commonly transmitted through foods. While approach 1 analysed national incidence and mortality of disease by pathogens commonly transmitted through foods estimated primarily by correcting surveillance data to account for underreporting and under-diagnosis, approach 2 relied on systematic reviews of studies identifying causative agents in patients with diarrhoea. abstract: BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1–3.3 billion) cases and 599,000 (95% UI 472,000–802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468–1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154–380 million), Shigella spp. (188 million; 95% UI 94–379 million) and Giardia lamblia (179 million; 95% UI 125–263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783–266,561), enteropathogenic E. coli (121,455; 95% UI 103,657–143,348), ETEC (73,041; 95% UI 55,474–96,984) and Shigella (64,993; 95% UI 48,966–92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods. url: https://doi.org/10.1371/journal.pone.0142927 doi: 10.1371/journal.pone.0142927 id: cord-000224-2lz03oqb author: Porter, Kristen A. title: Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag date: 2010-06-24 words: 6986.0 sentences: 313.0 pages: flesch: 44.0 cache: ./cache/cord-000224-2lz03oqb.txt txt: ./txt/cord-000224-2lz03oqb.txt summary: METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. We hypothesized that recapitulating endogenous expression of the entire class II antigen presentation pathway in producer cells via expression of CIITA would restore infectious virus release and provide a more physiologically relevant model for HIV-1 assembly studies. Virus release, both infectious and particle titers) were reduced when cells were transfected with either HLA-DR or other components of the MHC class II antigen presentation pathway ( Figure S2 ), confirming a correlation between Gag retention and reduced virus titers in the presence of HLA-DR, as previously demonstrated [8] . Together, these data suggest CIITA has two effects on the HIV replicative cycle in producer cells, both of which are independent of the MHC II antigen processing pathway; i) it does not induce HLA-DR, mediated intracellular retention of Gag and ii) it increases the infectivity of HIV virions. abstract: BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892040/ doi: 10.1371/journal.pone.0011304 id: cord-002935-jq1xumrh author: Postnikova, Elena title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date: 2018-03-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Identifying effective antivirals for treating Ebola virus disease (EVD) and minimizing transmission of such disease is critical. A variety of cell-based assays have been developed for evaluating compounds for activity against Ebola virus. However, very few reports discuss the variable assay conditions that can affect the results obtained from these drug screens. Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate. In these studies, we show that altering cell-based assay conditions can have an impact on apparent drug potency as measured by the EC(50). These results further support the importance of developing standard operating procedures for generating reliable and reproducible in vitro data sets for potential antivirals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864066/ doi: 10.1371/journal.pone.0194880 id: cord-303331-xolksoy3 author: Pourghasemi, Hamid Reza title: Assessment of the outbreak risk, mapping and infection behavior of COVID-19: Application of the autoregressive integrated-moving average (ARIMA) and polynomial models date: 2020-07-28 words: 5988.0 sentences: 312.0 pages: flesch: 55.0 cache: ./cache/cord-303331-xolksoy3.txt txt: ./txt/cord-303331-xolksoy3.txt summary: A geographic information system (GIS)-based machine learning algorithm (MLA), support vector machine (SVM), was used for the assessment of the outbreak risk of COVID-19 in Fars Province, Iran whereas the daily observations of infected cases were tested in the—polynomial and the autoregressive integrated moving average (ARIMA) models to examine the patterns of virus infestation in the province and in Iran. The aims of the present study were to analyze the risk factors of coronavirus outbreak and test the SVM model for mapping areas with a high risk of human infection with the virus in Fars Province, Iran. Accordingly, in this research, we selected sixteen most relevant effective factors for the outbreak risk mapping of COVID-19 in Fars Province of Iran, which includes minimum temperature of coldest month (MTCM), maximum temperature of warmest month (MTWM), precipitation in wettest month (PWM), precipitation of driest month (PDM), distance from roads, distance from mosques, distance from hospitals, distance from fuel stations, human footprint, density of cities, distance from bus abstract: Infectious disease outbreaks pose a significant threat to human health worldwide. The outbreak of pandemic coronavirus disease 2019 (COVID-19) has caused a global health emergency. Thus, identification of regions with high risk for COVID-19 outbreak and analyzing the behaviour of the infection is a major priority of the governmental organizations and epidemiologists worldwide. The aims of the present study were to analyze the risk factors of coronavirus outbreak for identifying the areas having high risk of infection and to evaluate the behaviour of infection in Fars Province, Iran. A geographic information system (GIS)-based machine learning algorithm (MLA), support vector machine (SVM), was used for the assessment of the outbreak risk of COVID-19 in Fars Province, Iran whereas the daily observations of infected cases were tested in the—polynomial and the autoregressive integrated moving average (ARIMA) models to examine the patterns of virus infestation in the province and in Iran. The results of the disease outbreak in Iran were compared with the data for Iran and the world. Sixteen effective factors were selected for spatial modelling of outbreak risk. The validation outcome reveals that SVM achieved an AUC value of 0.786 (March 20), 0.799 (March 29), and 86.6 (April 10) that displays a good prediction of outbreak risk change detection. The results of the third-degree polynomial and ARIMA models in the province revealed an increasing trend with an evidence of turning, demonstrating extensive quarantines has been effective. The general trends of virus infestation in Iran and Fars Province were similar, although a more volatile growth of the infected cases is expected in the province. The results of this study might assist better programming COVID-19 disease prevention and control and gaining sorts of predictive capability would have wide-ranging benefits. url: https://www.ncbi.nlm.nih.gov/pubmed/32722716/ doi: 10.1371/journal.pone.0236238 id: cord-000321-ee7q7jhv author: Powell, Michael L. title: Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA date: 2011-02-08 words: 9458.0 sentences: 433.0 pages: flesch: 51.0 cache: ./cache/cord-000321-ee7q7jhv.txt txt: ./txt/cord-000321-ee7q7jhv.txt summary: The features identified in caliciviral TURBS suggest a model for termination-reinitiation in which post-termination 40S subunits are tethered to the mRNA through interactions between the mRNA (through motif 1) and 18S rRNA, initiation factors are recruited and the AUG restart codon located, processes which may require precise RNA folding (involving motif 2) within the TURBS. Analysis of primary and secondary structural features of the BM2 signal has revealed that it contains a short TURBS (of 45 nt) which is largely single-stranded, with motif 1 likely to be located in the apical loop of a metastable stem-loop structure when the ribosome is positioned at the termination codon of the upstream ORF [11] . Importantly, mutation of the motif 1 homologue such that it was fully complementary to yeast 18S rRNA led to a significant (p,0.01) increase in BM2fluc synthesis relative to the wild-type BM2 reporter ( Figure 4C ), supporting the view that mRNA:rRNA base pairing is a key determinant in BM2 ORF expression. abstract: Termination-dependent reinitiation is used to co-ordinately regulate expression of the M1 and BM2 open-reading frames (ORFs) of the dicistronic influenza B segment 7 RNA. The start codon of the BM2 ORF overlaps the stop codon of the M1 ORF in the pentanucleotide UAA UG and ∼10% of ribosomes terminating at the M1 stop codon reinitiate translation at the overlapping AUG. BM2 synthesis requires the presence of, and translation through, 45 nt of RNA immediately upstream of the UAA UG, known as the ‘termination upstream ribosome binding site’ (TURBS). This region may tether ribosomal 40S subunits to the mRNA following termination and a short region of the TURBS, motif 1, with complementarity to helix 26 of 18S rRNA has been implicated in this process. Here, we provide further evidence for a direct interaction between mRNA and rRNA using antisense oligonucleotide targeting and functional analysis in yeast cells. The TURBS also binds initiation factor eIF3 and we show here that this protein stimulates reinitiation from both wild-type and defective TURBS when added exogenously, perhaps by stabilising ribosome-mRNA interactions. Further, we show that the position of the TURBS with respect to the UAA UG overlap is crucial, and that termination too far downstream of the 18S complementary sequence inhibits the process, probably due to reduced 40S tethering. However, in reporter mRNAs where the restart codon alone is moved downstream, termination-reinitiation is inhibited but not abolished, thus the site of reinitiation is somewhat flexible. Reinitiation on distant AUGs is not inhibited in eIF4G-depleted RRL, suggesting that the tethered 40S subunit can move some distance without a requirement for linear scanning. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035654/ doi: 10.1371/journal.pone.0016822 id: cord-254117-2ttwaegh author: Priest, Patricia C. title: Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study date: 2011-01-05 words: 4187.0 sentences: 186.0 pages: flesch: 44.0 cache: ./cache/cord-254117-2ttwaegh.txt txt: ./txt/cord-254117-2ttwaegh.txt summary: The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). This evaluation of thermal image scanning was carried out as part of a larger study to measure the prevalence of seasonal influenza infection in arriving airline travellers and the effectiveness of a screening questionnaire for detecting those with influenza infection. To assess the utility of fever as a screening test for influenza infection (MT-PCR result), sensitivity, specificity, and population PPV for influenza were estimated for each tympanic temperature threshold, and the ITIS threshold used above. The greatest potential for the use of ITIS to screen incoming or departing travellers for infectious diseases such as a pandemic strain of influenza would be as the first stage of screening; that is, to identify and select out a high risk group for further assessment, for example by questionnaire, body core temperature measurement, and/or respiratory sample collection. abstract: BACKGROUND: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. METHODS: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). FINDINGS: Using front of face ITIS for prediction of tympanic temperature ≥37.8°C, the area under the ROC curve was 0.86 (95%CI 0.75–0.97) and setting sensitivity at 86% gave specificity of 71%. The PPV in this population of travellers, of whom 0.5% were febrile using this definition, was 1.5%. We identified influenza virus infection in 30 travellers (3 Type A and 27 Type B). For ITIS prediction of influenza infection the area under the ROC curve was 0.66 (0.56–0.75), a sensitivity of 87% gave specificity of 39%, and PPV of 2.8%. None of the 30 influenza-positive travellers had tympanic temperature ≥37.8°C at screening (95%CI 0% to 12%); three had no influenza symptoms. CONCLUSION: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were not much better than chance at identifying travellers likely to be influenza-infected. Although febrile illness is more common in influenza A infections than influenza B infections, many influenza A infections are afebrile. Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country. url: https://www.ncbi.nlm.nih.gov/pubmed/21245928/ doi: 10.1371/journal.pone.0014490 id: cord-342133-khrljehj author: Principi, Nicola title: Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease date: 2015-08-12 words: 5116.0 sentences: 243.0 pages: flesch: 49.0 cache: ./cache/cord-342133-khrljehj.txt txt: ./txt/cord-342133-khrljehj.txt summary: To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). To evaluate the circulation of the different hBoV types and the possible relationships between viral load, virus genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children attending the emergency room of the Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection arising between November 1 and March 31 during 3 winters (2009-2010, 2011-2012, and 2013-2014) . Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children abstract: To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1–2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease. url: https://doi.org/10.1371/journal.pone.0135640 doi: 10.1371/journal.pone.0135640 id: cord-000736-6f8vyziv author: Pripuzova, Natalia title: Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens date: 2012-08-17 words: 6818.0 sentences: 328.0 pages: flesch: 54.0 cache: ./cache/cord-000736-6f8vyziv.txt txt: ./txt/cord-000736-6f8vyziv.txt summary: FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). The analytical sensitivity of each primer set was determined in the single virus testing using FDA/CBER panels (kindly provided by Dr. Stephen Kerby, FDA/CBER) consisting of various amounts of the viruses (0-1,000 genome copies/ml) spiked into the ''''normal'''' human plasma. The results of sensitivity testing of the real-time PCR array primer sets specific for HIV-1, HIV-2, HBV, HCV, and WNV the with FDA/CBER analytical plasma panels. Tm and C(t) values obtained with primer sets specific for HIV-1, HCV, or HBV in testing of 17 human clinical samples in the format of PCR array targeting eight different viruses. abstract: BACKGROUND: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV. It detected 100–1,000 geq/ml of plasma of HIV-1 subtypes (A – G), group N and CRF (AE and AG) isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. CONCLUSIONS: The viral array described here demonstrated adequate performance in the testing of donors’ clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422334/ doi: 10.1371/journal.pone.0043246 id: cord-319845-oob2ktnz author: Proença-Modena, José Luiz title: Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea date: 2011-06-20 words: 5857.0 sentences: 269.0 pages: flesch: 51.0 cache: ./cache/cord-319845-oob2ktnz.txt txt: ./txt/cord-319845-oob2ktnz.txt summary: Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. This article reports a cross-sectional study of HBoV in ARI patients from Ribeirão Preto, Brazil, in which the shedding of VP1 mRNA in respiratory secretions was used as surrogate marker for active HBoV replication, to look for correlations with viral load, and presence of particular clinical manifestations and simultaneous detection of other respiratory viruses. The results of this cross-sectional study of HBoV in ARI patients from Ribeirão Preto, Brazil, indicate that shedding of VP1 mRNA in respiratory secretions, as a marker of HBoV replication, correlates positively with high viral load, presence of diarrhea, and lack of co-infection by other respiratory viruses. abstract: Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>10(8) copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections. url: https://www.ncbi.nlm.nih.gov/pubmed/21701591/ doi: 10.1371/journal.pone.0021083 id: cord-278224-sq7tokbx author: Protopopova, Alexandra title: Behavioral predictors of subsequent respiratory illness signs in dogs admitted to an animal shelter date: 2019-10-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Individual variability is evident in behavior and physiology of animals. Determining whether behavior at intake may predict subsequent illness in the animal shelter may influence the management of dogs housed at animal shelters and reduce overall disease. While normally associated with mild disease and low mortality rates, respiratory disease nevertheless poses significant challenges to the management of dogs in the stressful environment of animal shelters due to its highly infectious nature. Therefore, the aim of the study was to explore whether behavior at intake can predict subsequent occurrence and progression of upper respiratory disease in dogs at animal shelters. In a correlational study, 84 dogs were assessed throughout their stay at a city animal shelter. The dogs were subjected to a behavioral assessment, 1 min in-kennel behavioral observations across two observation periods, and the collection of urinary cortisol:creatinine (C:C) ratio. The occurrence and progression of upper respiratory disease was monitored through repeated clinical exams (rectal temperature and the occurrence of nasal and ocular discharge, and presence of coughing and sneezing). A basic PLS Path regression model revealed that time in the shelter (estimate = .53, p < .001), and sociability (estimate = .24, p < .001) and curiosity scores (estimate = .09, p = .026) were associated with increased illness. Activity and anxiety scores, however, were not associated with illness. Urinary C:C, taken on the first full day, did not predict subsequent illness when accounting for time. Limitations included attrition of dogs, a small percentage receiving vaccinations, and continuous and non-systematic rotation of dogs in the kennels. Understanding if behavior can predict subsequent illness may improve shelter management practices, and in turn, result in improved live-release outcomes. url: https://doi.org/10.1371/journal.pone.0224252 doi: 10.1371/journal.pone.0224252 id: cord-291756-ejh1r8h4 author: Pérez-Fuentes, María del Carmen title: Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population date: 2020-06-25 words: 3766.0 sentences: 197.0 pages: flesch: 49.0 cache: ./cache/cord-291756-ejh1r8h4.txt txt: ./txt/cord-291756-ejh1r8h4.txt summary: title: Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population AIMS: The objective of this study was therefore to analyze the effect of exceptionally stressful situations, such as the current health risk, on the cognitive and emotive state of the individual, that is, perceived threat and emotional state on affect and mood. RESULTS: The results showed that the perception of threat from COVID-19 was related positively to negative affect and emotional signs, that is, sadness-depression, anxiety and anger-hostility. The starting hypothesis was that perception of threat in the exceptional state of health emergency caused by COVID-19, affects one''s emotional situation (Model 1), and this, in turn, affects perception of risk (Model 2), in which positive and negative affect balances act as mediators in these relationships (Fig 1) . abstract: AIMS: The objective of this study was therefore to analyze the effect of exceptionally stressful situations, such as the current health risk, on the cognitive and emotive state of the individual, that is, perceived threat and emotional state on affect and mood. METHOD: This was a cross-sectional study with snowball sampling. The sample came to 1014 Spanish adults (67.2% women and 32.8% men). The Perception of Threat from COVID-19 questionnaire, the Affective Balance Scale and the Mood Evaluation Scale were used. RESULTS: The results showed that the perception of threat from COVID-19 was related positively to negative affect and emotional signs, that is, sadness-depression, anxiety and anger-hostility. There was a direct positive effect of perceived threat from COVID-19 on sadness-depression, anxiety and anger-hostility moods, while anxiety and anger-hostility had a direct positive effect on perception of threat from the virus. Thus, there was a circular relationship, in which perceived threat influenced the presence of negative mood, and negative mood, in turn, linked to emotions of irritation and agitation from a present situation, promoted the feeling of threat. CONCLUSIONS: A negative affective balance increases both one’s perception of threat from COVID-19 and negative mood. Thus, knowing the emotional and cognitive effects on the population would enable measures to be put into service to facilitate their effective coping. url: https://doi.org/10.1371/journal.pone.0235305 doi: 10.1371/journal.pone.0235305 id: cord-000689-8lvzab4i author: Qi, Yilin title: The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin date: 2012-06-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375254/ doi: 10.1371/journal.pone.0039072 id: cord-295559-yc8q62z8 author: Qian, Zhaohui title: Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation date: 2013-10-03 words: 7303.0 sentences: 303.0 pages: flesch: 50.0 cache: ./cache/cord-295559-yc8q62z8.txt txt: ./txt/cord-295559-yc8q62z8.txt summary: Coronavirus S proteins are Class I viral fusion proteins like the HIV envelope (env), influenza hemagglutinin (HA) and paramyxovirus fusion (F) glycoproteins [17] , which typically require protease cleavage between the S1 and S2 domains ( Figure 1A ) to permit conformational changes in S2, activated by receptor binding and/or low pH, that mediate membrane fusion leading to virus entry and syncytia formation [3, 17, 18] . In addition to entry by endocytosis, we showed that, like SARS-CoV [21, 22] , MERS pseudovirions could enter susceptible Vero E6 cells at the plasma membrane if virions were first bound to cell surface receptors at 4°C at neutral pH in the presence of NH 4 Cl to inhibit acidification of endosomes, and also treated briefly at room temperature with trypsin to cleave the viral S protein. abstract: Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World Eptesicus fuscus bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents NH(4)Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS pseudovirions with uncleaved S protein were adsorbed at 4°C to Vero E6 cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma membrane and syncytia formation. When 293T cells producing MERS pseudotypes co-expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH, and the pseudovirions produced were non-infectious and deficient in S protein. These experiments show that if S protein on MERS pseudovirions is uncleaved, then viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S is cleaved, either during virus maturation by serine proteases or on pseudovirions by trypsin in extracellular fluids, then viruses enter at the plasma membrane at neutral pH and cause massive syncytia formation even in cells that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells within endosomes or at the plasma membrane depends upon the host cell type and tissue, and is determined by the location of host proteases that cleave the viral spike glycoprotein and activate membrane fusion. url: https://doi.org/10.1371/journal.pone.0076469 doi: 10.1371/journal.pone.0076469 id: cord-281665-6n7aq4k9 author: Qiu, Sangsang title: Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models date: 2015-05-20 words: 3982.0 sentences: 213.0 pages: flesch: 49.0 cache: ./cache/cord-281665-6n7aq4k9.txt txt: ./txt/cord-281665-6n7aq4k9.txt summary: This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. This study describes the economic burden on patients with tuberculosis, identifies related factors by comparing two areas with different management models, and provides a policy recommendation for the tuberculosis control system in China. Significant factors related to the total out-of-pocket costs were study setting (t = -3.10, P = 0.002), age (t = -4.04, P < 0.001), number of clinical visits (t = 4.46, P < 0.001), residence (t = 3.19, P = 0.002), diagnosis delay (t = 3.47, P = 0.001), hospitalization (t = 15.04, P < 0.001), intake of liver protective drugs (t = 2.78, P = 0.006) and intake of second-line drugs (t = 2.87, P = 0.004) ( Table 5) . abstract: OBJECTIVE: China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. METHODS: There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. RESULTS: The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983–6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. CONCLUSION: Under the current “free of diagnosis and treatment” policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients. url: https://doi.org/10.1371/journal.pone.0126770 doi: 10.1371/journal.pone.0126770 id: cord-351990-aham72b9 author: Radin, Jennifer M. title: Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations date: 2014-12-30 words: 4511.0 sentences: 220.0 pages: flesch: 43.0 cache: ./cache/cord-351990-aham72b9.txt txt: ./txt/cord-351990-aham72b9.txt summary: METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. This study aimed to describe characteristics associated with specific respiratory pathogens, as well as the etiology, seasonality, and coinfection rates among three US populations: military recruits, Department of Defense (DoD) beneficiaries, and civilians living near the US-Mexico border. Additionally, the following demographic and clinical signs and symptoms were collected from each FRI and SARI case: sex, age, study population, month of illness, pneumonia, sore throat, cough, nausea, shortness of breath, congestion, pink eye, body ache, headache, temperature, number of days of symptoms before seeking care, and date of seeking care. abstract: BACKGROUND: Diagnostic tests for respiratory infections can be costly and time-consuming. Improved characterization of specific respiratory pathogens by identifying frequent signs, symptoms and demographic characteristics, along with improving our understanding of coinfection rates and seasonality, may improve treatment and prevention measures. METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Clinical and demographic questionnaire data and respiratory swabs were collected from participants, tested by PCR for nine different respiratory pathogens and summarized. Age stratified characteristics of civilians positive for influenza and recruits positive for rhinovirus were compared to other and no/unknown pathogen. Seasonality and coinfection rates were also described. RESULTS: A total of 1444 patients met the FRI or SARI case definition and were enrolled in this study. Influenza signs and symptoms varied across age groups of civilians. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. Coinfections were found in 6% of all FRI/SARI cases tested and were most frequently seen among children and with rhinovirus infections. Clear seasonal trends were identified for influenza, rhinovirus, and respiratory syncytial virus. CONCLUSIONS: The age-stratified clinical characteristics associated with influenza suggest that age-specific case definitions may improve influenza surveillance and identification. Improving identification of rhinoviruses, the most frequent respiratory infection among recruits, may be useful for separating out contagious individuals, especially when larger outbreaks occur. Overall, describing the epidemiology of pathogen specific respiratory diseases can help improve clinical diagnoses, establish baselines of infection, identify outbreaks, and help prioritize the development of new vaccines and treatments. url: https://www.ncbi.nlm.nih.gov/pubmed/25549089/ doi: 10.1371/journal.pone.0114871 id: cord-000410-av8b8g8c author: Radoshitzky, Sheli R. title: Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry date: 2011-07-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131282/ doi: 10.1371/journal.pone.0021398 id: cord-352222-zq9o66i4 author: Rajatonirina, Soatiana title: Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012 date: 2013-09-12 words: 4137.0 sentences: 245.0 pages: flesch: 46.0 cache: ./cache/cord-352222-zq9o66i4.txt txt: ./txt/cord-352222-zq9o66i4.txt summary: BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. Our study aimed to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old hospitalised in one of the four main public hospitals in Antananarivo. In our study, Streptococcus pneumoniae was the most common bacterial pathogen as in other studies of hospitalised patients with acute respiratory illness, and Haemophilus influenzae type B was the next most frequent [16] [17] [18] [19] . abstract: BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. In these low-income countries, most patients with acute respiratory infection (ARI), whether it is mild or severe, are still treated empirically. The aim of the study was to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. We collected demographic, socio-economic, clinical and epidemiological data, and samples for laboratory analysis. Deaths, rapid progression to respiratory distress during hospitalisation, and hospitalisation for more than 10 days were considered as severe outcomes. We used multivariate analysis to study the effects of co-infections. RESULTS: From November 2010 to July 2012, a total of 290 patients were enrolled. Co-infection was found in 192 patients (70%). Co-infections were more frequent in children under 36 months, with a significant difference for the 19–24 month-old group (OR: 8.0). Sixty-nine percent (230/290) of the patients recovered fully and without any severe outcome during hospitalisation; the outcome was scored as severe for 60 children and nine patients (3%) died. Risk factors significantly associated with worsening evolution during hospitalisation (severe outcome) were admission at age under 6 months (OR = 5.3), comorbidity (OR = 4.6) and low household income (OR = 4.1). CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. These results highlight the need for implementation of targeted public health policy to reduce the contribution of respiratory diseases to childhood morbidity and mortality in low income countries. url: https://www.ncbi.nlm.nih.gov/pubmed/24069161/ doi: 10.1371/journal.pone.0072839 id: cord-000609-dpcgl6ig author: Raju, Sammeta V. title: Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia date: 2012-03-19 words: 4083.0 sentences: 253.0 pages: flesch: 43.0 cache: ./cache/cord-000609-dpcgl6ig.txt txt: ./txt/cord-000609-dpcgl6ig.txt summary: Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. The current report directly measured the adenosineinduced chloride secretion of airway epithelia under the exposure of physiologically relevant concentrations of alcohol and found that ethanol attenuates epithelial CFTR-mediated chloride transport by modulating cellular cAMP levels. To explore if ethanol affects adenosine-activated ion transport function of airway epithelium, we employed air-liquid interface cultures of Calu-3 cells, a system widely used to investigate airway epithelial electrophysiological properties [27, 28] . These results not only confirm that ethanol modulates adenosine-cAMP signaling but also suggest that phosphodiesterase inhibitors may be useful as the potential therapeutic agents for improving the airway epithelial ion transport and mucociliary clearance in alcoholic patients. abstract: Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC)) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B) adenosine receptor (A(2B)AR), largely abolished the adenosine-stimulated chloride transport, suggesting that A(2B)AR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307712/ doi: 10.1371/journal.pone.0032112 id: cord-000050-tfcerilc author: Rao, Srinivas title: Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date: 2008-06-18 words: 5605.0 sentences: 256.0 pages: flesch: 44.0 cache: ./cache/cord-000050-tfcerilc.txt txt: ./txt/cord-000050-tfcerilc.txt summary: METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. After optimization of injection conditions, alternative multivalent DNA vaccine regimens were analyzed and compared for magnitude and breadth of neutralizing antibodies, as well as protective efficacy after challenge in mouse and chicken models of HPAI H5N1 infection. The ability of chickens to generate specific antibodies was assessed with three strains that showed broad cross protection in mouse studies (A/Vietnam/1203/2004, A/Anhui/ 1/2005 and A/Indonesia/05/2005), administered individually or in combination, by different injection methods. abstract: BACKGROUND: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses. METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device. CONCLUSIONS/SIGNIFICANCE: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657001/ doi: 10.1371/journal.pone.0002432 id: cord-001455-n7quwr4s author: Rapin, Noreen title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans date: 2014-11-12 words: 3719.0 sentences: 198.0 pages: flesch: 50.0 cache: ./cache/cord-001455-n7quwr4s.txt txt: ./txt/cord-001455-n7quwr4s.txt summary: title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses. We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23. We used samples collected during the experiment to address the question: Can hibernating bats respond to infection by activating genes responsible for innate immune and stress responses? We determined levels of transcripts for several immune and stress response genes (Table 1) in lungs from infected and control bats. abstract: Recently bats have been associated with the emergence of diseases, both as reservoirs for several new viral diseases in humans and other animals and, in the northern Americas, as hosts for a devastating fungal disease that threatens to drive several bat species to regional extinction. However, despite these catastrophic events little Information is available on bat defences or how they interact with their pathogens. Even less is known about the response of bats to infection during torpor or long-term hibernation. Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses. Lesions due to fungal infection and, in some cases, secondary bacterial infections, were restricted to the skin. However, we were unable to obtain sufficient amounts of RNA from these sites. We therefore examined lungs for response at an epithelial surface not linked to the primary site of infection. We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23. In conclusion, hibernating bats can respond to experimental P. destructans infection by activating expression of innate immune response genes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229191/ doi: 10.1371/journal.pone.0112285 id: cord-346586-fxxceffl author: Razanajatovo, Norosoa Harline title: Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013 date: 2018-11-21 words: 4150.0 sentences: 213.0 pages: flesch: 49.0 cache: ./cache/cord-346586-fxxceffl.txt txt: ./txt/cord-346586-fxxceffl.txt summary: CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Following the A/H1N1/2009 influenza pandemic that was associated with a high morbidity and an increased risk of mortality among particular groups [13] , a number of countries have strengthened vigilance for the surveillance of severe diseases and deaths in order to rapidly detect new viruses and to provide information in assessing the impact on the population and having operational preparedness plans. A meta-analysis of data from Africa reported that the incidence of RSV in lower acute respiratory infections that required hospitalization ranged from 10-18 per 1000 person year for infants and 3-9 per 1000 person year for children under 5 years of age [26] . abstract: BACKGROUND: Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar. METHODS: It is a prospective surveillance of SARI in 2 hospitals for 3 years. Nasopharyngeal swabs, sputum, and blood were collected from SARI patients enrolled and tested for viruses and bacteria. Epidemiological and clinical information were obtained from case report forms. RESULTS: Overall, 876 patients were enrolled in the study, of which 83.1% (728/876) were tested positive for at least one pathogen. Viral and bacterial infections occurred in 76.1% (667/876) and 35.8% (314/876) of tested samples, respectively. Among all detected viruses, respiratory syncytial virus (RSV) was the most common (37.7%; 348/924) followed by influenza virus A (FLUA, 18.4%; 170/924), rhinovirus (RV, 13.5%; 125/924), and adenovirus (ADV, 8.3%; 77/924). Among bacteria, Streptococcus pneumoniae (S. pneumoniae, 50.3%, 189/370) was the most detected followed by Haemophilus influenzae type b (Hib, 21.4%; 79/370), and Klebsiella (4.6%; 17/370). Other Streptococcus species were found in 8.1% (30/370) of samples. Compared to patients aged less than 5 years, older age groups were significantly less infected with RSV. On the other hand, patients aged more than 64 years (OR = 3.66) were at higher risk to be infected with FLUA, while those aged 15–29 years (OR = 3.22) and 30–64 years (OR = 2.39) were more likely to be infected with FLUB (influenza virus B). CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Amongst young children, the demonstrated burden of RSV should guide clinicians for a better case management of children. These findings reveal the need to develop point-of-care tests to avoid overuse of antibiotics and to promote vaccine that could reduce drastically the RSV hospitalizations. url: https://www.ncbi.nlm.nih.gov/pubmed/30462659/ doi: 10.1371/journal.pone.0205124 id: cord-272655-qeojdpez author: Remolina, Yuly Andrea title: Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia date: 2015-11-17 words: 4309.0 sentences: 204.0 pages: flesch: 42.0 cache: ./cache/cord-272655-qeojdpez.txt txt: ./txt/cord-272655-qeojdpez.txt summary: OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Under this initiative, countries have developed surveillance systems by following cases of influenza-like illness and severe acute respiratory infections (SARIs), which are clinically diagnosed among patients with fever, coughing or sore throat, difficulty breathing and the need for hospitalization [3] . In our study, viruses were identified as the most frequent causal agents of SARI requiring hospitalization in 2012, with most cases showing a high rate of viral co-infection, a high degree of morbidity, prolonged hospital stays and frequent needs for ICU management and mechanical ventilation. abstract: OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. SETTING: Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. PARTICIPANTS: Ninety-one adult patients with acute respiratory infection (55% were female). MEASUREMENTS: Viral identification, intensive care unit admission, hospital stay, and mortality. RESULTS: Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. CONCLUSIONS: The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. url: https://doi.org/10.1371/journal.pone.0143152 doi: 10.1371/journal.pone.0143152 id: cord-277409-q5wx313k author: Resende, Lucilene Aparecida title: Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge date: 2016-08-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T(0)), during the post-vaccination protocol (T(3rd)) and after early (T(90)) and late (T(885)) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection. url: https://www.ncbi.nlm.nih.gov/pubmed/27556586/ doi: 10.1371/journal.pone.0161169 id: cord-002939-6a3ga6v9 author: Ribeiro, Ana Freitas title: Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of Sao Paulo, Brazil, 2009 date: 2018-03-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: To investigate the factors associated with death and describe the gestational outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case-control study (deaths and recovered) in hospitalized pregnant women with laboratory-confirmed influenza A(H1N1)pdm09 with severe acute respiratory illness (SARI) in the state of São Paulo from June 9 to December 1, 2009. All cases were evaluated, and four controls that were matched by the epidemiological week of hospitalization of the case were randomly selected for each case. Cases and controls were selected from the National Disease Notification System-SINAN Influenza-web. The hospital records from 126 hospitals were evaluated, and home interviews were conducted using standardized forms. A total of 48 cases and 185 controls were investigated. Having had a previous health visit to a healthcare provider for an influenza episode before hospital admission was a risk factor for death (adjusted OR (OR(adj)) of 7.93, 95% CI 2.19–28.69). Although not significant in the multiple analysis (OR(adj) of 2.13, 95% CI 0.91–5.00), the 3(rd) trimester deserves attention, with an OR = 2.22, 95% CI 1.13–4.37 in the univariate analysis. Antiviral treatment was a protective factor when administered within 48 hours of symptom onset (OR(adj) = 0.16, 95% CI 0.05–0.50) and from 48 to 72 hours (OR(adj) = 0.09, 95% CI 0.01–0.87). There was a higher proportion of fetal deaths and preterm births among cases (p = 0.001) and live births with low weight (p = 0.019), compared to control subjects who gave birth during hospitalization. After discharge, control subjects had a favorable neonatal outcome. Early antiviral treatment during the presence of a flu-like illness is an important factor in reducing mortality from influenza in pregnant women and unfavorable neonatal outcomes. It is important to monitor pregnant women, particularly in the 3(rd) trimester of gestation, with influenza illness for diagnosis and early treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868799/ doi: 10.1371/journal.pone.0194392 id: cord-315343-ywgoqlxj author: Ribeiro, Haroldo V. title: City size and the spreading of COVID-19 in Brazil date: 2020-09-23 words: 5473.0 sentences: 233.0 pages: flesch: 58.0 cache: ./cache/cord-315343-ywgoqlxj.txt txt: ./txt/cord-315343-ywgoqlxj.txt summary: Our results indicate small towns are proportionally more affected by COVID-19 during the initial spread of the disease, such that the cumulative numbers of cases and deaths per capita initially decrease with population size. However, during the long-term course of the pandemic, this urban advantage vanishes and large cities start to exhibit higher incidence of cases and deaths, such that every 1% rise in population is associated with a 0.14% increase in the number of fatalities per capita after about four months since the first two daily deaths. Investigating whether this behavior generalizes to other places and how different quantities such as the number of cases and deaths scale with city size are thus important elements for a better understanding of the spreading of COVID-19 in urban areas. To test for an increasing urban advantage for the treatment of COVID-19 during the initial spread of the disease, we investigate the scaling relation between the number of hospital intensive care unit (ICU) beds and city population. abstract: The current outbreak of the coronavirus disease 2019 (COVID-19) is an unprecedented example of how fast an infectious disease can spread around the globe (especially in urban areas) and the enormous impact it causes on public health and socio-economic activities. Despite the recent surge of investigations about different aspects of the COVID-19 pandemic, we still know little about the effects of city size on the propagation of this disease in urban areas. Here we investigate how the number of cases and deaths by COVID-19 scale with the population of Brazilian cities. Our results indicate small towns are proportionally more affected by COVID-19 during the initial spread of the disease, such that the cumulative numbers of cases and deaths per capita initially decrease with population size. However, during the long-term course of the pandemic, this urban advantage vanishes and large cities start to exhibit higher incidence of cases and deaths, such that every 1% rise in population is associated with a 0.14% increase in the number of fatalities per capita after about four months since the first two daily deaths. We argue that these patterns may be related to the existence of proportionally more health infrastructure in the largest cities and a lower proportion of older adults in large urban areas. We also find the initial growth rate of cases and deaths to be higher in large cities; however, these growth rates tend to decrease in large cities and to increase in small ones over time. url: https://arxiv.org/pdf/2005.13892v2.pdf doi: 10.1371/journal.pone.0239699 id: cord-314908-kp2jznwb author: Roczniewska, Marta title: I believe I can craft! introducing Job Crafting Self-Efficacy Scale (JCSES) date: 2020-08-10 words: 9293.0 sentences: 532.0 pages: flesch: 53.0 cache: ./cache/cord-314908-kp2jznwb.txt txt: ./txt/cord-314908-kp2jznwb.txt summary: To better predict these behaviors, we introduce the concept of job crafting self-efficacy (JCSE) and define it as an individual''s beliefs about their capability to modify the demands and resources of their job to better fit their needs. In this project we integrate Social Cognitive Theory and the Job Demands-Resources model [6, 7] to introduce the concept of job crafting self-efficacy (JCSE). Based on the assumptions of Social Cognitive Theory, we also expect that these specific beliefs predict matching job-crafting behaviors, for example, individuals who feel self-efficacious with respect to increasing challenging job demands are more likely to start new projects or learn about new developments at work and try them out. abstract: Job crafting is beneficial for employees and organizations. To better predict these behaviors, we introduce the concept of job crafting self-efficacy (JCSE) and define it as an individual’s beliefs about their capability to modify the demands and resources of their job to better fit their needs. This article describes the development and validation of a scale to measure JCSE. We conducted a qualitative study to design and four quantitative studies to test the psychometric properties of this scale among Polish and American employees in both paper-and-pencil and online versions. Three independent (N(1) = 364; N(2) = 432; N(3) = 403) confirmatory factor analyses demonstrated a good fit to a 3-factor solution comprising JCSE beliefs about increasing (a) structural job resources, (b) social job resources, and (c) challenging job demands. The 9-item JCSE Scale had good internal consistency, high time stability, and good validity. It correlated positively with general self-efficacy. JCSE explained unique variance in job crafting behaviors over and above general self-efficacy, and was more important in predicting job crafting than contextual factors. We demonstrate the role of social cognitions in shaping job redesign behaviors and provide a useful tool to evaluate the effectiveness of interventions dedicated to empowering JCSE. url: https://www.ncbi.nlm.nih.gov/pubmed/32776992/ doi: 10.1371/journal.pone.0237250 id: cord-270647-vn4kirrx author: Romero-Espinoza, Jose A. title: Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015 date: 2018-02-15 words: 3513.0 sentences: 201.0 pages: flesch: 48.0 cache: ./cache/cord-270647-vn4kirrx.txt txt: ./txt/cord-270647-vn4kirrx.txt summary: OBJECTIVES: To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. Both groups differ with respect to the associated virus and bacteria: while asthma exacerbations have been associated to a specific rhinovirus infection, pneumonia can be related to a wide range of bacterial, fungal and viral agents, with a high prevalence of Respiratory Syncytial Virus (RSV) [2, 7] . Here we describe the virome and bacteriome present in the Upper Respiratory Tract of hospitalized children clinically diagnosed with asthma and pneumonia, during an acute exacerbation and an ARI episode respectively, at the National Institute of Respiratory Diseases (INER, Mexico City) during 2014 and 2015 winter seasons. Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations abstract: BACKGROUND: Acute asthma exacerbations and pneumonia are important causes of morbidity and mortality in children and may coexist in the same children, although symptom overlap may lead to difficulties in diagnosis. Microbial and viral diversity and differential abundance of either may play an important role in infection susceptibility and the development of acute and chronic respiratory diseases. OBJECTIVES: To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. METHODS: During the winter seasons of 2013–2014 and 2014–2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were selected based on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics analysis pipeline. RESULTS: The Asthma group was represented mainly by RV-C, BoV-1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found in both groups with a similar amount of reads. About bacterial composition Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia. Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both asthma and pneumonia. CONCLUSIONS: Our results show a complex viral and bacterial composition in asthma and pneumonia groups with a strong association of RV-C presence in asthmatic children. We observed Streptococcus pneumoniae and Haemophilus influenzae concurrently in both groups. url: https://doi.org/10.1371/journal.pone.0192878 doi: 10.1371/journal.pone.0192878 id: cord-275395-w2u7fq1g author: Romero-Severson, Ethan Obie title: Change in global transmission rates of COVID-19 through May 6 2020 date: 2020-08-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We analyzed COVID-19 data through May 6th, 2020 using a partially observed Markov process. Our method uses a hybrid deterministic and stochastic formalism that allows for time variable transmission rates and detection probabilities. The model was fit using iterated particle filtering to case count and death count time series from 55 countries. We found evidence for a shrinking epidemic in 30 of the 55 examined countries. Of those 30 countries, 27 have significant evidence for subcritical transmission rates, although the decline in new cases is relatively slow compared to the initial growth rates. Generally, the transmission rates in Europe were lower than in the Americas and Asia. This suggests that global scale social distancing efforts to slow the spread of COVID-19 are effective although they need to be strengthened in many regions and maintained in others to avoid further resurgence of COVID-19. The slow decline also suggests alternative strategies to control the virus are needed before social distancing efforts are partially relaxed. url: https://doi.org/10.1371/journal.pone.0236776 doi: 10.1371/journal.pone.0236776 id: cord-266799-t7lqlv41 author: Rotejanaprasert, Chawarat title: Preliminary estimation of temporal and spatiotemporal dynamic measures of COVID-19 transmission in Thailand date: 2020-09-24 words: 5033.0 sentences: 265.0 pages: flesch: 45.0 cache: ./cache/cord-266799-t7lqlv41.txt txt: ./txt/cord-266799-t7lqlv41.txt summary: This study thus aims to estimate and compare disease dynamic measures in several dimensions that can be augmented with epidemiological summary statistics to monitor the COVID-19 situation for each location and time at different stages of the epidemic. The data in this study were from confirmed COVID-19 cases in 77 provinces of Thailand from January 12 th 2020 through June 30 th 2020 provided in the daily reports of the Department of Disease Control, Thai Ministry of Public Health (MOPH). During the early stage of an epidemic curve caused by emerging diseases, the exponential growth (EG) rate, denoted by r, can be related to the initial reproduction rate and can be described as the change in number of new cases per time unit [15] . We wanted to provide information that could be used to help design effective control strategies for the current COVID-19 situation in Thailand after the disease has spread to different provinces across the country much of which was from cluster outbreaks originating from several super spreader events. abstract: BACKGROUND: As a new emerging infectious disease pandemic, there is an urgent need to understand the dynamics of COVID-19 in each country to inform planning of emergency measures to contain its spread. It is essential that appropriate disease control activities are planned and implemented in a timely manner. Thailand was one of the first countries outside China to be affected with subsequent importation and domestic spread in most provinces in the country. METHOD: A key ingredient to guide planning and implementation of public health measures is a metric of transmissibility which represents the infectiousness of a disease. Ongoing policies can utilize this information to plan appropriately with updated estimates of disease transmissibility. Therefore we present descriptive analyses and preliminary statistical estimation of reproduction numbers over time and space to facilitate disease control activities in Thailand. RESULTS: The estimated basic reproduction number for COVID-19 during the study ranged from 2.23–5.90, with a mean of 3.75. We also tracked disease dynamics over time using temporal and spatiotemporal reproduction numbers. The results suggest that the outbreak was under control since the middle of April. After the boxing stadium and entertainment venues, the numbers of new cases had increased and spread across the country. DISCUSSION: Although various scenarios about assumptions were explored in this study, the real situation was difficult to determine given the limited data. More thorough mathematical modelling would be helpful to improve the estimation of transmissibility metrics for emergency preparedness as more epidemiological and clinical information about this new infection becomes available. However, the results can be used to guide interventions directly and to help parameterize models to predict the impact of these interventions. url: https://doi.org/10.1371/journal.pone.0239645 doi: 10.1371/journal.pone.0239645 id: cord-002602-2qvyhjlp author: Roy, Amrita title: Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants date: 2017-07-10 words: 8987.0 sentences: 456.0 pages: flesch: 57.0 cache: ./cache/cord-002602-2qvyhjlp.txt txt: ./txt/cord-002602-2qvyhjlp.txt summary: Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Therefore, our results suggest that in the Zika NS2B-NS3pro complex, NS2B has a portion of residues undergo μs-ms dynamics which made their NMR peaks too broad to be detectable; while the rest of NS2B is highly disordered and lacks tight tertiary packing, which results in a narrowly-dispersed HSQC spectrum (S2B Fig) . Together with recent reports on the crystal structures of Zika NS2B-NS3pro complexes in both open and closed conformations [34, 43] , our current results reveal that in solution the NS2B residues over Arg73-Lys100 are highly disordered in the open conformation. Unfortunately, as previously observed on Dengue-2 NS2B-NS3pro complexes [21, 30, 43] , our linked Zika complex also underwent significant μs-ms dynamics, thus making its NMR signals too broad to be detected (Fig 1A and 1B) . abstract: The recent Zika viral (ZIKV) epidemic has been associated with severe neurological pathologies such as neonatal microcephaly and Guillain-Barre syndrome but unfortunately no vaccine or medication is effectively available yet. Zika NS2B-NS3pro is essential for the proteolysis of the viral polyprotein and thereby viral replication. Thus NS2B-NS3pro represents an attractive target for anti-Zika drug discovery/design. Here, we have characterized the solution conformations and catalytic parameters of both linked and unlinked Zika NS2B-NS3pro complexes and found that the unlinked complex manifested well-dispersed NMR spectra. Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Upon binding to the well-characterized serine protease inhibitor, bovine pancreatic trypsin inhibitor (BPTI), only the extreme C-terminal residues (L86-K100) remain disordered. Additionally, we have identified five flavonoids and one natural phenol rich in edible plants including fruits and vegetables, which inhibit Zika NS2B-NS3pro in a non-competitive mode, with Ki ranging from 770 nM for Myricetin to 34.02 μM for Apigenin. Molecular docking showed that they all bind to a pocket on the back of the active site and their structure-activity relationship was elucidated. Our study provides valuable insights into the solution conformation of Zika NS2B-NS3pro and further deciphers its susceptibility towards allosteric inhibition by natural products. As these natural product inhibitors fundamentally differ from the currently-known active site inhibitors in terms of both inhibitory mode and chemical scaffold, our finding might open a new avenue for development of better allosteric inhibitors to fight ZIKV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503262/ doi: 10.1371/journal.pone.0180632 id: cord-268816-nth3o6ot author: Roy, Satyaki title: Factors affecting COVID-19 infected and death rates inform lockdown-related policymaking date: 2020-10-23 words: 5733.0 sentences: 363.0 pages: flesch: 56.0 cache: ./cache/cord-268816-nth3o6ot.txt txt: ./txt/cord-268816-nth3o6ot.txt summary: The features in the order shown under "Feature name" are: GDP, inter-state distance based on lat-long coordinates, gender, ethnicity, quality of health care facility, number of homeless people, total infected and death, population density, airport passenger traffic, age group, days for infection and death to peak, number of people tested for COVID-19, days elapsed between first reported infection and the imposition of lockdown measures at a given state. Unless otherwise stated, the feature set comprises GDP, gender, ethnicity, health care, homeless, lockdown type, population density, airport activity, and age groups, whereas the output labels consist of infected and death scores on a scale of 0-6. Although proposing a machine learning algorithm that works best on COVID-19 data is not the purpose of this study, it is worth reporting that decision tree classifier (DT) slightly outperforms the other algorithms for both cases of infected and death scores. abstract: BACKGROUND: After claiming nearly five hundred thousand lives globally, the COVID-19 pandemic is showing no signs of slowing down. While the UK, USA, Brazil and parts of Asia are bracing themselves for the second wave—or the extension of the first wave—it is imperative to identify the primary social, economic, environmental, demographic, ethnic, cultural and health factors contributing towards COVID-19 infection and mortality numbers to facilitate mitigation and control measures. METHODS: We process several open-access datasets on US states to create an integrated dataset of potential factors leading to the pandemic spread. We then apply several supervised machine learning approaches to reach a consensus as well as rank the key factors. We carry out regression analysis to pinpoint the key pre-lockdown factors that affect post-lockdown infection and mortality, informing future lockdown-related policy making. FINDINGS: Population density, testing numbers and airport traffic emerge as the most discriminatory factors, followed by higher age groups (above 40 and specifically 60+). Post-lockdown infected and death rates are highly influenced by their pre-lockdown counterparts, followed by population density and airport traffic. While healthcare index seems uncorrelated with mortality rate, principal component analysis on the key features show two groups: states (1) forming early epicenters and (2) experiencing strong second wave or peaking late in rate of infection and death. Finally, a small case study on New York City shows that days-to-peak for infection of neighboring boroughs correlate better with inter-zone mobility than the inter-zone distance. INTERPRETATION: States forming the early hotspots are regions with high airport or road traffic resulting in human interaction. US states with high population density and testing tend to exhibit consistently high infected and death numbers. Mortality rate seems to be driven by individual physiology, preexisting condition, age etc., rather than gender, healthcare facility or ethnic predisposition. Finally, policymaking on the timing of lockdowns should primarily consider the pre-lockdown infected numbers along with population density and airport traffic. url: https://www.ncbi.nlm.nih.gov/pubmed/33095811/ doi: 10.1371/journal.pone.0241165 id: cord-000581-ewx5xhrb author: Rudge, James W. title: Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories date: 2012-02-21 words: 5718.0 sentences: 218.0 pages: flesch: 36.0 cache: ./cache/cord-000581-ewx5xhrb.txt txt: ./txt/cord-000581-ewx5xhrb.txt summary: This study was conducted as part of the AsiaFluCap project (www.asiaflucap.org), the overall aim of which is to conduct health systems analyses to support capacity development for responding to pandemic influenza across six countries and territories in Asia, specifically: Cambodia, Indonesia, Lao PDR, Taiwan, Thailand and Vietnam. Estimating resource needs, gaps, and associated mortality In our baseline scenario, resource gaps were estimated assuming that 12% of ''''general'''' hospital resources (beds, ventilators and human resources) are available for care of pandemic influenza cases, with the remaining 88% required for maintaining essential healthcare services, as in a previous pilot study for Thailand [20] , and based on previous reports [25] [26] . Figure 1 presents the geographical distribution of estimated resource gaps across provinces (or districts in the case of Indonesia) in each study country for the modeled pandemic influenza scenario, under our baseline assumptions and point estimates for parameter values. abstract: BACKGROUND: Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283680/ doi: 10.1371/journal.pone.0031800 id: cord-346067-zly8p0y7 author: Ruiz-Irastorza, Guillermo title: Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data date: 2020-09-22 words: 4513.0 sentences: 221.0 pages: flesch: 52.0 cache: ./cache/cord-346067-zly8p0y7.txt txt: ./txt/cord-346067-zly8p0y7.txt summary: title: Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data Our therapeutic protocol was updated on April 3 rd 2020, including the recommendation of MP for patients with COVID-19 pneumonia with altered/worsening inflammatory parameters (lymphopenia, thrombocytopenia, rising ferritin, D-dimers and or C-reactive protein) and clinical deterioration, particularly those showing impending respiratory failure with decreasing SpO2/FiO2 values. Other independent predictors of death included a previous diagnosis of arterial hypertension, the use of non-pulse glucocorticoids, a high-risk CURB65 category and SpO2/FiO2 at week 2 ( Table 2 ). Glucocorticoid use, however, should not be indiscriminate, but rather restricted to patients with laboratory evidence of inflammation and progressing respiratory compromise, and best used as short-course pulse therapy (125-250 mg/d of methyl-prednisolone during 3 days) administered during the second week after the onset of symptoms, where the hyperinflammatory reaction takes usually place. abstract: OBJECTIVE: To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Comparative observational study using data collected from routine care at Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain in patients with COVID-19 pneumonia. We compared patients who received week-2-MP (125–250 mg/d x3) with those who did not, with the end-points time to death and time to death or endotracheal intubation. RESULTS: We included 242 patients with COVID-19 pneumonia and elevated inflammatory markers at admission. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died and 31 (12.8%) suffered death or intubation. The adjusted HRs for death and death or intubation for patients in the week-2-MP group were 0.35 (95%CI 0.11 to 1.06, p = 0.064) and 0.33 (95%CI 0.13 to 0.84, p = 0.020), respectively. These differences were specifically seen in the subcohort of patients with a SpO2/FiO2 at day 7 lower than 353 (adjusted HR 0.31, 95% CI 0.08 to 1.12, p = 0.073 and HR 0.34, 95%CI 0.12 to 0.94, p = 0.038, respectively) but not in patients with higher SpO2/FiO2. Patients receiving out-of-week-2-MP, non-pulse glucocorticoids or no glucocorticoids had an increased adjusted risk for both outcomes compared with week-2-MP group: HR 5.04 (95% CI 0.91–27.86), HR 10.09 (95% CI 2.14–47.50), HR 4.14 (95% CI 0.81–21.23), respectively, for death; HR 7.38 (95% CI 1.86–29.29), HR 13.71 (95% CI 3.76–50.07), HR 3.58 (95% CI 0.89–14.32), respectively, for death or intubation. These differences were significant only in the subgroup with low SpO2/FiO2. CONCLUSIONS: Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point. url: https://doi.org/10.1371/journal.pone.0239401 doi: 10.1371/journal.pone.0239401 id: cord-347317-qcghtkk0 author: Russo, Lucia title: Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach date: 2020-10-30 words: 9776.0 sentences: 397.0 pages: flesch: 51.0 cache: ./cache/cord-347317-qcghtkk0.txt txt: ./txt/cord-347317-qcghtkk0.txt summary: For the estimation of the day-zero of the outbreak in Lombardy, as well as of the "effective" per-day transmission rate for which no clinical data are available, we have used the proposed SEIIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March. Among the perplexing problems that mathematical models face when they are used to estimate epidemiological parameters and to forecast the evolution of the outbreak, two stand out: (a) the uncertainty regarding the day-zero of the outbreak, the knowledge of which is crucial to assess the stage and dynamics of the epidemic, especially during the first growth period, and (b) the uncertainty that characterizes the actual number of the asymptomatic infected cases in the total population (see e.g. abstract: INTRODUCTION: Italy became the second epicenter of the novel coronavirus disease 2019 (COVID-19) pandemic after China, surpassing by far China’s death toll. The disease swept through Lombardy, which remained in lockdown for about two months, starting from the 8th of March. As of that day, the isolation measures taken in Lombardy were extended to the entire country. Here, assuming that effectively there was one case “zero” that introduced the virus to the region, we provide estimates for: (a) the day-zero of the outbreak in Lombardy, Italy; (b) the actual number of asymptomatic infected cases in the total population until March 8; (c) the basic (R(0))and the effective reproduction number (R(e)) based on the estimation of the actual number of infected cases. To demonstrate the efficiency of the model and approach, we also provide a tentative forecast two months ahead of time, i.e. until May 4, the date on which relaxation of the measures commenced, on the basis of the COVID-19 Community Mobility Reports released by Google on March 29. METHODS: To deal with the uncertainty in the number of the actual asymptomatic infected cases in the total population Volpert et al. (2020), we address a modified compartmental Susceptible/ Exposed/ Infectious Asymptomatic/ Infected Symptomatic/ Recovered/ Dead (SEIIRD) model with two compartments of infectious persons: one modelling the cases in the population that are asymptomatic or experience very mild symptoms and another modelling the infected cases with mild to severe symptoms. The parameters of the model corresponding to the recovery period, the time from the onset of symptoms to death and the time from exposure to the time that an individual starts to be infectious, have been set as reported from clinical studies on COVID-19. For the estimation of the day-zero of the outbreak in Lombardy, as well as of the “effective” per-day transmission rate for which no clinical data are available, we have used the proposed SEIIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March. This was accomplished by solving a mixed-integer optimization problem. Based on the computed parameters, we also provide an estimation of the basic reproduction number R(0) and the evolution of the effective reproduction number R(e). To examine the efficiency of the model and approach, we ran the simulator to “forecast” the epidemic two months ahead of time, i.e. from March 8 to May 4. For this purpose, we considered the reduction in mobility in Lombardy as released on March 29 by Google COVID-19 Community Mobility Reports, and the effects of social distancing and of the very strict measures taken by the government on March 20 and March 21, 2020. RESULTS: Based on the proposed methodological procedure, we estimated that the expected day-zero was January 14 (min-max rage: January 5 to January 23, interquartile range: January 11 to January 18). The actual cumulative number of asymptomatic infected cases in the total population in Lombardy on March 8 was of the order of 15 times the confirmed cumulative number of infected cases, while the expected value of the basic reproduction number R(0) was found to be 4.53 (min-max range: 4.40- 4.65). On May 4, the date on which relaxation of the measures commenced the effective reproduction number was found to be 0.987 (interquartiles: 0.857, 1.133). The model approximated adequately two months ahead of time the evolution of reported cases of infected until May 4, the day on which the phase I of the relaxation of measures was implemented over all of Italy. Furthermore the model predicted that until May 4, around 20% of the population in Lombardy has recovered (interquartile range: ∼10% to ∼30%). url: https://www.ncbi.nlm.nih.gov/pubmed/33125393/ doi: 10.1371/journal.pone.0240649 id: cord-339026-eu11larc author: Ryals, Renee C. title: The effects of PEGylation on LNP based mRNA delivery to the eye date: 2020-10-29 words: 4786.0 sentences: 257.0 pages: flesch: 46.0 cache: ./cache/cord-339026-eu11larc.txt txt: ./txt/cord-339026-eu11larc.txt summary: Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. Most intriguingly, these particles successfully transfect RPE, Müller glia, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. Since the subretinal injection places the LNPs in close proximity to the RPE, we utilized this method to understand how PEGylation and size may impact intracellular delivery ( In general, for all particles, luciferase activity in the eye was measurable at 4 hours post-injection, increased to a maximum level at 24 hours post-injection and decreased by 48 hours post-injection (Figs 2B and 3B). abstract: Gene therapy is now an effective approach to treat many forms of retinal degeneration. Delivery agents that are cell-specific, allow for multiple dosing regimens, and have low immunogenicity are needed to expand the utility of gene therapy for the retina. We generated eight novel lipid nanoparticles (LNPs) ranging in size from 50 nm to 150 nm by changing the PEG content from 5% to 0.5%, respectively. Subretinal injections of LNP-mRNA encoding luciferase revealed that 0.5% PEG content within nanoparticles elicits the highest expression. Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. To investigate mechanisms of LNP delivery to the eye, we injected mCherry mRNA using the subretinal approach in apoE(-/-) and Mertk(-/-) mice. RPE transfection was observed in both mouse models suggesting that LNP intracellular delivery is not solely dependent on apolipoprotein adsorption or phagocytosis. To investigate LNP penetration, particles were delivered to the vitreous chamber via an intravitreal injection. The 0.5% PEG particles mediated the highest luciferase activity and expression was observed in the Müller glia, the optic nerve head and the trabecular meshwork, but failed to reach the RPE. Overall, particles containing less PEG (~150 nm in size) mediated the highest expression in the eye. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. url: https://doi.org/10.1371/journal.pone.0241006 doi: 10.1371/journal.pone.0241006 id: cord-001207-yjaiybwf author: Sachsenröder, Jana title: The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium date: 2014-02-19 words: 5919.0 sentences: 302.0 pages: flesch: 49.0 cache: ./cache/cord-001207-yjaiybwf.txt txt: ./txt/cord-001207-yjaiybwf.txt summary: faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. However, it is not known so far, whether probiotic bacteria can also influence the general composition of the faecal virome, e.g. by changing the composition of the bacterial community, which represents the host population for bacteriophages, or by direct interactions with specific viruses. Faecal samples from sows and their piglets experimentally fed with or without the probiotic bacterium were analyzed using a process-controlled deep sequencing method. As the detection rate of the bacteriophages is -besides technical factors -also dependent on the amount of viruses initially present in the analyzed sample, improved deep sequencing methods enabling quantitative analyses should be developed in future for comparative virome investigations. abstract: BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929612/ doi: 10.1371/journal.pone.0088888 id: cord-000588-3wok0n21 author: Sainz, Juan title: Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection date: 2012-02-27 words: 5506.0 sentences: 293.0 pages: flesch: 41.0 cache: ./cache/cord-000588-3wok0n21.txt txt: ./txt/cord-000588-3wok0n21.txt summary: The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. Based on these observations, the objective of the present study was to investigate the role of tagging and potentially functional single-nucleotide polymorphisms (SNPs) located within the DC-SIGN, Dectin-1, Dectin-2, MCP-1/CCL2 and CCR2 genes on IPA susceptibility. Of note is that two SNPs showing genetic interaction in this model were not significantly associated with an increased risk of IPA infection in the univariate analysis (CCR2 rs3918358 and Dectin-2 rs7134303 ). abstract: The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1 (rs3901533 T/T) and Dectin-1 (rs7309123 G/G) genotypes and DC-SIGN (rs4804800 G), DC-SIGN (rs11465384 T), DC-SIGN (7248637 A) and DC-SIGN (7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37–22.77; OR = 4.91 95%CI 1.52–15.89; OR = 2.75 95%CI 1.27–5.95; OR = 2.70 95%CI 1.24–5.90; OR = 2.39 95%CI 1.09–5.22 and OR = 2.05 95%CI 1.00–4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1 (rs3901533_T) allele and Dectin-1 (rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288082/ doi: 10.1371/journal.pone.0032273 id: cord-010369-x9z8dg6a author: Saito, Kyoko title: Comparative characterization of flavivirus production in two cell lines: Human hepatoma-derived Huh7.5.1-8 and African green monkey kidney-derived Vero date: 2020-04-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Flaviviridae is a family of enveloped viruses with a positive-sense single-stranded RNA genome. It contains many viruses that threaten human health, such as Japanese encephalitis virus (JEV) and yellow fever virus (YFV) of the genus Flavivirus as well as hepatitis C virus of the genus Hepacivirus. Cell culture systems highly permissive for the Flaviviridae viruses are very useful for their isolation, propagation, and diagnosis, an understanding of their biology, and the development of vaccines and antiviral agents. Previously, we isolated a human hepatoma HuH-7-derived cell clone, Huh7.5.1–8, which is highly permissive to hepatitis C virus infection. Here, we have characterized flavivirus infection in the Huh7.5.1–8 cell line by comparing with that in the African green monkey kidney-derived Vero cell line, which is permissive for a wide spectrum of viruses. Upon infection with JEV, Huh7.5.1–8 cells produced a higher amount of virus particles early in infection and were more susceptible to virus-induced cell death than Vero cells. Similar outcomes were obtained when the cells were infected with another flavivirus, YFV (17D-204 strain). Quantification of cellular and extracellular viral RNA revealed that high JEV production in Huh7.5.1–8 cells can be attributed to rapid viral replication kinetics and efficient virus release early in infection. In a plaque assay, Huh7.5.1–8 cells developed JEV plaques more rapidly than Vero cells. Although this was not the case with YFV plaques, Huh7.5.1–8 cells developed higher numbers of YFV plaques than Vero cells. Sequence analysis of cDNA encoding an antiviral RNA helicase, RIG-I, showed that Huh7.5.1–8 cells expressed not only a full-length RIG-I mRNA with a known dominant-negative missense mutation but also variants without the mutation. However, the latter mRNAs lacked exon 5/6−12, indicating functional loss of RIG-I in the cells. These characteristics of the Huh7.5.1–8 cell line are helpful for flavivirus detection, titration, and propagation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182267/ doi: 10.1371/journal.pone.0232274 id: cord-001781-afg1nmib author: Saksena, Sumeet title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam date: 2015-09-23 words: 7626.0 sentences: 395.0 pages: flesch: 49.0 cache: ./cache/cord-001781-afg1nmib.txt txt: ./txt/cord-001781-afg1nmib.txt summary: We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. The results presented here highlight three main findings: 1) when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor; but in peri-urban landscapes emergence factors converge, including higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture; 2) high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks; as are 3) landscapes where intensive and extensive forms of poultry production are co-located. Hence diseases associated with rice production are likely to peak in peri-urban areas given other risk factors such as land-use diversity, CTI, and distance to infrastructure. abstract: Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model’s predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580613/ doi: 10.1371/journal.pone.0138138 id: cord-048471-7jszm1nd author: Salim, Omar title: Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus date: 2008-05-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Jena Virus (JV), a bovine Norovirus, causes enteric disease in cattle and represents a potential model for the study of enteric norovirus infection and pathogenesis. The positive sense RNA genome of JV is organised into ORF1 (non-structural proteins), ORF2 (major capsid protein) and ORF3 (minor capsid protein). The lack of a cell culture system for studying JV replication has meant that work to date has relied upon in vitro systems to study non-structural protein synthesis and processing. PRINCIPAL FINDINGS: Only two of the three major ORF1 proteins were identified (p110 and 2C) following in vitro translation of JV RNA, the N-term protein was not detected. The N-term encoding genomic sequence (5′GS) was tested for IRES-like function in a bi-cistronic system and displayed no evidence of IRES-like activity. The site of translation initiation in JV was determined to be at the predicted nucleotide 22. Following the insertion of an epitope within the 5′GS the JV N-term protein was identified in vitro and within RNA transfected cells. CONCLUSIONS: The in vitro transcription/translation system is currently the best system for analysing protein synthesis and processing in JV. Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function, most likely involved in translation initiation in an IRES-like manner. This was not the case and, following determination of the site of translation initiation the N-term protein was detected using an epitope tag, both in vitro and in vivo. Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease. These findings indicate that the block to noroviral replication in cultured cells lies elsewhere. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364642/ doi: 10.1371/journal.pone.0002169 id: cord-350398-w75flrwv author: Sampath, Rangarajan title: Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry date: 2012-06-29 words: 11138.0 sentences: 581.0 pages: flesch: 50.0 cache: ./cache/cord-350398-w75flrwv.txt txt: ./txt/cord-350398-w75flrwv.txt summary: Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry. In addition to detecting the threat organisms, the biothreat assay described here also detects virulence factors associated with three of the agents: Bacillus anthracis (pXO1 and pXO2), Yersinia pestis (pla and caf), and Vibrio cholera (ctx1). PCR primers were designed to conserved regions within the selected target genes such that the targeted threat agent was clearly identified and differentiated from its near-neighbor species ( Table 1) . In the biothreat assay, the Francisella biocluster is identified by two genus-specific primer pairs targeting the asd (BCT2328) and galE (BCT2332) genes ( Table 1) . abstract: Technology for comprehensive identification of biothreats in environmental and clinical specimens is needed to protect citizens in the case of a biological attack. This is a challenge because there are dozens of bacterial and viral species that might be used in a biological attack and many have closely related near-neighbor organisms that are harmless. The biothreat agent, along with its near neighbors, can be thought of as a biothreat cluster or a biocluster for short. The ability to comprehensively detect the important biothreat clusters with resolution sufficient to distinguish the near neighbors with an extremely low false positive rate is required. A technological solution to this problem can be achieved by coupling biothreat group-specific PCR with electrospray ionization mass spectrometry (PCR/ESI-MS). The biothreat assay described here detects ten bacterial and four viral biothreat clusters on the NIAID priority pathogen and HHS/USDA select agent lists. Detection of each of the biothreat clusters was validated by analysis of a broad collection of biothreat organisms and near neighbors prepared by spiking biothreat nucleic acids into nucleic acids extracted from filtered environmental air. Analytical experiments were carried out to determine breadth of coverage, limits of detection, linearity, sensitivity, and specificity. Further, the assay breadth was demonstrated by testing a diverse collection of organisms from each biothreat cluster. The biothreat assay as configured was able to detect all the target organism clusters and did not misidentify any of the near-neighbor organisms as threats. Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry. url: https://www.ncbi.nlm.nih.gov/pubmed/22768032/ doi: 10.1371/journal.pone.0036528 id: cord-313506-6bb4q7nv author: Sano, Akiko title: Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle date: 2013-10-24 words: 6695.0 sentences: 313.0 pages: flesch: 54.0 cache: ./cache/cord-313506-6bb4q7nv.txt txt: ./txt/cord-313506-6bb4q7nv.txt summary: We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). Therefore, in an effort to improve B cell development and hIgG production in Tc cattle, we sought to enhance pre-BCR function by engineering a new HAC into which, in addition to the hIGH, hIGK and hIGL chromosome loci that carry the entire human immunoglobulin gene repertoire, the human VpreB (hVPREB1) and λ5 (hIGLL1) genomic loci from human chromosome 22 (hChr22) was incorporated, and part of CH and TM domains, CH2-TM, of hIGHM gene, was replaced by the corresponding bovine gene sequence (bovinization of the CH2-TM domains of hIGHM). doi: 10.1371/journal.pone.0078119.g002 DT40 colonies were screened with genomic PCR (data not shown) for the correctly modified hChr2, and clone K53 was identified and selected for the final HAC construction ( Figure 5 ). abstract: Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle. url: https://doi.org/10.1371/journal.pone.0078119 doi: 10.1371/journal.pone.0078119 id: cord-001605-8p06bpt1 author: Sapmak, Ariya title: The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei date: 2015-04-13 words: 5165.0 sentences: 308.0 pages: flesch: 53.0 cache: ./cache/cord-001605-8p06bpt1.txt txt: ./txt/cord-001605-8p06bpt1.txt summary: title: The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type. marneffei MCO participates in conidial DHN-melanin synthesis, we combined 55 fungal MCO sequences and performed alignments using CLUSTALW (http://www.genome.jp/ tools/clustalw/). marneffei PbrB, this clade comprises of characterized laccases functioning in conidial DHN-melanin synthesis. Talaromyces (Penicillium) marneffei pbrB Gene Cytoplasmic protein extracts from the wild type and ΔpbrB mutant cultured in brain heart infusion broth at 37°C for 3 days were capable of catalyzing L-DOPA (data not shown). abstract: Talaromyces marneffei (Basionym: Penicillium marneffei) is a significant opportunistic fungal pathogen in patients infected with human immunodeficiency virus in Southeast Asia. T. marneffei cells have been shown to become melanized in vivo. Melanins are pigment biopolymers which act as a non-specific protectant against various stressors and which play an important role during virulence in fungi. The synthesis of the two most commonly found melanins in fungi, the eumelanin DOPA-melanin and the allomelanin DHN-melanin, requires the action of laccase enzymes. The T. marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. A strain carrying a PbrB-GFP fusion shows that pbrB is expressed at high levels during asexual development (conidiation) but not in cells growing vegetatively. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395095/ doi: 10.1371/journal.pone.0122728 id: cord-276577-06boh550 author: Schanzer, Dena L. title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling date: 2009-08-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33% (95%CI 32–34%), varying from 30–40% depending on the season and region. CONCLUSIONS: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza. url: https://doi.org/10.1371/journal.pone.0006681 doi: 10.1371/journal.pone.0006681 id: cord-348243-e5tdb08v author: Schermer, Bernhard title: Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay date: 2020-11-02 words: 3958.0 sentences: 236.0 pages: flesch: 56.0 cache: ./cache/cord-348243-e5tdb08v.txt txt: ./txt/cord-348243-e5tdb08v.txt summary: METHODS: To avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK). To allow for the comparison of different nucleic acid detection methods for SARS-CoV-2 we collected redundant material from nasopharyngeal swabs obtained for qPCR testing in clinical routine due to suspected COVID-19. We first tested two recently described assays for SARS-CoV-2 detection on isolated RNA from patient samples. In summary, our multiplex RT-LAMP protocol is a simple and sensitive way to detect SARS-CoV-2 RNA from clinical samples. Currently, a test based on our multiplexed RT-LAMP assay would-in contrast to a good specificity-most likely miss to identify those infected patients with very low amounts of viral RNA in the nose or throat and would not yet reach the sensitivity of the gold-standard qPCR assays. abstract: BACKGROUND: Rapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose. METHODS: To avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK). RESULTS: Whilst specificity of standard RT-LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed RT-LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel RT-LAMP assays with SHERLOCK. CONCLUSION: In summary, this approach reveals one-step multiplexed RT-LAMP assays as a prime-option for the development of easy and cheap POC test kits. url: https://doi.org/10.1371/journal.pone.0238612 doi: 10.1371/journal.pone.0238612 id: cord-330749-xt4aa2ur author: Schilling, Stefan title: Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries date: 2014-10-28 words: 4124.0 sentences: 192.0 pages: flesch: 41.0 cache: ./cache/cord-330749-xt4aa2ur.txt txt: ./txt/cord-330749-xt4aa2ur.txt summary: The term highly infectious diseases (HID) defines mostly viral and bacterial infections that (i) are easily transmissible from person to person; (ii) cause a life-threatening clinical illness with no or few treatment options; and (iii) pose a threat for both health care workers and the public, thus requiring specific infection control measures and public health planning [1] . Despite such efforts, no pooled data on isolation facilities resources, such as infrastructure design, technical equipment, capacity and access to intensive care, do exist. The study presented was performed by the European Network for Highly Infectious Diseases, EuroNHID, and set up to compare the operational management, resources, and technical equipment among isolation facilities with recommendations published. Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries abstract: BACKGROUND: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. METHODS AND FINDINGS: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. CONCLUSION: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised. url: https://doi.org/10.1371/journal.pone.0100401 doi: 10.1371/journal.pone.0100401 id: cord-272878-6f0q661e author: Schnepf, Nathalie title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France date: 2011-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009–2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management. url: https://www.ncbi.nlm.nih.gov/pubmed/21858150/ doi: 10.1371/journal.pone.0023514 id: cord-299509-7xjdryoq author: Scholte, Florine E. M. title: Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates date: 2013-08-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that re-emerged in 2004 and has caused massive outbreaks in recent years. The lack of a licensed vaccine or treatment options emphasize the need to obtain more insight into the viral life cycle and CHIKV-host interactions. Infectious cDNA clones are important tools for such studies, and for mechanism of action studies on antiviral compounds. Existing CHIKV cDNA clones are based on a single genome from an individual clinical isolate, which is expected to have evolved specific characteristics in response to the host environment, and possibly also during subsequent cell culture passaging. To obtain a virus expected to have the general characteristics of the recent E1-226V CHIKV isolates, we have constructed a new CHIKV full-length cDNA clone, CHIKV LS3, based on the consensus sequence of their aligned genomes. Here we report the characterization of this synthetic virus and a green fluorescent protein-expressing variant (CHIKV LS3-GFP). Their characteristics were compared to those of natural strain ITA07-RA1, which was isolated during the 2007 outbreak in Italy. In cell culture the synthetic viruses displayed phenotypes comparable to the natural isolate, and in a mouse model they caused lethal infections that were indistinguishable from infections with a natural strain. Compared to ITA07-RA1 and clinical isolate NL10/152, the synthetic viruses displayed similar sensitivities to several antiviral compounds. 3-deaza-adenosine was identified as a new inhibitor of CHIKV replication. Cyclosporin A had no effect on CHIKV replication, suggesting that cyclophilins -opposite to what was found for other +RNA viruses- do not play an essential role in CHIKV replication. The characterization of the consensus sequence-based synthetic viruses and their comparison to natural isolates demonstrated that CHIKV LS3 and LS3-GFP are suitable and representative tools to study CHIKV-host interactions, screen for antiviral compounds and unravel their mode of action. url: https://www.ncbi.nlm.nih.gov/pubmed/23936484/ doi: 10.1371/journal.pone.0071047 id: cord-002973-bkr4ndl2 author: Seifi, Morteza title: Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms date: 2018-04-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Mutations in PITX2 have been implicated in several genetic disorders, particularly Axenfeld-Rieger syndrome. In order to determine the most reliable bioinformatics tools to assess the likely pathogenicity of PITX2 variants, the results of bioinformatics predictions were compared to the impact of variants on PITX2 structure and function. The MutPred, Provean, and PMUT bioinformatic tools were found to have the highest performance in predicting the pathogenicity effects of all 18 characterized missense variants in PITX2, all with sensitivity and specificity >93%. Applying these three programs to assess the likely pathogenicity of 13 previously uncharacterized PITX2 missense variants predicted 12/13 variants as deleterious, except A30V which was predicted as benign variant for all programs. Molecular modeling of the PITX2 homoedomain predicts that of the 31 known PITX2 variants, L54Q, F58L, V83F, V83L, W86C, W86S, and R91P alter PITX2’s structure. In contrast, the remaining 24 variants are not predicted to change PITX2’s structure. The results of molecular modeling, performed on all the PITX2 missense mutations located in the homeodomain, were compared with the findings of eight protein stability programs. CUPSAT was found to be the most reliable in predicting the effect of missense mutations on PITX2 stability. Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903617/ doi: 10.1371/journal.pone.0195971 id: cord-000833-m6abyuvx author: Sekiguchi, Satoshi title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date: 2012-12-17 words: 5915.0 sentences: 348.0 pages: flesch: 50.0 cache: ./cache/cord-000833-m6abyuvx.txt txt: ./txt/cord-000833-m6abyuvx.txt summary: The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. These observations, in addition to the modified histology activity index (HAI) scores, indicated that expression of HCV proteins caused chronic hepatitis in the CN2-29 (+/2) /MxCre (+/2) mice because a weak, though persistent, immune response followed an initial bout of acute hepatitis ( Figure S1 ). To determine whether activation of the host immune response caused the reduction with HCV protein levels in the livers of CN2-29 (+/2) /MxCre (+/2) mice, we used a highly attenuated VV strain, LC16m8, to generate three rVVs [12] . To determine whether rVV-N25 treatment induced the same effect in other strains of HCV transgenic mice, we analyzed RzCN5-15 (+/2) /MxCre (+/2) mice, which express all HCV proteins; in these mice, chronic hepatitis was resolved within 28 days of immunization with rVV-N25. abstract: Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/−))/MxCre((+/−)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524174/ doi: 10.1371/journal.pone.0051656 id: cord-322533-adqqm0n9 author: Sha, Dexuan title: Spatiotemporal analysis of medical resource deficiencies in the U.S. under COVID-19 pandemic date: 2020-10-14 words: 5189.0 sentences: 232.0 pages: flesch: 49.0 cache: ./cache/cord-322533-adqqm0n9.txt txt: ./txt/cord-322533-adqqm0n9.txt summary: The study duration was mainly from February 15, 2020 to May 1, 2020 in the U.S. Multiple data sources were used to extract local population, hospital beds, critical care staff, COVID-19 confirmed case numbers, and hospitalization data at county level. Then, we developed two medical resource deficiency indices that measured the local medical burden based on the number of accumulated active confirmed cases normalized by local maximum potential medical resources, and the number of hospitalized patients that can be supported per ICU bed per critical care staff, respectively. In this report, three fundamental elements or features, i.e. ventilators, ICU beds, and critical care staff (CCS) were identified as medical resources to plan for or manage a COVID-19 pandemic, and it would be wise to consider the interconnections among these factors in a spatiotemporal data analysis framework. abstract: Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in Wuhan, China as an infectious disease, and has quickly resulted in an ongoing pandemic. A data-driven approach was developed to estimate medical resource deficiencies due to medical burdens at county level during the COVID-19 pandemic. The study duration was mainly from February 15, 2020 to May 1, 2020 in the U.S. Multiple data sources were used to extract local population, hospital beds, critical care staff, COVID-19 confirmed case numbers, and hospitalization data at county level. We estimated the average length of stay from hospitalization data at state level, and calculated the hospitalized rate at both state and county level. Then, we developed two medical resource deficiency indices that measured the local medical burden based on the number of accumulated active confirmed cases normalized by local maximum potential medical resources, and the number of hospitalized patients that can be supported per ICU bed per critical care staff, respectively. Data on medical resources, and the two medical resource deficiency indices are illustrated in a dynamic spatiotemporal visualization platform based on ArcGIS Pro Dashboards. Our results provided new insights into the U.S. pandemic preparedness and local dynamics relating to medical burdens in response to the COVID-19 pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/33052956/ doi: 10.1371/journal.pone.0240348 id: cord-001021-nag4at49 author: Shaheen, Hussam H. title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris date: 2013-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression. This results in a separation between antibody affinity maturation and full-length mAb production platforms. Here, we report for the first time, a method in Glyco-engineered Pichia pastoris that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell. This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored "bait" Fc, which results in targeting functional “half” IgGs to the cell wall of Pichia pastoris without interfering with the secretion of full length mAb. We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries. Coupled with Glyco-engineered Pichia pastoris , this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707868/ doi: 10.1371/journal.pone.0070190 id: cord-000366-u4649rtx author: Shan, Tongling title: Genomic Characterization and High Prevalence of Bocaviruses in Swine date: 2011-04-15 words: 2887.0 sentences: 161.0 pages: flesch: 55.0 cache: ./cache/cord-000366-u4649rtx.txt txt: ./txt/cord-000366-u4649rtx.txt summary: Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Presently, the bocavirus genus contains eight members: bovine parvovirus, canine minute virus (CnMV), human bocavirus 1-4 (HBoV1-4), a gorilla bocavirus and a partially sequenced chimpanzee bocavirus [1, 6, 7] . In 2009, a porcine bocalike virus (PBo-likeV) was reported in swine feces with postweaning multisystemic wasting syndrome in Sweden and 1854 bp of its partial genome sequenced [27] . Finally, partial genome sequences of 2.4 Kb from another clade of porcine bocaviruses labeled 6V and 7V where also identified yielding three major bocavirus groups in swine (PBo-likeV, PBoV1/PBoV2, and 6V/7V). abstract: Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Phylogenetic analysis indicated that PBoV1-H18 was very closely related to a ∼2 Kb central region of a porcine bocavirus-like virus (PBo-LikeV) from Sweden described in 2009. PBoV2-A6 was very closely related to the porcine bocavirus genomes PBoV-1 and PBoV2 from China described in 2010. Among 340 fecal samples collected from different age, asymptomatic swine in five Chinese provinces, the prevalence of PBoV1-H18 and PBoV2-A6 related viruses were 45–75% and 55–70% respectively, with 30–47% of pigs co-infected. PBoV1-A6 related strains were highly conserved, while PBoV2-H18 related strains were more diverse, grouping into two genotypes corresponding to the previously described PBoV1 and PBoV2. Together with the recently described partial bocavirus genomes labeled V6 and V7, a total of three major porcine bocavirus clades have therefore been described to date. Further studies will be required to elucidate the possible pathogenic impact of these diverse bocaviruses either alone or in combination with other porcine viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078135/ doi: 10.1371/journal.pone.0017292 id: cord-305303-82n96ukr author: Shapira, Assaf title: Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date: 2012-02-16 words: 10132.0 sentences: 431.0 pages: flesch: 42.0 cache: ./cache/cord-305303-82n96ukr.txt txt: ./txt/cord-305303-82n96ukr.txt summary: As shown in Figure 2 , similar numbers of surviving colonies were observed when the cells were transfected with the plasmids encoding mCherry-NS3 activated MazF or the red fluorescent protein alone, suggesting that expression of NS3-activable ribonuclease in naïve HEK293 T-REx cells (that do not express NS3) cause minimal toxicity, if any. The ER membrane-targeted zymoxin colocalizes with NS3 protease in vivo Previously we described a HEK293 cell line which inducibly expresses (by addition of tetracycline) a fusion between EGFP and the coding sequence of the full length NS3 (including the helicase domain) followed by NS4A from HCV 1a genotype [10] . When infection reached ,50% (about 50% of the cultured cells showed expression of the HCV-core protein, as detected by immuno-staining and fluorescence microscopy), the mixed culture and a culture of uninfected cells were treated with NS3 activated MazF or uncleavable-MazF encoding adenoviruses at MOI of ,3. abstract: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases. url: https://www.ncbi.nlm.nih.gov/pubmed/22359682/ doi: 10.1371/journal.pone.0032320 id: cord-335272-jypxi99z author: Sharma, Anupam Joya title: A cross-sectional study of psychological wellbeing of Indian adults during the Covid-19 lockdown: Different strokes for different folks date: 2020-09-03 words: 9794.0 sentences: 515.0 pages: flesch: 52.0 cache: ./cache/cord-335272-jypxi99z.txt txt: ./txt/cord-335272-jypxi99z.txt summary: Moreover, both qualitative and quantitative study findings suggested that greater frequency of calling family members during lockdown could strengthen social relationships and increase social empathy. In response, our study of Indian adults unpacks how social factors such as sexual orientation, relationship status, and residence in high-infection areas, could be linked with several psychological outcomes during the lockdown. Next, we fitted separate multivariable linear regression models to estimate the association of the independent variables (sexual orientation, relationship status, high-risk group, and living in a state with high number of cases) with psychological outcomes (anxiety, depressive symptoms, Internet addiction and pornography consumption) adjusted for the sociodemographic covariates-age, gender, annual income, educational qualification, place of residence-and for individual personal resources (optimism and resilience). Our quantitative and qualitative findings both suggest that LGBT adults, compared to the heterosexuals, are at a higher risk of developing anxiety, depressive symptoms, and using pornography during the lockdown. abstract: The psychological impacts of the lockdown due to the Covid-19 pandemic are widely documented. In India, a family-centric society with a high population density and extreme social stratification, the impact of the lockdown might vary across diverse social groups. However, the patterning in the psychological impact of the lockdown among LGBT adults and persons known to be at higher risk of the complications of Covid-19 (such as persons with comorbidities or a history of mental illness) is not known in the Indian context. We used mixed methods (online survey, n = 282 and in-depth interviews, n = 14) to investigate whether the psychological influence of the lockdown was different across these groups of Indian adults. We fitted linear and logistic regression models adjusted for sociodemographic covariates. Thematic analysis helped us identify emergent themes in our qualitative narratives. Anxiety was found to be higher among LGBT adults (β = 2.44, CI: 0.58, 4.31), the high-risk group (persons with comorbidities) (β = 2.20, CI:0.36, 4.05), and those with a history of depression/loneliness (β = 3.89, CI:2.34, 5.44). Persons belonging to the LGBT group reported a greater usage of pornography than the heterosexuals (β = 2.72, CI: 0.09, 5.36) during the lockdown. Qualitative findings suggested that LGBT adults likely used pornography and masturbation to cope with the lockdown, given the limited physical access to sexual partners in a society that stigmatizes homosexuality. Moreover, both qualitative and quantitative study findings suggested that greater frequency of calling family members during lockdown could strengthen social relationships and increase social empathy. The study thereby urgently calls for the attention of policymakers to take sensitive and inclusive health-related decisions for the marginalized and the vulnerable, both during and after the crisis. url: https://doi.org/10.1371/journal.pone.0238761 doi: 10.1371/journal.pone.0238761 id: cord-322446-ddv86eoy author: Sharma, Kulbhushan title: SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus date: 2011-05-27 words: 8437.0 sentences: 512.0 pages: flesch: 56.0 cache: ./cache/cord-322446-ddv86eoy.txt txt: ./txt/cord-322446-ddv86eoy.txt summary: We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. Analysis of 9b-YFP localization showed that in addition to the extranuclear region, some amount of 9b was also present within the nucleus similar to the SARS-CoV infected cells (Fig. S1 , panel (i), (ii) and (iii)). Panel (ii) shows that even in in-vitro transport assay, SARS-CoV 9b protein localizes in both cytoplasm as well as nucleus. As shown in panel (v), the SARS-CoV 9b protein was able to enter the nucleus even in the presence of WGA showing that its entry is independent of active transport pathway. The SARS-CoV 9b protein triggers caspase 3 mediated apoptosis when retained in the nucleus of mammalian cells While performing pulse-chase assays, we found that a significant number of Vero E6 cells, in which nuclear export of 9b has been inhibited (either by treating with LMB or using NES deficient 9b), were showing caspase 3 dependent apoptosis. abstract: BACKGROUND: 9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood. PRINCIPAL FINDINGS/METHODOLOGY: In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. CONCLUSION/SIGNIFICANCE: Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV. url: https://doi.org/10.1371/journal.pone.0019436 doi: 10.1371/journal.pone.0019436 id: cord-339392-2ocz784l author: Sharma, Kulbhushan title: Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation date: 2011-06-15 words: 6208.0 sentences: 375.0 pages: flesch: 51.0 cache: ./cache/cord-339392-2ocz784l.txt txt: ./txt/cord-339392-2ocz784l.txt summary: BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. It is known that under stress conditions the expression level of Hsp40 is enhanced and its cellular localization changes from cytoplasmic to nuclear [38] , however its distribution in influenza virus infected cells was not studied. Taken together, these results suggest that during IAV infection, NP induces the dissociation of the P58 IPK -Hsp40 complex leading to an inhibition of PKR activation and downregulation of eIF2a phosphorylation. In case of influenza virus infection, viral NS1 protein is known to bind directly to PKR and inhibit its activation [20, 21] . abstract: BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection. url: https://doi.org/10.1371/journal.pone.0020215 doi: 10.1371/journal.pone.0020215 id: cord-353410-tbmtg88k author: Sharma, Shreela V. title: Using a rapid assessment methodology to identify and address immediate needs among low-income households with children during COVID-19 date: 2020-10-01 words: 3942.0 sentences: 205.0 pages: flesch: 56.0 cache: ./cache/cord-353410-tbmtg88k.txt txt: ./txt/cord-353410-tbmtg88k.txt summary: Due to COVID-19-related school closures, states were under "shelter in place" orders, and Brighter Bites administered a rapid assessment survey to identify social needs among their families. While overall results of the qualitative thematic analysis for the n = 1048 participants are presented elsewhere (Sharma et al., under review) , a qualitative analysis of participant responses in the high-risk group revealed four major themes presented in Table 2 : fear of contracting COVID-19, disruption of employment status, financial hardship, and exacerbated food insecurity. Conducting a COVID-19 rapid response survey was a purposeful decision on part of Brighter Bites to identify those with highest need during this time of crisis and develop a framework to immediately address a variety of social needs among those in the "high risk" category. abstract: OBJECTIVE: Brighter Bites is a school-based health promotion program that delivers fresh produce and nutrition education to low-income children and families. Due to COVID-19-related school closures, states were under “shelter in place” orders, and Brighter Bites administered a rapid assessment survey to identify social needs among their families. The purpose of this study is to demonstrate the methodology used to identify those with greatest social needs during this time (“high risk”), and to describe the response of Brighter Bites to these “high risk” families. METHODS: The rapid assessment survey was collected in April 2020 across Houston, Dallas, Washington DC, and Southwest Florida. The survey consisted of items on disruption of employment status, financial hardship, food insecurity, perceived health status and sociodemographics. The open-ended question “Please share your greatest concern at this time, or any other thoughts you would like to share with us.” was asked at the end of each survey to triage “high risk” families. Responses were then used to articulate a response to meet the needs of these high risk families. RESULTS: A total of 1048 families completed the COVID-19 rapid response survey, of which 71 families were triaged and classified as “high risk” (6.8% of survey respondents). During this time, 100% of the “high risk” participants reported being food insecure, 85% were concerned about their financial stability, 82% concerned about the availability of food, and 65% concerned about the affordability of food. A qualitative analysis of the high-risk group revealed four major themes: fear of contracting COVID19, disruption of employment status, financial hardship, and exacerbated food insecurity. In response, Brighter Bites pivoted, created, and deployed a framework to immediately address a variety of social needs among those in the “high risk” category. Administering a rapid response survey to identify the immediate needs of their families can help social service providers tailor their services to meet the needs of the most vulnerable. url: https://www.ncbi.nlm.nih.gov/pubmed/33002052/ doi: 10.1371/journal.pone.0240009 id: cord-274241-biqbsggu author: Shaw, Timothy I. title: Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date: 2012-11-15 words: 6003.0 sentences: 339.0 pages: flesch: 52.0 cache: ./cache/cord-274241-biqbsggu.txt txt: ./txt/cord-274241-biqbsggu.txt summary: Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. To address some of these deficiencies, we have performed transcriptome sequencing and analysis of spleen, lung, kidney and poly-IC-stimulated primary kidney cells to identify genes of interest for assessing the host response to TCRV infection. There were 20,145 contigs that mapped to Pteropus alecto, Australian flying fruit bat, and 18,359 that overlapped between genomic and transcriptome sequences for all three datasets ( Figure 5 ). abstract: The Jamaican fruit bat (Artibeus jamaicensis) is one of the most common bats in the tropical Americas. It is thought to be a potential reservoir host of Tacaribe virus, an arenavirus closely related to the South American hemorrhagic fever viruses. We performed transcriptome sequencing and annotation from lung, kidney and spleen tissues using 454 and Illumina platforms to develop this species as an animal model. More than 100,000 contigs were assembled, with 25,000 genes that were functionally annotated. Of the remaining unannotated contigs, 80% were found within bat genomes or transcriptomes. Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. We also identified 466 immune-related genes, which may be useful for studying Tacaribe virus infection of this species. The Jamaican fruit bat transcriptome dataset is a resource that should provide additional candidate markers for studying bat evolution and ecology, and tools for analysis of the host response and pathology of disease. url: https://www.ncbi.nlm.nih.gov/pubmed/23166587/ doi: 10.1371/journal.pone.0048472 id: cord-000375-fvfl0bn1 author: Shen, Ching-I title: The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus date: 2011-05-06 words: 4026.0 sentences: 208.0 pages: flesch: 55.0 cache: ./cache/cord-000375-fvfl0bn1.txt txt: ./txt/cord-000375-fvfl0bn1.txt summary: This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry. In contrast to the finding for MAA/MAL-I, abundant SNA signals were mainly restricted to the mucin + cells (ratio of SNA + /mucin + cells, 0.8560.09, n = 368) ( Fig. 2A) , indicating that the goblet cells expressed SAa2-6Gal terminal glycan. To determine whether a single basal cells can express both SAa2-3Gal and SAa2-6Gal, CTE cells were triple-stained with K14 primary antibody (Cy5-2u Ab, purple), FITC-conjugated MAA (green) and biotin-labeled SNA (detected by Cy3-Streptovidin, red) (Figs. In humans, by contrast, both ciliated and goblet cells can be labeled with MAA/MAL-I and SNA [19, 20] , indicating that these two epithelial cells have both types of influenza viral receptors. abstract: Sialic acids (SAs) linked to galactose (Gal) in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively. We demonstrate that chicken tracheal ciliated cells express α2,3-linked SA, while goblet cells mainly express α2,6-linked SA. In addition, the plant lectin MAL-II, but not MAA/MAL-I, is bound to the surface of goblet cells, suggesting that SA2,3-linked oligosaccharides with Galβ1–3GalNAc subterminal residues are specifically present on the goblet cells. Moreover, both α2,3- and α2,6-linked SAs are detected on single tracheal basal cells. At a low multiplicity of infection (MOI) avian influenza virus H6N1 is exclusively detected in the ciliated cells, suggesting that the ciliated cell is the major target cell of the H6N1 virus. At a MOI of 1, ciliated, goblet and basal cells are all permissive to the AIV infection. This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089607/ doi: 10.1371/journal.pone.0018894 id: cord-004068-d66lwylf author: Shimoda, Tomoko title: Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections date: 2019-12-27 words: 4676.0 sentences: 221.0 pages: flesch: 43.0 cache: ./cache/cord-004068-d66lwylf.txt txt: ./txt/cord-004068-d66lwylf.txt summary: A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. Furthermore, we propose that fomites warmed to human body core temperature may help to control bacterial survival in dry environments, and that such a strategy may prohibit the emergence of human pathogenic bacteria in hospital environments, eventually reducing the need for antibiotics as well as disinfectants. A heatmap generated with the high-resolution infrared sensor showed that in contrast to the stainless steel pipe without the heater, the surface temperature on the heated pipe was maintained at body core temperature (Fig 5A) , indicating that it is an effective tool to monitor the influence of temperature on bacterial survival on a dry surface. Taken together, we concluded that the handrail device warmed to human body core temperature prohibited the prolonged survival of some bacteria and a yeast-like fungus responsible for nosocomial infections on a dry surface. abstract: We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934310/ doi: 10.1371/journal.pone.0226952 id: cord-295536-dbpt4dhr author: Shook, Natalie J. title: Disease avoidance in the time of COVID-19: The behavioral immune system is associated with concern and preventative health behaviors date: 2020-08-20 words: 4592.0 sentences: 270.0 pages: flesch: 40.0 cache: ./cache/cord-295536-dbpt4dhr.txt txt: ./txt/cord-295536-dbpt4dhr.txt summary: This study examined whether individual differences in BIS reactivity (germ aversion, pathogen disgust sensitivity) were associated with concern about COVID-19 and engagement in recommended preventative health behaviors (social distancing, handwashing, cleaning/disinfecting, avoiding touching face, wearing facemasks). Germ aversion and pathogen disgust sensitivity were the two variables most consistently associated with COVID-19 concern and preventative health behaviors, while accounting for demographic, health, and psychosocial covariates. In general, younger age, higher income, more populated location of residence, more recent illness, better perceived health, having/had COVID-19, greater religiosity, greater extraversion, greater conscientiousness, greater perceived infectability, greater germ aversion, and greater pathogen disgust sensitivity were associated with engaging in most (at least three) of the preventative health behaviors more frequently. When demographic, health, social, personality, and BIS variables were considered simultaneously, greater germ aversion and pathogen disgust sensitivity were most consistently associated with COVID-19 concern and preventative behaviors. abstract: The coronavirus disease 2019 (COVID-19) poses a serious global health threat. Without a vaccine, behavior change is the most effective means of reducing disease transmission. Identifying psychological factors that may encourage engagement in preventative health behaviors is crucial. The behavioral immune system (BIS) represents a set of psychological processes thought to promote health by encouraging disease avoidance behaviors. This study examined whether individual differences in BIS reactivity (germ aversion, pathogen disgust sensitivity) were associated with concern about COVID-19 and engagement in recommended preventative health behaviors (social distancing, handwashing, cleaning/disinfecting, avoiding touching face, wearing facemasks). From March 20 to 23, 2020, a US national sample (N = 1019) completed an online survey. Germ aversion and pathogen disgust sensitivity were the two variables most consistently associated with COVID-19 concern and preventative health behaviors, while accounting for demographic, health, and psychosocial covariates. Findings have implications for the development of interventions intended to increase preventative health behaviors. url: https://doi.org/10.1371/journal.pone.0238015 doi: 10.1371/journal.pone.0238015 id: cord-000715-zl1s82yi author: Shulman, Lester M. title: Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition date: 2012-07-16 words: 4786.0 sentences: 248.0 pages: flesch: 50.0 cache: ./cache/cord-000715-zl1s82yi.txt txt: ./txt/cord-000715-zl1s82yi.txt summary: These samples were selected from among archived stool samples previously tested for enterovirus and MS2 after extraction by QIAamp Viral RNA Mini Kit. A sufficient number of samples with high, intermediate, and low levels of inhibitors were chosen for re-analysis to enable comparison between extraction procedures at each of these levels of inhibition. Analysis of variance ( Fig. 3 , part 2), indicated that there was no significant difference (paired t-test, P.0.05) between the inhibition of rRT-PCR of the MS2 external control and the added enterovirus (P.0.05) for protocols A, C, and D. Stool suspensions (N = 185) prepared for routine analysis of clinical stool samples sent to the Central Virology Laboratory (CVL) at Chaim Sheba Medical Center in Israel were used to evaluate the efficiency of four different RNA extraction systems in excluding inhibitors of rRT-PCR. abstract: Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397973/ doi: 10.1371/journal.pone.0039455 id: cord-273594-vmbhok1u author: Sichelstiel, Anke title: Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation date: 2014-06-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation url: https://doi.org/10.1371/journal.pone.0098440 doi: 10.1371/journal.pone.0098440 id: cord-313107-6cfenpxm author: Singh, Anirudh K. title: Evaluation of pooled sample analysis strategy in expediting case detection in areas with emerging outbreaks of COVID-19: A pilot study date: 2020-09-22 words: 2889.0 sentences: 124.0 pages: flesch: 50.0 cache: ./cache/cord-313107-6cfenpxm.txt txt: ./txt/cord-313107-6cfenpxm.txt summary: In this context, a pooled sample testing strategy was evaluated in the setting of emerging disease outbreak in 3 central Indian districts to assess if the cost of the test and turn-around time could be reduced without compromising its diagnostic characteristics and thus lead to early containment of the outbreak. At the reported point prevalence of 4.8% in this study, the negative predictive value of qRT-PCR on pooled samples was around 96% suggesting that the adoption of this strategy as an effective screening tool for COVID-19 needs to be carefully evaluated. We hypothesized that testing of pooled respiratory samples, collected from potentially infected individuals, could lead to faster laboratory confirmation and quicker containment of the emerging infection in these districts and, thus, undertook this study to evaluate the diagnostic concordance between the strategies of pooled vs. abstract: Timely diagnosis of COVID-19 infected individuals and their prompt isolation are essential for controlling the transmission of SARS-CoV-2. Though quantitative reverse transcriptase PCR (qRT-PCR) is the method of choice for COVID-19 diagnostics, the resource-intensive and time-consuming nature of the technique impairs its wide applicability in resource-constrained settings and calls for novel strategies to meet the ever-growing demand for more testing. In this context, a pooled sample testing strategy was evaluated in the setting of emerging disease outbreak in 3 central Indian districts to assess if the cost of the test and turn-around time could be reduced without compromising its diagnostic characteristics and thus lead to early containment of the outbreak. From 545 nasopharyngeal and oropharyngeal samples received from the three emerging districts, a total of 109 pools were created with 5 consecutive samples in each pool. The diagnostic performance of qRT-PCR on pooled sample was compared with that of individual samples in a blinded manner. While pooling reduced the cost of diagnosis by 68% and the laboratory processing time by 66%, 5 of the 109 pools showed discordant results when compared with induvial samples. Four pools which tested negative contained 1 positive sample and 1 pool which was positive did not show any positive sample on deconvolution. Presence of a single infected sample with Ct value of 34 or higher, in a pool of 5, was likely to be missed in pooled sample analysis. At the reported point prevalence of 4.8% in this study, the negative predictive value of qRT-PCR on pooled samples was around 96% suggesting that the adoption of this strategy as an effective screening tool for COVID-19 needs to be carefully evaluated. url: https://www.ncbi.nlm.nih.gov/pubmed/32960929/ doi: 10.1371/journal.pone.0239492 id: cord-329727-h47q76y8 author: Sisó-Almirall, Antoni title: Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona date: 2020-08-21 words: 3441.0 sentences: 201.0 pages: flesch: 53.0 cache: ./cache/cord-329727-h47q76y8.txt txt: ./txt/cord-329727-h47q76y8.txt summary: CONCLUSION: Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts. Therefore, this study aimed to describe the clinical, biological and radiological manifestations, the evolution, treatments and mortality rate of patients with COVID-19 infection in the population of Barcelona city and determine the most important predictors of a poor prognosis. Signs and symptoms, the main available haematological and biochemical data and the results of imaging tests were recorded, as were comorbidities, the evolution, the hospitalization rate, intensive care unit (ICU) admission and the treatments received. This study summarizes the clinical, biological and radiological characteristics, evolution and prognostic factors of patients with COVID-19 disease in primary and community healthcare. https://doi.org/10.1371/journal.pone.0237960.t002 In bold, statistically significant independent predictive factors associated with hospitalization, death or ICU admission (logistic multivariate regression adjusted for age and sex). abstract: BACKGROUND: In addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community. AIM: To determine clinical factors of a poor prognosis in patients with COVID-19 infection. DESIGN AND SETTING: Descriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000. METHOD: Examination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Logistic multivariate regression models adjusted for age and sex were constructed to analyse independent predictive factors associated with death, ICU admission and hospitalization. RESULTS: We included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged ≥ 65 years): 123 (38.2) were health workers (doctors, nurses, auxiliaries). Predictors of ICU admission or death were greater age (OR = 1.05; 95%CI = 1.03 to 1.07), male sex (OR = 2.94; 95%CI = 1.55 to 5.82), autoimmune disease (OR = 2.82; 95%CI = 1.00 to 7.84), bilateral pulmonary infiltrates (OR = 2.86; 95%CI = 1.41 to 6.13), elevated lactate-dehydrogenase (OR = 2.85; 95%CI = 1.28 to 6.90), elevated D-dimer (OR = 2.85; 95%CI = 1.22 to 6.98) and elevated C-reactive protein (OR = 2.38; 95%CI = 1.22 to 4.68). Myalgia or arthralgia (OR = 0.31; 95%CI = 0.12 to 0.70) was protective factor against ICU admission and death. Predictors of hospitalization were chills (OR = 5.66; 95%CI = 1.68 to 23.49), fever (OR = 3.33; 95%CI = 1.89 to 5.96), dyspnoea (OR = 2.92; 95%CI = 1.62 to 5.42), depression (OR = 6.06; 95%CI = 1.54 to 40.42), lymphopenia (OR = 3.48; 95%CI = 1.67 to 7.40) and elevated C-reactive protein (OR = 3.27; 95%CI = 1.59 to 7.18). Anosmia (OR = 0.42; 95%CI = 0.19 to 0.90) was the only significant protective factor for hospitalization after adjusting for age and sex. CONCLUSION: Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts. url: https://www.ncbi.nlm.nih.gov/pubmed/32822413/ doi: 10.1371/journal.pone.0237960 id: cord-001186-jkg7qkj6 author: Skowronski, Danuta M. title: Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk date: 2014-01-27 words: 8871.0 sentences: 412.0 pages: flesch: 40.0 cache: ./cache/cord-001186-jkg7qkj6.txt txt: ./txt/cord-001186-jkg7qkj6.txt summary: During spring-summer 2009, several observational studies from Canada reported that prior receipt of the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness, with estimated risk or odds ratios of 1.4-2.5 compared to those unvaccinated [1] . Protein microarray results were consistent with ELISA but in addition showed vaccine-induced HA1 antibody to the seasonal H1 antigen, for which values were significantly higher in vaccinated animals relative to pre-immunization and compared to placebo from day 28, most pronounced from day 49 after the first TIV dose (i.e. three weeks after two-dose vaccine series completion) ( Figure 2 ). Lower neutralizing antibody to A(H1N1)pdm09 even at Ch+14 among vaccinated versus placebo ferrets, although not statistically significant, is consistent with human immunogenicity trials showing blunting of pandemic H1N1 vaccine-induced responses in association with prior seasonal vaccine receipt [53] [54] [55] [56] . abstract: During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903544/ doi: 10.1371/journal.pone.0086555 id: cord-333853-p2kbjwpy author: Smee, Donald F. title: Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) date: 2011-10-13 words: 4585.0 sentences: 222.0 pages: flesch: 48.0 cache: ./cache/cord-333853-p2kbjwpy.txt txt: ./txt/cord-333853-p2kbjwpy.txt summary: title: Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. Ad5-vectored mouse interferon (mDEF201) resulted in sustained IFN levels [16] , that completely protected mice from a lethal Western equine encephalitis virus infection when given intramuscularly at 10 7 plaque forming units (PFU)/ mouse up to 7 days prior to virus challenge [16] . The extent of inhibition of lung Intranasal treatments with mDEF201 (10 7 PFU/mouse) were given one time only on the indicated day prior to virus exposure. abstract: An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. mDEF201 was administered as a single intranasal treatment either prophylactically or therapeutically at doses of 10(6) to 10(8) plaque forming units/mouse. When the prophylactic treatment was given at 56 days prior to infection, it protected 90% of animals from death (100% protection for treatments given between 1–49 days pre-infection), with minimal weight loss occurring during infection. Surviving animals re-challenged with virus 22 days after the primary infection were protected from death, indicating that mDEF201 did not compromise the immune response against the initial infection. Post-exposure therapy was given between 6–24 h after vaccinia virus exposure and protection was afforded by a 10(8) dose of mDEF201 given at 24 h, whereas a 10(7) dose was effective up to 12 h. Comparisons were made of the ability of mDEF201, given either 28 or 1 day prior to infection, to inhibit tissue virus titers and lung infection parameters. Lung, liver, and spleen virus titers were inhibited to nearly the same extent by either treatment, as were lung weights and lung hemorrhage scores (indicators of pneumonitis). Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. In contrast, viral titers and lung infection parameters were high in the placebo group on day 5 of the infection. These results demonstrate the long-acting prophylactic and treatment capacity of mDEF201 to combat vaccinia virus infections. url: https://www.ncbi.nlm.nih.gov/pubmed/22022603/ doi: 10.1371/journal.pone.0026330 id: cord-340195-425rd7ul author: Smith, Kristine M. title: Zoonotic Viruses Associated with Illegally Imported Wildlife Products date: 2012-01-10 words: 4427.0 sentences: 210.0 pages: flesch: 48.0 cache: ./cache/cord-340195-425rd7ul.txt txt: ./txt/cord-340195-425rd7ul.txt summary: Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence. Our study is the first to establish surveillance for zoonotic viruses in wild animal products illegally imported into the United States in an effort to prevent the transmission of infectious agents from these shipments. To date, four groups of HTLV viruses found in humans are believed to have originated from corresponding STLV strains in NHP species (including mangabeys, baboons, and chimpanzees) via multiple transmission events [35] . In summary, our study establishes initial surveillance methodology to detect and identify zoonotic pathogens and species of origin of wildlife products entering the United States. abstract: The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence. url: https://doi.org/10.1371/journal.pone.0029505 doi: 10.1371/journal.pone.0029505 id: cord-256837-100ir651 author: Smith, Steven B. title: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date: 2012-03-14 words: 8447.0 sentences: 415.0 pages: flesch: 38.0 cache: ./cache/cord-256837-100ir651.txt txt: ./txt/cord-256837-100ir651.txt summary: Several recent studies have generated multiple mRNA microarray gene expression datasets derived from experiments involving the infection of human cell-lines or animal models with one or more of the major respiratory viruses [21] [22] [23] . Through a systematic analysis of these respiratory virus-human host gene expression datasets, we determined common sets of genes and pathways involved in host responses to viral infections. A total of seven different respiratory viruses were analyzed, represented by fifteen unique Gene Expression Omnibus (GEO) datasets (indicated by GEO Series or GSE accession numbers), nine different human cell types, and seven different array platforms for a total of 28 unique comparisons. This assumption is based on the occurrence of genes that are differentially expressed in infection models for at least five of the seven respiratory viruses, have involvement in a number of relevant pathways related to host immune response, and encode for known drug targets. abstract: BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention. url: https://doi.org/10.1371/journal.pone.0033174 doi: 10.1371/journal.pone.0033174 id: cord-339920-dr5bvpm0 author: Soberman, Roy J. title: CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2 date: 2012-10-17 words: 7447.0 sentences: 406.0 pages: flesch: 54.0 cache: ./cache/cord-339920-dr5bvpm0.txt txt: ./txt/cord-339920-dr5bvpm0.txt summary: We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1 2/2 macrophages showed a marked decrease in the generation of both IL-6 and CCL5 (Rantes) in response to stimulation by both Pam 2 CSK 4 and HSV-1, whereas no difference was observed in the generation of any cytokine/chemokine in response to the TLR4 ligand bacterial lipopolysaccharide (LPS). These results indicated that CD200R1 directly controls the inducible surface expression of TLR2 either directly or secondary to decreased viral replication and that it may play a role in the amplification of HSV-1 infection. The lack of difference in brain leukocyte scores, and in CCL2 (MCP-1), CCL5 (Rantes), and IL-6 levels indicated that CD200R1 2/2 mice had equivalent or modestly reduced brain inflammation, rather than an enhanced, inflammatory response to HSV-1 infection compared to CD200R1 +/+ mice (see above). abstract: The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(−/−) peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(−/−) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(−/−) mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(−/−) mice and CD200R1(−/−) fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence. url: https://doi.org/10.1371/journal.pone.0047740 doi: 10.1371/journal.pone.0047740 id: cord-353245-es7b1rs0 author: Song, Deping title: Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013 date: 2015-03-19 words: 4259.0 sentences: 176.0 pages: flesch: 55.0 cache: ./cache/cord-353245-es7b1rs0.txt txt: ./txt/cord-353245-es7b1rs0.txt summary: Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5''-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. Genetic characteristics were observed between the two groups: 1) compared to genome sequences of the members in G1, four insertions, 20803G, 20810CAGGGTGTCAA20820, 20830G, 21042AAT21044 and two deletions, 20842A, 21097CGTGAT21102, existed in the N-terminal domain (NTD) of the S protein in G 2 members; 2) the three field PEDV strains of JS2008, JS2008new and SD-M together with two attenuated PEDV strains, DR13 and vaccine_KC189944, were clustered into subgroup 1b. Notably, an amino acid substitution was found in the middle of one neutralizing epitope Phylogenetic trees based on the complete genome, aa sequences of structural proteins and ORF3 of PEDV strains. Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China abstract: Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious, acute enteric viral disease of swine characterized by vomiting, watery diarrhea, dehydration and death. To identify and characterize the field PEDVs associated with the outbreaks of severe diarrhea in piglets in Jiangxi, 2013, the complete genome sequences of two representative strains of PEDV, designated CH/JX-1/2013 and CH/JX-2/2013, were determined and analyzed. The genome sequences of both emergent Jiangxi PEDV strains, CH/JX-1/2013 and CH/JX-2/2013, were 28,038 nucleotides in length excluding 3’ poly (A) tail. Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5´-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. The nucleotide identity between the two Jiangxi strains (CH/JX-1/2013 and CH/JX-2/2013) and 30 strains of PEDV identified ante-2010 and post-2010 ranged from 96.3–97.0% and 97.3–99.7%, respectively. Multiple nucleotide and deduced amino acid mutations were observed in the ORF1a/b, S, ORF3, E, M and N genes among the current field PEDV strains when compared to the CV777 strain. Some of the mutations altered the amino acid charge and hydrophilicity, and notably, there was an amino acid substitution in the middle of one neutralizing epitope (L1371I) of the S gene of both CH/JX-1/2013 and CH/JX-2/2013. Taken together, the accumulated genetic variations of the current field PEDV strains might have led to antigenic changes of the viruses, which might confer the less effectiveness or failure of the CV777-based vaccines currently being widely used in Jiangxi, China. url: https://doi.org/10.1371/journal.pone.0120310 doi: 10.1371/journal.pone.0120310 id: cord-281124-4nhy35xn author: Soowannayan, Chumporn title: RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date: 2011-08-03 words: 5596.0 sentences: 259.0 pages: flesch: 53.0 cache: ./cache/cord-281124-4nhy35xn.txt txt: ./txt/cord-281124-4nhy35xn.txt summary: To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. In a preliminary attempt to identify an RNA packaging signal in the GAV genome, EMSAs were performed using ssRNAs synthesized to various genome regions including (i) an ORF1b gene 39-region spanning the relative position to the genome packaging signal identified in MHV [28] , (ii) a 39-terminal genome region corresponding in position to the region in the infectious bronchitis virus (IBV) genome reported to contain an RNA binding domain [29] and (iii) the 59-genomic RNA terminus which, in coronaviruses, has also been reported to interact specifically with N protein [30] . abstract: Gill-associated virus (GAV) infects Penaeus monodon shrimp and is the type species okavirus in the Roniviridae, the only invertebrate nidoviruses known currently. Electrophoretic mobility shift assays (EMSAs) using His(6)-tagged full-length and truncated proteins were employed to examine the nucleic acid binding properties of the GAV nucleocapsid (N) protein in vitro. The EMSAs showed full-length N protein to bind to all synthetic single-stranded (ss)RNAs tested independent of their sequence. The ssRNAs included (+) and (−) sense regions of the GAV genome as well as a (+) sense region of the M RNA segment of Mourilyan virus, a crustacean bunya-like virus. GAV N protein also bound to double-stranded (ds)RNAs prepared to GAV ORF1b gene regions and to bacteriophage M13 genomic ssDNA. EMSAs using the five N protein constructs with variable-length N-terminal and/or C-terminal truncations localized the RNA binding domain to a 50 amino acid (aa) N-terminal sequence spanning Met(11) to Arg(60). Similarly to other RNA binding proteins, the first 16 aa portion of this sequence was proline/arginine rich. To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. Moreover, as the synthetic peptide formed higher-order complexes in the presence of RNA, the domain might also play some role in protein/protein interactions stabilizing the helical structure of GAV nucleocapsids. url: https://www.ncbi.nlm.nih.gov/pubmed/21857914/ doi: 10.1371/journal.pone.0022156 id: cord-342519-tjr6dvtt author: Souza, Thiago Moreno L. title: H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis date: 2010-11-30 words: 5166.0 sentences: 293.0 pages: flesch: 48.0 cache: ./cache/cord-342519-tjr6dvtt.txt txt: ./txt/cord-342519-tjr6dvtt.txt summary: The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. Because the analysis of this novel viral infection in cancer patients is an important component of the 2009 pandemics, we conducted a prospective cohort study aimed at evaluating the clinical course of influenza infection, the duration of viral shedding, H1N1pdm evolution and the emergence of antiviral resistance in hospitalized cancer patients with a severe H1N1pdm infection in a reference cancer center during the winter of 2009 in Brazil. Although prolonged influenza A shedding has been observed for a cancer patient infected with the H3N2 seasonal virus [15] , more detailed data on H1N1pdm secretion in severely ill cancer patients are required. abstract: BACKGROUND: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. METHODS: We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. RESULTS: A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. CONCLUSIONS: Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation. url: https://doi.org/10.1371/journal.pone.0014158 doi: 10.1371/journal.pone.0014158 id: cord-337913-eu2gn4bl author: Stojanov, Ana title: Does Perceived Lack of Control Lead to Conspiracy Theory Beliefs? Findings from an online MTurk sample date: 2020-08-17 words: 7933.0 sentences: 414.0 pages: flesch: 48.0 cache: ./cache/cord-337913-eu2gn4bl.txt txt: ./txt/cord-337913-eu2gn4bl.txt summary: Across six studies conducted online using MTurk samples, we observed no effect of control manipulations on conspiracy theory beliefs, while replicating previously reported correlational evidence of their association. Given the significance and potential consequences of widespread conspiracy beliefs [38, 39] , and the plausible but largely unsubstantiated role of control in their appeal, we here report three studies to test the effects of lack of control on conspiracy theory beliefs using a standard priming paradigm and a validated measure of conspiracy ideation, which reflects the belief that a powerful entity lies behind significant social or political events and that the conventional (official) truth is not the "real" truth. In a recent meta-analysis of experimental manipulations of control on conspiracy beliefs [68] conducted on 45 effect sizes across 23 studies (including those reported here), we found no moderating effect of sample type (MTurk vs. abstract: It is widely believed that conspiracy theory beliefs are the product of perceived lack of control. However, to date there is mixed evidence, at best, to support this claim. We consider the reasons why conspiracy theory beliefs do not appear to be based in any straightforward way on control beliefs, interrogating existing findings and presenting new data that call the relationship into question. Across six studies conducted online using MTurk samples, we observed no effect of control manipulations on conspiracy theory beliefs, while replicating previously reported correlational evidence of their association. The results suggest that conspiracy beliefs are not suitable for compensating for threats to control. We discuss possible reasons for the discrepancy between experimental and correlational effects and examine the limitations of the studies. url: https://www.ncbi.nlm.nih.gov/pubmed/32804940/ doi: 10.1371/journal.pone.0237771 id: cord-286404-eggkqq3b author: Strayer, David R. title: Effect of disease duration in a randomized Phase III trial of rintatolimod, an immune modulator for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome date: 2020-10-29 words: 5439.0 sentences: 266.0 pages: flesch: 47.0 cache: ./cache/cord-286404-eggkqq3b.txt txt: ./txt/cord-286404-eggkqq3b.txt summary: CONCLUSION/SIGNIFICANCE: Analysis of ETT from a Phase III trial has identified within the ITT population, a subset of ME/CFS patients with ≥2 fold increased exercise response to rintatolimod. In the AMP-516 Phase III clinical trial, patients with severe ME/CFS demonstrated significant improvement in the primary endpoint, exercise treadmill tolerance (ETT), compared to placebo controls following the twice weekly for 40 weeks systemic administration [12] of the selective TLR3 dsRNA agonist, rintatolimod (Ampligen 1 ) [10, 11]. Effect of ME/CFS duration in response to rintatolimod fewer patients and reduced statistical power compared to the ITT population (n = 208), the placebo-adjusted mean increase in ETT (Δ = 23.6) within the Target Subset (n = 75) was statistically significant. This post-hoc analysis of the successful AMP-516 double-blind, placebo-controlled, randomized, Phase III trial has identified a subgroup of patients defined primarily by the length of ME/CFS symptoms (2-8 years) with an increased likelihood of a clinically beneficial response to rintatolimod. abstract: BACKGROUND: Rintatolimod is a selective TLR3 agonist, which has demonstrated clinical activity for ME/CFS in Phase II and Phase III double-blind, placebo-controlled, randomized, multi-site clinical trials. METHODS AND FINDINGS: A hypothesis-based post-hoc analysis of the Intent to Treat (ITT) population diagnosed with ME/CFS from 12 independent clinical sites of a Phase III trial was performed to evaluate the effect of rintatolimod therapy based on disease duration. The clinical activity of rintatolimod was evaluated by exercise treadmill tolerance (ETT) using a modified Bruce protocol. The ITT population (n = 208) was divided into two subsets of symptom duration. Patients with symptom duration of 2–8 years were identified as the Target Subset (n = 75); the remainder (<2 year plus >8 year) were identified as the Non-Target Subset (n = 133). Placebo-adjusted percentage improvements in exercise duration and the vertical rise for the Target Subset (n = 75) were more than twice that of the ITT population. The Non-Target Subset (n = 133) failed to show any clinically significant ETT response to rintatolimod when compared to placebo. Within the Target Subset, 51.2% of rintatolimod-treated patients improved their exercise duration by ≥25% (p = 0.003) despite reduced statistical power from division of the original ITT population into two subsets. CONCLUSION/SIGNIFICANCE: Analysis of ETT from a Phase III trial has identified within the ITT population, a subset of ME/CFS patients with ≥2 fold increased exercise response to rintatolimod. Substantial improvement in physical performance was seen for the majority (51.2%) of these severely debilitated patients who improved exercise duration by ≥25%. This magnitude of exercise improvement was associated with clinically significant enhancements in quality of life. The data indicate that ME/CFS patients have a relatively short disease duration window (<8 years) to expect a significant response to rintatolimod under the dosing conditions utilized in this Phase III clinical trial. These results may have direct relevance to the cognitive impairment and fatigue being experienced by patients clinically recovered from COVID-19 and free of detectable SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00215800. url: https://doi.org/10.1371/journal.pone.0240403 doi: 10.1371/journal.pone.0240403 id: cord-262876-civfvk45 author: Su, Tong title: Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China date: 2013-06-24 words: 4492.0 sentences: 244.0 pages: flesch: 43.0 cache: ./cache/cord-262876-civfvk45.txt txt: ./txt/cord-262876-civfvk45.txt summary: title: Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration. Three groups of participants in Shanghai, China, were enrolled in this cross-sectional epidemiological study: health professionals, medical students, and community residents. Moreover, the knowledge level was also significantly different among clinicians, public health physicians, nurses, and medical technicians, especially in correctly answering 5 questions (Table S2) . Figure 3 presents the key contents concerning disaster medicine training prioritized by health professionals, medical students, and community residents. Figure 4 presents the most interested contents of disaster medicine training prioritized by health professionals, medical students, and community residents. In this study, we evaluated the current knowledge levels and training needs of disaster medicine among health professionals, medical students, and community residents in Shanghai, China. abstract: BACKGROUND: Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education. METHODS: A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%. RESULTS: Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p<0.001), whereas public health students performed better than clinical medical students (p<0.001). In community residents, education background significantly affected the knowledge level on disaster medicine (p<0.001). Training needs of disaster medicine were generally high among the surveyed. ‘Lecture’ and ‘practical training’ were preferred teaching methods. The selected key and interested contents on disaster medicine training were similar between health professionals and medical students, while the priorities chosen by local residents were quite different from health professionals and medical students (p<0.001). CONCLUSIONS: Traditional clinical-oriented medical education might lead to a huge gap between the knowledge level on disaster medicine and the current needs of disaster preparedness. Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration. url: https://doi.org/10.1371/journal.pone.0067041 doi: 10.1371/journal.pone.0067041 id: cord-281815-zvs5qe8x author: Subramanian, Shoba title: Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3 date: 2009-04-09 words: 5953.0 sentences: 267.0 pages: flesch: 45.0 cache: ./cache/cord-281815-zvs5qe8x.txt txt: ./txt/cord-281815-zvs5qe8x.txt summary: The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Treatment of erythrocytic parasites with cysteine protease inhibitors or disruption of the falcipain-2 gene results in accumulation of undegraded hemoglobin in the food vacuole, confirming a role for this enzyme in hemoglobin hydrolysis [6, 10] . To better characterize the roles of falcipain-2 and falcipain-3, we evaluated activities of these proteases against a library of small peptide substrates, a series of larger peptides spanning the sequences of a and b globin, and intact human hemoglobin. Falcipain-2 and falcipain-3 demonstrated a marked preference for cleavage of small peptide substrates with P 2 Leu, but the enzymes showed less specificity against larger peptides and intact hemoglobin, with hydrolysis at multiple sites. Despite the presence of multiple proteases in the food vacuole, it is noteworthy that treatment of cultured parasites with specific inhibitors of cysteine proteases fully blocked the hydrolysis of hemoglobin, highlighting the key role for the falcipains in this process [22] . abstract: The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1) – P(4) amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2) position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent (18)O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2) Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents. url: https://doi.org/10.1371/journal.pone.0005156 doi: 10.1371/journal.pone.0005156 id: cord-000063-tex6bgab author: Sui, Hong-Yan title: Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication date: 2009-05-22 words: 3501.0 sentences: 189.0 pages: flesch: 50.0 cache: ./cache/cord-000063-tex6bgab.txt txt: ./txt/cord-000063-tex6bgab.txt summary: Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. It was further demonstrated that no siRNA-resistant viral mutation appeared in siM2 targeting sequence even after the virus was cultured in the shRNA expressing stable cell line for 40 passages. A recent report by Zhou et al [30] also showed that several siRNAs targeting NP and M genes exhibited effective inhibition against influenza A virus replication in cultured MDCK cells and in animal models. Taken together, all the findings about effective RNAi target, lentiviral vector delivery and the establishment of stable shRNA expressing cell lines in our study provide rational information for the development of siRNAs as prophylaxis and therapy for influenza virus infection in humans. abstract: RNA interference (RNAi) provides a powerful new means to inhibit viral infection specifically. However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics. In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells. Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication. The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1. In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression. A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed. Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682565/ doi: 10.1371/journal.pone.0005671 id: cord-285433-ehnu83qe author: Sun, Hongliu title: Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry date: 2015-08-21 words: 4698.0 sentences: 265.0 pages: flesch: 54.0 cache: ./cache/cord-285433-ehnu83qe.txt txt: ./txt/cord-285433-ehnu83qe.txt summary: METHODS: An antibody analysis method is reported for the detection and identification of CMV antibodies in serum using a biosensor based on high spatial resolution imaging ellipsometry (BIE). As such, the concentration of CMV antibody in serum was quantitatively detected by BIE and then compared using ELISAs. Silicon wafers were purchased from the General Research Institute for Nonferrous Metals (China). Compared to blank controls areas, the purified CMV antibody and patient serum sample detection areas had markedly thicker films, with the average grayscale value displaying significant increases, while negative control areas did not (Fig 1) . Quantitative detection of CMV antibodies in clinical serum 41 CMV patients (Table A in S2 File) with quantitative results by ELISA were tested with BIE (Fig 4) . Thus, this label-free method may avoid some Detection of CMV antibodies in patient serum using BIE. abstract: BACKGROUND: Cytomegalovirus (CMV) is the most common infectious cause of mental disability in newborns in developed countries. There is an urgent need to establish an early detection and high-throughput screening method for CMV infection using portable detection devices. METHODS: An antibody analysis method is reported for the detection and identification of CMV antibodies in serum using a biosensor based on high spatial resolution imaging ellipsometry (BIE). CMV antigen (CMV-3A) was immobilized on silicon wafers and used to capture CMV antibodies in serum. An antibody against human immunoglobulin G (anti-IgG) was used to confirm the IgG antibody against CMV captured by the CMV-3A. RESULTS: Our results show that this assay is rapid and specific for the identification of IgG antibody against CMV. Further, patient serum was quantitatively assessed using the standard curve method, and the quantitative results were in agreement with the enzyme-linked immunosorbent assay. The CMV antibody detection sensitivity of BIE reached 0.01 IU/mL. CONCLUSIONS: This novel biosensor may be a valuable diagnostic tool for analysis of IgG antibody against CMV during CMV infection screening. url: https://doi.org/10.1371/journal.pone.0136253 doi: 10.1371/journal.pone.0136253 id: cord-353866-0r1b44id author: Sun, Hongpeng title: Changes of Adult Population Health Status in China from 2003 to 2008 date: 2011-12-02 words: 3421.0 sentences: 185.0 pages: flesch: 54.0 cache: ./cache/cord-353866-0r1b44id.txt txt: ./txt/cord-353866-0r1b44id.txt summary: Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. This study aimed to describe the male and female adult Chinese population health status in multiple dimensions, including overall morbidity, presence of illness in the last 2 weeks and chronic disease in the last 6 months, and healthy behavior as regards smoking, alcohol consumption, and physical activity, using data from the most recent National Health Services Surveys by the Chinese government in 2003 and 2008. However, overall Chinese adult population health status has not been improved due to short time and small proportion of residents performing frequent exercise; hence it seems that the prevalence and burden of chronic diseases will continue to grow. abstract: OBJECTIVES: The purpose of this study was to examine the change in health status of China's adult population between the years of 2003 and 2008 due to rapid economic growth and medical system improvement. METHODS: Data from the third and fourth Chinese national health services surveys covering 141,927 residents in 2003 and 136,371 residents in 2008 who were aged >18 years were analyzed. RESULTS: Chinese respondents in 2008 were more likely to report disease than in 2003. Smoking slightly decreased among men and women, and regular exercise showed much improvement. Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. CONCLUSIONS: Chinese adults in 2008 had worse health status than in 2003 in terms of presence of chronic disease. China's reform of health care will face more complex challenges in coming years from the deteriorating health status in Chinese adults. url: https://www.ncbi.nlm.nih.gov/pubmed/22164286/ doi: 10.1371/journal.pone.0028411 id: cord-271660-5sfkhg19 author: Sun, Hsin-Yun title: Impact of introducing fluorescent microscopy on hospital tuberculosis control: A before-after study at a high caseload medical center in Taiwan date: 2020-04-03 words: 3884.0 sentences: 192.0 pages: flesch: 40.0 cache: ./cache/cord-271660-5sfkhg19.txt txt: ./txt/cord-271660-5sfkhg19.txt summary: METHODS: We measured the impact of switch to fluorescent microscopy on the smear detection rate of culture-confirmed pulmonary TB, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately 400 TB cases annually) in Taipei. Hospitalized patients had typical presentations of pulmonary TB if they had: (a) a prolonged cough for >3 weeks; (b) clinical suspicion of pulmonary TB based on chest radiography, such as cavitary pulmonary lesions, upper lobe diseases, or miliary lesions; or (c) already received a confirmed diagnosis of pulmonary TB by a positive sputum culture of Mycobacterium tuberculosis, positive acid-fast stain (AFS), or positive TB PCR, before the hospitalization. Our previous survey on age/sex-standardised TB incidence ratio of HCWs (using general population as reference)---the excess TB risk that are attributable to nosocomial TB transmission---in Medical Center A showed a drop of this risk, from 3.11 in 2006 to 1.37 in 2012 [23] , and the decrease in time-to-isolation and total non-isolated infectious patient-days was in parallel in the present study. abstract: BACKGROUND: Undiagnosed tuberculosis (TB) patients hospitalized because of comorbidities constitute a challenge to TB control in hospitals. We aimed to assess the impact of introducing highly sensitive fluorescent microscopy for examining sputum smear to replace conventional microscopy under a high TB risk setting. METHODS: We measured the impact of switch to fluorescent microscopy on the smear detection rate of culture-confirmed pulmonary TB, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately 400 TB cases annually) in Taipei. Multivariable Cox regression was applied to adjust for effects of covariates. The effect attributable to the improved smear detection rate was determined using causal mediation analysis. RESULTS: After switch to fluorescence microscopy, median non-isolated infectious duration decreased from 12.5 days to 3 days (P<0.001). Compared with conventional microscopy, fluorescence microscopy increased sputum smear detection rate by two-fold (for all patients: from 22.8% to 48.1%, P<0.001; for patients with cavitary lung lesion: from 43% to 82%, P = 0.029) and was associated with a 2-fold higher likelihood of prompt respiratory isolation (odds ratio mediated by the increase in sputum smear detection rate: 1.8, 95% CI 1.3–2.5). Total non-isolated infectious patient-days in hospital decreased by 69% (from 4,778 patient-days per year to 1,502 patient-days per year). CONCLUSIONS: In a high TB caseload setting, highly sensitive rapid diagnostic tools could substantially improve timing of respiratory isolation and reduce the risk of nosocomial TB transmission. url: https://www.ncbi.nlm.nih.gov/pubmed/32243434/ doi: 10.1371/journal.pone.0230067 id: cord-280471-cqypwi5d author: Sun, Hua-Bao title: The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19 date: 2020-09-25 words: 4324.0 sentences: 202.0 pages: flesch: 57.0 cache: ./cache/cord-280471-cqypwi5d.txt txt: ./txt/cord-280471-cqypwi5d.txt summary: To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. Characteristic chest CT imaging patterns, positive nucleic acid detection in nasal and throat swab samples, normal or decreased numbers of peripheral white blood cells, decreased numbers of lymphocytes and increased levels of inflammatory cytokines are the key factors in the diagnosis of COVID-19 [3] . The total number of lymphocytes, the percentages of lymphocyte subtypes and the levels of inflammatory cytokines (TNF-α and IL-6) secreted by CD4+ helper T lymphocytes in the peripheral blood were detected by hematology counter and flow cytometer, respectively. In the COVID-19 patients in the general, severe and critical groups, the numbers of peripheral lymphocytes and CD4+ T lymphocytes and the ratio of CD4+/CD8+ lymphocytes were significantly lower than those in the normal control group. abstract: To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32976531/ doi: 10.1371/journal.pone.0239532 id: cord-003503-t6cnjwpd author: Sung, Ming-Hua title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan date: 2019-03-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The porcine epidemic diarrhea virus (PEDV) that emerged and spread throughout Taiwan in 2014 triggered significant concern in the country’s swine industry. Acknowledging the absence of a thorough investigation at the geographic level, we used 2014 outbreak sequence information from the Taiwan government’s open access databases plus GenBank records to analyze PEDV dissemination among Taiwanese pig farms. Genetic sequences, locations, and dates of identified PEDV-positive cases were used to assess spatial, temporal, clustering, GIS, and phylogeographic factors affecting PEDV dissemination. Our conclusion is that S gene sequences from 2014 PEDV-positive clinical samples collected in Taiwan were part of the same Genogroup 2 identified in the US in 2013. According to phylogenetic and phylogeographic data, viral strains collected in different areas were generally independent of each other, with certain clusters identified across different communities. Data from GIS and multiple potential infection factors were used to pinpoint cluster dissemination in areas with large numbers of swine farms in southern Taiwan. The data indicate that the 2014 Taiwan PEDV epidemic resulted from the spread of multiple strains, with strong correlations identified with pig farm numbers and sizes (measured as animal concentrations), feed mill numbers, and the number of slaughterhouses in a specifically defined geographic area. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402684/ doi: 10.1371/journal.pone.0213153 id: cord-334955-gnu92up6 author: Sutton, Jeannette title: COVID-19: Retransmission of official communications in an emerging pandemic date: 2020-09-16 words: 7800.0 sentences: 324.0 pages: flesch: 41.0 cache: ./cache/cord-334955-gnu92up6.txt txt: ./txt/cord-334955-gnu92up6.txt summary: In this research, we examine message features shown in prior disasters to increase or decrease message retransmission under imminent threat conditions to develop models of official risk communicators'' messages shared online from February 1, 2020-April 30, 2020. We develop a lexicon of keywords associated with risk communication about the pandemic response, then use automated coding to identify message content and message structural features. They found that actionable and instructive messages and those that included a visual image were highly shared regardless of the time period; however, daily updates in the form of forecasts or current weather conditions involving little uncertainty, as well as message features that increase interaction, such as direct replies and URLs, decreased message passing. Messages that include information sharing decreases retransmission; however, this content increased post emergency declaration by 61%. abstract: As the most visible face of health expertise to the general public, health agencies have played a central role in alerting the public to the emerging COVID-19 threat, providing guidance for protective action, motivating compliance with health directives, and combating misinformation. Social media platforms such as Twitter have been a critical tool in this process, providing a communication channel that allows both rapid dissemination of messages to the public at large and individual-level engagement. Message dissemination and amplification is a necessary precursor to reaching audiences, both online and off, as well as inspiring action. Therefore, it is valuable for organizational risk communication to identify strategies and practices that may lead to increased message passing among online users. In this research, we examine message features shown in prior disasters to increase or decrease message retransmission under imminent threat conditions to develop models of official risk communicators’ messages shared online from February 1, 2020-April 30, 2020. We develop a lexicon of keywords associated with risk communication about the pandemic response, then use automated coding to identify message content and message structural features. We conduct chi-square analyses and negative binomial regression modeling to identify the strategies used by official risk communicators that respectively increase and decrease message retransmission. Findings show systematic changes in message strategies over time and identify key features that affect message passing, both positively and negatively. These results have the potential to aid in message design strategies as the pandemic continues, or in similar future events. url: https://www.ncbi.nlm.nih.gov/pubmed/32936804/ doi: 10.1371/journal.pone.0238491 id: cord-254000-pbzcupjg author: Suvannachart, Pukkapol title: Repeatability, reproducibility, agreement, and safety of Tono-Pen tip cover for intraocular measurement using latex and polyethylene wrap date: 2020-09-28 words: 3623.0 sentences: 264.0 pages: flesch: 60.0 cache: ./cache/cord-254000-pbzcupjg.txt txt: ./txt/cord-254000-pbzcupjg.txt summary: PURPOSE: To evaluate repeatability, reproducibility, and agreement of intraocular pressure measurement with Tono-Pen using Ocufilm and polyethylene wrap tip cover in human eyes. For the right eye, 4 measurements using polyethylene wrap tip cover were done by two examiners (A and B) in random order to assess intra-observer repeatability and inter-observer reproducibility. For the left eye, 4 measurements were done by examiner A using both polyethylene wrap tip cover and Ocufilm in random order to assess intra-observer repeatability and agreement. RESULTS: For examiner A, the repeatability of polyethylene wrap tip cover was -0.34, 95% limits of agreement (LOA) were -3.04 to 2.36, and ICC was 0.93 in the right eyes. For IOP measurement with TP, our previous eye model and study conducted in canine eyes showed good repeatability and agreement between the custom-made polyethylene wrap (PW) tip cover and OF without causing any ocular surface complications [13, 14] . abstract: PURPOSE: To evaluate repeatability, reproducibility, and agreement of intraocular pressure measurement with Tono-Pen using Ocufilm and polyethylene wrap tip cover in human eyes. METHODS: This is a cross-sectional, experimental study. A gas-sterilized, polyethylene wrap was used as an alternative for Tono-Pen tip cover. For the right eye, 4 measurements using polyethylene wrap tip cover were done by two examiners (A and B) in random order to assess intra-observer repeatability and inter-observer reproducibility. For the left eye, 4 measurements were done by examiner A using both polyethylene wrap tip cover and Ocufilm in random order to assess intra-observer repeatability and agreement. Bland-Altman plot and intraclass correlation coefficient (ICC) were used in all analyses. Cost minimization analysis was evaluated. RESULTS: For examiner A, the repeatability of polyethylene wrap tip cover was -0.34, 95% limits of agreement (LOA) were -3.04 to 2.36, and ICC was 0.93 in the right eyes. As for the left eyes, the repeatability of polyethylene wrap tip cover was -0.33, 95% LOA were -3.01 to 2.36, and ICC was 0.93. For examiner B, the repeatability of polyethylene wrap tip cover was -0.02, 95% LOA were -2.88 to 2.83, and ICC was 0.92. The inter-observer reproducibility of polyethylene wrap tip cover was 0.36, 95% LOA were -3.34 to 4.07, and ICC was 0.90. The repeatability of Ocufilm was -0.42, 95% LOA were -2.75 to 1.91, and ICC was 0.95. The agreement of polyethylene wrap tip cover and Ocufilm was -0.71, 95% LOA were -5.18 to 3.76, and ICC was 0.83. There were no allergic reactions or serious complications. From the cost minimization analysis, the local cost for polyethylene tip cover was approximately 8 times lower compared to Ocufilm. CONCLUSIONS: Tono-pen with Ocufilm and polyethylene wrap tip cover were used to measure the intraocular pressure. The polyethylene wrap tip cover demonstrated acceptable repeatability, reproducibility, and agreement with Ocufilm in normotensive eyes, and had a good safety profile. url: https://doi.org/10.1371/journal.pone.0239875 doi: 10.1371/journal.pone.0239875 id: cord-000580-dcid9emx author: Sällman Almén, Markus title: The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date: 2012-02-20 words: 4662.0 sentences: 237.0 pages: flesch: 48.0 cache: ./cache/cord-000580-dcid9emx.txt txt: ./txt/cord-000580-dcid9emx.txt summary: We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. By combining the results of the phylogenetic analysis and BLAST classification, we created a schematic overview of the organisms'' gene repertoire and a schematic picture of the Dispanin family''s evolutionary history, which suggests that the invertebrate Dispanins share more similarity towards the DSPC and D subfamilies than DSPA and B ( Figure 2 ). We provide evidence that the four IFITM genes together with ten additional human genes, known as TUSC5, TMEM233, PRRT2, TMEM90A, DSPC2, TMEM90B, TMEM91, AC023157, AL160276 and AC068580, form a novel gene family that we call the Dispanins, which refers to the 2TM membrane topology that is common to all identified members. abstract: The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282796/ doi: 10.1371/journal.pone.0031961 id: cord-336420-1a2u9p4t author: Söderman, Martina title: Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study date: 2016-06-16 words: 4200.0 sentences: 208.0 pages: flesch: 46.0 cache: ./cache/cord-336420-1a2u9p4t.txt txt: ./txt/cord-336420-1a2u9p4t.txt summary: title: Frequent Respiratory Viral Infections in Children with Febrile Neutropenia A Prospective Follow-Up Study Advances in molecular methods have increased the sensitivity of viral diagnostics tests, with recent studies reporting the detection of respiratory viruses in the nasopharynx in 44-57% of childhood febrile neutropenia episodes using real-time polymerase chain reaction (PCR) [3] [4] [5] 12] . Viral nucleic acids were extracted from the NPA with a MagAttract Virus Mini M48 kit (Qiagen, Sollentuna, Sweden) and analyzed with in-house real-time PCRs for the following 16 viruses: adenovirus (HAdV); bocavirus (HBoV); coronaviruses NL63/OC43/229E/HKU1 (HCoV); enterovirus (EV); influenza virus A, including A(H1N1)pdm09 and B (Flu); metapneumovirus (HMPV); parainfluenza viruses 1-3 (PIV); respiratory syncytial virus (RSV) and rhinovirus (RV) [19] . These results support the theory holding that there is a causal relationship between respiratory viral infections and episodes of febrile neutropenia, but proving this theory will require more longitudinal studies with asymptomatic neutropenic control cohorts. abstract: OBJECTIVE: Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. STUDY DESIGN: Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. RESULTS: At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. CONCLUSION: The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts. url: https://doi.org/10.1371/journal.pone.0157398 doi: 10.1371/journal.pone.0157398 id: cord-002094-7tewne3a author: Tago, Damian title: The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases date: 2016-06-14 words: 6293.0 sentences: 303.0 pages: flesch: 53.0 cache: ./cache/cord-002094-7tewne3a.txt txt: ./txt/cord-002094-7tewne3a.txt summary: Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The idea behind control strategies such as the MRP and vaccination [7] is that removing infected nodes or immunizing susceptible ones are efficient mechanisms to fight the spread of a disease. If an infectious disease is detected at t = 1, a farmer sufficiently close to the infected zone will face the risk that the restricted zone (RZ) will expand to include his location by the next period (with probability q). In the case of non-vector-borne diseases, i.e. when the transmission channel is restricted to the trade network, the MRP is an effective control strategy. The MRP becomes significantly less efficient when infected nodes that have not been detected spread the disease through both trade and geographic networks. abstract: One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions. This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account. Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed. Financial aid to farmers can be justified by public health concerns, not only for equity. This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907430/ doi: 10.1371/journal.pone.0157450 id: cord-352219-z245sb3s author: Tallam, Aravind title: Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date: 2016-02-12 words: 9117.0 sentences: 467.0 pages: flesch: 43.0 cache: ./cache/cord-352219-z245sb3s.txt txt: ./txt/cord-352219-z245sb3s.txt summary: Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Putative transcriptional regulators of IRG1 were hypothesized from the resulting GRN and tested using siRNA-mediated gene silencing experiments in mouse and human macrophages under LPS stimulation. Although the human data were obtained from primary cells, while the mouse analysis was conducted using the macrophage cell line RAW264.7, it is tempting to speculate that the transcriptional machinery inducing IRG1 expression, with the exception of IRF1, is mostly species-specific, as highlighted by the different transcriptional regulators identified in the two species (Table 1) . abstract: Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels. url: https://doi.org/10.1371/journal.pone.0149050 doi: 10.1371/journal.pone.0149050 id: cord-290120-fd26t8ja author: Tan, Chew Yee title: First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia date: 2020-07-24 words: 6606.0 sentences: 358.0 pages: flesch: 53.0 cache: ./cache/cord-290120-fd26t8ja.txt txt: ./txt/cord-290120-fd26t8ja.txt summary: title: First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia Given that PCV3 is increasingly reported in countries including Thailand and U.S. with whom Malaysia shares trade and geographical relationship; and that PCV3 is associated with several clinical presentations that affect productivity, there is a need to study the presence and molecular characteristics of PCV3 in Malaysian swine farms. Results revealed that PCV3 is present in Peninsular Malaysia at a molecular prevalence of 17.02%, with inguinal lymph nodes and lungs showing the highest molecular detection rates of 81.82% and 71.43% respectively. To test for association between PCV3 molecular detection status and age group, health status, farm standing sow population and distance from neighbouring farms, Chi-square tests were performed with statistical significance level set at p < 0.05. PCV3 infection susceptibility has been suggested to be associated with the age of wild boar, with juvenile animals showing statistically lower detection rates, unlike reports described in domestic pigs [37, 48] . abstract: Porcine circovirus type 3 (PCV3) is a newly emerging virus in the swine industry, first reported recently in 2016. PCV3 assembles into a 2000 bp circular genome; slightly larger than PCV1 (1758–1760 bp), PCV2 (1766–1769 bp) and PCV4 (1770 bp). Apart from being associated with porcine dermatitis and nephropathy syndrome (PDNS), PCV3 has been isolated from pigs with clinical signs of reproductive failures, myocarditis, porcine respiratory disease complex (PRDC) and neurologic disease. Given that PCV3 is increasingly reported in countries including Thailand and U.S. with whom Malaysia shares trade and geographical relationship; and that PCV3 is associated with several clinical presentations that affect productivity, there is a need to study the presence and molecular characteristics of PCV3 in Malaysian swine farms. Twenty-four commercial swine farms, three abattoirs and retail shops in Peninsular Malaysia were sampled using convenience sampling method. A total of 281 samples from 141 pigs, including 49 lung archive samples were tested for PCV3 by conventional PCR. Twenty-eight lung samples from wild boar population in Peninsular Malaysia were also included. Nucleotide sequences were analyzed for maximum likelihood phylogeny relationship and pairwise distances. Results revealed that PCV3 is present in Peninsular Malaysia at a molecular prevalence of 17.02%, with inguinal lymph nodes and lungs showing the highest molecular detection rates of 81.82% and 71.43% respectively. Despite wide reports of PCV3 in healthy animals and wild boars, no positive samples were detected in clinically healthy finishers and wild boar population of this study. PCV3 strain A1 and A2 were present in Malaysia, and Malaysian PCV3 strains were found to be phylogenetically related to Spanish, U.S. and Mexico strains. url: https://www.ncbi.nlm.nih.gov/pubmed/32706778/ doi: 10.1371/journal.pone.0235832 id: cord-301811-ykpiorgo author: Tanaka, Takuma title: Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing date: 2020-10-28 words: 5530.0 sentences: 296.0 pages: flesch: 55.0 cache: ./cache/cord-301811-ykpiorgo.txt txt: ./txt/cord-301811-ykpiorgo.txt summary: title: Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing We estimated the numbers of undiagnosed symptomatic patients and the lower bound of the number of total infected individuals per diagnosed patient before and after the declaration of the state of emergency in Hokkaido, Japan. The present analysis uses the distributions of the cluster size and patients'' time from onset to diagnosis, which are released by the health officials, to estimate the model parameters. At the same time, the nodes in the connected component containing the diagnosed node are also removed from the network, which corresponds to the contact tracing of the infected individuals (Fig 2, gray open circles) . In this paper, we have formulated a model to describe the spreading of infection and the quarantine of infected individuals, and estimated the number of undiagnosed symptomatic and asymptomatic COVID-19 patients in Hokkaido. abstract: Estimating the percentages of undiagnosed and asymptomatic patients is essential for controlling the outbreak of SARS-CoV-2, and for assessing any strategy for controlling the disease. In this paper, we propose a novel analysis based on the birth-death process with recursive full tracing. We estimated the numbers of undiagnosed symptomatic patients and the lower bound of the number of total infected individuals per diagnosed patient before and after the declaration of the state of emergency in Hokkaido, Japan. The median of the estimated number of undiagnosed symptomatic patients per diagnosed patient decreased from 1.7 to 0.77 after the declaration, and the median of the estimated lower bound of the number of total infected individuals per diagnosed patient decreased from 4.2 to 2.4. We will discuss the limitations and possible expansions of the model. url: https://www.ncbi.nlm.nih.gov/pubmed/33112895/ doi: 10.1371/journal.pone.0241170 id: cord-048492-4z38v9rg author: Tang, Julian W. title: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006) date: 2008-07-23 words: 4458.0 sentences: 202.0 pages: flesch: 48.0 cache: ./cache/cord-048492-4z38v9rg.txt txt: ./txt/cord-048492-4z38v9rg.txt summary: In this study, an analysis is presented of 281 Hong Kong influenza A(H3N2) hemagglutinin (HA) and neuraminidase (NA) full-length, dated sequences collected over 10 years (1997-2006) to assist the ongoing efforts to elucidate the underlying basis for the seasonality of influenza A(H3N2). One example of such possible viral persistence between influenza seasons was found, with HA and NA sequences from the same viruses (5251Jan02 and 5267Jan03, as indicated in Figures S1 and S2 for the HA and NA phylogenetic trees, respectively), showing a similar clustering pattern for both these genes, separated by at least one year. A similar analysis was recently performed using dated whole genome influenza A(H3N2) sequences from New York, New Zealand and Australia, downloaded from publicly available databases, in an attempt to test two competing hypotheses: whether seasonal influenza A(H3N2) viruses continuously ''migrate'' around the world, particularly between Northern and Southern hemispheres; or whether the virus remains ''latent'' in one location and reactivates each year to produce the familiar pattern of influenza seasonality [19] . abstract: BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2481298/ doi: 10.1371/journal.pone.0002768 id: cord-263684-3535k3op author: Tang, Julian W. title: Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms date: 2013-06-24 words: 5292.0 sentences: 211.0 pages: flesch: 52.0 cache: ./cache/cord-263684-3535k3op.txt txt: ./txt/cord-263684-3535k3op.txt summary: Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. This study is part of a longer-term project that aims to demonstrate the effects of door-opening motions using a variety of doors, with and without the passage of a human figure, on the movement of potentially contaminated air into and out of an isolation room, using both a small-scale, Reynolds-number-equivalent model in water, and a full-scale model in air. In the small-scale water-tank models used in these experiments, the compartment outside the isolation room, into or from which The series of 4 snapshots with each dooropening, manikin movement scenario were taken with respect to the following events, rather than at specific times: food dye movement due to door-opening motions alone then with any initial manikin movement -manikin interaction and any entrainment food dye -final food dye movements once the manikin had come to rest at its destination position. abstract: Hospital isolation rooms are vital for the containment (when under negative pressure) of patients with, or the protection (when under positive pressure) of patients, from airborne infectious agents. Such facilities were essential for the management of highly contagious patients during the 2003 severe acute respiratory syndrome (SARS) outbreaks and the more recent 2009 A/H1N1 influenza pandemic. Many different types of door designs are used in the construction of such isolation rooms, which may be related to the space available and affordability. Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. Careful scaling considerations involved in the design and construction of these water-tank models enabled these results to be accurately extrapolated to the full-scale situation. Four simple types of door design were tested: variable speed single and double, sliding and hinged doors, in combination with the moving human figure. The resulting video footage was edited, synchronized and presented in a series of split-screen formats. From these experiments, it is clear that double-hinged doors pose the greatest risk of leakage into or out of the room, followed by (in order of decreasing risk) single-hinged, double-sliding and single-sliding doors. The relative effect of the moving human figure on spreading any potential contamination was greatest with the sliding doors, as the bulk airflows induced were large relative to those resulting from these door-opening motions. However, with the hinged doors, the airflows induced by these door-opening motions were significantly greater. Further experiments involving a simulated ventilated environment are required, but from these findings alone, it appears that sliding-doors are far more effective for hospital isolation room containment. url: https://www.ncbi.nlm.nih.gov/pubmed/23826109/ doi: 10.1371/journal.pone.0066663 id: cord-337630-ojhk5opy author: Tasic, Velibor title: Clinical and Functional Characterization of URAT1 Variants date: 2011-12-16 words: 5356.0 sentences: 313.0 pages: flesch: 45.0 cache: ./cache/cord-337630-ojhk5opy.txt txt: ./txt/cord-337630-ojhk5opy.txt summary: reported that mutations in gene SLC22A12 encoding the URAT1 transporter were responsible for most cases of idiopathic renal hypouricaemia [3] . It is noteworthy that reports of idiopathic renal hypouricaemia secondary to mutations in uric acid transporters URAT1 and GLUT9 were initially reported from Japan, Korea and China [23] . Since the hypouricaemia was associated with an elevated FE urate , we undertook mutational analysis of SLC22A12 which revealed a heterozygous missense mutation, leading to amino acid change R434C. SLC22A12 encodes the protein URAT1 and loss of function mutations are responsible for majority of patients with idiopathic renal hypouricaemia. reported a W258X homozygous mutation in a 7 year old child, whose mother and brother were also heterozygous for W258X and had mild hypouricaemia and abnormally high FE urate , whilst his father who was also heterozygous for W258X, had a normal serum uric acid level of 4.6 mg/dL [23] . abstract: Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia. url: https://www.ncbi.nlm.nih.gov/pubmed/22194875/ doi: 10.1371/journal.pone.0028641 id: cord-312493-wbhji81g author: Tay, Ee Laine title: Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance date: 2013-10-11 words: 4303.0 sentences: 216.0 pages: flesch: 49.0 cache: ./cache/cord-312493-wbhji81g.txt txt: ./txt/cord-312493-wbhji81g.txt summary: For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. Four independent surveillance data sources were used: (i) the Victorian GPSS, (ii) sentinel data from the Melbourne Medical Deputising Service (MMDS), (iii) routine laboratoryconfirmed influenza (LAB data) from the Victorian Infectious Diseases Reference Laboratory (VIDRL) and the (iv) Victoria Admitted Episode Dataset (VAED) for hospital admissions. Comparison of thresholds derived from different datasets revealed variations in defining the start of a season but relatively good agreement in describing the end and intensity of influenza seasons, except in the hospital data after the pandemic year. abstract: INTRODUCTION: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). METHODS: For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. RESULTS: The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. CONCLUSIONS: Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics. url: https://www.ncbi.nlm.nih.gov/pubmed/24146973/ doi: 10.1371/journal.pone.0077244 id: cord-330110-pamxy4av author: Teissier, Elodie title: Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date: 2011-01-25 words: 9268.0 sentences: 438.0 pages: flesch: 48.0 cache: ./cache/cord-330110-pamxy4av.txt txt: ./txt/cord-330110-pamxy4av.txt summary: Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. By combining surface plasmon resonance, fluorescence and NMR spectroscopy approaches, we showed that Arb directly interacts with the phospholipid membrane interface, with an affinity in the micromolar range, comparable to the concentration inhibiting HCVpp membrane fusion by 50% (IC50). Altogether our results demonstrate that Arb interacts with the polar head of phospholipid membranes and protein motifs enriched in aromatic residues, suggesting that the inhibitory activity of Arb on HCV entry and fusion could involve both types of interactions. Conversely, Arb inhibition of HCVpp membrane fusion, as assessed by a in vitro model system where the only proteins present are the viral glycoproteins, could merely reflect the interaction of Arb on lipids and/or on motifs present in HCV glycoproteins of any genotype. abstract: The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection. url: https://doi.org/10.1371/journal.pone.0015874 doi: 10.1371/journal.pone.0015874 id: cord-002624-59nznqsd author: Ti, Jinfeng title: Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies date: 2017-07-26 words: 4050.0 sentences: 210.0 pages: flesch: 53.0 cache: ./cache/cord-002624-59nznqsd.txt txt: ./txt/cord-002624-59nznqsd.txt summary: title: Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked immunosorbent assay (ELISA). In this study, one linear B-cell epitope was identified and characterized with one monoclonal antibody against TMUV NS1 protein. To screen the antigenic epitope of TMUV NS1 mAb, 35 short peptide fusion proteins were successfully expressed in prokaryotic expression system and purified. A pane of 16-AA polypeptides of NS1 protein was expressed and one 16-AA polypeptide NS1-27 was screened and identified by 3G2 mAb. In order to accurately map the B-cell epitope, a set of truncated fusion oligopeptides of NS1-27 were expressed. The B-cell epitope of TMUV NS1 protein could apply into the development of detection methods to investigate whether the detected antibody was a result of inactivated vaccine immunization or live virus infection. abstract: This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked immunosorbent assay (ELISA). In this study, NS1 protein was expressed in prokaryotic expression system and purified. One mAb against NS1 protein was generated from Balb/c mice immunized with recombinant protein NS1. A set of 35 partially-overlapping polypeptides covering the entire NS1 protein was expressed with PGEX-6P-1 vector and screened with mAb 3G2. One polypeptide against the mAb was acquired and identified by indirect ELISA and western-blot. To map the epitope accurately, one or two amino acid residues were removed from the carboxy and amino terminal of polypeptide sequentially. A series of truncated oligopeptides were expressed and purified. The minimal determinant of the linear B cell epitope was recognized and identified with mAb 3G2. The accurate linear B-cell epitope was (269)DEKEIV(274) located in NS1 protein. Furthermore, sequence alignment showed that the epitope was highly conserved and specific among TMUV strains and other flavivirus respectively. The linear B-cell epitope of TMUV NS1 protein could benefit the development of new vaccines and diagnostic assays. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528836/ doi: 10.1371/journal.pone.0181177 id: cord-302189-3xab3yxc author: Tillmann, Ramona Liza title: Sensitive Commercial NASBA Assay for the Detection of Respiratory Syncytial Virus in Clinical Specimen date: 2007-12-26 words: 1777.0 sentences: 90.0 pages: flesch: 45.0 cache: ./cache/cord-302189-3xab3yxc.txt txt: ./txt/cord-302189-3xab3yxc.txt summary: Thereby, NASBA turned out to be the most sensitive method with a total number of 80 RSV positive samples out of a cohort of 251 nasopharyngeal washings from patients suffering from clinical symptoms, followed by the inhouse RT-PCR (62/251) and ELISA (52/251). Despite an increasing number of newly detected respiratory pathogen the human Respiratory syncytial virus (RSV) remains the single most prevalent etiologic agent in pediatric viral respiratory tract infection [1, 2, 3] . In relation to the positive test results obtained with the NucliSENSH EasyQ NASBA, the relative sensitivity of the RT-PCR was 77,5% compared to 65% obtained with the NOWH RSV ELISA. The results showed that from the three tested methods for molecular diagnosis of RSV the NucliSENSH EasyQ NASBA (bioMerieux, Nürtingen, Germany) detected the most RSV positive samples in a cohort of 251 nasopharyngeal samples of pediatric patients hospitalized with respiratory disease. abstract: The aim of the study was to evaluate the usability of three diagnostic procedures for the detection of respiratory syncytial virus in clinical samples. Therefore, the FDA cleared CE marked NOW® RSV ELISA, the NucliSENS® EasyQ RSV A+B NASBA, and a literature based inhouse RT-PCR protocol were compared for their relative sensitivities. Thereby, NASBA turned out to be the most sensitive method with a total number of 80 RSV positive samples out of a cohort of 251 nasopharyngeal washings from patients suffering from clinical symptoms, followed by the inhouse RT-PCR (62/251) and ELISA (52/251). Thus, NASBA may serve as a rapid and highly sensitive alternative for RSV diagnostics. url: https://www.ncbi.nlm.nih.gov/pubmed/18159240/ doi: 10.1371/journal.pone.0001357 id: cord-260728-4w23kwzu author: Timmermans, Ans title: Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia date: 2016-03-30 words: 7411.0 sentences: 381.0 pages: flesch: 50.0 cache: ./cache/cord-260728-4w23kwzu.txt txt: ./txt/cord-260728-4w23kwzu.txt summary: Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. Between May 2010 and December 2012, we collected specimens and surveillance data for influenza and other viral respiratory pathogens from a subset of outpatients presenting with influenza-like-illness (ILI) at four sentinel sites-located in five health centers and hospitals in Battambang, Oddar Meanchey, Pailin and Banteay Meanchey provinces in Cambodia (Fig 1) . A subset of 164 culture-negative specimens (collected between May 2010 and April 2012), where we found a higher proportion (5.6%) of non-polio enteroviruses in children less than 5 years old as compared with previous studies (1%) in Cambodia [2] , were tested for enterovirus and rhinovirus by two separate nested RT-PCR methods adapted from Coiras et al., 2004 and Singh et al., 2002 [29,30] , one for simultaneous detection of pan-enteroviruses and rhinoviruses, and the other specific for enterovirus 71 (EV71). abstract: Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1–77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution. Further research about the burden of adenovirus and non-polio enteroviruses as etiologic agents in acute respiratory infections in Cambodia is also needed. url: https://doi.org/10.1371/journal.pone.0152529 doi: 10.1371/journal.pone.0152529 id: cord-001219-517gka4h author: Timpka, Toomas title: Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign date: 2014-03-07 words: 5805.0 sentences: 247.0 pages: flesch: 37.0 cache: ./cache/cord-001219-517gka4h.txt txt: ./txt/cord-001219-517gka4h.txt summary: We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. A hypothetical explanatory model was constructed to inform the analysis of the main research question; i.e. to what extent selfreported intentions to perform protective behaviors during influenza outbreaks can be explained by perceptions of threat and the ability to cope as outlined in the PMT, self-assessments of health status, trust in official information, and sociodemiographic factors. abstract: Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946657/ doi: 10.1371/journal.pone.0091060 id: cord-000166-36bfeoqv author: Tracht, Samantha M. title: Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) date: 2010-02-10 words: 5846.0 sentences: 336.0 pages: flesch: 59.0 cache: ./cache/cord-000166-36bfeoqv.txt txt: ./txt/cord-000166-36bfeoqv.txt summary: We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. With the implementation of N95 respirators Table 3 exhibits a reduction in the cumulative number of cases of almost 200,000, or a 19% decrease, when 10% of the population wears masks and they are 20% effective. With 10% of the population wearing N95 respirators with effectiveness at 20% in reducing both susceptibility and infectivity there is a 19% reduction in the cumulative number of cases. Even at 50% effectiveness in reducing both susceptibility and infectivity and with 50% of the population wearing surgical masks only a 6% reduction in the number of cumulative cases is seen. abstract: On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818714/ doi: 10.1371/journal.pone.0009018 id: cord-273175-bao8xxe2 author: Tran, Viet-Thi title: COVID-19–related perceptions, context and attitudes of adults with chronic conditions: Results from a cross-sectional survey nested in the ComPaRe e-cohort date: 2020-08-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: To avoid a surge of demand on the healthcare system due to the COVID-19 pandemic, we must reduce transmission to individuals with chronic conditions who are at risk of severe illness with COVID-19. We aimed at understanding the perceptions, context and attitudes of individuals with chronic conditions during the COVID-19 pandemic to clarify their potential risk of infection. METHODS: A cross-sectional survey was nested in ComPaRe, an e-cohort of adults with chronic conditions, in France. It assessed participants’ perception of their risk of severe illness with COVID-19; their context (i.e., work, household, contacts with external people); and their attitudes in situations involving frequent or occasional contacts with symptomatic or asymptomatic people. Data were collected from March 23 to April 2, 2020, during the lockdown in France. Analyses were weighted to represent the demographic characteristics of French patients with chronic conditions. The subgroup of participants at high risk according to the recommendations of the French High Council for Public Health was examined. RESULTS: Among the 7169 recruited participants, 63% patients felt at risk because of severe illness. About one quarter (23.7%) were at risk of infection because they worked outside home, had a household member working outside home or had regular visits from external contacts. Less than 20% participants refused contact with symptomatic people and <20% used masks when in contact with asymptomatic people. Among patients considered at high risk according to the recommendations of the French High Council for Public Health, 20% did not feel at risk, which led to incautious attitudes. CONCLUSION: Individuals with chronic conditions have distorted perceptions of their risk of severe illness with COVID-19. In addition, they are exposed to COVID-19 due to their context or attitudes. url: https://doi.org/10.1371/journal.pone.0237296 doi: 10.1371/journal.pone.0237296 id: cord-331652-oc5s1if2 author: Trudeau, Michaela P. title: Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) date: 2016-06-24 words: 5988.0 sentences: 294.0 pages: flesch: 52.0 cache: ./cache/cord-331652-oc5s1if2.txt txt: ./txt/cord-331652-oc5s1if2.txt summary: title: Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. Therefore, the objective of this study was to determine if thermal and non-thermal methods of microbial inactivation, as well as the use of selected feed additives, are effective in reducing the survival of PEDV in experimentally contaminated swine feed. The PEDV showed a high thermal resistance in the dry feed samples and it was completely inactivated (3.0 log reduction) at each of the tested temperatures within 30 min. abstract: Infection with porcine epidemic diarrhea virus (PEDV) causes diarrhea, vomiting, and high mortality in suckling pigs. Contaminated feed has been suggested as a vehicle of transmission for PEDV. The objective of this study was to compare thermal and electron beam processing, and the inclusion of feed additives on the inactivation of PEDV in feed. Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. At the end of incubation, the virus titers were determined by inoculation of Vero-81 cells and the virus inactivation kinetics were modeled using the Weibull distribution model. The Weibull kinetic parameter delta represented the time or eBeam dose required to reduce virus concentration by 1 log. For thermal processing, delta values ranged from 16.52 min at 120°C to 1.30 min at 145°C. For eBeam processing, a target dose of 50 kGy reduced PEDV concentration by 3 log. All additives tested were effective in reducing the survival of PEDV when compared with the control sample (delta = 17.23 days). Activate DA (0.81) and KEM-GEST (3.28) produced the fastest inactivation. In conclusion, heating swine feed at temperatures over 130°C or eBeam processing of feed with a dose over 50 kGy are effective processing steps to reduce PEDV survival. Additionally, the inclusion of selected additives can decrease PEDV survivability. url: https://www.ncbi.nlm.nih.gov/pubmed/27341670/ doi: 10.1371/journal.pone.0158128 id: cord-318614-518giv0m author: Tsai, Jih-Jin title: A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos date: 2019-07-10 words: 4825.0 sentences: 213.0 pages: flesch: 49.0 cache: ./cache/cord-318614-518giv0m.txt txt: ./txt/cord-318614-518giv0m.txt summary: A pan-dengue virus (DENV) RT-iiPCR, targeting the 5'' untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease. Testing with the pan-DENV RT-iiPCR, the analytical and clinical performance of the fully automatic POCKIT Central system was comparable to those of the semi-automatic POCKI combo system, which was validated previously to offer performances equivalent to the CDC DENV1-4 real-time RT-PCR for the detection of DENV in human serum [7, 24, 26] . abstract: BACKGROUND: The insulated isothermal PCR (iiPCR) technology enables consistent PCR amplification and detection in a simple heating device. A pan-dengue virus (DENV) RT-iiPCR, targeting the 5’ untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. Working on the same technologies, a compact automated sample-in-answer-out system (POCKIT Central Nucleic Acid Analyser) has been available commercially for iiPCR, minimizing human error risks and allowing easy molecular bio-detection near points of need. Here, we evaluated the analytical and clinical performance of the pan-DENV RT-iiPCR on the fully automated system by comparison to those on the semi-automated system. METHODOLOGY/PRINCIPAL FINDINGS: Testing sera containing serial diluted DENV-1, -2, -3, or -4 cell culture stock, the pan-DENV RT-iiPCR system had similar 100% detection endpoints on the two systems; i.e. at 1, 10, 1 and 10 PFU/ml, respectively, on the fully automated system, and at 10, 1, 10 and 10 PFU/ml, respectively, on the semi-automated system. Furthermore, both fully automated and semi-automated PCR system can detect all four DENV serotypes in mosquitos. Clinical performance of the reagent on the two systems was evaluated by testing 60 human serum samples. Both systems detected the same 40 samples (ten DENV-1, -2, -3, and -4 positive each) and did not detect the other 20; 100% agreement (κ = 1) was found between the two systems. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease. url: https://doi.org/10.1371/journal.pone.0218139 doi: 10.1371/journal.pone.0218139 id: cord-002834-2htnywef author: Tsuchiaka, Shinobu title: Genetic diversity and recombination of enterovirus G strains in Japanese pigs: High prevalence of strains carrying a papain-like cysteine protease sequence in the enterovirus G population date: 2018-01-11 words: 2976.0 sentences: 154.0 pages: flesch: 52.0 cache: ./cache/cord-002834-2htnywef.txt txt: ./txt/cord-002834-2htnywef.txt summary: title: Genetic diversity and recombination of enterovirus G strains in Japanese pigs: High prevalence of strains carrying a papain-like cysteine protease sequence in the enterovirus G population Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C–3A junction site. The insertion sequences were aligned and compared with those of the PL-CP of EV-G strains from the USA and Belgium and with the PL-VP sequences in the genome of nidoviruses including porcine and bovine toroviruses by phylogenetic analysis and pairwise sequence comparison (Fig 2 and S2 Table) . The G2-PL-CP strain HgYa2-1 showed high homology Genetic diversity and recombination of enterovirus G strains in Japanese pigs to G2 strains in the tree for VP4-VP3 and VP1, whereas HgYa2-1 showed high similarity with G1-PL-CP lineage 1 strains in regions P2 and P3 (Fig 3A) . abstract: To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs, metagenomics sequencing was performed on fecal samples from pigs with or without diarrhea, collected between 2014 and 2016. Fifty-nine EV-G sequences, which were >5,000 nucleotides long, were obtained. By complete VP1 sequence analysis, Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains), G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five strains), and a new genotype (one strain). Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C–3A junction site. This paper presents the first report of the high prevalence of viruses carrying PL-CP in the EV-G population. Furthermore, possible inter- and intragenotype recombination events were found among EV-G strains, including G1-PL-CP strains. Our findings may advance the understanding of the molecular epidemiology and genetic evolution of EV-Gs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764308/ doi: 10.1371/journal.pone.0190819 id: cord-001090-qg2r691d author: Twin, Jimmy title: The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis date: 2013-09-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total RNA extraction, followed by physical subtraction of human rRNA and whole transcriptome amplification. The metatranscriptome was sequenced using Roche 454 titanium chemistry. The bioinformatics pipeline MG-RAST and desktop DNA analysis platforms were utilised to analyse results. Bacteria of the genus Prevotella (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%). Comparison of the abundances of several bacteria to quantitative PCR (qPCR) screening of extracted DNA revealed comparable relative abundances. This suggests a correlation between what was present and transcriptionally active in this sample: however distinct differences were seen when compared to the microbiome determined by 16S rRNA gene amplicon sequencing. To assess the presence of P. amnii in a larger pool of samples, 90 sexually active women were screened using qPCR. This bacterium was found to be strongly associated with BV (P<0.001, OR 23.3 (95%CI:2.9–190.7)) among the 90 women. CONCLUSIONS/SIGNIFICANCE: This study highlighted the potential of metatranscriptomics as a tool for characterising metabolically active microbiota and identifying targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785445/ doi: 10.1371/journal.pone.0076892 id: cord-001603-vlv8x8l8 author: Ul-Haq, Zaheer title: 3D Structure Prediction of Human β1-Adrenergic Receptor via Threading-Based Homology Modeling for Implications in Structure-Based Drug Designing date: 2015-04-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dilated cardiomyopathy is a disease of left ventricular dysfunction accompanied by impairment of the β(1)-adrenergic receptor (β(1)-AR) signal cascade. The disturbed β(1)-AR function may be based on an elevated sympathetic tone observed in patients with heart failure. Prolonged adrenergic stimulation may induce metabolic and electrophysiological disturbances in the myocardium, resulting in tachyarrhythmia that leads to the development of heart failure in human and sudden death. Hence, β(1)-AR is considered as a promising drug target but attempts to develop effective and specific drug against this tempting pharmaceutical target is slowed down due to the lack of 3D structure of Homo sapiens β(1)-AR (hsβADR1). This study encompasses elucidation of 3D structural and physicochemical properties of hsβADR1 via threading-based homology modeling. Furthermore, the docking performance of several docking programs including Surflex-Dock, FRED, and GOLD were validated by re-docking and cross-docking experiments. GOLD and Surflex-Dock performed best in re-docking and cross docking experiments, respectively. Consequently, Surflex-Dock was used to predict the binding modes of four hsβADR1 agonists. This study provides clear understanding of hsβADR1 structure and its binding mechanism, thus help in providing the remedial solutions of cardiovascular, effective treatment of asthma and other diseases caused by malfunctioning of the target protein. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393300/ doi: 10.1371/journal.pone.0122223 id: cord-000008-3dgjv0x1 author: Vali, Bahareh title: HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date: 2008-10-20 words: 5253.0 sentences: 236.0 pages: flesch: 47.0 cache: ./cache/cord-000008-3dgjv0x1.txt txt: ./txt/cord-000008-3dgjv0x1.txt summary: In response to stimulation with HIV peptide pool, untreated co-infected individuals showed significantly higher frequencies of intra-hepatic CD4 + T-cells producing IFN-c, compared to HCV mono-infected [0.1660.05% vs 0.0260.01%, p,0.05], and HAART-treated co-infected individuals [0.1660.05% vs 0.0360.05%, p,0.05] (Figure 2a ). Therapy naïve co-infected subjects had greater IFN-c producing CD8 + T-cells in response to HIV peptides compared to HCV mono-infected individuals [1.3960.37% vs 0.0260.0%, p,0.05], and HAART was associated with a significant reduction in the frequencies of these cells [1.3960.37% vs 0.3060.26%, p,0.05] (figure 2b). The tetramer cytokine response pattern was shown to be different in the liver compared to blood of the same individual, with diminished intra-hepatic tetramer-specific IFN-c responses and an increase in both CD107a and TNF-a responses, with the majority of SL9 tetramer positive cells expressing these two markers. Therapy naïve co-infected individuals demonstrated a higher frequency of intra-hepatic CD8 + T-cells that produce TNF-a in response to both HCV and HIV antigen stimulation compared to HCV mono-infected individuals. abstract: BACKGROUND AND AIMS: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses. METHODS: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry. RESULTS: HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4(+) T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8(+) and CD4(+) T-cells producing IFN-γ and TNF-α were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8(+) T-cells produced more of the fibrogenic cytokine, TNF-α. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4(+) T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses. CONCLUSION: The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565067/ doi: 10.1371/journal.pone.0003454 id: cord-310061-nro623aa author: Valitutto, Marc T. title: Detection of novel coronaviruses in bats in Myanmar date: 2020-04-09 words: 3678.0 sentences: 192.0 pages: flesch: 48.0 cache: ./cache/cord-310061-nro623aa.txt txt: ./txt/cord-310061-nro623aa.txt summary: Historically, bats have been linked to highly pathogenic viruses that pose a serious threat to human health, including the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the hemorrhagic ebola and Marburg filoviruses, and paramyxoviruses such as Nipah virus [10, 11, [13] [14] [15] [16] [17] [18] . The 2002-2003 SARS epidemic, the emergence of MERS in people in 2012, and the ongoing COVID-19 pandemic have prompted substantial interest in detecting coronaviruses of bat origin due to public health concern and their pandemic potential [10, [13] [14] [15] [16] [17] [18] . In addition to human-associated CoVs, bats are also hosts of coronaviruses that infect production animals, and have been implicated in the emergence and origin of swine acute diarrhea syndrome (SADS), transmissible gastroenteritis virus (TGEV) in pigs, and porcine epidemic diarrhea (PED), which can cause considerable losses [23] [24] [25] [26] . abstract: The recent emergence of bat-borne zoonotic viruses warrants vigilant surveillance in their natural hosts. Of particular concern is the family of coronaviruses, which includes the causative agents of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, Coronavirus Disease 2019 (COVID-19), an epidemic of acute respiratory illness originating from Wuhan, China in December 2019. Viral detection, discovery, and surveillance activities were undertaken in Myanmar to identify viruses in animals at high risk contact interfaces with people. Free-ranging bats were captured, and rectal and oral swabs and guano samples collected for coronaviral screening using broadly reactive consensus conventional polymerase chain reaction. Sequences from positives were compared to known coronaviruses. Three novel alphacoronaviruses, three novel betacoronaviruses, and one known alphacoronavirus previously identified in other southeast Asian countries were detected for the first time in bats in Myanmar. Ongoing land use change remains a prominent driver of zoonotic disease emergence in Myanmar, bringing humans into ever closer contact with wildlife, and justifying continued surveillance and vigilance at broad scales. url: https://www.ncbi.nlm.nih.gov/pubmed/32271768/ doi: 10.1371/journal.pone.0230802 id: cord-255576-738khdwv author: Van Duyne, Rachel title: Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery date: 2012-07-10 words: 9845.0 sentences: 517.0 pages: flesch: 56.0 cache: ./cache/cord-255576-738khdwv.txt txt: ./txt/cord-255576-738khdwv.txt summary: We have previously shown that Tax interacts directly with the cellular Rb (Retinoblastoma) protein and targets Rb for degradation via the proteasome pathway, resulting in a decrease in Rb protein expression in HTLV-1 infected cells and a dysregulation of the cell cycle [47] . Collectively, these data indicate that the Drosha in Tax-containing and HTLV-1 infected cells is mostly functionally inactive and the functional suppression of Drosha is dependent on its interaction with a small region of the N-terminus of Tax. We have shown above that Drosha is downregulated, degraded, and mostly inactive in HTLV-1 infected cells, however, it was not clear what effect this dysregulation of Drosha would have on viral replication. Collectively, these data indicate that proteins, such as IKK-b, among others, may directly be regulated by the Tax/Drosha interaction in HTLV infected cells. abstract: The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus. url: https://www.ncbi.nlm.nih.gov/pubmed/22808228/ doi: 10.1371/journal.pone.0040662 id: cord-295781-b831y105 author: VanLeuven, James T. title: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses date: 2017-06-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract. url: https://www.ncbi.nlm.nih.gov/pubmed/28575086/ doi: 10.1371/journal.pone.0178408 id: cord-001071-bjx5td52 author: Vanhems, Philippe title: Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors date: 2013-09-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI). A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures. METHODS AND FINDINGS: We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital. Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds. The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights. 14,037 contacts were recorded overall, 94.1% of which during daytime. The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period. Contact patterns were qualitatively similar from one day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders. CONCLUSIONS: Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals. The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days. This variability is however associated with a marked statistical stability of contact and mixing patterns across days. Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770639/ doi: 10.1371/journal.pone.0073970 id: cord-323185-n0rubc72 author: Varshney, Bhavna title: SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b date: 2012-01-12 words: 5667.0 sentences: 345.0 pages: flesch: 51.0 cache: ./cache/cord-323185-n0rubc72.txt txt: ./txt/cord-323185-n0rubc72.txt summary: Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. In this study, we confirmed the putative interaction of 3b and RUNX1b and observed in vivo recruitment of 3b on the RUNX1 binding element on the IL2 promoter in transiently transfected human T, jurkat cells. We next determined the positive effect of 3b-RUNX1b interaction on the expression of RUNX1b regulated chemokine MIP-1a, reported to be upregulated in SARS-CoV infected monocyte derived dendritic cells. To investigate whether 3b-RUNX1b interaction leads to the recruitment of 3b on RUNX1 binding elements on the endogenous IL2 promoter, ChIP assays were performed in RUNX1b/CBFb endogenously expressing jurkat cells that are abortively infected by SARS-CoV. To investigate the effect of SARS-CoV 3b protein on the RUNX1b transcriptional activity, reporter gene assays were performed using the mouse IL2 promoter. abstract: BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection. url: https://doi.org/10.1371/journal.pone.0029542 doi: 10.1371/journal.pone.0029542 id: cord-340937-6mpob1nx author: Varshney, Mohit title: Initial psychological impact of COVID-19 and its correlates in Indian Community: An online (FEEL-COVID) survey date: 2020-05-29 words: 3662.0 sentences: 217.0 pages: flesch: 51.0 cache: ./cache/cord-340937-6mpob1nx.txt txt: ./txt/cord-340937-6mpob1nx.txt summary: The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Event–revised (IES-R) scale. The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Eventrevised (IES-R) scale. The current study investigated the initial psychological impact of COVID-19 outbreak in Indian population. Despite the limitations, this study provides the first cross-sectional data on actual level of psychological impact among Indian community; and how mental health of people is affected during a pandemic of this nature. Our survey is one of the first mental health related data from India, during the initial phase of COVID-19 pandemic and indicated that a significant proportion of them have had a psychological impact during the crisis. abstract: BACKGROUND: The pandemic of Corona Virus (COVID-19) hit India recently; and the associated uncertainty is increasingly testing psychological resilience of the masses. When the global focus has mostly been on testing, finding a cure and preventing transmission; people are going through a myriad of psychological problems in adjusting to the current lifestyles and fear of the disease. Since there is a severe dearth of researches on this issue, we decided to conduct an online survey to evaluate its psychological impact. METHODS: From 26(th) to 29(th) March an online survey (FEEL-COVID) was conducted using principles of snowballing, and by invitation through text messages to participate. The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Event–revised (IES-R) scale. RESULTS: There were a total of 1106 responses from around 64 cities in the country. Out of these 453 responses had at least one item missing; and were excluded from the analysis. The mean age of the respondents was around 41 years with a male female ratio of 3:1 and around 22% respondents were health care professionals. Overall approximately one third of respondents had significant psychological impact (IES-R score > 24). Higher psychological impact was predicted with younger age, female gender and comorbid physical illness. Presence of physical symptoms and contact history predicted higher psychological impact, but did not reach statistical significance. CONCLUSION: During the initial stages of COVID-19 in India, almost one-third respondents had a significant psychological impact. This indicates a need for more systematic and longitudinal assessment of psychological needs of the population, which can help the government in formulating holistic interventions for affected individuals. url: https://www.ncbi.nlm.nih.gov/pubmed/32470088/ doi: 10.1371/journal.pone.0233874 id: cord-290446-43h1r4pm author: Vazquez, Leonardo title: Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus date: 2017-07-27 words: 8840.0 sentences: 422.0 pages: flesch: 53.0 cache: ./cache/cord-290446-43h1r4pm.txt txt: ./txt/cord-290446-43h1r4pm.txt summary: This spacer provided a reasonably dynamic loop, according to our NMR data, which included narrow chemical shift dispersion (S2A Fig As depicted in Fig 1A, we designed the nsp1 constructs so as to avoid truncating their secondary-structure elements. The full-length nsp1 fusion protein has only a few missing peaks, indicating a well-folded 3D domain, which causes a wide dispersion of chemical shifts and allows straightforward identification of backbone HN signals. The SSP indicates the propensity ranging from -1 to 1 to adopt backbone conformations typical for extended β-strands or helical structures, respectively, according to the effect of these conformations on the chemical shifts of backbone atoms, [39] [40] [41] As shown in Fig 7, with the SSP algorithm it was possible to define very well the secondarystructure elements of the folded globular domain of nsp1 (orange bars in the uppermost graph). abstract: The cotranslational folding is recognized as a very cooperative process that occurs after the nearly completion of the polypeptide sequence of a domain. Here we investigated the challenges faced by polypeptide segments of a non-vectorial β-barrel fold. Besides the biological interest behind the SARS coronavirus non-structural protein 1 (nsp1, 117 amino acids), this study model has two structural features that motivated its use in this work: 1- its recombinant production is dependent on the temperature, with greater solubility when expressed at low temperatures. This is an indication of the cotranslational guidance to the native protein conformation. 2- Conversely, nsp1 has a six-stranded, mixed parallel/antiparallel β-barrel with intricate long-range interactions, indicating it will need the full-length protein to fold properly. We used non-denaturing purification conditions that allowed the characterization of polypeptide chains of different lengths, mimicking the landscape of the cotranslational fold of a β-barrel, and avoiding the major technical hindrances of working with the nascent polypeptide bound to the ribosome. Our results showed partially folded states formed as soon as the amino acids of the second β-strand were present (55 amino acids). These partially folded states are different based on the length of polypeptide chain. The native α-helix (amino acids 24–37) was identified as a transient structure (~20–30% propensity). We identified the presence of regular secondary structure after the fourth native β-strand is present (89 amino acids), in parallel to the collapse to a non-native 3D structure. Interestingly the polypeptide sequences of the native strands β2, β3 and β4 have characteristics of α-helices. Our comprehensive analyses support the idea that incomplete polypeptide chains, such as the ones of nascent proteins much earlier than the end of the translation, adopt an abundance of specific transient folds, instead of disordered conformations. url: https://doi.org/10.1371/journal.pone.0182132 doi: 10.1371/journal.pone.0182132 id: cord-000666-je9t4i6q author: Verbist, Katherine C. title: IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection date: 2012-05-18 words: 7210.0 sentences: 302.0 pages: flesch: 47.0 cache: ./cache/cord-000666-je9t4i6q.txt txt: ./txt/cord-000666-je9t4i6q.txt summary: ( Figure 2E) ; however, these animals seemed to regain control of viral replication by day 4 p.i., which perhaps corresponds with the early entry of cells of the adaptive immune response as anti-influenza specific CD8 T cells are first detectable in the lung airways by d6 post infection by flow cytometry ( [34] and data not shown). We observed significant reductions in the numbers of NK cells in the lung airways of influenza-infected animals in which IL-15 was blocked at time points associated with their arrival at the site of infection, and failure of these cell populations to accumulate had implications in early viral control (Figure 2) . doi:10.1371/journal.pone.0037539.g002 frequencies, numbers, CD122 expression, and BrdU incorporation were specific to the lung airways (the sight of treatment), as NK cells isolated from spleens were similar in control and IL-15ctreated animals ( Figure 3C and data not shown). abstract: Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356330/ doi: 10.1371/journal.pone.0037539 id: cord-048360-n9sih438 author: Villard, Viviane title: Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date: 2007-07-25 words: 4794.0 sentences: 228.0 pages: flesch: 45.0 cache: ./cache/cord-048360-n9sih438.txt txt: ./txt/cord-048360-n9sih438.txt summary: To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. Here, we focus on the Pf parasite erythrocytic stage, a target of protective antibodies and describe a straightforward, rapid procedure based on bioinformatic analysis of a-helical coiled-coil motifs and peptide synthesis. With regard to the structural features and cellular location prediction of the proteins corresponding to the peptides selected for ADCI assays ( Table 1) , 15 of the proteins contain a pentapeptide conforming to the PEXEL consensus [19, 20; 21, 22] , but that none of these have a position within the amino acid sequence that conforms to the location of known active PEXEL motifs (see Materials and Methods and membrane segments, and none of them has a GPI anchor. In conclusion, an approach combining a genome-wide search by bioinformatics of a-helical coiled coil protein motifs and chemical synthesis can lead to the rapid identification and development of new malaria vaccine candidates. abstract: To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920550/ doi: 10.1371/journal.pone.0000645 id: cord-000912-6l6c7jpq author: Vitelli, Alessandra title: Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus date: 2013-03-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594242/ doi: 10.1371/journal.pone.0055435 id: cord-000742-0r4z1zea author: Vittecoq, Marion title: High Influenza A Virus Infection Rates in Mallards Bred for Hunting in the Camargue, South of France date: 2012-08-27 words: 5923.0 sentences: 304.0 pages: flesch: 53.0 cache: ./cache/cord-000742-0r4z1zea.txt txt: ./txt/cord-000742-0r4z1zea.txt summary: We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife. Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions. However, to our knowledge no study ever aimed at investigating the potential role of hand-reared Mallards released for hunting in the epidemiology of AIV, despite the very large number of ducks being released in the wild annually. Our results highlighted that: i) GBF represent an epidemiological compartment into which important AIV outbreaks can occur; ii) a significant proportion of Mallards wintering in the Camargue are infected by LPAIV, including H5 strains that are known to be able to evolve to HPAIV in domestic birds [30] . abstract: During the last decade, the role of wildlife in emerging pathogen transmission to domestic animals has often been pointed out. Conversely, far less attention has been paid to pathogen transmission from domestic animals to wildlife. Here, we focus on the case of game restocking, which implies the release of millions of animals worldwide each year. We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife. We sampled Mallards (cloacal swabs) from several game duck facilities in 2009 and 2010 before their release. A very high (99%) infection rate caused by an H10N7 strain was detected in the game bird facility we sampled in 2009. We did not detect this strain in shot ducks we sampled, neither during the 2008/2009 nor the 2009/2010 hunting seasons. In 2010 infection rates ranged from 0 to 24% in hand-reared ducks. The 2009 H10N7 strain was fully sequenced. It results from multiple reassortment events between Eurasian low pathogenic strains. Interestingly, H10N7 strains had previously caused human infections in Egypt and Australia. The H10 and N7 segments we sequenced were clearly distinct from the Australian ones but they belonged to the same large cluster as the Egyptian ones. We did not observe any mutation linked to increased virulence, transmission to mammals, or antiviral resistance in the H10N7 strain we identified. Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions. Measures implemented to limit transmission from wildlife to domestic animals as well as measures to control transmission from domestic animals to wild ones need to be equally reinforced. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428329/ doi: 10.1371/journal.pone.0043974 id: cord-000359-y0m1utug author: Walpita, Pramila title: Vaccine Potential of Nipah Virus-Like Particles date: 2011-04-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071823/ doi: 10.1371/journal.pone.0018437 id: cord-336441-m6pur6td author: Wang, Changjian title: Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model date: 2019-02-11 words: 5186.0 sentences: 282.0 pages: flesch: 45.0 cache: ./cache/cord-336441-m6pur6td.txt txt: ./txt/cord-336441-m6pur6td.txt summary: title: Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model Based on the apparent energy consumption data, a systematic and comprehensive city-level total carbon accounting approach was established and applied in Guangzhou, China. g. Stochastic impacts by regression on population, affluence, and technology (STIRPAT) model) are the most commonly applied methods for the scientific evaluation and quantitative analysis of factors influencing city-level carbon emissions, especially the Logarithmic Mean Divisia Index (LMDI) method based on the IDA framework. [51] performed a multi-sectoral decomposition analysis of city-level greenhouse gas emissions in Tianjin from 2001 to 2009, including the agricultural, industrial, transportation, commercial and other sectors, and the results showed that economic growth was the most important driver for emissions increments while energy efficiency was primarily responsible for emissions reductions. abstract: Based on the apparent energy consumption data, a systematic and comprehensive city-level total carbon accounting approach was established and applied in Guangzhou, China. A newly extended LMDI method based on the Kaya identity was adopted to examine the main drivers for the carbon emissions increments both at the industrial sector and the residential sector. Research results are listed as follow: (1) Carbon emissions embodied in the imported electricity played a significant important role in emissions mitigation in Guangzhou. (2) The influences and impacts of various driving factors on industrial and residential carbon emissions are different in the three different development periods, namely, the 10(th) five-year plan period (2003–2005), the 11(th) five-year plan period (2005–2010), and the 12(th) five-year plan period (2010–2013). The main reasons underlying these influencing mechanisms were different policy measures announced by the central and local government during the different five-year plan periods. (3) The affluence effect (g-effect) was the dominant positive effect in driving emissions increase, while the energy intensity effect of production (e-effect-Production), the economic structure effect (s-effect) and the carbon intensity effect of production (f-effect-Production) were the main contributing factors suppressing emissions growth at the industrial sector. (4) The affluence effect of urban (g-effect-AUI) was the most dominant positive driving factor on emissions increment, while the energy intensity effect of urban (e-effect-Urban) played the most important role in curbing emissions growth at the residential sector. url: https://www.ncbi.nlm.nih.gov/pubmed/30742627/ doi: 10.1371/journal.pone.0210430 id: cord-356132-1nisyl5r author: Wang, Huiyao title: The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey date: 2020-05-14 words: 3022.0 sentences: 148.0 pages: flesch: 43.0 cache: ./cache/cord-356132-1nisyl5r.txt txt: ./txt/cord-356132-1nisyl5r.txt summary: The population with younger age (F = 102.04), unmarried (t = 15.28), with history of visiting Wuhan in the past month (t = -40.86), with history of epidemics occurring in the community (t = -10.25), more concern with media reports (F = 21.84), perceived more impacts of the epidemic outbreak (changes over living situations, F = 331.71; emotional control, F = 1863.07; epidemic-related dreams, F = 1642.78) and negative coping style (t = 37.41) had higher level of psychological distress. The general mainland Chinese population with unmarried, history of visiting Wuhan in the past month, perceived more impacts of the epidemic and negative coping style had higher level of psychological distress in the early stages of COVID-19 epidemic. Unmarried, history of visiting Wuhan, more serious changes over living situations, more difficult of emotional control, higher frequency of epidemic-related dreams, and negative coping style in the general population showed higher level of psychological distress. abstract: As the epidemic outbreak of 2019 coronavirus disease (COVID-19), general population may experience psychological distress. Evidence has suggested that negative coping styles may be related to subsequent mental illness. Therefore, we investigate the general population’s psychological distress and coping styles in the early stages of the COVID-19 outbreak. A cross-sectional battery of surveys was conducted from February 1–4, 2020. The Kessler 6 psychological distress scale, the simplified coping style questionnaire and a general information questionnaire were administered on-line to a convenience sample of 1599 in China. A multiple linear regression analysis was performed to identify the influence factors of psychological distress. General population’s psychological distress were significant differences based on age, marriage, epidemic contact characteristics, concern with media reports, and perceived impacts of the epidemic outbreak (all p <0.001) except gender (p = 0.316). The population with younger age (F = 102.04), unmarried (t = 15.28), with history of visiting Wuhan in the past month (t = -40.86), with history of epidemics occurring in the community (t = -10.25), more concern with media reports (F = 21.84), perceived more impacts of the epidemic outbreak (changes over living situations, F = 331.71; emotional control, F = 1863.07; epidemic-related dreams, F = 1642.78) and negative coping style (t = 37.41) had higher level of psychological distress. Multivariate analysis found that marriage, epidemic contact characteristics, perceived impacts of the epidemic and coping style were the influence factors of psychological distress (all p <0.001). Epidemic of COVID-19 caused high level of psychological distress. The general mainland Chinese population with unmarried, history of visiting Wuhan in the past month, perceived more impacts of the epidemic and negative coping style had higher level of psychological distress in the early stages of COVID-19 epidemic. Psychological interventions should be implemented early, especially for those general population with such characteristics. url: https://doi.org/10.1371/journal.pone.0233410 doi: 10.1371/journal.pone.0233410 id: cord-354547-eomm1sl5 author: Wang, Jibin title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date: 2009-03-16 words: 6319.0 sentences: 295.0 pages: flesch: 51.0 cache: ./cache/cord-354547-eomm1sl5.txt txt: ./txt/cord-354547-eomm1sl5.txt summary: title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding In this study, we report that interaction between coronavirus membrane protein (M) and actin with functional implication in facilitating virion assembly and budding. Similarly, analysis of cells expressing the M protein either on its own or together with the Myc-tagged actin by Western blot with anti-M polyclonal antibodies showed the detection of the full-length glycosylated (two upper bands) and unglycosylated (25 kDa) forms of the M protein (Fig. 2, lanes 5 and 6) . In cells transfected with both wild type and MD5 constructs with or without IBV infection, detection of similar amounts of M protein was observed (Fig. 5b, top two panels, lanes 1 and 2) , suggesting that both constructs were expressed at similar efficiencies. abstract: Coronavirus M protein is an essential component of virion and plays pivotal roles in virion assembly, budding and maturation. The M protein is integrated into the viral envelope with three transmembrane domains flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. In this study, we showed co-purification of the M protein from coronavirus infectious bronchitis virus (IBV) with actin. To understand the cellular factors that may be involved in virion assembly, budding and maturation processes, IBV M was used as the bait in a yeast two-hybrid screen, resulting in the identification of β-actin as a potentially interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation and immunofluorescence microscopy in mammalian cells, and mutation of amino acids A159 and K160 on the M protein abolished the interaction. Introduction of the A159-K160 mutation into an infectious IBV clone system blocks the infectivity of the clone, although viral RNA replication and subgenomic mRNA transcription were actively detected. Disruption of actin filaments with cell-permeable agent cytochalasin D at early stages of the infection cycle led to the detection of viral protein synthesis in infected cells but not release of virus particles to the cultured media. However, the same treatment at late stages of the infection cycle did not affect the release of virus particles to the media, suggesting that disruption of the actin filaments might block virion assembly and budding, but not release of the virus particles. This study reveals an essential function of actin in the replication cycle of coronavirus. url: https://doi.org/10.1371/journal.pone.0004908 doi: 10.1371/journal.pone.0004908 id: cord-281161-u896icp9 author: Wang, Jing title: The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates date: 2012-05-17 words: 6854.0 sentences: 317.0 pages: flesch: 49.0 cache: ./cache/cord-281161-u896icp9.txt txt: ./txt/cord-281161-u896icp9.txt summary: We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. As shown in Table 2 , similar IgG1 and IgG2a humoral immune responses against the influenza viruses were induced in the mice vaccinated previously with rRBD plus rOv-ASP-1 adjuvant and those administered with PBS only. As shown in Table 3 , all of the NHPs vaccinated with rRBD protein plus 50 mg (n = 2), 100 mg rOv-ASP-1 (n = 2) or 500 mg CpG (n = 1) as the adjuvant developed RBDspecific IgG antibody response with increasing antibody level after each boost. Secondly, using two concentration of the rOv-ASP-1 adjuvant, 50 or 100 mg, and rRBD as the vaccine antigen, we were able to induce after three immunizations high titers of neutralizing antibodies (1:3,500-1:6,392) that much exceed what is needed for protection against SARS-CoV infection in vivo (.1:500) [56] . abstract: Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant. url: https://doi.org/10.1371/journal.pone.0037019 doi: 10.1371/journal.pone.0037019 id: cord-355874-nz6eqcdb author: Wang, Le title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia date: 2016-09-14 words: 3067.0 sentences: 160.0 pages: flesch: 54.0 cache: ./cache/cord-355874-nz6eqcdb.txt txt: ./txt/cord-355874-nz6eqcdb.txt summary: title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia In this study, we used the GeXP-based assay for simultaneous detection of 20 types/subtypes of viruses in 1699 nasopharyngeal specimens collected from hospitalized children with CAP. To evaluate the sensitivity of the GeXP assay, nucleic acid from all 20 target viruses and the internal control pcDNA3.1 (+) DNA were mixed to make the template pool. In the present study, we applied multiplex RT-PCR together with automated capillary electrophoresis, namely the GeXP-based assay, to detect virus in 1699 nasopharyngeal specimens from hospitalized children with CAP. We showed that the GeXP-based assay had high sensitivity and specificity for simultaneous detection of multiple viruses, and about 65% of cases tested were positive for virus. The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/ subtypes abstract: The GeXP-based assay has recently been developed for simultaneous detection of multiple pathogens. So far, the application of the GeXP assay to test larger clinical samples has hardly been reported. Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. Rapid and accurate diagnosis of virus infection is important for the clinical management of CAP. In this study, we explored the GeXP assay for simultaneous detection of 20 types/subtypes of viruses in hospitalized children with CAP. A total of 1699 nasopharyngeal swabs were prospectively collected and viral nucleic acid was extracted and assayed. Using viral genomic DNA or RNA as template, we showed that at the concentration of 10(4) copies of DNA or RNA of each virus/μl, all 20 target viruses were simultaneously identified by the GeXP assay. Fifteen control microorganisms, in contrast, failed to be amplified by the assay. About 65% of cases tested in this study had viral infection, with patients aged <3 years having a 70% positive rate, significantly higher than that in patients aged > 3 years (40%). The most frequently detected virus was RSV followed by PIV3, HRV, ADV and HBoV. Seasonal distribution analysis revealed that RSV was the most predominant in autumn and winter, while in spring and summer PIV3 and RSV were the most frequently identified with similar positive percentages. One hundred twenty randomly-chosen samples tested by the GeXP assay were re-evaluated by mono-RT-PCR, the results showed 97.5% diagnosis agreement between these 2 methods. Our findings suggest that the GeXP assay could be a valuable diagnostic tool for virus infection in pediatric patients with CAP. url: https://www.ncbi.nlm.nih.gov/pubmed/27627439/ doi: 10.1371/journal.pone.0162411 id: cord-000140-5kapn32k author: Wang, Pei-Gang title: Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins date: 2009-12-15 words: 7780.0 sentences: 396.0 pages: flesch: 53.0 cache: ./cache/cord-000140-5kapn32k.txt txt: ./txt/cord-000140-5kapn32k.txt summary: METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Our data demonstrate that newly synthesized proteins need 8 hours to be translocated through the secretory pathway and released into the supernatant as mature RSPs. To further characterize secreted DV1 RSPs, we performed sucrose gradient fractionation on RSPs concentrated from supernatant of HeLa-prME cells. To identify host factors that could either enhance or reduce production of DV RSPs, we first developed a quantitative assay to relatively quantify levels of secreted particles in supernatant of HeLa-prME cells. abstract: BACKGROUND: Flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prM and E envelope proteins and are believed to undergo the same maturation process. Dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native forms of prM and E. METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. A stable HeLa cell line expressing DV1 prME was established (HeLa-prME) and RSPs were analyzed by immunofluorescence and transmission electron microscopy. We found that E protein is mainly present in the endoplasmic reticulum (ER) where assembly of RSPs could be observed. Biochemical characterization of DV1 RSPs secretion revealed both prM protein cleavage and homodimerization of E proteins before their release into the supernatant, indicating that RSPs undergo a similar maturation process as dengue virus. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Knockdown of 23 genes resulted in a significant reduction in DV RSP secretion, whereas for 22 others we observed an increase of RSP levels in cell supernatant. CONCLUSIONS/SIGNIFICANCE: Our data describe the efficient production of RSPs containing native prM and E envelope proteins for all dengue serotypes. Dengue RSPs and corresponding producing cell lines are safe and novel tools that can be used in the study of viral egress as well as in the development of vaccine and drugs against dengue virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790604/ doi: 10.1371/journal.pone.0008325 id: cord-324410-be2ith3z author: Wang, Qi title: Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry date: 2007-06-13 words: 3772.0 sentences: 160.0 pages: flesch: 48.0 cache: ./cache/cord-324410-be2ith3z.txt txt: ./txt/cord-324410-be2ith3z.txt summary: These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce the crystal structures of small-molecule guest-host complexes. Herein we report the results of our docking studies with 161 selected crystal structures of small-molecule guest-host complexes using the EUDOC program. These results show that the program is able to reproduce all 161 crystal structures and that the average interaction energy of these small-molecule complexes (250.1 kcal/mol) is nearly half of that of the 153 small molecule-bound protein complexes we studied in previous tests (2108.5 kcal/mol). The results also demonstrate the significant influence of crystal packing on small-molecule complex crystal structures and suggest that the EUDOC program is able to predict 3D structures of small-molecule guest-host complexes with reasonable reliability. abstract: EUDOC is a docking program that has successfully predicted small-molecule-bound protein complexes and identified drug leads from chemical databases. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce crystal structures of small-molecule complexes. Of 161 selected crystal structures of small-molecule guest-host complexes, EUDOC reproduced all these crystal structures with guest structure mass-weighted root mean square deviations (mwRMSDs) of <1.0 Å relative to the corresponding crystal structures. In addition, the average interaction energy of these 161 guest-host complexes (−50.1 kcal/mol) was found to be nearly half of that of 153 previously tested small-molecule-bound protein complexes (−108.5 kcal/mol), according to the interaction energies calculated by EUDOC. 31 of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if neighboring hosts in the crystal structure of a guest-host complex were not included as part of the multimeric host system, whereas two of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if water molecules were excluded from the host system. These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions. url: https://www.ncbi.nlm.nih.gov/pubmed/17565384/ doi: 10.1371/journal.pone.0000531 id: cord-296691-cg463fbn author: Wang, Ren title: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing date: 2013-04-09 words: 5831.0 sentences: 334.0 pages: flesch: 46.0 cache: ./cache/cord-296691-cg463fbn.txt txt: ./txt/cord-296691-cg463fbn.txt summary: title: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. They have played significant roles in functional genomics research for discovery of novel genes together with identifying different protein groups (e.g. proteins with signal peptides) other than the whole genome [27] [28] [29] , developing SSRs and SNPs markers [30] [31] [32] [33] [34] , allowing large-scale expression analysis [35] , improving genome annotation [36] , and elucidating phylogenetic relationships [37] . Hence, determination of the genetic pathways and specific genes involved in Amaryllidaceae alkaloids biosynthesis and some other aspects of Lycoris could be beneficial for humans and enrich our knowledge and understanding of functional genomics and biological research. abstract: BACKGROUND: Lycoris aurea, also called Golden Magic Lily, is an ornamentally and medicinally important species of the Amaryllidaceae family. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for L. aurea using high-throughput sequencing technology. METHODOLOGY AND PRINCIPAL FINDINGS: Total RNA was isolated from leaves with sodium nitroprusside (SNP), salicylic acid (SA), or methyl jasmonate (MeJA) treatment, stems, and flowers at the bud, blooming, and wilting stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, a total of 937,990 high quality reads (308.63 Mb) with an average read length of 329 bp were generated. Clustering and assembly of these reads produced a non-redundant set of 141,111 unique sequences, comprising 24,604 contigs and 116,507 singletons. All of the unique sequences were involved in the biological process, cellular component and molecular function categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. Furthermore, 6,386 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. CONCLUSIONS: The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in L. aurea. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will provide useful information for functional genomic research in future. url: https://www.ncbi.nlm.nih.gov/pubmed/23593220/ doi: 10.1371/journal.pone.0060449 id: cord-296435-6dergkha author: Wang, Tiehua title: Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study date: 2014-04-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10(3)/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10(3)/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality. url: https://doi.org/10.1371/journal.pone.0094124 doi: 10.1371/journal.pone.0094124 id: cord-265138-i5m3ax7g author: Wang, Xi-Ling title: Model Selection in Time Series Studies of Influenza-Associated Mortality date: 2012-06-20 words: 4196.0 sentences: 240.0 pages: flesch: 45.0 cache: ./cache/cord-265138-i5m3ax7g.txt txt: ./txt/cord-265138-i5m3ax7g.txt summary: METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. Four model selection criteria were considered in this study: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV). Two recent studies in Canada and Hong Kong have demonstrated the estimates of influenza-associated hospitalization derived from Poisson regression models reasonably matched the numbers of patients with laboratory confirmed influenza infections [17, 29] . abstract: BACKGROUND: Poisson regression modeling has been widely used to estimate influenza-associated disease burden, as it has the advantage of adjusting for multiple seasonal confounders. However, few studies have discussed how to judge the adequacy of confounding adjustment. This study aims to compare the performance of commonly adopted model selection criteria in terms of providing a reliable and valid estimate for the health impact of influenza. METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. The performance of these criteria was evaluated by the bias and root-mean-square error (RMSE) of estimates from the pre-determined coefficients of influenza proxy variable. These four criteria were subsequently applied to an empirical hospitalization dataset to confirm the findings of simulation study. RESULTS: GCV consistently provided smaller biases and RMSEs for the influenza coefficient estimates than QAIC, QBIC and PACF, under the different simulation scenarios. Sensitivity analysis of different pre-determined influenza coefficients, study periods and lag weeks showed that GCV consistently outperformed the other criteria. Similar results were found in applying these selection criteria to estimate influenza-associated hospitalization. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. These findings shall help standardize the Poisson modeling approach for influenza disease burden studies. url: https://doi.org/10.1371/journal.pone.0039423 doi: 10.1371/journal.pone.0039423 id: cord-267189-xq70rn1j author: Wang, Xinyu title: Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China date: 2016-01-15 words: 3037.0 sentences: 156.0 pages: flesch: 56.0 cache: ./cache/cord-267189-xq70rn1j.txt txt: ./txt/cord-267189-xq70rn1j.txt summary: To trace the evolution of canine coronavirus (CCoV), 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs) targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity. A phylogenetic analysis using partial S gene sequences demonstrated that the 26 CCoV-IIa strains were closely related to three reference strains, 5281 (Japan), TN-449 (USA), and 1086-IIa (Brazil), and differed genetically from reference strains from China and other countries (Fig 2A) . This result demonstrated that vaccination for other canine viruses did not effect CCoV infections in the dog population in Heilongjiang province, northeast China. abstract: To trace the evolution of canine coronavirus (CCoV), 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs) targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. M gene RT-PCRs showed that 28.36% (57/201) of the samples were positive for CCoV; of the 57 positive samples, CCoV-I and CCoV-II accounted for 15.79% (9/57) and 84.21% (48/57), respectively. A sequence comparison of the partial M gene revealed nucleotide homologies of 88.4%–100% among the 57 CCoV strains, and 88.7%–96.2% identity between the 57 CCoV strains and the Chinese reference strain HF3. The CCoV-I and CCoV-II strains exhibited genetic diversity when compared with reference strains from China and other countries. The 57 CCoV strains exhibited high co-infection rates with canine kobuvirus (CaKV) (33.33%) and canine parvovirus-2 (CPV-2) (31.58%). The CCoV prevalence in diarrheic dogs differed significantly with immunization status, regions, seasons, and ages. Moreover, 28 S genes were amplified from the 57 CCoV-positive samples, including 26 CCoV-IIa strains, one CCoV-IIb strain, and one CCoV-I strain. A sequence comparison of the partial S gene revealed 86.3%–100% nucleotide identity among the 26 CCoV-IIa strains, and 89.6%–92.2% identity between the 26 CCoV-IIa strains and the Chinese reference strain V1. The 26 CCoV-IIa strains showed genetic diversity when compared with reference strains from China and other countries. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity. url: https://doi.org/10.1371/journal.pone.0146975 doi: 10.1371/journal.pone.0146975 id: cord-002043-z1b7pj3s author: Wang, Xue-Yang title: Comparative Transcriptome Analysis of Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV in Susceptible and Near-Isogenic Resistant Strains date: 2016-05-11 words: 5879.0 sentences: 359.0 pages: flesch: 42.0 cache: ./cache/cord-002043-z1b7pj3s.txt txt: ./txt/cord-002043-z1b7pj3s.txt summary: obtained numerous differentially expressed genes (DEGs) involved in metabolism, immunity, and inflammatory responses in Microtus fortis following infection with Schistosoma japonicum based on comparative transcriptome analysis [20] . reported that several genes related to physical barriers, immune response, proteolytic/metabolic enzymes, heat-shock proteins, and hormonal signaling were possibly involved in silkworm resistance against Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) infection; although these genes might be induced by the virus in order to increase infectivity [21] . After BmNPV infection, the expression levels of 4 genes were down-regulation in BC9 and A35 (resistant strain) (Fig 6) , which was consistent with the transcriptome data. Based on their role in apoptosis activation, hosts need to increase the expression level of these genes to promote apoptosis when exposed to a virus; this supposition explains the up-regulation of genes involved in apoptosis in the transcriptome following BmNPV infection. abstract: Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens causing severe economic losses in sericulture. However, the molecular mechanism of silkworm resistance to BmNPV remains largely unknown. Here, the recurrent parent P50 (susceptible strain) and the near-isogenic line BC9 (resistance strain) were used in a comparative transcriptome study examining the response to infection with BmNPV. A total of 14,300 unigenes were obtained from two different resistant strains; of these, 869 differentially expressed genes (DEGs) were identified after comparing the four transcriptomes. Many DEGs associated with protein metabolism, cytoskeleton, and apoptosis may be involved in the host response to BmNPV infection. Moreover, some immunity related genes were also altered following BmNPV infection. Specifically, after removing genetic background and individual immune stress response genes, 22 genes were found to be potentially involved in repressing BmNPV infection. These genes were related to transport, virus replication, intracellular innate immune, and apoptosis. Our study provided an overview of the molecular mechanism of silkworm resistance to BmNPV infection and laid a foundation for controlling BmNPV in the future. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864234/ doi: 10.1371/journal.pone.0155341 id: cord-001343-3euy4u9k author: Wang, Yadong title: A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices date: 2014-06-27 words: 4088.0 sentences: 161.0 pages: flesch: 40.0 cache: ./cache/cord-001343-3euy4u9k.txt txt: ./txt/cord-001343-3euy4u9k.txt summary: In recognition of the national need for an in-service program to target the''''level four'''' health staff as defined by WADEM, i.e.''h ealth workers who played lead roles in disaster health management'''' [20] , China''s Ministry of Health (MoH) commissioned the Capital Medical University in 2010 to develop and implement a competency-based curriculum to help strengthen the performance of the new cadre of HERO staff. We assessed tasks, roles and responsibilities, and training needs of HERO staff through face-to-face interviews of eleven experienced key informants; they included health emergency experts from the government, the military and the academic sector, and senior staff of HEROs. We also explored their awareness of existing training activities and the associated relative strengths and weaknesses, their preferences on modes of curriculum delivery and the optimal duration of in-service training. abstract: OBJECTIVE: To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings. METHODS: The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China’s policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel. FINDINGS: Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills. CONCLUSION: This study adds to the emerging literature on China’s enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074095/ doi: 10.1371/journal.pone.0100892 id: cord-000851-uylgyhs8 author: Wang, Zhenya title: Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro date: 2013-01-07 words: 4519.0 sentences: 213.0 pages: flesch: 47.0 cache: ./cache/cord-000851-uylgyhs8.txt txt: ./txt/cord-000851-uylgyhs8.txt summary: faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased. The results from quantitative RT-PCR shown in Fig. 5 reveal a decreased expression of these mediators when compared to the non-treated samples (SwIV-infected 3D4/21-cells without E. faecium effectively protects host cells from swine influenza virus infection and are in support of the above author''s hypothesis, that probiotics are not only useful to inhibit enteric viruses, but may also have potential for the control of respiratory viruses. faecium before SwIV-infection and a 1 h treatment after completion of virus infection also led to a 2-3 log-unit loss of virus titer, the probiotic must alter host cell factors which apparently results in an inhibition of influenza virus multiplication. faecium in SwIV-infected 3D4/21 cells, the reduced inflammatory response caused by some cytokines at the cellular level may contribute to the antiviral effect of the probiotic. abstract: The control of infectious diseases such as swine influenza viruses (SwIV) plays an important role in food production both from the animal health and from the public health point of view. Probiotic microorganisms and other health improving food supplements have been given increasing attention in recent years, but, no information on the effects of probiotics on swine influenza virus is available. Here we address this question by assessing the inhibitory potential of the probiotic Enterococcus faecium NCIMB 10415 (E. faecium) on the replication of two porcine strains of influenza virus (H1N1 and H3N2 strain) in a continuous porcine macrophage cell line (3D4/21) and in MDBK cells. Cell cultures were treated with E. faecium at the non-toxic concentration of 1×10(6) CFU/ml in growth medium for 60 to 90 min before, during and after SwIV infection. After further incubation of cultures in probiotic-free growth medium, cell viability and virus propagation were determined at 48 h or 96 h post infection. The results obtained reveal an almost complete recovery of viability of SwIV infected cells and an inhibition of virus multiplication by up to four log units in the E. faecium treated cells. In both 3D4/21- and MDBK-cells a 60 min treatment with E. faecium stimulated nitric oxide (NO) release which is in line with published evidence for an antiviral function of NO. Furthermore, E. faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased. Since we obtained experimental evidence for the direct adsorptive trapping of SwIV through E. faecium, this probiotic microorganism inhibits influenza viruses by at least two mechanisms, direct physical interaction and strengthening of innate defence at the cellular level. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538747/ doi: 10.1371/journal.pone.0053043 id: cord-354000-jxqskt4k author: Warren, Cody J. title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 words: 4420.0 sentences: 265.0 pages: flesch: 47.0 cache: ./cache/cord-354000-jxqskt4k.txt txt: ./txt/cord-354000-jxqskt4k.txt summary: Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. abstract: Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking. url: https://doi.org/10.1371/journal.pone.0096579 doi: 10.1371/journal.pone.0096579 id: cord-001599-pfdnmzx2 author: Wee, Yin Shen title: Age-Related Onset of Obesity Corresponds with Metabolic Dysregulation and Altered Microglia Morphology in Mice Deficient for Ifitm Proteins date: 2015-04-09 words: 6017.0 sentences: 327.0 pages: flesch: 45.0 cache: ./cache/cord-001599-pfdnmzx2.txt txt: ./txt/cord-001599-pfdnmzx2.txt summary: Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. As we maintain these animals as homozygous deletion lines, over time we have observed a pronounced enhanced weight gain and an obesity phenotype (e.g., [21] [22] [23] ) in older IfitmDel mice compared to C57BL/6 controls. In this report we quantify the obesity phenotype and link this to altered leptin/neuropeptide signaling, and demonstrate abnormal microglia morphology in the IfitmDel animal. Based upon the previously described findings that the absence of the Ifitm proteins can alter cellular induction pathways following type I interferon treatment, we tested whether or not the IfitmDel animals would have an altered response, compared to WT, to chronic Poly I:C treatment. abstract: The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This animal breeds normally with no obvious defect in development. The IfitmDel animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months of age and under normal feeding conditions. The increased weight corresponds with elevated fat mass, and in tolerance tests they are hyporesponsive to insulin but respond normally to glucose. Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels of serum leptin suggesting a defect in leptin/leptin receptor signaling. Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. Also elevated in hypothalamus of IfitmDel mice were pro-inflammatory cytokine expression and reduced IL-10. Anatomical analysis of the hypothalamus using immunohistochemistry revealed that microglia exhibit an abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC challenge. These abnormalities extend the phenotype of the IfitmDel mouse beyond abnormal responses to viral challenge to include a metabolic phenotype and weight gain. Further, this novel phenotype for the IfitmDel mouse could be related to abnormal neuropeptide production, inflammatory status and microglia status in the hypothalamus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391874/ doi: 10.1371/journal.pone.0123218 id: cord-308764-9z4qcoqz author: Wei, Lin title: Transcriptome Analysis of Houttuynia cordata Thunb. by Illumina Paired-End RNA Sequencing and SSR Marker Discovery date: 2014-01-02 words: 5253.0 sentences: 298.0 pages: flesch: 51.0 cache: ./cache/cord-308764-9z4qcoqz.txt txt: ./txt/cord-308764-9z4qcoqz.txt summary: cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata and used Illumina paired-end sequencing technology to generate a large-scale EST database and develop a set of SSR markers. For further assessment of the assembly quality and development of new molecular markers, all 63,954 unigenes generated in this study were used to mine potential microsatellites, which were defined as di-to hexa-nucleotide SSRs with a minimum of four repetitions for all motifs. Here, the N50 length of the unigenes was 1,051 bp and the average length was 679 bp, which suggests that the relatively short reads from Illumina paired-end sequencing for this non-model organism have been effectively and accurately assembled. abstract: BACKGROUND: Houttuynia cordata Thunb. is an important traditional medical herb in China and other Asian countries, with high medicinal and economic value. However, a lack of available genomic information has become a limitation for research on this species. Thus, we carried out high-throughput transcriptomic sequencing of H. cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development. PRINCIPAL FINDINGS: Illumina paired-end sequencing technology produced over 56 million sequencing reads from H. cordata mRNA. Subsequent de novo assembly yielded 63,954 unigenes, 39,982 (62.52%) and 26,122 (40.84%) of which had significant similarity to proteins in the NCBI nonredundant protein and Swiss-Prot databases (E-value <10(−5)), respectively. Of these annotated unigenes, 30,131 and 15,363 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. In addition, 24,434 (38.21%) unigenes were mapped onto 128 pathways using the KEGG pathway database and 17,964 (44.93%) unigenes showed homology to Vitis vinifera (Vitaceae) genes in BLASTx analysis. Furthermore, 4,800 cDNA SSRs were identified as potential molecular markers. Fifty primer pairs were randomly selected to detect polymorphism among 30 samples of H. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata in the future. CONCLUSIONS: This is the first application of Illumina paired-end sequencing technology to investigate the whole transcriptome of H. cordata and to assemble RNA-seq reads without a reference genome. These data should help researchers investigating the evolution and biological processes of this species. The SSR markers developed can be used for construction of high-resolution genetic linkage maps and for gene-based association analyses in H. cordata. This work will enable future functional genomic research and research into the distinctive active constituents of this genus. url: https://doi.org/10.1371/journal.pone.0084105 doi: 10.1371/journal.pone.0084105 id: cord-048446-gaemgm0t author: White, Laura Forsberg title: Transmissibility of the Influenza Virus in the 1918 Pandemic date: 2008-01-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century. METHODOLOGY/PRINCIPAL FINDINGS: We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918. Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak. This analysis shows the basic reproductive number to be slightly lower in the Maryland communities (between 1.34 and 3.21) than for the enclosed populations on the ships (R(0) = 4.97, SE = 3.31). Additionally the effective reproductive number declined to sub epidemic levels more quickly on the ships (within around 10 days) than in the communities (within 30–40 days). The mean serial interval for the ships was consistent (3.33, SE = 5.96 and 3.81, SE = 3.69), while the serial intervals in the communities varied substantially (between 2.83, SE = 0.53 and 8.28, SE = 951.95). CONCLUSIONS/SIGNIFICANCE: These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza. The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2204055/ doi: 10.1371/journal.pone.0001498 id: cord-002889-fie121ns author: White, Michael title: Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer date: 2018-02-23 words: 4872.0 sentences: 222.0 pages: flesch: 47.0 cache: ./cache/cord-002889-fie121ns.txt txt: ./txt/cord-002889-fie121ns.txt summary: Human and mouse mesothelin share sequence similarity, expression patterns, and biochemical characteristics, [7] , and the homeostatic function of mesothelin in mammals is unknown: the gene can be deleted without apparent effect in mice PLOS C57Bl6 mice and thus can be grown in syngeneic mice to allow for study of an anti-tumor immune response in an immunocompetent mouse model. In order to create a putative therapeutic anti-mesothelin vaccine, we inserted the mouse mesothelin gene into the poxvirus MVA genome under a viral promoter so that mesothelin would be expressed in any cells infected with the recombinant virus. To determine whether the viruses expressing mesothelin protein were able to induce an immune response in mice, we first attempted to measure anti-mesothelin antibody in vaccinated mouse sera. In comparison, there were very few spots (1-3) in response to stimulation with Lewis Lung cells that do not express mouse mesothelin, and mice vaccinated with MVA, MVAmeso and MVAmesoA35Del viruses all had good responses to restimulation with vaccinia virus (124, 147, and 148 spots respectively). abstract: Pancreatic cancer is the 5(th) leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells. In addition, the MVA virus has oncolytic properties in vitro as it can replicate in and kill Panc02 pancreatic adenocarcinoma cell line tumor cells, even though it is unable to replicate in most mammalian cells. Deletion of the A35 gene in MVA improved T cell responses as expected. However, we were unable to demonstrate inhibition of Panc02 tumor growth in immunocompetent mice with pre-vaccination of mice, boosts, or even intratumoral injections of the recombinant viruses. Vaccine efficacy may be limited by shedding of mesothelin from tumor cells thus creating a protective screen from the immune system. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825036/ doi: 10.1371/journal.pone.0193131 id: cord-299953-sasfvcun author: Whitehead, Ashley B. R. title: Burden of exposure to infectious bursal disease virus, infectious bronchitis virus, Newcastle disease virus, Mycoplasma gallisepticum, and intestinal parasites in introduced broiler chickens on the Galapagos date: 2018-09-24 words: 4442.0 sentences: 220.0 pages: flesch: 55.0 cache: ./cache/cord-299953-sasfvcun.txt txt: ./txt/cord-299953-sasfvcun.txt summary: The objective of the study reported here was to measure the burden of exposure to infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), Mycoplasma gallisepticum (MG), and intestinal parasites in a sample of broiler chickens on 13 farms on Santa Cruz Island and San Cristobal Island in July 2017. Study results are relevant because (i) they provide new baseline data on the burden of exposure to avian pathogens in broiler farms, (ii) justify the need to verify standard operating procedures in hatcheries that supply (non-vaccinated) day-old chicks to the Galapagos and (iii) to implement enhanced biosecurity standards on broiler chicken farms to mitigate risk of disease transmission between broilers, backyard poultry, and wild birds on the Galapagos. abstract: Diseases in introduced broilers can possibly spill over to wild birds on the Galapagos. Knowledge about the current burden of exposure to pathogens in broilers on the Galapagos is very limited. The objective of the study reported here was to measure the burden of exposure to infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), Mycoplasma gallisepticum (MG), and intestinal parasites in a sample of broiler chickens on 13 farms on Santa Cruz Island and San Cristobal Island in July 2017. Blood serum samples were tested for detection of antibodies to IBDV, IBV, NDV, and MG by using an IDEXX Enzyme-linked Immunosorbent Assay. In addition, fecal samples and pen bedding environmental samples were processed and analyzed for diagnosis of intestinal parasite eggs under a compound light microscope. The frequency of seropositive broilers to IBDV was 74/130 or 56% (95% CI = 48, 65%), to IBV was 27/130 or 20% (14, 28%), and to NDV was 1/130 or 0.7% (0.1, 4%). All broilers tested negative to MG antibodies. Eimeria spp. infection was common in study broilers. Finally, we observed interaction between broiler chickens and wild birds (finches) inside broiler pens, as well as the presence of backyard chickens inside property limits of study farms. This study produced evidence that exposure to IBDV, IBV, and intestinal parasites in broilers on Santa Cruz Island and San Cristobal Island is important. Study results are relevant because (i) they provide new baseline data on the burden of exposure to avian pathogens in broiler farms, (ii) justify the need to verify standard operating procedures in hatcheries that supply (non-vaccinated) day-old chicks to the Galapagos and (iii) to implement enhanced biosecurity standards on broiler chicken farms to mitigate risk of disease transmission between broilers, backyard poultry, and wild birds on the Galapagos. url: https://www.ncbi.nlm.nih.gov/pubmed/30248128/ doi: 10.1371/journal.pone.0203658 id: cord-253436-dz84icdc author: Wille, Michelle title: High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl date: 2016-03-03 words: 2019.0 sentences: 103.0 pages: flesch: 54.0 cache: ./cache/cord-253436-dz84icdc.txt txt: ./txt/cord-253436-dz84icdc.txt summary: In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. Despite few studies, small samples sizes and differences in prevalence, what is clear, is that in the Northern Hemisphere waterfowl species, especially dabbling and diving ducks are important in the epidemiology of avian CoVs. It is interesting to note that these patterns are very similar to those found in low pathogenic influenza A viruses: high prevalence in waterfowl and gulls in the Northern Hemisphere [30] , and little host species and temporal structuring within waterfowl derived viruses in the conserved polymerase genes (such as PB2, PB1) [31] . abstract: Coronaviruses (CoVs) are found in a wide variety of wild and domestic animals, and constitute a risk for zoonotic and emerging infectious disease. In poultry, the genetic diversity, evolution, distribution and taxonomy of some coronaviruses have been well described, but little is known about the features of CoVs in wild birds. In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. The highest prevalence was found in the diving ducks—mainly Greater Scaup (Aythya marila; 51.5%)—and the dabbling duck Mallard (Anas platyrhynchos; 19.2%). Sequences from two of the Greater Scaup CoV fell into an infrequently detected lineage, shared only with a Tufted Duck (Aythya fuligula) CoV. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. A single Black-headed Gull represented the only positive sample from the order Charadriiformes. Globally, Anas species represent the largest fraction of avian CoV sequences, and there seems to be no host species, geographical or temporal structure. To better understand the eitiology, epidemiology and ecology of these viruses more systematic surveillance of wild birds and subsequent sequencing of detected CoV is imperative. url: https://doi.org/10.1371/journal.pone.0150198 doi: 10.1371/journal.pone.0150198 id: cord-338594-wft7yy6j author: Winkler, Michael title: Rhesus macaque IFITM3 gene polymorphisms and SIV infection date: 2017-03-03 words: 4633.0 sentences: 277.0 pages: flesch: 48.0 cache: ./cache/cord-338594-wft7yy6j.txt txt: ./txt/cord-338594-wft7yy6j.txt summary: In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. Polymorphisms in several immune-relevant gene loci such as MHC or KIR are associated with the transmission and course of disease in SIV infected rhesus macaques and HIV-1 infected humans [36, 37] . Immune-related IFITM proteins have been established as important antiviral effectors of the interferon response, and a polymorphism in the human IFITM3 gene has been found to be associated with disease severity and progression in FLUAV and HIV-1 infection [27, 33] . Notably, all polymorphism in the coding region were silent and strong evidence for an association of rhIFITM3 polymorphisms with disease progression and viral load in SIV infected animals was not obtained. abstract: Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals. url: https://www.ncbi.nlm.nih.gov/pubmed/28257482/ doi: 10.1371/journal.pone.0172847 id: cord-312817-gskbu0oh author: Witte, Carmel title: Spatiotemporal network structure among “friends of friends” reveals contagious disease process date: 2020-08-06 words: 5924.0 sentences: 274.0 pages: flesch: 44.0 cache: ./cache/cord-312817-gskbu0oh.txt txt: ./txt/cord-312817-gskbu0oh.txt summary: These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown. Thus, the population represents a group of birds for which 1) a near-complete social network could be assembled from housing records that tracked dynamic movement over time, and 2) avian mycobacteriosis disease status could be determined for any bird that died. Although disease clustering among friends of friends could represent a contagious process, there is a possibility that some of the association could be explained by homophily, i.e., that connected birds could be more alike than the general bird population in terms of species, behavior, susceptibility, enclosure characteristics, etc. For this test, we evaluated disease clustering between a subject and its friends of friends from different enclosures that could not have transmitted infection based on the timing of the contact. abstract: Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel “friends-of-friends” strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown. url: https://doi.org/10.1371/journal.pone.0237168 doi: 10.1371/journal.pone.0237168 id: cord-351387-i0zamkpd author: Witte, Katrin title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date: 2015-09-25 words: 4360.0 sentences: 220.0 pages: flesch: 49.0 cache: ./cache/cord-351387-i0zamkpd.txt txt: ./txt/cord-351387-i0zamkpd.txt summary: In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. In the first setting, PBMCs were stimulated with EPs 7630 (3 and 30 μg/ml), Escherichia coli 0127:B8 lipopolysaccharide (TLR4 ligand; 100 ng/ml; Sigma-Aldrich), polyinosinic-polycytidylic acid [poly (I:C); 10 μg/ml; Sigma-Aldrich], a cytokine mixture of IL-1β, IL-2 and IL-12 (10 ng/ml each; R&D systems), anti-CD3 (Orthoclone; Cilag) and anti-CD28 (R&D systems) monoclonal antibodies (1 μg/ml each), or were left without specific treatment (0.1% ethanol as solvent control) for 4 and 24 h, before cell culture supernatant was recovered for ELISA cytokine production analysis. Our data show that EPs 7630 strongly and dose-dependently induced the production of the pro-inflammatory cytokines TNF-α and IL-6 in human blood immune cells. abstract: Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. url: https://www.ncbi.nlm.nih.gov/pubmed/26406906/ doi: 10.1371/journal.pone.0138075 id: cord-000269-v4jochbe author: Wittekindt, Nicola E. title: Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date: 2010-10-18 words: 5886.0 sentences: 314.0 pages: flesch: 44.0 cache: ./cache/cord-000269-v4jochbe.txt txt: ./txt/cord-000269-v4jochbe.txt summary: cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. The microbial community of mule deer lymph nodes Detection of protein-coding and ribosomal RNA transcripts provides strong support for the presence of viable and replicating microorganisms. As an alternative approach to identifying bacterial microorganisms present in lymph node tissue, we utilized amplicon DNA library sequencing technology. abstract: The ongoing emergence of human infections originating from wildlife highlights the need for better knowledge of the microbial community in wildlife species where traditional diagnostic approaches are limited. Here we evaluate the microbial biota in healthy mule deer (Odocoileus hemionus) by analyses of lymph node meta-transcriptomes. cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Protein-coding and 16S ribosomal RNA (rRNA) sequences were taxonomically profiled using protein and rRNA specific databases. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Residents of skin and rumen, and those ubiquitous in mule deer habitat dominated classifiable bacterial species. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. Among viruses, a novel gamma retrovirus and other members of the Poxviridae and Retroviridae were identified. We additionally evaluated bacterial diversity by amplicon sequencing the hypervariable V6 region of 16S rRNA and demonstrate that overall taxonomic diversity is higher with the meta-transcriptomic approach. These data provide the most complete picture to date of the microbial diversity within a wildlife host. Our research advances the use of meta-transcriptomics to study microbiota in wildlife tissues, which will facilitate detection of novel organisms with pathogenic potential to human and animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956653/ doi: 10.1371/journal.pone.0013432 id: cord-292777-oztmw8jo author: Wong, Michelle title: Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia date: 2013-07-16 words: 3300.0 sentences: 179.0 pages: flesch: 38.0 cache: ./cache/cord-292777-oztmw8jo.txt txt: ./txt/cord-292777-oztmw8jo.txt summary: In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. In this study we thus sought to determine the contribution of microbial translocation to FUO episodes in an adult febrile neutropaenic cohort using endotoxin and sCD14 concentrations in the plasma as markers for microbial translocation. In this cohort of iatrogenic neutropaenic adults, we found elevated plasma levels of endotoxin and sCD14 in febrile neutropaenic episodes where no other microbiological findings have been documented, implicating microbial translocation as a potential contributor towards their febrile status. Adding to the field, we have, in our study, in addition to measuring plasma endotoxin concentrations, also measured the host receptor for LPS, sCD14 in an attempt to determine the contribution of microbial translocation to fever as a clinical outcome. abstract: In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212). url: https://doi.org/10.1371/journal.pone.0068056 doi: 10.1371/journal.pone.0068056 id: cord-336615-jfnj6l41 author: Wong, Sarah Sze Wah title: In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections date: 2014-01-22 words: 7875.0 sentences: 434.0 pages: flesch: 54.0 cache: ./cache/cord-336615-jfnj6l41.txt txt: ./txt/cord-336615-jfnj6l41.txt summary: We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Second, the increased incidence of invasive candidiasis caused by non-albicans Candida (NAC) species, such as Candida glabrata, Candida tropicalis, Candida krusei or Candida parapsilosis, has been a major concern [13, 14] , because these infections are often associated with higher mortality and antifungal resistance than those caused by C. The antifungal activity of small molecules was assessed by disk diffusion and broth dilution assays (see below) using four groups of Candida isolates. abstract: Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. url: https://www.ncbi.nlm.nih.gov/pubmed/24465737/ doi: 10.1371/journal.pone.0085836 id: cord-001620-yy5gq0ki author: Woo, Hye-Min title: Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5 date: 2015-04-22 words: 3871.0 sentences: 213.0 pages: flesch: 55.0 cache: ./cache/cord-001620-yy5gq0ki.txt txt: ./txt/cord-001620-yy5gq0ki.txt summary: These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus. Subtype H5 is known as highly pathogenic in protein (GST-H5-HA1) was incubated with 100 μL of glutathione agarose beads in 100 μL of binding buffer (50 mM Tris/HCl; pH 8.0, 150 mM NaCl, 1.5 mM MgCl 2 , 2 mM DTT, and 1% [w/v] BSA) for 30 min at room temperature with occasional shaking. To select specific ssDNA aptamers that can distinguish H1-HA1 from H5-HA1, counter-SELEX was performed with an ssDNA library of 88-mers containing a randomized sequence region of 45 nucleotides in the center, followed by lambda exonuclease digestion, as shown in Fig 1A. To confirm that the selected aptamers were bound to the sialic acid-binding region of HA1, we performed a flow cytometry analysis (Fig 7) . abstract: Surface protein hemagglutinin (HA) mediates the binding of influenza virus to host cell receptors containing sialic acid, facilitating the entry of the virus into host cells. Therefore, the HA protein is regarded as a suitable target for the development of influenza virus detection devices. In this study, we isolated single-stranded DNA (ssDNA) aptamers binding to the HA1 subunit of subtype H1 (H1-HA1), but not to the HA1 subunit of subtype H5 (H5-HA1), using a counter-systematic evolution of ligands by exponential enrichment (counter-SELEX) procedure. Enzyme-linked immunosorbent assay and surface plasmon resonance studies showed that the selected aptamers bind tightly to H1-HA1 with dissociation constants in the nanomolar range. Western blot analysis demonstrated that the aptamers were binding to H1-HA1 in a concentration-dependent manner, yet were not binding to H5-HA1. Interestingly, the selected aptamers contained G-rich sequences in the central random nucleotides region. Further biophysical analysis showed that the G-rich sequences formed a G-quadruplex structure, which is a distinctive structure compared to the starting ssDNA library. Using flow cytometry analysis, we found that the aptamers did not bind to the receptor-binding site of H1-HA1. These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406500/ doi: 10.1371/journal.pone.0125060 id: cord-002890-g7aje88u author: Wood, Paul L. title: Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses date: 2018-02-23 words: 3276.0 sentences: 177.0 pages: flesch: 39.0 cache: ./cache/cord-002890-g7aje88u.txt txt: ./txt/cord-002890-g7aje88u.txt summary: In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. In this study, we asked if differences in host''s responses to live, multiplying Leptospira versus killed leptospires, present in the vaccine, are reflected in the serum lipidome of these two groups of horses. Our results show that serum levels of cyclic phosphatidic acids (cPA), diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens were elevated in both vaccinated and naturally infected horses. Our data indicate that the immune response induced by vaccination has a more dramatic effect than leptospiral infection on sphingomyelin synthesis in horses. abstract: Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses. This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825116/ doi: 10.1371/journal.pone.0193424 id: cord-335859-k37jivp6 author: Wu, Daphne C. title: Predictors of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey date: 2020-10-21 words: 3112.0 sentences: 160.0 pages: flesch: 52.0 cache: ./cache/cord-335859-k37jivp6.txt txt: ./txt/cord-335859-k37jivp6.txt summary: To understand the socio-demographic predictors of COVID symptoms, we conducted a logistic regression analysis where the outcome was self-reported symptoms suggestive of COVID infection which we defined in this study as the respondent reporting himself/herself and/or at least one member of the household having had a combination of fever (with or without hallucinations) and any of i) difficulty breathing/shortness of breath or ii) dry cough so severe that it disrupts sleep or iii) a loss of a sense of smell in the past month; and the explanatory variables were gender (male, female, or other), education level (high school and under, or some college/ university and higher), province, age, ethnicity (Indigenous, English and other European, or others), visible minority (defined as persons, other than Aboriginal peoples, who are nonwhite in race or colour) [6] , and number of household members. abstract: Random population-based surveys to estimate prevalence of SARS-CoV2 infection causing coronavirus disease (COVID-19) are useful to understand distributions and predictors of the infection. In April 2020, the first-ever nationally representative survey in Canada polled 4,240 adults age 18 years and older about self-reported COVID experience in March, early in the epidemic. We examined the levels and predictors of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than in older adults, and among visible minorities. Overall, only 3% of respondents and/or household members reported testing for SARS-CoV-2. Being tested was associated with having COVID symptoms, Indigenous identity, and living in Quebec. Periodic nationally representative surveys of symptoms, as well as SARS-CoV-2 antibodies, are required in many countries to understand the pandemic and prepare for the future. url: https://doi.org/10.1371/journal.pone.0240778 doi: 10.1371/journal.pone.0240778 id: cord-003377-9vkhptas author: Wu, Tong title: The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia date: 2018-12-19 words: 4969.0 sentences: 267.0 pages: flesch: 49.0 cache: ./cache/cord-003377-9vkhptas.txt txt: ./txt/cord-003377-9vkhptas.txt summary: title: The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). The indicator for wild bird habitat used in this study was the set of "Important Bird and Biodiversity Areas" (IBAs) for "migratory and congregatory waterbirds" identified by BirdLife The live poultry trade poses different avian influenza risks in different regions of the world Table 1 . Our first specification (Model 1) included a number of factors related to disease risk but excluded both live poultry imports and biosecurity measures. abstract: In the past two decades, avian influenzas have posed an increasing international threat to human and livestock health. In particular, highly pathogenic avian influenza H5N1 has spread across Asia, Africa, and Europe, leading to the deaths of millions of poultry and hundreds of people. The two main means of international spread are through migratory birds and the live poultry trade. We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). Across all three regions, we found per-capita GDP (a proxy for modernization, general biosecurity, and value-at-risk) to be risk reducing. A more specific biosecurity measure–general surveillance–was also found to be mitigating at the all-regions level. However, there were important inter-regional differences. For the EU and ASEAN, intra-bloc live poultry imports were risk reducing while extra-bloc imports were risk increasing; for ECOWAS the reverse was true. This is likely due to the fact that while the EU and ASEAN have long-standing biosecurity standards and stringent enforcement (pursuant to the World Trade Organization’s Agreement on the Application of Sanitary and Phytosanitary Measures), ECOWAS suffered from a lack of uniform standards and lax enforcement. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300203/ doi: 10.1371/journal.pone.0208197 id: cord-340387-ohkjheat author: Wynne, James W. title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date: 2013-01-07 words: 7004.0 sentences: 390.0 pages: flesch: 52.0 cache: ./cache/cord-340387-ohkjheat.txt txt: ./txt/cord-340387-ohkjheat.txt summary: title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. Considering that in other mammalian species, immunoglobulins IgG, IgM and IgA are present in relatively high abundance in serum and tissues, we anticipated that bats would possess a similar immunoglobulin profile. IgG-depleted samples were fractionated by affinity chromatography on immobilised anti-Fab-specific antibodies adopting the same procedure as that described for immobilised Protein A and G except that the binding and washing buffer consisted of 0.3 M NaCl in 50 mM phosphate buffer, pH 7.4. Two major bands were detected by reducing SDS-PAGE in the eluate from both serum and plasma samples; a 66-70 kDa band representative of IgM H , and a 25 kDa band representative of immunoglobulin light chain ( Fig. 3A and 3B ). abstract: There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed within this study can be used in the future to examine class-specific antibody response within this important viral host. url: https://www.ncbi.nlm.nih.gov/pubmed/23308125/ doi: 10.1371/journal.pone.0052930 id: cord-309471-lr68epyb author: Xia, Jingya title: Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs date: 2014-12-08 words: 7010.0 sentences: 312.0 pages: flesch: 42.0 cache: ./cache/cord-309471-lr68epyb.txt txt: ./txt/cord-309471-lr68epyb.txt summary: Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The presence of memory B cells in the culture is therefore detected as a TLR-agonist-induced increase in the number of antigen-specific, ASCs. To test for the presence of memory B cells at peripheral tissues, we stimulated lymphocyte populations isolated from bone marrow, spleen, vagina/cervix, or spinal cord/sensory ganglia of previously infected guinea pigs with a combination of LPS and CpG oligonucleotides and quantified HSV-specific ASC by ELISPOT. On day 7 post infection, HSV-specific, IFN-c-secreting T cells from the spleen, vagina/cervix, and lumbosacral ganglia and the adjacent spinal cord were quantified using a pair Peripheral Tissue-Resident Immune Memory to HSV-2 of previously described anti-guinea pig IFN-c -specific monoclonal antibodies [27] in an IFN-c ELISPOT assay. abstract: Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4(+) and CD8(+) resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation. url: https://doi.org/10.1371/journal.pone.0114652 doi: 10.1371/journal.pone.0114652 id: cord-299491-8rfm0jxh author: Xiao, Shenglan title: Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong date: 2017-07-20 words: 4765.0 sentences: 218.0 pages: flesch: 53.0 cache: ./cache/cord-299491-8rfm0jxh.txt txt: ./txt/cord-299491-8rfm0jxh.txt summary: Like many other respiratory viruses, the SARS-CoV is suspected to spread from an infected person to the susceptible via three basic transmission routes, i.e., the long-range airborne, close contact and fomite routes [14] [15] [16] , as shown in Fig 1. Several studies have proposed probable evidence for the airborne spread of the SARS-CoV based on the consistencies between bio-aerosol concentration distributions and reported attack rates [19] [20] [21] , but no mechanism-based investigations exist for the fomite route. To investigate the role the fomite route plays in SARS-CoV transmission, we conducted a detailed modelling study of the largest hospital outbreak in Hong Kong [20] , in which the distribution of reported attack rates of inpatients showed a statistically significant spatial pattern. A multi-agent model ( Fig 2) was developed to simulate the possible spread of the viruses from the index patient to the susceptible by air flow and surface touching, and to calculate the possible exposure doses and infection risks for each hypothesis. abstract: The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission. url: https://www.ncbi.nlm.nih.gov/pubmed/28727803/ doi: 10.1371/journal.pone.0181558 id: cord-298131-zolwjl9u author: Xiao, Shuqi title: Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date: 2010-06-29 words: 9349.0 sentences: 429.0 pages: flesch: 39.0 cache: ./cache/cord-298131-zolwjl9u.txt txt: ./txt/cord-298131-zolwjl9u.txt summary: Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. To investigate the regulation of the host response to the N-PRRSV virus, we considered the global gene expression profiles in lungs using Solexa/Illumina''s DGE system, a tag-based transcriptome sequencing method. From the data presented in the paper, a model for the relationship between pulmonary gene expression profiles and infection pathology can be surmised in Figure 7 , N-PRRSV virus replicates and spreads by subverting host innate immune response and hijacking host lipid metabolism as well as inducing an antiapoptotic and anti-inflammatory state, as indicated by suppression expression of SPI IFN, IFN-a, down-regulation expression of proapoptotic genes for BAK, APR-1, SARP3, high levels expression of genes involved in lipid metabolism, such as APOE, LDLB, PIK3C3, anti-apoptotic genes for MCL1, BCL2A1, CHFR, ADM, NFKB, IL10, and anti-inflammatory molecule PGE2 as well as CD163. abstract: Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS. url: https://www.ncbi.nlm.nih.gov/pubmed/20614006/ doi: 10.1371/journal.pone.0011377 id: cord-000267-xroo7z7g author: Xiao, Xiaodong title: Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model date: 2010-10-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr) V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs) against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252) and two anti-V-specific human mAb (m253, m254) by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954148/ doi: 10.1371/journal.pone.0013047 id: cord-316853-vaea6siv author: Xie, Nanzhen title: Prevalence of depressive symptoms among nurses in China: A systematic review and meta-analysis date: 2020-07-07 words: 4363.0 sentences: 229.0 pages: flesch: 47.0 cache: ./cache/cord-316853-vaea6siv.txt txt: ./txt/cord-316853-vaea6siv.txt summary: Therefore, the primary aim of this study is to quantitatively assess the prevalence of depressive symptoms in nurses from Chinese mainland and its primary related influencing factors by systematic review and meta-analysis. The following information was extracted from all included studies: title, year of publication, province, sample size, number of positive cases, diagnostic methods and other potential factors that may affect the prevalence of depressive symptoms in nurses and that was provided in the studies. In addition, subgroup analysis was performed based on other potential sources of heterogeneity, such as province, regions (Northwest, Southwest, Northeast, South, Central, East and North China), severity of depressive symptoms, department, gender, age, job title, marriage, education background, shift work and hospital grade (if available). abstract: BACKGROUND: Depression is one of the most common mental disorders, profoundly impacting an individual’s performance and quality of life. Due to their unique working conditions, nursing is counted among the occupational groups at high risk for developing depression. Because of the shortage of nursing resources in China, Chinese nurses suffer from heavy daily workloads more than those in many other countries. Therefore, this study aimed to evaluate the overall prevalence of depressive symptoms and analyse the potential risk factors of depressive symptoms in Chinese nurses. METHODS: A systematic literature search in PubMed, EMBASE, Web of Science, the Chinese BioMedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), and the Weipu and Wanfang databases up to Dec 31st, 2019 was performed regarding the prevalence of depressive symptoms in Chinese nurses. Eligibility assessment and data extraction were performed independently by 2 researchers, and meta-analysis was used to synthesize the data. Heterogeneity was evaluated using Cochran’s Q test and quantified using the I(2) statistic. To explore the potential source of heterogeneity, subgroup analyses were also performed. In addition, both funnel plot and Egger’s tests were adopted to assess publication bias. RESULTS: A total of 102 studies published from 1996 to 2019 covering 22 provinces were included for further analysis. The total number of participants was 52,592, with a range of 46 to 7205 per study. The overall prevalence of depressive symptoms in Chinese nurses was 43.83% (95%CI: 40.26%-47.42%), and 31.12% (95%CI: 27.30%-35.07%) were classified as mild degrees of depressive symptoms. The prevalence of depressive symptoms may be significantly affected by region, province or municipality and department marital status. Moreover, an increasing trend in the prevalence of depressive symptoms was observed in recent years. CONCLUSION: The results presented a high prevalence of depressive symptoms among Chinese nurses, which suggests interventional programmes by health decision-makers to improving the mental state of nurses is needed urgently, especially in nurses with high risk factors for depressive symptoms. Furthermore, the nationwide investigation of depressive symptoms prevalence should be performed with a standard diagnostic tool, which may be more useful for policy makers and planners. url: https://doi.org/10.1371/journal.pone.0235448 doi: 10.1371/journal.pone.0235448 id: cord-350842-4m82l5t8 author: Xing, Jun title: Study of the mental health status of medical personnel dealing with new coronavirus pneumonia date: 2020-05-19 words: 3219.0 sentences: 150.0 pages: flesch: 47.0 cache: ./cache/cord-350842-4m82l5t8.txt txt: ./txt/cord-350842-4m82l5t8.txt summary: Factors affecting the mental health and status of medical personnel based on their significance from high to low are: the degree of suspicion that they were infected when the novel coronavirusrelated symptoms occurred, the level of concern whether they and their family members have been infected, age, whether they have supported in affected areas in Hubei Province, designated hospitals, and other places for the novel coronavirus, and whether family members support them working on the front line (p < 0.05). The results of this study have shown that the factors affecting the mental health status of medical personnel based on the significance from high to low are: the degree of suspicion that they were infected when the novel coronavirus-related symptoms occurred, the level of concern whether they and their family members have been infected, age, whether they have supported in affected areas in Hubei Province, designated hospitals, and other places for the novel coronavirus, and whether their family members support them working on the front line. abstract: This paper studied the relationship between personality traits and mental health conditions of medical personnel to provide a basis and reference for the implementation of targeted education on mental health. A self-report inventory, the Symptom Checklist-90 (SCL-90), was used to investigate the mental health status of 548 medical personnel dealing with the new coronavirus pneumonia in eight provinces and cities of China. The overall mean SCL-90 score and mean values of factors (somatization, obsessive-compulsive, anxiety, phobic anxiety, and psychoticism) of the medical personnel were significantly higher than in the norm group (p < 0.05), while their average interpersonal sensitivity score was significantly lower (p < 0.01). In addition, personal factors affecting the mental health status of medical personnel were identified (all p < 0.05). The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China. url: https://www.ncbi.nlm.nih.gov/pubmed/32428041/ doi: 10.1371/journal.pone.0233145 id: cord-000460-h3owwjao author: Xiong, Jing title: Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date: 2011-09-26 words: 4313.0 sentences: 212.0 pages: flesch: 41.0 cache: ./cache/cord-000460-h3owwjao.txt txt: ./txt/cord-000460-h3owwjao.txt summary: However, with LPS stimulation numbers of platelets staining positive for both plateletand leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. Alternatively, comparable activation of leukocyte as well as platelet result in formation of cell-derived microvesicles (MV) which may contribute to increased thrombogenic propensity of the blood, pro-inflammatory immune processes and thus cardiovascular risk [15, 16, 17, 18, 19, 20, 21, 22] . Therefore, the present study was designed to test the hypothesis that acute exposure to a sentinel dose of LPS would induce MV production and exchange of specific proteins/ receptors between platelets and leukocytes via TLR4 activation. The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice. abstract: BACKGROUND: Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis. Platelets are sentinel markers of toll-like receptor 4 (TLR4) activation. Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry. Numbers of platelet- or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS. However, with LPS stimulation numbers of platelets staining positive for both platelet- and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated by My88 and TRIF. Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained positive for platelet antigens. CONCLUSIONS/SIGNIFICANCE: Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation. In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool. Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180459/ doi: 10.1371/journal.pone.0025504 id: cord-330079-pdaowkop author: Xu, Lin title: Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China date: 2012-09-11 words: 4469.0 sentences: 205.0 pages: flesch: 50.0 cache: ./cache/cord-330079-pdaowkop.txt txt: ./txt/cord-330079-pdaowkop.txt summary: To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. In our current study, we screened throat swab specimens from patients with acute respiratory tract infection symptoms for HBoV and other common respiratory viruses over a 12-month period using polymerase chain reaction (PCR) methods, and in addition, the molecular phylogeny and complete genome sequences of 2 HBoV strains were also analyzed. Of the 3460 samples collected from patients with respiratory tract infection symptoms and signs enrolled in the study during the period between March 2010 and February 2011, detection for 7 viruses, namely, Influenza, PIV, RSV, HMPV, HCoV, AdV and HBoV, showed that 1275 (36.8%) were found positive for one single virus and 112 (3.2%) were infected by more than one virus. abstract: Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra–genotype recombinant strain among HBoV1 variants. url: https://doi.org/10.1371/journal.pone.0044876 doi: 10.1371/journal.pone.0044876 id: cord-280482-o887a7q9 author: Xu, Suming title: Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study date: 2016-09-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1ß, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC/BPS research. url: https://doi.org/10.1371/journal.pone.0163829 doi: 10.1371/journal.pone.0163829 id: cord-293072-giakcaki author: Xu, Wan-Xiang title: A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date: 2017-10-12 words: 5303.0 sentences: 227.0 pages: flesch: 52.0 cache: ./cache/cord-293072-giakcaki.txt txt: ./txt/cord-293072-giakcaki.txt summary: The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. abstract: There is a need to develop better methods for epitope mapping and/or identification of antibody-recognizing motifs. Here, we describe improved biosynthetic peptide (BSP) method using a newly developed plasmid pXXGST-3 as vector, which has a viral E7 gene in the cloning sites of pXXGST-1. It is crucial to employ pXXGST-3 instead of pXXGST-1, since it makes use of the BSP method simpler and easier to perform, and more cost-effective for epitope mapping. These merits are embodied in two aspects: i) convenient recovery of double enzyme-digested product due to the existence of 315 bp inserted between BamH I and Sal I sites, and thus greatly reducing the production of self-ligation clones, and ii) no longer requiring control protein when screening recombinant (r-) clones expressing 8/18mer peptides by running polyacrylamide gel electrophoresis. The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. This improved GST188-BSP method provides a powerful alternative tool for epitope mapping. url: https://doi.org/10.1371/journal.pone.0186097 doi: 10.1371/journal.pone.0186097 id: cord-000341-d3a06n3f author: Xu, Wanghui title: Screening of Random Peptide Library of Hemagglutinin from Pandemic 2009 A(H1N1) Influenza Virus Reveals Unexpected Antigenically Important Regions date: 2011-03-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The antigenic structure of the membrane protein hemagglutinin (HA) from the 2009 A(H1N1) influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS) against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify “hot spots” or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060926/ doi: 10.1371/journal.pone.0018016 id: cord-331885-8zmuhebu author: Xu, Xiuyan title: Risk factor analysis combined with deep learning in the risk assessment of overseas investment of enterprises date: 2020-10-02 words: 3796.0 sentences: 208.0 pages: flesch: 43.0 cache: ./cache/cord-331885-8zmuhebu.txt txt: ./txt/cord-331885-8zmuhebu.txt summary: To evaluate the overseas investment risks of enterprises and expand the application and development of deep learning methods in risk assessment, 15 national clusters are utilized as samples to analyze and discuss the overseas investment risk indicators of enterprises. Second, the Deep Neural Network (DNN) is introduced; a risk evaluation model is constructed for enterprise overseas investment. The results show that the major source of overseas investment risks includes basic resources, political systems, economic and financial development, and environmental protection. To build a risk assessment model for overseas investment of enterprises and evaluate investment risks scientifically and effectively, the Deep Neural Network (DNN) based on deep learning is introduced, which is an innovation. The above analysis suggests that a country''s infrastructure, health care conditions, economic development level, environmental protection conditions, and political system are the key components that affect its risks of enterprise overseas investment [29, 30] . abstract: To evaluate the overseas investment risks of enterprises and expand the application and development of deep learning methods in risk assessment, 15 national clusters are utilized as samples to analyze and discuss the overseas investment risk indicators of enterprises. First, based on the indicator system of overseas investment risks, five major types of investment risks are identified. Second, the Deep Neural Network (DNN) is introduced; a risk evaluation model is constructed for enterprise overseas investment. Finally, the investment attractiveness index in the Fraser risk assessment learning label is adopted as the evaluation results of the model. According to the classification of risks, the model is trained and its performance is tested. The results show that the major source of overseas investment risks includes basic resources, political systems, economic and financial development, and environmental protection. The corresponding risk score is high. North American country clusters and Oceanian country clusters have lower investment risks, while the investment risks in Africa, Latin America, and Asia are affected by multiple factors of the specific cities. This is closely related to the resources and legal systems possessed by the country clusters. This is of great significance for enterprises to conduct risk assessment in overseas investment. url: https://doi.org/10.1371/journal.pone.0239635 doi: 10.1371/journal.pone.0239635 id: cord-352200-i05h8csb author: Xu, Yi title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date: 2012-04-27 words: 5286.0 sentences: 278.0 pages: flesch: 47.0 cache: ./cache/cord-352200-i05h8csb.txt txt: ./txt/cord-352200-i05h8csb.txt summary: title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. As a whole, 81388 distinct unigenes have been identified and the results indicated that SRBSDV infection can potentially perturb primary metabolism and the ubiquitin-proteasome pathway of WBPH and activate immune regulatory systems, such as RNA interfering, autophagy and antimicrobial peptide production. However, some unigenes were obtained only from viruliferous or non-viruliferous samples (data not shown) and we believe these differences may be caused by distinctions that arise from long-term ecological adaptation to virus infection. In addition, GO analysis also showed a similar distribution of gene functions for non-viruliferous and viruliferous WBPH (Figure 4 ), indicating that the number of genes expressed in each GO category was not significantly affected by SRBSDV infection. abstract: BACKGROUND: The white backed planthopper (WBPH), Sogatella furcifera (Horváth), causes great damage to many crops by direct feeding or transmitting plant viruses. Southern rice black-streaked dwarf virus (SRBSDV), transmitted by WBPH, has become a great threat to rice production in East Asia. METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. Over 25 million reads of high-quality DNA sequences and 81388 different unigenes were generated using Illumina technology from both viruliferous and non-viruliferous WBPH. WBPH has a very similar gene ontological distribution to other two closely related rice planthoppers, Nilaparvata lugens and Laodelphax striatellus. 7291 microsatellite loci were also predicted which could be useful for further evolutionary analysis. Furthermore, comparative analysis of the two transcriptomes generated from viruliferous and non-viruliferous WBPH provided a list of candidate transcripts that potentially were elicited as a response to viral infection. Pathway analyses of a subset of these transcripts indicated that SRBSDV infection may perturb primary metabolism and the ubiquitin-proteasome pathways. In addition, 5.5% (181 out of 3315) of the genes in cell cytoskeleton organization pathway showed obvious changes. Our data also demonstrated that SRBSDV infection activated the immunity regulatory systems of WBPH, such as RNA interference, autophagy and antimicrobial peptide production. CONCLUSIONS/SIGNIFICANCE: We employed massively parallel pyrosequencing to collect ESTs from viruliferous and non-viruliferous samples of WBPH. 81388 different unigenes have been obtained. We for the first time described the direct effects of a Reoviridae family plant virus on global gene expression profiles of its insect vector using high-throughput sequencing. Our study will provide a road map for future investigations of the fascinating interactions between Reoviridae viruses and their insect vectors, and provide new strategies for crop protection. url: https://www.ncbi.nlm.nih.gov/pubmed/22558400/ doi: 10.1371/journal.pone.0036238 id: cord-262748-v4xue7ha author: Xu, Yongtao title: Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine date: 2015-12-04 words: 4636.0 sentences: 253.0 pages: flesch: 40.0 cache: ./cache/cord-262748-v4xue7ha.txt txt: ./txt/cord-262748-v4xue7ha.txt summary: Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The predictive support vector machine model for selfderived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process. In view of the important role of E proteins in virus fusion process and common mechanism of action of self-derived peptides, we developed a SVM model to predict the antiviral activities of self-derived peptides using sequence-based statistical scores as input features. Because similar sequences are often associated with similar structure and function, the sequence-based property AVPalign would account for the activities of the self-derived peptide inhibitors which regulate the virus fusion by mimicking the binding to E proteins. The prominent performance of EAPscoring model indicates the sequence-based stability feature of self-derived peptides may reflect their potential of binding to E proteins so as to regulate the virus entry process. abstract: The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process. url: https://www.ncbi.nlm.nih.gov/pubmed/26636321/ doi: 10.1371/journal.pone.0144171 id: cord-000723-wo20st5w author: Xu, Zhenqiang title: Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method date: 2012-07-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Exhaled breath condensate (EBC) is increasingly being used as a non-invasive method for disease diagnosis and environmental exposure assessment. By using hydrophobic surface, ice, and droplet scavenging, a simple impaction and condensing based collection method is reported here. Human subjects were recruited to exhale toward the device for 1, 2, 3, and 4 min. The exhaled breath quickly formed into tiny droplets on the hydrophobic surface, which were subsequently scavenged into a 10 µL rolling deionized water droplet. The collected EBC was further analyzed using culturing, DNA stain, Scanning Electron Microscope (SEM), polymerase chain reaction (PCR) and colorimetry (VITEK 2) for bacteria and viruses. Experimental data revealed that bacteria and viruses in EBC can be rapidly collected using the method developed here, with an observed efficiency of 100 µL EBC within 1 min. Culturing, DNA stain, SEM, and qPCR methods all detected high bacterial concentrations up to 7000 CFU/m(3) in exhaled breath, including both viable and dead cells of various types. Sphingomonas paucimobilis and Kocuria variants were found dominant in EBC samples using VITEK 2 system. SEM images revealed that most bacteria in exhaled breath are detected in the size range of 0.5–1.0 µm, which is able to enable them to remain airborne for a longer time, thus presenting a risk for airborne transmission of potential diseases. Using qPCR, influenza A H3N2 viruses were also detected in one EBC sample. Different from other devices restricted solely to condensation, the developed method can be easily achieved both by impaction and condensation in a laboratory and could impact current practice of EBC collection. Nonetheless, the reported work is a proof-of-concept demonstration, and its performance in non-invasive disease diagnosis such as bacterimia and virus infections needs to be further validated including effects of its influencing matrix. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405091/ doi: 10.1371/journal.pone.0041137 id: cord-000813-gagakqw4 author: Xue, Mei title: Identification of a Conserved B-cell Epitope on Reticuloendotheliosis Virus Envelope Protein by Screening a Phage-displayed Random Peptide Library date: 2012-11-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The gp90 protein of avian reticuloendotheliosis-associated virus (REV-A) is an important envelope glycoprotein, which is responsible for inducing protective antibody immune responses in animals. B-cell epitopes on the gp90 protein of REV have not been well studied and reported. METHODS AND RESULTS: This study describes the identification of a linear B-cell epitope on the gp90 protein by screening a phage-displayed 12-mer random peptide library with the neutralizing monoclonal antibody (mAb) A9E8 directed against the gp90. The mAb A9E8 recognized phages displaying peptides with the consensus motif SVQYHPL. Amino acid sequence of the motif exactly matched (213)SVQYHPL(219) of the gp90. Further identification of the displayed B cell epitope was conducted using a set of truncated peptides expressed as GST fusion proteins and the Western blot results indicated that (213)SVQYHPL(219) was the minimal determinant of the linear B cell epitope recognized by the mAb A9E8. Moreover, an eight amino acid peptide SVQYHPLA was proven to be the minimal unit of the epitope with the maximal binding activity to mAb A9E8. The REV-A-positive chicken serum reacted with the minimal linear epitopes in Western blot, revealing the importance of the eight amino acids of the epitope in antibody-epitope binding activity. Furthermore, we found that the epitope is a common motif shared among REV-A and other members of REV group. CONCLUSIONS AND SIGNIFICANCE: We identified (213)SVQYHPL(219) as a gp90-specific linear B-cell epitope recognized by the neutralizing mAb A9E8. The results in this study may have potential applications in development of diagnostic techniques and epitope-based marker vaccines against REV-A and other viruses of the REV group. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504085/ doi: 10.1371/journal.pone.0049842 id: cord-352511-gkm7i62s author: Yamada, Yoshiyuki title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells date: 2009-07-02 words: 5731.0 sentences: 317.0 pages: flesch: 55.0 cache: ./cache/cord-352511-gkm7i62s.txt txt: ./txt/cord-352511-gkm7i62s.txt summary: title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins. In this study, we report that acquisition of the cell-cell fusion activity by point mutations in the spike (S) protein of avian coronavirus infectious bronchitis virus (IBV) plays a critical role in adaptation and/or selection of a variant that infects cultured cells. Sequence comparison of two S protein constructs, S(EP3) and S(CK), cloned from EP3 and CK-adapted IBV strains, respectively, showed amino acid substitutions at 31 positions (Fig. 1a) . abstract: Coronavirus host and cell specificities are determined by specific interactions between the viral spike (S) protein and host cell receptor(s). Avian coronavirus infectious bronchitis (IBV) has been adapted to embryonated chicken eggs, primary chicken kidney (CK) cells, monkey kidney cell line Vero, and other human and animal cells. Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. Expression of S protein derived from Vero- and CK-adapted strains showed efficient induction of membrane fusion. However, expression of S protein cloned from the third passage of IBV in chicken embryo (EP3) did not show apparent syncytia formation. By construction of chimeric S constructs and site-directed mutagenesis, a point mutation (L857-F) at amino acid position 857 in the heptad repeat 1 region of S protein was shown to be responsible for its acquisition of the cell–cell fusion activity. Furthermore, a G405-D point mutation in the S1 domain, which was acquired during further propagation of Vero-adapted IBV in Vero cells, could enhance the cell–cell fusion activity of the protein. Re-introduction of L857 back to the S gene of Vero-adapted IBV allowed recovery of variants that contain the introduced L857. However, compensatory mutations in S1 and some distant regions of S2 were required for restoration of the cell–cell fusion activity of S protein carrying L857 and for the infectivity of the recovered variants in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins. url: https://www.ncbi.nlm.nih.gov/pubmed/19572016/ doi: 10.1371/journal.pone.0006130 id: cord-276898-ia80cy8j author: Yamanaka, Atsushi title: Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus date: 2014-03-25 words: 3833.0 sentences: 190.0 pages: flesch: 48.0 cache: ./cache/cord-276898-ia80cy8j.txt txt: ./txt/cord-276898-ia80cy8j.txt summary: Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient''s throat swab using Vero cells, in which syncytium formation was observed. Here, we report an imported case of an RTI associated with an orthoreovirus, which is classified to the species of Nelson Bay orthoreovirus, in a patient who returned to Japan from Bali, Indonesia in November 2007. Interestingly, S1segment of Miyazaki-Bali/2007 showed 94% homology to that of Kampar virus originated in Malaysia, while it did 48-59% homology to those of the other orthoreoviruses in the genus of Nelson Bay orthoreovirus. S2-segment of Miyazaki-Bali/2007 had the highest homology with being approximately 92-94% in nucleotide sequences to those of HK23629/07, HK46886/09, and HK50842/10, which also seem to have originated in Indonesia [6, 20] , while it showed 83-90% homology to those of Kampar, Melaka, Pulau, Sikamat, and Nelson Bay viruses. abstract: A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low. url: https://www.ncbi.nlm.nih.gov/pubmed/24667794/ doi: 10.1371/journal.pone.0092777 id: cord-000374-gt2pwc9b author: Yang, Albert C. title: Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index date: 2011-05-04 words: 5304.0 sentences: 279.0 pages: flesch: 43.0 cache: ./cache/cord-000374-gt2pwc9b.txt txt: ./txt/cord-000374-gt2pwc9b.txt summary: With these considerations in mind, in the present study, we introduce a bottom-up genotype-phenotype analysis to investigate the association between genetic polymorphisms and autonomic control of heart rate dynamics, using three common polymorphisms in genes encoding b-adrenergic receptor (b-AR) as an example. The analyses of the present study were two-fold: 1) a nonrandomness index [17] derived from the IBS method was applied to quantify the nonlinear aspect of HRV according to b-AR genotype and to test the correlation of this index with standard HRV indices; and 2) using agglomerative hierarchical cluster analysis, we unsupervisedly categorized these subjects into clusters based on pairwise dissimilarity among heart rate dynamics, and then we investigated the association of these clustering patterns with b-AR gene polymorphisms. The data presented in this study demonstrate a significant association of a common b 2 -AR polymorphism, Arg16Gly, with the non-randomness index, a nonlinear HRV measure derived from the IBS method. abstract: BACKGROUND: Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype–phenotype analysis to investigate the association between β-AR gene polymorphisms and heart rate dynamics. METHODS: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6±10.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β(1)-AR Ser49Gly, β(2)-AR Arg16Gly and β(2)-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. RESULTS: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β(2)-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. CONCLUSIONS: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms. Our results provide evidence that β(2)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087751/ doi: 10.1371/journal.pone.0019232 id: cord-269453-30l6rzgo author: Yang, Po title: Feasibility study of mitigation and suppression strategies for controlling COVID-19 outbreaks in London and Wuhan date: 2020-08-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Recent outbreaks of coronavirus disease 2019 (COVID-19) has led a global pandemic cross the world. Most countries took two main interventions: suppression like immediate lockdown cities at epicenter or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both strategies have their apparent merits and limitations; it becomes extremely hard to conduct one intervention as the most feasible way to all countries. Targeting at this problem, this paper conducted a feasibility study by defining a mathematical model named SEMCR, it extended traditional SEIR (Susceptible-Exposed-Infectious-Recovered) model by adding two key features: a direct connection between Exposed and Recovered populations, and separating infections into mild and critical cases. It defined parameters to classify two stages of COVID-19 control: active contain by isolation of cases and contacts, passive contain by suppression or mitigation. The model was fitted and evaluated with public dataset containing daily number of confirmed active cases including Wuhan and London during January 2020 and March 2020. The simulated results showed that 1) Immediate suppression taken in Wuhan significantly reduced the total exposed and infectious populations, but it has to be consistently maintained at least 90 days (by the middle of April 2020). Without taking this intervention, we predict the number of infections would have been 73 folders higher by the middle of April 2020. Its success requires efficient government initiatives and effective collaborative governance for mobilizing of corporate resources to provide essential goods. This mode may be not suitable to other countries without efficient collaborative governance and sufficient health resources. 2) In London, it is possible to take a hybrid intervention of suppression and mitigation for every 2 or 3 weeks over a longer period to balance the total infections and economic loss. While the total infectious populations in this scenario would be possibly 2 times than the one taking suppression, economic loss and recovery of London would be less affected. 3) Both in Wuhan and London cases, one important issue of fitting practical data was that there were a portion (probably 62.9% in Wuhan) of self-recovered populations that were asymptomatic or mild symptomatic. This finding has been recently confirmed by other studies that the seroprevalence in Wuhan varied between 3.2% and 3.8% in different sub-regions. It highlights that the epidemic is far from coming to an end by means of herd immunity. Early release of intervention intensity potentially increased a risk of the second outbreak. url: https://doi.org/10.1371/journal.pone.0236857 doi: 10.1371/journal.pone.0236857 id: cord-355259-779czzzx author: Yang, Xiaoyun title: A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus date: 2014-10-15 words: 6143.0 sentences: 324.0 pages: flesch: 47.0 cache: ./cache/cord-355259-779czzzx.txt txt: ./txt/cord-355259-779czzzx.txt summary: Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract. To this purpose, we applied swine influenza virus to a model we previously set up using porcine respiratory mucus, pseudorabies virus (PRV) and single particle tracking (SPT) [20] . This does not only confirm the beneficial effect of neuraminidase on releasing SIV from respiratory mucus, but also highlights bidirectional synergistic interactions between influenza virus and bacterial infections. abstract: Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. Sialic acids present on the epithelial surface have long been considered to be determinants of influenza virus tropism. However, mucus which is also rich in sialic acids may serve as the first barrier of selection. It was investigated how influenza virus interacts with the mucus to infect epithelial cells. Two techniques were applied to track SIV H1N1 in porcine mucus. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. Furthermore, the effects of neuraminidase on SIV getting through or binding to the mucus were studied by using zanamivir, a neuraminidase inhibitor (NAI), and Arthrobacter ureafaciens neuraminidase. The distribution of the diffusion coefficient shows that 70% of SIV particles were entrapped, while the rest diffused freely in the mucus. Additionally, SIV penetrated the porcine mucus with time, reaching a depth of 65 µm at 30 min post virus addition, 2 fold of that at 2 min. Both the microscopic diffusion and macroscopic penetration were largely diminished by NAI, while were clearly increased by the effect of exogenous neuraminidase. Moreover, the exogenous neuraminidase sufficiently prevented the binding of SIV to mucus which was reversely enhanced by effect of NAI. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract. url: https://doi.org/10.1371/journal.pone.0110026 doi: 10.1371/journal.pone.0110026 id: cord-262832-5iejckwx author: Yen, Muh-Yong title: Taipei''s Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease date: 2009-11-23 words: 5998.0 sentences: 285.0 pages: flesch: 51.0 cache: ./cache/cord-262832-5iejckwx.txt txt: ./txt/cord-262832-5iejckwx.txt summary: In launching countermeasures to bring the AHC outbreak under control, the Taipei Department of Health was also able to test its system and fine-tune its public health response for future EIDs. To evaluate the effectiveness of these intervention measures, daily surveillance was conducted to analyze the incidence rate and temporal-spatial distribution of new AHC cases. This risk communication program focused on communicating directly to the public through three routes: (1) schools delivered a Taipei Department of Health letter signed by the mayor (that detailed AHC information and prevention methods) for students to take home to their parents, (2) the mayor held a press conference to discuss the epidemic and offer guidance to citizens for preventing the spread of the disease, and (3) over 2.2 million short message services (SMS) messages, a communication tool for exchanging short text messages between mobile telephonic devices, were delivered to all Taipei mobile phone numbers. abstract: BACKGROUND: In September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei. METHODOLOGY AND PRINCIPAL FINDINGS: Having noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean±SD: 2.6±3.2 vs. 4.39±4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2±1.7 days vs. 3.9±4.0 days, p<0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p<0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% vs. 14.92%, p<0.001), (2) a short epidemic period of AHC (13 vs. 34 days), and (3) a quick drop in risk level (1∼2 weeks) in Taipei districts that border Keelung (the original domestic epicenter). CONCLUSIONS AND SIGNIFICANCE: The timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/19956722/ doi: 10.1371/journal.pone.0007962 id: cord-316287-4i1grvlr author: Yim, Sung Sun title: Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS) date: 2014-10-10 words: 6372.0 sentences: 281.0 pages: flesch: 51.0 cache: ./cache/cord-316287-4i1grvlr.txt txt: ./txt/cord-316287-4i1grvlr.txt summary: During the cultivation for regeneration of sorted cells, differential growth rates among various clones (particularly non-specific clones) due to unregulated protein expression and differing cell viability can decrease the library screening efficiency, resulting in more rounds of sorting (longer duration) to isolate the potential antibody candidate [12] . The whole FACS screening rounds of the synthetic human antibody library against each viral antigen could be done in one day, and these results show that repeated FACS screening without regeneration of the sorted cells can be a rapid and efficient method to isolate potential antibody candidates in case of urgent requirements. For the FACS screening of a human synthetic antibody (scFv) library, three fluorescent antigen probes were chemically synthesized: (i) FITC-CRDNWHGSNRPW as an N1 epitope of H1N1 influenza virus [13] ; (ii) FITC-NSTTFHQALLDPRVRGLYF-PAGG as a PreS2 epitope of HBV [14] ; and (iii) FITC-PVTNVRGDLQVLAQK as a VP1 epitope of FMDV [15] . abstract: Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS). First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv) was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D) values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼10(6)). These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required. url: https://doi.org/10.1371/journal.pone.0108225 doi: 10.1371/journal.pone.0108225 id: cord-001761-yvd1n42f author: Yoshimura, Takeo title: Controlled Microwave Heating Accelerates Rolling Circle Amplification date: 2015-09-08 words: 4411.0 sentences: 223.0 pages: flesch: 48.0 cache: ./cache/cord-001761-yvd1n42f.txt txt: ./txt/cord-001761-yvd1n42f.txt summary: Analysis of the temperature profiles of each RCA component subjected to microwave heating revealed the selectivity heating of buffer components compared with primers, template DNA, dNTP, and RNase-free water. To determine the component of RCA by microwave selectivity heating, we measured the temperatures of the five components (circularized template with primers, dNTPs, ThermoPol Buffer, Bst-LF, and RNase-free water) of the RCA and MW-RCA mixtures for 10 min from 13°C to 60°C. To reveal the effect of the selectivity heating in MW-RCA, we compared the efficiency of DNA amplification in the RCA and MW-RCA reactions mixtures containing a 4-fold excess concentration of each RCA component (dNTP, template-primers, Bst-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ). We performed MW-RCA reactions containing a four-fold higher concentration of each RCA component [dNTP, template-primers, Bst DNA polymerase-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ] to identify a link between microwave selective heating and DNA amplification. abstract: Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562646/ doi: 10.1371/journal.pone.0136532 id: cord-001099-jirkkkvy author: Yousuf, Mohammad A. title: Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells date: 2013-10-11 words: 7110.0 sentences: 372.0 pages: flesch: 46.0 cache: ./cache/cord-001099-jirkkkvy.txt txt: ./txt/cord-001099-jirkkkvy.txt summary: Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling. Initial binding is followed by a secondary interaction between the arginine-glycine-aspartic acid (RGD) motif in the viral capsid penton base and cellular integrins α v β 3 , α v β 5, and α V β 1 [42] [43] [44] [45] This secondary interaction is thought to induce a host cell signaling cascade resulting in clathrin mediated endocytosis [46] [47] [48] , and possibly, activation of the rab5 dependent classical endosomal pathway [49] . Herein, we show that HAdV-D37, an etiologic agent of epidemic keratoconjunctivitis, enters primary human corneal fibroblasts predominantly via lipid rafts and caveolae, suggesting both redundancy and cell specificity in mechanisms of adenoviral entry. To further examine the role of lipid raft microdomains in HAdV-D37 entry, we treated corneal cells with both Cy3-labeled virus and 488-CTXB, and tracked their cellular localization over time ( Figure 1C ). abstract: The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795695/ doi: 10.1371/journal.pone.0077462 id: cord-002901-u4ybz8ds author: Yu, Chanki title: Acral melanoma detection using a convolutional neural network for dermoscopy images date: 2018-03-07 words: 3513.0 sentences: 180.0 pages: flesch: 52.0 cache: ./cache/cord-002901-u4ybz8ds.txt txt: ./txt/cord-002901-u4ybz8ds.txt summary: We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist''s and non-expert''s evaluation. CONCLUSION: Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet. In the result of group B by the training of group A images, CNN also showed a higher diagnostic accuracy (80.23%) than that of the non-expert (62.71%) but was similar to that of the expert (81.64%). abstract: BACKGROUND/PURPOSE: Acral melanoma is the most common type of melanoma in Asians, and usually results in a poor prognosis due to late diagnosis. We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. METHODS: A total of 724 dermoscopy images comprising acral melanoma (350 images from 81 patients) and benign nevi (374 images from 194 patients), and confirmed by histopathological examination, were analyzed in this study. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist’s and non-expert’s evaluation. RESULTS: The accuracy (percentage of true positive and true negative from all images) of the convolutional neural network was 83.51% and 80.23%, which was higher than the non-expert’s evaluation (67.84%, 62.71%) and close to that of the expert (81.08%, 81.64%). Moreover, the convolutional neural network showed area-under-the-curve values like 0.8, 0.84 and Youden’s index like 0.6795, 0.6073, which were similar score with the expert. CONCLUSION: Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841780/ doi: 10.1371/journal.pone.0193321 id: cord-328206-iylw1bvw author: Yu, Daojun title: Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date: 2012-11-09 words: 4070.0 sentences: 209.0 pages: flesch: 48.0 cache: ./cache/cord-328206-iylw1bvw.txt txt: ./txt/cord-328206-iylw1bvw.txt summary: In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. So AllGlo quadruplex quantitative PCR has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, it is easy for designing the probes and primers of multiplex qPCR and can increase the detection throughput. Two aliquots were used for the detection of HPV6-11 and HPV16-18 mixed types by TaqMan uniplex probe fluorescence quantitative PCR (Guangzhou Da''an Diagnostic Co., Ltd., China). Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. abstract: BACKGROUND: Human papillomaviruses (HPV) are classified into high-risk HPV and low-risk HPV. The most common high-risk HPV types in cervical cancer are HPV 16 and 18, and the most common low-risk types causing genital warts are HPV 6 and HPV 11. In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. METHODS: The specificity, the sensitivity, the detection limit, the reproducibility and the standard curve of this method were examined. Finally, clinical samples that had been tested previously by TaqMan PCR and HPV GenoArray (GA) test were used to verify the accuracy and sensitivity of the method. RESULTS: The assay has a sensitivity of 10(1) to 10(2) copies/test and a linear detection range from 10(1) to 10(8) copies/test. The mean amplification efficiencies for HPV 6, 11, 16, and 18 were 0.97, 1.10, 0.93 and 1.20, respectively, and the mean correlation coefficient (r(2)) of each standard curve was above 0.99 for plasmid templates ranging from 10(3) to 10(7) copies/test. There was 100% agreement between the AllGlo quadruplex quantitative PCR, HPV GA test and TaqMan uniplex qPCR methods. CONCLUSIONS: AllGlo quadruplex quantitative PCR in a single tube has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, and a wide linear range of detection. The convenient single tube format makes this assay a powerful tool for the studies of mixed infections by multiple pathogens, viral typing and viral load quantification. url: https://www.ncbi.nlm.nih.gov/pubmed/23152833/ doi: 10.1371/journal.pone.0048972 id: cord-309621-6jj19xpr author: Yu, Pin title: Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus date: 2017-02-24 words: 4645.0 sentences: 214.0 pages: flesch: 41.0 cache: ./cache/cord-309621-6jj19xpr.txt txt: ./txt/cord-309621-6jj19xpr.txt summary: The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. Although there have been several studies in animal models on the pathogenic mechanisms of MERS-CoV infection, little is known about the comparative pathology and inflammatory cell response in rhesus macaques or common marmosets infected with this virus. Pathological findings in the rhesus macaque tissues HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A) , pulmonary oedema (Fig 1B) , haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C) , and the infiltration of inflammatory cells. Using immunohistochemical techniques and an ISH analysis, we confirmed that MERS-CoV protein and viral RNA were distributed in the lungs of rhesus macaques and common marmosets and that they were primarily located in the pneumocytes and inflammatory cells. abstract: Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments. url: https://www.ncbi.nlm.nih.gov/pubmed/28234937/ doi: 10.1371/journal.pone.0172093 id: cord-290833-m0wodqr3 author: Yuan, Lvfeng title: Synthetic surfactin analogues have improved anti-PEDV properties date: 2019-04-11 words: 3580.0 sentences: 195.0 pages: flesch: 51.0 cache: ./cache/cord-290833-m0wodqr3.txt txt: ./txt/cord-290833-m0wodqr3.txt summary: In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The production of designer surfactins, made by changing the number and composition of amino acids and fatty acids has proven to be an effective strategy for screening large numbers of lipopeptides for biological activity, but most current research focuses on their anticancer [4] , antimicrobial [5] and insulin delivery [6] properties but not on their antiviral potential. Time of addition assays were performed to determine whether the SLP5 exerts its anti-PEDV effect at the same stage during infection as surfactin. As expected for a normal component of the cell membrane, DEPE did not affect PEDV replication at any stage, while SLP5 and surfactin exhibited antiviral activity at specific stages. SLP5 also has two fewer hydrophobic amino acids than surfactin, this reduces the cost of synthesis while having little effect on antiviral activity. abstract: Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity. In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The main goal of our study was to develop a safer drug; a surfactin analogue with high anti-PEDV activity and low hemolytic activity. Compared with surfactin, one of the analogues we developed, SLP5, has lower hemolytic activity, with the same antiviral activity. The selectivity index of SLP5 is 52, while the SI for surfactin is 4, in other words, the safe and effective concentration range of SLP5 is 12 times greater than that of surfactin. Like surfactin, SLP5 has a direct antiviral effect on PEDV. Structurally, SLP5 is a linear lipopeptide with three carboxyl groups. Surfactin derivatives similar to SLP5 could be obtained by lactone bond hydrolyzation of surfactin, as well as total synthesis. url: https://doi.org/10.1371/journal.pone.0215227 doi: 10.1371/journal.pone.0215227 id: cord-001162-z8cbbit3 author: Yun, Heather C. title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection date: 2014-01-08 words: 3365.0 sentences: 160.0 pages: flesch: 41.0 cache: ./cache/cord-001162-z8cbbit3.txt txt: ./txt/cord-001162-z8cbbit3.txt summary: title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection While coinfections with viral pathogens including 2009 H1N1 have been described in patients with respiratory infections, few prospective studies have related these to clinical presentation and outcomes in adults since molecular diagnostics became available, and none in the setting of high background rates of adenovirus. [12] [13] [14] [15] [16] [17] We sought to describe the epidemiology of 2009 H1N1 and adenovirus in a basic training population, and to correlate differences in clinical presentations and outcomes with each respective pathogen and in coinfections. Subject enrollment was variable throughout the study period, depending on rates of clinical illness within the training population, as well as availability of study personnel to enroll trainees, and given that 2009 H1N1 influenza virus PCR was done as part of clinical care, there could have been some differences in those who enrolled vs. abstract: BACKGROUND: In 2009, pandemic H1N1 influenza virus (2009 H1N1) emerged worldwide, causing morbidity and mortality that disproportionately affected young adults. Upper respiratory infection (URI), largely due to adenovirus, is an endemic cause of morbidity in military training. Whether clinical presentations differ or excess morbidity results from coinfection is unclear. METHODS: The Center for Advanced Molecular Detection evaluates epidemiology and rapid diagnostics of respiratory pathogens in trainees with URI. From May 1, 2009, to November 30, 2009, demographic, clinical, and PCR data from throat and nasal specimens for adenovirus and 2009 H1N1 were prospectively collected. RESULTS: 375 trainees with URI enrolled and were tested for both adenovirus and 2009 H1N1 by PCR (median age 20; 89% male). Adenovirus PCR was positive in 72% (96% serotype E-4) and 2009 H1N1 in 20%. Males were more likely to have adenovirus and females more likely to have 2009 H1N1 (p = 0.047). Subjects with 2009 H1N1 presented an average of 1 week earlier in training, had shorter illness duration before enrollment, less sore throat, diarrhea, and fewer abnormal findings on throat exam. Coryza and cough were more common with 2009 H1N1 compared to adenovirus. Subjects with 2009 H1N1 were less likely to have adenovirus than those without, despite persistently high frequencies of adenovirus detections during peak 2009 H1N1 weeks (15% vs. 83%, p < 0.01). Coinfection with adenovirus and 2009 H1N1 was rare (4%). Rates of hospitalization and pneumonia did not differ between the adenovirus, 2009 H1N1, or coinfected groups. CONCLUSION: Military trainees with 2009 H1N1 vs. adenovirus have differing clinical presentations, and males are more likely to have adenovirus. Despite high frequencies of adenovirus infection, coinfection with adenovirus and 2009 H1N1 is rare and apparently does not result in increased morbidity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885690/ doi: 10.1371/journal.pone.0085094 id: cord-002848-w6q1x1zs author: Zhang, Ailian title: Immunostimulatory activity of water-extractable polysaccharides from Cistanche deserticola as a plant adjuvant in vitro and in vivo date: 2018-01-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A safe and effective vaccine adjuvant is important in modern vaccines. Various Chinese herbal polysaccharides can activate the immune system. Cistanche deserticola (CD) is a traditional Chinese herb and an adjuvant candidate. Here, we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate immune responses in vitro and in vivo. In a dose-dependent manner, WPCD significantly promoted the maturation and function of murine marrow-derived dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II, CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and TNF-α via toll-like receptor4 (TLR4), as indicated by in vitro experiments. In addition, its immunomodulatory activity was also observed in mice. WPCD effectively improved the titers of IgG, IgG(1) and IgG(2a) and markedly enhanced the proliferation of T and B cells, the production of IFN-γ and IL-4 in CD4(+) T cells and the expression level of IFN-γ in CD8(+) T cells better than Alum. Furthermore, WPCD could markedly up-regulate the expression levels of CD40 and CD80 on DCs in spleen and down-regulate the Treg frequency. The study suggests that polysaccharides of Cistanche deserticola are a safe and effective vaccine adjuvant for eliciting both humoral immunity and cellular immunity by activating DCs via TLR4 signaling pathway. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779666/ doi: 10.1371/journal.pone.0191356 id: cord-001368-ymp1pj3r author: Zhang, Chao title: Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro date: 2014-07-28 words: 4430.0 sentences: 236.0 pages: flesch: 50.0 cache: ./cache/cord-001368-ymp1pj3r.txt txt: ./txt/cord-001368-ymp1pj3r.txt summary: title: Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro Scorpions are a rich source of antimicrobial peptides: (1) androctonin isolated from the hemolymph of Androctonus australis, shows marked sequence similarity to tachyplesins, polyphemusins and gomesin [3, 4] ; (2) hadrurin from the venom of Hadrurus aztecus, which is hemolytic [5] ; (3) opistoporin-1, which possesses hemolytic activity, and opistoporin-2, both from the venom of the South African scorpion Opistophtalmus carinatus [6] ; (4) scorpine, which is the subject of this study, arising from the venom of Pandinus imperator, was shown to have anti-bacterial and anti-plasmodial activity in vitro [7] , and has shown a potent toxic effect on sexual and asexual stages of Plasmodium berghei and Plasmodium falciparum, respectively, and also a strong inhibition of dengue 2 virus (DENV-2) infection [8] . abstract: Scorpine, a small cationic peptide from the venom of Pandinus imperator, which has been shown to have anti-bacterial and anti-plasmodial activities, has potential important applications in the pharmaceutical industries. However, the isolation of scorpine from natural sources is inefficient and time-consuming. Here, we first report the expression and purification of recombinant scorpine in Escherichia coli, using small ubiquitin-related modifier (SUMO) fusion partner. The fusion protein was expressed in soluble form in E. coli, and expression was verified by SDS-PAGE and western blotting analysis. The fusion protein was purified to 90% purity by nickel–nitrilotriacetic acid (Ni(2+)–NTA) resin chromatography. After the SUMO-scorpine fusion protein was cleaved by the SUMO protease, the cleaved sample was reapplied to a Ni(2+)–NTA column. Tricine/SDS-PAGE gel results indicated that Scorpine had been purified successfully to more than 95% purity. The recombinantly expressed Scorpine showed anti-bacterial activity against two standard bacteria including Staphylococcus aureus ATCC 29213 and Acinetobacter baumannii ATCC 19606, and clinically isolated bacteria including S. aureus S, S. aureus R, A. baumannii S, and A. baumannii R. It also produced 100% reduction in Plasmodium falciparum parasitemia in vitro. Thus, the expression strategy presented in this study allowed convenient high yield and easy purification of recombinant Scorpine for pharmaceutical applications in the future. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113386/ doi: 10.1371/journal.pone.0103456 id: cord-339157-wj47xeqj author: Zhang, Chao title: Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease date: 2018-05-23 words: 3062.0 sentences: 174.0 pages: flesch: 55.0 cache: ./cache/cord-339157-wj47xeqj.txt txt: ./txt/cord-339157-wj47xeqj.txt summary: RESULTS: The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. According to the "diagnosis and treatment guideline on hand-foot-and-mouth disease (2010)", patients younger than 60 months with severe symptoms including meningitis, pulmonary edema, and mild cases without any nervous system lesions or pulmonary edema were included in this study. The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls (P<0.001). The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls (P<0.001). In the present study, we found that the concentrations of Ang II and NA were increased in serum of HFMD cases with mild or severe symptoms. abstract: BACKGROUND: Hand-foot-and-mouth disease (HFMD) is generally considered as a mild exanthematous disease to infants and young children worldwide. HFMD cases are usually mild and self-limiting but for few cases leads to complicated severe clinical outcomes, and even death. Previous studies have indicated that serum Ang II levels in patients with H7N9 infection were related to the severity of infection. However, the mechanisms underlying the pathogenesis of severe HFMD remain unclear. This study was undertaken to clarify the role of the renin-angiotensin system (RAS) in the progression of severe HFMD. METHODS: In the present study, 162 children including HFMD patients and healthy controls were recruited. The data was analyzed by time-series fashion. Concentrations of angiotensin II (Ang II) and noradrenaline (NA) in serum of patients were measured with ELISA. We established a mouse model for enterovirus 71 (EV71) infection and determined concentrations of Ang II, NA in tissue lysates at 3, 5 and 7 days post infection (dpi). RESULTS: The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. Additionally, the concentrations of Ang II and NA in serum of severe cases were significantly higher than those mild cases and the increased concentrations of Ang II and NA showed the same time trend during the progression of HFMD in the severe cases. Furthermore, the concentrations of Ang II and NA in target organs of EV71-infected mice including brains, skeletal muscle, and lungs were increased with the progression of EV71 infection in mice. Histopathological alterations were observed in the brains, skeletal muscle and lungs of EV71-infected mice. CONCLUSION: Our study suggested that activation of the RAS is implicated in the pathogenesis of severe HFMD. url: https://doi.org/10.1371/journal.pone.0197861 doi: 10.1371/journal.pone.0197861 id: cord-335505-s013j5ex author: Zhang, Chen title: Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China date: 2013-08-22 words: 3186.0 sentences: 173.0 pages: flesch: 44.0 cache: ./cache/cord-335505-s013j5ex.txt txt: ./txt/cord-335505-s013j5ex.txt summary: BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. The RVP Fast assay simultaneously detects the following viruses: respiratory syncytial virus (RSV); influenza(IFV) A (H1, H3, and H5) and B viruses; parainfluenza viruse (PIV) 1, 2, 3, and 4; human metapneumovirus (hMPV); adenovirus(ADV); piconavirus(PIC) which includes enterovirus (EV) and rhinovirus (RV); human coronaviruse(HCoV) NL63, HKU1, 229E, and OC43; and human bocavirus(BoCA). To find the reason that causes severe infection, we performed complete comparison between VSARI patients and the SARI, including clinical signs, number of viral target, gender, and age(Table 3, Figure 2B ). To find the association between virus infection and clinical signs in SARI, binary logistic regression was performed between 4 commonly diagnosed respiratory abnormality, including anhelation, respiratory failure, heart failure and pleural effusion, and the viral target detected by xTAG® RVP FAST. abstract: BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. METHODS: Cohort of 370 hospitalized children (1 to 72 months) with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA) specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed. RESULTS: Viral pathogen was detected in 350 (94.29%) of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV) (54.05%), respiratory syncytial virus (RSV) (51.08%), human bocavirus (BoCA) (33.78%), human parainfluenzaviruse type 3 (PIV3) (15.41%), and adenovirus (ADV) (12.97%). Pandemic H1N1 was the dominant influenza virus (IFV) but was only detected in 20 (5.41%) of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV) among suburb participants were significantly higher than that of urban area (P<0.05). Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05). CONCLUSION: Piconaviruses (EV/RV) and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients. url: https://doi.org/10.1371/journal.pone.0072606 doi: 10.1371/journal.pone.0072606 id: cord-279421-rxocrgfu author: Zhang, Dan title: Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection date: 2016-04-04 words: 2863.0 sentences: 134.0 pages: flesch: 48.0 cache: ./cache/cord-279421-rxocrgfu.txt txt: ./txt/cord-279421-rxocrgfu.txt summary: title: Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection In the present study, an improved single-tube multiplex reverse transcription PCR assay for simultaneous detection of 13 respiratory viruses was evaluated and compared with a previously reported two-tube assay as the reference method using clinical nasopharyngeal aspirates samples. In conclusion, our results demonstrates the one-tube assay revealed significant improvements over the two-tube assay in terms of the better sensitivity, more accurate quality control, less nonspecific amplification, more cost-effective and shorter turn-around time and will be a valuable tool for routine surveillance of respiratory virus infection in China. In the present study, we adopted the two-tube assay as a reference, and have been progressively optimized and substantially improved the performance of simultaneous detection of thirteen respiratory viruses types/subtypes, the most frequently detected viral agents of respiratory tract infections documented by Beijing Monitoring Network for Pneumonia between 2012-2014 (unpublished data), in a single-tube assay while maintaining excellent sensitivity and specificity. abstract: Respiratory viruses are among the most important causes of human morbidity and mortality worldwide, especially for infants and young children. In the past years, a few commercial multiplex RT-PCR assays have been used to detect respiratory viruses in spite of the high cost. In the present study, an improved single-tube multiplex reverse transcription PCR assay for simultaneous detection of 13 respiratory viruses was evaluated and compared with a previously reported two-tube assay as the reference method using clinical nasopharyngeal aspirates samples. Of 310 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 226 (72.90%, 226/310) and 214 (69.03%, 214/310) positive for one or more viruses were identified by the single-tube and the two-tube assays, respectively, with combined test results showing good concordance (Kappa value = 0.874). Individually, the single-tube assay for adenovirus (Adv), human metapneumovirus (HMPV), human rhinovirus (HRV), parainfluenza virus type 1 (PIV1), parainfluenza virus type 3 (PIV3) and parainfluenza virus type 4 (PIV4) showed the significantly superior sensitivities to those of the two-tube assay. No false positives were found. In conclusion, our results demonstrates the one-tube assay revealed significant improvements over the two-tube assay in terms of the better sensitivity, more accurate quality control, less nonspecific amplification, more cost-effective and shorter turn-around time and will be a valuable tool for routine surveillance of respiratory virus infection in China. url: https://www.ncbi.nlm.nih.gov/pubmed/27043208/ doi: 10.1371/journal.pone.0152702 id: cord-000077-d441jam3 author: Zhang, Hao-Jie title: The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability date: 2009-07-03 words: 5426.0 sentences: 267.0 pages: flesch: 54.0 cache: ./cache/cord-000077-d441jam3.txt txt: ./txt/cord-000077-d441jam3.txt summary: Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. As shown in Fig. 3A , similar levels of Pr160 gag-pol , Gag protein (Pr55 Gag ) and capsid protein p24 (CA p24) were found in cells transfected with the wild type or mutant constructs, indicating that the expression and stability of RT precursor protein were not affected by the mutations. To study if the RTs in the viral particles of Y271A and I274A mutants were degraded by proteolysis that made them undetectable, pseudoviruses of wild type and mutants were generated in the presence or absence of indinavir, a highly specific inhibitor of HIV-1 protease. abstract: Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln(269)-Arg(277)) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160(gag-pol) mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701634/ doi: 10.1371/journal.pone.0006108 id: cord-344782-ond1ziu5 author: Zhang, Jing title: Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi) date: 2018-10-24 words: 6003.0 sentences: 280.0 pages: flesch: 49.0 cache: ./cache/cord-344782-ond1ziu5.txt txt: ./txt/cord-344782-ond1ziu5.txt summary: Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Following the detection of the novel virus, in November 2015 (about 6 months after the cessation of the outbreak) an intensive survey of the parts of the river where affected turtles had been detected [2] was undertaken by groups of biologists and ecologists and samples collected from a wide range of aquatic species and some terrestrial animals (n = 360) to establish the size of the remaining population and whether any other animals were carrying this virus. BRV, as a novel nidovirus, was isolated from tissues of diseased animals, very high levels of viral RNA were detected in tissues with marked pathological changes and in situ hybridisation assays demonstrated the presence of specific viral RNA in lesions in kidneys and eye tissue-two of the main affected organs. abstract: In mid-February 2015, a large number of deaths were observed in the sole extant population of an endangered species of freshwater snapping turtle, Myuchelys georgesi, in a coastal river in New South Wales, Australia. Mortalities continued for approximately 7 weeks and affected mostly adult animals. More than 400 dead or dying animals were observed and population surveys conducted after the outbreak had ceased indicated that only a very small proportion of the population had survived, severely threatening the viability of the wild population. At necropsy, animals were in poor body condition, had bilateral swollen eyelids and some animals had tan foci on the skin of the ventral thighs. Histological examination revealed peri-orbital, splenic and nephric inflammation and necrosis. A virus was isolated in cell culture from a range of tissues. Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Its closest relatives are nidoviruses that have recently been described in pythons and lizards, usually in association with respiratory disease. In contrast, in the affected turtles, the most significant pathological changes were in the kidneys. Real time PCR assays developed to detect this virus demonstrated very high virus loads in affected tissues. In situ hybridisation studies confirmed the presence of viral nucleic acid in tissues in association with pathological changes. Collectively these data suggest that this virus is the likely cause of the mortalities that now threaten the survival of this species. Bellinger River Virus is the name proposed for this new virus. url: https://doi.org/10.1371/journal.pone.0205209 doi: 10.1371/journal.pone.0205209 id: cord-000413-h2e6h076 author: Zhang, Jingyu title: A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13 date: 2011-07-11 words: 4445.0 sentences: 233.0 pages: flesch: 56.0 cache: ./cache/cord-000413-h2e6h076.txt txt: ./txt/cord-000413-h2e6h076.txt summary: To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. We showed that the decreased amount of the high and intermediate molecular weight multimers were dramatically reduced by mAb SZ34 in a concentration-dependent manner under shear stress (Figure 2 ), further confirming the role of SZ34 in decreasing the susceptibility of VWF to proteolytic cleavage by ADAMTS13 under physiologically relevant conditions. abstract: The size of von Willebrand factor (VWF), controlled by ADAMTS13-dependent proteolysis, is associated with its hemostatic activity. Many factors regulate ADAMTS13-dependent VWF proteolysis through their interaction with VWF. These include coagulation factor VIII, platelet glycoprotein 1bα, and heparin sulfate, which accelerate the cleavage of VWF. Conversely, thrombospondin-1 decreases the rate of VWF proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of VWF. To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. Additionally, the epitope of anti-VWF mAb (SZ34) was mapped using recombinant proteins in combination with enzyme-linked immunosorbent assay and Western blot analysis. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. The binding epitope of SZ34 mAb is located between A1555 and G1595 in the central A2 domain of VWF. These data show that an anti-VWF mAb against the VWF-A2 domain (A1555-G1595) reduces the proteolytic cleavage of VWF by ADAMTS13 under shear stress, suggesting the role of this region in interaction with ADAMTS13. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133621/ doi: 10.1371/journal.pone.0022157 id: cord-350443-ca5avyjf author: Zhang, Lei title: Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy date: 2012-02-16 words: 7958.0 sentences: 383.0 pages: flesch: 49.0 cache: ./cache/cord-350443-ca5avyjf.txt txt: ./txt/cord-350443-ca5avyjf.txt summary: This study reviews trends in notifiable infectious diseases in China, in their historical context, discusses the current epidemiological state of these infections and their implications for disease surveillance and public health interventions. The total number of diagnosed and death cases were estimated by multiplying morbidity and mortality rates by the overall Chinese population in the study years. In 2008, the three most frequently reported disease types included viral hepatitis (38.3%), bacterial infections (33.3%) and STIs and HIV (9.8%), which account for 5.4, 4.8 and 1.4 million diagnosed cases respectively during the period 2005-2008 (Table 1) . Second, the rapid rise in the number of notified cases of STIs, especially HIV infection, and viral hepatitis in China is associated with growth of the sex industry, increasingly frequent risky sexual behaviours and an increasing number of sexual partners in the general Chinese population. abstract: This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens. url: https://doi.org/10.1371/journal.pone.0031076 doi: 10.1371/journal.pone.0031076 id: cord-339796-gccnvh0z author: Zhang, Si Min title: Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins date: 2015-07-31 words: 9073.0 sentences: 403.0 pages: flesch: 45.0 cache: ./cache/cord-339796-gccnvh0z.txt txt: ./txt/cord-339796-gccnvh0z.txt summary: The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. Here we describe the roles of the Trp residues in the membrane-active MPER sequence in anti-HIV fusion inhibitor design and a surprising role in the biosynthesis of viral structural proteins. abstract: The membrane proximal external region (MPER) is a highly conserved membrane-active region located at the juxtamembrane positions within class I viral fusion glycoproteins and essential for membrane fusion events during viral entry. The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. The inclusion of the MPER N-terminal sequence contributes to the membrane reactivity and anti-viral efficacy of the first two anti-HIV peptidyl fusion inhibitors T20 and T1249. As a type I transmembrane protein, Env also interacts with the cellular membranes during its biosynthesis and trafficking. Here we investigated the roles of MPER membrane-active sequences during both viral entry and assembly, specifically, their roles in the design of peptidyl fusion inhibitors and the biosynthesis of viral structural proteins. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. Furthermore, as compared to C-terminal dimerization, N-terminal dimerization of MPER peptides and N-terminal extension with five helix-forming residues enhanced their anti-viral efficacy substantially. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. The data suggest a role of the gp41 MPER in the membrane-reactive events during both viral entry and budding, and provide insights into the future development of anti-viral therapeutics. url: https://doi.org/10.1371/journal.pone.0134851 doi: 10.1371/journal.pone.0134851 id: cord-001910-6zfz2ns5 author: Zhang, Xianming title: Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome date: 2016-01-08 words: 3991.0 sentences: 241.0 pages: flesch: 53.0 cache: ./cache/cord-001910-6zfz2ns5.txt txt: ./txt/cord-001910-6zfz2ns5.txt summary: title: Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Therefore, we hypothesized that abdominal muscle activity during mechanically ventilation increases lung injury in severe acute respiratory distress syndrome. In an oleic acid-induced model of experimental ARDS in beagles, our findings suggested that abdominal muscle activity during mechanically ventilation increases lung injury in severe acute respiratory distress syndrome. In an oleic acid-induced ARDS model, our study showed that BIPAP AP had lower mRNA expression of IL-6 and IL-8 in lung tissues and less total cumulative histopathological lung injury scores compared with BIPAP SB group. abstract: OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712828/ doi: 10.1371/journal.pone.0145694 id: cord-000539-uh3q65we author: Zhang, Yi title: Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice date: 2012-01-03 words: 4620.0 sentences: 247.0 pages: flesch: 51.0 cache: ./cache/cord-000539-uh3q65we.txt txt: ./txt/cord-000539-uh3q65we.txt summary: BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. In the present mouse model, the number of leukocytes observed in the BALF of virus-infected mice significantly increased compared with the control mice on day 8 p.i. Different counts in BALF showed that the proportion of neutrophils dramatically increased. abstract: BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus. METHODOLOGY PRINCIPAL FINDINGS: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. CONCLUSIONS/SIGNIFICANCE: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250439/ doi: 10.1371/journal.pone.0029347 id: cord-001126-uqr00nzd author: Zhang, Zhicheng title: Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1 date: 2013-11-26 words: 4902.0 sentences: 226.0 pages: flesch: 45.0 cache: ./cache/cord-001126-uqr00nzd.txt txt: ./txt/cord-001126-uqr00nzd.txt summary: In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. To explore whether the evolution of codon usage bias in TTSuV2 CDS had been driven by mutation pressure alone or whether translation selection from its host has also contributed, we first compared the correlation between general nucleotide composition (A%, T%, G%, C%, GC%) and nucleotide composition at the third codon position (A 3S %, T 3S %, G 3S %, C 3S %, GC 3S %) using the Spearman''s rank correlation analysis method (Table 4) . These results further support the conclusion that composition constraints under mutational bias is an important factor determining synonymous codon usage pattern in TTSuV2, and but that other factors, such as natural selection, contributed. abstract: Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2, have become widely distributed in pig-farming countries in recent years. In this study, we performed a comprehensive analysis of synonymous codon usage bias in 41 available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of TTSuV2 and TTSuV1. TTSuV codon usage patterns were found to be phylogenetically conserved. Values for the effective number of codons (ENC) indicated that the overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant, the most frequently occurring codons had an A or C at the third codon position. Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were located in different quadrants of the first two major axes. A plot of the ENC revealed that compositional constraint was the major factor determining the codon usage bias for TTSuV2. In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the corresponding host sequence indicated that the codon usage pattern of TTSuV2 was similar to that of TTSuV1. However the similarity was low for each virus and its host. These conclusions provide important insight into the synonymous codon usage pattern of TTSuV2, as well as better understangding of the molecular evolution of TTSuV2 genomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841265/ doi: 10.1371/journal.pone.0081469 id: cord-314651-e4uaw5fy author: Zhao, Guangyu title: Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus date: 2015-12-23 words: 4167.0 sentences: 184.0 pages: flesch: 44.0 cache: ./cache/cord-314651-e4uaw5fy.txt txt: ./txt/cord-314651-e4uaw5fy.txt summary: After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. To assess viral replication and histopathologic damage following MERS-CoV infection, mice were euthanized with overdose inhalational carbon dioxide, and tissues included lungs, kidneys, livers, spleens, intestines and brains were harvested on indicated time points. Although a transgenic mouse model expressing human DPP4 was also established, and its immune response was studied after infection with MERS-CoV [16] , the transgenic mice in the study died on day 6 with only progressive pneumonia and mild perivascular cuffing in brain, and no neurological disorder or other multi-organ damage was observed. abstract: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/26701103/ doi: 10.1371/journal.pone.0145561 id: cord-000434-ff2zadol author: Zhao, Rongmao title: Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus date: 2011-08-19 words: 5752.0 sentences: 307.0 pages: flesch: 51.0 cache: ./cache/cord-000434-ff2zadol.txt txt: ./txt/cord-000434-ff2zadol.txt summary: The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs. Influenza A viruses (IAVs), members of the Orthomyxoviridae family, are highly contagious to a variety of avian and mammalian species. To confirm that these antibodies can recognize the HA antigen, the reactivity of the anti-peptide sera were evaluated by Western blot and ELISA against the purified HA0 protein of H1N1pdm virus. The sensitivity and specificity of peptide-ELISA versus HI test was 96.5% and 74.4%, respectively, indicating the potential of the peptide-ELISA method in detecting antibody against H1-subtype IAVs. In the present study, we identified immunodominant linear B cell epitopes on the H1N1pdm virus HA protein by a peptide scanning approach using H1N1pdm patients sera. To screen the H1-subtype specific epitopes, a set of 50 peptides spanning the amino acid sequences of the HA protein ectodomain of pandemic A/H1N1 2009 (H1N1pdm) influenza virus strain A/ California/04/2009 were synthesized. abstract: Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ(2) = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158760/ doi: 10.1371/journal.pone.0023374 id: cord-267605-efb10j3u author: Zheng, Li-Zhen title: Steroid-Associated Hip Joint Collapse in Bipedal Emus date: 2013-10-21 words: 5851.0 sentences: 249.0 pages: flesch: 46.0 cache: ./cache/cord-267605-efb10j3u.txt txt: ./txt/cord-267605-efb10j3u.txt summary: The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. Accordingly, the aim of the current study was to establish a SAON model in bipedal emus, with potentials to bone structural deterioration with subsequent femoral head collapse, a condition seen in SAON patients attributed to similar biomechanics or loading ratio imposed onto the hip joint [23, 24] . Using a combined pulsed LPS and MPS induction protocol previously established for SAON quadrupedal rabbits [11, 13] , the present study established a SAON model in bipedal emus characterized with subchondral bone deterioration and hip joint collapse, an experimental model mimicking human ON often developed at hip joint with femoral head collapse. abstract: In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients. url: https://doi.org/10.1371/journal.pone.0076797 doi: 10.1371/journal.pone.0076797 id: cord-252739-1manzf3l author: Zheng, Yueming title: Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants date: 2012-12-12 words: 4007.0 sentences: 250.0 pages: flesch: 56.0 cache: ./cache/cord-252739-1manzf3l.txt txt: ./txt/cord-252739-1manzf3l.txt summary: The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. Consistent with previous reports, the effects of KCNE1 on KCNQ1 include increase in overall current amplitude, slowing of the activation and deactivation kinetics, and removal of inactivation (Fig. 4A) . The common phenotype of these mutants is reduction of IKs current, which are commonly thought to be mediated by the KCNQ1/KCNE1 complex [2, 3] , as a result of decrease in either channel activity or trafficking efficiency. abstract: The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC(50) of 4.61±1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/23251633/ doi: 10.1371/journal.pone.0051820 id: cord-000326-a18rch1f author: Zhou, Jun-Wei title: Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes date: 2011-02-24 words: 4829.0 sentences: 276.0 pages: flesch: 50.0 cache: ./cache/cord-000326-a18rch1f.txt txt: ./txt/cord-000326-a18rch1f.txt summary: This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. Several additional lines of evidence also indicated the possible involvement of APOM in the development of diabetes and metabolic disturbances: 1) the human APOM gene is located within a high susceptibility region (6q21-q23) to type 2 diabetes (T2D) in genome-wide linkage analyses [6] . 2) SNP rs805296 (T-778C) in APOM promoter has been associated with the levels of plasma total cholesterol (TC) and fasting plasma glucose (FPG) in non-diabetic participants, 3) SNP rs805296 has also been associated with the susceptibility to T2D and coronary artery disease among the Northern Chinese [7, 8] . While our results did not support an association between APOM and T2D susceptibility in Hong Kong Chinese, subgroup analyses found SNP as well as haplotype associations between APOM and metabolic traits in T2D. abstract: This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044746/ doi: 10.1371/journal.pone.0017324 id: cord-327534-f2wvh6la author: Zhou, Peng title: IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation date: 2014-08-06 words: 7736.0 sentences: 377.0 pages: flesch: 52.0 cache: ./cache/cord-327534-f2wvh6la.txt txt: ./txt/cord-327534-f2wvh6la.txt summary: To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Regions containing putative IRF3 or IRF7 binding sites were identified from 2221 to 270 bp from the ATG of the bat IFN-b gene by comparison with human IFN promoters and cloned into the pGL4.1 expression vector (Promega). Analysis of the putative bat IRF7 promoter region around 1000 bp upstream of the start site of the ORF resulted in the identification of two IFN stimulated response elements (ISREs) and one nuclear factor kappa B (NF-kB) binding site. Our results demonstrate that even with a significant difference in its MyD88 binding region, bat IRF7 is still capable of inducing IFN-a transcription via MyD88 ( Figure 5 ). abstract: As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats. url: https://doi.org/10.1371/journal.pone.0103875 doi: 10.1371/journal.pone.0103875 id: cord-263276-keyu60in author: Zhou, Weimin title: Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia date: 2013-11-18 words: 3813.0 sentences: 191.0 pages: flesch: 50.0 cache: ./cache/cord-263276-keyu60in.txt txt: ./txt/cord-263276-keyu60in.txt summary: METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. The present study was undertaken to describe the profiles of HHVs and other respiratory viruses associated with hospital-based CAP and non-CAP among infants and young children in a rural area of China using comprehensive and sensitive molecular diagnostic techniques. In this study, the viral prevalence in sputum specimens of childhood with non typical bacterial CAP was investigated using sensitive molecular diagnostic methods for HHVs and 15 respiratory viruses, and viruses were detected in 99.6% of the children. In summary, our study on the prevalence of HHVs and other respiratory viruses in infants and young children with CAP identified a detectable virus in more than 99.6% of case participants, in which CMV, HHV-6, EBV, RSV and HBoV were clearly predominant (.25%) and contributed significantly to the spectrum of CAP in a rural area of China. abstract: OBJECTIVE: Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance. METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed. RESULTS: High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control. CONCLUSIONS: With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children. url: https://www.ncbi.nlm.nih.gov/pubmed/24260230/ doi: 10.1371/journal.pone.0079477 id: cord-340718-amfs4zay author: Zhu, Gengping title: Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus date: 2014-04-01 words: 2395.0 sentences: 103.0 pages: flesch: 42.0 cache: ./cache/cord-340718-amfs4zay.txt txt: ./txt/cord-340718-amfs4zay.txt summary: CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Since the first case was reported, researchers focused on improving diagnosis, understanding location of origin, and methods of cure; however, little is known about the geographic potential of H7N9 or environmental correlates of its transmission, except Butler [3] and He and Chen [4] , who presented ideas based on lessons from the previous avian influenza threat (i.e. H5N1), and Shi [5] and Fang [6] , who mapped the spread potential of H7N9 using spatial regression method. Effective and predictive risk maps can provide a useful means by which to design targeted surveillance efforts [3] [4] [5] [6] , and ecological niche modeling approaches are offering novel views of the geography of potential for disease transmission [9, 18] . abstract: BACKGROUND: In late March 2013, a new avian-origin influenza virus emerged in eastern China. This H7N9 subtype virus has since infected 240 people and killed 60, and has awakened global concern as a potential pandemic threat. Ecological niche modeling has seen increasing applications as a useful tool in mapping geographic potential and risk of disease transmission. METHODOLOGY/PRINCIPALS: We developed two datasets based on seasonal variation in Normalized Difference Vegetation Index (NDVI) from the MODIS sensor to characterize environmental dimensions of H7N9 virus. One-third of well-documented cases was used to test robustness of models calibrated based on the remaining two-thirds, and model significance was tested using partial ROC approaches. A final niche model was calibrated using all records available. CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Areas identified as presenting high risk for H7N9 spread tend to present consistent NDVI values through the year, whereas unsuitable areas show greater seasonal variation. url: https://www.ncbi.nlm.nih.gov/pubmed/24690878/ doi: 10.1371/journal.pone.0093390 id: cord-327257-doygrgrc author: Zhu, Jocelyn title: Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs date: 2020-07-28 words: 3686.0 sentences: 221.0 pages: flesch: 50.0 cache: ./cache/cord-327257-doygrgrc.txt txt: ./txt/cord-327257-doygrgrc.txt summary: title: Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs This study employed deep-learning convolutional neural networks to stage lung disease severity of Coronavirus Disease 2019 (COVID-19) infection on portable chest x-ray (CXR) with radiologist score of disease severity as ground truth. Deep-learning convolutional neural network (CNN) was used to predict lung disease severity scores. In conclusion, deep-learning CNN accurately stages disease severity on portable chest x-ray of COVID-19 lung infection. This study tested the hypothesis that deep-learning convolutional neural networks accurately stage disease severity on portable chest x-rays using radiologists'' severity scores as ground truths associated with COVID-19 lung infection. Deep-learning AI, specifically a convolutional neural network, is well suited to extract information from CXR and stage disease severity by training using chest radiologist determination of disease severity scores. In conclusion, deep-learning convolutional neural networks accurately stage lung disease severity on portable chest x-rays associated with COVID-19 lung infection. abstract: This study employed deep-learning convolutional neural networks to stage lung disease severity of Coronavirus Disease 2019 (COVID-19) infection on portable chest x-ray (CXR) with radiologist score of disease severity as ground truth. This study consisted of 131 portable CXR from 84 COVID-19 patients (51M 55.1±14.9yo; 29F 60.1±14.3yo; 4 missing information). Three expert chest radiologists scored the left and right lung separately based on the degree of opacity (0–3) and geographic extent (0–4). Deep-learning convolutional neural network (CNN) was used to predict lung disease severity scores. Data were split into 80% training and 20% testing datasets. Correlation analysis between AI-predicted versus radiologist scores were analyzed. Comparison was made with traditional and transfer learning. The average opacity score was 2.52 (range: 0–6) with a standard deviation of 0.25 (9.9%) across three readers. The average geographic extent score was 3.42 (range: 0–8) with a standard deviation of 0.57 (16.7%) across three readers. The inter-rater agreement yielded a Fleiss’ Kappa of 0.45 for opacity score and 0.71 for extent score. AI-predicted scores strongly correlated with radiologist scores, with the top model yielding a correlation coefficient (R(2)) of 0.90 (range: 0.73–0.90 for traditional learning and 0.83–0.90 for transfer learning) and a mean absolute error of 8.5% (ranges: 17.2–21.0% and 8.5%-15.5, respectively). Transfer learning generally performed better. In conclusion, deep-learning CNN accurately stages disease severity on portable chest x-ray of COVID-19 lung infection. This approach may prove useful to stage lung disease severity, prognosticate, and predict treatment response and survival, thereby informing risk management and resource allocation. url: https://doi.org/10.1371/journal.pone.0236621 doi: 10.1371/journal.pone.0236621 id: cord-351868-w4d45fue author: Zuwała, Kaja title: The Nucleocapsid Protein of Human Coronavirus NL63 date: 2015-02-20 words: 6708.0 sentences: 421.0 pages: flesch: 53.0 cache: ./cache/cord-351868-w4d45fue.txt txt: ./txt/cord-351868-w4d45fue.txt summary: Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. In order to test subcellular localization of the N protein in LLC-MK2 cells, the maxFP-Green-N/NL63-N encoding RNA was prepared based on the original plasmid. For EMSA assay 10 μg of RNA or DNA corresponding in sequence to the N-NL63 gene (prepared in the same manner as for the transfection of eukaryotic cells) was incubated in buffered solution (5 mM Tris, 50 mM NaCl, pH8.0) with 10 μg of the NTD or CTD for 30 minutes at room temperature. The constructs of NTD and CTD used in this study were designed based on literature data, HCoV-NL63 N protein amino acid sequence alignment with known homologs and on the comparative analysis of currently available crystal structures of these homologs. abstract: Human coronavirus (HCoV) NL63 was first described in 2004 and is associated with respiratory tract disease of varying severity. At the genetic and structural level, HCoV-NL63 is similar to other members of the Coronavirinae subfamily, especially human coronavirus 229E (HCoV-229E). Detailed analysis, however, reveals several unique features of the pathogen. The coronaviral nucleocapsid protein is abundantly present in infected cells. It is a multi-domain, multi-functional protein important for viral replication and a number of cellular processes. The aim of the present study was to characterize the HCoV-NL63 nucleocapsid protein. Biochemical analyses revealed that the protein shares characteristics with homologous proteins encoded in other coronaviral genomes, with the N-terminal domain responsible for nucleic acid binding and the C-terminal domain involved in protein oligomerization. Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. Furthermore, no significant alteration in cell cycle progression in cells expressing the protein was observed. This is in stark contrast with results obtained for other coronaviruses, except for the SARS-CoV. url: https://www.ncbi.nlm.nih.gov/pubmed/25700263/ doi: 10.1371/journal.pone.0117833 id: cord-254025-j1l0mder author: de Melo, Andreia C. title: Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute date: 2020-10-26 words: 3366.0 sentences: 178.0 pages: flesch: 50.0 cache: ./cache/cord-254025-j1l0mder.txt txt: ./txt/cord-254025-j1l0mder.txt summary: According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p <0.001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). As shown in Table 3 , mortality related to COVID-19 was significantly associated to older age (P < .001 for patients between 60 to 74 years and P = .002 for patients aged 75 years or older), metastatic cancer (P < .001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). abstract: OBJECTIVE: This study aimed to describe the demographic and clinical characteristics of cancer inpatients with COVID-19 exploring clinical outcomes. METHODS: A retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR. RESULTS: The mean age was 55.3 years (SD ± 21.1). Comorbidities were present in 110 (60.8%) cases. The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22 [12.2%]). Among hematological malignancies, lymphoma (20 [11%]) and leukemia (10 [5.5%]) predominated. Metastatic disease accounted for 90 (49.7%) cases. In total, 63 (34.8%) had recently received cytotoxic chemotherapy. The most common complications were respiratory failure (70 [38.7%]), septic shock (40 [22.1%]) and acute kidney injury (33 [18.2%]). A total of 60 (33.1%) patients died due to COVID-19 complications. For solid tumors, the COVID-19-specific mortality rate was 37.7% (52 out of 138 patients) and for hematological malignancies, 23.5% (8 out of 34). According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p <0.001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). After multivariate analysis, cases with admission due to symptoms of COVID-19 (P = .027) and with two or more metastatic sites (P < .001) showed a higher risk of COVID-19-specific death. CONCLUSION: This is the first Brazilian cohort of cancer patients with COVID-19. The rates of complications and COVID-19-specific death were significantly high. url: https://www.ncbi.nlm.nih.gov/pubmed/33104715/ doi: 10.1371/journal.pone.0241261 id: cord-011496-r8e19t0c author: de Rooij, Doret title: Development of a competency profile for professionals involved in infectious disease preparedness and response in the air transport public health sector date: 2020-05-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Recent infectious disease outbreaks highlight the importance of competent professionals with expertise on public health preparedness and response at airports. The availability of a competency profile for this workforce supports efficient education and training. Although competency profiles for infectious disease control professionals are available, none addresses the complex airport environment. Therefore, the main aim of this study is to develop a competency profile for professionals involved in infectious disease preparedness and response at airports in order to stimulate and direct further education and training. METHODS: We developed the competency profile through the following steps: 1) extraction of competencies from relevant literature, 2) assessment of the profile in a national RAND modified Delphi study with an interdisciplinary expert group (n = 9) and 3) assessment of the profile in an international RAND modified Delphi study with an airport infectious disease management panel of ten European countries (n = 10). RESULTS: We systematically studied two competency profiles on infectious disease control and three air transport guidelines on event management, and extracted 61 relevant competencies for airports. The two RAND modified Delphi procedures further refined the profile, mainly by specifying a competency’s target group, the organizational level it should be present on, and the exact actions that should be mastered. The final profile, consisting of 59 competencies, covers the whole process from infectious disease preparedness, through the response phase and the recovery at airports. CONCLUSION: We designed a profile to support training and exercising the multidisciplinary group of professionals in infectious disease management in the airport setting, and which is ready for use in practice. The many adaptations and adjustments that were needed to develop this profile out of existing profiles and air transport guidelines suggest that other setting-specific profiles in infectious disease control are desirable. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241746/ doi: 10.1371/journal.pone.0233360 id: cord-342476-0rupk21u author: van Rijn, Anneloes L. title: The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease date: 2019-10-24 words: 4036.0 sentences: 220.0 pages: flesch: 44.0 cache: ./cache/cord-342476-0rupk21u.txt txt: ./txt/cord-342476-0rupk21u.txt summary: The sensitivity, specificity and predictive values of mNGS were calculated based on 24 PCR positive and 1120 PCR negative target results of 88 samples and the normalized read counts (Table 5 ). The following markers were tested for potential associations with clinical severity of exacerbation (exacerbation severity, self-reported exacerbation severity), length of exacerbation and a decrease/increase in FEV 1 (control visit compared to baseline): mNGS pathogen positive versus negative exacerbation (qPCR targets), the number of normalized reads (log, cutoff of �5normalized reads) for the different target viruses (species level). The Shannon diversity scores for bacteriophages (normalized reads, cut-off of �5normalized reads) were comparable for COPD exacerbations of viral aetiology in PCR positive versus negative patients (Fig 5) . In this study, the respiratory virome in patients with COPD exacerbations was analysed with both mNGS and qPCR, and combined with clinical data. abstract: INTRODUCTION: Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations. OBJECTIVES: To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS. STUDY DESIGN: 88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006–2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations. RESULTS: By mNGS, 24/88 samples tested positive. Sensitivity and specificity, as compared with PCR, were 96% and 98% for diagnostic targets (23/24 and 1093/1120, respectively). Additional viral pathogens detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral normalized species reads (log value) (p = 0.002). Patients with viral pathogens had lower percentages of bacteriophages (p<0.001). No correlation was found between viral reads and clinical markers. CONCLUSIONS: The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any pathogenic respiratory viral infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome during infection, with potential consequences for the bacterial populations, during infection. url: https://www.ncbi.nlm.nih.gov/pubmed/31647831/ doi: 10.1371/journal.pone.0223952 id: cord-305900-ht7hb2rc author: van den Brand, Judith M. A. title: Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets date: 2012-08-08 words: 9461.0 sentences: 442.0 pages: flesch: 47.0 cache: ./cache/cord-305900-ht7hb2rc.txt txt: ./txt/cord-305900-ht7hb2rc.txt summary: Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. To this end, we inoculated ferrets with either seasonal human H3N2, pH1N1, or HPAI H5N1 virus, and performed detailed virological and pathological analyses at time points from 0.5 to 14 dpi, as well as measuring virus excretion, clinical signs, and hematological parameters. Comparable with the pattern of antigen expression in the respiratory tissues, high virus titers were seen in the nasal concha from 0.5 to 4 dpi with a peak on 1 dpi (Figure 3) . However, in the current study, we found very little H3N2 infection (based on virus antigen expression) in any cell types of the ferret lower respiratory tract ( Figure 3 ). abstract: Humans may be infected by different influenza A viruses—seasonal, pandemic, and zoonotic—which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues—including the central nervous system—for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets. url: https://www.ncbi.nlm.nih.gov/pubmed/22905124/ doi: 10.1371/journal.pone.0042343 id: cord-323433-9km824uh author: van den Wijngaard, Cees C. title: Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work? date: 2010-04-29 words: 4787.0 sentences: 244.0 pages: flesch: 49.0 cache: ./cache/cord-323433-9km824uh.txt txt: ./txt/cord-323433-9km824uh.txt summary: We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks. Geographic analysis methods -such as space-time scan statistics -may further increase the sensitivity of syndromic surveillance for detection of local outbreaks or of regional differences in regular seasonal epidemic diseases [2, 6] . The objective of this study was to evaluate to what extent syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. Of these, 6 belonged to influenza and/ or RSV related clusters (Figure 2a When repeating the weekly analyses with restricted time or spatial windows, both Legionnaires'' disease outbreaks were still detected with the same timeliness. abstract: BACKGROUND: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. METHODS AND FINDINGS: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999–2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999–2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline). CONCLUSIONS: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks. url: https://www.ncbi.nlm.nih.gov/pubmed/20454449/ doi: 10.1371/journal.pone.0010406 id: cord-048483-umvrwgaw author: van der Sande, Marianne title: Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population date: 2008-07-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Governments are preparing for a potential influenza pandemic. Therefore they need data to assess the possible impact of interventions. Face-masks worn by the general population could be an accessible and affordable intervention, if effective when worn under routine circumstances. METHODOLOGY: We assessed transmission reduction potential provided by personal respirators, surgical masks and home-made masks when worn during a variety of activities by healthy volunteers and a simulated patient. PRINCIPAL FINDINGS: All types of masks reduced aerosol exposure, relatively stable over time, unaffected by duration of wear or type of activity, but with a high degree of individual variation. Personal respirators were more efficient than surgical masks, which were more efficient than home-made masks. Regardless of mask type, children were less well protected. Outward protection (mask wearing by a mechanical head) was less effective than inward protection (mask wearing by healthy volunteers). CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection. Masks worn by patients may not offer as great a degree of protection against aerosol transmission. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440799/ doi: 10.1371/journal.pone.0002618 id: cord-309043-dlmx12vt author: von Brunn, Albrecht title: Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date: 2007-05-23 words: 6706.0 sentences: 341.0 pages: flesch: 52.0 cache: ./cache/cord-309043-dlmx12vt.txt txt: ./txt/cord-309043-dlmx12vt.txt summary: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. There are reports that a number of MHV and SARS-CoV replicase proteins colocalize and eventually interact in cytoplasmic membrane bound complexes, in which viral RNA synthesis occurs [18, 19] . We therefore cloned the SARS-CoV ORFeome by recombinatorial cloning (GATEWAY technology) and performed a genome-wide analysis for viral protein interactions by yeast-two-hybrid (Y2H) matrix screen. To systematically study the subcellular localization of viral proteins within eukaryotic HeLa cells the SARS-CoV ORFs were transfected in eukaryotic vectors with either N-or C-terminal Flag tags and detected with an anti-Flag antibody. In this study we report the cloning of the complete ORFeome of SARS-CoV and the results of a matrix-based yeast two-hybrid screen of pairwise viral protein-protein interactions. abstract: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies. url: https://www.ncbi.nlm.nih.gov/pubmed/17520018/ doi: 10.1371/journal.pone.0000459 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel