Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 48 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 15507 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 43 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 48 FDA 8 patient 8 drug 7 RNA 6 SARS 6 COVID-19 5 test 4 product 4 donor 4 cell 4 States 4 PCR 4 HIV 4 Drug 3 vaccine 3 dna 3 clinical 3 University 3 United 3 EMA 3 Administration 3 Act 2 virus 2 viral 2 study 2 safety 2 result 2 report 2 gene 2 finding 2 disease 2 conclusion 2 blood 2 antibiotic 2 animal 2 U.S. 2 Medical 2 Hospital 2 Health 2 HCV 2 Food 2 European 2 CoV-2 2 Center 2 Case 1 vector 1 variant 1 type 1 treatment 1 transfusion Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 3530 % 3354 patient 2532 blood 1926 study 1843 donor 1748 product 1707 drug 1705 cell 1453 result 1308 disease 1279 transfusion 1276 use 1217 time 1176 method 1100 test 1082 system 1030 testing 1018 case 978 treatment 976 sample 966 infection 950 virus 947 risk 931 level 896 year 874 finding 865 group 831 vaccine 828 antibody 827 datum 819 unit 806 platelet 802 development 787 day 786 conclusion 752 process 742 safety 699 information 691 health 662 type 650 assay 646 number 626 laboratory 612 quality 607 therapy 596 plasma 587 imaging 579 procedure 556 gene 554 activity Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 1393 FDA 730 Case 579 RBC 573 Study 530 Design 517 US 493 Studies 483 Background 477 SARS 423 States 388 ICH 388 CT 385 al 359 COVID-19 355 MRI 328 CoV-2 319 et 318 Drug 307 United 303 Health 300 Blood 293 HIV 289 RNA 274 Report 262 EU 258 PCR 243 University 241 Purpose 239 C 235 A 228 HCV 224 Food 224 Committee 219 . 216 Administration 209 - 208 Center 204 EMA 199 Hospital 186 MR 186 ABO 184 Medical 178 B 175 European 174 WHO 169 Methods 169 Member 168 RHD 168 MD 165 PLT Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 1717 it 1157 we 693 they 234 he 200 them 156 i 83 she 58 us 37 you 28 themselves 28 itself 26 him 23 one 12 her 5 me 5 himself 2 yourself 2 ourselves 2 igg4 1 y]ou 1 srbcs 1 s 1 ours 1 ns3/4a 1 mtorc1 1 mg 1 magpixv 1 isog 1 herself 1 fomepizole 1 c.1136c 1 aw4).the Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 24590 be 4867 have 2684 use 1680 include 927 provide 927 perform 916 develop 886 base 855 identify 811 show 793 report 788 increase 774 require 760 do 658 follow 653 associate 597 compare 593 reduce 589 evaluate 586 test 565 make 529 find 523 receive 506 treat 485 determine 485 approve 448 demonstrate 446 relate 443 allow 433 improve 425 need 418 result 400 lead 396 assess 389 involve 386 review 386 detect 383 establish 360 consider 360 cause 349 present 348 obtain 345 occur 342 ensure 340 produce 334 give 318 suggest 313 describe 306 know 300 indicate Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 2136 not 1872 - 1544 clinical 1526 also 1194 high 1169 other 1013 more 961 such 906 new 755 well 690 low 677 human 672 most 650 first 648 however 646 viral 632 anti 616 only 595 positive 581 available 577 specific 547 pediatric 528 important 510 medical 494 significant 492 regulatory 489 as 488 many 476 different 475 potential 465 patient 462 non 439 several 431 further 429 common 406 negative 405 large 386 single 367 therapeutic 367 current 347 additional 346 severe 341 early 338 small 337 public 332 effective 331 diagnostic 321 prior 319 then 314 less Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 206 most 125 good 104 least 79 high 70 Most 36 large 36 great 28 low 15 late 10 small 9 old 9 big 9 bad 8 early 5 young 3 strong 3 long 3 close 2 steep 2 postt 2 new 2 near 2 hot 2 fresh 2 easy 2 common 1 wide 1 wealthy 1 strict 1 simple 1 sharp 1 safe 1 poor 1 montelukast 1 little 1 happy 1 fast 1 dirty 1 clean 1 cheap 1 -E 1 -4/2016 1 -3/2016 Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 466 most 78 least 13 well 1 highest 1 freshest 1 fewest 1 astrocytomas Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 7 doi.org 5 bit.ly 3 www.fda.gov 3 heman 2 www.nytimes.com 2 www.niams.nih.gov 2 www.msdiscovery.com 2 www.collaborativedrug.com 2 figshare.com 2 creativecommons 1 www.usatoday.com 1 www.ta 1 www.sgh.org.sa 1 www.sfda.gov.sa 1 www.rcsb.org 1 www.nist.gov 1 www.ncbi.nlm.nih.gov 1 www.ncbi.nlm 1 www.nature.com 1 www.miamiherald.com 1 www.miamiher 1 www.isbtweb.org 1 www.idsociety.org 1 www.fe 1 www.ema.europa.eu 1 www.debra.org 1 www.cdc.gov 1 www.cap.org 1 www.accessdata.fda.gov 1 www.accessdata.fda.-gov 1 www 1 pubs.acs.org 1 pedsd 1 patents.google.com 1 network.bethematchclinical.org 1 medicalxpress.com 1 medical.olympusamerica.com 1 doi 1 creativecommons.org 1 bucshon.house.gov 1 bit 1 apps.who.int Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 3 http://heman 2 http://www.msdiscovery.com/spectrum.html 2 http://doi.org/10.1016/j.vaccine.2020.09.067 2 http://creativecommons 1 http://www.usatoday.com/story/ 1 http://www.ta 1 http://www.sgh.org.sa 1 http://www.sfda.gov.sa/ 1 http://www.rcsb.org/ 1 http://www.nytimes.com/2016/09/13/us/zika-testdelays-florida-pregnant.html?_r¼0 1 http://www.nytimes.com/2016/09/13/us/zika-test-delays-flor 1 http://www.nist.gov/node/ 1 http://www.niams.nih.gov/health_info/epidermolysis_ 1 http://www.niams.nih.gov/health_info/epider 1 http://www.ncbi.nlm.nih.gov/clinvar/ 1 http://www.ncbi.nlm 1 http://www.nature.com/ 1 http://www.miamiherald.com/news/health-care/arti 1 http://www.miamiher 1 http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-bloodgroup-terminology/ 1 http://www.idsociety.org/Content.aspx?id¼4682 1 http://www.fe 1 http://www.fda.gov/safety/recallsmarket-withdrawals-safety-alerts 1 http://www.fda.gov/regulatory-information/searchfda-guidance-documents/meta-analyses-randomizedcontrolled-clinical-trials-evaluate-safety-human-drugs-orbiological 1 http://www.fda.gov/ 1 http://www.ema.europa.eu/en/medicines 1 http://www.debra.org/research-trials 1 http://www.collaborativedrug.com/pages/public_access 1 http://www.collaborativedrug.com/ 1 http://www.cdc.gov/flu/professionals/diagnosis/molecu 1 http://www.cap.org/ShowProperty?nodePath=/UCMCon/Con 1 http://www.accessdata.fda.gov/scripts/cder/daf/ 1 http://www.accessdata.fda.-gov/scripts/ 1 http://www 1 http://pubs.acs.org/doi/10.1021/acsnano.0c03822 1 http://pedsd 1 http://patents.google.com/patent/WO2008135762A1/ 1 http://network.bethematchclinical.org/workarea/downloadasset 1 http://medicalxpress.com/news/2016-10-lab-constraints-zikaresults.html 1 http://medical.olympusamerica.com/sites/default/files/ 1 http://figshare.com/articles/Ebola_active_cpds_pharmacophore/ 1 http://figshare.com/articles/A_pharmacophore_of_ebola_active_ 1 http://doi.org/10.1038/ 1 http://doi.org/10.1007/s40629-020-00126-6 1 http://doi.org/10.1007/s40629-020-00126- 1 http://doi.org/10.1007/s4025 1 http://doi.org/10.1007/s10557-020-06976-0 1 http://doi 1 http://creativecommons.org/licenses/by/4.0/ 1 http://bucshon.house.gov/news/documentsingle.aspx?DocumentID=3841 Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 4 snarayan@childrensnational.org 3 nkadom@childrensnational.org 3 drvikasmenghani@gmail.com 3 dristuna@yahoo.com 2 usha.nagaraj@osumc.edu 2 suraj.serai@cchmc.org 2 mjl1213@yumc.yonsei.ac.kr 2 kurianj@email.chop.edu 2 kim.cecil@cchmc.org 2 jaraque@georgiahealth.edu 2 eiblanco74@gmail.com 2 e.nhihuynh@gmail.com 2 andrea.doria@sickkids.ca 2 amitsensation@yahoo.co.in 2 alokjaju@gmail.com 2 ahmad.aouthmany@utoledo.edu 2 henrietta.rosenberg@mountsinai.org 1 tsai@childrens.harvard.edu 1 tkelly@chw.org 1 teresaliang86@gmail.com 1 taylorchung12@gmail.com 1 tanyasupakul@yahoo.com 1 swestra@partners.org 1 sumitsingh78@yahoo.com 1 sthawai2@jhmi.edu 1 states@email.chop.edu 1 stanescu@u.washington.edu 1 spalasis@yahoo.com 1 shilpavhegde@gmail.com 1 shawn.parnell@seattlechildrens.org 1 scorpion68kd@yahoo.com 1 schmitzk@ohsu.edu 1 sblumer@montefiore.org 1 rxkrishn@texaschildrens.org 1 run4boston@gmail.com 1 rudyavar@gwmail.gwu.edu 1 rubioeva@yahoo.com 1 ramy.jalbout@yahoo.com 1 rami.nachabe@philips.com 1 radhakrp@ucmail.uc.edu 1 pkhanna@uw.edu 1 nskwatra@childrensnational.org 1 nrssbabu@gmail.com 1 nosaka-s@ncchd.go.jp 1 nkang26@gmail.com 1 nicholas.stence@childrenscolorado.org 1 neal540@gmail.com 1 nbodmer@gmail.com 1 nathaneg@med.umich.edu 1 mkitazono@gmail.com Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 48 fda approved drugs 10 fda approved drug 6 patient did not 6 testing is not 5 fda approved small 5 patients did not 5 results are available 4 fda does not 4 system was then 4 tests are not 3 % had ligamentous 3 % had severe 3 % were male 3 case based approach 3 donor is not 3 donors are not 3 donors were igm 3 fda approved antiviral 3 fda approved rejuvenation 3 fda has recently 3 fda is responsible 3 patient does not 3 patient was not 3 patients were not 3 results were available 3 samples did not 3 samples were not 3 studies are generally 3 studies are necessary 3 studies are ongoing 3 studies have not 3 testing is also 3 time was similar 3 transfusion related acute 3 transfusions were not 3 treatment is available 3 use is not 2 % had osteochondral 2 % had reaction 2 % received at 2 % were cases 2 % were controls 2 % were female 2 % were normal 2 antibodies are not 2 antibodies is not 2 blood is not 2 case report assessment 2 cell is not 2 cells are capable Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 2 antibodies are not detectable 2 donors are not currently 2 donors were not able 2 patients were not subsequently 2 transfusion had no effect 1 % found no link 1 % had no change 1 % had no clinical 1 antibodies is not well 1 antibody is not demonstrable 1 blood is not always 1 blood is not trivial 1 cases was not previously 1 cells are not available 1 disease is not clinically 1 donor had no identifiable 1 donor has not yet 1 donor reported no clinical 1 donor were not significant 1 donors are not law 1 donors reported no significant 1 drugs are not inherently 1 fda has not formally 1 findings are not present 1 findings are not specific 1 findings were not present 1 group found no association 1 group found no decreases 1 group include not only 1 infection are not well 1 infections are not life 1 levels are not equivalent 1 patient had no change 1 patient had no other 1 patient was not recently 1 patient was not statistically 1 patients are not subsequently 1 patients had no complications 1 patients had no history 1 patients had no pre 1 patients had no us 1 patients required no transfusion 1 patients showed no significant 1 products are not available 1 products are not readily 1 products was not significantly 1 result does not necessarily 1 results found no antibiotic 1 results were not available 1 risk was not formally A rudimentary bibliography -------------------------- id = cord-328471-oz99upzz author = Ahmad, Jamshaid title = SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp) – A drug repurposing study date = 2020-07-23 keywords = FDA; RNA; SARS summary = In this global health emergency, drug repurposing (or repositioning) is one of the fast track option that involves screening of existing FDA approved drugs for the identification of potential molecules that can disrupt the function of key proteins of the SARS-CoV-2 and can be used for treatment against COVID-19. Whereas, Demoxytocin showed ten H-bonds with both active site Asp760 and Asp761 and other key residues e.g. Trp617, Tyr619, Lys621, Ser682, Glu811, Lys621, Tyr619, Trp617, Ser682 and Glu811 with dock score -9.68kcal/mol and ligand efficiency of -0.142 (Supplementary Figure S3) . Colistin (polymyxin E, polypeptide antibiotics) showed most of the H-bonding with Lys551, Trp617, Tyr619, Asp618, Ser682, Asp684, Asn691, and both catalytic residues i.e. Asp760, Asp761, with a docking score of -9.24kcal/mol and ligand efficiency of -0.113 (Supplementary Figure S5) . Examorelin, Lypressin, Ornipressin, and Colistin are also common drugs in both form of RdRp. Only one H-bond with His810 and other non-covalent interactions were observed for Examorelin showed a docking score of -12.139 kcal/mol and ligand efficiency of -0.187. doi = 10.1016/j.heliyon.2020.e04502 id = cord-018566-dd5gw66t author = Armbruster, Walter J. title = The Political Economy of US Antibiotic Use in Animal Feed date = 2018-05-30 keywords = FDA; Health; United; animal; antibiotic summary = This chapter examines the evidence for antibiotic resistance in the United States and globally, the public health implications, and the impact of—and related industry and political responses to—antibiotic use in animal feed. The major stakeholders include pharmaceutical companies, production integrators, feed suppliers, farm groups, producers, restaurants, food retailers, the public, the medical community, the scientific community, government regulators and policy makers. In 1969, the United Kingdom''s (UK) Parliament received the Swann Report, which concluded that using antimicrobials at sub-therapeutic levels in food-producing animals created risks to human and animal health (Joint Committee on the use of Antibiotics in Animal Husbandry and Veterinary Medicine 1969). This scenario could be exacerbated to the extent FSIS approves additional international facilities, local regulations, and inspections as "equivalent to the United States." Future trade agreements will need to include provisions which address reduced use of medically important antibiotics in producing food animals. doi = 10.1007/978-3-319-92138-9_15 id = cord-017208-7oew461e author = Aurigemma, Rosemarie title = Regulatory Aspects in the Development of Gene Therapies date = 2005 keywords = FDA; animal; cell; dna; gene; product; safety; study; vector summary = Table 1 Beyond a Good Idea: What the Successful Investigator Has Already Done With a Project Leading to Commercial Development Defined candidate biologic (or molecule) Made comparisons with similar products Characteristics of product are consistent with pharmaceutical requirements Production scale is adequate Product characterization is adequate Laboratory reference standard exists In vitro potency assay has been developed Stability studies develop confidence product is a "drug" Reproducible model systems have confirmed in vivo activity with clinical product Early animal work includes some toxicology Scale-up requirements practical for initial clinical trials In general, reflects experience and scientific maturity of investigator In addition to the US agencies that develop the regulations that govern drug development and licensing, the International Conference on Harmonization (ICH) was formed in April 1990 involving the United States, the European Union, and Japan to address the issue of globalizing such regulations. doi = 10.1007/978-1-59259-785-7_29 id = cord-276414-kicu0tv5 author = Bahadur Gurung, Arun title = In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors date = 2020-06-10 keywords = FDA; SARS summary = Interestingly, the anti-migraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. In the present study, we have explored the possibilities of FDA approved drugs as potential inhibitors of the coronavirus main protease, a therapeutically important drug target playing a salient role in the maturation and processing of the viral polyproteins and are vital for viral replication and transcription. Interestingly, the antimigraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. doi = 10.1016/j.sjbs.2020.06.005 id = cord-016640-pvlg3nkp author = Baron, Ellen Jo title = Technical and Clinical Niches for Point of Care Molecular Devices date = 2012-04-05 keywords = FDA; PCR; POC summary = POCT infectious disease molecular assays may be developed to detect speci fi c • infections for which a rapid response is desirable. The most widely used molecular test at patient POC sites is the real-time PCR (RT-PCR) assay for detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) [ 2 ] . Another rapid molecular test has been FDA-cleared for multiplex detection of 15 respiratory viruses, including adenovirus, 2 coronavirus strains, 5 in fl uenza strains, human metapneumovirus, parain fl uenza virus types 1-4, RSV, and rhino-enterovirus, with a time-to-result of 1-1.5 h using a novel multiplex PCR and array detection format [ 14 ] . Although other PCR methods for virus detection and identi fi cation in respiratory secretions are available and show excellent sensitivities and speci fi cities, they are not candidates for POC tests due to their complexity, long performance time, or format that leads to inef fi ciencies when performing non-batch (such as stat) testing [ 14 ] . doi = 10.1007/978-1-4614-3970-7_33 id = cord-018770-uy76mc2j author = Connelly-Smith, Laura S. title = Donor Evaluation for Hematopoietic Stem and Progenitor Cell Collection date = 2019-11-28 keywords = FDA; HPC; Marrow; donor summary = With the increasing incidence of hematopoietic allogeneic cell transplantation (allo-HCT), the importance of securing a cellular product, safely from a donor, and ensuring that the product is without additional risk to the recipient, continues to be of paramount importance. Various registries have developed HPC donor-screening questionnaires and their use recommended, to elicit medical history and to identify high-risk behaviors associated with risk of disease transmission (AABB n.d.-a; National Marrow Donor Program 2002) . One such questionnaire that is freely available is the hematopoietic progenitor cell (HPC), Apheresis and HPC, Marrow Donor History Questionnaire (DHQ) (Appendix 4.1) developed by the AABB Inter-organizational DHQ-HPC Task Force to provide establishments with a standardized tool to screen allogeneic HPC donors for communicable disease risk factors in accordance with requirements of the FDA, AABB, FACT, and the NMDP (AABB n.d.-a). Areas to be evaluated and documented during history and physical examination (H&P) of potential allogeneic/syngeneic donors of peripheral blood stem cells or marrow. doi = 10.1007/978-3-319-55131-9_4 id = cord-335776-e5wjsk8t author = Costantino, Ryan C. title = The U.S. medicine chest: Understanding the U.S. pharmaceutical supply chain and the role of the pharmacist date = 2020-08-18 keywords = FDA; U.S.; USPSC summary = Despite years of effort raising concerns about the USPSC, pharmacists and pharmacy technicians continue to spend a substantial amount of time and energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes related to low-quality medications. The U.S. pharmaceutical supply chain is complex, global, and goes beyond FDPs. The 2020 American Pharmacists Association House of Delegates has rightly asserted that "The quality and safety of pharmaceutical and other medical products and the global pharmaceutical and medical product supply chain are essential to the United States national security and public health." Pharmacy professionals on the front line engage with patients, identify medication-related issues, and engage in drug-procurement decisions. 1, 2 Over the past decades, the U.S. pharmaceutical supply chain (USPSC) has increasingly relied on international sources for pharmaceuticals and pharmacists continue to dedicate a sizable amount of energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes of low-quality medications. doi = 10.1016/j.japh.2020.07.018 id = cord-339122-7vvqtk84 author = Deb, Chaarushena title = Covid-19, Single-Sourced Diagnostic Tests, and Innovation Policy date = 2020-07-07 keywords = FDA; diagnostic; test summary = 16 An appropriate model for diagnostic testing development, including innovation incentives, should go beyond simply discouraging test monopolies and promoting confirmatory testing, by also allowing for low R&D costs for test development and yielding fast delivery of high quality tests-preventing the errors highlighted in the Covid-19 testing response from occurring in both emergency and non-emergency situations. And thus any sort of incentive model that relies on granting market exclusivity -such as the traditional patent system, FDA approval exclusivity, or trade secret protection -raises the same sorts of issues, if on a smaller scale, as those grimly demonstrated by the failure of U.S. SARS-CoV-2 testing at the onset of the Covid-19 pandemic, which ultimately resulted in the loss of many lives. But for diagnostic tests which rely on confirmatory testing, innovative improvements, and robust access to supply, single-sourcing creates a host of serious problems. doi = 10.1093/jlb/lsaa053 id = cord-322915-zrjx31ev author = Demain, Arnold L title = Microbial drug discovery: 80 years of progress date = 2009-01-09 keywords = FDA; HIV; Streptomyces; antibiotic; cell; drug; gram; natural; new; product summary = Evidence of the importance of natural products in the discovery of leads for the development of drugs for the treatment of human diseases is provided by the fact that close to half of the best selling pharmaceuticals in 1991 were either natural products or their derivatives. In addition to the antibiotic-resistance problem, new families of anti-infective compounds are needed to enter the marketplace at regular intervals to tackle the new diseases caused by evolving pathogens. 28 Among the novel class of antimicrobial agents used in treating resistance to Gram-positive infections, we can also mention the cyclic lipopeptide antibiotic daptomycin produced by Streptomyces roseosporus. 44 Other applications include antitumor drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, hypocholesterolemic drugs, ruminant growth stimulants, insecticides, herbicides, coccidiostats, antiparasitics vs coccidia, helminths and other pharmacological activities. Considering that animal health research and the development of new anti-infective product discovery have decreased, the discovery of new antibiotics has decreased over the past 15 years, with few new drug approvals. doi = 10.1038/ja.2008.16 id = cord-294108-uvnh0s9r author = Dube, Taru title = Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector date = 2020-10-25 keywords = COVID-19; CoV-2; FDA; Phase; RNA; SARS; patient; vaccine; virus summary = [2, [8] [9] [10] This article discusses SARS-CoV-2 nanostructure, the virus biology in connection to its epidemiology, clinical manifestations, and potential and future therapeutic options including repurposed drugs, vaccine/protein therapies, immune therapies, and nanotherapeutics. Mechanisms such as inhibition of viral enzymes (DNA and RNA polymerases, 3CL pro, TMPRSS2, reverse transcriptase, neuraminidase, endonucleases, and other proteases) or processes such as ACE2 cellular receptor inhibitors and endosomal acidification mediators prohibiting viral fusion; molecules interfering with glycosylation of the viral protein, viral assembly, new viral particle transport, and release, and immunomodulation of cytokine release can be potential targets in developing various antiviral drugs for the SARS-CoV-2. [85] A randomized, placebo-controlled, Phase IV clinical trial assessing the safety and efficacy of umifenovir as an adjuvant therapy to the combined therapeutic regimen of IFN 1a, lopinavir/ritonavir and hydroxychloroquine in moderate to severe COVID-19 patients (NCT04350684) is underway. doi = 10.1002/adtp.202000172 id = cord-269975-1ebmq7t8 author = Duplantier, Allen J. title = Combating biothreat pathogens: ongoing efforts for countermeasure development and unique challenges date = 2020-05-27 keywords = Burkholderia; Ebola; FDA; RNA; host; infection; treatment; virus summary = None of the filoviruses or henipaviruses has any FDA-approved therapeutics or vaccines available for prevention or treatment of human disease, and while ribavirin is sometimes used to treat Lassa fever, it is not a terribly effective drug against this viral infection [28] . Many of the therapeutics that are in different stages of either preclinical or clinical development for select biothreat pathogens include small molecule antivirals (Tables 7.3 and 7.4), antibody (or antibody cocktails) against viruses or bacteria/virulence factors (Table 7 .5), and combination drug therapy (Table 7 .6). Although no FDA-approved HDT therapies are yet available for treating infectious diseases, we have summarized in this section the antimicrobial Primary screening of small molecule chemical libraries in the phenotypic HCI assay will identify compounds that inhibit pathogen infection as well as those that may contribute to cellular toxicity. doi = 10.1016/b978-0-12-818480-6.00007-2 id = cord-001513-p7v5p036 author = Ekins, Sean title = A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus date = 2014-12-12 keywords = EBOV; FDA; VP35 summary = Common features pharmacophore for EBOV actives Two papers from 2013 described compounds active as inhibitors of different EBOV strains in vitro and in vivo, namely amodiaquine and chloroquine in one study 8 , clomiphene and toremifene in another 9 . These suggest that the receptor-ligand based approach results in a general similarity across the nine structures, likely indicating the similar binding mode and importance of features for interfering with this generally hydrophobic pocket for protein-protein interactions. In silico docking of molecules in VP35 structure Redocking the 4IBI ligand in the protein resulted in an RMSD of 3.02Å, which generally indicates the difficulty of predicting orientations for compounds binding in what is a relatively hydrophobic and shallow pocket ( Figure S1 ). Pharmacophores, receptor ligand models and docking data for FDA-approved drugs inhibiting the Ebola virus, 10.5256/f1000research.5741.d38449 35 . doi = 10.12688/f1000research.5741.2 id = cord-269194-b1wlr3t7 author = Engstrom-Melnyk, Julia title = Chapter 5 Clinical Applications of Quantitative Real-Time PCR in Virology date = 2015-12-31 keywords = CMV; FDA; HCV; HIV; HIV-1; PCR; RNA; viral summary = Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats. With the development and administration of newer drugs that target specific biological processes of HIV, routine and clinical monitoring of viral loads using a real-time quantitative PCR assay continues to be critical to predict treatment failure and early emergence of drug resistance mutations, within a timeframe that would increase subsequent treatment success. doi = 10.1016/bs.mim.2015.04.005 id = cord-274061-ynqxgyw6 author = Epstein, Jay S. title = Blood system changes since recognition of transfusion‐associated AIDS date = 2013-10-17 keywords = AIDS; FDA; States; United; blood summary = In a set of 14 recommendations directed primarily at federal agencies, the IOM called for a more responsive and integrated decision-making process including establishment of a Blood Safety Council reporting to a designated Blood Safety Director within HHS and a standing "expert panel" to assure communication of blood product risks and alternatives to their use both to care providers and to the public. Several possible strategies were presented, including deferral of blood donations by persons known to be at increased risk for AIDS and the use of surrogate tests to identify persons at increased risk of transmission, such as those with detectable antibody to hepatitis B core antigen (anti-HBc) or low CD4/CD8 T-cell ratios. The Transfusion Transmitted Virus Study, supported by the National Heart, Lung and Blood Institute, published a retrospective analysis of a prospective study that showed that alanine aminotransferase (ALT) testing of donors might effect a 30% reduction in TAH incidence. doi = 10.1111/trf.12373 id = cord-288567-1nmk9qhr author = Frieden, Ilona J. title = Management of infantile hemangiomas during the COVID pandemic date = 2020-05-16 keywords = FDA; infantile summary = The use of beta-blockers in the treatment of IH has revolutionized care, and recent American Academy of Pediatrics (AAP) clinical practice guidelines (CPG) emphasize that early therapeutic intervention is critical for complicated IH to prevent medical complications or permanent disfigurement. We give recommendations to help guide decisions about when telehealth may be an alternative to in-office visits, including initiation, dosage changes, and continued evaluation for those patients requiring treatment. [2] [3] [4] [5] [6] [7] [8] [9] Consensus recommendations prior to the FDA/EMA approval in 2014 included the following 10 : (a) screening for contraindications to propranolol, (b) performing or obtaining documentation of, a recent normal cardiovascular and pulmonary history and examination, (c) obtaining key historical data including poor feeding, dyspnea, tachypnea, diaphoresis, wheezing, heart murmur, or family history of heart block or arrhythmia, and (d) prolonged in-office monitoring. doi = 10.1111/pde.14196 id = cord-303865-vd3qr32o author = Gianturco, Stephanie L. title = Outsourcing facilities and their place in the U.S. drug supply chain date = 2020-08-28 keywords = Drug; FDA summary = Although it is preferable for providers to use Food and Drug Administration (FDA)eapproved, commercially available drug products, there are times when drug products need to be compounded to meet a patient-specific need. 4 FDA does not intend to take action against outsourcing facilities that compound drug products using bulk drug substances in category 1, in which information supports their clinical use or need, and FDA was unable to identify significant safety risks. Outsourcing facilities can provide hospitals and independent practices with ready-to-use sterile drug products because they can compound drug products on a larger scale and are not limited by the requirement of a patient-specific prescription. Challenges that limit the use of outsourcing facilities in the U.S. drug supply chain include a lack of a finalized 503B Bulks List, inconsistences in the inspection process, and lack of transparency in compliance status. doi = 10.1016/j.japh.2020.07.021 id = cord-253840-xudra8tp author = Gillette, Michael title = Reflections of the Angiotensin Receptor Blocker Recall by the FDA and Repercussions on Healthcare date = 2020-04-21 keywords = FDA; arb; recall summary = Over the preceding 12-24 months, healthcare providers have encountered an alarming number of recalls related to cardiovascular medications, particularly with angiotensin receptor blockers (ARBs). ARBs, such as valsartan and losartan, represent a class of medications that in randomized controlled clinical trials (RCTs) have been shown to reduce blood pressure (BP) in hypertensive patients and impart cardiovascular benefits in diabetic nephropathy, systolic heart failure, left ventricular dysfunction, and following stroke [1] [2] [3] [4] [5] [6] [7] [8] 10] . This is particularly important given the recent outbreak of the coronavirus disease 2019 (COVID19) and speculation that ACE-Is or ARBs could increase the risk of infection through upregulation of angiotensin converting enzyme-2 receptors (ACE2) thereby leading to inappropriate discontinuation by patients or providers [16] . Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial doi = 10.1007/s10557-020-06976-0 id = cord-280571-ntgt5hy9 author = Ginocchio, Christine C. title = Strengths and Weaknesses of FDA-Approved/Cleared Diagnostic Devices for the Molecular Detection of Respiratory Pathogens date = 2011-05-01 keywords = FDA; Mycobacterium; RSV; test summary = In addition to RADTs, there are U.S. Food and Drug Administration (FDA)-approved/cleared nonmolecular-based viral diagnostic methods with a more rapid time to result, compared with traditional viral tube culture, eg, direct fluorescent antibody (DFA) testing and rapid cell culture. Although these 8 viruses are responsible for a large number of respiratory tract infections, bocavirus, selected coronaviruses (229E, OC43, NL63, and HKU-1), parainfluenza 4, and rhinovirus are also important causes of respiratory disease and are generally only detected using NAATs. Because antiviral therapies are currently limited to the treatment of influenza A, influenza B, cytomegalovirus pneumonia, and varicella zoster virus pneumonia, it is often argued that the specific identification of other viruses is not relevant, because the information would not change patient management. With clinical integration of real-time polymerase chain reaction (PCR) and FDA-approved/cleared simple cartridge-based NAATs, laboratories of all sizes are now able to perform molecular diagnostic tests. doi = 10.1093/cid/cir046 id = cord-022039-y0l943xg author = Gruber, Marion F. title = Regulation and Testing of Vaccines date = 2017-07-17 keywords = Act; BLA; CBER; FDA; Guidance; industry; product; vaccine summary = Section 901 of Title IX of the FDAAA authorizes the FDA to require certain postmarketing studies and clinical trials for prescription drug and biological products approved under the FDA should take action in response to such reports and whether the current pharmacovigilance plan is adequate. Critical information to be contained in the BLA include data derived from nonclinical laboratory and clinical studies that demonstrate that the manufactured product meets prescribed requirements for safety, purity, and potency. Following completion of IND studies demonstrating the safety and efficacy of the vaccine for a specific use and population the sponsor can submit a BLA to obtain a license for a new vaccine under section 351 of the PHS Act for commercial manufacture and distribution of the product. doi = 10.1016/b978-0-323-35761-6.00079-1 id = cord-026653-094bk0t0 author = Gülsen, Askin title = Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events* date = 2020-06-24 keywords = EMA; FDA; HSR; patient; reaction; report; severe summary = This review will evaluate reports of allergic and substance-specific infusion reactions (IR), injection-site reactions (ISR), hypersensitivity reactions (HSR), urticaria, and anaphylaxis caused by BSs. The most common indications for the use of biologics in lung diseases are allergic and severe uncontrolled asthma. The Australian Public Assessment report and the FDA label did not observe an increase in the incidence of severe immunological and anaphylactic reactions related to the use of nintedanib [25, 26] . According to the recent BCCA Drug Manual, it was reported that HSR including anaphylaxis can develop in ≤ 1 % (severe < 1 %), IRs in 1 % (severe ≤ 1 %), and immune-mediated rash in 8-18 % ( severe ≤ 1 %) of patients [58] . The FDA''s 2019 label reported infusion-related reactions in 11-24 % of patients (placebo 7-18.0 %), acute urticaria in 1-2 %, acute HSRs in 1.5 %, pruritus in 4 %, and serious IRs and anaphylaxis in < 1 % [159] . doi = 10.1007/s15007-020-2550-1 id = cord-268283-eja8fkwv author = Iftikhar, Hafsa title = Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach date = 2020-06-09 keywords = 3cl; FDA; SARS; drug summary = In this regard, several recent studies have been conducted using computational methods to screen libraries of approved drugs or drug-like molecules to identify potential inhibitors of different viral proteins, particularly, RdRp and 3CL-protease [13] [14] [15] [16] [17] . Here, we applied a computer aided drug discovery approach by targeting three important enzymes (RdRp, 3CL-protease and helicase) of SARS-CoV-2 and identified three FDA-approved drugs and three other drug-like molecules as potential therapeutics. In this study, we used a virtual screening based strategy to identify already approved drugs or drug-like molecules that can bind to any of the three key viral enzymes, 3CL-protease, RdRp and helicase, and potentially inhibit the function of these enzymes. In our studies we performed computational screening by targeting three important enzymes of SARS-CoV-2 including RdRp, 3CL-protease and helicase, to identify not only the already approved drugs for repurposing but also the drug candidates or lead structures that can be chemically modified to develop potential drugs. doi = 10.1016/j.compbiomed.2020.103848 id = cord-290895-tb0xald0 author = Indu, Purushothaman title = Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach date = 2020-10-26 keywords = COVID-19; FDA; SARS summary = title: Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach Virtual screening was performed to find out the lead antiviral drug molecules against main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) using COVID-19 Docking Server. RESULTS: Out of 65 FDA approved small molecule antiviral drugs screened, Raltegravir showed highest interaction energy value of -9 kcal/mol against Mpro of SARS-CoV-2 and Indinavir, Tipranavir, and Pibrentasvir exhibited a binding energy value of ≥ -8 kcal/mol. In this study, FDA J o u r n a l P r e -p r o o f approved small molecule antiviral drugs were screened against protein targets of SARS-CoV-2 using a computational based approach. In our study, other screened antiviral drugs such as Indinavir, Tipranavir, and Pibrentasvir showed dock energy value more than -8 kcal/mol and these drugs might also serve as an inhibitors of Mpro target of SARS-CoV-2. doi = 10.1016/j.jiph.2020.10.015 id = cord-333732-dtfmcqh6 author = Johnson, Walter G title = Legislating in the Time of a Pandemic: Window of Opportunity or Invitation for Recklessness? date = 2020-06-15 keywords = Act; FDA; VALID summary = 24 However, the early enforcement decisions and lack of early engagement with industry had already discouraged many clinical laboratories from developing or seeking authorization for LDTs, 25 and the delayed availability of testing during the initial weeks of the pandemic significantly exacerbated the spread of the virus in the U.S. The U.S. legislative process for any given issue is characterized by static inertia interrupted by an occasional "policy window" opened by external changes or events that suddenly catapult a specific issue to the forefront of Congressional attention. Using the window of opportunity created by COVID-19, with the demonstrated urgency to reform emergency norms, to enact the comprehensive reform of diagnostics regulation provided by the VALID Act would therefore exemplify the type of crisis-based lawmaking that has been successful in the past to create much of our public health legislation. doi = 10.1093/jlb/lsaa042 id = cord-033420-pjtyv0pv author = Kalokairinou, Louiza title = The promise of direct-to-consumer COVID-19 testing: ethical and regulatory issues date = 2020-09-23 keywords = COVID-19; DTC; FDA; test summary = Although the provision of DTC tests has potential benefits—such as expanding access to testing and reducing the risk of exposure for consumers and medical personnel—it also raises significant ethical and regulatory concerns. The second part discusses five primary issues for DTC COVID-19 tests: test accuracy; potential misinterpretation of results; misleading claims and other misinformation; privacy concerns; and fair allocation of scarce resources. The second part identifies five primary ethical and regulatory issues for DTC COVID-19 tests: uncertainty over the accuracy of test results; potential misinterpretation of test results by users; misleading product promotion and misinformation; privacy concerns; and fair allocation of scarce resources. We conclude with recommendations for regulators, companies, and other relevant stakeholders that can help ensure high-quality, accurate, and equitably distributed COVID-19 tests, and inform the ethical provision of DTC health tests during public health crises. doi = 10.1093/jlb/lsaa069 id = cord-276460-nmugz0oh author = Katz, Louis M. title = Computer-Based Blood Donor Screening: A Status Report date = 2007-01-31 keywords = CASI; FDA; FTFI; WSAQ; donor summary = Further enhancements of the basic CASI system include pictures illustrative of the content of the question; response inputs via touch screen; inclusion of back, help, and skip commands to improve accuracy and completeness of responses, staff review modules for assessment of completed DHQs, direct printing of the DHQ with provision for signatures, and electronic transfer of final interview data to other associated computer systems. In a similar study using essentially the same system at another regional blood center, Cumming et al 24 found that with a combination of FTFI and WSAQ, the rate of deferrals of first-time donors for high-risk behavior was 5.8 per 1000, whereas after installation of an AVT-CASI system the rate increased to 11.2 per 1000, a 93% increase. Cumming et al, 24 in their recent study at a regional blood center, found that in the first year after implementing an AVT-CASI system, the elicitation of information resulting in donor deferrals increased substantially. doi = 10.1016/j.tmrv.2006.08.001 id = cord-002626-jzwwses4 author = Kaul, Karen L. title = The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care date = 2017-07-16 keywords = BRAF; CLIA; FDA; NGS; clinical; laboratory; patient; test; testing summary = Clinical laboratories have thus had to develop new assays or modified the existing FDA-approved ones to detect high-risk HPV genotypes in head and neck cancer specimens. The vast majority of reporting laboratories utilized LDPs. 57 KRAS and RAS family gene mutation analysis is also critical in the management of patients with non-small-cell lung cancer (NSCLC) and other tumors, 58 for which FDA approval of kits has not occurred; LDPs or off-label use of kits is required. 74, 75 The FDA approval of anti-EGFR therapies based on clinical trial outcomes data resulted in the need for clinical laboratories to test tumor tissue for the EGFR-sensitizing mutations in order for patients to be eligible for treatment. During those ground-breaking first 15 years of the targeted cancer therapy era, if the laboratory community had been prohibited from providing high-quality, standardized LDP-based testing under existing CLIA guidelines, the negative consequences to patient care in the past and the future would have been substantial. doi = 10.1177/2374289517708309 id = cord-317720-gbi11oxx author = Lefferts, Joel A. title = Implementation of an Emergency Use Authorization Test During an Impending National Crisis date = 2020-05-14 keywords = FDA; RNA summary = Concerned that the efforts of state laboratories would be further impacted by lack of resources, we began to identify sources -including the WHO, the CDC, and commercial vendors -of the required primers and probes for the reverse transcriptase polymerase chain reaction (RT-PCR) detection of the virus and placed orders for test reagents from potential suppliers. The document provided guidance for high complexity testing laboratories developing SARS-CoV-2 tests for submission for Emergency Use Authorization (EUA) status with respect to required validation experiments and reporting to the FDA. Initially laboratories were required to spike RNA transcripts into previously extracted nucleic acid from negative samples for the CDC assay to determine the limit of detection but this had its own challenges of not representing extraction of true clinical samples and issues with degradation were identified. Our plan included the production of enough contrived clinical specimens and control material to proceed with validation or verification of the multiple (laboratory-developed and CDC EUA) tests that we were evaluating. doi = 10.1016/j.jmoldx.2020.05.001 id = cord-304056-2bo0s0hz author = Lezotre, Pierre-Louis title = Part I State of Play and Review of Major Cooperation Initiatives date = 2014-12-31 keywords = APEC; ASEAN; Committee; Community; EMA; European; FDA; GCC; GMP; Health; ICH; Member; SADC; States; Steering summary = ▸ To maintain a forum for a constructive dialogue between regulatory authorities and the pharmaceutical industry on the real and perceived differences in the technical requirements for product registration in the EU, US, and Japan in order to ensure a more timely introduction of new medicinal products, and their availability to patients; ▸ To contribute to the protection of public health from an international perspective (added upon revision in 2000); ▸ To monitor and update harmonized technical requirements leading to a greater mutual acceptance of research and development data; ▸ To avoid divergent future requirements through harmonization of selected topics needed as a result of therapeutic advances and the development of new technologies for the production of medicinal products; ▸ To facilitate the adoption of new or improved technical research and development approaches which update or replace current practices, where these permit a more economical use of human, animal, and material resources, without compromising safety; ▸ To facilitate the dissemination and communication of information on harmonized guidelines and their use such as to encourage the implementation and integration of common standards. doi = 10.1016/b978-0-12-800053-3.00002-1 id = cord-354445-lnvc7mmf author = Lichtenstein, David title = 4 Cleaning and Disinfecting Gastrointestinal Endoscopy Equipment date = 2019-12-31 keywords = AER; Administration; Drug; FDA; HLD; endoscope summary = Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. Salmonella is a serious primary pathogen, and Pseudomonas is ubiquitous in many water sources, and although both these pathogens have been associated most frequently with endoscopic transmission, they are both sensitive to multiple agents, including glutaraldehyde, and other HLDs. Transmission of bacterial pathogens from flexible endoscopes has been rare since the adoption of the current 2011 multisociety reprocessing guideline, 45, 160 with the exception of duodenoscope-related infections (discussed later). Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes doi = 10.1016/b978-0-323-41509-5.00004-9 id = cord-334847-lf1grybz author = Lynch, Holly Fernandez title = Regulatory Flexibility for COVID-19 Research date = 2020-07-07 keywords = COVID-19; FDA summary = Clinical research is critical to combatting COVID-19, but regulatory requirements for human subjects protection may sometimes pose a challenge in pandemic circumstances. Although regulators have offered some helpful guidance for research during the pandemic, we identify further compliance challenges regarding IRB review and approval, informed consent, emergency research, and research involving incarcerated people. Strict regulatory compliance may be challenging amidst a public health emergency, but participant protection and high-quality science remain essential.(1) In recognition of these considerations, FDA and the Office for Human Research Protections (OHRP) within the Department of Health and Human Services (HHS) have issued guidance on conducting research during the COVID-19 pandemic.(2) Although this guidance offers a helpful start, gaps remain and additional regulatory flexibility is warranted in some instances. To ensure that this research proceeds efficiently and ethically, we offer suggestions to proactively address regulatory compliance challenges regarding IRB review and approval, informed consent, and inclusion of vulnerable populations. doi = 10.1093/jlb/lsaa057 id = cord-273099-zkk5d6gd author = Muzumdar, Jagannath M. title = Vaccine supply, demand, and policy: A primer date = 2016-01-01 keywords = Act; FDA; States; United; vaccine summary = According to the authors, an integrated policy approach that preserves incentives for market entry and innovation in the vaccine industry while addressing parental vaccine concerns and increasing immunization funding and reimbursement for both providers and patients is needed. 2 Push strategies seek to address supply-side issues in the vaccine market by providing direct assistance to ease the burden of research, development, and production costs, whereas pull strategies are designed to manipulate demand for vaccines, thereby improving the likelihood of a return on investment by increasing the number of immunizations administered. The United Kingdom has taken a lead in promoting an International Financing Facility for Immunization (IFFIm) 69 IFFIm has raised more than $1 billion in capital markets to immunize poor children in developing nations against Reviews VACCINE POLICY vaccine-preventable diseases. doi = 10.1331/japha.2009.09007 id = cord-287758-da11ypiy author = Mônica Vitalino de Almeida, Sinara title = COVID-19 therapy: what weapons do we bring into battle? date = 2020-09-10 keywords = ACE2; COVID-19; CoV-2; Coronavirus; FDA; FIG; MERS; RNA; SARS; drug; patient; viral summary = The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell. doi = 10.1016/j.bmc.2020.115757 id = cord-256852-lrz17bdx author = Nayyar, Gaurvika M. L. title = Responding to the Pandemic of Falsified Medicines date = 2015-06-03 keywords = FDA; drug; medicine; quality summary = 15 The U.S. Institute of Medicine (IOM) has published a report "Countering the Problem of Falsified and Substandard Drugs." 16 The IOM recommendations to "stem the global trade" in such products are laudable in advising that the U.S. Food and Drug Administration (FDA), the National Institute of Standards and Technology, and other U.S. and international pharmaceutical and financing agencies be more actively involved in setting standards and financing improvements; yet this report falls far short of making a strong call for standardized, agreed-upon quality assessment technologies; an international law convention; and a more activist, internationally recognized lead organization, all three of which are essential for stopping the many health threats of fake drugs. doi = 10.4269/ajtmh.14-0393 id = cord-016293-pyb00pt5 author = Newell-McGloughlin, Martina title = The flowering of the age of Biotechnology 1990–2000 date = 2006 keywords = FDA; Genome; NIH; RNA; U.S.; University; Venter; cell; disease; dna; gene; human; plant; sequence; technology summary = In the course of the project, especially in the early years, the plan stated that "much new technology will be developed that will facilitate biomedical and a broad range of biological research, bring down the cost of many experiments (mapping and sequencing), and finding applications in numerous other fields." The plan built upon the 1988 reports of the Office of Technology Assessment and the National Research Council on mapping and sequencing the human genome. These DNA chips have broad commercial applications and are now used in many areas of basic and clinical research including the detection of drug resistance mutations in infectious organisms, direct DNA sequence comparison of large segments of the human genome, the monitoring of multiple human genes for disease associated mutations, the quantitative and parallel measurement of mRNA expression for thousands of human genes, and the physical and genetic mapping of genomes. doi = 10.1007/1-4020-5149-2_4 id = cord-017413-ymo9h7wb author = Nurudeen, Sahadat Kemi title = Selecting and Screening Donors date = 2012-10-19 keywords = ASRM; FDA; donation; donor; oocyte summary = In these fi rst cases of donation, gametes were obtained primarily from women already undergoing Screening of egg donors is an intricate • and multifaceted process that includes obtaining informed consent; securing a detailed medical, genetic, psychosocial, and reproductive history; performing a thorough physical examination; and testing for speci fi c infectious diseases. Screening women interested in becoming oocyte donors is an intricate and multifaceted process that includes obtaining informed consent, taking a thorough medical history, performing a complete medical examination, testing for infectious diseases, providing a genetic screen, and evaluating the donor psychologically. The screening process has evolved since the introduction of oocyte donation with recommendations and evidence provided by the American Society for Reproductive Medicine (ASRM), the US Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and state health departments (Table 4 .1 ) [ 8, 9 ] . doi = 10.1007/978-1-4471-2392-7_4 id = cord-022053-idft1p6d author = Pecora, Nicole title = New Technologies for the Diagnosis of Infection date = 2017-07-21 keywords = Biotyper; FDA; MALDI; PCR; TOF; Vitek; identification summary = Organisms commonly identified this way include spirochetes, mycobacteria, DNA viruses, Aspergillus, Candida, and Toxoplasma, although special reference laboratories (e.g., The Infectious Disease Pathology Branch at the Centers for Disease Control and Prevention) have a wide range of antibodies for common to exotic pathogens for tissue confirmation. These include highly sensitive probes for use in direct specimens, to alternative amplification methods, rapid assays of single targets, and multiplexed systems that allow for the detection of many organisms in one assay. Application of RNA-ISH to Aspergillus and Candida in FFPE showed less sensitivity than real-time PCR with sequencing (gold standard), although some FISH-positive, PCRnegative cases with obvious fungal elements were seen, suggesting refinements of this technique may be valuable for rapid identification of these common organisms, especially if mucormycosis is in the differential. Comparative evaluation of the Bruker Biotyper and Vitek MS matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry systems for identification of yeasts of medical importance doi = 10.1016/b978-0-323-44585-6.00006-0 id = cord-291626-lxa8pvt3 author = Pelfrene, E. title = Monoclonal antibodies as anti-infective products: a promising future? date = 2019-01-31 keywords = FDA; antibody; mAbs; monoclonal summary = Additionally, the FDA recently licensed ibalizumab as a rescue therapy in heavily treatmentexperienced adults with multidrug-resistant HIV-1 infection and also previously approved raxibacumab (in 2012) and obiltoxaximab (in 2016), both intended for treatment of inhalational anthrax (in combination with appropriate antibacterial medicines) and for prophylaxis when alternative therapies are not available or are not appropriate [5e7] . François et al., ''Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in patients with severe pneumonia caused by Staphylococcus aureus: first in man trial,'' abstract 1992, paper presented at European Congress of Clinical Microbiology and Infectious Diseases 2017) [34, 38] . Compassionate use Benefits seriously ill patients who cannot be treated satisfactorily or cannot enrol in ongoing clinical trials Pertains to unauthorized medicinal products for chronically, seriously debilitating or life-threatening diseases, with no satisfactory treatment authorized in EU; targeted at a group of patients rather than individual; or undergoing centralized MAA or clinical trials EMA, European Medicines Agency; FDA, US Food and Drug Administration; HTA, health technology assessment bodies; MAA, marketing authorization application; SA, scientific advice. doi = 10.1016/j.cmi.2018.04.024 id = cord-332038-icyut3xa author = Pillaiyar, Thanigaimalai title = A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery date = 2020-04-02 keywords = Alzheimer; FDA; Parkinson; cancer; disease; drug summary = Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. While numerous studies suggest the potent anticancer activities of drug 20, the overall benefit is limited as it is associated with serious side effects including the gastrointestinal and renal toxicities. The recent phase 3 clinical trial studies using the occurrence of colorectal adenomas as a biomarker for cancer as a primary endpoint at 1 year after intervention revealed that metformin reduced both occurrence and number of adenomas/polyps in the patients at low dosage level. Out of the approved drugs, data for bexarotene have provided proof of concept as potential candidate for the treatment of Alzheimer''s disease as noted above, whereas acitretin (93, Figure 7) , which is known to penetrate tissues including brain may also be a promising candidate for AD [177] . doi = 10.1016/j.ejmech.2020.112275 id = cord-278174-znc99yos author = Ramsey, Glenn title = Managing recalls and withdrawals of blood components date = 2004-01-31 keywords = FDA; HIV; blood summary = Abstract Donor centers are issuing a growing number of recalls and market withdrawals to hospital transfusion services about blood components. Using the FDA''s categories of donor center biological product deviations, we provide recommendations to consider for when to notify the recipient''s physician, after postdonation information is received about a previously transfused blood component. If a blood product has been transfused from a donor who should have been ineligible at the time of donation, then "we recommend that the establishments consider notifying the treating physician of those recipients about the post donation information, including whether the donor developed suspected SARS." Donors are deferred for 28 days after recovering from suspected SARS or for 14 days after exposure to a person with SARS or travel to SARS-risk areas. doi = 10.1016/j.tmrv.2003.10.005 id = cord-280040-xphxlaat author = Rutala, William A. title = Disinfection and Sterilization in Health Care Facilities An Overview and Current Issues date = 2016-09-30 keywords = FDA; disinfection; level summary = [6] [7] [8] Because of noncompliance with recommended reprocessing procedures, the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) issued a health advisory alerting health care providers and facilities about the public health need to properly maintain, clean, and disinfect and sterilize reusable medical devices in September 2015. There is excellent evidence in the scientific literature that environmental contamination plays an important role in the transmission of several key health care-associated pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycinresistant Enterococcus (VRE), Acinetobacter sp, norovirus, and Clostridium difficile. Comparison of ultraviolet irradiation versus hydrogen peroxide for room decontamination UV devices and HP systems have their own advantages and disadvantages ( Table 5) , 53 and there is now ample evidence that these no-touch systems can reduce environmental contamination with health care-associated pathogens and reduce HAIs. 84 However, each specific marketed system should be studied and its efficacy demonstrated before being introduced into health care facilities. doi = 10.1016/j.idc.2016.04.002 id = cord-299323-riotkgj4 author = Seo, Yurim title = Elements of Regulatory Dissonance: Examining FDA and EMA Product Labeling of New Vaccines (2006–2018) date = 2020-10-13 keywords = EMA; FDA summary = The key documents examined were the U.S. Food & Drug Administration''s (FDA) Package Inserts (PIs), U.S. Centers for Disease Control and Prevention''s (CDC) Vaccine Information Statements (VISs), and the European Medicines Agency''s (EMA) Summary of Product Characteristics (SmPCs) and Package Leaflets (PLs). Although efforts by the International Council for Harmonization (ICH) to harmonize technical requirements for registering drugs and biologics have produced a number of useful guidelines that are used around the world, such efforts have not been extended to the regulatory review process or product labeling [1] . This study compared vaccine prescribing information and patient information leaflet languages between FDA/Centers for Disease Control and Prevention (CDC) and EMA. The centralized route allows companies to submit a single Marketing Authorization Application (MAA) to EMA that leads to the product''s approval in all countries within the European Economic Area (i.e., the 27 member states of the EU plus Iceland, Liechtenstein and Norway). doi = 10.1016/j.vaccine.2020.09.067 id = cord-308284-r546ypur author = Simpson, Shmona title = Navigating facilitated regulatory pathways during a disease X pandemic date = 2020-10-23 keywords = European; FDA; Medicines; clinical; product summary = Several potential regulatory scenarios may exist and co-exist during an epidemic: for example, (a) de-novo candidates requiring rapid development and regulatory assessment (b) de-novo products requiring assessment when the typical package of clinical efficacy data may not be available, (c) approval of de novo or repurposed products for "emergency" use only in specific populations (d) for compassionate use in specific (e.g., "named") individuals of an unauthorized medicine (e) conditional or accelerated authorization before the completion of efficacy studies or, (f) use of a licensed product outside of its approved use (e.g., for another indication, dosage regimen, or population). Conditional term-limited approval 22 FDA''s Expanded Access (EA) is a program designed for patients with an immediately life-threatening disease to access a product that has clinical trial data (putatively showing an acceptable benefit-risk profile)-but does not yet have marketing authorization. doi = 10.1038/s41541-020-00249-5 id = cord-352579-ndcbmgfj author = Takahashi, Takuto title = Pharmacogenomics of COVID-19 therapies date = 2020-08-18 keywords = COVID-19; FDA; drug; patient; variant summary = In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). Summary of clinical implications of pharmacogenomics for COVID19 We found evidence that several genetic variants may alter the pharmacokinetics of hydroxychloroquine, azithromycin, ribavirin, lopinavir/ritonavir and possibly tocilizumab, which hypothetically may affect clinical response and toxicity in the treatment of COVID-19. As previously described in this review, hydroxychloroquine, chloroquine and azithromycin can individually increase risk for QT prolongation, and those drugs have been used in combination in COVID-19 patients. doi = 10.1038/s41525-020-00143-y id = cord-003118-58ta20fg author = Van Norman, Gail A. title = Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies date = 2018-06-25 keywords = FDA; drug summary = Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the "single-patient" investigational new drug [IND] application). Spurred by patient advocacy during the early days of the acquired immunodeficiency syndrome (AIDS) epidemic in the late 1980s, and facilitated by subsequent legislative efforts over the next 20 years, regulatory initiatives permit the FDA to release drugs for use in individual patients through expanded access (EA) INDs (4, 5) , in many cases allowing emergency treatment with nonapproved drugs within hours of application, and nonemergency treatment within an average of 4 days (6) . Releasing investigational new drugs to individual patients who are facing certain death or disability seems to be a relatively uncomplicated decision, but allowing EA to entire groups of patients for treatment with an investigational new drug presents more complex regulatory, logistical, and ethical challenges for scientists, commercial entities, and the FDA. doi = 10.1016/j.jacbts.2018.02.001 id = cord-326922-bajpr5a2 author = Watson, C. James title = Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors date = 2020-11-02 keywords = Administration; Drug; FDA; Food; States; compound summary = In the modern-day United States (US), medications are by-inlarge manufactured in commercial facilities, and this production is regulated and overseen by the US Food and Drug Administration (FDA). Furthermore, a new form of large-scale compounding has become commonplace, whereby pharmacies produce bulk volumes of medications which are not available commercially, and broadly distribute them to healthcare practices and individual patients. Patient harm caused by compounded medications has been the focus of media, medical, and legislative attention in recent years, especially following a multistate, multi-fatality outbreak of fungal meningitis caused by contaminated steroid injections compounded at a pharmacy in Framingham, MA [2, 3, 5, 6] . We categorized errors under the conceptual framework described by Sarah Sellers, PharmD, MPH, former board member for the FDA''s Advisory Committee on Pharmacy Compounding, in testimony to the US Senate Committee on Health, Education, Labor, and Pensions, namely, that "suprapotency," "subpotency," and "contamination" are the primary risks associated with pharmaceutical compounding [59] . doi = 10.1007/s13181-020-00814-3 id = cord-010119-t1x9gknd author = nan title = Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date = 2017-09-04 keywords = ABO; Anti; Background; Blood; CD36; Case; Center; DAT; DTT; Design; FDA; FFP; HBV; HCV; HIV; HLA; Hospital; IPC; MTP; Medical; Medicine; NAT; PCR; PLT; RBC; RHD; Red; Studies; Study; System; TPE; University; WBC; ZIKV; Zika; cd341; cell; conclusion; day; dna; donor; finding; method; patient; platelet; result; sample; table; test; transfusion; type summary = Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). doi = 10.1111/trf.14286 id = cord-014687-0am4l5ms author = nan title = SPR 2012 date = 2012-03-29 keywords = ACR; ADC; Administration; Case; Center; Children; College; DWI; Dr.; Drug; FDA; Food; Hospital; Imaging; MDCT; MRI; Materials; Medical; NF1; PET; Pediatric; Purpose; Radiology; Report; SPR; Society; University; child; clinical; conclusion; diagnosis; finding; image; patient; result; review; study summary = This presentation will focus on recent developments that have lead to a better understanding of the embryopathogenesis for fibropolycystic liver diseases (including choledochal cysts and Caroli disease), histopathological findings that have led to new classification systems for of pediatric vascular anomalies, technological advances and contrast agents in magnetic resonance imaging that are useful to characterize and limit the differential diagnosis of hepatic masses. Disclosure: Dr. Annapragada has indicated that he is a stock holder and consultant for Marval Biosciences Inc. Paper #: PA-067 Cardiovascular Image Quality Using a Nanoparticle CT Contrast Agent: Preliminary Studies in a Pig Model Rajesh Krishnamurthy, Radiology, Texas Children''s Hospital, rxkrishn@texaschildrens.org; Ketan Ghaghada, Prakash Masand, Abhay Divekar, Eric Hoffman, Ananth Annapragada Purpose or Case Report: Image quality in a separate study using a long circulating, liposomal-based nanoscale blood pool iodinated contrast agent (NCTX) suggests clinical utility in pediatrics, potentially reducing difficulties in contrast-CT of children with congenital heart disease (CHD) including the size of intravenous cannula, need for accurate timing, inability to simultaneously opacify multiple targets of interest (requiring repeated contrast administration and/or repeated imaging). doi = 10.1007/s00247-012-2356-8 id = cord-024833-e6vcf4un author = nan title = Forum date = 2019-12-19 keywords = Dec; FDA; Institute; drug; patient; report; safety summary = Approximately 80% of US hospitals rely on data and recommendations from the ECRI Institute to protect patients from unsafe practices and ineffective products, while the ISMP''s efforts to improve safety in patients have resulted in changes to clinical practice and public policy, including improvements in drug labelling, packaging, preparation and administration. The FDA has now announced the availability of a draft document entitled "Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff", which outlines the agency''s approach to timely postmarketing analyses of drugs and biologics, and "includes a high-level overview of tools, methods, and signal detection and evaluation activities, using varied data sources, for drug safety surveillance to provide a broader context and a general overview of our overarching effort and commitment in this area", says Woodcock. Analysis of spontaneous ADR reports to the European Medicine Agency''s EudraVigilance database has identified new safety signals for asthma drugs in paediatric patients, say authors of a study published in Drug Safety. doi = 10.1007/s40290-019-00321-z