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.

                               Eric Lease Morgan <emorgan@nd.edu>
                                                     May 27, 2019


Number of items in the collection; 'How big is my corpus?'
----------------------------------------------------------
786


Average length of all items measured in words; "More or less, how big is each item?"
------------------------------------------------------------------------------------
6451


Average readability score of all items (0 = difficult; 100 = easy)
------------------------------------------------------------------
47


Top 50 statistically significant keywords; "What is my collection about?"
-------------------------------------------------------------------------
66	Fig
62	RNA
60	virus
46	patient
44	cell
38	figure
38	MERS
34	infection
30	dna
28	respiratory
28	disease
24	Ebola
22	PCR
21	PEDV
21	China
19	RSV
18	IFN
17	vaccine
17	protein
17	influenza
15	Health
13	SARS
13	HIV
12	ICU
11	health
11	gene
10	Zika
10	ZIKV
10	IBV
10	HCV
10	East
9	study
9	HIV-1
8	viral
8	human
8	chinese
8	animal
8	USA
8	HBV
8	H1N1
8	ELISA
8	EBOV
7	risk
7	die
7	bat
7	activity
7	United
7	Middle
7	EVD
7	CMV


Top 50 lemmatized nouns; "What is discussed?"
---------------------------------------------
23569	virus
22525	cell
19136	patient
18969	%
16300	infection
15036	study
11336	disease
11235	protein
7874	case
7486	result
7095	group
7079	time
6874	analysis
6359	response
6337	influenza
6202	datum
6160	treatment
6096	gene
5744	level
5662	day
5633	method
5628	vaccine
5338	model
5181	effect
5100	activity
5015	risk
4935	antibody
4931	year
4902	system
4858	control
4732	sample
4694	health
4668	mouse
4511	type
4480	factor
4365	number
4211	expression
4195	rate
3986	p
3909	use
3734	detection
3705	population
3664	strain
3656	sequence
3639	child
3602	host
3597	role
3376	assay
3335	receptor
3300	animal


Top 50 proper nouns; "What are the names of persons or places?"
--------------------------------------------------------------
13228	al
10532	et
10050	.
4836	Fig
4728	RNA
2919	MERS
2763	PCR
2371	China
2303	CoV
2285	C
1887	T
1724	Health
1699	PEDV
1613	IFN
1591	A
1508	Table
1459	B
1444	Ebola
1414	S
1260	SARS
1214	HIV
1191	USA
1150	RSV
1096	RT
1071	II
1045	United
1040	mg
984	HBV
977	East
945	ZIKV
941	IBV
914	States
897	University
896	DNA
857	CD4
855	HCV
851	Zika
841	Middle
825	de
824	M
805	•
803	N
797	HIV-1
787	PBS
751	H1N1
749	mRNA
736	Africa
730	ELISA
724	Influenza
719	HA


Top 50 personal pronouns nouns; "To whom are things referred?"
-------------------------------------------------------------
12683	we
9177	it
3645	they
2871	i
1195	them
917	he
679	she
425	us
300	you
277	itself
197	one
152	themselves
46	her
37	me
31	him
17	nsp15
13	isgf3
8	u
8	s
7	yourself
7	ns3/4a
7	mrnas
7	imagej
7	ifitm3
7	herself
5	ourselves
5	ours
5	il-4rα
4	itims
4	himself
3	irbcs
3	hifnα
3	's
2	z004
2	t98hr
2	oneself
2	myself
2	mtorc1
2	interleukin-15
2	hlj-073
2	his
1	−
1	™
1	α2-macroglobulin
1	Þ
1	z2-cy5
1	z"ikv
1	yÞ
1	y903mxcj
1	y


Top 50 lemmatized verbs; "What do things do?"
---------------------------------------------
154175	be
26173	have
17402	use
8744	show
7647	include
6281	base
5460	associate
5366	increase
4929	report
4920	perform
4909	do
4527	follow
4498	identify
4366	find
4247	compare
3981	induce
3546	develop
3463	provide
3459	detect
3388	infect
3326	cause
3222	reduce
3147	suggest
3135	require
2886	describe
2821	observe
2808	determine
2743	bind
2698	indicate
2676	treat
2625	lead
2605	consider
2596	relate
2572	demonstrate
2536	present
2518	result
2507	contain
2324	occur
2316	make
2261	evaluate
2196	improve
2176	obtain
2156	know
2105	reveal
2041	remain
2030	give
1989	involve
1969	mediate
1962	test
1947	target


Top 50 lemmatized adjectives and adverbs; "How are things described?"
---------------------------------------------------------------------
12310	not
11267	-
8834	high
8451	also
8426	viral
7216	other
7083	respiratory
6499	human
6242	more
5553	clinical
5546	such
5374	low
5236	however
4924	well
4922	different
4384	only
4382	most
4347	specific
4099	immune
4010	first
3550	positive
3536	significant
3388	infectious
3228	new
3177	acute
3105	non
3033	severe
3025	as
3009	further
2873	early
2807	large
2786	then
2759	anti
2598	important
2587	significantly
2427	similar
2416	respectively
2344	long
2339	many
2331	several
2270	single
2263	antiviral
2256	small
2201	laparoscopic
2172	molecular
2158	common
2104	same
2097	therefore
2065	negative
2061	thus


Top 50 lemmatized superlative adjectives; "How are things described to the extreme?"
-------------------------------------------------------------------------
1121	most
592	high
555	least
519	good
435	Most
293	large
227	low
126	great
60	early
57	strong
57	close
56	bad
53	late
49	small
45	big
44	short
32	long
27	near
25	simple
17	common
14	fast
13	AuNPs
12	old
9	young
9	poor
8	deadly
7	broad
6	new
6	deep
6	-t
5	vRNA
4	weak
4	tremeGENE
4	safe
4	narrow
4	mild
4	-I
3	wide
3	rare
3	postt
3	postharv
3	p=0.016
3	cold
3	MOST
2	windy
2	vRNPs
2	thick
2	southernmost
2	slow
2	sick


Top 50 lemmatized superlative adverbs; "How do things do to the extreme?"
------------------------------------------------------------------------
3261	most
532	least
103	well
5	lowest
5	fast
4	worst
3	highest
2	youngest
2	long
2	-tag
1	®
1	shortest
1	scfv
1	operationalise
1	near
1	clustalw
1	cfdna
1	aunps
1	-www
1	-so
1	-i
1	-biotin


Top 50 Internet domains; "What Webbed places are alluded to in this corpus?"
----------------------------------------------------------------------------
99	doi.org
38	orcid.org
17	www.ncbi.nlm.nih.gov
16	www.mdpi.com
15	github.com
14	www
14	creativecommons.org
12	www.frontiersin.org
10	www.who.int
10	blast.ncbi.nlm.nih.gov
9	www.cbs.dtu.dk
7	creativecommons
5	tools.iedb.org
5	dx.doi.org
4	www.r-project.org
4	osf.io
4	doi
3	www.ebi.ac.uk
3	www.dovepress.com
3	www.cdc.gov
3	talk.ictvonline.org
3	dx
3	creat
2	wwwnc
2	www.who
2	www.syfpeithi.de
2	www.rcsb.org
2	www.megasoftware.net
2	www.ictv.global
2	www.genome.jp
2	www.blast2go.com
2	www.bioinformatics.babraham.ac.uk
2	web
2	viralzone.expasy.org
2	talk
2	string-db.org
2	primerexplorer.jp
2	ouhsc.edu
2	npg.nature.com
2	metascape.org
2	lke.utp.edu.pl
2	keras.io
2	internettrend.co.kr
2	github
2	en.wikipedia.org
2	crdd.osdd.net
2	codonw.sourceforge.net
2	clinicaltrials.gov
2	biocomp.chem.uw.edu.pl
2	bat1k.ucd.ie


Top 50 URLs; "What is hyperlinked from this corpus?"
----------------------------------------------------
14	http://www
11	http://creativecommons.org/licenses/by/4.0/
7	http://doi.org/10.1101/19008417
7	http://doi.org/10.1101/19004465
7	http://creativecommons
7	http://blast.ncbi.nlm.nih.gov/Blast.cgi
5	http://www.frontiersin.org/articles/10.3389/fmicb
4	http://www.cbs.dtu.dk/services/
4	http://doi.org/10.1128/mBio
4	http://doi.org/
4	http://doi
3	http://www.who.int/emergencies/mers-cov/en/
3	http://github.com/hackl/tikz-network
3	http://dx
3	http://creat
2	http://wwwnc
2	http://www.who
2	http://www.r-project.org/
2	http://www.r-project.org
2	http://www.ncbi.nlm.nih.gov/
2	http://www.ncbi.nlm.nih.gov
2	http://www.megasoftware.net/
2	http://www.ictv.global
2	http://www.genome.jp/kegg/
2	http://www.frontiersin.org/articles/10.3389/fimmu
2	http://www.blast2go.com/
2	http://web
2	http://talk
2	http://primerexplorer.jp/e/
2	http://ouhsc.edu/platelets/ditp.html
2	http://npg.nature.com/
2	http://metascape.org
2	http://lke.utp.edu.pl
2	http://keras.io/
2	http://internettrend.co.kr/trendForward.tsp
2	http://github.com/rnajena/bats
2	http://github.com/chjiao/VirBin
2	http://github.com/
2	http://github
2	http://dx.doi.org/10.7717/
2	http://doi.org/10
2	http://creativecommons.org/
2	http://codonw.sourceforge.net/
1	http://zikalliance.tghn.org/about/
1	http://www2c.cdc.gov/podcasts/player.asp?f=8632573
1	http://www.youtube.com/watch?v=DVJNWefmHjE
1	http://www.youku.com
1	http://www.who.int/influenza/human_animal_interface/2017_10_30_tableH5N1.pdf?ua=1
1	http://www.who.int/ihr/
1	http://www.who.int/csr/sars/country/table2004_04_21/


Top 50 email addresses; "Who are you gonna call?"
-------------------------------------------------
1	zhuli89@126.com
1	zhangb@smu.edu.cn
1	yannisun@cityu.edu.hk
1	xiyuxie89@126.com
1	xavier.lories@arlenda.com
1	whongning@163.com
1	wenying@gdciq.gov.cn
1	webmaster@eubs.org
1	vetschoice@guildinsurance.com.au
1	v.medvedev@univercells.com
1	stefan.acosta@med.lu.se
1	silviojr@ufv.br
1	sidiney@ufsj.edu.br
1	resen023@umn.edu
1	research@f1000.com
1	permissions@wiley.com
1	parkj@korea.ac.kr
1	nkengasongj@africa-union.org
1	n.perra@greenwich.ac.uk
1	mmdeoliveira@ufsj.edu.br
1	milyx117@163.com
1	marcelo.park@hc.fm.usp.br
1	maiblume@163.com
1	lena.schober@ipa.fraunhofer.de
1	lawrence.moon@kcl.ac.uk
1	journals.permissions@oup.com
1	jean-louis.romette@univmed.fr
1	hrhotline@ava.com.au
1	hexiaoen24@163.com
1	heijden@proteonic.nl
1	cs-japan@wiley.com
1	christine.burkard@roslin.ed.ac.uk
1	chienhai@163.com
1	battery203@163.com
1	avj@wiley.com
1	ahnik@korea.ac.kr
1	a.karampourian@sbmu.ac.ir
1	jkupiec@mednet.ucla.edu
1	hong.zhou@ucla.edu
1	1396320174@qq.com
1	13078431254@163.com


Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?"
-------------------------------------------------------------------------------
70	cells were then
31	data are available
25	results are consistent
24	cells were co
24	study did not
23	study are available
20	studies have also
18	activity is not
18	patients did not
18	results were not
18	study was not
17	cells were also
17	levels were significantly
16	results were consistent
15	% were male
15	group was significantly
15	patients were not
14	cells did not
14	group were significantly
14	study has several
13	cells were cultured
13	cells were further
13	groups were significantly
13	infection was not
13	virus infected cells
12	effect was not
12	patient did not
12	results did not
12	results were similar
12	treatment did not
12	virus was not
11	% were female
11	groups were similar
11	infection did not
11	studies did not
11	studies have not
11	vaccines are available
11	virus was first
10	results were also
10	studies are necessary
10	virus is not
9	case report data
9	cells were significantly
9	data are not
9	data were not
9	infection is not
9	patients had detectable
9	proteins are not
9	study does not
9	virus does not


Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?"
---------------------------------------------------------------------------------------
4	results were not significantly
3	disease is not fully
3	groups showed no significant
3	groups was not significant
3	study are not publicly
3	treatment did not significantly
3	virus is no longer
2	activity is not necessary
2	cases reported no symptoms
2	cells are not susceptible
2	cells has not only
2	data are not available
2	data were not available
2	data were not normally
2	disease is not only
2	genes were not statistically
2	levels are not significantly
2	levels were not different
2	methods were not satisfactory
2	patient had no further
2	patients had no detectable
2	patients had no relationship
2	protein is not essential
2	proteins are not essential
2	results have not yet
2	results were not as
2	studies are not ethical
2	studies have not yet
2	study found no association
2	vaccines are not widely
2	virus has not yet
1	% had no change
1	% had no formal
1	% had no significant
1	% had no training
1	% is not sufficient
1	% showed no signs
1	. are not consistent
1	. has no apparent
1	. reported no change
1	activities are not commonly
1	activities do not directly
1	activity is not as
1	activity is not detectable
1	activity is not dramatic
1	activity is not fully
1	activity is not present
1	activity is not significantly
1	activity is not solely
1	activity is not specific


Sizes of items; "Measures in words, how big is each item?"
----------------------------------------------------------
222162	cord-006849-vgjz74ts
182060	cord-009997-oecpqf1j
166047	cord-006854-o2e5na78
92230	cord-006466-e1phpqes
50613	cord-014597-66vd2mdu
32675	cord-032183-yqqqe325
29015	cord-015678-9b3eazd4
19358	cord-320053-uceukiie
18990	cord-286719-1xjmlwqr
18361	cord-301767-1jv20em8
17989	cord-274080-884x48on
17959	cord-015866-65zrbo1w
17749	cord-307046-ko3bdvo0
16347	cord-350836-1enteev7
16294	cord-022130-jckfzaf0
15843	cord-255339-oudj079q
15763	cord-009764-m9flptcv
15685	cord-303265-v6ci69n0
14893	cord-017148-o9qg2qta
14264	cord-016935-0wyl2h62
13993	cord-304488-t2jm1n77
13927	cord-327660-p1b07b4t
13173	cord-350019-4nlbu54e
12866	cord-103915-rzy7mejb
12783	cord-003596-6dg7i06i
12782	cord-277424-9aimvogs
12405	cord-018125-khhzlt9y
12249	cord-276907-b855tj7x
11854	cord-343596-w9rw2wak
11845	cord-018517-hrb1vt03
11845	cord-168862-3tj63eve
11584	cord-320674-skmxrkhf
11512	cord-017887-pj6pal35
11511	cord-282547-ehr9aaix
11388	cord-282251-r4on3lpr
11350	cord-017225-6ofi6mg5
11309	cord-269259-rpvl4vmu
11190	cord-253302-keh7s758
11112	cord-323987-gh1m05gi
11102	cord-267012-45tre8rn
11033	cord-318826-l922zqci
11025	cord-308884-erofmh39
11004	cord-328000-i9tzr13z
10978	cord-286136-gm6w590s
10973	cord-003441-810r5q03
10962	cord-304876-txaoz7oh
10751	cord-016814-tf17dpo5
10723	cord-003962-lg6gvgwt
10683	cord-312603-ear9cyri
10663	cord-252894-c02v47jz
10601	cord-280184-91d8i6ix
10577	cord-298032-3zlu8g8y
10440	cord-325112-7ie23c7f
10355	cord-332747-u46xryoo
10321	cord-003243-u744apzw
10271	cord-313777-eydkfqi2
10107	cord-254647-axyx03eg
10056	cord-312001-8p7scli8
10055	cord-011318-lw9vluxm
10040	cord-314915-b6aqwubh
9917	cord-003284-hjx2d5rq
9838	cord-256047-mabrmzd9
9832	cord-016575-bn15006x
9806	cord-286337-qk90xb3a
9775	cord-006892-n2ncamqh
9686	cord-281760-34wuttqw
9680	cord-351932-dn60t7qa
9640	cord-017534-0ai8chbu
9513	cord-273019-hbpfz8rt
9433	cord-323261-1of5ertf
9411	cord-280941-ds6x0yym
9409	cord-340629-1fle5fpz
9404	cord-322395-xeq4yix4
9387	cord-018454-sy21cpff
9369	cord-267965-84sotgds
9364	cord-018785-tcr5xlf8
9343	cord-017142-vx3rgs4r
9337	cord-333639-usgpe1cz
9284	cord-298805-ntpm68cg
9271	cord-027598-76656pok
9253	cord-313337-8w6bxqx4
9235	cord-262753-jld1ygxt
9215	cord-004017-gcmpatlb
9210	cord-317587-rrx2r4n2
9123	cord-263142-o8qbqxhx
9087	cord-331255-t85yioyl
9050	cord-276587-ynionj5r
8948	cord-003092-3owcqt3d
8937	cord-006039-vbq9izw3
8931	cord-003420-nnoni7qb
8921	cord-356094-sbtigcfr
8899	cord-292199-pl4d19w2
8897	cord-003602-wtestt8i
8876	cord-318495-1w74wf02
8844	cord-349011-kxhpdvri
8836	cord-301285-p83ondy8
8803	cord-003806-ctass7hz
8766	cord-017518-u2gsa4lg
8760	cord-333801-4pjdutgg
8739	cord-012035-rhpfpku9
8738	cord-334027-xhfmio7k
8656	cord-022708-rr3xua38
8644	cord-350389-6o9t2am7
8604	cord-285121-3cjr1rol
8592	cord-343107-oj1re34k
8567	cord-254181-nquozaxt
8527	cord-018239-n7axd9bq
8445	cord-282507-swxs5pr1
8419	cord-268149-narre5e7
8412	cord-003970-3e58229u
8386	cord-015527-ph576eji
8198	cord-018213-w6sh9f3h
8191	cord-301856-71syce4n
8181	cord-254317-n2knqj4z
8149	cord-347889-lpd1olqq
8120	cord-006971-5xgurlue
8115	cord-303186-2hxlx1j2
8058	cord-012374-excn1a10
8025	cord-318683-1yxurnev
8021	cord-329227-sqetz7h6
8010	cord-282204-j1slaefb
7979	cord-328940-8vtcochx
7978	cord-314567-purplsjn
7955	cord-260485-o5wpcxdp
7940	cord-016120-pz2q62i7
7926	cord-102233-50ldj8j7
7907	cord-335644-gt1ey9wz
7890	cord-003261-fz8ucwwm
7856	cord-352807-1yhxnvoh
7848	cord-022161-quns9b84
7844	cord-003318-abs9rvjk
7843	cord-003772-1345qct4
7817	cord-289321-ahl46ql9
7804	cord-319729-6lzjhn8j
7766	cord-268901-7cm6m1ol
7736	cord-267166-ecmayzr6
7722	cord-291295-7og5umiq
7703	cord-353553-adaow2w7
7693	cord-004020-qtwcbn7m
7680	cord-348131-pkovyjo6
7671	cord-003898-y6zpvw84
7659	cord-300083-qm27uw8r
7634	cord-011184-ohdukhqt
7626	cord-320979-25ytt84j
7600	cord-266127-phv08xe2
7592	cord-341907-vql8e2j3
7585	cord-306533-lvm11o4r
7582	cord-266487-ah3jclgw
7503	cord-003482-f1uvohf0
7492	cord-017903-92hnaiyc
7485	cord-342242-cynpob7b
7458	cord-003697-vmmlxr0o
7446	cord-003490-swlkjtyo
7426	cord-002957-gw2cow0d
7423	cord-273324-xhpv783y
7405	cord-346054-k84rcpav
7360	cord-004335-bw3tziup
7354	cord-016426-aw3wirmb
7335	cord-024742-hc443akd
7318	cord-255460-r5p5helx
7294	cord-284060-6eonuc8x
7286	cord-277265-p8pns7r9
7258	cord-288093-012ipcdr
7232	cord-266204-ipa017wz
7205	cord-017072-qwe1ne3q
7204	cord-333423-jhm7u8ka
7164	cord-313869-3x2qf3yu
7126	cord-007041-rloey02j
7115	cord-301810-vtgdqart
7111	cord-271122-3fsl5589
7111	cord-273326-gmw8gl2r
7107	cord-265642-7mu530yp
7102	cord-290253-hxxizipk
7037	cord-029717-wrueslce
7024	cord-018039-dw2xblyr
7021	cord-272728-inndwa61
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1955	cord-006325-3no74e74
1948	cord-003526-ykisq8nz
1942	cord-282062-h9smg0w9
1938	cord-319942-ava86u8y
1911	cord-297265-pwq5gir9
1894	cord-304066-rirbdhz3
1877	cord-275166-qduf08kp
1875	cord-272143-6ej3eibd
1851	cord-018459-isbc1r2o
1807	cord-014933-3jezc081
1802	cord-020750-zvwy7bgt
1776	cord-315355-a25ba7dz
1754	cord-325302-c4f58lsx
1742	cord-306450-sh2mrhoq
1727	cord-012607-bvxbzgx3
1673	cord-270703-c8mv2eve
1653	cord-346697-ixho9t5g
1627	cord-344184-ac2bhtdj
1621	cord-011189-c0ytamge
1620	cord-343206-9tqivs5f
1608	cord-331827-amg309uz
1601	cord-013523-hcd4bwy0
1579	cord-287131-svtdfeop
1541	cord-299421-xn17j7a6
1535	cord-299345-2i48ld8d
1526	cord-262017-utvy0i8l
1498	cord-103995-vok1dni9
1486	cord-304057-d2r92nji
1477	cord-012370-omz7kibf
1464	cord-325525-d1hsguds
1453	cord-005677-ijrghpco
1445	cord-268537-z7qga36v
1363	cord-277455-r69j2tnw
1290	cord-010919-h7d8z5z0
1261	cord-317254-6q4nzv9d
1249	cord-010854-mky7fufk
1209	cord-289096-wuegn0jg
1209	cord-314867-qg3hl5ft
1172	cord-286794-adbxzgvs
1112	cord-011800-8h7eiihp
1093	cord-012618-ulqajban
1089	cord-267816-84z9fp2u
916	cord-018832-g96earfl
826	cord-021055-ebcu3ywq
806	cord-320583-te8fv3gq
787	cord-319651-u7yrcto7
681	cord-268907-cv0mkpzd
677	cord-007337-if3ba9pk
668	cord-103770-4svaq0at
622	cord-012654-m8nlsutd
510	cord-284112-jobd5s4l
399	cord-012649-rxx5ash4
284	cord-011010-r8quizqn
153	cord-334109-9gv92yfh
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Readability of items; "How difficult is each item to read?"
-----------------------------------------------------------
77.0	cord-190332-uovhtaxb
72.0	cord-012649-rxx5ash4
68.0	cord-289584-rbp7p8s9
67.0	cord-268901-7cm6m1ol
65.0	cord-254317-n2knqj4z
64.0	cord-006773-61ezrjuq
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63.0	cord-002945-29nj4f05
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63.0	cord-344184-ac2bhtdj
62.0	cord-103242-78asegs6
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61.0	cord-255488-nvgz53su
61.0	cord-266288-buc4dd5y
61.0	cord-322629-kv83ekg0
61.0	cord-325302-c4f58lsx
61.0	cord-325525-d1hsguds
61.0	cord-354783-2iqjjema
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60.0	cord-022178-4oh02tlr
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60.0	cord-305156-w6iqeayr
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60.0	cord-348131-pkovyjo6
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59.0	cord-319942-ava86u8y
59.0	cord-324674-yd7idp90
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58.0	cord-010854-mky7fufk
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58.0	cord-269957-vd9ctqro
58.0	cord-291704-z6e7pmk8
58.0	cord-298166-045evk7g
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56.0	cord-304057-d2r92nji
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56.0	cord-309565-8syjr6k8
56.0	cord-310182-muybvyqa
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56.0	cord-340152-b4vg33ap
56.0	cord-342923-prgorr3d
56.0	cord-348063-5yd7hr5e
56.0	cord-350389-6o9t2am7
56.0	cord-353554-98uzivsk
56.0	cord-356242-tydil7d7
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55.0	cord-003404-eqgc8v7y
55.0	cord-003728-2sm0pgt7
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55.0	cord-023104-dpftawj3
55.0	cord-024742-hc443akd
55.0	cord-027598-76656pok
55.0	cord-257886-ytlnhyxr
55.0	cord-280442-jtvez46y
55.0	cord-284608-ba7wq52t
55.0	cord-286303-wo6356vq
55.0	cord-293562-69nnyq8p
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55.0	cord-347889-lpd1olqq
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54.0	cord-003334-ion97n4b
54.0	cord-003441-810r5q03
54.0	cord-011106-h20vbmbo
54.0	cord-011332-dzl09afq
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54.0	cord-012654-m8nlsutd
54.0	cord-016246-qqrv1npv
54.0	cord-103915-rzy7mejb
54.0	cord-252600-bvh1o64r
54.0	cord-255927-0tp4ig4o
54.0	cord-262036-wig4wdno
54.0	cord-269443-l8wj6dsy
54.0	cord-272973-kzaowysv
54.0	cord-276437-5gkdotvt
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54.0	cord-280957-cdd6ngf1
54.0	cord-284777-z7bd3a91
54.0	cord-286794-adbxzgvs
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54.0	cord-291295-7og5umiq
54.0	cord-291754-1zxztadu
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54.0	cord-300436-beb8k075
54.0	cord-307543-piust0s6
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54.0	cord-322395-xeq4yix4
54.0	cord-326558-6tss9ydx
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54.0	cord-334109-9gv92yfh
54.0	cord-342242-cynpob7b
54.0	cord-346697-ixho9t5g
54.0	cord-352231-awkkper2
54.0	cord-355465-qjtifwhd
53.0	cord-003482-f1uvohf0
53.0	cord-003507-22ylifqo
53.0	cord-003697-vmmlxr0o
53.0	cord-004069-nuep8nim
53.0	cord-005430-svidp7ar
53.0	cord-017531-fm8gl5b3
53.0	cord-022046-q1exf47s
53.0	cord-024741-j1wj47ah
53.0	cord-249962-ajnlbno7
53.0	cord-254747-vox5xsgd
53.0	cord-267791-v10eh408
53.0	cord-268537-z7qga36v
53.0	cord-270534-ebkwv4zo
53.0	cord-275643-lbikoyo3
53.0	cord-282466-r2sjv9ih
53.0	cord-289186-reyx10zo
53.0	cord-296487-m4xba78g
53.0	cord-300379-db79kb5c
53.0	cord-301285-p83ondy8
53.0	cord-302355-3se1wp8o
53.0	cord-304023-s22wi0t0
53.0	cord-308884-erofmh39
53.0	cord-319651-u7yrcto7
53.0	cord-320325-sjab8zsk
53.0	cord-322649-c99lszcu
53.0	cord-339235-8xslz4bs
53.0	cord-343390-y903mxcj
53.0	cord-351525-306syrrn
52.0	cord-003171-z22ekgtv
52.0	cord-003244-abs3tc3r
52.0	cord-003971-m59czkya
52.0	cord-004016-iaktm72a
52.0	cord-007337-if3ba9pk
52.0	cord-014914-7w8qxs4w
52.0	cord-015866-65zrbo1w
52.0	cord-016120-pz2q62i7
52.0	cord-016126-i7z0tdrk
52.0	cord-016575-bn15006x
52.0	cord-022161-quns9b84
52.0	cord-103523-46hn2249
52.0	cord-259182-2d5yedn2
52.0	cord-260946-n1ms8m9h
52.0	cord-263142-o8qbqxhx
52.0	cord-265679-7gzont7l
52.0	cord-279794-hn5vmic0
52.0	cord-287884-qxk1wfk8
52.0	cord-302401-oyhzn2kc
52.0	cord-302784-jkjdglns
52.0	cord-306450-sh2mrhoq
52.0	cord-308261-hxlebas8
52.0	cord-313869-3x2qf3yu
52.0	cord-317455-6qx0v28w
52.0	cord-324395-v5uiuhih
52.0	cord-335644-gt1ey9wz
52.0	cord-353325-41ke6vor
51.0	cord-003131-o7j6xq4s
51.0	cord-003138-9r1hg7ld
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51.0	cord-003318-abs9rvjk
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51.0	cord-009865-c5xj9asg
51.0	cord-010970-f79rnhc5
51.0	cord-011192-h0omskec
51.0	cord-012623-bc9fj29h
51.0	cord-014933-3jezc081
51.0	cord-017225-6ofi6mg5
51.0	cord-017534-0ai8chbu
51.0	cord-020544-kc52thr8
51.0	cord-032055-yddcme8z
51.0	cord-262094-b4yuh5y9
51.0	cord-262274-oununr9g
51.0	cord-267709-i2loz1xb
51.0	cord-268907-cv0mkpzd
51.0	cord-269259-rpvl4vmu
51.0	cord-274506-fzcuu4ma
51.0	cord-274773-3jhka8wl
51.0	cord-280941-ds6x0yym
51.0	cord-284484-oak1lfmi
51.0	cord-289205-or60zzjs
51.0	cord-290253-hxxizipk
51.0	cord-290833-m0wodqr3
51.0	cord-290861-5bxvenue
51.0	cord-294264-itz43cf6
51.0	cord-295491-zlah6u5s
51.0	cord-295640-mhfu0e9r
51.0	cord-320921-eumuid3r
51.0	cord-331641-u27ohm5p
51.0	cord-331835-nuhrd92z
51.0	cord-342124-jdv17u86
51.0	cord-343107-oj1re34k
51.0	cord-350964-0jtfc271
50.0	cord-002838-thygu6at
50.0	cord-002978-k676puoq
50.0	cord-003026-3l3kyypm
50.0	cord-003420-nnoni7qb
50.0	cord-003533-8m0vyxq8
50.0	cord-004020-qtwcbn7m
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50.0	cord-016361-upjhmfca
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50.0	cord-018066-s0zk9l6a
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50.0	cord-256855-s4pnq6j7
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50.0	cord-269093-x6taxwkx
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Item summaries; "In a narrative form, how can each item be abstracted?"
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cord-002828-ml6mgyf3	title: Application of extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome induced by avian influenza A (H7N9) viral pneumonia: national data from the Chinese multicentre collaboration Our study is aimed to investigate the current application, efficacy and safety of ECMO in for severe H7N9 pneumonia-associated acute respiratory distress syndrome (ARDS) in the Chinese population. Conclusions: ECMO is effective at improving oxygenation and ventilation of patients with avian influenza A (H7N9) induced severe ARDS. Conclusions: ECMO is effective at improving oxygenation and ventilation of patients with avian influenza A (H7N9) induced severe ARDS. Keywords: Extracorporeal membrane oxygenation (ECMO), Avian influenza A (H7N9), Acute respiratory distress syndrome (ARDS), Complications, Mortality Background Avian influenza A (H7N9) viral pneumonia can manifest with varying degrees of dyspnea and is associated with a mortality of~30% [1] . ECMO is effective at improving oxygenation and ventilation of patients with avian influenza A (H7N9)-induced severe ARDS.

cord-002838-thygu6at	In this work, we have used fluorescence in situ hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization. The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication. In this study, we have analyzed CCL5 mRNA expression patterns in the rat brain using in situ hybridization combined with immunohistochemistry to detect specific cell types (Grabinski et al., 2015; Lanfranco et al., 2017) . RNAscope in situ hybridization combined with immunohistochemistry revealed that in the CA1 region, in addition to neurons (Figures 6A1-4) , microglia (Figures 6B1-4) and oligodendrocytes (Figures 6E1-4) expressed CCL5 mRNA. Our data shows that under physiological conditions CCL5 mRNA is constitutively expressed in all glial cells (microglia, astrocytes and oligodendrocytes) as well as in a subset of neurons.

cord-002844-jv42o789	These results indicate that epigenetic modifications induced by influenza virus infection mainly target the histone component of host cell chromatin, with H3K79 residue methylation the most frequently modified. Dot1L inhibition caused an increase in viral replication, higher in cells infected with the natural isolates, which suggests a general role of H3K79 methylation in control of the influenza virus life cycle. At 8 h, we found a weak increase on IFNβ, IFN-stimulated gene 56 (ISG56) and interferon-induced protein Mx1 (Mx1) RNA levels after IFNαβ addition or influenza virus infection, and Dot1L inhibitor treatment did not significantly decreased their accumulation (Fig. 6B,C) . Given the role of H3K79 methylation in the control of IFN signaling, we analyzed the effect of Dot1L inhibitor on influenza virus replication in cells with normal or deficient IFN responses. Since H3K79 methylation does not affect influenza virus replication in cells with impaired IFN signaling, we analyzed the effect of Dot1L inhibitor in subsequent stages of viral infection.

cord-002853-vj8t28hn	BACKGROUND: We report a fatal case of disseminated adenovirus infection in a non-transplant haematology adult patient with chronic lymphocytic leukaemia who had completed combination chemoimmunotherapy a few months before developing respiratory symptoms. CASE PRESENTATION: This case started with an initial bacterial chest infection that responded to treatment, followed by an adenovirus pneumonitis that disseminated to his blood a week later with levels of up to 92 million adenovirus DNA copies/ml. We report here a case of adenovirus pneumonitis which led to a fatal disseminated adenovirus infection in an adult patient with chronic lymphocytic leukaemia (CLL) on chemotherapy. This patient''s chemotherapy regimen included fludarabine which has severe lymphopaenia as a recognised adverse effect, and which has been present in treatment regimens where various other viral reactivations have occurred, including hepatitis B [10] [11] [12] , BK virus [13] , herpes simplex and Epstein-Barr viruses [14] , cytomegalovirus [15] , as well as adenovirus [16] .

cord-002874-9rxv6fy9	Here we applied this approach to test the efficacy of the 222-nm far-UVC light to inactivate influenza A virus (H1N1) carried by aerosols in a benchtop aerosol UV irradiation chamber, which generated aerosol droplets of sizes similar to those generated by human coughing and breathing. If these results are confirmed in other scenarios, it follows that the use of overhead low-level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases such as influenza and tuberculosis. In conclusion, we have shown for the first time that very low doses of far-UVC light efficiently inactivate airborne viruses carried by aerosols. If these results are confirmed in other scenarios, it follows that the use of overhead very low level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases.

cord-002889-fie121ns	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).

cord-002893-d7hetoq0	
cord-002906-llstohys	OBJECTIVES: The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. 1 Therefore, to facilitate public health decisions about intervention and management in controlling the spread of infectious diseases, it is crucial to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. 18, 19 Here we assess that if, how, and to what extent, under different scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. We also estimated the age-specific admission infection fraction (IF) for each age group, including child (0-14 years), teenage and adult (15-64 years) , and elderly (65+ years), for different human behaviors or influenza risk perceptions.

cord-002926-7ereip3x	title: Dysregulated T-Helper Type 1 (Th1):Th2 Cytokine Profile and Poor Immune Response in Pregnant Ferrets Infected With 2009 Pandemic Influenza A(H1N1) Virus This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response. This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response. To determine whether a similar phenotype is present in pregnant ferrets, we measured the expression levels of inflammatory cytokines and chemokines by quantitative real-time polymerase chain reaction in the trachea (representative of the upper respiratory tract), lungs (representative of the lower respiratory tract), and bronchoalveolar lavage to evaluate responses in resident or infiltrating immune cells lining the airways [6] of pregnant and nonpregnant animals following infection.

cord-002932-5e7xrd1y	In the ferret model, these studies demonstrated that the inoculation of animals with highly pathogenic avian influenza H5N1 virus via the aerosol route led to higher nasal wash virus titers, earlier onset of clinical signs, and/or a broader spectrum of disease compared with infection via intranasal inoculation despite no difference in lethality [9] [10] [11] . On day 3 post-infection, VN3040 virus was recovered from nasal swabs of two and three animals in the conventional and aerosol method groups, respectively, and the mean virus titers were comparable between the two groups. Cynomolgus macaques were inoculated with 4 ml of a 10 7 PFU/ml solution of the highly pathogenic H5N1 avian influenza virus A/Vietnam/ UT3040/2004 strain (VN3040) through the aerosol route by using the ultrasonic nebulizer NE-U17 (defined as "the aerosol method group"). In contrast, VN3040 replicated well in the right-and left-lower lung lobes of the infected animals in the conventional method group [the virus mean titers were 3.51 and 4.75 log 10 (PFU/g), respectively].

cord-002945-29nj4f05	Detection of bovine viral diarrhoea virus 1 subgenotype 1c in extracts from cattle samples using quantitative real time PCR (qPCR). For cattle infected with BVDV-1c strain Trangie, one of the four animals tested positive on Day 2 post-infection, while all the other samples were negative throughout the sampling period (Table 1) . For cattle infected with BVDV-1c strain Trangie, one of the four animals tested positive on Day 2 post-infection, while all the other samples were negative throughout the sampling period (Table 1) . BVDV-1c was not detected via qPCR in the nasal swab or serum samples collected from all animals on Day 21, Day 28, Day 42 and Day 55 post-infection and were deemed to be negative (data not shown). BVDV-1c was not detected via qPCR in the nasal swab or serum samples collected from all animals on Day 21, Day 28, Day 42 and Day 55 post-infection and were deemed to be negative (data not shown).

cord-002948-hl9ysaxj	An experimental study with LPAIV H9N2 (A/chicken/Iran/SH-110/99(H9N2)) and an IBV live vaccine (H120 strain) was conducted concerning clinical signs, gross lesions, viral shedding, and mortality. Chickens, co-infected simultaneously with LPAIV H9N2 (A/Chicken/Iran/SH110/99) and IBV (IBV/4/91), reported severe clinical signs (respiratory distress, facial edema, conjunctivitis, depression, lacrimation, ruffled feathers, whitish watery diarrhea, and nasal discharge which continued until eight days post-infection), gross lesions (tracheal congestion, air saculitis, lung hyperemia, tubular cast formation in the tracheal bifurcation which extended to the lower bronchi, swollen kidney, and hemorrhagic pancreas and intestine), and mortality rate (5%), which were significantly different when compared with chickens infected separately with the same virus. In contrast, chickens infected with same LPAIV H9N2 strains alone showed no clinical signs, no virus was recovered from their blood, and there was lower replication efficiency in respiratory tissues [25] . Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses

cord-002952-13v4qvhg	• With broader adoption by scientists, journals, and funding agencies, preprints can complement peer-reviewed publication and ensure the early, open, and transparent dissemination of science relevant to the prevention and control of disease outbreaks. On February 10, 2016, more than 30 of the world''s largest and most prestigious public health journals and funding agencies issued a landmark statement on the importance of preprints and data sharing in public health emergencies such as the Ebola and Zika epidemics [2] . It is unclear to what extent journals are able to accelerate publication in outbreaks, but it is clear that every time there is an editorial or peer review decision, rejection, or revision there are delays, and that preprint posting precludes delays in broad access to the information. Despite this need and the 2016 statement on preprints and data sharing, less than 5% of Ebola and Zika journal articles were posted as preprints prior to publication in journals.

cord-002957-gw2cow0d	The aims of the current study were therefore to assess the performance of Reverse Phase (RP) and Hydrophobic Interaction Liquid Chromatography (HILIC) separation methods for Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) metabolomic profiling of bovine plasma and identify plasma metabolomic markers capable of differentiating between vaccinated and nonvaccinated calves following intranasal challenge with BPI3V. The selected panel of 383 unique AMRTPs (S3 Table) differentiating animals of different vaccination status at various time-points post-BPI3V challenge were deconvoluted to identify parent ion mass, adducts and low energy fragments using low and high energy data (Function 1 and 2 respectively), yielding 26 parent ions for elemental composition determination. The metabolomic profiling performed here in this study on post-BPI3V challenge acquired samples, has identified a unique panel of plasma metabolites which differ between vaccinated and non-vaccinated animals, and significantly are involved in recognised immune response mechanisms.

cord-002967-yy3bennu	Modulations of the ubiquitinproteasome proteolytic system, however, are not a general finding in cancer cachexia, as shown by studies reporting that it is not differently activated with respect to controls in the muscle of patients affected by non-small-cell lung cancer (NSCLC; [11] ) or esophageal cancer [12] . Finally, carfilzomib, an irreversible selective inhibitor of proteasome chymotrypsin-like activity, was shown to improve cachexia in tumor-bearing mice by inhibiting muscle protein breakdown [31] . Glutamine supplementation was reported to attenuate muscle protein wasting in cancer patients [68] , as well as to improve the energy balance in rats bearing the Walker 256 tumor [69] . Last but not least, treatments aimed at preventing/correcting the metabolic alterations underlying cancer-induced muscle wasting might also impinge on tumor-targeted therapies improving their effectiveness and/ or enhancing patient tolerance to chemotherapy.

cord-002978-k676puoq	In addition to FARP testing, which was performed solely for study purposes, the following microbiology studies were completed on the BAL sample as part of each patient''s routine clinical care: Gram stain, fungal smear, acid-fast smear, routine cultures (bacterial, fungal, viral, and mycobacterial), real-time PCR for influenza, respiratory syncytial virus (RSV), Pneumocystis jirovecii (PJP), adenovirus, and Legionella spp. e results of this study suggest that the FARP may be useful in the evaluation of ICH with suspicion of lower respiratory tract infection, as the yield of this test was higher in ICH (32%) compared to non-ICH patients (8%) (p � 0.02) ( Tables 2 and 3 ). e yield of routine microbiology testing (e.g., cultures and individual real-time PCR assays) in the ICH cohort was 25%, compared to the FARP being positive in 27% of NP swabs and 24% of BAL specimens.

cord-002982-zwvesrct	More recently, a loop-mediated isothermal amplification (LAMP) assay was successfully designed for field use in the grape powdery mildew pathosystem; however, false negatives or false positives were prevalent in grower-conducted assays due to the difficulty in perceiving the magnesium pyrophosphate precipitate at low DNA concentrations. The detection of airborne pathogen inoculum has been improved through the development of quantitative PCR (qPCR) assays that allow for near real-time monitoring of inoculum concentration (Carisse et al., 2009b; Rogers, Atkins & West, 2009; Temple & Johnson, 2011; Thiessen et al., 2016) . The use of a fluorescence resonance energy transfer (FRET)-based probe, allows for specific detection of LAMP products and target quantification from field samples without inhibiting amplification , and several portable fluorescence-reading LAMP devices have been made commercially available, such as the Genie (Optigene Ltd., West Sussex, UK) and Bioranger (Diagenetix, Inc., Honolulu, HI, USA).

cord-002985-2rtk9ppu	We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [(18)F]FDG and [(18)F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([(89)Zr]SAC55). Taken together, the radiolabeled anti-LTA mAb, [(89)Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. In conclusion, we have demonstrated the ability of an anti-LTA mAb immunoPET imaging probe to discriminate infection from non-specific inflammation in a preclinical mouse model of PJI.

cord-003006-lk2ny1wd	These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP). Lastly, VP35 is a suppressor of RNA silencing, functionally equivalent to the human immunodeficiency virus (HIV-1) Trans-activator of transcription (Tat) protein and important for viral evasion of the innate immune response [34] . The authors propose that this mutation is likely a result of EBOV adaptation to the human host, as several viral variants have been seen to increase human cell infectivity while decreasing virus entry in nonhuman primates [83] [84] [85] . In addition, many ebolavirus proteins are seen to interact with immune cells, causing cell activation and/or cell death and facilitating both viral replication and spread (e.g., by recruiting monocytes to infected cells or by increasing vascular leakage) as well as enabling immune evasion (e.g., antibody neutralisation by sGP and by cleaved GP), roles that were previously solely attributed to VP24 and VP35.

cord-003011-vclnb0eh	title: Predictors of In-Hospital Mortality among Patients with Pulmonary Tuberculosis: A Systematic Review and Meta-analysis The aim of this systematic review and meta-analysis is to identify predictors of in-hospital mortality among patients with PTB. Methods: We searched MEDLINE, EMBASE, and Global Health, for cohort and case-control studies that reported risk factors for in-hospital mortality in PTB. We therefore conducted a systematic review and meta-analysis to establish predictors of in-hospital mortality among patients with pulmonary TB. Eligible trials met the following criteria 1 : cohort or case-control design 2 ; explored risk factors for in-hospital mortality among patients with pulmonary TB in an adjusted analysis. This systematic review and meta-analysis is expected to serve as a basis for evidence to reduce in-hospital mortality in TB patients, and as a guide for future research based on identified knowledge gaps. Predictors of in-hospital mortality among patients with pulmonary tuberculosis: a protocol of systematic review and meta-analysis of observational studies

cord-003018-qrt07zmz	Using a www.oncotarget.com flow cytometer-based screening assay with Dox-treated and untreated iNTCP cells, we identified a hybridoma clone producing anti-NTCP mAb, clone 9A8 ( Figure 2B ). To test whether the 9A8 antibody can inhibit HBV infection, we pretreated iNTCP cells and primary human hepatocytes with 9A8 mAb and subsequently infected cells with wild type HBV and HBV encoding a luciferase reporter gene (HBV-NL) [21] . iNTCP cells (G) and primary human hepatocytes (H) were infected with HBV or its reporter virus (HBV-NL) respectively, in the presence of 9A8 mAb. Anti-HBs mAb (clone 33A4, which recognizes the PreS1 domain) was used as a control. In this study, we generated iNTCP cells, which have high NTCP expression and high susceptibility to HBV infection, and also developed a monoclonal antibody (mAb) that recognizes cell-surface NTCP. Although primary hepatocytes express NTCP at low levels for the uptake of bile acids, endogenous NTCP in hepatocellular carcinoma cell lines is not sufficient to achieve successful infection with HBV in vitro.

cord-003026-3l3kyypm	However, since 1998, the Chinese government has enacted several national biodiversity conservation regulations, such as the Natural Forest Protection Project and Ecological Forest Compensation, which have been effective in improving environmental conditions in many areas Xu et al., 2009) . What now remains to be done is to pull this societal potential and information together to facilitate large-scale forest restoration efforts that is critically needed for primate conservation. Since so many primate species in China are only hanging on as small remnant populations that are often only composed of a few groups (e.g., the cao vit gibbon population is estimated to only involve 18 groups occupying forest patches of only 2 000 hm 2 with only 3-4 groups in China (Fan et al., 2011) ) the only way to effectively promote conservation of these primates in the wild is through restoration.

cord-003044-9uqa39j9	
cord-003063-mowj6wyl	
cord-003070-6oca1mrm	On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. The computational results showed that the RPiRLS classifier outperformed the RPiRLS-7G classifier in terms of various performance measurements, indicating that the diversity of amino acids at a sequence is important for the prediction of RPIs. The performance of predicting RPIs was evaluated by using 10-fold stratified cross-validation on the RPI2662 data set. For the RPI369 data set as shown in Table 4 , the performance of the RPiRLS method was 0.85, 0.92, 0.84 and 0.86 for predictive accuracy, AUC, specificity and sensitivity, respectively. The work presented here provided a computational method, called RPiRLS, to classify RNA-protein pairs as interacting or non-interacting by integrating a sequence-based derived kernel with regularized least squares.

cord-003085-7krf1yxz	When analysis was limited to detection in blood, CMV infection without antiviral drug treatment or reactivation was not significantly associated with higher mortality (OR: 1.69, 95%CI 0.81–3.54, I(2) = 52%, n = 722; OR: 1.49, I(2) = 63%, n = 469). Thus, to acquire a better understanding of the potential role of CMV infection in contributing to mortality in critically ill patients, especially those not receiving antiviral agents and CMV detected in blood, we performed a meta-analysis of data available in the literature, focusing on the outcome in immunocompetent ICU patients with CMV infection. We obtained information on basic study characteristics (author, year of publication, country of origin, study period, setting, and study design), characteristic population, the site and detection method of sample, CMV seropositivity, CMV infection incidence, all-cause mortality, length of ICU/hospital stay, length of mechanical ventilation, and administration of antiviral drugs.

cord-003091-uvfppirt	
cord-003092-3owcqt3d	These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses. Deep genomic sequencing of nine sets of paired clinical samples (primary nasal swabs in viral transport medium) and culture isolates (culture harvest from zero passage virus) led to discovery of a number of HN mutations associated with rapid evolution in culture. To assess the frequency of mutations identified earlier, we also performed deep sequencing of 118 HPIV-3 clinical samples and culture isolates from the University of Washington Virology Laboratory, allowing us to confirm that the alterations associated with brief exposure to culture for viral isolation were almost entirely found in the sequences of culture isolates and found commonly within populations of viruses in those isolates.

cord-003099-a0acr28o	In vitro studies in which influenza-infected alveolar macrophages were subsequently stimulated with bacterial lipopolysaccharide (LPS), a bacterial compound that induces a profound innate immune response, revealed increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 [4] [5] [6] [7] [8] , indicative of a priming effect on these cells by influenza. Likewise, murine influenza infection resulted in increased levels of pro-inflammatory cytokines in both plasma and lungs, and enhanced pulmonary neutrophil influx upon pneumococcal infection 7 days later [10] . In the present study, we demonstrate that a systemic LPS challenge in the acute phase of influenza infection (4 days post-infection) results in an enhanced pulmonary, but not systemic pro-inflammatory cytokine response. Our results are in accordance with in vitro data reporting a cellular priming effect of influenza observed upon secondary stimulation with LPS [4] [5] [6] [7] [8] , as well as with other murine in vivo studies that report increased inflammation and pulmonary neutrophil influx or sequestration upon a secondary bacterial infection or LPS challenge in the acute phase of influenza infection [9, 10] .

cord-003109-3eeykk89	The results of in vivo studies showed that the levels of triglycerides (TG), total cholesterol (TCHO) and low-density lipoprotein cholesterol/high density lipoprotein cholesterol (LDL-C/HDL-C) were significantly decreased (p<0.05) in the liver of rats treated with preserved eggs. The results shown in this study demonstrated that preserved eggs may be a novel functional food involved with antilipemic, anti-inflammatory activity as well as the effect on accelarating the apoptosis of Caco-2 cells. Studies have shown that preserved egg white hydrolysates show anti-inflammatory effects in vitro and in vivo experiments and can significantly decrease the expression levels of IL-8 and TNF-α (Zhao et al., 2017) . The levels of liver lipid and inflammatory factors in rats before and after treatment, as well as the ability of preserved eggs to inhibit tumor cells in vitro were investigated. The results showed that preserved egg digests can significantly induced the cell apoptosis by up-regulating caspase-3 levels in Caco-2 cells.

cord-003118-58ta20fg	
cord-003122-a3f4l6iu	
cord-003127-1t0mklwi	Ten countries were directly impacted, three of which experienced significant outbreaks (Guinea, Liberia, and Sierra Leone), while seven countries reported one or more EVD cases without widespread human-to-human transmission (Italy, Mali, Nigeria, Senegal, Spain, the UK, and the US) [9, 10] . Specifically, we 1) conduct a quantitative analysis of country-specific factors in Guinea, Liberia, and Sierra Leone and 2) conduct a qualitative analysis of patterns of disease incidence and transmission among all countries with ≥1 case of EVD to draw lessons learned from the 2014 West African Ebola outbreak for managing emerging transnational health security threats. Although four new confirmed cases were diagnosed in Guinea during March 17-28, the WHO Director-General declared on March 29, 2016 the end of the Public Health Emergency of International Concern regarding the EVD outbreak in West Africa [9] .

cord-003130-p2h8p5bm	
cord-003131-o7j6xq4s	Results revealed that prostate cancer pathology and cell proliferation in CXCL9+DMAB mice were significantly greater compared with the C57+DMAB mice. In addition, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that CXCL9 mRNA expression in clinical samples was positively associated with clinical pathological stages of prostate cancer. The results demonstrated that high expression of CXCL9 downregulated the levels of IL-6 and TGF-β in tumor tissues compared with C57+DMAB mice (Fig. 3A and B) . Therefore, it was concluded that CXCL9 reduced the secretion of IL-6 and TGF-β via the reduction of the number of T cells in immune organs and the tumor microenvironment, and promoted the development of prostate cancer. CXCL9 overexpression reduced the number of T cells in immune organs and the tumor microenvironment, and reduced the secretion of IL-6 and TGF-β2, and thereby promoted the development of prostate cancer.

cord-003133-6gjepq1h	In this review, we provide a detailed discussion of the currently developed biosensors based on the aforementioned unique optical features of GNPs. Mainly, we focus on four different plasmonic biosensing methods, including localized surface plasmon resonance (LSPR), surface-enhanced Raman spectroscopy (SERS), fluorescence enhancement, and quenching caused by plasmon and colorimetry changes based on the coupling of GNPs. We believe that the topics discussed here are useful and able to provide a guideline in the development of novel GNP-based biosensors in the future. Each section individually focuses on one of the following: LSPR, SERS, plasmon-enhanced fluorescence and quenching, and colorimetry changes based on the coupling of plasmonic GNPs. One of the most well-established unique optical characteristics of GNPs that is widely utilized for the development of biosensors is their localized surface plasmon resonance (LSPR) phenomenon [19, 20] .

cord-003138-9r1hg7ld	title: A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial BACKGROUND: Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. falciparum in tissue culture flasks for in vitro production of Good Manufacturing Practice (GMP) grade blood stage malaria cell banks was recently described [8] . Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines

cord-003158-mhlqnj52	Previous studies have demonstrated that the HCV JFH1 NS5A C-terminal is a flexible region which is capable of accommodating foreign gene inserts (such as EGFP, 720bp and Rennilla luciferase [Rluc] , 930bp) and still permit HCV replication and viral production (18, 19, (24) (25) (26) (27) (28) (29) . In this study, we used the JFH1-AM120 as a vector to explore if infectious reporter virus would be produced following insertion of LacZ gene that was three time larger than Rluc, into the NS5A C-terminus. This result provided evidence that fusion protein of NS5A and β-galactosidase can be co-expressed in Huh7.5 cells after transfection of JFH1-AM120-LacZ RNA. Our results demonstrate that the LacZ reporter gene can be inserted into the NS5A C-terminus of HCV JFH1-AM120 and will express the predicted NS5A-LacZ fusion protein, which can be detected by western blotting three days after RNA transfection of cells.

cord-003169-bdw5ke4i	
cord-003171-z22ekgtv	title: Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment METHODS: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A(H2N2) viruses were performed across age groups in Rochester, New York, and Hong Kong, China. In this study, we evaluated population immunity using HAI assays against human and avian H2N2 influenza strains in different age groups in the United States and Hong Kong. The prevalence of titers ≥1:40 against the test viruses is shown for sera from Rochester and Hong Kong in persons born before the 1957 H2N2 pandemic, during the years that H2N2 circulated (1957-1968), or after 1968 is shown in Figure 1 . The comparability of data from 2 geographically separated areas of the world, Rochester and Hong Kong, argues for the representativeness and generalizability of such studies that aim to assess population immunity to viruses of pandemic concern.

cord-003173-ymsl7snv	BACKGROUND: Foodborne norovirus outbreak data in Japan from 2005–2006, involving virological surveillance of all symptomatic and asymptomatic individuals, were reanalyzed to estimate the asymptomatic ratio of norovirus infection along with the risk of infection and the probability of virus shedding. METHODS: Employing a statistical model that is considered to capture the data-generating process of the outbreak and virus surveillance, maximum likelihood estimation of the asymptomatic ratio was implemented. RESULTS: Assuming that all norovirus outbreaks (n = 55) were the result of random sampling from an identical distribution and ignoring genogroup and genotype specificities, the asymptomatic ratio was estimated at 32.1% (95% confidence interval [CI], 27.7–36.7). The present study aims to estimate the asymptomatic ratio of norovirus infection, reanalyzing foodborne outbreak data with laboratory testing in Japan, along with other parameters, including virus shedding frequency and the risk of infection.

cord-003219-iryb3v0z	title: Predictors of survival in patients with influenza pneumonia-related severe acute respiratory distress syndrome treated with prone positioning CONCLUSIONS: In the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ARDS, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning. After multivariate Cox regression analysis, PSI, renal replacement therapy and increased dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning. The present study in influenza pneumonia-related ARDS patients receiving prone positioning also found that increased dynamic driving pressure (hazard ratio 1.372, 95% confidence interval 1.095-1.718; p = 0.006) was identified as After multivariate Cox regression analysis, it was found that PSI, renal replacement therapy and increased dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumoniarelated ARDS receiving prone positioning.

cord-003232-nquw7qga	This review examines the recent discovery of novel influenza viruses in bats and cattle, the evolving complexity of influenza virus host range including the ability to cross species barriers and geographic boundaries, and implications to animal and human health. In addition, we discussed the growing complexity of influenza virus-host interactions and highlighted the key research questions that need to be answered for a better understanding of the emergence of pandemic influenza viruses. Ability to infect a wide range hosts is a key contributing factor to the complex and seemingly expanding genetic diversity of IAVs. It is now well established that IAVs infect domestic pets such as dogs and cats, adding to the list of host species that could potentially expose humans to influenza viruses. Although influenza viruses infect humans and a wide range of animals and birds, cattle were never considered to be susceptible to influenza virus infection.

cord-003243-u744apzw	METHODOLOGY AND PRINCIPAL FINDINGS: We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations. We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYM-FASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations.

cord-003244-abs3tc3r	In 1978, the national Expanded Program on Immunization (EPI) in China started to implement a standard schedule for the routine administration of one dose of measles-containing vaccine (MCV1) among children between 8 and 24 months of age. In the present study, we compared the age-specific R of measles infections between different age groups by using laboratory and clinically confirmed data collected from 2009 to 2016. The R values estimated for children aged 7-15 years were low across the study period in general, even though the values also increased since 2012, indicating that primary and secondary school students had a limited contribution to measles transmissions. In this study, we compared the age-specific R of measles infections between different age groups, using laboratory and clinically confirmed data from 2009 to 2016 for Guangdong Province.

cord-003246-3ajfb18m	Previous studies have shown that lung injury in patients with HFMD is associated with neurogenic pulmonary edema (NPE) after EV71 infection of the brainstem, rather than with direct viral invasion (Jiang et al. Protein edema in the alveolar space with fibrin exudation was observed inside, and some alveoli were filled with mononuclear cells, alveolar macrophages, exfoliated epithelial cells and cell debris (G); the alveolar septum was widened, the capillaries in the septum were highly dilated and congested, with infiltration of inflammatory cells (H); intrapulmonary bronchitis and bronchiolitis, diffuse or focal infiltration of inflammatory cells in the wall and surrounding tissues (I, J); compensatory emphysema phenomenon of ruptured alveolar wall and fusion of pulmonary alveoli (K); the lymph nodes near the hilar bronchus indicated a reactive hyperplasia, germinal center enlargement, paracortical zone atrophy, and lymphocyte depletion (L) (black arrow). Lung tissues of EV71 infected patients with severe HFMD showed interstitial pneumonia and positive viral antigens in the pulmonary epithelial cells and macrophages.

cord-003254-yiqdsf9z	Herein, we present a new statistical method for detecting overlapping genes in different reading frames that relies on only a single nucleotide sequence of a gene or genome. For the synonymous mutation test (C), codons that preserve the original amino acid sequence are randomly generated and the length of ORFs on alternative reading frames subsequently measured (note that codon replacement is not restricted to the example mutations shown in the figure, all of which occur in the third nucleotide positions, and that codon replacement with the original codon is also possible). Accordingly, whole genome sequences were downloaded from 2548 reference linear RNA viruses available on GenBank; this produced a total of 6408 coding regions that were used to estimate the sensitivity and false discovery rate of each test. where C is the empirical cumulative distribution function of the theoretical distribution of lengths calculated by permuting codons in the original coding sequence: that is, C(L) is the Simple Method to Detect Candidate Overlapping Genes .

cord-003261-fz8ucwwm	L * is only expressed by TMEV and is important for infection of macrophages, persistence of the virus in mice and inhibiting RNase L (van Eyll and Michiels, 2000; Sorgeloos et al., 2013) , 2B * results from a frameshifting mechanism conserved in cardioviruses that regulates the ratio of structural and non-structural proteins translated over time. (2012) , which was based on Influenza virus infection and suggests that PKR triggers the formation of "antiviral stress granules" that serve as a recruitment platform for dsRNA and RIG-like helicases, thereby enhancing IFN production. Like 3C proteases of other picornaviruses that were shown to target critical factors involved in IFN induction such as RIG-I (Barral et al., 2009) , EMCV 3C was reported to cleave TRAF family member-associated NF-kB activator (TANK) in infected cells, thus disrupting the complex involving TBK1, IKKe and IRF3 and limiting type I IFN production (Huang et al., 2017) .

cord-003270-vu9b5a14	
cord-003284-hjx2d5rq	Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. To analyze the genetic stability of the recombinant ZIKV harboring the point mutation A175V in the coding region of the NS2A protein (rZIKV-RGN-mNS2A), total RNA was purified from Vero cells infected with viruses from passage 1 (P1) to passage 5 (P5) using the RNeasy minikit (Qiagen), according to the manufacturer''s specifications. To investigate whether the reduced RNA synthesis of rZIKV-RGN-mNS2A in Vero cells could result in viral attenuation in vivo, the ability of the mutant virus to induce pathogenesis was analyzed in A129 mice and compared with that of the parental rZIKV-RGN ( Figure 6 ).

cord-003307-snruk3j2	BACKGROUND: Despite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate. Based on the high burden of PcP and the likelihood of unfavorable outcome particularly in non-HIV-positive patients, chemoprophylaxis with trimethoprim-sulfame thoxazole (TMP-SMX) is recommended in high-risk populations [13] . We here report comprehensive epidemiological, clinical, laboratory, therapeutic and outcome data on 240 cases of PcP, including a high percentage of non-HIV-positive patients, in a tertiary care center over the last 17 years. For every patient, clinical data on demographic characteristics, underlying disease, status of immune competence, treatment regimens of immunosuppression, PcP therapy regimen and mortality, were gathered in the study database. Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: a retrospective cohort study

cord-003318-abs9rvjk	Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. We therefore inferred that testosterone (8) was first glycosylated at the 17β-hydroxyl group by OsSGT1 to form T-17β-G (8a), which was then selectively acetylated at C-6 0 of sugar moiety to yield the 6 0 -AT-17β-G (8b) by a soluble bacterial acetyltransferase ( Supplementary Information Fig. S52) . The optimal pH and temperature of OsSGT1-catalyzed reaction using the cell-free extract of BL21(DE3)[pET28a-OsSGT1þp-Gro7] as the biocatalyst were first determined to be alkaline pH value of 11 and 50 1C, respectively (Supplementary Information Fig. S62 ).

cord-003325-d3d1n9qa	
cord-003334-ion97n4b	Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Considering that we observed a significant reduction in the IBV induced morbidity and mortality of in ovo CpG ODN pre-treated birds correlating with varying degrees of increased macrophages, CD4+, and CD8α+ T cells in the tracheal and lung tissues, we needed to further elucidate the mechanisms by which these immune cells were efficiently recruited.

cord-003357-4qrg6lqu	Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen. Viral infections played an important role in pediatric lower respiratory tract infections, and the corresponding common viral pathogens were influenza A and B virus (IAV and IBV), parainfluenza virus (PIV, type 1 to 3), respiratory syncytial virus (RSV) and human adenovirus (ADV) (Pavia, 2011) . In this report, the prevalence of common viruses in the lower respiratory tract infection of hospitalized adult patients from Harbin, China was explored in hopes of revealing the clinical and pathogenic features of respiratory viruses. The overall detection rate of viral infection among hospitalized adult patients in this report is 14.5%, which was consistent with the result of 16.8% in the age group above 14 years old by a national survey from 2009 to 2013 in China (Feng et al., 2014) .

cord-003376-2qi4aibx	title: Effect of cytomegalovirus reactivation on the time course of systemic host response biomarkers in previously immunocompetent critically ill patients with sepsis: a matched cohort study Cytomegalovirus (CMV) reactivation is observed in 14-41% of intensive care unit (ICU) patients without known prior immune deficiency [1] [2] [3] and is associated with increased morbidity and mortality [4] [5] [6] . Therefore, this longitudinal study aimed to investigate whether the temporal course of seven host response biomarkers, including both pro-and anti-inflammatory cytokines, in previously immunocompetent ICU patients with sepsis differs between patients with and without CMV reactivation. Time trends of various markers within patients were described by symmetric percentage differences relative to their levels 2 days prior to CMV viremia onset (Fig. 2 for primary comparison, Additional file 1: Figure S1 for secondary comparison). We performed an explorative study to compare time trends of host response biomarkers in patients with reactivation that were matched to non-reactivating control patients who were either seropositive or seronegative for CMV.

cord-003377-9vkhptas	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.

cord-003378-0ozhye9q	
cord-003382-v3w1wi5c	
cord-003396-yu6mw601	By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. On the other hand, the dynamic network marker/biomarker (DNM/DNB) method was developed to quantitatively identify the tipping point or the critical state during the dynamic evolution of a complex system based on the observed data. To further reliably identify the critical state of flu outbreak, we developed a new method called the landscape DNM, which explores F I G U R E 1 Schematic illustration to detect early-warning signals of influenza outbreak based on the DNM method. C, Based on the historical and current clinic records, and regional geographic characteristics of a city, the DNM score is able to provide the early-warning signals of the upcoming influenza outbreak as a real-time indicator monitoring both the local and global records as well as the network structure, and the detailed algorithm is provided below.

cord-003404-eqgc8v7y	We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. In vitro studies reported that monocytes from G6PD-deficient individuals had increased susceptibility to dengue virus serotype 2 infections along with higher viral replication [5, 6] . Herein, we investigated the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. Out of 212 enrolled patients, 16 were excluded (2 did not have Glucose-6-phosphate dehydrogenase deficiency on dengue infection in children sufficient blood volume, 11 had a negative dengue result, and 3 lacked quantitative G6PD results). Severe dengue was not associated with a G6PD deficiency phenotype nor genotype variants whether we used a cut off of < 30% (i.e. only including hemizygous males and homozygous females) or a cut off of < 60%, corresponding to classes I to III of the WHO classification (Table 5) .

cord-003420-nnoni7qb	The −1 PRF efficiencies induced by a downstream dnaX hairpin in the presence of upstream internal SD mediated duplexes with different spacings toward the frameshifting site ( Figure S1B ,D) were similar to those reported in vivo [12] , indicating that the experimental platform can faithfully reproduce this −1 PRF model system. To compare upstream hairpins with SD anti-SD duplexes in frameshifting regulation, we used the A6G slippery sequence with a modified pseudoknot (mPK) derived from the infectious bronchitis virus (IBV) 1a/1b gene [14, 23] , and the CUUUGA frameshifting site of RF2 for −1 and +1 PRF analysis, respectively ( Figure 1) . (D) Radioactivity-based +1 PRF assay by SDS-PAGE analysis of 35 S methionine-labeled in vitro translation products, with calculated +1 frameshifting efficiencies shown, for different upstream duplex constructs in (A).

cord-003425-c5jdp5jv	RESULTS: Clinical characteristics revealed that HAdV-7 infection caused more severe pneumonia, toxic encephalopathy, respiratory failure, longer mean hospitalization, significantly lower white blood cell (WBC) and platelet counts, compared to those of HAdV-3. In the present study, therefore, we undertook a comprehensive analysis of the comparative clinical features of HAdV-3 and HAdV-7 infection, as well as a serial of experiments, were performed to better understand the association between severity of the disease and the serotypes of HAdVs. Participants, demographic data, clinical data analysis Patients ranging in age from 1 month to 16 years and requiring inpatient treatment due to acute respiratory tract infections (ARTI) at the Department of Respiratory Medicine, Children''s Hospital of Chongqing Medical University between June, 2009 and May, 2015, were enrolled in this study. Since type-specific adenovirus infection is known to cause different tissue tropisms and clinical manifestations as indicated before, viral loads and fitness of HAdV-3 and HAdV-7 were evaluated in several human epithelial cells to determine if there were differences.

cord-003441-810r5q03	Specifically, that CCHFV vOTU DUB activity is not as promiscuous towards ubiquitinated host proteins as it first seemed based on the overexpression studies, but appears to be restricted to a targeted subset of cellular substrates associated with suppression of RIG-I-mediated early cellular responses to infection. Additionally, a structure of the FARV vOTU provides details into the structural nature of the additional residues in Hughes orthonairovirus vOTUs. Structureinformed mutagenesis of FARV vOTU identified residues involved specifically in di-Ub binding, representing the first report of the role of a second site involved in di-Ub binding in nairovirus vOTUs. This novel enzymatic and structural data not only provides insight into the nature of vOTU diversity, but also lays a foundation for understanding the impact of the vOTU interaction with the innate immune response and its connection to viral pathogenesis. Intriguingly, the vOTUs showed a diverse range of activity towards Ub. In general, vOTUs can be divided into groups possessing high (CCHFV, HAZV, NSDV/GANV, TAGV), moderate (DUGV, KUPEV, FARV, QYBV, ISKV), or low activity (ERVEV, DGKV, LPHV, HpTV-1) (Fig 2A) .

cord-003447-kbpvt5on	This study interviewed pig traders operating at Uganda''s only registered pork abattoir to describe their characteristics, business practices, biosecurity practices, and pig health management and reporting practices. Given pig traders'' important role in supplying pork for a rapidly expanding consumer base and linking farmers with consistent markets, a better understanding of their practices and motivations around purchasing, transportation, and pig health management is needed. Therefore, the objectives of this study were to (1) describe pig trader characteristics, trading practices, biosecurity practices, pig health management, and reporting practices and (2) map source locations of pigs purchased to supply pork through the major abattoir in Uganda. Furthermore, we observed trader brands on pigs at slaughter (e.g., number or letter carved on the animal at the time of purchase) and asked participants who had completed the interview if they could identify the trader who supplied the pig.

cord-003466-599x0euj	MAIN TEXT: The 1918 H1N1 pandemic virus spread across Europe, North America, and Asia over a 12-month period resulting in an estimated 500 million infections and 50–100 million deaths worldwide, of which ~ 50% of these occurred within the fall of 1918 (Emerg Infect Dis 12:15-22, 2006, Bull Hist Med 76:105-115, 2002). Influenza viruses have posed a continual threat to global public health since at least as early as the Middle Ages, resulting in an estimated 3-5 million cases of severe illness and 291,243-645,832 deaths annually worldwide, according to a recent estimate [1] . To be considered a pandemic, an influenza virus must: i) spread globally from a distinct location with high rates of infectivity resulting in increased mortality; and ii) the hemagglutinin (HA) cannot be related to influenza strains circulating prior to the outbreak nor have resulted from mutation [14, 15] .

cord-003472-ml4pbewf	
cord-003482-f1uvohf0	Quantitative probe-based reverse transcription PCR (qRT-PCR) was performed on seruminoculated Vero cell supernatants, serum, brain, lung, liver, spleen, kidney, urinary bladder, prostate and testes from bats from both studies. Brain and testicular tissues stained with both goat polyclonal goat anti-Iba1 (green) and monoclonal 4G-2 flavivirus E specific antibodies (red) showed co-localization (yellow) of ZIKV antigen in cytoplasm of activated microglial cells with their characteristic morphology in the cerebral cortex of infected bats 10 dpi in the time course study and 28 day dpi in the pilot study (Fig 9) . Two bat infection experiments were conducted in this investigation; 1) a pilot study to determine susceptibility of Jamaican fruit bats to ZIKV infection, and 2) a time course study to better understand pathophysiology and chronology of events pertaining to the dynamics of viremia, viral tropism, replication and shedding of the virus in a New World bat species.

cord-003490-swlkjtyo	The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. This current study focused on investigating the concept of θ and ω for direct contact transmission of a virulent strain of foot-and-mouth disease virus (FMDV) amongst juvenile domestic pigs, and examining the impact of pre-clinical transmission on simulated outbreak size and severity within a US swine production system assuming either optimal or suboptimal response conditions. The most noteworthy findings from this approach were the substantial changes in the modeled estimates of the duration of latency and subclinical infectiousness (ω) when defining the onset of infectiousness by either the occurrence of clinical signs of FMD in donor pigs or by any detection of FMDV RNA in OPF.

cord-003507-22ylifqo	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.

cord-003514-yyzbv7ys	
cord-003523-byxuruk1	
cord-003526-ykisq8nz	title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis BACKGROUND: We report hereby a severe case of Hantavirus Pulmonary Syndrome" (HPS) induced by Maripa virus in French Guiana and describe the mechanism of severity of the human disease. CONCLUSIONS: The severity of HPS caused by the virus Maripa in French Guiana can be explained by the tropism of hantavirus for the microvascular endothelial cell leading to a CLS. We report here a human case of acute Maripa virus related pulmonary syndrome managed in the ICU of French Guiana with a clear evidence of associated capillary leak syndrome responsible for the severity of the disease. Two patients with severe capillary leak syndrome caused by a Puumala hantavirus infection were successfully treated with a bradykinin receptor antagonist [11, 12] . Hantavirus pulmonary syndrome caused by Maripa virus in French Guiana

cord-003527-1ahxau9k	
cord-003533-8m0vyxq8	We present a case series of severe leptospirosis with cardiac involvement observed during a period of one month at Colombo-North Teaching Hospital, Sri Lanka. CASE PRESENTATION: We report here five patients with severe leptospirosis complicated with cardiac involvement, admitted to a single medical ward, Colombo-North Teaching Hospital, Sri Lanka during a one-month period. In this case series, we describe a series of male patients with severe leptospirosis with cardiac involvement, presented to a single medical ward during a period of one month. By day eleven of illness he was completely recovered clinically and full blood count, liver function tests, renal function tests and ECG were normal. Patient was discharged from the ward on day 7 of illness with complete recovery and normal full blood count, renal and liver function tests. Despite adequate fluid resuscitation patient developed shock with low urine output on the same day of admission.

cord-003539-tazd6dvm	
cord-003571-upogtny6	In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. age patterns; history of epidemiology; influenza; mortality; pandemic; prior immunity One hundred years after the fact, the 1918 influenza pandemic remains one of the most important epidemics of the modern medical era; it was significant for its impact on both human health and the development of epidemiology and other medical sciences.

cord-003596-6dg7i06i	The rise of mRNA nanomedicines is rapidly advancing their applications in a wide range of biomedical fields, such as vaccination, protein-replacement therapy, gene editing, and cell reprogramming and engineering. The four major biomedical applications of mRNA nanomedicine include: 1) nanovaccines derived from antigen-encoded mRNA for the activation of the immune system; 2) proteinreplacement therapy for the treatment of genetic disorder diseases and cancer due to the mutation or loss of protein expression; 3) gene-editing achieved by the co-delivery of Cas9-encoded mRNA and gRNA; and 4) cell programming and engineering through the introduction of mRNA encoding for transcript factors or other functional molecules. In other studies, SAM vaccines encoding influenza antigens were successfully delivered to DCs by chitosan-nanoparticles and PEI-based polyplexes, which were also reported to successfully induce humoral and cellular immune responses in mice [145, 146] . Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo

cord-003600-cpbbjm13	Glutathione (GSH), a significant antioxidant molecule, levels are lower in G6PD individuals, and theoretically, the probability of oxidative stress and haemolysis due to exercise in individuals with G6PD deficiency is increased, whereas dietary supplementation with antioxidants may have beneficial effects on various aspects of this enzymopathy. RESULTS: There is little evidence indicating that G6PD deficiency can cause perturbations in redox status, haemolysis, and clinical symptoms such as fatigability and myoglobinuria, especially after intense exercise, compared to individuals with normal enzyme levels. Finally, since GSH levels are lower in G6PD deficiency, it would be interesting to examine the effects of antioxidant or cysteine donor supplements on redox status after exercise in these individuals. As mentioned earlier, there are reports in the literature that come from case studies with no rigid research designs, which report that heavy exercise in G6PD-deficient individuals caused clinical signs of haemolysis, muscle degeneration, myalgia, and myoglobinuria, which may be attributed to increased oxidative stress [15, 16, [24] [25] [26] .

cord-003602-wtestt8i	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. The core control system predicts bistability and hysteresis bifurcation when delayed down-regulation of miR-451 activities along certain molecular pathways would induce glioma cells to stay longer in the proliferative phase despite relatively low glucose concentrations, making this mechanism a therapeutic target. In the current investigation, we aim to regulate the amount of glucose and drug infusions to up-regulate miR-451 and mTOR above its threshold values inducing cell proliferation Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy avoiding migration to neighboring tissues. The mutual antagonistic mechanism Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy between miR-451 (mTOR) and AMPK complex and the cell''s strategic metabolic adaptation support the survival of cancer cells even in a nutrient-deprived microenvironment [14, 55] .

cord-003612-bp7sray2	
cord-003615-vpzzsdld	
cord-003623-n01rgqyv	To evaluate the ability of our system comprising seven filovirus-specific indirect ELISAs to predict the filovirus species most antigenically similar to the species responsible for past infection, we tested seven Marburg virus convalescent serum 35 or whole blood 36 samples collected from experimentally inoculated ERBs. Five of these samples www.nature.com/scientificreports www.nature.com/scientificreports/ were collected four weeks post primary Marburg virus inoculation 35, 36 , while two of the samples were collected at 23 and 27 weeks post primary inoculation following a "natural" boost (i.e., Marburg virus-specific antibody levels waned in these bats and then increased following contact with infectious cagemates) 36 . Although significant levels of serological IgG cross-reactivity were observed between the prime-boost filovirus-specific antisera and some of the filovirus antigens, when the overall covariance of the seven-individual indirect ELISAs in the system were considered, we were able to predict the filovirus species responsible for past infection 100% of the time using as little as 25 μL of sera (each serum was tested against each antigen in duplicate).

cord-003629-xogzl1lv	
cord-003634-iq0e1qp1	
cord-003646-kjkuet78	
cord-003655-uo0hdrgc	Here, we describe a protocol for the preparation and ex vivo infection of lung slices from different mammalian host species with various respiratory paramyxoviruses expressing fluorescent reporter proteins, and suggest follow-up experiments including immunohistochemistry, flow cytometry and confocal microscopy. The combination of these viable lung slices with recombinant viruses expressing fluorescent reporter proteins [7] [8] [9] allows for accurate, sensitive and reproducible assessment of respiratory virus infection and dissemination over time. We have validated this technique by infecting lung slices of multiple host species (cotton rats, ferrets, dogs and macaques) with various paramyxoviruses expressing fluorescent reporter proteins (measles virus (MV), canine distemper virus (CDV), human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV)) [10] . Using a (blunt-end) needle or flexible catheter, the fresh lungs are inflated through the trachea (or primary bronchus, if inflation of a half lung or single lobe is desired) with low-melting point agarose mixed with culture medium.

cord-003684-q10zmids	Considering an earthquake-prone country, Iran is ranked as one of the world''s most dangerous countries OBJECTIVE: In this article, we describe the actions taken by emergency medical service (EMS) after the earthquake in Kermanshah, Varzaghan, and Bam and compared the strengths and weaknesses of the emergency response program and the limitations and challenges of this system in dealing with these major crises. The following criteria have been used for comparison of earthquakes: The first criterion is the comparison of seismology, geotechnical and texture data; the second criterion is the magnitude of the human damage caused by 3 earthquakes; the third criterion: the notification process and rapid warning system of the medical emergency services system; the fourth criterion: the coordination and pre-hospital Emergency system''s surge capacity program; the fifth criterion: distribution system and transfer of patients and injured.

cord-003685-jcvrqeew	The APPs have demonstrated their role as early markers of inflammation in veterinary medicine, thus several APPs were tested in marine mammals, such as C-reactive protein (CRP), serum amyloid-A (SAA), and Haptoglobin (Hp). To examine the humoral response, species-specific antibodies against IgG were produced and used to evaluate serum IgG levels in killer whale by radial immunodiffusion assay (41) and by competitive ELISA in bottlenose dolphins (42, 43) . Serum total protein analysis were used to assess health status in several cetaceans species such as pantropical spotted dolphins (Stenella attenuata) (48), beluga (49) , minke whales (Balaenoptera acutorostrata) (50) and killer whales (51) as well as in other marine mammals, like harbor seals (Phoca vitulina) (52) and walruses (Odobenus rosmarus) (53) . The availability of sensitive markers of inflammation both for free-ranging and managed marine mammals is nowadays considered fundamental to evaluate the health status and, in rehabilitation setting, to monitor the response to therapy and to define the prognosis.

cord-003697-vmmlxr0o	Here, we developed a highly efficient bioreactor to generate high titers of HuNoV-specific IgY in chicken yolks using a recombinant vesicular stomatitis virus expressing HuNoV capsid protein (rVSV-VP1) as an antigen. HuNoV is the major food-and water-borne virus that accounts for more than 95% of nonbacterial acute gastroenteritis worldwide, but this percentage may be underestimated due to In this study, we developed a highly efficient bioreactor for large-scale production of chicken egg yolk IgY antibodies using rVSV-VP1 as an antigen. Percent of blocking activity was calculated by comparing the OD values measured with or without blocking by the chicken IgYs. As shown in Figure 5 , total IgY antibodies isolated from egg yolks of rVSV-VP1 vaccinated groups were capable of blocking the binding of HuNoV VLP to HBGAs (A, B, or O 

cord-003701-i70ztypg	
cord-003715-deqiets2	
cord-003728-2sm0pgt7	The aim of the study was the detection and molecular characterisation of BPIV3 and BRSV from nasal swabs and lung samples of cows in and around the Erzurum region of eastern Turkey. Gene-specific primers in a molecular method (RT-PCR) identified BRSV (fusion gene) and BPIV3 (matrix gene) strains at the genus level. The aim of this study was the detection and molecular characterisation of BPIV3 and BRSV strains retrieved from nasal swabs and lung samples of cows in the eastern region of Turkey. In this study, BRSV and BPIV3 virus strains were detected in pool of 155 lung tissue and nasal swab samples collected from cattle from Erzurum and neighbouring provinces. BPIV3 and BRSV were detected by other researchers with serological and virological methods in cases of lower respiratory tract infections in cattle in Turkey (2, 6, 41) .

cord-003738-el0wyu74	
cord-003743-zy5m8xc8	
cord-003764-141u6ax7	
cord-003772-1345qct4	title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. A strong IFITM3 clustering with a ring-like appearance indicating vesicle coating was observed in both IAV-infected A549 cells ( Figure 5A ) and HSAEpCs at 10 h p.i.

cord-003779-5yhoiv76	
cord-003787-hfnht8wa	We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital-attending population (31.7%) in southern Vietnam. Hypothesising that HEV GT3 and GT4 are common zoonotic pathogens in Vietnam, we aimed to estimate (i) the HEV seroprevalence in a hospital-attending population, as a proxy for the general population, (ii) the HEV seroprevalence in individuals working in close contact with pigs (farmers, family members of farmers, animal workers, veterinarians and abattoir workers) and (iii) the prevalence of HEV infection in pigs. Although the seroprevalence in both populations increased with age, the prevalence of anti-HEV IgG was higher in children in the hospital population than in children enrolled in the farm cohort study (Figure 3 ). This study aimed to measure the prevalence of faecal HEV shedding on pig farms and the seroprevalence of HEV in the human population in southern Vietnam (Dong Thap province).

cord-003803-1t4xyayf	title: Successful management of refractory respiratory failure caused by avian influenza H7N9 and secondary organizing pneumonia: a case report and literature review Human infected with avian influenza A H7N9 virus were first confirmed on March 30th, 2013 in China [1, 2] , with high incidence of severe respiratory failure, high intensive care unit (ICU) admission and mortality. However, refractory severe respiratory failure caused by OP secondary to avian influenza H7N9 virus infection was first reported in this case. In these cases reported, OP onset mostly at the second to third week in the course of influenza, and occurred after the releasing of primary virus infection; And the OP is complicated with respiratory failure, and no evidence of other pathogen was found; And the main findings on HRCT for this kind of OP were GGO and consolidation.

cord-003806-ctass7hz	These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Here we explore how the combination of evolution during the process of vaccine manufacture and during its within-host dynamics following vaccination could affect the immune responses elicited by a recombinant vector vaccine and reduce its efficacy-the specific interaction between evolution and immunity. Again, the problem is complicated by the limited duration of the infection: reduced antigen production due to vaccine evolution depends not only on interference between the two genomes but also on overall growth and the extent to which it affects the level of immunity to vaccine and vector. The evolutionary consequences should be the same for both types of inferiority, reducing the long term generation of antigen levels within the host, but adaptive immunity would be irrelevant to vaccine evolution during manufacturing and during early growth within the host.

cord-003825-tkqxb1ql	The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. Comparison of serum and oral fluid antibody responses after vaccination with modified live (MLV) porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in PRRS endemic farms

cord-003827-65s65ojc	MATERIALS AND METHODS: We subjected RAW 264.7 mouse macrophages to clinically relevant levels of tumor-treating fields (0.9 V/cm, 150 kHz) and evaluated alterations in cytokine expression and release, as well as cell viability. RESULTS AND DISCUSSION: Our results indicated that tumor-treating fields treatment at 0.9 V/cm decreased cell viability and increased cytokine messenger RNA/protein levels, as well as levels of nitric oxide and reactive oxygen species, relative to controls. 16 RAW 264.7 cells were treated with TTFs or LPS for 24 hours, and the mRNA expression levels of proinflammatory cytokines such as IL-1b and TNF-a were determined ( Figure 3A) . 17 Tumor-treating fields-administered RAW 264.7 cells showed increased phosphorylation of IkB-a and p65, indicating that the p65 subunit of NF-kB was released from IkB-a, allowing for its translocation to the nucleus to regulate the transcription of many genes that activate macrophages (Figure 4 ).

cord-003861-qeao4ghg	To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. To better understand the role of correlated evolution and positive selection in the evolutionary dynamics of viruses infecting humans, we constructed a nearly exhaustive viral data set spanning all dsDNA, dsRNA, ssRNA, and ssDNA viruses deposited in GenBank (as of August 2017), and conducted an extensive survey of correlated evolution and diversifying selection in these viruses, asking more specifically about the prevalence of these two processes in each viral type, independently or jointly, with the specific hypothesis that the genes affected by both processes encode functions that are most critical to each viral life cycle.

cord-003866-3gwbc7z9	
cord-003898-y6zpvw84	title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications The aim of this study was to utilize RNA sequencing (RNAseq) technology to not only reveal the hNEC responses (from multiple individuals) against influenza infection, but also to identify those genes with high magnitude changes to serve as potential reference markers of the innate responses of influenza infection. After deriving the transcriptomes by RNAseq, we then further investigated whether the changes in expression of genes resulted in alterations in secretory cytokines and chemokines early in the infection of hNECs. Initially, we detected significant reductions in multiple cytokines at 8 hpi, with the exception of IL-15 which was increased ( Figure S2 ). In conclusion, RNAseq technology allowed us to accurately quantify the magnitude of gene expression changes, as well as the relevant enriched pathways during H3N2 influenza virus infection of hNECs, which can serve as a baseline for future clinical studies.

cord-003915-kje8lvgl	
cord-003917-bswndfvk	
cord-003921-8r8z0otz	PURPOSE OF REVIEW: Hepatic ischemia-reperfusion injury (IRI), an inevitable event during liver transplantation, represents a major risk factor for the primary graft dysfunction as well as the development of acute and chronic rejection. In IRI-LT pathophysiology, both Kupffer cells (donor-origin) and liver-infiltrating bone marrow-derived macrophages (recipient-origin) play dominant roles in priming innate immune responses [9] [10] [11] , with the majority of studies focusing on macrophage regulation [12, 13] . Indeed, hepatocyte-specific HMGB1 deficient mice showed decreased hepatic necrosis and neutrophil accumulation, whereas the number of their macrophages remained unchanged in acetaminophen-induced liver injury model [28] . In addition, CXCL1 blocking antibody alleviated hepatic infiltration in necrotic cellinduced neutrophil mobilization model [31] , whereas in a carbon tetrachloride (CCl4)-induced acute liver injury, defective CXCL2 expression in TLR2-knockout or S100A9-knockout mice was accompanied by suppressed hepatic neutrophil recruitment [32] . CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury

cord-003926-ycdaw2vh	
cord-003932-25dcnext	IPAC strategies in place prior to the QI study included: mandatory core competency training for all clinical staff on hire and renewal every 2 years; a healthy workplace policy that required healthcare workers to Open access stay home if they were ill; droplet and contact precautions for patients with respiratory symptoms including patient placement (single room and cohorting); routine daily and terminal environmental cleaning of horizontal and high touch surfaces; monthly hand hygiene directly observed audits (compliance rate ~88%-92%); multiplex RV testing via polymerase chain reaction (turnaround time ~24 hours); antiviral treatment and prophylaxis for confirmed cases of influenza and exposed roommates and annual influenza vaccination campaign with uptake of 76% for staff and ~65% for patients.

cord-003945-esnyjoq5	title: Customized one-step preparation of sgRNA transcription templates via overlapping PCR Using short primers and its application in vitro and in vivo gene editing However, conventional methods of generating sgRNA either direct synthesis sgRNA or requires plasmid construction for PCR amplification to make transcription templates [7] , which is either expensive or cumbersome and requires several steps to produces gRNAs. Cell & Bioscience In the present study, we described a simplified and customized in vitro synthesis approach utilizing multiple overlapping primers to synthesize DNA fragment for six selected gene loci as the transcription templates of sgR-NAs by a single-step sequential primer extension under appropriate conditions, and tested the cleave efficiency to targeted loci by using these sgRNAs combined with Cas9 nuclease in vitro and in vivo. Summary, we demonstrated an approach by combining CRISPR/Cas9 gene editing technology with multiple overlapping primers to synthesize DNA fragment as the template of sgRNA to substitute the conventional method.

cord-003948-npijn7co	
cord-003962-lg6gvgwt	The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. The results showed that the mutations of the residues D84 and E90 (e.g., D84N, D84R, E90R, E90Q, etc.) did not have much effect on PLP2 DUB activity, as the corresponding mutants could efficiently cleave K63 or K48 polyubiquitin chains into monomers ( Figure 4A , lanes 3, 4, 7, and 8).

cord-003970-3e58229u	Porcine reproductive and respiratory syndrome virus (PRRSV), the etiological agent of PRRS, is one of the most important endemic viruses affecting the swine industry in the United States (Holtkamp et al., 2013) and globally (Stadejek et al., 2013; VanderWaal and Deen, 2018) . Porcine reproductive and respiratory syndrome virus was first recognized almost simultaneously in Europe (Wensvoort et al., 1991) and North America (Collins et al., 1992) in the late 1980s and early 1990s, but genetic differences suggested a much earlier evolutionary divergence between the North American and European viral types. Here, we describe the temporal dynamics of PRRSV occurrence in a swine-dense region of the United States, characterizing these patterns according to ORF5 genetic lineages and sub-lineages. Porcine reproductive and respiratory syndrome virus diversity of Eastern Canada swine herds in a large sequence dataset reveals two hypervariable regions under positive selection

cord-003971-m59czkya	When the phylogenetic analysis was conducted based on the amino acids encoded by the segment of N gene, the main evolutionary relationship persisted between parrot bornavirus (PaBV-4), aquatic bornavirus (ABBV-1, ABBV-2), variegated squirrel bornavirus (VSBV-1) and Borna disease virus (BoDV-1) (Figure 6(b) ). The third phylogenetic approach, based on the P gene segment, revealed that members of Mammalian 2 orthobornavirus species are the most related to PaBV-4 genotypes than of all bornaviruses detected and reported in wild birds, other than parrots (Figure 7(a) ). Namely, within genotypes detected in wild-bird samples, Borna disease virus (BoDV-1) is the most evolutionarily distant from parrot bornavirus (PaBV-4) (Figure 7(a) ). When the analysis was conducted based on the amino acid sequence encoded by the P gene segment, the main phylogenetic relationship remained between aquatic bird bornavirus (ABBV-1 to 2), parrot bornavirus (PaBV-4), variegated squirrel bornavirus (VSBV-1) and Borna disease virus (BoDV-1) genotypes (Figure 7(b) ).

cord-003972-d56i2sur	
cord-003993-3bozjfv7	
cord-003997-heo6mtxk	
cord-004016-iaktm72a	The Ag@cur-P(MEO 2 MA) core-doped shell hybrid NPs were prepared by free radical precipitation polymerization (FRPP) of the stimuli-responsive MEO 2 MA monomer in the presence of TEGDMA (crosslinking agent), using curcumin-decorated Ag@cur NPs as seeds (Fig. 1) . However, the dual key-role of curcumin, as reducing agent and growth-polymerization promoter in this specific synthesis, required additional investigation to understand and optimize the chemical variables (solubility, concentration and reaction temperature) in order to achieve homogeneous, monodisperse and mononuclear Ag@cur-P(MEO 2 MA) core-shell nanohybrids. The presence of hydrophobic curcumin nearby the metallic surface led to precipitation-polymerization of P(MEO 2 MA) around the AgNPs previously formed (Fig. 1B,C) ; and the resulting Ag@cur-P(MEO 2 MA) nanoparticles were born negatively charged due to the persulfate groups from the APS initiator, which promotes their colloidal stability.

cord-004017-gcmpatlb	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.

cord-004020-qtwcbn7m	A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Gossypol-treated ZIKV was incubated with Vero E6 cells at 37 • C for 1 h in the presence of DMEM containing serial dilutions of each of the other three natural products identified, such as curcumin, digitonin, and conessine, or anti-ZIKV compound control (bortezomib). Based on Table 1 , four "hit" natural products, including gossypol, curcumin, digitonin, and conessine ( Figure 2A -D), were selected, since they demonstrated inhibitory activity against ZIKV infection with no obvious cytotoxicity in Vero E6 cells when observed under a microscope. Since gossypol demonstrated the highest antiviral activity individually against all ZIKV strains tested, we next investigated the potential combinatorial effects of the combination of gossypol with three other natural products identified, namely curcumin, digitonin, and conessine, as well as anti-ZIKV compound control (bortezomib).

cord-004031-sw60qbbj	
cord-004034-mjkixqhs	METHODS: A total of 335 anticoagulated whole-blood samples obtained from both a healthy and ill cat population were examined for the presence of FIV and FeLV with two methods: ELISA and PCR. [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] The aim of this study was to estimate the prevalence of these retrovirus infections in domestic cats in Hungary, to evaluate the main factors affecting the infection rate and to examine the phylogenetic relations of the FIV strains detected. Phylogenetic characterisation of feline immunodeficiency virus in naturally infected cats in Croatia indicates additional heterogeneity of subtype B in Europe Analysis of the genetic diversity and phylogenetic relationship of Italian isolates of feline immunodeficiency virus indicates a high prevalence and heterogeneity of subtype B Naturally acquired feline immunodeficiency virus (FIV) infection in cats from western Canada: prevalence, disease associations, and survival analysis

cord-004058-j11yaga2	Reproducibility can be improved by constraining bias through appropriate experimental design, randomization of tissues, effective use of multidisciplinary collaborations, and valid masking procedures. Following key principles of semiquantitative scoring will not only enhance descriptive tissue evaluation but also improve quality, reproducibility, and rigor of tissue studies. Semiquantitative scoring can be applied to macroscopic and microscopic tissue changes, allowing generation of robust data that are amenable to statistical analysis and evaluation of experimental groups. [3] [4] [5] [6] [7] [8] In the preclinical area, which utilizes models (eg, animal, tissue/cell cultures, etc.) of human diseases/conditions, semiquantitative scoring is regularly used to compare experimental groups. 33, 34 Specifically, statistical and pathological analyses are common components in translational studies, but trained statisticians and board-certified pathologists are often omitted from these multidisciplinary teams, leading to data interpretations that are more prone to errors.

cord-004069-nuep8nim	A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 .

cord-004161-1apf9w7j	title: Recombinant Lactobacillus casei Expressing Capsid Protein VP60 can Serve as Vaccine Against Rabbit Hemorrhagic Disease Virus in Rabbits Three groups of rabbits (n = 6), immunized with pPG-eGFP-VP60/LC393, inactivated vaccine, or PBS, were challenged with 1 mL RHDV crude liver extract (at a viral RNA copy number of 1.0 × 10 5.79 ) administered via intramuscular injection into the leg at 37 d after the first vaccination ( Figure 2) . Three groups of rabbits (n = 6), immunized with pPG-eGFP-VP60/LC393, inactivated vaccine, or PBS, were challenged with 1 mL RHDV crude liver extract (at a viral RNA copy number of 1.0 × 10 5.79 ) administered via intramuscular injection into the leg at 37 d after the first vaccination ( Figure 2) . casei pPG-eGFP-VP60/LC393 and effectiveness of the inactivated virus vaccine in rabbits after oral and intramuscular immunization. casei pPG-eGFP-VP60/LC393 and effectiveness of the inactivated virus vaccine in rabbits after oral and intramuscular immunization.

cord-004256-83crtevc	title: Development of a tool to assess oral health-related quality of life in patients hospitalised in critical care AIMS AND OBJECTIVES: Oral health deteriorates following hospitalisation in critical care units (CCU) but there are no validated measures to assess effects on oral health-related quality of life (OHQoL). A major limiting factor to further research is the absence of a validated tool to measure oral health-related quality of life in CCU patients. Therefore, the aim of this study was to develop and validate a suitable tool to assess the impact of critical care on oral health-related quality of life (OHQoL) and to investigate patient-reported outcome measures of OHQoL in patients hospitalised in a CCU.

cord-004335-bw3tziup	Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. Thus, infection with viruses such as HIV-1 or EBOV tightly upregulates Siglec-1 expression on APCs, as they directly trigger or indirectly promote the release of type I IFNs via immune activating factors (Figure 1 ). Thus, HIV-1 and EBOV infections trigger an immune activation state that upregulates Siglec-1 expression on DCs, a situation that might favor early viral dissemination events in an otherwise antiviral environment [80] .

cord-004587-htgjwcgs	Based on this approach, we suggest a stage model for the categorization of biological threats as "incident," "crisis," "severe crisis," or "disaster." The need for central coordination is a defining characteristic to qualify a biological incident as "unusual." Based on the identified shortages, the necessary response strategies can be derived. Eine strikte Trennung der Vorsorgeplanung nach diesen Zuständigkeiten ist nicht zweckmäßig unter Berücksichtigung der Tatsache, dass sowohl die zum Management notwendigen Ressourcen als auch das betroffene Schutzgut der Bevölkerungsgesundheit in beiden Fällen (Bioterrorismus und natürliches Seuchengeschehen) identisch sind. In Reaktion auf die wachsende Besorgnis um bioterroristische Anschläge entstand im Jahr 2002 mit dem "Bund-Länder-Rahmenkonzept zu notwendigen fachlichen Vorbereitungen und Maßnahmen zur Seuchenbekämpfung nach bioterroristischen Anschlägen (Teil Pocken)" ein erstes umfassendes Konzept zum Management außergewöhnlicher biologischer Gefahrenlagen [13] . Im Rahmen der Regelungen des Bund-Länder-Informationsverfahrens (siehe § 5 IfSG) wird von "epidemisch bedeutsamen Fällen" gesprochen, diese werden jedoch an keiner Stelle -auch nicht in der daBasierend auf diesem Ansatz schlagen wir ein Stufenmodell zur Kategorisierung biologischer Gefahrenlagen in "Lage", "Krise", "schwere Krise" und "Katastrophe" vor.

cord-005028-3ncj61il	To compare the newborn infant parasympathetic evaluation system (NIPE) scores with a validated clinical scale using two different nebulizers in children with bronchiolitis admitted to a PICU. NIPE monitoring showed a variation in comfort during nebulization in the patient with bronchiolitis, though correlation with CBS was poor. The aim of this study was (1) to evaluate whether the NIPE system could be a useful tool for the continuous monitoring of discomfort and pain, compared to the clinical COMFORT Behavior Scale when nebulizing children with bronchiolitis admitted to a PICU; and (2) to determine whether NIPE values vary when two different nebulization systems are used. In summary, this study demonstrates the variation in discomfort during nebulization in the patient with bronchiolitis with NIPE monitoring, although it does not seem to correlate well with the clinical evaluation. Clinical scales like the Comfort Behavior Scale are good tools to evaluate the discomfort and pain generated by nebulization in nonsedated patients breathing spontaneously, presenting with bronchiolitis.

cord-005280-a23oy0sz	Although ROS play an important role in pathogen resistance and cellular signalling, they are also broadly recognized as harmful reactive particles to cell as they damage intracellular proteins, lipids and nucleic acids. The homeostasis of ROS plays an important role in reducing oxidative damage and fulfil energy demand. Relatively high levels of ROS may cause oxidative damage or induce apoptosis during immunological defences or pathological conditions. However, ROS themselves could activate extracellular signal-regulated kinase (ERK) by targeting proteins Gαi and Gα0 and protect cardiac cell from oxidative damage [18] . Apart from oxidative damage, ROS also serve as signalling molecules and play an important role in homeostasis, metabolism, growth and differentiation [3] . PGC-1α could protect neural cells from oxidative damage by reducing ROS level via antioxidative enzymes GPx1 and SOD2 [15] . ROS regulate vascular cell proliferation and apoptosis with their fundamental role in metabolism.

cord-005430-svidp7ar	Overall, high TRM rates rather than DAM contribute to the poor outcomes of Pt-non-CR, suggesting that not only disease control but also management of transplant-related complications is required for allo-HSCT in ATL patients. A nationwide retrospective study of allo-HSCT for the treatment of ATL [15] demonstrated several pretransplantation factors that are associated with poor survival rates, such as poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS) rating, higher age, male sex, non-complete remission (non-CR) at transplantation, and the use of unrelated cord blood as the stem cell source. In ATL patients, a high level of sIL-2R (2000 U/ mL or higher) at transplantation is known to be a significant risk factor for poor overall survival and disease progression after allo-HSCT [21] . A nationwide retrospective study of allo-HSCT in ATL patients revealed transplantation outcomes similar to that of the whole cohort in our study, that is, 3-year overall survival, cumulative incidence of TRM, and disease-associated death rates were 33%, 37%, and 21%, respectively [15] .

cord-005589-ocnce92z	In this point-of-view review paper, a group of experts discuss the main controversies in SCAP: the role of severity scores to guide patient settings of care and empiric antibiotic therapy; the emergence of pathogens outside the core microorganisms of CAP; viral SCAP; the best empirical treatment; septic shock as the most lethal complication; and the need for new antibiotics. The IDSA/ATS criteria remain the most pragmatic and robust tools to predict patients requiring ICU admission We recommend empirically covering PES pathogens in SCAP when at least two specific risk factors are present Corticosteroids can be used in cases of refractory shock and high systemic inflammatory response Based on available data, new antibiotics providing existing limitations in empiric therapy (including macrolide resistant species and MRSA) are needed 38.6% previously) and reduced delayed ICU admissions. A recent observational study found that corticosteroid administration as adjuvant therapy to standard antiviral treatment in critically ill patients with severe influenza pneumonia was associated with increased ICU mortality [46] .

cord-005677-ijrghpco	The impact of global warming on diseases requiring intensive care has been extrapolated from some existing data regarding a change in the spread of infectious diseases [6] , an (further) alteration of the function of the respiratory system-especially in patients suffering from chronic lung diseases-an expected increase in kidney diseases, an expansion of cognitive disorders due to heat waves, particularly in the elderly, and some adverse effects on the cardiovascular system. [16] To our knowledge, there is presently no specific activity in intensive care medicine to face current and future challenges in the context of global warming and climate change, although it is expected that intensive care medicine will need more specialized capacities, better knowledge on the part of the intensivists, and better preparation for worst-case scenarios (heat stroke waves or infectious outbreaks) to manage the consequences of climate change adequately.

cord-005808-w0763esk	CONCLUSION: Administration of corticosteroids in patients with severe influenza pneumonia is associated with increased ICU mortality, and these agents should not be used as co-adjuvant therapy. Therefore, the aim of the present study was to identify the factors associated with corticosteroid use and its impact on intensive care unit (ICU) mortality using propensity score (PS) matching analysis in ICU patients with influenza pneumonia. Our results strongly suggest that administration of corticosteroids as co-adjuvant therapy to standard antiviral treatment in critically ill patients with severe influenza pneumonia is associated with increased ICU mortality. Three recent systematic reviews and meta-analyses [41] [42] [43] concluded that corticosteroid therapy is significantly associated with mortality, even in the subgroup of patients with influenza hospitalized in or outside the ICU. In a homogeneous group of critically ill patients with severe influenza pneumonia, after adequate adjustment by PS matching and competing risks, co-adjuvant corticosteroid therapy was significantly associated with increased ICU mortality.

cord-006039-vbq9izw3	In this Review, we emphasize the need to focus on host interactions with Plasmodium parasites at various tissue levels and the importance of targeting local and specific organ failure and/or pathologies during, as well as long after, infection. Overall, while the process of sequestration is not completely understood, it is known to cause obstruction of blood flow in small capillaries and post-capillary venules (PCVs), endothelial cell activation and inflammation and severe pathology in many organs including lung, adipose tissue, spleen and brain 52, 53, 65, 66 (FIG. This unique brain pathology, known as cerebral malaria, involves convulsions, coma and high fever and develops with the presence of mostly ring-stage infected erythrocytes in the periphery (suggesting a sequestration of late-stage parasites in the organs) [69] [70] [71] . Malaria is a serious disease with acute life-threatening and long-term complications, all of which can be attributed to local but specific organs in which Plasmodium Figure 4 | Infected red blood cells in gut and bone marrow niches.

cord-006285-kkxdmzk9	The present work reports the comparative assessment of the functional changes which take place in human ECV-304 endothelial cell sublines obtained previously by the long-term culturing of cells after exposure to varying infectious doses (IDs) of influenza A virus, and/or bacterial lipopolysaccharide (LPS). It has been demonstrated that, in the course of long-term culturing (six passages) after exposure to pathogenic agents (influenza virus and/or LPS), endothelial cells maintain changes in their migratory activity, permeability, and expression of mRNA for cytokines TNFα and TGFβ (along with the changes in their proliferation activity, which has been demonstrated earlier). The comparative study of the human endothelial ECV-304 cell sublines carried out in the present work and in our previous work (Smirnova et al., 2018) has demonstrated that the infection of nonpermissive cells with influenza A virus (both in high and in very low doses) and exposure to LPS can change migratory, proliferation, and apoptotic activity of cells and impair cell barrier function.

cord-006325-3no74e74	A more severe outcome was observed for RSV-bacteria-associated pneumonia compared with RSV pneumonia: length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). In conclusion, we did not observe major differences in the epidemiology of bacterial superinfections in RSV-positive pneumonia compared to reports on post-influenza pneumonia. RSV and bacteria coinfection was statistically associated with a more severe outcome than RSV-positive pneumonia as length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). It is probably due to the systematic testing strategy associated to a Species distribution of pathogenic bacteria involved in RSV-positive pneumonia (CAP) and hospital-acquired pneumonia (HAP) sampling bias toward influenza-like illness. Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France

cord-006466-e1phpqes	Whole exome sequencing revealed a heterozygous mutation, previously reported (c.1425+1G>T) Conclusions: In summary, this report emphasizes the suspicion of a combined immunodeficiency in the presence of multiple abscesses by Mycoplasma, the usefulness of rDNA 16s in order to achieve proper Objectives: We describe a 15-year-old male patient with novel heterozygous mutation of EP300 gene; his first manifestations were initially characterized by infections, cytopenia and hypogammaglobulinemia suggesting a Common Variable Immunodeficiency (CVID), but later on, persisting lymphopenia was suggestive of a combined immunodeficiency. Conclusions: Close monitoring of immune function in early life for patients with CHH and CID as well as the availability of suitable donors assists in determining management, including HSCT Introduction/Background: Leukocyte Adhesion Deficiency (LAD) represents a group of distinct inherited disorders, which inhibit the normal extravasation of neutrophils and their recruitment to sites of infection or inflammation.

cord-006701-q8qh1kas	We have used placenta-derived decidua stromal cells (DSCs) to treat graft-versus-host disease and found an immunomodulatory and anti-inflammatory effect. The second patient was a 34-year old woman who was admitted 8 months after allogeneic hematopoietic stem cell transplantation due to hemolysis, impaired sensorium below arcus, and difficulty in ambulation. We have used placenta-derived decidua stromal cells (DSCs) for acute and chronic GVHD, ARDS and hemorrhagic cystitis [8] [9] [10] [11] . Electrophysiological investigation following DSCs infusion showed some improvement with more frequent motor unit activity, especially in the right arm. The day after the DSC infusion, she had normal sensation on neurological examination and subjectively in the lower abdomen and legs. The patient was examined with TMS and SEPs every 3-5 months up to a year after the onset of neurological symptoms. Placenta-derived decidua stromal cells for treatment of severe acute graft-versus-host disease

cord-006737-7h8vvim7	BACKGROUND: This study aimed to study the osteo-preservative effects of captopril, an inhibitor on angiotensin-converting enzyme (ACE), on bone mass, micro-architecture and histomorphology as well as the modulation of captopril on skeletal renin-angiotensin system (RAS) and regulators for bone metabolism in mice with bilateral orchidectomy. The mRNA expressions of renin receptor, angiotensinogen, carbonic anhydrase II, matrix metalloproteinase-9, and tumor necrosis factor-alpha were significantly decreased in tibia of ORX mice following treatment with captopril. This study demonstrated that the treatment with captopril effectively attenuated the orchidectomy-induced pathological alterations of micro-structure of trabecular bone at lumbar vertebra (LV)-4, distal metaphysis of femur and proximal metaphysis of tibia as observed by histological staining, moreover, bone mineral density (BMD) at both LV-2 and LV-5 was significantly enhanced in ORX mice in response to captopril treatment for 6 weeks. This study demonstrated that captopril effectively reversed orchidectomy-induced down-regulation of B1R protein expression in mice, indicating that bradykinin receptor was involved in management of captopril on bone metabolism in ORX mice.

cord-006750-cg2i2bae	PURPOSE OF REVIEW: Diffuse alveolar hemorrhage (DAH) is a rare but devastating manifestation of antiphospholipid syndrome (APS) patients with or without other systemic autoimmune diseases. In our experience, two different presentations of aPL-positive patients with DAH exist: (a) acute-with moderate to severe pulmonary hemorrhage (with varying degrees of respiratory failure) requiring hospitalization and (b) chronic-with mild hemoptysis, dyspnea, and/or positive imaging findings, usually seen as an outpatient. Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review Pulmonary capillaritis, alveolar hemorrhage, and recurrent microvascular thrombosis in primary antiphospholipid syndrome Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome Primary antiphospholipid syndrome associated with diffuse alveolar hemorrhage and pulmonary thromboembolism

cord-006773-61ezrjuq	First, we observed that the Foxp3 expression level in mini-BAL samples was not significantly different between Tfr cells and non-Tfr Treg cells (Fig. 2b) . The IL-10 expression by non-Tfr Treg cells and Tfr cells was lower in healthy controls and significantly higher in ARDS PBMCs and ARDS mini-BAL (Fig. 3c) . The higher IL-10 and TGF-β in ARDS mini-BAL compared to autologous PBMCs likely indicated that the Tfr and non-Tfr Treg cells in the lung infiltrates were further activated. As a result, the suppression studies were performed using Tfr cells from PBMCs. Since the Tfr cells from Fig. 2 The frequency of Treg cells and Tfr cells in the mini-BAL from ARDS patients at day 1, day 2, and day 3 after disease onset. NS not significant Fig. 3 The expression of inhibitory molecules by non-Tfr Treg cells and Tfr cells from healthy controls and ARDS patients.

cord-006849-vgjz74ts	Methods: We are performing this procedures within a prospective randomized trial that is design to compare the long term results of LRYGB-B versus the standard laparoscopic Roux-en-Y gastric bypass.The video shows our technique in a case of a 46 years old female with a BMI of 46 Kg/m2. Material and methods: We present a video of the surgical intervention of a 32-year-old patient, with functional dyspepsia, with a casual diagnosis of a pseudocystic mass of the right colon after performing a CT scan: giant diverticulum of the hepatic colon angle with fecaloid content inside it under tension The patient goes to the emergency room for acute abdominal pain, pending colonoscopy, antibiotic treatment is established, and a laparoscopic approach is decided upon after the patient''s evolution. Method: We present the case of a 65-year-old patient with surgical antecedent of laparoscopic low anterior resection due to rectal cancer, presenting in postoperative period an anastomosis leakage with severe peritonitis was identified and a laparotomy with end colostomy was performed.

cord-006854-o2e5na78	Totally Laparoscopic ALPPS Combined with the Microwave Ablation for a Patient with a Huge HCC Hua Zhang; Department of Hepatopancreatobiliary Surgery, West China Hospital, Sichuan University Introduction: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel technique for resecting hepatic tumors that were previously considered unresectable due to the insufficient future liver remnant (FLR) which may result in postoperative liver failure (PLF). Not only does this case show that a large epiphrenic diverticulm can be successfully resected via the trans-abdominal laparoscopic approach, this case makes the argument that patients undergoing any minimally-invasive epiphrenic diverticulectomy and myotomy, with or without fundoplication, may be successfully managed with early post-operative contrast studies and dietary advancement, thus decreasing their length of hospitalization and overall cost of treatment. Introduction: There are reports of increased operative duration, blood loss and postoperative morbidity, caused by difficulties in obtaining good visualization and in controlling bleeding when laparoscopic resection is performed in obese patients with colon cancer.

cord-006892-n2ncamqh	For example, chemical conjugation of mannoside-based saccharides on the surface of Rabbit hemorrhagic disease virus (RHDV) VLP selectively targets the mannose receptor expressed on the surface of APCs, inducing increased uptake and alteration of antigen cross-presentation in murine dendritic cells [57] . While the induction of a potent humoral immune response and the subsequent production of anti-VLP antibodies is the primary desired outcome of most commercial VLP vaccines, these is increasing appreciation for the role of vaccine-induced cell-mediated immunity [123] [124] [125] . Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Antigen incorporated in virus-like particles is delivered to specific dendritic cell subsets that induce an effective antitumor immune response in vivo

cord-006971-5xgurlue	43, 44 Various nanomaterials have been utilized in nucleic acid-based biosensors due to properties such as large surface area, high conductivity, and strong affinity toward bioreceptor probes with reactive groups such as thiols leading to high sensitivity and low limits of detection. 72 Hybridization of DNA probes with long single-stranded nucleic acids requires the target first being completely denatured to remove inhibitory secondary structure, followed by time for limited numbers of denatured target genomes to interact with surface-bound probe DNAs. Hybridization in this context is similar to hybridization performed in nuclease protection assays, which use long RNA probes (200-500 bases) with a short 95°C denaturation step followed by 12-16 hr incubations at high temperatures (55-65°C) in high ionic strength solutions to reduce secondary structure formation and achieve efficient and specific hybridization.

cord-007028-zid9e20z	The healthcare-associated (HA) viral respiratory infection (VRI) transmission index (number of HA VRIs per 100 inpatient community-associated VRIs) was 59% lower during the months in which visitor restrictions were implemented. During VRPP periods, visitors were screened by the concierge staff in the lobby of the children''s hospital for symptoms of viral respiratory and gastrointestinal illness before being granted access to patient care areas and screened again by bedside nurses in patient rooms. Our data indicate that VRPPs implemented in the winter at a freestanding children''s hospital are associated with reduced hospital transmission of respiratory viruses compared with that in nonwinter months when VRPPs are not in place. Although VRPPs are often limited to the winter months when community incidence of RSV and influenza rises, our data also suggest that seasonal VRPPs can result in unacceptably frequent hospital transmission of respiratory viruses, particularly rhinovirus/enterovirus, during nonwinter months.

cord-007041-rloey02j	We sequenced virus populations in parallel using both MinION and Illumina, allowing us to corroborate the inferences of AssociVar. This then allowed us to directly infer relationships between mutations and to deduce the entire genome sequences of viral strains in the population. We then determined the population frequency of each mutation at passage 1 and passage 15 through whole genome deep sequencing as described below, using Illumina and MinION. After applying AssociVar to the data, we were able to identify five out of the six mutations appearing at a frequency above 10% in the Illumina results in p15A, and all eight positions within the p15B sample (Figure 4 , Supplementary Table S2 ). We applied AssociVar to sequencing data from an evolved population of phages where Illumina sequencing was available, allowing us to corroborate whether mutations we found based on analysis of the MinION data alone were indeed real.

cord-007075-sl45z4i0	title: A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract METHODS: Patients with confirmed RSV in upper and lower respiratory tract and new chest X-ray abnormalities were randomized (1:1), stratified by supplemental oxygen and ribavirin use, to receive oral presatovir 200 mg or placebo every 4 days for 5 doses. Patients presenting any time post-HCT with upper and lower respiratory tract RSV infection documented ≤6 days before start of study treatment and evidence of new abnormalities on chest X-ray obtained ≤48 hours from screening were eligible for inclusion. Primary and secondary efficacy endpoints did not differ appreciably between patients treated with presatovir relative to placebo in subgroups defined by absolute lymphocyte count on day 1, presence of GVHD, time from onset of RSV symptoms to study treatment, and timing of RSV infection after HCT (Supplemental Tables 6-9 ).

cord-007337-if3ba9pk	Imagen hipodensa circular de unos 4 cm de diámetro, con contorno bien definido, localizada en hemitórax izquierdo, lóbulo inferior con base pleural, aunque por imagen sugiere lesión pulmonar (menos probable origen pleural). Se pauta tratamiento antibiótico con amoxicilina/clavulánico, analgesia con metamizol y tramadol, con buena evolución clínica, analítica (antígeno de Legionella y Streptococcus en orina: negativos, serología de Figura 1 Imagen hipodensa circular de unos 4 cm de diámetro, con contorno bien definido, localizada en hemitórax izquierdo, lóbulo inferior con base pleural, aunque por imagen sugiere lesión pulmonar (menos probable origen pleural). gérmenes frente a Coxiella burnetii, Mycoplasma, Legionella y Chlamydophila pneumoniae negativos, VSG, PCR y serie blanca normal) y radiografía de tórax con resolución de la condensación por lo que se da el alta a los 7 días de su ingreso con el diagnóstico de neumonía redonda basal izquierda.

cord-007425-l9c1x7tb	A small subset of non-clinical deployers also participated in a three-day training designed in collaboration with the Center for the Study of Traumatic Stress (CSTS; Bethesda, Maryland USA) to train individuals to assess and address the well-being and resilience of themselves and their teammates in the field during a deployment. Senior CDC leadership tasked their Office of Safety, Security, and Asset Management''s (OSSAM) WorkLife Wellness Office (WWO) to set up a pre-deployment screening process to reduce the likelihood of deploying someone at-risk of negative mental health outcomes in an emergency response. 7 The CSTS also recommended that the CDC consider using Psychological First Aid (PFA) as the foundation for its resilience-supporting training initiative; 8 PFA could be described as a pragmatic, evidence-informed, public health or population-based framework designed to help non-clinicians organize a response to trauma at the individual or community level.

cord-007532-1fpx9pxs	authors: Corless, Inge B.; Nardi, Deena; Milstead, Jeri A.; Larson, Elaine; Nokes, Kathleen M.; Orsega, Susan; Kurth, Ann E.; Kirksey, Kenn M.; Woith, Wendy The aim of this Academy policy is to fill this gap by identifying the essential role of nurses and community health workers during the time just prior to the confirmation of a potential epidemic and focuses on the early identification of infectious pathogens and prevention of further transmission. In addition to preparing frontline community workers to promptly identify potential emerging or re-emerging infection, appropriate national nursing councils and public health entities could be charged with the responsibility of developing and sharing early reporting networks. The policy recommendations provided below will strengthen national health security through the enhanced recognition and expansion of the individuals who are initial points of contact in the community as well as the role of nurses and nursing organizations in responding to and preventing potential global pandemics.

cord-007786-cu831tl7	We suggest that in patients with hypotensive shock, fluid bolus therapy (30 mL/kg) with isotonic crystalloids be commenced (ungraded) and, if available, early initiation of vasopressor medication (ungraded) Timing of enteral feeding in cerebral malaria We suggest not to use a strategy of permissive hypercapnia to achieve ventilation with low tidal volumes in patients with cerebral malaria, because of the high incidence of brain swelling in these patients (ungraded) Fluid management in severe dengue We recommend not to use prophylactic platelet transfusion for thrombocytopenia in the absence of active bleeding complications or other risk factors (uncontrolled arterial hypertension, recent stroke, head trauma or surgery, continuation of an anticoagulant treatment, existing hemorrhagic diathesis) (1B) acidosis [14, 15] , and transpulmonary thermodilution-guided rapid fluid resuscitation resulted in pulmonary edema in 8/28 (29%) patients [15] . There are several randomized clinical trials comparing crystalloid with colloid fluid management for the treatment of patients with severe dengue and compensated shock.

cord-009590-3w2weox4	Because it is difficult to differentiate viral and bacterial infection on the basis of clinical presentation in LRTI, our secondary aim was to evaluate if l‐ and d‐lactate may serve as markers of local inflammation as representatives of neutrophils and bacteria, respectively. Increased markers of neutrophilic inflammation in sputum have been found to be associated with bacterial infection in COPD exacerbations (3), potentially leading to increased levels of both L-lactate and D-lactate. Increased markers of neutrophilic inflammation in sputum have been found to be associated with bacterial infection in COPD exacerbations (3), potentially leading to increased levels of both L-lactate and D-lactate. Altogether, we aimed to assess the utility of sputum L-lactate and sputum D-lactate as markers of pulmonary neutrophilic inflammation and bacterial invasion in the lungs of patients admitted with acute LRTI. Our study has shown that L-lactate in sputum is associated with the neutrophil invasion in the lungs Mixed bacterial/viral LRTI n = 2 (7.7%).

cord-009764-m9flptcv	However, it does not seem to provide Note: aOCT-anatomical optical coherence tomography, COPD-chronic obstructive pulmonary disease, DI-deep inspiration, FEV 1 -forced expiratory volume in 1 s, FOT-forced oscillation technique, FRC-functional residual capacity, HRCT-high-resolution computed tomography, LABA-long-acting b2agonist, MCh-methacholine, PC 20 -the provocative concentration of methacholine causing a 20% decline in FEV 1 , Raw-airway resistance, RV-residual volume, SABA-short-acting b2-agonist, SBNW-single breath nitogen washout, TLC-total lung capacity, VC-vital capacity, and V D -dead volume. Forced oscillation technique can be used to estimate ASM strain during a DI from FRC to TLC because Rrs and its inverse, respiratory system conductance (abbreviated Grs), represent proper proxies of airway caliber when measured near the resonant frequency (6-10 Hz) [70] . The estimation of ASM strain during a DI from FRC to TLC is often accomplished by measuring the changes in resistance at different lung volumes.

cord-009813-o8ai730r	
cord-009865-c5xj9asg	title: First detection of spring viraemia of carp virus in common carp (Cyprinus carpio L.) affected by a septicaemic disease in Mexico This study describes the diagnosis of an SVCV pathogen isolated in October 2015 from wild common carp inhabiting a natural lagoon in central Mexico. However, since this pathogen was detected in fish inhabiting a natural body of water without tributaries or effluents, it is difficult to estimate the risk of SVCV for other wild/feral cohabitating cyprinid species in the lagoon. Primary among these diseases is the spring viraemia of carp virus (SVCV), a notifiable pathogen according to the World Organization for Animal Health (OIE, 2017a) and a virus responsible for mortalities associated with acute haemorrhaging. This report describes an SVCV rhabdovirus as the cause of an infective outbreak among wild common carp in Mexico.

cord-009936-5k4xk3hs	
cord-009997-oecpqf1j	Completed cranial radiation and proceeded to allogeneic stem cell transplant with unrelated cord marrow donor and is disease free at approximately day +200.Case 2: 5 year-old female diagnosed with FLT3 and MLL negative AML and completed treatment per COG AAML1031 study on the low risk arm without Bortezomib. Design/Method: This study was a retrospective chart review that included patients 3 to 23 years old with sickle cell disease type SS and S 0 followed at St. Christopher''s Hospital for Children. Background: Hydroxyurea, chronic blood transfusion, and bone marrow transplantation can reduce complications, and improve survival in sickle cell disease (SCD), but are associated with a significant decisional dilemma because of the inherent risk-benefit tradeoffs, and the lack of comparative studies. Brown University -Hasbro Children''s Hospital, Providence, Rhode Island, United States Background: Despite clinical advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant source of disease-related morbidity.

cord-010705-lez9dcao	
cord-010818-yz0gynn0	OBJECTIVE: To study the effect of early and late onset preeclampsia (EOPE, LOPE, respectively) on outcomes of late preterm infants. The objective of our study was to investigate the effects of early and late onset preeclampsia on the outcomes of late preterm infants, with the primary objective being respiratory outcomes. Late preterm infants born between 34 +0 and 36 +6 gestation to a mother with early onset preeclampsia between January 2014 and July 2015 were included in the study. Gouyon et al., using a large cohort from France, reported higher risk of severe respiratory morbidity, in late preterm infants of mothers with hypertensive disorder of pregnancy [9] . Respiratory morbidity, defined by the need for oxygen, CPAP or mechanical ventilation was higher at each gestational age in infants of hypertensive mothers but reached statistical significance only at 37 weeks. compared outcomes of late preterm infants of mothers with preeclampsia, gestational hypertension and normotensive pregnancies in a large cohort from the Netherlands [25] .

cord-010854-mky7fufk	Ein hohes Maß an Flexibilität und Teamgeist ermöglichten es, den Leichnam der Tochter auf die Station zu bringen, damit sich Fr. F. Ziel dieses Leitthemenbeitrags ist es, das BA-SIS-Modell der KI vorzustellen, das einen Rahmen vorgibt, wie Angehörige speziell auf Intensivstationen begleitet werden können, wenn eine nahestehende Person verstorben ist. Empathie bedeutet somit auch, die belastenden negativen Gefühle der Gefühlsansteckung und des Mitgefühls zu regulieren, damit Intensivpersonal von diesen negativen Gefühlen nicht überschwemmt wird. Die Übernahme der Gefühle von anderen Personen erfolgt unbemerkt, ist deshalb nicht steuerbar und kann als Basisprozess empathischen Verhaltens betrachtet werden. Crisis intervention · Team · Empathy · Intensive care unit · Posttraumatic growth · BASIS model in der Vergangenheitsform gesprochen wird [10] . Wo (auf der Station oder beim Bestatter) Angehörige fragen auch immer wieder, ob sie nicht etwas "zur Beruhigung" haben können. ich konnte nichts tun, außer auf der Couch zu sitzen und zuzuschauen, wie die anderen Familienangehörigen das Begräbnis planten.

cord-010863-m36kxc4x	title: The Golden Hour: a quality improvement initiative for extremely premature infants in the neonatal intensive care unit CONCLUSIONS: Implementation of an evidence-based, Golden Hour protocol is an effective intervention for reducing hypothermia and hypoglycemia in extremely premature infants. Evaluation of short-term outcomes and other process Fig. 1 Golden Hour algorithm initial airway management was based on the infant''s gestational age and assessment of risk factors for respiratory failure. Implementation of an evidence-based GH protocol was effective at significantly improving euglycemia, euthermia, and time to completion of admission stabilization for EP-ELBW infants in our NICU. Following project implementation, admission temperatures in our unit for infants <27 weeks'' gestation consistently fell within the Vermont Oxford Network''s reported ranges for similar type NICUs. Although we did not consistently meet our goal of completion within the first 60 min after birth, we made significant improvements in time from baseline.

cord-010884-g4gesvzt	
cord-010919-h7d8z5z0	Durch sie können Erkrankungen erfolgreich eliminiert und allgemeine Gesundheitsziele erreicht werden, wie die Senkung von Kindersterblichkeit, gesundes Altern oder die Reduzierung von Ungleichheiten in der Gesundheit. Nicht nur, weil es mittlerweile Impfstoffe gegen deutlich mehr Erreger gibt (einschließlich solcher, die Krebs verursachen, wie Hepatitis B oder humane Papillomviren), sondern auch, weil Impfen inzwischen breiter gedacht wird und als integraler Bestandteil eines funktionierenden Gesundheitssystems mit Relevanz für alle Altersgruppen gilt. Barrieren, die die Umsetzung von Impfstrategien und die Entfaltung des tatsächlichen Public-Health-Potenzials der verfügbaren Impfungen behindern (wie Impfskepsis, niedrige Impfquoten und eine Ungleichheit bei der Inanspruchnahme von Impfungen auf subnationaler Ebene oder durch Risikogruppen), bleiben Probleme, mit denen fast alle Länder konfrontiert sind. Wir hoffen, dass dieses Themenheft, das wichtige Entwicklungen auf den genannten Gebieten zusammenfasst, zum Verständnis der Bedeutung und des Potenzials von Impfungen für die globale Gesundheit beitragen kann.

cord-010933-xuztu95a	Uncertainty in patient resource demand is caused by several stochastic processes, including the number and timing of arrivals and discharges, length of stay (LOS), unit transfers, health improvement and deterioration, surgical complications, and same-day cancellations for outpatient and surgical appointments. Developing and applying an accurate model to forecast patient resource demand for multiple time periods into the future improves both the cost and safety of providing care when coupled with an adaptive staffing strategy. Most models make simplifying assumptions to manage tractability and fit data availability, including assuming stationary or cyclic demand patterns [16, 17, 36] , exponential-based inter-arrival times and LOS distributions [17, 36, 48, 49] , patient homogeneity [10, 31, 36] , singleday forecasts [47] , and point estimates instead of probability mass functions (PMFs) [14, 31] . The goal of this study is to forecast an accurate approximation for the multi-period PMF of bed demand using the exact surgical schedule at the time of the forecast, non-stationary inter-arrival times, and patient-level duration-varying LOS distributions.

cord-010970-f79rnhc5	title: Evaluation of diaphragm ultrasound in predicting extubation outcome in mechanically ventilated patients with COPD BACKGROUND: To explore the value of the right hemi-diaphragmatic excursion (DE) and its variation in predicting extubation outcome in mechanically ventilated patients with COPD. The previous studies have showed that the DE measured by ultrasound could be used to assess respiratory effort, and while diaphragmatic thickening fraction was shown to be correlated strongly with diaphragm strength and ventilator support level, the right DE assessed by ultrasound was more reliable, more feasible, and more repeatable [12] [13] [14] [15] [16] [17] [18] . Therefore, the aim of our study was to explore the value of the right DE and its variation assessed by ultrasound in predicting extubation outcome in mechanically ventilated patients with COPD.

cord-011010-r8quizqn	key: cord-011010-r8quizqn cord_uid: r8quizqn [1] , which retrospectively analyzed a large cohort of patients admitted to the surgical intensive care unit. Although results are encouraging in the quest to find evidence that supports the relevance of intensivist in the management of post-surgical patients, two questions have come up in the interpretations of the results. Firstly, parameters of intraoperative management which may affect the postoperative incidence of acute kidney injury (AKI) were not sufficiently included in the contributors of propensity score. Secondly, in the sensitivity analysis of AKI according to admission time, there were only two time-points where the associations were significant and there seems no dose-response relationship between the duration of nonintensivist coverage and the incidence of AKI. Admission to the surgical intensive care unit during intensivist coverage is associated with lower incidence of postoperative acute kidney injury and shorter ventilator time Prediction and prevention of acute kidney injury after cardiac surgery

cord-011029-sbds5sda	We compared the prognostic value of ∆PCO(2) on intensive care unit (ICU) admission to an original algorithm combining ∆PCO(2), ERO(2) and lactate to identify different risk profiles. An algorithm incorporating ICU admission values of ∆PCO(2), ERO(2) and lactate defined a high-risk profile that predicted prolonged ICU and hospital stays better than ∆PCO(2) alone. Surrogate markers like central venous to arterial PCO 2 difference (ΔPCO 2 ), oxygen extraction ratio (ERO 2 ) and lactate are used to evaluate this adequacy [2, 3] . In this pilot study, we evaluate the prognostic value of ΔPCO 2 at the time of ICU admission and compare it to an original algorithm combining ΔPCO 2 , ERO 2 and lactate to identify different risk profiles after elective conventional cardiac surgery. The algorithm combining ΔPCO 2 with ERO 2 and lactate identified 12 patients with a low-risk profile and 13 patients with a high-risk profile at the time of admission.

cord-011050-vt1b8ukw	The current study seeks to expand the knowledge in this area by assessing the moderating influence of social support on the association between economic forms of abuse and economic hardship in a community-based sample of women. Importantly for the current study, CCT posits that IPV survivors will have lower levels of economic stability compared to others, as an abusive partner uses various tactics (including physical and emotional violence and their resulting mental and physical health consequences, as well as tactics of EA) to increase economic dependence in order to enhance their control over all aspects of life (Stark 2007; Postmus et al. Bivariate correlations between abuse exposure, key study variables, and demographic characteristics were analyzed (See Table 3 Table 4 presents the results for linear regression models that assess the impact of the interaction between appraisal and tangible social support and economic abuse on participants'' level of material hardship experience.

cord-011073-uiabpbxd	Oriental theileriosis, a tick-borne disease of bovids caused by members of the Theileria orientalis complex, has a worldwide distribution. orientalis complex, including conventional polymerase chain reaction (PCR), nested-PCR, reverse line blot hybridisation assay (RLB), loop-mediated isothermal amplification (LAMP), real-time/quantitative PCR (qPCR) using hydrolysis probes and multiplexed tandem PCR (MT-PCR) assays (Table 2) . nPCR Members of the Theileria orientalis complex have been detected in cattle blood samples in Brazil, Iran, South Africa, Uganda and the USA using semi-nested or nested PCR (nPCR) assay employing the SSU or ITS loci (Chae et al. orientalis allow for a rapid and accurate diagnosis (mainly for the two pathogenic genotypes chitose and ikeda), some assays can be expensive for routine use due to individual testing of blood samples, particularly when outbreaks of oriental theileriosis occur in cattle herds. Development and evaluation of a real-time PCR assay for the quantitative detection of Theileria annulata in cattle

cord-011103-sstpidvk	CONCLUSIONS: Among critically ill trauma patients, acute kidney injury, injury to the spine, face or sternum, massive transfusion and intensive care unit length of stay were associated with VAP. Variables collected from the patients'' medical records and trauma database included age, race, gender (demographics), presenting vital signs, injury type and severity, the presence of ventilator-associated pneumonia, hospital and intensive care unit length of stay and survival data. We found that, among critically ill trauma patients admitted to the intensive care unit, injury to the spine, face or sternum, massive transfusion, acute kidney injury and intensive care unit length of stay were associated with ventilator-associated pneumonia (VAP). Among critically ill trauma patients admitted to the intensive care unit, acute kidney injury, injury to the spine, face or sternum, massive transfusion and intensive care unit length of stay were associated with VAP.

cord-011106-h20vbmbo	Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. In addition, we assessed hibiscus tea extract''s potential as a candidate for novel anti-IAV drug and as an inactivating agent for whole-virus vaccines. PR8 virus propagated in allantoic fluid was mixed with an equal amount of neutral and acidic pH PBS, Hib[crude], frHibis, or PCA. 50 μl PBS, formalin-, β-PL-, or acidic Hib[crude]-inactivated PR8 virus vaccine was intranasally administered in mice (first vaccination) under light anesthesia with isolflurane (Intervet K.K., Tokyo, Japan). The neutralized Hib[crude] in the blood loses potent anti-IAV activity due to acid, and the low-pH-independent antiviral activity is inadequate to inactivate virus in vivo.

cord-011146-r3nv14ph	When evaluating transport time intervals, time required for evaluation by the transport team was associated with increased risk of clinical deterioration. Several factors have been associated with adverse neonatal outcomes after transport: the condition of an infant around the time of transport and provision of intensive care during transport have both been linked to increased morbidity and mortality [11, 12] . The goal of this study was to identify maternal and neonatal risk factors, transport characteristics and transport time intervals that are associated with increased risk of clinical deterioration during transport. Increased risk of clinical deterioration was also associated with a low Apgar score at 5 min, the need for delivery room resuscitation and greater birth defect severity (Levels 4 and 5). We did find that transports teams that take longer than 60 min to arrive at the referring NICU were associated with increased risk of clinical deterioration.

cord-011184-ohdukhqt	In this review, we will discuss the identified plant-based bioactive proteins and peptides and the in vitro, in vivo results for the treatment of diabetes. Till date, plant secondary metabolites, mainly small molecules are the established source of new drugs to treat various diseases (Verpoorte 1998) , however, advancement in analytical technique, sophisticated purification methodology and in vitro assay system pointed out the researchers Fig. 1 Uses of therapeutic peptides and proteins in various disease conditions (Loganathan 2016) 1 3 to look beyond the small molecules. Many peptides are reported from different plants for the treatment of diabetes as shown in Tables 2 and 3 through various known targets such as (a) Alpha-glucosidase inhibitors (b) Alpha-amylase inhibitors (c) Dipeptidyl peptidase-IV inhibitors (d) Inhibitors of the glucose transporter system (e) Insulin mimetics Plant-derived bioactive peptides inhibit the enzymes like alpha-glucosidase, alpha-amylase, dipeptidyl peptidase-IV and glucose transporter systems involved in type 2 diabetes.

cord-011189-c0ytamge	The real impact of MDRs on the outcomes of ICU patients is debatable, but despite this controversy, the incidence of MDRs is related to poor quality-of-care, as an expression of reduced compliance to hand hygiene [14] , and a high burden of antibiotic exposure [15] . De-escalation decreases the time of antibiotic use, but a short exposure still exists; in this way, a single antibiotic dose may be enough to treat severe infections such as Fig. 1 Two different mindsets in the decision making process to initiate antibiotics to critically ill patients who are getting worse. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensivecare-unit-acquired infection: a quasi-experimental, before and after observational cohort study

cord-011192-h0omskec	As an example, one study examined mortality rates among children with stage 3 AKI who were and were not receiving critical care; patients who developed AKI while in the intensive care unit (ICU) had an increased risk of death (likelihood ratio 14.3, 95th CI 9.2-22.4) whereas those on acute care wards did not (likelihood ratio 1.22, 95th CI 0.7-2.1) [1] . Across both acute and critical care populations, AKI is associated with longer lengths of stay, non-recovery of baseline renal function, and chronic renal disease including proteinuria, hypertension, and chronic kidney disease (CKD). Perhaps, the best illustration of the mortality impact of AKI among neonates is the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study which evaluated the incidence of and outcomes following AKI across 2162 newborns from 24 pediatric institutions (Table 1 ) [19] . Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study

cord-011209-ms5t5fx7	
cord-011234-awbubjy4	This study represents the largest case-controlled retrospective review of the MBSAQIP PUF database comparing perioperative outcomes in laparoscopic-and robotic-assisted revisional/ conversional bariatric surgery. Our case-control matched analysis of 2288 revisional bariatric cases revealed longer operative duration and hospital length of stay, and higher rates of ICU admission, aggregate leak and bleeding complications in the robotic-assisted bariatric surgery compared to conventional laparoscopy. Taking into consideration the above outlined study limitations, the findings of this case-control matched analysis comparing these two surgical approaches for revision/conversion metabolic and bariatric surgery show that using the robotic platform is overall safe, but is associated with longer operative times and a higher rate of some perioperative outcome measures.

cord-011242-4e2krzxe	OBJECTIVE: Evaluate renal outcomes and early predictive factors in infants with congenital posterior urethral valves who required catheter or surgical urinary tract decompression within the first 7 days of life. Given the challenges associated with the heterogeneity of this patient population, the aim of this study was to isolate a specific cohort of infants with severe LUTO caused by PUV who presented and had intervention in the first week of life, to evaluate renal outcomes and early predictive factors. Covariates included birth gestational age, race, prenatal, and postnatal ultrasound (US) findings, presence of vesicoureteral reflux, nadir creatinine in first year of life, duration of follow-up, other renal or urologic surgical interventions, and any respiratory support required during the newborn or follow-up period. In this cohort, 50% of infants with PUV who presented and required catheter or surgical urinary tract decompression in the first week of life developed significant renal insufficiency or ESRD during the study period.

cord-011248-mszlz4jk	To investigate the use of two-site regional oxygen saturations (rSO(2)) and end tidal carbon dioxide (EtCO(2)) to assess the effectiveness of resuscitation and return of spontaneous circulation (ROSC). Although NIRS technology has been validated and used in many clinical scenarios, limited studies have examined the role of two-site rSO 2 monitoring during cardiac arrest to assess the effectiveness of chest compressions and detection of ROSC without interrupting resuscitation efforts [19] [20] [21] [22] . In this swine pediatric VF arrest model, two-site rSO 2 obtained by NIRS technology, and EtCO 2 correlates with cardiac output changes during CPR and can be used to guide resuscitations efforts and detect ROSC without interrupting resuscitation efforts. Further studies are required to explore the use of two-site rSO 2 and capnography as a tool for early detection of CA, monitor effectiveness of chest compression, and detection of ROSC among critically ill pediatric patients who suffer from cardiac arrest.

cord-011266-ot7es8zd	title: Incidence, Risk Factors, and Outcomes of Ventilator-Associated Pneumonia in Traumatic Brain Injury: A Meta-analysis Ventilator-associated pneumonia (VAP) is one of the most severe complications in patients with traumatic brain injury (TBI) and is considered a risk factor for poor outcomes. In addition, previous studies have demonstrated that the risk factors for VAP among patients with TBI include smoking, higher injury severity score (ISS), tracheostomy, diabetes, and so on [8] [9] [10] [11] [12] . Two people extract data from eligible articles independently, including study characteristics (first author, publication time, country, number of patients, number of VAP, gender, age, study design, the definition of VAP, the severity of TBI), incidence, risk factors, and indexes representing clinical outcomes (mortality, mechanical ventilation time, intensive care unit (ICU) length of stay, hospital length of stay), so as to provide a comprehensive description of VAP among patients with TBI.

cord-011282-hgzneooy	Following the resolution adopted at the first International Clinical Engineering and Health Technology Management Congress [8] that took place in Hangzhou, China, in October 2015, senior members from the CE profession from around the world who participated in the Global CE Summit [9] initiated the international project seeking evidence to the hypothesis that the engagement of CE and BE in guiding HT deployment positively impacts patient outcomes while the null hypothesis was that there is no difference. Safety and Quality services that dependent on complex technological systems is critical for outcomes and therefore identified with its own group of data Technology management group was the next category to be reviewed where CE/BME contributions to organized, integrate, manage, and improve safe and efficient sustainable HT. Overall this review identified evidence from 400 case studies received from 125 countries where management of medical devices (as main component of health technologies) made a positive difference over the past twelve years.

cord-011310-fm578rm5	Several guidelines recommend the screen-and-treat strategy, i.e. active search for the presence of Helicobacter pylori infection and its eradication to prevent the possibility of gastric cancer. Furthermore, no differences in the eradication regimen are currently recommended, depending on whether the treatment is given for a clinically evident disease, e.g. for complicated ulcer disease or MALT lymphoma from prevention strategies in population-based settings. The recent guidelines of ASEAN (Association Southeast Asian Nations) countries support eradication to prevent gastric cancer by considering this strategy as costeffective, depending on the disease burden in the relevant community [19] . An expert group hosted by IARC has suggested the need for interventional strategies to decrease the burden of gastric cancer [1, 22] ; however, experts recommended that this be done by the means of well-designed clinical studies evaluating the feasibility, acceptance, costs, effectiveness and adverse consequences.

cord-011318-lw9vluxm	Inside host cells, especially DCs, Brucella modulates the expression of surface molecules related to maturation, costimulation, migration and/or Ag presentation, as well as influences cytokine production (Billard et al. In a comparative study, human monocyte-derived GM-DCs were infected with different intracellular bacterial pathogens: Orientia tsutsugamushi the etiologic agent of scrub typhus, Coxiella burnetii responsible for Q fever, and Brucella. Despite the impaired GM-DC maturation observed in the experiments of Billard et al., Brucella infection was slightly detected based on the immune response, since low cytokine levels were induced. abortus 2308 (1000 bacteria/cell) to infect murine DCs, observing upregulation of costimulatory molecules, as well as significant cytokine production. With the exception of bovine-derived DCs, this pathogen infects and replicates inside DCs. Brucella recognition at the outside of the eukaryotic cell is mediated by TLRs and signaling triggers the immune response, as shown by cytokine production. Central role of MyD88-dependent dendritic cell maturation and proinflammatory cytokine production to control Brucella abortus infection

cord-011325-r42hzazp	Even if only based on a temporal sequence of events, it is important that such safety concerns are rapidly investigated with robust epidemiological studies to allow mitigation procedures to be put in place if an association is confirmed or, if unfounded, to have the necessary evidence to sustain public confidence in the vaccination programme without which coverage drops and disease control is lost. The self-controlled case-series method (SCCS) was designed for rapid unbiased assessment in vaccine safety studies using available disease surveillance data that may not be amenable to cohort analysis. As with all vaccine safety studies, but particularly in the case of narcolepsy and Pandemrix™ where the association was completely unexpected, the key to demonstrating causality was consistency of results from well-designed studies in different settings. Risk of narcolepsy after AS03 adjuvanted pandemic A/ H1N1 2009 influenza vaccine in adults: a case-coverage study in England

cord-011332-dzl09afq	PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1–66.6%) for VAP, 8.9% (95% CI, 6.2–11.5%) for primary, 15.1% (95% CI 11.6–18.5%) for secondary and 5.0% (95% CI 3.2–6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. The case report forms include information on the following: invasive devices (mechanical ventilation [MV] and central venous catheters [CVCs]), HAIs (VAP, primary BSIs, catheter-related BSIs, and secondary BSIs), neutropenia (white blood cell [WBC] count < 1000/mm 3 or acute leukemia) before admission (duration and nadir), and outcomes at discharge from ICU (infections [date of diagnosis, pathogen] and death.

cord-011400-zyjd9rmp	Researchers have approached this reconstruction task from a variety of angles, resulting in many different methods, including thresholding the correlation between time series [6] , inversion of deterministic dynamics [7] [8] [9] , statistical inference of graphical models [10] [11] [12] [13] [14] and of models of epidemic spreading [15] [16] [17] [18] [19] [20] , as well as approaches that avoid explicit modeling, such as those based on transfer entropy [21] , Granger causality [22] , compressed sensing [23] [24] [25] , generalized linearization [26] , and matching of pairwise correlations [27, 28] . [32] proposed a method to infer community structure from time-series data that bypasses network reconstruction by employing a direct modeling of the dynamics given the group assignments, instead. We take two empirical networks, the with E ¼ 39430 edges, and a food web from Little Rock Lake [46] , containing N ¼ 183 nodes and E ¼ 2434 edges, and we sample from the SIS (mimicking the spread of a pandemic) and Ising model (representing simplified interspecies interactions) on them, respectively, and evaluate the reconstruction obtained via the joint and separate inference with community detection, with results shown in Fig. 2 .

cord-011503-bz6iwfan	The inclusion criteria were cross-sectional, longitudinal, case-control, and cohort studies; of children aged 0–18 years whose parents are high-risk substance misusers; reporting on their health, psychological, substance use, educational, and social outcomes. To be included, studies must report on parental substance misuse that meets one of the following criteria: a pattern of alcohol consumption that leads to the presence of physical or psychological problems (typically over 35 units per week for women and over 50 units per week for men); frequent illicit drug misuse (more than once per month as defined by the Crime Survey for England and Wales); and alcohol or illicit drug abuse defined as a maladaptive pattern of drinking/drug use, leading to clinically significant impairment or distress, as manifested by at least one related problem in a 12-month period (failure to fulfill major role obligations, use in situations in which it is physically hazardous, alcohol or drug-related legal problems, having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol or drugs; American Psychiatric Association, 2013).

cord-011800-8h7eiihp	Recognizing challenges of COPD management in China, he and colleagues performed the largest epidemiologic investigation on the national disease burden, highlighting that approximately 36% of patients with COPD remained asymptomatic on presentation, that biomass fuel combustion might be the main risk factor for COPD in women (particularly in rural areas), and that simple practical approaches (eg, installation of exhaust fans and replacing biomass with biogas) may significantly ameliorate the rate of lung function decline and reduce the incidence of COPD. His comments on improving air quality to reduce the burden on chronic respiratory diseases have inspired scientists and clinicians to dedicate themselves to the prevention and management of air pollution in China. Biomass fuels are the probable risk factor for chronic obstructive pulmonary disease in rural South China Community based integrated intervention for prevention and management of chronic obstructive pulmonary disease (COPD) in Guangdong, China: cluster randomised controlled trial

cord-011975-8vl45xb7	BACKGROUND: Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH) and its contribution to hospital complications, length of intensive care unit stay, and functional outcome. The main goal of the current study was (1) to quantify the rate of swallowing disorders after SAH by using a simple clinical assessment tool, (2) to identify early predictors of dysphagia in all severity grades of SAH patients, and (3) to evaluate how dysphagia contributes to hospital complications, length of ICU stay, and poor outcome. CT computed tomography, EVD external ventricular drain, ICU intensive care unit, IQR interquartile range Statistical analysis was performed using the Wilcoxon rank-sum test (*), the Chi-square test ( †), and the linear-by-linear association test for trend ( ‡) Although it is well known that the high incidence of swallowing disorders after ischemic stroke contributes to impaired quality of life and poor functional outcome, only few studies report the incidence of dysphagia following SAH [9, 10] .

cord-012035-rhpfpku9	In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. Intriguingly, it was found that preparation via a high concentration The clinical trials can be found at https://www.clinicaltrials.gov TRAIL-based gene delivery and therapeutic strategies HH Zhong process (i.e., a small reaction volume) resulted in large PEI/DNA complexes that had a higher gene transfection efficiency than their small counterparts prepared at a low concentration (Fig. 3 ) [54] . reported a novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TRAIL in adipose-derived mesenchymal stem cells (AD-MSCs) [86] . Mesenchymal stem cells as a novel carrier for targeted delivery of gene in cancer therapy based on nonviral transfection

cord-012370-omz7kibf	title: Forensic genetic analysis of population of Madhya Pradesh with PowerPlex Fusion 6C(™) Multiplex System The study also presents the first global report on polymorphism in the Indian population on SE 33 autosomal STR loci and PP Fusion 6C Multiplex System. A few studies have been performed to characterize the population of Madhya Pradesh on autosomal STRs (described in Table S2 ) but these studies are based on 15 STR markers either using Identifiler/Identifiler Plus (Applied Biosystem, USA) or PowerPlex 16/16HS (Promega Corporation, Madison, USA). The most polymorphic and discriminatory STR loci in the studied population were SE 33 with values of 0.94 and 0.990, respectively. The data obtained in this study were compared with published Indian population data (Table S2 ) related to common 15 autosomal STR loci. With respect to the distribution of alleles at each STR locus, the loci were found to be substantially polymorphic in this population indicating good informativeness of all studied autosomal STR markers.

cord-012374-excn1a10	The increase of SAP18 expression inhibited the ERK/STAT3 signaling pathway, which regulates the differentiation of HSPCs into mo-MDSCs. Thus, these findings reveal a novel role for CXCR2 through which SAP18/ERK/STAT3 signaling regulates hematopoietic cells differentiation in the tumor microenvironment. A one-way ANOVA with repeated measures followed by a Dunnett''s post hoc test or a two-way ANOVA followed by Holm-Sidak''s post hoc test were used to determine the level of statistical significance (*p < 0.05; **p < 0.01; and ***p < 0.001; ns, not significant) Fig. 2 CXCR2 deficiency impairs the differentiation of myeloid progenitor cells into mo-MDSCs. a The percentage of mo-MDSCs and G-MDSCs induced from WT or CXCR2−/− bone marrow cells were detected by flow cytometry. The results showed that knocking down SAP18 in CXCR2−/− tumor-bearing mice increased the percentage of the genes that are consistently 1.5-fold upregulated or two-fold downregulated in 32D clone three cells transfected with CXCR2 or the empty vector, and both cells were incubated with CXCL1 and CXCL2 for 4 h.

cord-012607-bvxbzgx3	title: Progression to ambulation following lower limb fractures in an individual with a spinal cord injury: a case report INTRODUCTION: Patients with spinal cord injury (SCI) and concomitant lower limb fractures are a challenge to rehabilitate. The associated lower-extremity fractures can be a setback in individuals with an SCI, which can always pose a threat in achieving standing balance and gait training [8, 9] . The objective of this case report is to present a low-cost rehabilitation strategy that can be performed without loading the fractured lower limbs and help achieve functional goals. Although the Spinal Cord Injury Rehabilitation Evidence guidelines indicate that standing in a tilt table or in the parallel bars is a recommended therapy at the end of 4-6 weeks [13] , this is to be done only if the individual does not have an associated lower limb fracture. Conclusion "K-ing strategy" may be useful for progression to ambulation in SCI patients associated with foot and ankle fractures.

cord-012618-ulqajban	1 published in Signal Transduction and Targeted Therapy, Dr. Yu Liu and collaborators report that the differentiation block in UTX-null leukemia cells can be reverted by an LSD1 inhibitor, highlighting additional ways of targeting UTX-deficient malignancies. 2 A series of recent studies have established the role of UTX as a tumor suppressor in leukemia, lymphoma, pancreatic, and lung cancers. In many cancer models, the role of UTX as a tumor suppressor has been linked to epigenetic changes associated with UTX loss. 6, 9 Second, in pancreatic cancer models it was found that UTX-deficient cancer is sensitive to BET inhibitors, which restrain gene expression from super-enhancers that are altered by UTX loss. In AML, the loss of the H3K27 methyltransferase EZH2 induced resistance to cytarabine, 10 whereas in lymphoma models the loss of the H3K27 demethylase UTX sensitized the cells to this drug. Epigenetic drug library screening identified an LSD1 inhibitor to target UTX-deficient cells for differentiation therapy

cord-012623-bc9fj29h	title: Participant-reported priorities and preferences for developing a home-based physical activity telemonitoring program for persons with tetraplegia: a qualitative analysis OBJECTIVES: The purpose of this qualitative study was to explore perceptions and priorities of persons with spinal cord injury (SCI) for physical activity and to incorporate their feedback to inform future development of a physical activity program delivered via a telemonitoring platform. Another study measured the effects of a home-based exercise program in persons with chronic SCI, including outcome measures of metabolism, body composition, physical activity, energy intake, measures of health and wellbeing, resting metabolic rate, heart rate, and blood pressure, aerobic capacity, immune function, and adipose gene expression [23] . Here, we report the results of a qualitative study of priorities and preferences for developing a home-based physical activity telemonitoring program for persons with tetraplegia.

cord-012629-655dmp7c	Many people living with spinal cord injury (SCI) receive care from both SCI specialists and general practitioners (GPs). In this study, we distributed a survey assessing SCI specialists'' interest in and assessment of their communication with GPs, and whether these communications are influenced by the economies and the health-care systems in which they work. Nearly all respondents (91.6%) felt that the care they provided to their patients with SCI would be enhanced by improved communication with GPs. Among the participants who routinely communicated with their patients'' GPs (n = 47), 40.0% reported primarily corresponding by mail or fax and 28.9% by phone (15.6% through EHR, 11.1% in person, and 4.4% through other secure messaging systems). Neither participants'' home nations'' economic status nor the type of health-care system in which they worked influenced whether their patients also saw a GP, their comfort with serving as a GP for individuals with SCI, whether they routinely communicated with GPs, or their means of communicating with GPs. In grouping certain answers for analysis, several significant associations emerged.

cord-012649-rxx5ash4	authors: Krogh, Klaus; Halvorsen, Annette; Pettersen, Ann Louise; Biering-Sørensen, Fin title: Version 2.1 of the International Spinal Cord Injury Bowel Function Basic Data Set In the process of translation of the English version into Nordic languages (Danish, Icelandic, Norwegian, and Swedish) of the International Spinal Cord Injury Bowel Function Basic Data Set version 2.0 [1] some inconsistencies were recognized which here will be corrected and clarified: 1. For the variable "Surgical procedures on the gastrointestinal tract": In the data-collection form ''Hemorrhoidectomy, date performed YYYYMMDD'' was missing 2. In the Data-collection form "Less than once per month/Never" shall be together in one code, because the variable is describing the frequency ''within the last 4 weeks''which is also the description given in the Syllabus. International spinal cord injury bowel function basic data set (Version 2.0)

cord-012652-ymsag3iq	The aim of this survey was to characterize how physicians throughout the world working with patients who have SCD approach the prescribing of opioids for pain, and to compare the results to representative clinical practice guideline recommendations. When physicians who felt that opioids were sometimes appropriate in the treatment of chronic non-cancer neuropathic pain related to SCD were asked whether there was a maximum MME dosage that should be routinely prescribed for intractable pain, nearly half (46%) felt that there should be no specific limit on dose, indicating that it depends on an individual''s opioid tolerance. The practice patterns related to the prescription of opioids for chronic pain in persons with SCD in this international sample of clinicians differs in several key areas from those recommended in clinical practice guidelines published in the United States [11] , Canada [12] , Australia [15] , Great Britain [14] , South Africa [16] , and Germany [13] .

cord-012654-m8nlsutd	Regulation of RNA alternative splicing is a crucial process in RNA-binding proteins function, and aberrant splicing is often associated with various human diseases including cancers; 8 therefore, to discern how DNA-PKcs modulates bound RNAs, we sought to determine whether DNA-PKcs could affect CD44 alternative splicing. Specific primers to amplify the CD44 standard sequence and variants were designed, and qPCR was performed to examine the expression of different variants after U2OS cells were treated with NU7441 and NU7026, which target DNA-PKcs. The results showed that V4, V9, and V10 increased. In summary, our findings strongly support a model wherein the DNA-PKcs protein controls a variety of biological processes, including alternative splicing, through its RNA-binding activity. The human telomerase RNA component, hTR, activates the DNA-dependent protein kinase to phosphorylate heterogeneous nuclear ribonucleoprotein A1 Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer

cord-012719-5qa0e4xt	PURPOSE: To compare retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness in patients with unilateral exfoliation syndrome (XFS) and age-matched controls using spectral domain-optical coherence tomography (SD-OCT). In the present study, patients with unilateral XFS without glaucomatous optic nerve changes or visual field defects showed thinner RNFL and GCC thicknesses than those of control individuals. Besides the impact of IOP, we postulate that the reasons for the thin RNFL and GCC thickness in the present study are related to (1) systemic, or (2) local vascular factors, and Data are presented as mean ± SD (range); P value was calculated by one-way ANOVA ANOVA analysis of variance, RNFL retinal nerve fiber layer, XFS exfoliation syndrome a Although the p value by ANOVA demonstrated statistical borderline significance, post-hoc analysis was performed using Tukey''s test. In this study, thin RNFL and GCC thicknesses were also observed in the fellow eyes of patients with unilateral XFS, as compared with that of healthy control subjects.

cord-012791-dyk5mr1q	title: Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ(1–40), Aβ(1–42), amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. The present study revealed that (1) ICS II protects against LPSinduced inflammation in primary-cultured astrocytes; (2) the inhibitory effect of ICS II is due to regulation of the IKK/IκB/NF-κB signaling pathway; and (3) ICS II decreases Aβ 1-40 and Aβ 1-42 levels by downregulating APP and BACE1 expression (Fig. 7) . In conclusion, the current study revealed that ICS II exerts inhibitory effects on LPS-induced inflammation in astrocytes through the IKK/IκB/NF-κB/BACE1 signaling pathway, and thus ICS II may be a promising therapeutic agent for neuroinflammatory diseases, including AD.

cord-012823-i3yhaagz	UUO group displayed significant degree of renal dysfunction, interstitial fibrosis, oxidative stress, and activation of the TGF-β/Smad and Wnt/β-catenin signaling pathway in the kidney, these pathological changes were greatly ameliorated by pretreatment with AA. Our results showed that AA upregulated the expression of nuclear-localized sterol regulatory element-binding proteins-1 (nSREBP-1), enhanced 15d-PGJ2, activated PPAR-γ, and consequentially attenuated renal damage in unilateral ureteral occlusion (UUO) models. The treatment of mice with 15d-PGJ2 produced a significant attenuation of the UUO-induced increase in Col I, FN, and α-SMA expression, indicating an improvement in interstitial fibrosis, while the administration of GW9662 abolished the protective effect mediated by 15d-PGJ2 (Fig. 5b) . Our major novel findings include the following: (1) AA attenuates renal injury, oxidative stress, and fibrosis induced by the activation of PPAR-γ through increasing its Fig. 3 a PCA scores plot from control and UUO groups.

cord-012828-wsjob1p8	We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Some previous research has suggested that spinal cord injury induces inflammatory cytokine production by activating the nucleotide-binding domain-like receptor protein 3 inflammasome pathway, which is significantly suppressed by DRD1 agonists [14] . Therefore, in this study, we explored the mechanism of the anti-neuroinflammatory effects of isosibiricin in a BV-2 microglial model and highlighted that isosibiricin can significantly inhibit the production of multiple inflammatory mediators induced by bacterial lipopolysaccharide stimulation via targeting the DRD1/D2-dependent inflammasome pathway, providing a potential therapeutic strategy for inflammation-related neurological disorders. Isosibiricin inhibits the NLRP3/caspase-1 inflammasome pathway in LPS-or nigericin-treated BV-2 cells and LPS-treated Balb/c mice It has been reported that the expression of the pro-inflammatory mediator IL-1β significantly increases in DRD2-null mice compared with wild-type mice [24] .

cord-012995-1acymenq	We chose to further characterize a gene identified most frequently in our screen (echA) encoding a putative enoyl-CoA hydratase that, when disrupted, leads to a decrease in biofilm accumulation and increased susceptibility to multiple classes of antibiotics. We took interest in the gene encoding a putative enoyl-CoA hydratase (Axylo_0405) given the importance of homologous proteins in fatty acid signal biosynthesis and biofilm development among diverse bacterial species. Enoyl-CoA hydratases are central to the biosynthesis of a class of fatty acid signaling molecules, or diffusible signal factors (DSFs), that have been described in diverse bacterial species for their role in mediating virulence, motility and biofilm development. Since the CV staining approach used in the initial mutant screen relies on a dye that stains not only cells, but all biomass adhering to the microtiter plate, we elected to use additional biofilm assays to further characterize the biofilm phenotype of ΔechA, and whether disruption of the putative enoyl-CoA hydratase negatively impacts a specific stage of biofilm development (e.g. attachment, matrix production, maturation).

cord-013503-tjotro5h	By constraining a leaf metabolic model to the two conditions and using an appropriate flux sampling algorithm, we were able to explore inherent metabolic robustness to temperature and predict the metabolic changes required to support a photosynthetic acclimation response to cold. Using the experimental data shown in Fig. 3 to constrain the CO 2 input and the malate, fumarate, and starch accumulation reactions using the Arnold model (please see methods for further details), we were able to compute converged flux sampling distributions for all reactions. We did so for both control and cold conditions, which allowed us to overlay the sampling distributions of reaction fluxes and to assess changes required in plant metabolic behavior for acclimation (Fig. 4) . In order to demonstrate how the application of an objective function for an FBA analysis can lead to vastly different conclusions, we have overlaid FBA results for maximum biomass production (under the same model constraints as applied for the sampling) over the flux sampling distributions (Fig. 4) .

cord-013521-ec9rkxdn	METHODS: Participants were randomized to receive subcutaneous injections of either placebo or BoNTA with follow-up (office visit, telephone, or e-mail) at 2, 4, 8, and 12 weeks to assess the magnitude of pain relief post injection. Although our data did not meet statistical significance, we noted a higher proportion of participants reporting a marked change in average pain intensity from baseline to 8 and 12 weeks post-BoNTA vs. Participants were included if they reported chronic traumatic SCI (duration >6 months) and pain that has been: (1) present continuously for ≥1 month, (2) of at least moderate average intensity over the prior week (numeric pain rating scale [NPRS] score ≥ 4/10) and (3) diagnosed by an SCI provider as being at-level SCI pain with a high degree of certainty [14] . Participant H reported no pain reduction post-placebo, received BoNTA for P2 some months after 12-week follow-up for P1, then was lost to follow-up (Table 2) .

cord-013523-hcd4bwy0	INTRODUCTION: Spinal cord injury (SCI), specifically suprasacral SCI, results in high intravesical pressures, elevated post-void residual and urinary incontinence which are all risk factors for urinary tract infections (UTIs). Removal of these UTI risk factors and improving urinary drainage are goals of urologic management; however, when conservative interventions do not succeed, surgery may be a viable solution in select cases of rUTIs. CASE PRESENTATION: We present a case of complicated persisting rUTIs and associated urethral discharge in a middle-aged SCI male who manages his bladder with intermittent catheterization (IC). We detail the evaluation and management approach that leads to an eventual transurethral prostatectomy (TURP) as a final solution for his rUTIs. Fortunately, the surgical intervention was successful, and the patient is free of UTIs after 4 years of follow-up. DISCUSSION: In SCI male patients with rUTIs and suspected chronic prostatitis, TURP may be a valuable treatment option once all predisposing factors have been remediated.

cord-013546-3ff933jc	PURPOSE: To study the relationship between macular ganglion cell complex (GCC) thickness and visual field defects (VFD) caused by central nervous system (CNS) lesions in children and evaluate the possibility of predicting VFD according to GCC maps. METHODS: The GCC maps of a group of children with VFD due to CNS lesions with respect of the vertical meridian in at least one eye (study group), as well as of children with other neuro-ophthalmological problems and healthy children were presented to two masked evaluators, who were asked to predict the patients'' VFD on the basis of GCC damage: the evaluators classified VFD as normal, hemianopia (homonymous or heteronymous) or diffuse. The aim of this study was to evaluate the relationship between reduction in macular ganglion cell complex (GCC) thickness as detected with spectral-domain OCT and visual field defects caused by central nervous system lesions in children, as well as to determine whether it is possible to predict visual field defects from GCC maps.

cord-013803-d1sbfibq	title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis Previous studies demonstrated upregulation of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, IL-15 and IL-17 in the aqueous humour (AH) samples from autoimmune uveitis patients [1] [2] [3] [4] [5] . For these reasons, we analyzed the AH from patients with active uveitis associated with four systemic inflammatory diseases (sarcoidosis, VKH disease, BD and HLA-B27-related inflammation) for the presence of sCD30, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII. Compared with controls, TNF-α, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII levels were significantly higher in BD and HLA-B-27-associated uveitis. Among the cytokine and soluble cytokine receptors analyzed, TNF-α and sCD30 differed significantly between patients with BD, sarcoidosis, HLA-B27-associated uveitis and VKH disease (p = 0.029; p = 0.001, respectively) (Fig. 1a) .

cord-014597-66vd2mdu	Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line.

cord-014914-7w8qxs4w	This study examines the influence of building envelope features on interunit dispersion around multi-story buildings, when the presence of an upstream interfering building is also considered. In a downward dominated near-facade flow field, the presence of vertical envelope features forms dispersion channels to intensify the unidirectional spread. The large influences caused by the presence of envelope features extend the existing understanding of interunit dispersion based on flat-facade buildings. In general, the enhancing effect of the interunit dispersion due to the presence of vertical features still exists; the reentry ratios of the lower units, especially unit W2 are significantly increased. The basic influences of the presence of an upstream building and envelope features on the interunit dispersion are the same with those analyzed in previous section. This study examines the influence of the presence of an upstream building and envelope features on the natural ventilation performance and interunit dispersion of a multistory building using CFD method.

cord-014933-3jezc081	authors: Özdemir, Seray Karagöz; Iltar, Utku; Salim, Ozan; Yücel, Orhan Kemal; Erdem, Ramazan; Turhan, Özge; Undar, Levent The first aim of study was to determine the difference in frequency of febrile neutropenic episodes (FNEs) according to months and seasons. Febrile neutropenia (FEN) is the most common complication requiring hospitalization and causing mortality in patients with hematological cancer. The primary aim of the study was to investigate whether there is a relationship between the frequency of febrile neutropenic episodes (FNEs) and seasons in hematological cancer patients. In addition, neutrophil count, C-reactive protein (CRP) level, length of hospitalization, culture results of blood and other body specimens, isolated pathogens, detected foci of infection, and antibacterial, antiviral, or antifungal treatments were reviewed. The second aim of the study was to determine the type and frequency of pathogens detected in FNEs in patients with hematologic cancer.

cord-015527-ph576eji	Although we performed mappings, read countings, and normalization for all samples, bat genome assemblies and all six data sets ( Table 2 ; overall 1568 mappings), we only selected one comparison per data set to exemplarily show novel and significantly differential expressed ncRNAs (Supplementary Files S2.1-S2.15; divided by data set and input annotation). To give a better estimation of transcribed and potentially functional ncRNAs, we used six Illumina short-read RNA-Seq data sets derived from four bat species (Table 2) to estimate the expression levels of our novel annotations. To this end, we used the RNA-Seq data sets Field-2015 , Field-2018 , Hölzer-2019 and Weber-2019 (Table 2 ) as a basis to identify DE ncRNAs that were newly discovered in this study and were not part of the current NCBI or Ensembl genome annotations for this bat species.

cord-015678-9b3eazd4	A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. Chitosan and its derivatives have many desirable properties such as antioxidative and antimicrobial effects, mucoadhesiveness, biodegradability, and biocompatibility and can be manufactured in various formulations including hydrogels, films, membranes, porous sponges, nanoparticles, and nanofibers. Recyclable composite microspheres composed of cross-linked chitosan grafted with glutamic acid and having a core of Fe 3 O 4 nanoparticles coated with silica adsorb cationic dyes like methylene blue, crystal violet, and light yellow 7GL (Yan et al. While chitosan-based materials have been commercially launched as packaging and coating material in food industry, as an ingredient in cosmetics, and as ion exchanger in water treatment and are approved for human dietary use and wound dressing, their commercial applications in medicine as drug delivery systems or scaffold for tissue engineering are pending.

cord-015866-65zrbo1w	The a-subunit (113 Kd) binds ATP and ions (Na + and K + ) and contains an autophosphorylation site (P) but some isoforms like renal sodium-potassium have extra c subunit with FXYD2 the nucleotide binding site, adenosine base and phenylalanine 475 interaction forms hydrophobic stacking and three phosphate group bulge out in solution so that c-phosphate could reach to P-domain aspartic acid for phosphorylation. The vacuolar ATPases are ATP-dependent oligomeric protein proton pump, which regulate acidic pH in organelle compartment like phagosome and endosome for the separation of ligand from their receptors and transport proton (H + ) across the plasma membrane. The vacuolar ATPases are ATP-dependent oligomeric protein proton pump, which regulate acidic pH in organelle compartment like phagosome and endosome for the separation of ligand from their receptors and transport proton (H + ) across the plasma membrane.

cord-015930-18qznqp0	Given his unremarkable bone marrow biopsy 7 days before and elevated fibrinogen, the possibility of hemophagocytic lymphohistiocytosis (HLH) was dismissed as his hyperferritinemia and elevated sIL-2R were attributed to history of blood transfusion and occult infection. A recent consensus review on malignancy-associated HLH suggests tailoring treatment to the underlying trigger, performance status, organ function and additional therapies the patient is receiving [12] . In critically ill adults, however, the increased prevalence of conditions which elevate ferritin, such as infection, malignancy, autoimmune disease, liver injury and chronic blood transfusion make hyperferritinemia a nonspecific finding for HLH [26, 27] . While effective in inducing bone marrow remission [43] [44] [45] , CAR-T cells may be associated with the development of cytokine release syndrome (CRS) which frequently requires treatment in the ICU. Several important clinical syndromes, including HLH, MAS, IPS, and CRS can mimic sepsis and cause critical illness through immune dysregulation in the absence of infection.

cord-016120-pz2q62i7	This uneasiness with emotion, which is perceived to be opposite to journalistic objectivity, as well as the questioning of Chai''s sincerity, which is an innate paradox of the new documentary movement itself (some questioned whether the filmmakers are using the stories of the marginalized people for their own identity politics), provides a lens into the media consumption habits of the Chinese public in the first two decades of the twenty-first century. Chai left the CCTV in 2014 and returned to the public sphere in 2015 with her documentary Under the Dome, which uses a TED talk format to combine personal testimonials, graphs and data, animation, and interviews to investigate the causes of China''s air pollution. Chai''s embracing her own feelings of vulnerability, which dominated the beginning of her career, and using it to channel public feelings and drive news reporting has made her a distinctively controversial media personality.

cord-016126-i7z0tdrk	The present book chapter is intended to explore the potential of RV approach to select the probable vaccine candidates against coronavirus and validate the results using docking studies. Reverse vaccinology is based on same approach of computationally analysing the genome of pathogen and proceeds step by step to ultimately identify the highly antigenic, secreted proteins with high epitope densities. The most appropriate targets as vaccine candidates are those which possess the adhesion-like properties because they not only mediate the adhesion of pathogen''s proteins with cells of host but also facilitate transmission of virus. None of the 11 proteins of MERS-CoV possessed any clue of allergenicity as per prediction results from AlgPred and Allertop tools; it means that no vigorous immune responses will be mounted if the epitopes from these proteins will be adopted as vaccine candidates. Identification of potential antigens from non-classically secreted proteins and designing novel multitope peptide vaccine candidate against Brucella melitensis through reverse vaccinology and immunoinformatics approach

cord-016144-280kwlev	Further, modifications in PCR-based molecular detection techniques have generated a vast array of fast, reliable and specific assays which have widespread applications in veterinary diagnostics. The sensitivity of any genome detection-based method can be enhanced to a very high degree by manipulating any of the three pillars of the assay, i.e. by amplification of target, signal and probe. Common real-time PCRs include (1) SYBR green method where the fluorescent dye SYBR green binds to random dsDNA and can also give nonspecific amplification and (2) dual dyelabelled probe method which involves the use of sequence-specific DNA probes that are labelled with a fluorescent reporter, permitting specific detection after hybridization of the probe with its complementary sequence. To overcome these limitations and to increase efficiency comparable to symmetric PCRs, linear after the exponential (LATE)-PCR was developed based on primer pairs purposely designed for use at unequal concentrations to yield specific single-stranded DNA products in a robust way (Pierce et al.

cord-016146-2g893c2r	In this letter, we will present the views on how AI and ICT technologies can be applied to ease or solve social problems by sharing examples of research results from studies of social anxiety, environmental noise, mobility of the disabled, and problems in social safety. In this letter, I introduce research on the informatics platform for social problem solving, specifically based on spatio-temporal data, conducted by Hanyang University and cooperating institutions. The research focuses on social problems that involve spatio-temporal information, and applies social scientific approaches and data-analytic methods on a pilot basis to explore basic research issues and the validity of the approaches. Furthermore, (1) open-source informatics using convergent-scientific methodology and models, and (2) the spatio-temporal data sets that are to be acquired in the midst of exploring social problems for potential resolution are developed. Convergent approaches offer the new possibility of building an informatics platform that can interpret, predict and solve various social problems through the combination of social science and data science.

cord-016191-9gr6lh5w	The expert and technical labour force brought in to fulfil the increasing requirements of technological development and innovation affects the locally available native manpower in the fast changing Saudi Arabia, resulting in an imbalance on regional and urban scales, impacting upon economy, urban planning, transport, housing and employment and, in return, creating an over-urbanization (United Nations 2009 Khraif 2007 Khraif , 2001 Makki 1986 ). The International Database of US Census Bureau provides migration data-net migrants by year, which has been collected for Saudi Arabia and the other GCC states from 1993 to 2012-to compare the changes and its contribution to the population growth. Saudi Arabia is the largest country in the GCC in terms of both land area and population, thus having the highest level of international migration within the Arab world and beyond.

cord-016246-qqrv1npv	Since the earliest days of medicine, physicians have recognized that the human body can exhibit an abnormal rise in temperature, usually defined as fever, as an obvious symptom of illnesses. A century later, Carl August Wunderlich stated in the English translation of his treatise on ''Temperature in Diseases'' that he preferred to retain all his measurements in the centigrade scale, because the convenience of this scale will probably shortly lead to its general adoption by all scientific men. Their main applications generally fall outside the temperature range of the human body, but some patient-monitoring devices used in critical care employ thermocouples taped to the skin for continuous measurements over time. Since the earliest days of medicine, physicians have recognized that the human body can exhibit an abnormal rise in temperature, usually defined as fever, as an obvious symptom of certain illnesses.

cord-016283-b6yywn9f	
cord-016361-upjhmfca	When a new case of infectious disease is suspicious in Health Center, actors will collaborate to report it to Provincial Health Division through Health Zone Executive Team. This paper focuses precisely on improving the process of reporting health data from the peripheral level to the hierarchy for rapid decision-making and anticipate as much as possible the medical response using multi-agent systems (MAS). Two main ways of research can be studied in this paper: the use of mobile phone as a relevant medium to rapidly transfer medical data and the multi-agent system that is powerful to simulate organizational skills to anticipate diseases spreading. In the process described in Fig. 3 , the agents use some knowledge and tasks to perform a main goal together: collecting data in order to respond with efficiency to epidemic.

cord-016426-aw3wirmb	Studies have failed to show benefit for a combination of AST and isolation in reducing VRE infection or colonization; however, outbreaks of VRE have been successfully controlled in hospital settings with use of active surveillance, contact precautions, patient isolation, and cohorting [57] . A cluster randomized trial in intensive care units found that universal gown and glove use did not reduce overall acquisition of multidrug-resistant organisms (MDRO); there was, however, a small reduction in MRSA transmission noted as a secondary outcome [59] . Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin of colonized patients Analysis of data from the German Nosocomial Infection Surveillance System regarding the placement of patients with methicillin-resistant Staphylococcus aureus in private rooms in intensive care units Role of decolonization in a comprehensive strategy to reduce methicillin-resistant Staphylococcus aureus infections in the neonatal intensive care unit: an observational cohort study

cord-016478-gpl0zbvd	The differential diagnosis for anemia after solid organ transplant includes hemolysis, drug toxicities, iron deficiency, infection, posttransplant lymphoproliferative disorder, graft-vs.-host disease, and hemophagocytic syndrome. Sirolimus and calcineurin inhibitors such as tacrolimus and cyclosporine have been shown in renal and lung transplant recipients to cause hemolytic anemia, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome [15] [16] [17] . While this etiology is more often identified as a drug-related phenomenon, particularly due to the immunosuppressants required to prevent organ rejection (see next section), there have been multiple case reports associating CMV infection as a trigger of TMA in the posttransplant setting [53, 54] . When this is identified, numerous case studies in multiple different organ systems (lung, liver, kidney solid organ transplant) have reported that changing from one CI to another (tacrolimus to cyclosporine or vice versa) or to another class of medication such as sirolimus or mycophenolate mofetil can prevent further episodes of TMA from occurring [61] [62] [63] [64] .

cord-016575-bn15006x	Terpenes have a wide range of medicinal uses among which antiplasmodial activity is notable as its mechanism of action is similar to the popular antimalarial drug in use—chloroquine. Terpenes and terpenoids are terms that are often used interchangeably but the two terms have slight differences; terpenes are an arrangement of isoprene units that are naturally occurring, volatile, unsaturated 5-carbon cyclic compounds that give off a scent or a taste to defend itself from organisms that feed off of certain types of plants (see footnote 1). This plant contains many medicinal properties like anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory, and antiparasitic (Franklin et al. Beta-myrcene from Cannabis sativa, the plant which is high in terpenes, does not show an anti plasmodial effect but extracts from stem, leaves, and seeds of clove basil showed a good antiplasmodial activity (Small 2017; Kpoviessi et al. The results revealed that terpenes formed a major part of the extracts of medicinal plants that exerted antidepressant effects (Saki et al.

cord-016814-tf17dpo5	Despite increasing number of preclinical studies demonstrating that systemic MSC administration can prevent or treat experimental COPD and emphysema, clinical studies have not been able to reproduce the preclinical results and to date no efficacy or significantly improved lung function or quality of life has been observed in COPD patients. performed a Phase I, prospective, open-label study (NCT01306513) where they aimed to assess the safety and feasibility of intravenously infused bone marrow-derived MSCs for ten patients with severe emphysema that had serial lung volume reduction surgeries (LVRS). Current clinical trials that aimed to evaluate the effect of MSC administration in COPD patients differ in a wide range of factors such as routes of administration, number of MSC administered, number of administrations, use of fresh MSCs or culture-expanded MSCs. Furthermore, all the investigations discussed above, were phase I-II studies that were underpowered in order to detect potential efficacy and no improved pulmonary function or respiratory quality of life was observed.

cord-016928-yigz9qiz	The tissue damage is caused from a combination of either direct neuronal infection which activates intrinsic apoptosis or a hyperactive inflammatory response mediated by PICs or CD8+ cytotoxic T cells (CTLs) (Wang et al. Spread through aerosols, SARS-CoV primarily infect lung cells triggering an often fatal inflammatory response clinically called acute respiratory distress syndrome (ARDS) that starts with severe hypoxia, pulmonary edema progressing to systemic inflammation, and failure of multiple organs, culminating in high rate of mortality (Peiris et al. Although evidence suggests that SARS-CoV can infect multiple cell types, lung type-II pneumocytes and ciliated epithelial cells constitute primary sites of virus replication, consequent to which these cells undergo apoptotic and/or necrotic death attracting innate immune cells and activating them to secrete PICs (Sims et al. Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death

cord-016935-0wyl2h62	Probiotics such as Lactobacillus spp are more or less like stem cells utilized to replenish and rejuvenate the microbiome while prebiotics like fructose oligosaccharides (FOS) are microbiome fertilizers akin to mineral supplements or energy nutrients aimed at promoting the proliferation of select microbes in the invisible organ. Probiotics such as Lactobacillus spp are more or less like stem cells utilized to replenish and rejuvenate the microbiome while prebiotics like fructose oligosaccharides (FOS) are microbiome fertilizers akin to mineral supplements or energy nutrients aimed at promoting the proliferation of select microbes in the invisible organ. Despite the ability of our microbiota to respond and adjust to these situations, the invisible organ can be influenced by either taking in select beneficial microbes with known functional attributes or by consuming foods and plant products that promote the proliferation of specific microorganisms.

cord-017072-qwe1ne3q	Multiplex respiratory panels have the potential to improve patient management and lower overall healthcare costs by improving use of influenza antivirals, reducing inappropriate use of antibiotics and antivirals, reducing use of healthcare resource (e.g., additional laboratory or imaging procedures), informing appropriate infection control practices, and reducing length of hospital, emergency department, and intensive care unit (ICU) stay. In another study evaluating adult patients with a positive influenza result on a multiplex respiratory panel, Rappo [21] reported a significantly lower odds ratio for hospital admission (p = 0.046), a reduced length of stay (p = 0.040), reductions in antimicrobial duration (p = 0.032), and a reduction in the number of chest radiographs (p = 0.005). As with the individual molecular assays and the MALDI-TOF identification, numerous studies have shown that use of multiplex molecular blood culture panels dramatically reduces the time to organism identification [29] [30] [31] [32] which drives more appropriate pathogen-directed therapy. A retrospective study of the impact of rapid diagnostic testing on time to pathogen identification and antibiotic use for children with positive blood cultures

cord-017096-pnxjrtgo	Up-converting phosphor technology-based point-of-care testing (UPT-POCT) can detect bioterrorism agents from various samples with high sensitivity and specificity, in particular it shows robust performance for complicated samples, such as food, powder, viscera and grains. Sensitivity and specificity are crucial to the performance evaluation for a detection method, and the evaluations of UPT-POCT for detection of different bioterrorism agents are shown in Table 16 .1. cholerae in 102 field water samples obtained from sample collection sites in Guangzhou city (China), UPT-POCT is more sensitive than the isolation-culture method and colloidal gold immnochromatography assay, and its sensitivity could match that of real-time fluorescent PCR with fewer false positive results (Hao et al. Compared with these methods, the simple sampletreatment process based on its high tolerance, and the simple sample-loading manner of UPT-POCT, reduces the potential for the spread of bioterrorism agents in the detection process. Evaluation of up-converting phosphor technology-based lateral flow strips for rapid detection of Bacillus anthracis Spore, Brucella spp., and Yersinia pestis

cord-017137-6pmts7ui	When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—"microbial forensics." Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Herein the microbial forensics could be defined as "the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes" [21] . Microbial forensics has a role in such cases by applying scientific methods for the analysis of evidence from such a bioterrorism attack. The most reliable technique till date for microbial forensics is metagenomics-a culture-independent approach for identifying and enumerating microbes.

cord-017142-vx3rgs4r	Suspicion of cast nephropathy in newly diagnosed myeloma patients with serum FLC above 1000 mg/L should be high, especially if associated selective proteinuria composed of FLC/BJP exists, as the degree of renal injury is usually related to tumor load [55] . MM patients are at high risk for cardiac complications secondary multiple factors including an older age group of patients with underlying comorbidities, concurrent kidney involvement, MM-associated deposition disease, and/or anti-MM drug-related side effects. Cardiac amyloidosis can be clinically silent initially, and a MM patient presenting with progressive dyspnea, worsening edema with evidence of heart failure, or dysrhythmia presenting as syncope or hypotensive event requires a thorough work-up to rule out coexisting amyloid disease. Immunosuppression is mediated by disease-and treatment-related factors including decreased ratio of functional to dysfunctional immunoglobulins, defects in antibody opsonization, steroid-related T cell defects, secondary immunodeficiency related to chemotherapy, restricted pulmonary reserve from thoracic rib fractures and opiate use, mucosal damage, indwelling catheters, and presence of renal failure [53, 88, 100] .

cord-017148-o9qg2qta	These two trace elements display a common pivotal role in establishing the cellular antioxidant response as well as in mounting a proper immune response, which in turn may be useful to prevent excessive accumulation of senescent cells in aging and to reduce the senescence-associated increase of chronic inflammatory mediators. Old literature documented that zinc supplementation performed throughout the whole life span of rodents is able to delay some age-related cell-mediated immune modifications, such as the decreased circulating thymic hormone levels (Iwata et al. Dietary zinc and selenium are important nutritional factors for the immune response in protecting against the appearance of age-related diseases. These findings suggest that low dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and decreased influenza compliances (respiratory tract infections) with thus a possible impact on the maintenance of health conditions during aging.

cord-017149-cegevjw8	Only in recent years, starting in the mid-1990s, increased competition from within and outside their industries forced companies from large countries to source technological knowledge on a global scale. As a result, the top pharmaceutical companies today have R&D locations in all major markets, not just for the coordination of local clinical development projects but also for discovery research. A study of 9452 R&D sites across various industries (including automotive, engineering, electrical, IT, software, food, chemical and pharmaceutical companies) produced the following overall results concerning international R&D locations (see also von Zedtwitz and Gassmann 2016): As a result, pharma companies started to invest more strategically in R&D in China, in the expectation to access the natural resource base in China, and to tap into an increasingly large body of medical researchers and pharmaceutical scientists. AstraZeneca doubled down on its 2003 start in clinical research in China and in 2007 added a US$100 million investment in its new AstraZeneca Innovation Center in Shanghai.

cord-017225-6ofi6mg5	In addition to those arising in the areas of religious toleration, judicial practice, treatment of labor and forced abortion, which were extensively reported by the media in the past, some newly emerged problems concerning human rights violation are much more alarming, due to the size of population affected and the degree of challenge caused to the public''s psychological endurance and confidence in the social ethnics and administration of the nation. In addition to those arising in the areas of religious toleration, judicial practice, treatment of labor and forced abortion, which were extensively reported by the media in the past, some newly emerged problems concerning human rights violation are much more alarming, due to the size of population affected and the degree of challenge caused to the public''s psychological endurance and confidence in the social ethnics and administration of the nation.

cord-017272-r5en82s1	[11] pointed out that due to the accumulation of highly sophisticated spatial and spatiotemporal technology like GIS, GPS, remote sensing, and computer cartography, collectively termed as geographic information science, it becomes possible to model the disease process involving multiple spatiotemporal data obtained in different disciplines. Also, mobility has been one of a classical topic in the area of human ecology since it is associated with the question of how a population utilizes the environment spatially as well as temporally (time allocation studies). Time allocation studies observe the individuals in the targeted field and record the location and type of activity for a given period, which is useful to answer some of the basic questions in human Unlikely Large ecology or other related fields as noted above. A relatively large spatial scale study has been conducted covering approximately 80 × 200 km area in Belgium [3] , which compared regional exposure estimates for two representative air pollutants, NOx and ozone, under two alternative assumptions.

cord-017463-repm1vw9	We examine networks that contribute to global surveillance systems and highlight the role of social media and information technology in providing data to monitor new events of international importance. The IHR 2005 require countries to develop core capacities in public health, including surveillance systems and epidemiology services, that can analyse and act on surveillance information to detect and respond to diseases where and when they occur so that their potential to spread internationally is decreased. Surveillance and response teams detect early stage public health threats while control programmes gather disease (or condition) specific information to plan activities. These networks depend on cooperation of governments, public health workers and scientists to report cases, provide specimens and share information so that specific diseases can be controlled globally.

cord-017518-u2gsa4lg	These infection rates can be significantly reduced by the implementing and improving compliance with the "care bundles." This chapter will address the common nosocomial infections such as ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and surgical site infections (SSI), including preventive strategies and care bundles for the same. (a) Patient factors such as extremes of age, immunosuppression due to malignancy, acquired immunodeficiency syndrome (AIDS), patients requiring emergency admission to the intensive care unit (ICU), duration of stay more than 7 days, chronic illness like renal failure, diabetes mellitus, chronic liver disease, presence of indwelling catheters, ventilation, total parenteral nutrition, trauma, abdominal surgeries, and impaired functional status [44, 45] (b) Organizational factors such as the poor environmental hygiene inside the hospital or ICU, lack of efficient infection control measures, inadequate manpower such as an inadequate nurse to patient ratio or inadequate waste management staff, and inadequate equipment for patient use (c) Iatrogenic factors such as ignorance regarding infection control practices, lack of training in infection control, etc.

cord-017531-fm8gl5b3	All transport of infectious patients from the place of arrival to the hospital should take place in ambulances using the same infection control regime as for the individual infectious disease (contact infection, airborne infection, strict isolation); see isolation regimes; Chaps. • Ambulance staff and other personnel use the contact and airborne infection regime when picking up and transporting a patient. Short-time airborne isolation of exposed cases until the infection state is clarified/effect of antibacterial therapy 82.5.6 Anthrax After Staying in Turkey, Sick on the Plane Home 82.5.6.1 Patient: Strict Isolation-Air Pressure Isolate with Pressure [21, 22] Example: Two out of six people who have been on family visits in Turkey for a week, on farms with goats and skin production, are acutely ill on the plane home with cough, shortness of breath and fever. Less severe disease: isolation of index case and close contacts • Registering: All exposed persons are registered (name, address, telephone number) and followed up.

cord-017534-0ai8chbu	There is an increased need of isolates for patients with infections, especially due to pulmonary tuberculosis, MRSA, VRE, Clostridium difficile (CD), multiresistant gram-negative bacteria and other "multidrug-resistant organisms" (MDRO) [23, 24, 36, 37, [48] [49] [50] [51] . In 2009, a European investigation was done as regards the number of "high-level isolation rooms" (HIRs), i.e. airborne infection isolation units with negative pressure (not defined) with at least 6 air changes per hour and sluice (anteroom) [61] . CDC defines contact isolation, using gown and gloves when in contact with patients infected with resistant bacteria like MRSA and other MDROs (multidrug-resistant organisms), and single rooms are recommended [19] . Spread of pathogenic infectious agents through the air and droplets requires a defined negative pressure ventilation isolate and a system which reduces airborne infection in the patient''s room.

cord-017686-127xfkse	The post-Cold War reordering of the world proffers a multitude of examples of this progress: from emergent multipolarity (Flockhart 2016) to the rise of nongovernmental organizations (NGOs) and NSAs, from the human rights debates to gain access to HIV treatment to those to usher in the R2P (ICISS 2001), reconceptualizations of internal and external State responsibility have been pitted against each other. Although State sovereignty continues to be the building block of local, national, and international relations and global governance, its real power to enact responsibilities and assume accountability for the provision of the rights of its citizens has arguably waned-not uniformly but almost regardless of whether the State in question is considered consolidated, fragile, or failing/failed.

cord-017772-zpf1xjqi	In general, ICU patients who develop thrombocytopenia are sicker than patients with normal platelet counts, with higher illness severity scores, more need for vasoactive infusions, and more organ dysfunction [8, 9] . TMAs are a diverse group of disorders that can be classified broadly as primary (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, drug-mediated, etc.) or secondary to a systemic disorder (disseminated intravascular coagulation, severe hypertension, hemolysis with elevated liver enzymes and low platelets during pregnancy, etc.) [23] . The diagnosis of DIC should be suspected in any critically ill patient with thrombocytopenia, abnormal coagulation parameters (e.g., a prolonged prothrombin and partial thromboplastin times), MAHA, and laboratory evidence of fibrinolysis (e.g., an elevated d-dimer and reduced fibrinogen) [38] . Indeed, a recent systematic review did not identify a single high-quality study that investigated the impact of prophylactic platelet transfusions on bleeding rates in critically ill patients [72] .

cord-017857-fdn8c4hx	Since roughly the year 2000, the World Health Organization has collaborated with a large number of local actors and made a concentrated effort to protect the world''s population against emerging infectious diseases, such as severe acute respiratory syndrome (SARS), swine flu, Ebola and Zika. Without the capacity of organizations to produce binding decisions for their members, which makes planning for an uncertain future possible, pandemic preparedness would not be feasible—especially not on a global scale. Around the year 2000, the World Health Organization (WHO) started collaborating with a large number of local actors and made a concentrated effort to protect the world''s population against emerging infectious diseases such as severe acute respiratory syndrome (SARS), swine flu, Ebola and Zika. With regard to the WHO, which was established in 1948, I will discuss the question of how supranational coordination and planning for the future is rendered possible by building formal organizations and organizational networks at a global level.

cord-017887-pj6pal35	Functional mutagenesis studies have suggested that, at least in the cases of HIV-1 and influenza A viruses, the TM domains (TMDs) of fusion proteins are not merely membrane anchors, but play important roles in membrane fusion and viral infectivity. Apart from the channels and fusion proteins, some viruses have developed enzymatic domains anchored to the membrane, e.g., the polymerases of the hepatitis C virus and the neurominidase of the influenza viruses. Unlike many other broad-spectrum antivirals, Arbidol has an established mechanism of action against the HAs in influenza A and B viruses that involves the inhibition of virus-mediated membrane fusion and thus viral entry [50] . The NMR structure of the HIV-1 Env TMD may provide some clues for how other viral fusion proteins oligomerize in the membrane. Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes

cord-017903-92hnaiyc	These two facilities cared for seven Ebola virus disease (EVD) patients during the 2014-2016 outbreak, while another two were cared for at the National Institutes of Health''s Special Clinical Studies Unit, which had also developed HLCC capability. First, patients harboring diseases caused by pathogens that require handling under BSL-4 conditions in the laboratory would seem to be obvious candidates for clinical management under HLCC conditions. Lujo virus, an Old World arenavirus closely related to Lassa, was first described in 2008 as the cause of a single outbreak of viral hemorrhagic fever involving five patients in Lusaka, Zambia, and Johannesburg, South Africa (the name, Lujo, derives from the two cities) [20] . It would seem prudent to manage patients potentially harboring such diseases under HLCC conditions when feasible and to handle their causative viruses in a BSL-4 laboratory.

cord-018016-r7tg0s45	This work deals with developing an application where users can interactively view information about the infection in the form of plots, tables and maps. By viewing the data visualizations, users can analyze MERS cases better, find trends, monitor the disease and help authorities set detection and prevention guidelines. In the case of different cases analysis, the user can view the information as pie charts and maps, or tables. The analysis based on all cases reported in "all cities within Riyadh region" during January to February 2019 is shown in Fig. 2 . The table also has provision for searching values and selecting the number Application page corresponding to "Different Cases Analysis" tab for cities within a region of records to be displayed in a page. In this paper, we have created an interactive visualization tool for MERS Co-V infection cases based on details of cases reported in Saudi Arabia.

cord-018039-dw2xblyr	Keywords Mould · Bacteria · Endotoxin · Beta-1-3-glucan · Muramic acid Fungal DNA · Microbial volatile organic compounds (MVOC) · Mycotoxins Asthma · Respiratory symptoms Endotoxin: A cell-wall compound found in gram-negative bacteria (endotoxin can have different chain length of the 3-hydroxy acids in the molecule) Muramic acid (MuA): A cell-wall compound found mainly in gram-positive bacteria Ergosterol: A cell-wall compound found in mould (but also in plant materials) Beta 1-3 glucans: A group of cell-wall compounds in mould (but also in pollen)t Fungal DNA: DNA sequences specific for mould (general or species specific sequences) Bacterial DNA: DNA sequences specific for bacteria (general or species specific sequences) MVOC: Volatile organic compounds produced by microorganisms (but can have non-microbial sources as well) Secondary microbial metabolites: Chemical compounds produced by the secondary metabolism of microorganisms Mycotoxins: Chemical compounds with toxic properties produced by mould (a subgroup of secondary microbial metabolites) They concluded that there is sufficient evidence of a causal association between outdoor culturable fungal exposure and exacerbation in asthmatics sensitised to fungi.

cord-018066-s0zk9l6a	In order to achieve this, the article analyses the case of the refugee camp in city of Harmanly, close to the Bulgarian-Turkish border, and assesses the public health risks related to this specific situation. The purpose of our article is to collect, summarize and present epidemiological data related to migrants in Bulgaria and, on the basis of this information, to analyze the potential risks to public health (including risks to migrants) and to assess the capacity of Bulgaria''s healthcare system to cope with the refugee crisis. Following the 2012-2013 crisis, in February 2015 a WHO assessment mission to Bulgaria took place to access the country''s capacity to address the public health implications of sudden large-scale influxes of migrants [27] . Public health needs of migrants, refugees and asylum seekers in Europe, 2015: infectious disease aspects

cord-018125-khhzlt9y	It revised the definition at its 12th session in 1995 to read as follows: occupational safety and health should aim at: the promotion and maintenance of the highest degree of physical, mental and social well-being of workers in all occupations; the prevention amongst workers of departures from health caused by their working conditions; the protection of workers in their employment from risks resulting from factors adverse to health; the placing and maintenance of the worker in an occupational environment adapted to his physiological and psychological capabilities; and, to summarize, the adaptation of work to man and of each man to his job. Liberalization of world trade, rapid technological progress, significant developments in transport and communication, shifting patterns of employment, changes in work organization practices, the different employment patterns of men and women, and the size, structure and life cycles of enterprises and of new technologies can all generate new types and patterns of hazards, exposures and risks.

cord-018134-k4vdqlgs	• Gram-negative bacterial pneumonia that is most common in debilitated middle-aged and older men with alcoholism (about two-thirds of cases); high mortality rate • Tends to form a voluminous exudate that produces a homogeneous parenchymal consolidation containing an air bronchogram • Lobar enlargement (especially the right upper) with the characteristic bulging fissure sign (Fig. 6 .17) ○ Bulging fissure sign also in Haemophilus influenzae pneumonia (predominantly in compromised hosts, such as chronic pulmonary disease, immune deficiency, alcoholism, diabetes) (see Fig. e6 .22) • Most frequently result from infectious particles reaching the lung from an infected heart valve (especially the tricuspid), intravenous catheter, or injected debris • Persons at risk include drug abusers, immunocompromised patients, individuals with septal defects, and those with indwelling venous catheters, pacemakers, or prosthetic heart valves • Initially, multiple ill-defined round or wedge-shaped opacities with a swirling pattern that are usually peripheral and tend to involve the lower lobes (starry night sign -mimicking the brush strokes in van Gogh''s painting of that name) • Cavitary pulmonary nodules tend to develop rapidly (1-2 days) 

cord-018137-rmtyrbg0	Two equilibriums points were found, disease free and endemic equilibrium, and basic reproduction ratio [Formula: see text] was also calculated by the use of next generation matrix. Efforts to improve the use of antiretroviral treatment in some part of the world were still not enough to reduce a significant number of deaths, the HIV/AIDS epidemic claimed 3.1 million lives in 2005, of which about 570000 were children (UNAIDS/WHO [8] ). We shall study the global stabilities of both disease free and endemic equilibria by the use of Lyapunov function. Here we use the real data obtained from MOH, in which there were a total of 13646 HIV-1 positive reported cases in the year 2016, in the year 2016 to study and predict the dynamics of HIV in Turkey using our model. Stability analysis of an HIV/Aids epidemic model with treatment Stability analysis of an HIV/AIDS epidemic model with screening Global analysis of an HIV/AIDS epidemic model

cord-018213-w6sh9f3h	This time marked the initial formation of a working inter-departmental mechanism positioned to combat health emergencies through "paying equal attention to both prevention and response, and instilling continued collaboration for any event." On April 26th, Health Minister Chen Zhu convened a meeting of the MOH Leading Group and Expert Panel for Influenza Pandemic Prevention and Control, at which the attendees analyzed swine influenza situations in the United States and Mexico, predicted epidemic trends, and deliberated on domestic strategies and measures to cope with a swine flu pandemic. At the beginning of the Influenza A (H1N1) Epidemic, China established a national level emergency management mechanism directly under the leadership of the State Council that enabled cross-departmental joint prevention and control collaboration, which provided an effective organizational support and operation mechanism for the response efforts.

cord-018239-n7axd9bq	The following topics should be included in the travel advice consultation: 5 Vaccinations (general and country specific) 5 Country-specific diseases 5 Malaria prophylaxis 5 Mosquito prophylaxis (wearing bright long-sleeved clothes, avoiding perfume, staying in air-conditioned rooms, using a mosquito net, using insect repellents, staying inside at dawn and dusk) 5 Food consumption and drinking overseas (no consumption of ice cubes, uncooked meals, salads and food, which is exposed to flies, limited alcohol consumption) 5 UV protection (using sun cream, avoiding sun exposure between 11.00 and 15.00 o'' clock, remaining in shaded areas, wearing a hat and covering skin) 5 Fitness assessment for travelling, flying and diving 5 Challenges of different climates and their effects on the personal health (dehydration, hyperthermia) 5 Medications 5 Thrombosis counselling 5 Counselling on symptoms on return, which require review (fever, skin changes, abnormal bleeding, lymphadenopathy, diarrhoea) 5 Sexual transmitted diseases 5 Contraception 5 Rabies

cord-018454-sy21cpff	(continued) Identifying the disease subset might orientate the therapeutic strategy c Serum ferritin levels are significantly higher in the systemic subtype [110] , but high ferritin levels after adequate treatment may predict chronic articular course [61] d Calprotectin levels help rule out rheumatoid arthritis, but further studies are needed to validate it as a diagnostic biomarker because of no statistical difference between AoSD and septic patients, although the populations were small [42] e Elevated plasma levels of IL-1β, IL-6, and TNFα have been found during AoSD, but the cytokine profile is not specific and cannot differentiate AoSD patients from those with sepsis f S100A12 was found an efficient diagnostic and monitoring biomarker in systemic juvenile arthritis, but further studies are needed for validation in AoSD Procalcitonin, a marker of severe systemic infection, was also found elevated in patients with active AoSD and does not appear relevant to distinguish acute infection from AoSD flare [42, 113] .

cord-018459-isbc1r2o	This paper explores computational solutions for building phylogeny of species along with highlighting benefits of alignment-free methods of phylogenetics. This paper has reviewed various methods under phylogenetic tree construction from character to distance methods and alignment-based to alignment-free methods. In literature, various string processing algorithms are reported which can quickly analyse these DNA and RNA sequences and build a phylogeny of sequences or species based on their similarity and dissimilarity. Alignment-free methods overcome this limitation as they follow alternative metrics like word frequency or sequence entropy for finding similarity between sequences. These alignment-based algorithms can also be used with distance methods to express the similarity between two sequences, reflecting the number of changes in each sequence. Application of the phylogenetic tree can be explored for finding similarities among breast cancer subtypes based on gene data [14, 15] . Constructing phylogenetic trees using multiple sequence alignment

cord-018517-hrb1vt03	China''s health reforms remain encouragingly specific but not prescriptive on strategy; set in the decentralized governance structure, they avoid the issue of reliance on local government support for the national equity objective, leaving the detailed design of health service financing, human resource distribution and accountability, essential drug lists and application of clinical care pathways, etc. China''s health reforms remain encouragingly specific but not prescriptive on strategy; set in the decentralized governance structure, they avoid the issue of reliance on local government support for the national equity objective, leaving the detailed design of health service financing, human resource distribution and accountability, essential drug lists and application of clinical care pathways, etc.

cord-018623-of9vx7og	Further, human studies provided evidence pointing to the increased development of emotional problems and EDR-related disorders in patients with various types of AIDs, such as SLE and multiple sclerosis (MS), in a disease state/severity-dependent manner [12] [13] [14] [15] [16] [17] . Thus, it is not surprising that the inflammatory response and respective cytokines are supposed as one of the possible mechanisms linking the experience of negative emotions or ER-related disorders and the progression of cardiovascular diseases, of course along with the neuroendocrine system and apoptosis signaling pathways [27, 30, [32] [33] [34] [35] . Mice subjected to short-term (1-3 weeks) HFD also exhibited anxiety-like behaviors in addition to learning and memory impairments and had significantly higher levels of homovanillic acid-a metabolite of dopamine-in their hippocampus and cortex but without any alteration in the gene expression of inflammatory markers [89] . Increased emotional distress in daughters of breast cancer patients is associated with decreased natural cytotoxic activity, elevated levels of stress hormones and decreased secretion of Th1 cytokines

cord-018632-azrqz6hf	Artificial Intelligence (AI) offers new hope in not only effectively pre-empting, preventing and combating the threats of infectious disease epidemics, but also facilitating the understanding of health-seeking behaviors and public emotions during epidemics. The human population is currently able to access potentially useful massive data sources of infectious disease spread through sentinel reporting systems, national surveillance systems (usually operated by national or regional disease centers such as the Center for Disease Control (CDC)), genome databases, internet search queries (also called infodemiology and infoveillance studies) [10] [11] [12] , Twitter data analysis [13, 14] , outbreak investigation reports, transportation dynamics [15] , vaccine reports [16] and human dynamics information [17] . With such high fluxes of health-seeking behavior using computers, a group of Italian researchers'' evaluated Google Trends search queries for terms related to "Ebola" outbreak at the global level and across countries where primary cases of Ebola were reported [26] .

cord-018760-blwguyl4	Last two centuries have witnessed changes in global environmental factors such as rise in temperature leading to global warming, depletion of stratospheric ozone layer, loss of biodiversity and marked degradation in air and water quality due to atmospheric pollution, thereby causing upsurge in infectious and non-infectious diseases. Similarly, in India there is strong evidence linking lower respiratory tract infection to indoor air pollution caused by the use of solid fuels in household. Air pollution and occupational exposure may cause a variety of negative health outcomes, including reduced lung function in children as well as increased susceptibility to infections, airway inflammation and cardiovascular diseases. There should be general awareness of how changes in climate and environment lead to significant acute and chronic effects on human health.

cord-018785-tcr5xlf8	The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. The risk factors for development of CMV disease include donor seropositivity/recipient seronegativity(Dþ/RÀ), use of induction immunosuppression (antilymphocyte antibodies), donor age >60 years, simultaneous kidney-pancreas transplantation, treatment for acute rejection, impaired transplant function, and concurrent infection from other viruses (like EBV and HHV-6 and 7) (De Keyzer et al. The risk factors for PTLD include EBV naïve recipients who receive EBV seropositive organs, active primary EBV infection, younger recipient, coinfection by CMV and other viruses, prior splenectomy, second transplant, acute or chronic graft versus host disease, immunosuppressive drug regimen (OKT3 or polyclonal antilymphocyte antibody), and the type of organ transplanted.

cord-018832-g96earfl	title: Dynamical Behavior of an SVIR Epidemiological Model with Two Stage Characteristics of Vaccine Effectiveness and Numerical Simulation An SVIR epidemiological model with two stage characteristics of vaccine effectiveness is formulated. By constructing the appropriate Lyapunov functionals, it is proved that the disease free equilibrium of the system is globally stable when the basic reproduction number is less than or equal to one, and that the unique endemic equilibrium of the system is globally stable when the basic reproduction number is greater than one. Therefore, this paper studies the epidemiological model with two stage characteristics of vaccine effectiveness, On the basis of getting the basic reproductive number, by using appropriate functionals, the stability of the model is proved by the algebraic approach provided by the reference [8] . Global stability of an epidemic model with latent stage and vaccination An algebraic approach to proving the global stability of a class of epidemic models

cord-018884-os0faovj	There is increasing recognition of infections caused by respiratory viruses (RVs) as a major cause of morbidity and mortality in solid organ transplant (SOT) recipients, especially within the thoracic and pediatric population. Respiratory viral infections are typically caused by rhinovirus (RhVs), coronavirus (CoV), respiratory syncytial virus (RSV), influenza (FLU), parainfluenza (PIV), human metapneumovirus (hMPV), and adenovirus (AdV) ( Table 9 .1). Antiviral resistance is of considerable concern among immunocompromised patients infected with influenza virus, and testing should be strongly considered in SOT undergoing treatment who fails to have an appropriate clinical response within 3-5 days of initiating antiviral therapy or who has a relapsing course despite ongoing therapy. Adjunctive therapy with corticosteroids has been purposed for SOT with influenza and RSV and for lung transplant recipients with any RVs with LRTI because of the risk of both acute and chronic rejection [13] . Update in the treatment of non-influenza respiratory virus infection in solid organ transplant recipients

cord-018900-8n2iaogb	Des Weiteren versucht das Unternehmen, der Öffentlichkeit und den Medien zu vermitteln, dass es alles Mögliche unternimmt, um größere Schäden abzuwenden und die Situation wieder unter Kontrolle zu bekommen (Abb. 10.4). Erstaunlich sei auch, dass Unternehmen sich häufig nur um das Visum und die Schutzimpfungen des Entsendungspersonals kümmern, nicht aber um eine umfassende Sicherheitsvorsorge. Durch das "Issues Management" hat ein Unternehmen oder Organisation also die Möglichkeit, schnell, flexibel und vor allem sensibel auf jede Nachricht und Entwicklung zu reagieren, die für die Identität und Wahrnehmung der Unternehmensmarke wichtig ist und bei Nichtbeachtung Krisenpotenzial entwickeln kann. Durch das "Issues Management" hat ein Unternehmen oder Organisation also die Möglichkeit, schnell, flexibel und vor allem sensibel auf jede Nachricht und Entwicklung zu reagieren, die für die Identität und Wahrnehmung der Unternehmensmarke wichtig ist und bei Nichtbeachtung Krisenpotenzial entwickeln kann. Beim Eintritt eines Ernstfalls sind nicht nur technische Anlagen und die Funktionsfähigkeit des Unternehmens bedroht sondern auch das Leben von Menschen.

cord-018911-tpm2594i	(2006) used coarse resolution vegetation index data to model and predict the continental-scale relationship between climate-driven landscape change and Lyme disease. Like all zoonotic disease, the ecology of each species of Hantavirus is closely related to that of its host organism; thus, generalization of virus-landscape relationships cannot be made without considering the habitat characteristics of the reservoir host. A regional-scale analysis of rodent reservoirs of hantaviruses in Paraguay showed that the host species do indeed show patterns of land cover preference, even when land cover is mapped into very general categories. For example, mathematical models for hantavirus infection in rodents have been studied in the context of multiple host species, spatial spread, and environmental variability (Abramson and Kenkre 2002; Abramson et al. Many challenges remain in model formulation, analysis, and simulation of zoonotic disease dynamics that relate to landscape and climate and the wide range of temporal and spatial scales (Allen et al.

cord-020544-kc52thr8	However, if Dukoral is readily available and staff are properly trained in its use according to the guidelines that come with the vaccine, the COTS program PERMITS Dukoral''s use (ideally before an outbreak) in the following high-risk populations: refugee populations in which cholera is present, health care workers managing cholera cases, and communities in which the incidence rate is greater than 1 in 1000 annually." [2] Epidemiological Surveillance (specific to cholera)

cord-020750-zvwy7bgt	En la intersección entre el ser humano y los microbios hay un cuadrado que representa la convergencia de los factores que conducen a la aparición de una enfermedad infecciosa. Esto todavía no es realidad, pero grupos como el Global Disease Detection Program (GDD) de los CDC y la Global Outbreak Alert and Response Network de la OMS están vigilando sin descanso la evolución de la interacción entre microbios y seres humanos en todo el planeta, creando tecnología de seguimiento y respondiendo a los informes sobre el aumento de enfermedades y otras emergencias sanitarias 14 . Las enfermedades infecciosas emergentes son una amenaza para todos y cada uno de los habitantes del planeta y todo el mundo puede desempeñar un papel, ya sea en el retraso de la transmisión o la prevención.

cord-021055-ebcu3ywq	China has experienced significant biosecurity and biosafety challenges and is the only nation that has been subjected to a bioweapon assault. 2 The SARS epidemic served as a timeous practical reminder to both China and the world that emerging infectious diseases could significantly threaten national and global safety and security. [3] [4] [5] [6] [7] The 2004 SARS outbreak in North China resulted from a series of flaws in the biosafety protocol at a national institute in Beijing, 5 resulting in infection of four laboratory workers. We propose that the scope of biosecurity and biosafety should include all relevant areas with the potential to cause death, social disruption and panic, economic breakdown, and/or national crisis (e.g. emerging infectious diseases, bioweapons, bioterror, laboratory biosafety, antibiotic-resistant bacterial super-strains, harmful invasive plant or animal species, misuse of synthetic biological technology, misuse of human genetic information, etc.).

cord-021894-lq8yr710	Globally there are an estimated 33.8 million cases of RSV lower respiratory tract infection each year in children under 5 years of age, resulting in 3.4 million admissions to the hospital and 66 to 199 thousand deaths (with the majority in low-and middle-income countries). 42, 43 Severity of disease is associated with both infant risk factors (including lack of adaptive T cell response), 26,44 but also RSV virus specific factors (viral antigen load and direct cytotoxic effects). Respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the United States and Finland Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis

cord-021942-u63fnzy2	9 Important bacterial infections reported in crocodilians include Mycoplasma alligatoris, 10 Mycoplasma crocodyli, 11 and Chlamydia spp. An adenovirus-like infection in captive Nile Crocodiles (Crocodylus niloticus) has also been reported. Clinical signs associated with respiratory disease in crocodilians may include dyspnea, tachypnea, nasal discharge, excessive basking, abnormal swimming (either in circles or on one side of the body), and anorexia, among others. West Nile virus causes neurological signs in captive-reared American alligators raised indoors. Anorexia is likely the most common clinical sign associated with gastrointestinal disease in captive crocodilians. 45 A herpesvirus was identified via TEM from saltwater crocodiles (Crocodylus porosus) with concurrent pox virus and bacterial infection of the skin. 45 A herpesvirus was identified via TEM from saltwater crocodiles (Crocodylus porosus) with concurrent pox virus and bacterial infection of the skin. Association of West Nile virus with lymphohistiocytic proliferative cutaneous lesions in American alligators (Alligator mississippiensis) detected by RT-PCR

cord-022046-q1exf47s	Middle East respiratory syndrome (MERS) is an emerging infectious zoonotic disease caused by a novel coronavirus (CoV). 4 Surveillance of DCs in KSA has shown that MERS-CoV clade B has been enzootic in the camel population in Arabia Genetic deep sequencing methods (i.e., high-throughput sequencing) have been readily available to researchers since the disease was first reported. 8 Nevertheless, given the prevalence of MERS-CoV infection in the Middle East''s DC population and due to the potential for spillover to the human population in direct contact with DCs, the development of a vaccine for use in DCs may be feasible. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Detection of the Middle East respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient

cord-022130-jckfzaf0	Traversing the literature and interviews with a select number of stakeholders shows there that there is a large and diverse number of individuals and organisations that could potentially play a role in either preventing, disrupting or treating future bio-threats and In the biological context, surveillance is the ongoing collection, analysis, and interpretation of data to help monitor for pathogens in plants, animals, and humans; food; and the environment. It''s clear that the ''Five Eyes'' intelligence communities have worked extensively with other member states in counter-proliferation institutions such as the BWC and the Australia Group for several decades, but what remains still under developed is how global health security stakeholders and intelligence communities can work more collaboratively for the mutual goal of global health security regardless of whether the risks are natural pandemics or result from a bio-terror attack or theft of a dangerous select agent from a lab.

cord-022161-quns9b84	The crisis turned the global securitization of health issues into unprecedented levels, at the same time, aligned closely with human security frameworks and thus has significant impacts on national foreign and aid policies. After the August/September 2014 announcement by the WHO that Ebola was a ''public health emergency of international concern'' and the United Nations Security Council (UNSC) declaration that Ebola was a ''threat to international peace and security,'' many countries as well as international organizations, non-governmental organizations, companies and individuals participated in the fight against this unprecedented challenge to humanity. Of course, in the process of engaging in the global effort to fight Ebola, China did cooperate with many countries and international and regional organizations by providing financial support to the UN, the WHO and the AU, and assisting them in playing leading and coordinating roles.

cord-022178-4oh02tlr	Wie Sie gesehen haben, befasst sich die molekulare Evolutionsforschung mit der Evolution von Genen und Proteinen, vergleicht Nucleotid-und Aminosäuresequenzen verschiedener Organismen miteinander und rekonstruiert, welche Veränderungen während der Stammesgeschichte stattgefunden haben. Viele solcher Nucleotidsubstitutionen in der DNA haben keine Auswirkung auf ein Protein -selbst dann nicht, wenn die Veränderung an einem proteincodierenden Gen erfolgt, denn für die meisten Aminosäuren gibt es mehr als ein Codon (7 Abb. 14.4). Die Genome von Organismen zeichnen sich durch eine sehr unterschiedliche Größe aus, dagegen ist die Zahl der proteincodierenden Gene deutlich weniger variabel. (Vergleichen Sie beispielsweise den Reis mit den anderen Pflanzen.) Es überrascht nicht, dass für den Bau und die Aufrechterhaltung der Funktionen eines großen, vielzelligen Organismus mehr und komplexere genetische Informationen erforderlich sind als bei einem kleinen, einzelligen Bakterium. Die Gene für ribosomale RNA evolvieren wie alle anderen Teile des Genoms, und so sammeln sich in den rRNA-Genen verschiedener Arten mit der Zeit Unterschiede an.

cord-022663-n21jvt22	Subsequently, advanced treated water must meet the requirements of the SDWA and National Primary Drinking Water Regulation (NPDWR) maximum contaminant levels (MCLs) and abide by nonregulatory water quality standards for aesthetics in the National Secondary Drinking Water Regulation MCLs. Specific regulations, policies, provisions, and/or guidance for potable reuse have been developed in 15 states: Arizona, California, Florida, Hawaii, Idaho, Massachusetts, Nevada, New Mexico, North Carolina, Oklahoma, Oregon, Pennsylvania, Texas, Virginia, and Washington (USEPA 2017 While several recent pilot and demonstration-scale studies have been conducted, two notable full-scale potable reuse facilities have provided water directly into the distribution system: Big Spring Colorado River Municipal Water District (1.6 mgd) in 2013 and Wichita Falls (5 mgd) in 2014, both of which are in Texas. A challenge for potable reuse monitoring is how to effectively characterize pathogens, chemical constituents, and emerging contaminants in advanced treated water in an appropriate time frame.

cord-022708-rr3xua38	In the November 2018 report ''Motivation, Satisfaction and Retention: Understanding the importance of vets'' day to day work experiences'' from the BVA and the University of Exeter, two of the key findings included ''feeling like one fits in with those who have been successful before you, and having role models'' as being important to motivating veterinarians, facilitating their professional satisfaction and retaining them in the profession. The federal Department of Agriculture and Water Resources is currently leading a working group comprising representatives from state governments, the Australian Veterinary Association, RSPCA Australia and Food Standards Australia and New Zealand. The World Organisation for Animal Health (OIE) is currently developing their 7th strategic plan (2021-2024) and they too are looking at their future role, particularly on global issues such as food security, climate change, species conservation and the future of the veterinary profession.

cord-023104-dpftawj3	When threats emanate from this transboundary space, national governments are often surprised and discover that existing crisis management arrangements do not suffice. The bottom line is that we need to rethink traditional crisis management arrangements in order to prepare for these increasingly common type of threats. This roadmap hinges on a strategic choice between two options that emerge from our discussion of theory: move backward by decoupling from modern systems or move forward by strengthening transboundary crisis management capacities. Transboundary crises may come in different guises, but they share common characteristics that make them difficult to manage: The Transboundary Crisis brings a critical challenge to any administrative system that is based on boundaries and demarcation. By formulating transboundary crisis management as a collective action problem, we can apply theoretical insights from this body of research. Build transboundary crisis management institutions. New processes and forms of organization that can effectively address the Transboundary Crisis.

cord-023200-3caevjvh	The discovery of short, membrane interacting, amphipathic or hydrophobic sequences (known as membranotropic peptides) in both enveloped and non‐enveloped viruses suggests that these small peptides are strongly involved in breaching the host membrane and in the delivery of the viral genome into the host cell. [3, 4] The molecular details of the interactions at the interface of virus and cell surfaces are quite complex and highly variable, but there is a common idea that only a limited number of pathways allowing viruses to reach the sites of penetration exist, with enveloped and non-enveloped viruses presenting different and unrelated processes, but with general principles driving all fusion events. [16, 17] Viral fusion proteins undergo significant rearrangements from the pre-fusion to the post-fusion conformations which are triggered by either receptor binding, proteolytic cleavage or low endosomal pH, and eventually determine the exposure of previously sequestered hydrophobic peptides, loops, or patches, able to interact with and destabilize one or both the opposing membranes.

cord-023202-0iqhf2o5	Disordered proteins represent an important class of antigen in a wide range of human pathogens, and, contrary to widespread belief, they are frequently targets of protective antibody responses. [5] Finally, and perhaps most importantly, peptidebased approaches are limited because the antibody response to many protein antigens is dominated by conformational epitopes, which are difficult or impossible to capture effectively in a peptide-based design. Modified with permission from Ref. 43 Additional specific evidence for affinity maturation in antibodies targeting this epitope comes from recent studies of the antibody responses induced in clinical trials of the RTS,S vaccine, [49] and in the context of natural infection. Although the repetitive sequences in CSP have long been the focus of vaccine development efforts, recent studies have identified epitopes within the conserved N-terminal region that appear to contribute to the protective response to CSP in the context of natural immunity and vaccination.

cord-024741-j1wj47ah	Dass sich die „Macht" der Kunden und des Wettbewerbs gegenüber einem geschwächten Gegner vergrößert, verschärft die Herausforderung für das Management. Das ist insbesondere deshalb problematisch, als die Umsatzseite und hier nicht zuletzt das Thema "Preis" für eine Bewältigung der Krise von enormer Bedeutung sind, sowohl für die Überwindung der akuten Situation als auch für den Weiterbestand des Unternehmens. den passiven Kommunikationsstil und die beiden Optionen der Umsetzung der Preiskommunikation als Preiswerbung oder persönliche Preisvereinbarung, so ergibt sich das in Abb. 3 gezeigte Bild. Eine passive Preiswerbung könnte in der praktischen Umsetzung etwa in einer Anpassung von Preislisten und Preisauszeichnungen bestehen, sollte dies auf Druck des Marktes notwendig sein. Auch die breite Kommunikation, dass ein Überleben des Unternehmens für den Kunden von Nutzen ist bzw. dass sich aus der aktuellen Situation keine Risiken ergeben, kann den Einsatz aktiver Preiswerbung erfordern, zum Beispiel auch im Sinne einer Solidarisierung zwischen Kunden und Unternehmen.

cord-024742-hc443akd	We found that higher values of multiplexity significantly reduce the epidemic threshold especially when the temporal activation patterns of nodes present on multiple layers are positively correlated. In such a scenario the epidemic threshold is not affected by the multiplexity, its value is equivalent to the case of a monoplex, and the coupling affects only the layer featuring the smaller average connectivity. In particular, the study of a wide range of real systems shows a complex and case dependent phenomenology in which the topological features (i.e., static connectivity patterns) of coupling nodes can be either positively or negatively correlated [9] . To account for such observations and explore their effects on spreading processes, we consider three simple prototypical cases in which the activities of coupling nodes in the two layers are (i) uncorrelated, or (ii) positively and (iii) negatively correlated.

cord-027598-76656pok	title: A Smartphone Magnetometer-Based Diagnostic Test for Automatic Contact Tracing in Infectious Disease Epidemics This paper investigates how good a diagnostic test it would be, by evaluating the discriminative and predictive power of the smartphone magnetometer-based contact detection in multiple measures. Unfortunately, they either provide position information too coarse to be used for infectious contact detection [11] (GPS, cellular/Wi-Fi fingerprinting), require the infrastructure nearby (cellular/Wi-Fi), cannot be used indoors (GPS), consumes too much power for extended monitoring use (GPS) [12] , or could compromise privacy by exposing the identity of the device and eventually its owner (Bluetooth beacons). When the disease control authority performs an epidemiological investigation, they can use the smartphone magnetometer traces of the person confirmed infected and of the one suspected of a contact with the infected, in a system depicted in Fig. 1 .

cord-029717-wrueslce	Multiple regression analysis showed that environmental mastery, purpose in life and positive relationships, controlled for religiousness and psychological problems related to general mental health, predicted the variability of attitudes towards suicide and pro-preventive orientation. Our research question concerns whether it is possible for psychological well-being to predict ATS and ATSP among students of the helping professions, controlling for sociodemographic characteristics, religiousness and psychological problems related to their general mental health. It was hypothesized that higher level of eudaimonic well-being would have predictive validity for stronger orientation towards suicide prevention when controlling for sociodemographic variables (gender, economic situation, marital status), religious beliefs and psychological problems related to mental health. The central assumption of the present study was that the positive mental health of future gatekeepers could be related to a pro-preventive orientation towards suicide, which would have consequences for social policy.

cord-032055-yddcme8z	Nichtsdestotrotz gehören angeborene Herzfehler weiterhin zu den Fehlbildungen, die mit einer hohen Morbidität und Mortalität vergesellschaftet sind. Dies ist insofern von Bedeutung, da eine Zyanose mit vermehrter Lungenperfusion weniger ausgeprägt ist und daher klinisch übersehen werden kann. Die Zyanose entsteht durch eine vollständige Durchmischung von venösen und arteriellen Blut oder Fehlstellungen der großen Gefäße (Aorta, Pul monalarterie). Eine vollständige Mischung von arteriellen und venösen Blut findet sich ebenfalls bei komplexen Herzfehlern mit univentrikulären Herzen, bei der totalen Lungenvenenfehlmün dung oder dem Truncus arteriosus. Liegt keine pulmonale Obstruk tion vor, zeichnen sich diese Herzfehler durch ein klinisches Misch bild aus Zyanose und Herzinsuffizienz aus. Ist ein katheterinterventioneller Verschluss nicht möglich, kann der ASD mittels Direktnaht oder durch einen Patch operativ ver schlossen werden. Der Truncus arteriosus communis (TAC) hat nur einen Anteil von etwa 1% aller angeborenen Herzfehler und ist häufig (70%) mit einer Mikrodeletion 22q11 assoziiert.

cord-032062-30jrf3ec	Eine rasante Entwicklung hat in den letzten Jahren auch die Stammzelltransplantation genommen, sodass diese heute bei zahlreichen systemischen malignen und nichtmalignen Erkrankungen als kurative Therapieoption eingesetzt werden kann. Beim Typ FAB L3 handelt es sich um eine "reife" B-Zellneoplsie, die nach der neuen Klassifikation nicht mehr als lymphoblastisch sondern als akute Leukämie vom Burkitt-Typ bezeichnet wird und einer vollkommen anderen Behandlung bedarf (. Besonders ist die infektiöse Mononukleose zu erwähnen, bei der neben vergrößerten Lymphknoten und einer Hepatosplenomegalie auch eine Immunthrombozytopenie mit hämorrhagischer Diathese bestehen kann. Weitere klinische Differenzialdiagnosen sind Infektionskrank heiten, wie die Toxoplasmose, Zytomegalie oder auch AdenovirusinfektioAn die intensiveren Behandlungsphasen während etwa des ersten halben Jahres schließt sich die remissionserhaltende Dauertherapie, bei der ALL bis zu einer Gesamtdauer von mindestens 2 Jahren an. Diese können beinhalten: Aus diesen Gründen wird in den meisten Transplantationszentren eine engmaschige molekularbiologische Überwachung während des ersten Jahres nach Transplantation durchgeführt, um Patienten mit einem drohenden Rezidiv frühzeitig zu erkennen und einer Therapie (7 Abschn.

cord-032183-yqqqe325	Patients awaiting liver transplantation because of HBV-related end-stage liver disease or liver cancer should be given nucleoside analogues with strong HBV inhibition and low drug-resistance, or nucleotides analogues combination treatment, in order to reduce viral load and prevent graft re-infection. The objective of antiviral treatment for HBV-ACLF is to reduce viral load at an appreciably high rate, thereby promoting reduction in hepatocyte cell death and improved survival outcomes by prevention of decompensation related multiorgan complications in this group of severely ill patients. Response-Guided Therapy 4006 study [126] suggested continuous treatment with LAM (10 years) delayed clinical progression in patients with chronic hepatitis and advanced fibrosis by significantly reducing the incidence of the risk of hepatocellular carcinoma and hepatic decompensation.

cord-102233-50ldj8j7	We present an anisotropic extension of the isotropic osmosis model that has been introduced by Weickert et al.~(Weickert, 2013) for visual computing applications, and we adapt it specifically to shadow removal applications. In our shadow removal applications we estimate the local structure via a modified tensor voting approach (Moreno, 2012) and use this information within an anisotropic diffusion inpainting that resembles edge-enhancing anisotropic diffusion inpainting (Weickert, 2006, Gali''c, 2008). For a regular image domain Ω ⊂ R 2 and a stopping time T > 0, given a degraded image f ∈ L ∞ (Ω; R) and two smoothing parameters ρ, σ > 0, the anisotropic diffusion model in [37] looks for a solution u in a suitable function space satisfying the following initial value problem: In this section we present several numerical examples showing the application of the isotropic and anisotropic osmosis model to solve the shadow removal problem in synthetic and real-world images.

cord-102667-mtl1x7gz	Inclusion criteria were a primary outcome or thesis focused on suicide (including suicide completion, attempts, and thoughts or ideation) among medical students, postgraduate trainees, or attending physicians. Based on this scoping review, a public health approach, including surveillance and early warning systems, investigations of sentinel cases, and postvention may be impactful next steps in preventing physician deaths by suicide. Physician suicide is a significant problem for the medical community and general public and is 45 poorly understood, suggesting that important knowledge and implementation gaps towards 46 prevention remain. To address this gap, this literature review aims to describe the state of current 47 knowledge and research on physician suicidal behaviors among medical students, postgraduate 48 trainees, including residents and fellows, and physicians. Overall, suicidal ideation was the second most studied thesis among articles included in this literature 185 review, especially suicidal ideation among medical students.

cord-103242-78asegs6	However, existing review-based recommendation methods ignore the context-dependent (generated by user-interaction), real-time, and time-sensitive properties of TSC data. To bridge the above gaps, in this paper, we use video images and users'' TSCs to design an Image-Text Fusion model with a novel Herding Effect Attention mechanism (called ITF-HEA), which can predict users'' favorite videos with model-based collaborative filtering. Specifically, in the HEA mechanism, we weight the context information based on the semantic similarities and time intervals between each TSC and its context, thereby considering influences of the herding effect in the model. Based on the above motivations and challenges, we propose an Image-Text Fusion model with a novel Herding Effect Attention mechanism (called ITF-HEA). Herding Effect Attention on above, we design an HEA mechanism, which calculates the influence weights of TSC contexts by their semantic similarities and timestamp intervals in an LSTM-based encoder-decoder framework.

cord-103523-46hn2249	Here we show using complementary approaches that in the absence of NO2−, freshwater and marine anammox bacteria couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). However, it is still unknown whether anammox bacteria have EET 27 capability and can couple the oxidation of NH4 + with transfer of electrons to carbon-based 28 insoluble extracellular electron acceptors. However, it is still unknown whether anammox bacteria have EET 27 capability and can couple the oxidation of NH4 + with transfer of electrons to carbon-based 28 insoluble extracellular electron acceptors. Here we show using complementary approaches that in 29 the absence of NO2 -, freshwater and marine anammox bacteria couple the oxidation of NH4 + with 30 transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene 31 oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs).

cord-103554-11avjsqu	The aim of this study was to evaluate the extent to which transcranial magnetic stimulation (TMS) can identify discrete cortical representation of lower-limb muscles in healthy individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil could not reliably identify discrete cortical representations of resting lower-limb muscles when responses were measured using bipolar surface electromyography. Cortical representation was 4 mapped for seven resting lower-limb muscles involved in control of the knee joint (rectus femoris, vastus lateralis, vastus medialis, medial hamstring, lateral hamstring, medial gastrocnemius, and lateral gastrocnemius) and was quantified using size, CoG, hotspot and number of discrete peaks. The current results indicate bipolar surface EMG used with TMS delivered through a doublecone coil cannot reliably identify discrete cortical representation of lower-limb muscles in young, healthy individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil cannot reliably identify discrete cortical representations of resting lower-limb muscles when MEPs are measured using bipolar surface EMG.

cord-103770-4svaq0at	title: Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes Here, we used tumor-derived cell lines derived from the MMTV-Myc mouse model to investigate metabolic pathways that are differentially utilized between two subtypes of breast cancer. To determine metabolic profiles of histologically distinct mouse mammary tumor subtypes, 84 polar metabolites were extracted from tumor-derived cell lines and quantitated using LC-MS/MS. We found metabolites involved in several central carbon metabolic pathways to be differentially 86 abundant between EMT and papillary tumor-derived cell lines (Figure 2 ). In the EMT subtype, both oxidized and reduced forms of glutathione, a key metabolite in 88 redox homeostasis, are elevated ( Figure 2B ). Metabolites 92 increased in the papillary subtype include fructose bisphosphate (FBP; glycolysis); acetyl-CoA indicating relative metabolite differences between EMT and papillary tumor derived cell lines. (B) Representative bar graphs of metabolites with statistically significant differences between EMT and papillary subtypes.

cord-103915-rzy7mejb	We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. We also recently showed that injection of an adeno-associated viral vector (AAV) encoding full-length human NT3 (preproNT3, 30kDa) into forelimb muscles 24 hours after stroke in adult or elderly rats improved sensorimotor recovery 19 . We examined anatomical neuroplasticity in the C7 cervical spinal cord because we knew from experiments using adult and elderly rats that the less-affected corticospinal tract sprouts at this level (as well as other levels) after injection of AAV-NT3 into muscles including triceps brachii 19 . fMRI performed one week after stroke confirmed that somatosensory cortex was not active when the affected paw was stimulated in either vehicle or NT3 treated rats (p>0.05, Supplementary Fig. 6b ). Treatment of disabled arm muscles with NT3 protein, initiated 24 hours after stroke, caused changes in multiple locomotor circuits, and promoted a progressive recovery of sensory and motor function in rats.

cord-103995-vok1dni9	Here, we estimate key epidemiological parameters and use a dynamic mathematical model of measles transmission to evaluate the effectiveness of the reactive vaccination campaigns in the refugee camps. Our modeling results highlight the success of the vaccination campaigns in rapidly curbing transmission and emphasize the public health importance of maintaining high levels of vaccination in this population, where high birth rates and historically low vaccination coverage rates create suitable conditions for future measles outbreaks. The transmission coefficient, β, was estimated according to the relationship β = R0/N D, where N is the total 93 population (i.e., S + I + R) and D is the average duration of infectiousness ( The model uses one infected case as the initial value for the number of individuals in the infected compartment, I(0). 114 For this analysis, the SIR model was run for two years to estimate the impact of vaccination on the next outbreak.

cord-104008-luqvw0y8	Systematic reviews of intervention studies that evaluated school-based or school-linked 31 health services delivered by a health provider were included. Systematic reviews of intervention studies that evaluated school-based or school-linked 31 health services delivered by a health provider were included. Through a comprehensive literature search, the 71 overview aimed to identify health areas and specific school health service interventions that 72 have at least some evidence of effectiveness. Finally, 74 the overview aimed to identify the health areas and specific school health services 75 interventions for which no SRs were found, whether because the primary literature does not 76 exist or where there are primary studies but no SR has been conducted. It is difficult to determine overall effectiveness of school health services from this overview because the included SRs do not sufficiently cover the health areas most relevant for children and adolescents.

cord-168862-3tj63eve	However, recent uses of the term "network" have focused increasingly on connectivity patterns that are more general than graphs [98] : a network''s nodes and/or edges (or their associated weights) can change in time [70, 72] (see Section 3), nodes and edges can include annotations [26] , a network can include multiple types of edges and/or multiple types of nodes [90, 140] , it can have associated dynamical processes [142] (see Sections 3, 4, and 5) , it can include memory [152] , connections can occur between an arbitrary number of entities [127, 131] (see Section 6) , and so on. Following a long line of research in sociology [37] , two important ingredients in the study of networks are examining (1) the importances ("centralities") of nodes, edges, and other small network structures and the relationship of measures of importance to dynamical processes on networks and (2) the large-scale organization of networks [121, 193] .

cord-178421-tl4qtz2x	In spite of the fact that efficient compression methods for dense two-dimensional flow fields would be very useful for modern video codecs, hardly any research has been performed in this area so far. We present a framework for the compression of flow fields based on edge-aware homogeneous diffusion inpainting. Our method benefits from the piecewise smooth structure of motion fields by storing additional edge information for the inpainting process. [15] stores mask pixels on both sides of edges and uses homogeneous diffusion inpainting to reconstruct smooth regions in-between. The centrepiece of our codec is the edge-aware homogeneous diffusion that is used to reconstruct a flow field with only a small amount of known data. Our edge-aware homogeneous inpainting algorithm also requires a set of mask points to be able to reconstruct a flow field. Comparison of JPEG2000, BPG, and our edge-aware approach for two flow fields and a compression ratio of 400 : 1.

cord-190332-uovhtaxb	On a high level, the proof of Lemma 6 is done by keeping a set of "active" trackers while reconstructing a planar embedding E of G: we start, as a base case, with any simple s − t path in E and iteratively add faces to it until it matches E. By Lemma 5, there is at least one entry-exit pair in E with respect to face C, so any tracking set must contain a tracker on some vertex of C. While there exist non-adjacent vertices u, v / ∈ {s, t} of degree 2 in a 4-cycle, place a tracker on either u or v and remove it and its edges from the graph. We show that Tracking can be solved in linear time when the input graph has bounded clique-width, by applying Courcelle''s theorem [7, 8, 10 ], a powerful meta-theorem that establishes fixed-parameter tractability of any graph property that is expressible in monadic second order logic.

cord-249962-ajnlbno7	We apply the theory of convex mosaics to show that the average geometry of natural 2D fragments, from mud cracks to Earth''s tectonic plates, has two attractors:"Platonic"quadrangles and"Voronoi"hexagons. These patterns have been reproduced in experiments of mud and corn starch cracks, model 2D fragmentation systems, where the following have been observed: fast drying produces strong tension that drives the formation of primary (global) cracks that criss-cross the sample and make "X" junctions [25] [26] [27] (Fig. 3) ; slow drying allows the formation of secondary cracks that terminate at "T" junctions 26 ; and "T" junctions rearrange into "Y" junctions 25, 28 to either maximise energy release as cracks penetrate the bulk [29] [30] [31] , or during reopening-healing cycles from wetting/drying 32 (Fig. 3) . The cut model simulates regular primitive mosaics as primary fracture patterns by intersecting an initial cube with global planes (Fig.6 ) while the break model simulates irregular primitive mosaics resulting from secondary fragmentation processes.

cord-252230-s1qd3x1b	Thereafter, several groups identified autophagy-related proteins (ATGs), evolutionarily conserved molecules that control fundamental aspects of the macroautophagy pathway, including the formation of autophagosomes, double membrane vesicles that capture cellular cargo and subsequently deliver them to the lysosome for degradation (Tsukada and Ohsumi, 1993; Thumm et al., 1994; Harding et al., 1996) . Among these, macroautophagy (hereafter called autophagy) is the most well studied and genetically controlled by ATGs. Classic autophagy proceeds through multiple "canonical" steps that include (1) initiation by an autophagy-inducing signal, (2) nucleation of an isolation membrane or phagophore assembly site, (3) elongation and sealing of this double membrane around the cargo to be sequestered to form an autophagosome, (4) docking and fusion of the autophagosome with the lysosome to form an autolysosome, and (5) degradation of the vesicle contents by lysosomal enzymes ( Fig. 1 A) .

cord-252355-ol21ofj9	title: Low pathogenic avian influenza virus infection increases the staining intensity of KUL01+ cells including macrophages yet decrease of the staining intensity of KUL01+ cells using clodronate liposomes did not affect the viral genome loads in chickens When we infected day 6 chickens with H4N6 low pathogenic avian influenza virus (LPAIV), we observed that H4N6 LPAIV infection increased the staining intensity of KUL01+ cells in trachea, lungs and duodenum of chickens at 3 days post-infection. Then, we used clodronate liposomes intra-abdominally in 5 day-old chickens and found significant reduction of staining intensity of KUL01+ cells in trachea and duodenum but not in lungs at 4 days post-treatment. We also hypothesized that the decrease of the staining intensity of KUL01 marker + cells following intra-abdominal administration of clodronate liposomes will augment replication of low pathogenic avian influenza virus (LPAIV) in respiratory and intestinal tracts of chickens.

cord-252600-bvh1o64r	We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The structure-guided design of inhibitor (I) encompassed the following steps: (a) we first determined a high resolution X-ray crystal structure of MERS-CoV 3CLpro in complex with GC376 ( Fig. 2/Panel A) . Validation of this idea was obtained by synthesizing extended inhibitor GC813 and determining a high resolution X-ray crystal structure of the MERS-CoV 3CLpro:GC813 complex ( Fig. 2/Panel B) . More importantly, representative aldehyde bisulfite adduct compounds 10a and 10c display potent inhibition toward MERS-CoV in both enzyme and cell-based systems, with low cytotoxicity (CC 50 > 100 mM) ( Table 2 and Fig. 4 ).

cord-252894-c02v47jz	This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. Therefore, the aim of this study is to design a model that uses the infectious disease occurrence data provided by the KCDC, search query data from search engines that are specialized for South Korea, Twitter social media big data, and weather data such as temperature and humidity. Figure 1 shows the overall framework of the model used in this study including the data collection process and the comparison of models designed using the deep neural network (DNN) method, the long-short term memory (LSTM) method, the autoregressive integrated moving average (ARIMA) method, and the ordinary least squares (OLS) method.

cord-252959-ktet18wl	Subjects for whom the following criteria were applicable were excluded from the experiment: individuals with a body mass index (BMI) under 18 or over 35; individuals who exceeded the normal maximum alanine transaminase and aspartate transaminase levels by 2-fold; females who were pregnant or were breast-feeding; females of childbearing age who did not agree to use contraceptives via medically proven methods (e.g., condoms, lubricant, and femidom) during the test period; individuals with a fasting plasma dextrose concentration over 126 mg/dL; individuals with high blood pressure (systolic blood pressure of 160 mm Hg or diastolic blood pressure of 100 mm Hg); individuals continuously using medicine that could affect the effectiveness assessment (hyperlipidemia medicine, steroid medicines, hormone medicines, immunosuppressants, and antibiotics); individuals who require continuous treatment for psychiatric disorders such as anorexia, depression, and manic depression; individuals with systemic diseases such as immunity-related diseases, serious hepatic and renal insufficiencies, malignant tumors, pulmonary disease, collagenosis, multiple sclerosis, allergic skin conditions, and other autoimmune diseases; individuals with a medical history of drugs and clinically significant allergic reactions; individuals with a history of gastrointestinal disorders that could affect the absorption of the test foods or a history of gastrointestinal surgery (excluding a simple appendectomy or hernia operation); individuals who consumed medicine or herbal medicines within a month of participation in the experiment which could affect immunity; individuals who participated in a different human study or clinical test and took experimental products within 3 months of participation in this experiment (excluding human studies with cosmetics); and individuals whom the researchers otherwise determined might have difficulty completing the experiment.

cord-253056-765rs3e7	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.

cord-253120-yzb8yo90	This paper builds upon early experiments to empower individuals in this ecosystem by leveraging the value of these public health data assets and trusted communications, illustrating the possibilities for engaging consumers to support reducing the impact of emerging diseases, outbreaks and the next pandemic. If the odds of receiving accurate information during a pandemic are against you in the social media world, consider the opportunity if there were direct public health agency communication channels to individuals -by building on existing immunization networks. It was through these early experiments and the growing data assets in state immunization systems that create a framework and technical platform to accelerate the potential value of engaging individuals in response plans for pandemic preparedness planning and support of today''s outbreak. The next step is to begin to engage individuals to establish those that would be willing to provide ongoing information to public health specific to immunizations and disease occurrences.

cord-253302-keh7s758	Our atomic models of the portal and capsid/CATC, together with visualization of CATCs'' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Unlike the comparatively high occupancies of capsid-associated tegument proteins in alphaherpesviruses Wang et al., 2018) and betaherpesviruses Yu et al., 2017) , KSHV CATC binding sites are markedly partially and/or more flexibly occupied, leading to poorly resolved CATC structures in prior icosahedral reconstructions of KSHV (Dai et al., 2014 . Thus, to accurately assess the specific occupancy of penton vertex CATCs and to understand the structural basis of a CATC''s discriminatory association with portal and penton vertices, we relaxed 5-fold symmetry for penton vertex sub-particles and performed 3D focused classification of their CATC-binding registers ( Figure S1 ).

cord-253477-gptjqti7	title: Comparative protective immunity provided by live vaccines of Newcastle disease virus or avian metapneumovirus when co-administered alongside classical and variant strains of infectious bronchitis virus in day-old broiler chicks Abstract This study reports on the simultaneous administration of live NDV or aMPV subtype B vaccines alongside two live IBV (Massachusetts-H120 and 793B-CR88) vaccines in day-old maternal-antibody positive commercial broiler chicks. Infectious bronchitis virus (IBV), avian metapneumovirus (aMPV) and Newcastle Disease virus (NDV) are respiratory RNA viruses that primarily infect the tracheal epithelium of chickens [7] . Post challenge, high viral loads were present in the trachea (Fig. 2 For the kidney samples at 14 and 21 dpv, Groups B (IBV vaccinated) and C (NDV + IBV vaccinated) increased from 14 to 21 dpv (0.81 to 3.13 log REU and 1.15 to 1.42 log REU respectively) (Fig. 1) .

cord-253487-gl5lozn9	[8] [9] [10] A review of the hand hygiene monitoring throughout 1 organization found the data that were based on observation of practice did not accurately reflect infection control compliance, 11 contributed little to improving practice, were not considered the best use of time, and lacked local credibility. The Infection Control Continuous Quality Improvement (IC-CQI) tool was developed in an acute teaching hospital in London, with over 1,200 inpatient beds and 8,000 staff spread across 7 hospitals on separate sites, providing emergency, general medicine, surgery, critical care, maternity, neonatal, and cancer services. To create an IC-CQI tool and reporting framework the infection prevention team used the Pronovost Knowledge Translation Cycle 17 to review the current hand hygiene monitoring tool, and to develop a quality improvement data collection tool. Intermittent validation was then undertaken of IC-CQI results including hand hygiene product availability, isolation practices, appropriateness of use of personal protective equipment (PPE), and compliance with standards of invasive devices insertion and management throughout the implementation period.

cord-254181-nquozaxt	To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. To elucidate the target tissues of FeMV-GT2 we established protocols for the isolation of primary feline cells from various organs of cats (see section 2.2.) Experimental in vitro infection was performed using the LLC-MK2-adapted FeMV-GT2-Gordon strain. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above.

cord-254317-n2knqj4z	Porcine epidemic diarrhea virus (PEDV) variants having a large deletion in the N-terminal domain of the S1 subunit of spike (S) protein were designated as S1 NTD-del PEDVs. They replicate well in experimentally infected pigs. Effect of mucin, bile and bile acids on the infection of PEDV icPC22A and icPC22A-S1Δ197 in Vero and IPEC-DQ cells Viruses (icPC22A or icPC22A-S1Δ197) were mixed with different concentrations of BM (0, 0.1, 0.3, 0.5 mg/mL) or PGM (0, 0.5, 1.0, 2.5, 5.0 mg/mL). Compared with the peak fecal PEDV N gene shedding titer (11.6 ± 0.2 log 10 copies/mL) of piglets in the icPC22A group (1 dpi), pigs in the coinfection group had a significantly higher peak titer (13.6 ± 0.7 log 10 copies/mL) ( Fig. 1B and Table 2 ) at a delayed time point (1.5 dpi). S1 NTD-del PEDV replicated to a lower peak titer in coinfection than that in single virus infection in both Vero cells and IPEC-DQ cells.

cord-254647-axyx03eg	Industry 4.0 is a "strategic PCAST (2011) focuses in its report on advanced manufacturing, a family of activities that (1) depend on the use and coordination of information, automation, computation, software, sensing, and networking, and/or (2) make use of cutting-edge materials and emerging capabilities enabled by the physical and biological sciences, for example, nanotechnology, chemistry, and biology. Advanced manufacturing processes are characterized by innovative variables of a technological and organizational nature that tend to change with workplaces, processes and conventional work practices, and can generate, as well as traditional occupational risks, other so-called new and emerging risks (NERs) (Brocal and Sebastián, 2015a) . With this chapter, a general framework of the emerging risks linked with advanced manufacturing processes and technologies has been shown. The general framework of the emerging risks linked with advanced manufacturing processes and technologies has been shown using the CWA 16649:2013 as main reference.

cord-254747-vox5xsgd	Overall, current evidence indicates that the EndoU activity of CoV nsp15 is dispensable for viral RNA synthesis and virus replication in cell culture. It was first discovered that the EndoU activity of nsp15 mediates the evasion of host recognition of viral dsRNA by infecting primary macrophages with EndoU-deficient CoVs (Deng et al., 2017; Kindler et al., 2017) . Moreover, treatment with the PKR inhibitor did not affect IFN induction or RNase L-mediated ribosomal RNA degradation in the EndoU-deficient CoV infected-macrophages (Deng et al., unpublished data) . Macrophages infected by the EndoU-deficient CoVs exhibited an early, RNase L-mediated degradation of ribosomal RNA, demonstrating that the OAS-RNase L system was activated (Deng et al., 2017; Kindler et al., 2017) . Lack of MDA5 expression or treatment with the PKR inhibitor did not affect virus-induced RNA degradation (Deng et al., 2017; Kindler et al., 2017) , suggesting that the nsp15-mediated blockage of OAS-RNase L activation is independent of the MDA5-IFN and PKR pathways.

cord-255339-oudj079q	The most important zoonotic viral diseases of which eight were diagnosed (in dead or diseased animals or through antibody detection) on the Arabian Peninsula over the last years include rabies, Middle East Respiratory Syndrome (MERS-CoV), influenza virus (IFV), Alkhurma hemorrhagic fever, Crimean-Congo hemorrhagic fever (CCHF), Rift Valley fever (RVF), West Nile fever (WNV), and dengue fever virus. The same WHO epidemiological data suggest that in these 22 countries including Saudi Arabia, in recent years, there has been report of steadily increasing number of sporadic human cases, incidence, and outbreaks of the virus [122] . Surprisingly, the current review showed that during an outbreak, each of these eight most zoonotic viruses (rabies, MERS-CoV, influenza, AHFV, CCHFV, RVFV, DHFV, and WNV) which occurred and/or cases confirmed in Saudi Arabia particularly from (Jeddah and/or Makkah) areas with at least one or all of these eight zoonotic viral pathogenic diseases [33, 44, 46, 78, [96] [97] [98] [99] 121, 130, 156, 171] .

cord-255460-r5p5helx	A phase III clinical trial ''Breast Cancer Trial of Oral Everolimus-2 (BOLERO-2)'' that included everolimus in combination with exemestane was successfully completed in 2012 leading to the approval of everolimus by US FDA for the treatment of HR + , HER2 − advanced metastatic cancers that are resistant to letrozole or anastrazole [125, 126] . Docetaxel and paclitaxel are used as neoadjuvant or adjuvant therapy as single agent or in combination with other chemotherapeutic agents for the treatment of early, advanced and metastatic breast cancer in pre-and postmenopausal women. We thus conclude that comprehensive approach of selecting the most appropriate gene-protein-pathway-target-drug modeling via integration of system biology and bioinformatics holds the high potential of providing more efficient, safer and cost-effective chemotherapeutics for treatment of even the most stringent forms of breast cancer (metastatic and triple negative).

cord-255488-nvgz53su	An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. Alternative strategies for the creation of mouse models of MERS-CoV infection are generation of DPP4 humanized mice and adaptation of the virus to the animals. Similarly, our human DPP4 knock-in mouse model supported MERS-CoV replication but did not lead to a severe lung disease phenotype [33] . Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4 Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice

cord-255686-m0ox841z	14 In several cases, an explicit immune response was suggested by the authors to explain the catatonia, such as in paediatric autoimmune neuropsy chiatric disorders associated with streptococcal infection (PANDAS), 15 or in NmethylDaspartate receptor (NMDAR) encephalitis purportedly triggered by yellow fever vaccination, 16 herpes simplex virus infection, 17 or EpsteinBarr virus infection. The most noteworthy result from our systematic review is that 72% (249/346) of all cases of autoimmune catatonia reported were due to NMDAR encephalitis, despite the disorder only being described in 2007 (table 2) . One group reported 84 cases of paediatric catatonia of which they suspected 7 had an autoimmune origin, including two patients with evidence of inflammation who were responsive to immunosuppression but who could not be diagnosed with any known disorder.

cord-255927-0tp4ig4o	This experimental work is supported by field data from related Marburg viruses, first identified after African monkeys infected people in Europe [24] , which apparently persist within large colonies of cave-dwelling Egyptian fruit bats, and RESTV in Asian bats. Thus, together the evidence for bats being the true reservoir host for EVD causing viruses is convincing, but relies on serological evidence of infection rather than virus detection, and the role of nonhuman primates as reservoirs remains uncertain. In other systems, archived sample banks have helped identify Middle East respiratory syndrome coronavirus-seropositive camels in East Africa over 11-year (Kenya) and 30-year (Sudan and Somalia) periods, suggesting extensive virus circulation in camels prior to the first human outbreaks [35] [36] [37] [38] . All of these studies are limited by data, but Ayouba et al''s comprehensive study supports the assumption that bats, not primates, are likely reservoir hosts and that nonhuman primates may be viewed as both sentinels for human infection and victims of EVD [9, 15, 33, 51] .

cord-256047-mabrmzd9	The hydrolysis of ubiquitin linkages is conducted by a specific family of proteases: the DUBs. These enzymes can act at different stages of the protein ubiquitination process: (1) At the "initial" stage, by cleaving the ubiquitin precursors to supply ubiquitin monomers to the ubiquitination enzymes; (2) at the "intermediate" stage, by the regulated removal of ubiquitin moieties from proteins to alter their fate (stabilization, conformational change); and (3) at the "final" stage by the removal of ubiquitin chains from substrates addressed to the proteasome to facilitate their degradation and processing into ubiquitin monomers, free to enter a new ubiquitination cycle ( Figure 2 ) [54] [55] [56] . To date, only a few substrates, known to be directly targeted for degradation by autophagy in response to ubiquitination, have been shown to be regulated by a specific DUB ( Figure 3F ).

cord-256130-zhlvvuj4	Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. The aim of the present study was to evaluate levels of TTV and EBV in relation to the frequency of infectious events and acute rejections over time in a prospective manner in a single-center cohort of lung-transplanted patients. The total nucleic acid content was isolated from serum or whole blood samples and analyzed for TTV-, EBV-, and CMV-DNA load by real-time PCR. Comparison of TTV-and EBV-DNA levels in lung transplant recipients who received either Tacrolimus-or Cyclosporinebased therapy revealed that Cyclosporine-treated patients had significantly lower TTV-DNA levels in serum at month 6 post-LTx and onwards, compared with the Tacrolimustreated patients (Figure 1 ). However, we found no association between either TTV-or EBV-DNA load and infectious events or acute rejections, which suggests a limited clinical applicability as biomarkers predicting short-term outcomes related to the net state of immunosuppression.

cord-256300-emsvxxs5	We review here our current understanding of the mechanism used by CoVs to infect host cells based on recent structural and biochemical studies of S glycoprotein ectodomains in prefusion and postfusion states as well as complexes with known receptors or neutralizing antibodies. Recent structural work comparing recombinant S proteins from SARS-CoV and MERS-CoV in isolation and in complex with their cognate receptors or neutralizing antibodies suggested an activation mechanism for coronavirus fusion (Gui et al., 2017; Kirchdoerfer et al., 2018; Song et al., 2018; Walls et al., 2019; Yuan et al., 2017) . Major antigenic determinants of MHV and SARS-CoV S overlap with the fusion peptide region (Daniel et al., 1993; Zhang et al., 2004) and binding of neutralizing antibodies to this site could putatively prevent fusogenic conformational changes, as proposed for influenza virus hemagglutinin or HIV envelope (Corti et al., 2011; Kong et al., 2016; Lang et al., 2017) .

cord-256652-ent4vu3z	investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. These findings, combined with data from peptide array experiments ( Supplementary Fig. 7) , identify the N-terminal junction binding site of the most potent neutralizing antibodies as including the first unit of the NANP repeat region and flanking non-repeat sequences, providing a molecular basis for the dual specificity of these antibodies.

cord-256855-s4pnq6j7	Results showed that the 178 phytochemicals could be divided into high−, medium−, and low−total−score groups depending on their binding affinity with Keap1, and the high−total−score group consisted of 24 compounds with abundant oxygen or glycosides. In this study, molecular docking and 3D−QSAR were applied to evaluate the interaction effects between 178 phytochemicals and the Nrf2 binding site in Keap1. Docking calculation results (Table 1) showed that their binding affinity with Keap1 in descending order was shown and the Average Total_Score were as follows: phenylethanoid glycosides > tocopherols > flavones > flavanols > anthocyanins > flavonols > stibenes > flavanones > chalcones > carotenoids > isoflavonoids > phenolic acids > quinones > others > coumarins > terpenes > alkaloids > organosulfurs. To evaluate their activation effect on Nrf2, 11 different compounds including C3S, L5G, RUT, API, KAEM, αT, COP, MAG, PIP, EA, and ECH from high−, medium−, and low−total−score groups were selected for further studied on a cell model.

cord-256903-8lyw27gh	Dendritic cells (DC) as such, and their role in immunity were first described in the 1970s and in 1995 Ralph Steinman published a series of papers describing that a cellular receptor called "DEC-205" (now CD205) was expressed on mouse DC, was involved in antigen processing (58, 59) and was detected by the monoclonal antibody NLDC-145. Studies in mice, for example, have shown the efficacy of vaccines against FMDV, however these efficacy studies have failed to be translated to the target species (cattle and pigs), presumably due to fundamental differences in the immune systems of model organisms and target species and the ability of the virus to mutate in these animals (112) . The role of bovine γδ T cells and their WC1 co-receptor in response to bacterial pathogens and promoting vaccine efficacy: a model for cattle and humans

cord-257026-wea39mmt	The response to outbreak of severe acute respiratory syndrome in the early phase of the epidemic in 2003 reflected the severe shortage of well-trained epidemiological professionals in China [6] ; therefore, measures were taken to improve the overall competency in the public health system. Participants were asked to rate the degree of factors (8 items) hindering EFI performance, including (1) lack of professional investigators, (2) complexity of methods and processes, (3) insufficient funding, (4) lack of operational guidelines, (5) poor laboratory testing ability, (6) lack of training and drills, (7) uncooperative cases, and (8) lack of a support network. In addition, FEI capacity could also be improved through on-the-job public health practice and formal professional training. Participation in targeted FEI training programs was another key factor in self-rated FEI capacity for public health workforce.

cord-257524-69fcw7ol	This may result in what are known as "hidden outbreaks" in which spread is known to transpire in a localized environment (such as an endemic pathogen) but inquiries are not considered to be worthwhile in the larger context of global human health. These factors have been reviewed elsewhere [9] and include the grouping of susceptibles in both the healthcare environment as well as the community, changes in human consumption of natural habitats, territories, and food sources, increased amount and ease of international travel, globalized trade, and political strife. One of the best known examples of travel-related spread of a hidden outbreak into an epidemic is the SARS coronavirus [12] . In addition, a retrospective analysis of coccidioidomycosis in China revealed 38 cases involving no history or travel to endemic areas [57] suggesting the fungus already may be spreading globally with no defined routes identified. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally

cord-257656-z7zx46gd	title: The Emerging Role of Rhinoviruses in Lower Respiratory Tract Infections in Children – Clinical and Molecular Epidemiological Study From Croatia, 2017–2019 Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. This study aims to determine the RV prevalence, compare it with prevalence patterns of other common respiratory viruses, as well as to explore clinical and molecular epidemiological features of RV infections among hospitalized children with acute respiratory infection.

cord-257886-ytlnhyxr	title: Nucleocapsid protein of porcine reproductive and respiratory syndrome virus antagonizes the antiviral activity of TRIM25 by interfering with TRIM25-mediated RIG-I ubiquitination These results indicate for the first time that TRIM25 inhibits PRRSV replication and that the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination. The cells were lysed in RIPA lysis buffer after 36 h of transfection and the effects of siRNAs were analyzed by WB using an anti-TRIM25 monoclonal antibody (cat. To investigate whether TRIM25-mediated RIG-I ubiquitination is regulated by the PRRSV N protein, HEK293T cells grown in 6-well plates were co-transfected with pCAGGS-Flag-RIG-I (0.5 μg per well) and HA-ubiquitin (0.5 μg per well), and the indicated amounts of the Myc-N expression plasmids. The experiment revealed that TRIM25-mediated RIG-I ubiquitination was potentiated by Sendai virus (SEV) infection but was substantially suppressed by increasing the PRRSV N protein expression, in a dose-dependent manner (Fig. 5) .

cord-258052-y9pzsoqa	A key method for detecting the presence of an emerging infectious disease syndrome or a biological weapons exposure in an ED patient is to develop a general approach that seeks out key historical and physical examination clues. Any suspicion of smallpox should prompt infectious disease consultation, airborne isolation procedures, and notification of local, state, and national public health authorities. Any suspicion of a VHF should prompt immediate consultation with an infectious disease physician and state and local health authorities. 20 There are several experimental treatments and vaccines (which can be used for postexposure prophylaxis) that are available for filovirus infections and arenavirus infections that would likely be used in any domestic VHF cases caused by these groups of viruses. 22 MERS should be suspected in individuals with upper or lower respiratory infection after travel to the Middle East in the prior 2 weeks, and confirmatory molecular testing can be done in conjunction with state and local health authorities.

cord-258323-vdeffy4l	To detect expression of inflammasomes and complement components in MERS-CoV-infected THP-1 differentiated macrophages and hDPP4-Tg mice, 2 µg of total RNA from cells or the lung of mice we used as template for first-strand cDNA synthesis. IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). These results suggest that complement inhibition decreased the expression of pyroptosis indicators, IL-1β and caspase-1, in mice infected with MERS-CoV. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages.

cord-259051-6kuh4njb	title: MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018 BACKGROUND: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. METHODS: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. In this study, we use the epidemiological data of all MERS cases reported to date to WHO to describe secondary cases of MERS-CoV infection among healthcare workers and to identify the risk factors for death among healthcare workers with secondary infection.

cord-259182-2d5yedn2	Transfer of passive immunity from dam to the offspring is thus essentially lactogenic in the canine species, colostrum ensuring both nutrients and immunity provision: at two days of age, mean serum IgG concentration in the puppy rises up to 6-16 g/L, with 85-95% of the immunoglobulins originating from the colostral transfer (Pollock and Carmichael, 1982; Poffenbarger et al., 1991; Schäfer-Somi et al., 2005a; Greene and Schultz, 2006; Day, 2007; Chastant-Maillard et al., 2012; Fig. 1) . Even when evaluated to its maximum (two days of age), immunoglobulins concentrations or specific antibody titers acquired by the puppy after colostrum intake remain lower than in the adult dog, reaching between 50 and 77% of the maternal level (Mila et al., 2014a; Gillespie et al., 1958) . In case of free suckling (uncontrolled by the breeder), quality of PIT is strongly variable among litters, but also among puppies from the same litter, both evaluated via serum IgG concentration (general immunity) and via CPV2-specific antibody titer (specific immunity; Fig. 2 ) (Mila et al., 2014b) .

cord-259798-fnm1im98	CONCLUSIONS: Rapid molecular testing positively impacts patient management of ARTIs. Adopting assays with a shorter turn-around-time improves decision making by decreasing empirical antibiotic use and duration, decreasing chest x-rays, increasing timely oseltamivir administration, and reducing length of stay. While research has demonstrated that MRPs may have a positive impact on patient outcomes such as decreasing empiric antibiotic exposures, length of hospital stay (LOS), and improving timely oseltamivir treatment for influenza patients [9] [10] [11] [12] [13] [14] , there is a dearth of information on whether this clinical impact is conditional on the turn-around-time (TAT) of the MRP assay. We hypothesized that the rapid detection of respiratory pathogens by RP compared to RVP would be positively associated with changes in antibiotic treatment, initiation of oseltamivir and LOS on pediatric patients < 18 years old.

cord-259966-szkiilb1	METHODS: Investigators evaluated ill travelers returning from a mass gathering, and presenting to a GeoSentinel site between August 2015 and April 2019, and collected data on the nature of the event and the relation between final diagnoses and the mass gathering. CONCLUSIONS: Despite this surveillance being limited to patients presenting to GeoSentinel sites, our findings highlight the importance of respiratory diseases at mass gatherings, the need for pre-travel consultations before mass gatherings, and consideration of vaccination against influenza and pneumococcal disease. Diagnoses related to attendance at the three most common MGs -Umrah or Hajj, World Scout Jamboree, and Olympics -are presented in Table 1 . Ill MG attendees seen at a GeoSentinel site most frequently attended Umrah or Hajj, likely due to the large number of travelers to these pilgrimages.

cord-260334-xo8ruswo	Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV. We have used this transduced mouse model to test the capacity of the antiserum derived from the dual route immunisation to neutralise MERS-CoV in vivo, by passive transfer prior to challenge with the EMC2012 strain and we have demonstrated a significant reduction in viral load in lung tissue in transduced mice.

cord-260336-kwzo8puo	Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Student''s unpaired two-tailed t-test was used to monitor the distribution of Z2 in male A129 mouse body and testicular tissue and to analyze the difference of viral RNA level in sera or tissues between Z2-and vehicle-treated A129 mice. ZIKV RNA copies in (A) testes, (B) epididymides, and (C) sperm of Z2-or vehicle-treated ZIKV-infected male A129 mice at day 16 were detected by qRT-PCR. Zika virus infection in the testicular tissue not only damages male testicular tissue, resulting in pathological lesion of testes and epididymides, but also produces ZIKV-infected semen, causing infertility.

cord-260485-o5wpcxdp	This chapter also covers the cheetah''s phylogenetic (evolutionary relation based on genetic data) position among other felids (section "Species-Level Taxonomy"), the genetic structure of the subspecies and within geographical regions (section "Phylogeography"), an overview of additional genetic studies including kinship (section "additional Insights Into cheetah Genetics"), and implications of genetic findings for cheetah conservation (section "Discussion"). In the 1990s, a study based on restriction fragment length polymorphism (RFLP) inferred low levels of nucleotide variation (0.18% diversity) in cheetah mtDNa relative to comparable studies in other species (Menotti-Raymond and O''Brien, 1993; Table 6 .1). an early study of cheetah Mhc I based on RFLP markers showed reduced genetic diversity in cheetah (observed heterozygosity = 0.05-0.07) compared to other species, which was only comparable to that of lions from isolated populations (Gir Forest and Ngorongoro crater; Yuhki and O''Brien, 1990 ; Table 6 .1).

cord-260946-n1ms8m9h	Using this developed analytical technique, we are not only able to characterize dioxins and chlorinated triclosans from the transformation of triclosan in the presence of active chlorine in seawater mixture, but also investigated their formation yields and possible formation mechanisms and pathways under both dark and UV irradiation conditions. As shown in Fig.1 , many products were detected in the triclosan photo-transformation experiment, including several dioxins and chlorinated triclosan derivatives. With the same initial concentrations of triclosan and free chlorines, much more dioxins were formed under UV radiation and all of them, including 2,3,7,8-TeCDD were detected as the photo-transformation products of triclosan, given enough reaction time. Chlorinated triclosan derivatives and dioxins, including the most toxic 2,3,7,8-TeCDD, were measured as the photo-transformation products of triclosan in the presence of active chlorine in seawater matrix under both UV irradiation and dark conditions.

cord-261258-yd2p1buu	Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Immunization in the mouse model with a recombinant bacillus of Calmette-Guérin (BCG) that expresses the nucleoprotein (N) of hRSV (rBCG-N-hRSV) induce the production of neutralizing antibodies against hRSV and a T helper 1 (Th1) cellular immunity that protects from hRSV associated-lung pathology by decreasing the infiltration of inflammatory immune cells into the lungs and reduce viral loads in the airways of hRSV-infected mice (Bueno et al., 2008; Cautivo et al., 2010; Leyrat et al., 2014) Furthermore, a single low dose of this vaccine produced using current good manufacturing practices (cGMP), conferred protection against hRSV infection in the mouse model (Cespedes et al., 2017) .

cord-261303-xjbz9fw9	Today Mass Gathering Medicine focuses on the public health challenges to hosting events attended by a large enough number of people, at a specific site, for a defined period of time, likely to strain both the planning and response to the mass gathering of a community, state, or nation. Today mass gathering medicine focuses on the public health challenges to hosting events attended by a large enough number of people at a specific site for a defined period of time to strain the planning and response of a community, state, or nation. But it is useful to consider the World Cup as a sporting event on a par with the Summer Olympics and the more recently developed Para-Olympics while the Hajj as a mass gathering centering on Islamic belief is better understood within the context of other mass gatherings centered on other theist belief systems including the Hindu Kumbh Mehla, World Youth Day and other pilgrimages [8] [9] [10] .

cord-261914-qfim8nu5	This study aimed to analyze the complete genome sequence, i.e., 11 genome segments of the lapine rotavirus (LRV) identified in the intestine of a dead rabbit in the Republic of Korea (ROK) and to describe the genetic relationships between this lapine isolate [RVA/Rabbit-wt/KOR/Rab1404/2014/G3P[22] (Rab1404)] and other lapine isolates/strains. Additionally, the genome segments VP6 (I2), NSP1 (N2), and NSP5 (H3) of Rab1404 were closely related to those of bovine RVAs. This is the first report describing the complete genome sequence of an LRV detected in the ROK. The objective of this study was to analyze an LRV isolated from the intestine of a dead rabbit in 2014 in the ROK by performing a complete genomic sequence analysis of the 11 genome segments and to characterize the phylogenetic relationships between our isolate and other lapine isolates/strains.

cord-261962-sfa9d1ux	In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. • Our identification of the dominated routes, that is the close contact route (large droplet) for influenza, the fomite route for norovirus, and all 3 routes for SARS CoV, suggested the relative importance of different environment intervention for different infectious diseases in air cabins and probably also in other indoor environments. F I G U R E 1 Spatial distribution for 3 in-flight infection outbreaks, (A) norovirus, 26 (B) SARS CoV, 27 and (C) influenza A H1N1 28 of infectious pathogens from the index source passenger, which is also sometimes termed indirect contact route.

cord-262017-utvy0i8l	title: Talaromyces marneffei laboratory cross reactivity with Histoplasma and Blastomyces urinary antigen In the US when examining HIV-patients for suspected fungal infections, laboratory serological tests guide therapy until cultures are available. We present the case of a 35-year-old HIV patient originally from Thailand in which urine lab results were positive for Blastomyces and Histoplasma antigen, but biopsy showed T. Endemic to Southeast Asia, East Asia and China, Talaromyces marneffei is a dimorphic fungus capable of causing systemic fungal infections in immunocompromised patients (Supparatpinyo et al., 1994) . In the U.S. patients with HIV infection usually undergo testing for endemic fungal infections such as Blastomyces, Histoplasma, Coccidioides and Paracoccidioides. To our knowledge, this is the first case reporting systemic mycosis due toTalaromyces marneffei with associated hyponatremia secondary to SIADH and cross-reactivity with Blastomyces and Histoplasma in urine antigen testing.

cord-262036-wig4wdno	As shown in Fig. 1B , the terminal sialic acid was effectively removed in dSA-OVM after enzymatic hydrolysis, and its binding activity was obviously lower than that in the natural OVM. To analyze the role played by free sialic acid in the binding of OVM to HA, further experiments were carried out with different sequences of additions. Based on the above results, it was found that free sialic acid enhances the binding of OVM to influenza virus HA. It is indicating that sialic acid is involved in the binding of OVM to influenza virus, and additional free sialic acid could enhance the OVM antiviral process. The hemagglutinin of the influenza virus recognizes and binds to the ovomucin carbohydrate chain terminal sialic acid, and the interaction is greatly diminished after the sialic acid is removed. The addition of free sialic acid can promote the binding of ovomucin to hemagglutinin and enhance ovomucin anti-influenza virus activity.

cord-262094-b4yuh5y9	title: Separation and Quantification of Four Main Chiral Glucosinolates in Radix Isatidis and Its Granules Using High-Performance Liquid Chromatography/Diode Array Detector Coupled with Circular Dichroism Detection To clarify the chemical characterization of chiral glucosinolates—the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was developed to simultaneously separate and quantify the four main chiral glucosinolates: progoitrin, epiprogoitrin, and R,S-goitrin. Isatidis were performed using HPLC-UV-CD, which improved the limitation of high-cost chiral columns, complex operation of sample preparation, and simultaneous quantification of the characteristic glucosinolates. Isatidis were performed using HPLC-UV-CD, which improved the limitation of high-cost chiral columns, complex operation of sample preparation, and simultaneous quantification of the characteristic glucosinolates. As shown in Figure 1 , the chemical composition of progoitrin, epiprogoitrin, and R,S-goitrin in crude drugs, decoction pieces, and granules of R. As shown in Figure 1 , the chemical composition of progoitrin, epiprogoitrin, and R,S-goitrin in crude drugs, decoction pieces, and granules of R.

cord-262205-ax3i3d7f	The aim of this study is to explore stakeholders'' experiences on the health system''s preparedness and challenges, and to provide suggestions for preventing infectious diseases during the Arbaeen mass gathering. Health infrastructure defects in Iraq has three sub-themes (health abandonment in Iraq, the weaknesses in health culture and problems related to the health system); poor control of the causative factors of infectious diseases has three sub-themes (the underlying factors of the prevalence of contagious diseases, health system response to communicable diseases and ignoring the risks of the Arbaeen ceremony); the low perception of risk in pilgrims has three sub-themes (lack of awareness in pilgrims, fatalism in pilgrims and unhygienic belief in pilgrims); and the ineffectiveness of health education has two sub-themes (training shortage in the targeted group and educational content problems) that shows participant''s experiences of the health system''s challenges for coping with infectious diseases during the Arbaeen ceremony.

cord-262274-oununr9g	In this study, we analyzed the codon usage pattern of the S gene using complete coding sequences and complete PDCoV genomes to gain a deeper understanding of their genetic relationships and evolutionary history. When the actual ENC-plot values of these sequences are lower than the standard curve, it is suggestive of natural selection playing a role in driving codon usage bias (Fuglsang, 2008) . Overall, the above results indicate that the effect of mutation pressure is in all codon positions, but natural selection plays a major role driving the codon usage bias of PDCoV. We found that the A ≠ U, C ≠ G, for both the S gene and whole genomes, which indicates the inequivalent role of mutation pressure and natural selection in shaping the codon usage of PDCoV. Briefly, PDCoV has a low codon usage bias, which was affected by natural selection, mutation pressure, and dinucleotide abundancy.

cord-262585-5vjqrnwh	Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Molecular mimicry varies over a continuum, from one extreme that includes sequence and structural similarity (i.e., orthologs) of entire proteins, to another extreme of chemical similarity at only a few localized sites, as is the case for short linear motifs (SLiMs). Viral SLiMs are potentially useful in synthetic biology, to provide a toolkit for new functions, for example, to modulate immune responses or to complement and interact with newly developed adjuvants in a synergistic manner [9] . Research efforts to develop broad-spectrum antiviral compounds or design broadly cross-protective vaccine immunogens benefit directly from knowledge of gene products, protein functions, and motifs involved with viral immune interference. SLiMs are useful in synthetic biology, where minor edits can alter target specificity, modulate persistence, reprogram interactions with cell-signaling domains, and alter protein function in myriad other ways.

cord-262682-gsvswr7v	SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. Many vertebrate intestines (such as mice, rats, chickens, humans, and turkeys) harbor commensal organisms named segmented filamentous bacteria (SFB) that bind specifically to the host intestinal epithelium. The role of SFB in Th17 cell production was initially demonstrated when mice were inoculated with mouse, rat, and human microbiota containing bacterial spores similar to that of the genus Clostridium. Colonization and distribution of segmented filamentous bacteria (SFB) in chicken gastrointestinal tract and their relationship with host immunity

cord-262753-jld1ygxt	Analysis of sequence reads in the different fractions shows >60% of total cytoplasmic and polysome-associated reads map to the 5 viral genes by 6 hours post-infection, a time point at which robust host cell translational shut-off is observed. The cellular mRNAs that remain most polysome-associated following infection had longer half-lives, were typically larger, and were more AU rich, features that are shared with the viral mRNAs. Several of those mRNAs encode proteins known to positively affect viral replication, and using chemical inhibition and siRNA depletion we confirm that the host chaperone heat shock protein 90 (hsp90) and eukaryotic translation initiation factor 3A (eIF3A)—encoded by 2 such mRNAs—support viral replication. In the present study, we interrogate global mRNA translation in VSV infected cells using RNAseq analysis of the cytoplasmic mRNA transcriptome, and parallel sequencing of polysome-associated mRNAs. We obtain support for the model that an overabundance of viral mRNA contributes to host shut-off by leading to a re-distribution of cellular ribosomes onto viral mRNA.

cord-262923-kgzbd6w3	Here, we report the development of an improved molecular diagnostics tool that utilizes CRISPR/dCas9-mediated biosensor that couples a nuclease inactivated Cas9 (dCas9) and single microring resonator biosensor, enables label-free and real-time detection of pathogenic DNA and RNA. In this study, we developed an improved diagnostic tool by combining a CRISPR/dCas9 and an isothermal diagnostic approach based on SMR biosensor for simultaneous nucleic acid (RNA and DNA) amplification and detection with speed as well as high sensitivity and specificity. For simultaneous amplification and detection of nucleic acid, sequence specific primer of target was immobilized to the surface of the SMR biosensor and dCas9 RNP was in reaction chamber with single temperature for isothermal reaction with RPA. To achieve sensitive detection with dCas9 RNP on SMR biosensor, we constructed guide RNAs (gRNAs) targeting two tick-borne pathogens that have substantially overlapping clinical presentations: Orientia tsutsugamushi, the causative agent of scrub typhus (ST), and bunyavirus, the causative agent of severe fever with thrombocytopenia syndrome (SFTS) (Fig. 1B) .

cord-263142-o8qbqxhx	We examined blood and buccal swab specimens of domestic cats in Brazil for detection and quantification of each feline virus to evaluate their potential association with disease and transmissibility in animals with single or multiple retroviral infections. Buccal swab gDNA from 33 nested PCR-negative animals identified seven qPCR positive cats with a median pVL of −0.7 log10 copies/cell (201,363 copies/10 6 cells). Analysis of cats classified as potentially transmissible and non-transmissible found no statistical difference between FFV pVLs. Of 27 FeLV-positive cats diagnosed by serological and/or molecular assays, 26 with available PBMC gDNA were FeLV qPCR-positive with a median pVL of 2.11 log10 copies/cell (1.29 × 10 8 copies/10 6 cells) ( Figure 1B) . Testing of 35 buccal swab gDNA samples identified four qPCR-positive cats with a median FeLV pVL of −0.55 log10 copies/cell (2.91 × 10 5 copies/10 6 cells).

cord-263315-g7os15m1	title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. In human and mouse plasmacytoid dendritic cells (pDCs), which are professional interferon-producing cells specialized in recognizing viral RNA and DNA through the endosomal Toll-like receptors (TLRs) TLR7 and TLR9, respectively, PLSCR1 was described as a TLR9-binding protein that plays a significant role in type-1 interferon responses in pDCs by regulating TLR9 expression and trafficking [57] . Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts. Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts.

cord-263322-y4htkvux	title: Association between genetic polymorphisms and osteonecrosis in steroid treatment populations: a detailed stratified and dose-response meta-analysis The studies were included in our meta-analysis if they met the following criteria: (1) case-control or cohort studies comparing a population that suffered SONFH with a population that did not suffer after steroid treatment, (2) studies assessing the associations between genetic polymorphisms and SONFH, and (3) studies reporting the frequencies of specific alleles or the effect sizes of individual genotypes between cases and controls. First, the present study found that the ABCB1 rs1045642 mutation has a protective effect on SONFH, and the risk will be further reduced with increasing cumulative steroid dosage. Genetic association of the P-glycoprotein gene ABCB1 polymorphisms with the risk for steroid-induced osteonecrosis of the femoral head in Chinese population

cord-263391-18x4ann5	S ince the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 (1), more than 2,250 laboratory-confirmed cases have been reported to the World Health Organization (WHO); approximately one third of these cases were fatal. The Ministry of Health, Oman; Ministry of Health, Saudi Arabia; and Korea National Institute of Health, South Korea, donated convalescent serum and plasma samples from PCR-confirmed MERS-CoV-infected patients. We included MERS-CoV-negative serum with antibodies against other human coronavirus HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 (samples 3, 6, 7, 8, 13, 15, and 17) to test specificity of the assays ( Table 2 ). Participants detected pool A, the high-titer MERS-CoV antibody pool (sample 16) in all assays (Table 3) . The low-positive pool (pool C, sample 14) was only detected as positive in a single assay in the study, the Alpha Diagnostic International MERS NP ELISA performed in laboratory 05.

cord-264751-2l3cqhe2	8e11 The purpose of the present study is to describe all the cases with PRF occurring in children aged 0 18 years diagnosed and hospitalized at the pediatric departments of the Soroka University Medical Center, Beer-Sheva, Israel, during the period 2005 2016, and to compare their microbiologic laboratory, clinical, therapeutic and outcome characteristics in relation to the various etiologies of this syndrome. We conducted a retrospective study enrolling all the children aged 0 -18 years hospitalized at the pediatric departments of the Soroka University Medical Center, Beer-Sheva, Israel, during the period 01/2005 12/2016, with a diagnosis of purpuric rash accompanied by a fever >38 C. The aim of the present study was to determine the etiology of all cases of PRF occurring in children aged 0 18 years hospitalized in southern Israel during the period 2005 2016, and compare their microbiologic, laboratory, clinical, therapeutic and outcome characteristics in relation to the various etiologies of this syndrome.

cord-265282-v3n9ff16	For the SIQ based ordinary differential equation (ODE) model, we perform the task of parameter estimation, and apply optimal control theory to the controlled SIQ model, with the goal of minimizing the infectious compartment population and the cost of implementing the quarantine and isolation strategies. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach.

cord-265312-yfjme53q	This study compared the performances of three commercial transmissible gastroenteritis virus/porcine respiratory coronavirus (TGEV/PRCV) blocking enzyme-linked immunosorbent assays (ELISAs) using serum samples (n = 528) collected over a 49-day observation period from pigs inoculated with TGEV strain Purdue (n = 12), TGEV strain Miller (n = 12), PRCV (n = 12), or with virus-free culture medium (n = 12). All pigs in the negative-control group remained TGEV and PRCV seronegative throughout the monitoring period when tested with any of the three TGEV/PRCV differential blocking ELISA kits evaluated in this study ( The percentages of TGEV antibody-positive serum samples reported by the three commercial ELISA kits evaluated over the 50-day study period for pigs inoculated with TGEV strains Purdue and Miller are presented in Fig. 2A to F, respectively.

cord-265642-7mu530yp	Using protein expression systems it is possible to produce virus-like particles (VLPs), which are made up of monomers, which are able to multimerize into VLPs, and display the antigenic determinants of target pathogens on their surface. For example, in different laboratories different eukaryotic systems for viral protein expression, including plant cells, are used to produce VLPs which are used for vaccination against the hepatitis C virus (HCV) [36] . Antigen of the duck hepatitis A virus produced in the baculovirus expression system assembles into VLPs immediately in the cultured Spodoptera frugiperda (sf9) cells, while immunization of ducklings with the obtained VLPs induces a high level humoral immune response and protects them from developing the disease [46] . Expression vectors for foreign protein production in plants have been developed based on plant viruses, which allows obtaining plant-producing recombinant viruses or VLPs displaying the target antigen on their surface [101, 102] .

cord-265679-7gzont7l	In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. Vero cells cultured in 24-well plates were washed with PBS for 3 times and inoculated respectively with single medium, or single PEDV, or PEDV pre-incubated with different concentrations of Caerin1.1. PEDV suspensions containing different concentrations of Caerin1.1 were pre-incubated for 1 h at 37 • C, and were serially diluted before they were inoculated on the 80% confluent Vero cell monolayers grown in the 96-well plates, followed by washing 3 times with PBS. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1.

cord-266127-phv08xe2	Consistent to our previous results, Rbx1 expression was successfully knocked down in response to Rbx1 siRNA in RV-SA11-infected cells lysed at 9 hpi as well as in mock-infected control but not in RV-SA11-infected cells harvested FIGURE 1 Host RNA interference is blocked during early hours of RV-SA11 infection. Together, the data suggest that actively replicating RV-SA11 triggers attenuation in protein levels of AGO2 leading to functional blocking of RNAi during early time points (2-6 hpi) of infection. Sensitivity of ectopic GFP (pEGFP-N1) expression to siGFP was also reduced in RV-NSP1overexpressing cells ( Figure S4A ), indicating that RV-NSP1 might FIGURE 3 Rotaviral nonstructural protein 1 triggers ubiquitination and proteasomal degradation of AGO2. Rotavirus nonstructural protein 1 suppresses virus-induced cellular apoptosis to facilitate viral growth by activating the cell survival pathways during early stages of infection

cord-266204-ipa017wz	This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing "downstream" adaptive humoral and cellular responses to infectious pathogens and vaccines. A decade ago, we described the idea of vaccinomics and adversomics, based on the immune response network theory [5, 6] , which utilizes immunogenetics/imunogenomics and systems biology approaches to understand the basis for inter-individual variations in vaccineinduced immune responses in humans, as well as the basis for adverse side effects from vaccines [7] . Published data reveal that innate and adaptive immunity is decreased with age, but the systems-level mechanisms for these findings are unclear [66, 68] , particularly in regard to influenza and other viral vaccine responses where the morbidity, mortality, and associated healthcare costs are greater in older individuals [11] .

cord-266288-buc4dd5y	Classification of DNA sequences is an important issue in the bioinformatics study, yet most existing methods for phylogenetic analysis including Multiple Sequence Alignment (MSA) are time-consuming and computationally expensive. Here we propose a new Accumulated Natural Vector (ANV) method which represents each DNA sequence by a point in ℝ(18). The natural vector method performs well on many datasets (Deng et al., 2011; Yu et al., 2013b; Hoang et al., 2016; Li et al., 2016) , however, it only considers the number, average position and dispersion of positions of each nucleotide. In this paper, we propose a new Accumulated Natural Vector (ANV) method, which not only considers the basic property of each nucleotide, but also the covariance between them. In this paper, we propose an Accumulated Natural Vector approach, which projects each sequence into a point in R 18 , where the additional six dimensions describe the covariance between nucleotides.

cord-266455-rbblg4pu	Syndromic diagnostic testing using novel, rapid multiplexed molecular platforms represents a new opportunity for rapidly targeted antimicrobial therapy to improve patient outcomes and facilitate antibiotic stewardship. This is an FDA approved and CE marked platform that uses nested real-time PCR to detect 34 clinically important respiratory targets (15 semi-quantitative bacterial targets, 3 qualitative atypical bacterial targets, 8 [30] [31] [32] Furthermore, the pneumonia panel detects pathogens in a much higher proportion of samples than culture. Rapid syndromic molecular platforms have the potential to significantly improve the use of antibiotics and clinical outcomes in patient with pneumonia, but high quality randomised controlled trials are urgently required to evaluate their clinical impact. an observational study comparing the performance of two multiplex PCR platforms against routine microbiology for the detection of potential pathogens in patients with suspected hospital acquired/ventilator associated pneumonia (HAP/VAP) across

cord-266487-ah3jclgw	This paper presents a comprehensive particle swarm optimization (CPSO) method to locate a contaminant source in dynamic indoor environments with mechanical ventilation and develops a multi-robot source localization system to experimentally validate the method. In this study, considering the complexity of airflow and concentration distributions in dynamic indoor environments, we present a comprehensive particle swarm optimization (CPSO) method that integrates the IPSO algorithm with a source confirming algorithm and a strategy for escaping from local extremum areas to improve the success rate and efficiency of source localization. (2) A multi-robot source localization system was developed, and three robots were used to validate the presented method at two typical source locations (DS, in the downwind zone, and RS, in the recirculation zone) in a dynamic indoor environment with the air supply louvers of a cabinet air conditioner periodically swinging from left to right.

cord-266521-vovas81d	In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. While the ribozyme was not specifically regulated by a small molecule via an aptamer, this work paved the way for the subsequent riboswitches that employ allosterically regulated ribozymes (aptazymes) embedded in the 5 0 and/or 3 0 UTR to chemically regulate gene expression in mammalian cells (Figure 1a ) [13] [14] [15] [16] . A new mode of engineered RNA-based gene regulation in mammalian cells was demonstrated by controlling the accessibility of a miRNA target site by aptamer-ligand interaction

cord-267012-45tre8rn	While recombinant baculoviral vector expressing both VSV-G and influenza HA was shown to evoke both humoral and cellular immune responses and provided effective protection against lethal virus challenge in mouse and chicken hosts [26] , the high cytotoxicity of VSV-G protein [98] and its immediate inactivation by serum complement systems impedes the use of the element in a vaccine delivery vehicle [99] . The vaccine showed successful HA expression on its envelope, and mice vaccination studies showed that both the live and adjuvanted with inactive form of recombinant baculovirus induced HA-specific antibody responses and offered complete protection against lethal viral infection [101] . Moreover, recombinant baculovirus with CMV-polyhedrin dual promoter for expressing chimeric HA of H9N2 was shown to efficiently express HA in both mammalian and insect cells, induce strong immune response, and provide 100% protection against lethal H9N2 viral challenge in mice, unlike other vaccine candidates observed [34] .

cord-267042-nvwnbp2j	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.

cord-267139-r8rg0iqq	As many as 34% of patients with recent travel history are diagnosed with routine infections, but serious infections such as malaria, enteric fever, and dengue fever should be on the differential diagnosis due the high morbidity and mortality in children. As awareness of tropical illnesses rise in parents, such as the increase in multidrug-resistant bacteria worldwide or the emergence of epidemics with Zika virus in South America, families may be more anxious about serious infections as an etiologic factor of fevers. Because the causes and clinical outcomes associated with fevers in pediatric travelers vary from self-limited to deadly, a systems-based approach can lead to prompt diagnosis and treatment that evaluates for the most likely and serious diseases early in the illness course. A European study of travelers returning from Brazil in 2013 to 2016 reported that of the 29% of patients with travel-related complaints, 6% had dengue fever, 3% had chikungunya, and 3% had Zika virus infection.

cord-267166-ecmayzr6	While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This study takes advantage of the distinct tissue environments established during EAE and JHMV infection to characterize temporal alterations in gene expression profiles of BMDM versus microglia in a Th1 biased demyelination model. We next evaluated effector functions of BMDM versus microglia associated with JHMV-induced demyelination by comparing gene expression profiles using nCounter analysis of mRNA isolated from purified BMDM and microglia of infected CX3CR1 GFP/+ CCR2 RFP/+ mice. Using a similar approach with Nanostring analysis as in EAE, the present study used gene expression profiling to characterize both BMDM and microglia myeloid functions at various times post JHMV infection.

cord-267228-g2tf1jz6	Mice were immunized by lavage administration of the recombinant NC8-pSIP409-pgsA''-S-DCpep, which was observed to induce DC activation and high production of sIgA and IgG antibodies in experimental animals, while also eliciting production of significantly more IgA(+)B220(+) B cells. Compared with the saline group, the expression level of CD11c + CD40 + of DCs surface molecules in the LP cells of the small intestine was significantly increased in the NC8-pSIP409-pgsA''-S-DCpep group (P < 0.01) and NC8-pSIP409-pgsA''-S-Ctrlpep group (P < 0.05) experimental groups (Fig. 2B) . Unexpectedly, the level of IFN-γ in the supernatant of MLN cells cultured with the strains expressing S-DCpep was significantly higher in the group of mice orally immunized with recombinant NC8-pSIP409-pgsA''-S-Dcpep compare to the group of mice orally administered with saline (P < 0.01), NC8-pSIP409-pgsA''-S-Ctrlpep and NC8-pSIP409-pgsA'' groups (P < 0.05) (Fig. 6B ).

cord-267363-5qri915n	As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. As well as greatly expanding our knowledge of virus diversity, including the ''dark matter'' of highly divergent viruses that often elude characterization, these new data will enable us to determine the fundamental evolutionary and ecological processes that shape the virosphere, and better understand the virus-host interactions that lead to disease emergence.

cord-267709-i2loz1xb	title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Finally, our data demonstrates that the antiviral effects of IFITM1 on cellular proliferation and HBV replication are partially restored when HBc is co-expressed with BAF200 in HBV-infected cells. First, BAF200C was co-transfected with either empty vectors or HBc into 293T cells, then the whole cell lysate was immunoprecipitated by an anti-Flag antibody and then subjected to western blot by anti-HA antibodies to detect the interacting proteins. (d) HepG2 cells were co-transfected with the pGC-FU-Flag-BAF200 and pCMV-HA vectors or pCMV-HA-HBc, and co-IP assays were carried out with anti-HA antibody or IgG. We co-transfected HBc and BAF200 into HepG2 cells, treated the cells with 500 U/mL IFNα, and detected the expression of IFITM1 by western blot (Figure 2d ).

cord-267791-v10eh408	We conducted a systematic review of studies on PPE use for respiratory infections in healthcare settings in Pakistan. Face masks (or medical masks) and respirators are the most commonly used PPE to protect from influenza and other respiratory infection in healthcare settings. The aim of this study was to examine the use of PPE for respiratory infections in healthcare settings in Pakistan. Studies where PPE was examined for general infection control were also included, given respiratory protective equipment (face masks and/or respirators) was mentioned. Two studies examined the guidelines and current practices on the use of face masks/respirators for influenza, tuberculosis and SARS in Pakistan [21, 22] . Medical masks were generally used to protect from influenza, tuberculosis and other respiratory infections, while the use of respirators was limited to high-risk situations [21, 22] .

cord-267816-84z9fp2u	title: Severe Immune Thrombocytopenia Complicated by Intracerebral Haemorrhage Associated with Coronavirus Infection: A Case Report and Literature Review Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that causes isolated thrombocytopenia. We describe the case of a healthy man who presented with severe ITP complicated by intracranial haemorrhage following upper respiratory tract infection. LEARNING POINTS: Coronavirus can cause severe immune thrombocytopenic purpura (ITP). We present a case of severe thrombocytopenia complicated by intracranial haemorrhage following infection with a coronavirus, which has not previously been reported. Clinical presentation varies from the more common petechiae, purpura and mucous membrane bleeding (epistaxis or gum bleeding) to the rare severe gastrointestinal or intracranial bleeding, which has been reported in 1.4% of patients [3] . [8] described a patient with severe thrombocytopenia associated with varicella zoster infection whose platelet count returned to normal after antiviral treatment. Infection with coronavirus (CoV) has been associated with severe acute respiratory syndrome (SARS). In contrast, we report severe thrombocytopenia following mild coronavirus upper respiratory tract infection.

cord-267965-84sotgds	While advances in human genetic analysis have led to the identification of several host genes that regulate pathogen susceptibility in humans (Newport and Finan, 2011) , much of our understanding of how specific genes affect infectious disease pathogenesis in mammals has come from studies using mouse models (Masopust et al., 2017) . In contrast to the approaches discussed above, researchers have also studied the role of natural genetic variants by leveraging differential phenotypes across inbred strains, using classical genetic breeding strategies to identify pathogen susceptibility genes such as Oas1b, immune cell activating receptor Ly49H, and large interferon-induced GTPase Mx1 (Casanova et al., 2002) . Due to higher genetic diversity with novel allele combinations and epistatic interactions, the CC yields more phenotypic variation and extreme phenotypes than classical GRPs. The selection of founder strains and the breeding design, as well as higher levels of recombination, result in lower levels of long-range disequilibrium and population structure than classical GRPs, allowing for higher resolution quantitative trait locus (QTL) mapping (Iraqi et al., 2012; Threadgill et al., 2002) .

cord-268142-lmkfxme5	title: Animal modeling in bone research—Should we follow the White Rabbit? Our aim here is to provide a broad overview of animal modeling and its ethical implications, followed by a narrower focus on bone research and the role rabbits are playing in the current scenario. 12 Five key bioethical points are considered when assessing the moral status of animal subjects in research: the presence of life, the ability to feel and perceive stimuli, the level of cognitive behavior, the degree of sociability, and the ability to proliferate. Animal models have taught us much about bone disorders and have been central to developing many treatments throughout history. 8, 17, 51 Rabbits are appealing models for bone research. Rabbits have potential as bone models but conclusive studies are still lacking. Animal models for implant biomaterial research in bone: a review The laboratory rabbit: an animal model of atherosclerosis research Osteoporosis-bone remodeling and animal models

cord-268149-narre5e7	title: Traditional uses of medicinal plants used by Indigenous communities for veterinary practices at Bajaur Agency, Pakistan Most widely used medicinal plants with maximum use reports (URs) were Visnaga daucoides Gaertn., Foeniculum vulgare Mill., Solanum virginianum L., Withania somnifera (L.) Dunal, Glycyrrhiza glabra L., and Curcuma longa L. It has been recognized that plants have the capacity to combat several types of diseases ethnoveterinary medicines, a term generally used for folk skills, beliefs, knowledge, practices, methods related to animals'' health, and cure of various ailments in the rural areas [1] . Indigenous people of the study area are rich in traditional knowledge on veterinary medicines, which may be due to their close observation on domestic animals being considered as an important part of traditional lifestyle. Medicinal plants with high URs strengthen the concept that such species are more significant to the local population and useful in sharing the traditional knowledge with one another in the area.

cord-268537-z7qga36v	In this special topic "Herbal small RNAs, novel precision medicine from Mother Nature", we present four original articles that study the entry of small RNAs derived from herbs used in traditional Chinese medicine into mammalian cells and their function within human and mouse cells, and one review paper focusing on current trends in herb genomics (Du et al., 2017; Huang et al., 2018; Zhang et al., 2018; Li et al., 2019; Xin et al., 2018) . discovered thousands of unique small RNA sequences derived from 10 traditional Chinese medicine herbs in human blood samples and mice lung tissues (Huang et al., 2018) . These data suggest that large amounts of plant-derived small RNAs can enter mammalian cells and tissues, and the cross-kingdom regulation by mi-croRNAs proposed by Zhang Chenyu group may be a common phenomenon (Zhang et al., 2012 ).

cord-268553-2o4k24og	PURPOSE: The etiology of community-acquired pneumonia (CAP) in hospital patients is often ambiguous due to the limited pathogen detection. METHODS: Specimens collected from the lower respiratory tract of 195 CAP patients, viruses were measured by the Single-plex real-time PCR assay and the conventional culture method was exploited for bacteria. It is difficult to distinguish the cause of CAP induced by flu, other respiratory viruses or bacteria based solely on clinical symptoms, and the conventional lab biomarkers of viral and/or bacterial infections do not differ in influenza-positive compared with influenza-negative patients [6] . In the hospital, viral testing among patients with respiratory symptoms is uncommon [14] , and the determination of the microbiological etiology is severely hampered in CAP by the difficulty of obtaining specimens from the infected area (esp. influenza, as co-pathogens, often seem to be part of a mixed infection (virus and bacterium) in adults with CAP [26] , representing the most common combination with respiratory viruses [2] .

cord-268843-zml9lbve	In the Canadian province of Manitoba, our group has periodically managed young infants of Northern Cree First Nations (Aboriginal) descent presenting with early-onset and life-threatening viral, bacterial, Mycobacterial, and fungal infections, clinically resembling severe combined immune deficiency (SCID). Herein we describe the clinical presentation, immunologic features, and HSCT outcomes for the largest cohort of infants with IKBKB immune deficiency resulting from complete loss of IKKβ expression published to date. Supporting a more profound immune deficiency are the other six reported patients with IKBKB mutations, who also presented with severe bacterial, fungal and viral infections as young infants. Like IKBKB immune deficiency, patients with hypermorphic NFKBIA mutations that result in reduced degradation of IκBα, present with multiple and severe bacterial, fungal and viral infections starting at an early age, typically before 3-months.

cord-268901-7cm6m1ol	title: Synthesis of distal and proximal fleximer base analogues and evaluation in the nucleocapsid protein of HIV-1 The aims of this project were to develop a series of fleximer base analogues that not only possess inherent flexibility that can remain active when faced with binding site mutations, but also target a non-canonical, highly conserved target: the nucleocapsid protein of HIV (NC). The organozinc was added dropwise to a mixture of 15 (451 mg, 1.0 mmol), Pd (PPh 3 ) 4 (115 mg, 0.1 mmol) and CuI (10 mg, 0.05 mmol) in 40 mL of anhydrous THF and allowed to stir at room temperature for 24 h. The organozinc was added dropwise to a mixture of 15 (451 mg, 1.0 mmol), Pd (PPh 3 ) 4 (115 mg, 0.1 mmol) and CuI (10 mg, 0.05 mmol) in 40 mL of anhydrous THF and allowed to stir at room temperature for 24 h.

cord-268907-cv0mkpzd	title: An Urgent Need for Global Preparedness against the Reemergence of "Forgotten" Infectious Diseases in Korea We should not make these infectious diseases as "never-ending stories," and comprehensive global preparedness for preventing outbreaks is needed urgently. According to the report from Korean Centers for Disease Control and Prevention (KCDC) in 2016, vaccination rates between 0 and 3-year-old children for national essential vaccination were over 90%; BCG 97.8%, HepB 97.3%, DTaP 96.2%, IPV 97.6%, MMR 97.8%, Var 97.5%, JE 92.7%. 2 The vaccination rate in NIP was reported in young ages but there is little nation-wide survey data of their appropriateness of immune formation to prevent infection after vaccination. It is necessary to gain a comprehensive understanding of the characteristics of pathogens, hygiene levels, immunity status and changes in each age group, environmental alterations, dietary nutrition, vaccine supply, treatment modalities, international relationship of diseases, so on.

cord-269093-x6taxwkx	However, very few review studies have undertaken grouping according to similarities and differences to predict the personality and behavior of individuals with the help of social networking sites such as Facebook, Twitter, and Instagram. However, most of the studies have been done on Twitter, as it is more popular and newer than Facebook and Instagram particularly from 2015 to 2017, and more research needs to be done on other social media spheres in order to analyze the trending behaviors of users. The result section includes a table which provides the research paper analysis according to the year along with pie chart figures, data collection, and behavior analysis methods and classifications based on different methods with line graphs [9] . The results section includes the percentage of research on the three social networking sites, research papers according to year with bar graph representations, data collection and behavior analysis methods and classification based on the different methods with line graph representations.

cord-269259-rpvl4vmu	Significant brain invasion of CD8 + cytotoxic T lymphocytes (CD8 + T effector cells), which are thought to play a significant role in viral clearance in the TMEV model in mice (Libbey and Fujinami, 2011; DePaula-Silva et al., 2017) , was observed both in infected controls and infected mice treated with PLX5622, without significant inter-group difference (Fig. 4B ). The brain invasion of Foxp3 + regulatory T cells (Tregs) was increased in both infected controls and PLX5622-treated infected mice to a similar extent without significant inter-group difference (Fig. 4D) . The present data show that these consequences of microglia depletion are virus specific, because we did not observe a decrease but a significant increase in infiltration of Foxp3 + Tregs in hippocampus and spinal cord and only a relatively small reduction in brain invasion of CD4 + T cells in TMEV-infected, PLX5622-treated mice compared to infected controls, although the invasion of CD4 + CD44 + T cells was markedly reduced by microglia depletion.

cord-269287-vbuepdm4	The molecular analysis based on genomic sequences evidenced a geographical pattern of distribution of the analysed strains, suggesting a potential common evolutionary origin with CPV of Asian origin. In Nigeria, only recently the molecular analyses based on the partial VP2 gene sequence of CPV strains described the circulating CPV variants (Apaa, Daly, & Tarlinton, 2016; Dogonyaro et al., 2013; Fagbohun & Omobowale, 2018) . Based on the RFLP analysis, 54 CPV-positive TA B L E 1 Identification code, origin, age, vaccination and clinical status, strain and sequence information of the dogs selected for molecular investigation Amino acid change I60V in NS1 also lies at the same residue in the NS2-encoding sequence. In this study, sequence analysis revealed aa changes previously described mainly in NS1/NS2 gene sequences of CPV-2a/2c strains of Asian origin. The molecular analysis based on long genome sequences evidenced the geographical origin of the analysed strains rather than the clustering based only on the CPV antigenic variant.

cord-269443-l8wj6dsy	In this study, we compared the immunomodulatory effects on the CD4 T cells of M1, M2a and M2c macrophages with the macrophages that directly and indirectly cultured with MSCs. We analyzed the changes in CD14, CD64, CD80, CD163 and CD200R expression to evaluate macrophage phenotypes, and the changes in CD4, IFN-g, IL-4, IL-17a and FoxP3 expression to evaluate T helper subsets using the FACS method. As a result, according to our data, the interactions between MSCs and macrophages may lead to differentiation of macrophage cells into an immunosuppressive phenotype, and these macrophages may suppress the T lymphocyte subgroups at least as effectively as MSCs. However, our data obtained from in vitro experiments should be supported by future in vivo studies. We observed that the CD14 expressions of the MEM-D and MEM-ID groups showed a similar pattern to the M2c group, suggesting that MSCs can differentiate macrophage cells into the M2c-like phenotype through direct or indirect effects.

cord-269702-20sldbte	Thus, this is the first time the DRC Government and partners are Response to the Ebola virus disease outbreak in the Democratic Republic of the Congo AAA screening. The global health community learned from the 2014-16 west Africa Ebola virus disease outbreak that a speedy response was vital to control the outbreak. 5 At the continental level, within 2 days of declaration of the outbreak the Africa Centres for Disease Control and Prevention (Africa CDC), which one of us (JNN) leads, had activated its Emergency Operation Center in Addis Ababa, Ethiopia; deployed an advance team of epidemiologists to Kinshasa to assist the Ministry of Heath; and briefed an extraordinary session of the Permanent Representative Committee of the 55 African Union member states. In future, the response to a potential tenth outbreak of Ebola virus disease in DRC must be led by the country''s national public health institute.

cord-269957-vd9ctqro	We have previously demonstrated that 3-hydroxyphthalic anhydride (3HP)-modified bovine beta-lactoglobulin (3HP-β-LG) is highly effective in inhibiting entry of pseudovirus (PsV) of highand low-risk human papillomavirus (HPV) into the target cell. In 2012, Jiang''s group reported that 3HP-modified bovine beta-lactoglobulin (3HPβ-LG) could also inhibit entry into the target cell of the pseudovirus (PsV) of non-enveloped virus, HPV (high-risk HPV16 and HPV18, and low-risk HPV6) (Lu et al., 2013) . As we proposed before, 3HP-β-LG inhibited HPV PsV entry into the target cell possibly through the binding of the negatively charged residues in 3HP-β-LG with the positively charged residues in a protein on the surface of the viral particle, thereby blocking the interaction between viral protein and receptor on the target cell (Lu et al., 2013) . These results suggested that 3HP-β-LG may bind to the positively charged sites in the C-terminal region of L1 protein on the HPV surface to block the interaction between the viral particle and cell receptor.

cord-270103-g9a72xf6	Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. Some nucleoside analog drugs targeting specific viral polymerases (acyclovir for herpesviruses, zidovudine for human immunodeficiency virus (HIV), and sofosbuvir for hepatitis C virus (HCV)) have been successful in clinical trials [2] [3] [4] [5] and are currently in use for the treatment of virus-infected patients. However, in recent years, the antiviral activity of gemcitabine has also been reported against a broad range of RNA viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), HCV, poliovirus (PV), influenza A virus (IAV), HIV, and enteroviruses (EV) [13] [14] [15] [16] [17] [18] . Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion

cord-270143-muxrxvyo	A high diversity of coronaand paramyxoviruses have been detected in different bat species at study sites worldwide, including Africa, however no biosurveillance studies from Rwanda have been reported. In this study, samples from bats collected from caves in Ruhengeri, Rwanda, were tested for the presence of coronaand paramyxoviral RNA using reverse transcription PCR assays. Although several surveillance studies have been implemented to detect potential zoonotic viruses in bats, including from countries in the Congo basin and East Africa, limited information is available for Rwanda. Confirmation of species identification of bats, in which viral RNA was detected, was performed by amplifying the cytochrome b (cyt b) or cytochrome oxidase one (COI) gene region and determining the DNA sequence. aegyptiacus-derived viral sequence (BatPV/Rou_aeg/UP438/RWA/2008) grouped within a Henipavirus-related clade and was near identical to a paramyxoviral sequence detected in the same host species previously reported from Kenya [36] .

cord-270286-76mrzaxi	We also compared 30-day mortality, emergency department (ED) length of stay, time-interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In our time series analysis study, we reported that the implementation of the bacteremia prediction rule successfully reduced the blood culture rate without any significant 30-day mortality and antibiotics regimen changes. Finally the target population only included patients with CAP and this would limit the broad application of the Table 4 Blood culture results with contamination and antibiotics regimen changes before and after implementation of bacteremia prediction model. In conclusion, the implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30day mortality and antibiotics regimen. In conclusion, the implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30day mortality and antibiotics regimen.

cord-270534-ebkwv4zo	title: Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model One of these candidates, MV vac2 -MERS-S(H) (Malczyk et al., 2015) , is based on the measles virus (MV) vaccine platform technology (Mühlebach, 2017) , and encodes the MERS-CoV spike protein (S) as an additional antigen in the backbone of recombinant MV vac2 (del Valle et al., 2007) resembling vaccine strain Moraten that is authorized and in use in the US since 1968. (G) Secretion of IFN-γ after antigen-specific re-stimulation of splenocytes harvested 32 days post prime immunization and after co-culture with JAWSII (left) or DC2.4 (middle) dendritic cells transgenic for MERS-N (black) or untransduced controls (NC, white). To assess the capacity of the different MV vac2 -MERS-S(H) vaccine preparations to induce MERS-CoV S-specific cellular immune responses, splenocytes of mice, which had already been tested for humoral responses ( Fig. 2A) , were isolated and analyzed 49 days after immunization for antigen(Ag)-dependent IFN-γ secretion using ELISpot assay.

cord-270703-c8mv2eve	We implemented a real-time report to distribute respiratory pathogen data for our 8-hospital system to anyone with an Internet connection and a web browser. We implemented a real-time report to distribute respiratory pathogen data for our 8-hospital system to anyone with an Internet connection and a web browser. To address these local needs in a major US metropolitan area, our clinical microbiology laboratory implemented an online dashboard to distribute respiratory pathogen data for our 8-hospital system to clinicians, epidemiologists, infection control practitioners, system leadership, and the public. Development of this report began in the Fall 2017, before the respiratory virus season, during which influenza reached an epidemic status across the United States that resulted in supply shortages, testing difficulties, and a widespread public health crisis [4, 5] . In summary, our microbiology laboratory implemented a near real-time Internet report to distribute respiratory pathogen data for our 8-hospital system to clinicians, hospital epidemiologists, infection control committees, system leadership, and the public.

cord-270911-z637eh2z	title: Differentiated human airway organoids to assess infectivity of emerging influenza virus airway organoid | proximal differentiation | influenza virus | infectivity I nfluenza A viruses (IAVs) can infect a diversity of avian and mammalian species, including humans, and have the remarkable capacity to evolve and adapt to new hosts (1) . Current in vitro models for studying influenza infection in the human respiratory tract involve shortterm cultures of human lung explants and primary airway epithelial cells. We chose to compare the infectivity of H7N2 with that of H7N9/Ah in the PD organoids as a proof of concept, to verify that the differentiated AOs can indeed simulate human airway epithelium in the context of influenza virus infection. Fig. 4 shows that viral loads in the cell lysate and medium of H7N9/ Ah-infected organoids increased gradually after inoculation; the viral titer increased more than 3 log 10 units within 24 h, indicating a robust viral replication.

cord-271106-srym2kh4	title: Effect of Immunomodulatory Supplements Based on Echinacea Angustifolia and Echinacea Purpurea on the Posttreatment Relapse Incidence of Genital Condylomatosis: A Prospective Randomized Study In conclusion, the presence of a latent infection causes condylomatosis relapse; in order to reduce the relapse risk an induction of a protective immune response seems to be essential to allow rapid viral clearance from genital areas surrounding lesion and treatment zones. EP and EA dry root extracts seem to be a valid adjuvant therapy in reducing relapse incidence of lesions in patients treated for genital condylomatosis. Therapy with HPVADL18 is effective in reducing relapse incidence of lesions in patients treated for genital condylomatosis. In conclusion, HPVADL185 seems to be a valid adjuvant therapy in reducing relapse incidence of lesions in patients treated for genital condylomatosis.

cord-271122-3fsl5589	Acute infection with non-cytopathic bovine viral diarrhea virus (BVDV) in mid-gestation increases abortion rates or causes the birth of persistently infected calves. In cultured bovine endometrial cells, experimental infection with ncp BVDV inhibited a variety of immune pathways normally activated in response to a challenge with bacterial lipopolysaccharide (LPS), including downregulation of many interferon-stimulated genes (ISGs), which are an important part of uterine defense mechanisms [40, 41] . Establishment of persistent infection with non-cytopathic bovine viral diarrhoea virus in cattle is associated with a failure to induce type I interferon A field investigation of the effects of bovine viral diarrhea virus infection around the time of insemination on the reproductive performance of cattle The effect of infection with bovine viral diarrhea virus on the fertility of Swiss dairy cattle Embryos produced from fertilization with bovine viral diarrhea virus (BVDV)-infected semen and the risk of disease transmission to embryo transfer (ET) recipients and offspring

cord-271752-h05sten7	The main second section contains the key facts (causative agents, diagnostic procedures and therapeutic measures) associated with the major infectious syndromes affecting returned travelers [gastrointestinal syndrome (acute or persistent diarrhea); febrile syndrome with no obvious source of infection; localized cutaneous lesions; and respiratory infections]. • General evaluation of the returned traveler with a potential infection -The need to evaluate the asymptomatic traveler -The main syndromes associated with imported infectious diseases -Evaluation of the traveler with severe infectious disease -Evaluation of the traveler with potentially transmissible diseases and isolation precautions • Main infectious syndromes in the returned traveler -Acute or persistent diarrhea -Fever of unknown origin -Localized cutaneous lesions -Respiratory infections -Eosinophilia -Neurological infections -Urinary tract infections • Special characteristics of the pregnant traveler • Special characteristics of the immunocompromised traveler General methodology of the document A systematic review of the bibliography was performed to evaluate all data concerning the causes, diagnostic methods and therapeutic options for infections imported by travelers.

cord-272143-6ej3eibd	We have evaluated these infections in children with humoral immunodeficiencies who required immunoglobulin replacement therapy, considering their relationship with symptoms, lung function, bacterial co‐infection, and outcomes. CONCLUSIONS: In our experience, viral respiratory tract infections can cause significant respiratory symptoms and impaired lung function, in children with HID, despite immunoglobulin replacement therapy. Children with severe T-cell immunodeficiencies present impaired clearance of respiratory viruses, and pulmonary complications of viral infections are leading causes of morbidity and mortality in this group of patients. 1 However, the role of respiratory viruses in children with other types of primary immunodeficiency (PID), mainly those with humoral immunodeficiencies (HID) or diseases of immune dysregulation, has hardly been studied. 2, 7 We report, to the best of our knowledge, the first study that analyses respiratory viruses in pediatric patients with predominantly antibody deficiency who required IRT, considering their relationship with clinical symptoms and pulmonary function, bacterial co-infection, treatment and outcomes.

cord-272378-umvi0veu	MicroRNAs are single-stranded non-coding RNAs that are typically 18-25 nucleotides (nts) in length and are best known for their role in the post-transcriptional regulation of gene expression. However, it is possible that the frequency of MREs in the entire transcriptome of a given cell contributes to the dynamic gene regulatory process by acting as a sponge for mature miRNAs, thus regulating their functional availability. Thus, gene expression regulation is a complex process involving the dynamic interactions between miRNA-mRNA-lncRNA-circRNA. This Special Issue of Genes, entitled "MicroRNA Regulation in Health and Disease" consists of a series of articles spanning the clinical realm from colorectal cancer to pulmonary fibrosis. Somatostatin (SST) analogues were used to control the proliferation and symptoms of neuroendocrine tumors (NETs) in an article by Døssing et al., entitled "Somatostatin Analogue Treatment Primarily Induce miRNA Expression Changes and Up-Regulates Growth Inhibitory miR-7 and miR-148a in Neuroendocrine Cells" [15] .

cord-272728-inndwa61	At PID 3 when vomiting had ceased, mean numbers of serotonin-positive EC cells per microscopic area (×250) were significantly (P < .05) increased in duodenum but reduced in ileum of the PEDV-inoculated pigs, compared with the corresponding negative controls, but they did not differ in mid-jejunum and colon (Table 1) . Histologic lesions and the distribution based on Table 1 Mean numbers ( ± SDM) of serotonin-positive enterochromaffin cells by immunohistochemistry in the crypt layers and entire or lower half of villi of duodenum, mid-jejunum, ileum, and colon per microscopic area, at ×250 magnification, of conventional 9-day-old nursing pigs inoculated with virulent US PEDV strain PC21A or mock at post-inoculation days (PIDs) 1, 3, and 5.

cord-272744-j4q7pcfa	Generally, epidemic spreading is considered to be a dynamic process in which the disease is transmitted from one individual to another via physical contact in peer-to-peer networks. Therefore, the effect of behavioral changes arises in three aspects [27] : (i) disease state of the individuals, e.g., vaccination [38] [39] [40] [41] [42] ; (ii) epidemic transmission and recovery rate [35, 43] ; (iii) topological structure of contact network, e.g., the adaptive process [44] [45] [46] [47] . Considering the two small peaks of information in Fig. 1 (b1) and (b2), we can also find the same relationship between the the two dynamic processes as that of two largest peaks, suggesting also the possible coupling effect of the awareness of epidemics and the infected cases of dengue. Inspired by the empirical results, we propose a network based nonlinear model to describe the interaction between epidemic spreading and information diffusion in this section.

cord-272973-kzaowysv	PEDV NA, IgG and IgA were detected in the serum of piglets born to immunized gilts, demonstrating the transfer of antibodies through colostrum and milk. In the present study, we investigated the immunogenicity of ORFV-PEDV-S recombinant virus in pregnant gilts and its ability to induce passive immunity and protection in piglets born to immunized animals. Animals in G1 seroconverted to PEDV, presenting detectable levels of IgG, IgA and NA a week after challenge of the piglets (day 7 post-birth; Fig. 1 ). Notably, passive transfer of antibodies from gilts to piglets was observed in both G2 and G3, as PEDV-specific IgG, IgA and NAs were detected in serum of piglets born to immunized gilts following ingestion of colostrum and milk. Additionally, passive transfer of antibodies from gilts to piglets was observed, as PEDV-specific IgG, IgA and NAs were detected in serum of piglets born to immunized gilts following ingestion of colostrum and milk.

cord-273019-hbpfz8rt	Studies on the herpes simplex virus-1 (HSV-1) infection on Vero, BHK-21 and PtK 2 cells reported transportation of viral tegument-capsid by dynein to the cytoplasmic side of NPC [22, 23] . In order to construct these compartments, viruses alter host''s fatty acid metabolism, induce rearrangement of the membrane constituents and also recruit cellular machinery to produce proteins essential for its replication [59, 60] . Upregulation of mitophagy and degradation of the mitochondrial antiviral signalling protein (MAVS) in order to attenuate the antiviral immune response in non-small cell lung cancer (NSCLC) cells was reported upon measles virus infection [83] . The expression of matrix protein (M) of human parainfluenza virus type 3 (HPIV3) in HEK293T and HeLa cells was reported to induce mitophagy resulting in the suppression of type1 interferon response [84] . Many viruses or viral proteins are reported to localize to peroxisomes and/or exploit their functions to facilitate their replication in the host cells [108] .

cord-273324-xhpv783y	For example, as POC technologies for HIV viral load and early infant diagnosis were being developed, there was tremendous emphasis on quality, given the complexity of the test and lessons learned from HIV RDTs. Malaria is estimated to be the cause of at least a million deaths a year worldwide, most of which are in sub-Saharan Africa. Although national TB programmes provide a robust architecture for the implementation of new technologies, challenges associated with the near-POC NAT assay remain as barriers -affordability (molecular assays are device-based and costly, even with subsidy), expertise (more technically demanding than lateral flow RDTs) and sustainability 46 , in addition to power and per-test time. Such tests can only be created by forming strong collaborative partnerships across many disciplinary boundaries, and we look toward a future when data connectivity linking cost-effective ASSURED diagnostics to laboratory systems will form the backbone of health care systems and provide real-time data for evidence-based disease control and prevention strategies, more efficient health systems and improved patient outcomes.

cord-273326-gmw8gl2r	In this line, and contrary to above mentioned report [73] , CQ, an FDA-approved anti-inflammatory 4-aminoquinoline and an autophagy inhibitor widely used as an anti-malaria drug that is administered to pregnant women at risk of exposure to Plasmodium parasites, was shown to have anti-ZIKV activity in different cell types (Vero cells, human brain microvascular endothelial cells (hBMECs), and human neural stem cells (NSCs)), affecting early stages of the viral life cycle, possibly by raising the endosomal pH and inhibiting the fusion of the envelope protein to the endosomal membrane [74, 75] . Similarly, by using a drug repurposing screening of over 6000 molecules, it was found that emricasan, a pan-caspase inhibitor that restrains ZIKV-induced increases in caspase-3 activity and is currently in phase 2 clinical trials in chronic hepatitis C virus (HCV)-infected patients, protected human cortical neural progenitor cells (NPC) in both monolayer and three-dimensional organoid cultures, showing neuroprotective activity without suppression of viral replication [82] .

cord-273973-3uxg97tu	Always consider previous microbiological data and local epidemiology with regards to empiric antibiotics CAP should include empiric coverage for atypicals along with community-associated organisms HAP and VAP should include broad gram-positive coverage, especially MRSA, along with broad gram-negative coverage, including ESBLs and CREs if warranted Influenza is the only virus with approved treatment, oseltamavir; therefore, this should be started empirically if there is a concern Antifungals should not be started empirically, even in lung transplant recipients; however, fungal infections should be worked up thoroughly pathogen, source control, and adjustment of immunosuppression is the hallmark of treatment. Always consider previous microbiological data along with local epidemiology with regards to empiric antibiotic decisions Asymptomatic bacteriuria should only be treated in renal transplant patients during the first month posttransplantation Antimicrobials should be tailored to the causative agent, with durations that generally range from 7 to 21 days depending on the clinical context Fluconazole is the treatment of choice for cystitis and pyelonephritis if Candida is the causative organism

cord-274080-884x48on	For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity.

cord-274293-kzmch37j	Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Therefore, we performed a comparative proteomic analysis to determine the effects of lycorine at the protein level in GD178-infected MDCK cells to understand its mode of action. The functional classification of DEPs was conducted by KEGG enrichment analysis, and each protein was assigned to at least one of the following pathways: human T-lymphotropic virus-1 infection pathway (path: ko05166), cell adhesion molecules (CAMs) (path: ko04514), epidermal growth factor receptor tyrosine kinase inhibitor resistance (path: ko01521), Janus kinase-STAT signaling pathway (path: ko04630), and pancreatic cancer (path: ko05212) (Fig. 3C) . As a result, AIV infection may induce Nup93 to complete the viral cycle, and the process of protein targeting into Nup93 after lycorine treatment may partly be explained by the blockage of vRNPs in the host cellular nucleus. Functional proteomic studies of lycorine-treated MDCK cells on highly pathogenic avian influenza H5N1 virus infection

cord-274506-fzcuu4ma	While PLpro cuts the first three cleavage sites of its polyprotein, 3CLpro is responsible for cleavage of the remaining eleven locations resulting in release of a total of 16 non-structural proteins (nsp) in both SARS-and MERS-CoVs. The homodimeric form of 3CLpro is active in the presence of substrates. In this study, we used a proteolytic method to probe MERS-CoV 3CLpro inhibitory compounds with a synthetic peptide labelled with the EDANS-DABCYL FRET (Fluorescence resonance energy transfer) pair (Liu et al., 2005) . The proteolytic assay using MERS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The four compounds showed the severely reduced fluorescent intensity and thus represented their MERS-CoV 3CLpro inhibitory activity. In this study, we assayed the inhibitory activity of various flavonoids against MERS-CoV 3CLpro. The analysis of the four compounds with their homologs using an induced-fit docking study provided an insight of flavonoid scaffolds required to bind with MERS-CoV 3CLpro.

cord-274773-3jhka8wl	title: Pathogenicity of porcine deltacoronavirus (PDCoV) strain NH and immunization of pregnant sows with an inactivated PDCoV vaccine protects 5‐day‐old neonatal piglets from virulent challenge High levels of IgG antibodies and NA were also detected in the serum of neonatal piglets born to immunized sows, which suggests that the antibodies were successfully transferred through the colostrum and milk. The protective efficacy of passive immunity elicited by the inactivated PDCoV vaccine against challenge with a highly pathogenic virulent strain in neonatal piglets born to immunized sows was investigated. These results suggest that within the first week, IgG antibodies in colostrum and milk of immunized sows could provide protection for piglets against TGEV virulent challenge. Moreover, high levels of IgG antibodies and NA responses were detected in serum, which protected the piglets against virulent PDCoV challenge. Pathogenicity of porcine deltacoronavirus (PDCoV) strain NH and immunization of pregnant sows with an inactivated PDCoV vaccine protects 5-day-old neonatal piglets from virulent challenge

cord-274900-s7ft1491	title: Prevalence and clinical impact of VIral Respiratory tract infections in patients hospitalized for Community-Acquired Pneumonia: the VIRCAP study Whilst epidemiology and clinical features of viral respiratory tract infections (VRTIs) were mainly explored in children and outpatients [7, 8] , a few data show increasing prevalence rates also in hospitalized patients, particularly in elderly and in presence of comorbidities such as asthma, chronic obstructive pulmonary disease or immunosuppression [9] [10] [11] . CAP was defined as acute lower respiratory tract infection characterized by the presence of two or more signs and symptoms (among fever, cough, dyspnoea, pleuritic pain, crackles or bronchial breath at pulmonary auscultation), associated with at least one among (a) radiological findings (opacity or infiltrate at radiography or computed tomography interpreted as pneumonia by the attending physician), (b) serum levels of inflammatory markers above normal values and (c) neutrophilic leucocytosis, in patients hospitalized no longer than 48 h [1] .

cord-275162-2239dk45	On follow-up, children with viral infection (Group I) had adverse outcome in form of greater worsening of Shwachman clinical scores, number of pulmonary exacerbations requiring antibiotic usage [4 (2.1%)] and [2.8 (1.7%)], need for intravenous antibiotics 30.4% vs. CONCLUSION: Acute viral infection in children with CF affected course of illness on follow-up, including frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12–18 months. This retrospective cohort study demonstrated that CF children who had suffered a viral respiratory infection had worse outcome in follow-up in the form of lower CF scores, higher use of intravenous antibiotics, higher rate of hospitalization and higher mortality as compared with matched controls who did not have viral respiratory infection. C O N C L U S I O N Following the viral respiratory infections in children with CF who were already nutritionally compromised, there were frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12-18 months.

cord-275166-qduf08kp	Adenovirus was the most prevalent virus (50%; n = 81), followed by influenza virus (45.68%, n = 74), rhinovirus (40.12%; n = 65), enterovirus (25.31%; n = 41), and respiratory syncytial virus (16.05%; n = 26), whereas Streptococcus pneumoniae (17%; n = 29), Moraxella catarrhalis (15.43%; n = 25), and Haemophilus influenzae (8.02%; n = 13) were the most commonly isolated bacteria. Respiratory tract infections (RTIs) such as acute otitis media, sinusitis, bronchitis, and community-acquired pneumonia are a leading cause of infectious disease-related morbidity, hospitalization, and mortality among children worldwide, particularly in low-income countries. 1 According to World Health Organization (WHO), the prevalence of hospitalized children under 5 years with acute respiratory infections (ARIs) is estimated to be 20% and 90% of those were due to pneumonia. 4, 5 However, primary infections with viral pathogens can predispose to secondary bacterial infections, and the most frequently isolated bacteria in ARIs include Streptococcus pneumonia and Haemophilus influenzae.

cord-275643-lbikoyo3	The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. CONCLUSION: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways. Following SeV challenge of HEK-293 cells, the expression of genes involved in the type I IFN and NF-κB signaling pathways was downregulated in the presence of HCoV-OC43 structural or accessory proteins (Fig. 4) . Similar to influenza A NS1 protein, HCoV-OC43 structural (M and N) and accessory (ns2a and ns5a) proteins were able to inhibit the transcriptional activity of antiviral response elements, ISRE, IFN-β promoter, and NF-κB-RE, and to downregulate the expression of several genes involved in the activation of an antiviral response.

cord-275719-ru33ubss	Despite the lack of established methods of biological sample preparation for transmission electron microscopy (TEM) at this time, Helmut Ruska was able to characterize the morphology of several viruses and he developed a rough viral classification based on the size and shape of the viral particles. 4 TEM was rapidly adopted for its first major use in clinical virology: the differential diagnosis of smallpox, caused by the variola virus Abbreviations: ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; EMEA, European Medicines Agency; FDA, Food and Drug Administration; FPERT, fluorescent product-enhanced reverse transcription; LCMV, lymphocytic choriomeningitis virus; PCR, polymerase chain reaction; SARS, severe acute respiratory syndrome; SFTS, severe fever with thrombocytopenia syndrome; TEM, transmission electron microscopy from the poxvirus family, and chickenpox, caused by the varicellazoster virus of the herpes family, based on investigations of fluid samples from the vesicles on the patients'' skin. Detection of retrovirus-like particles by transmission electron microscopy (TEM) with negative staining in bulk harvests of rodent cells used for the production of biological products.

cord-276364-zyw5aukk	Over the past few decades, a growing body of research has defined the critical role of this pathway in facilitating infection by numerous +RNA RNA viruses, including poliovirus (PV) [7, 8] , Coxsackievirus B3 (CVB3) [9, 10] , CVB4 [11] , Enterovirus 71 (EV71) [12] , Human rhinovirus (HRV) [13] , Foot-and-mouth disease virus (FMDV) [14] , encephalomyocarditis virus (EMCV) [15] , Dengue virus (DENV) [16, 17] , Zika virus (ZIKV) [18, 19] , Hepatitis C virus (HCV) [20] , Mouse hepatitic virus (MHV), Newcastle disease virus (NDV) [21] , Severe and acute respiratory syndrome coronavirus (SARS-CoV) [22] , Chikungunya virus (ChikV) [23] , and Japanese encephalitis virus (JEV) [24] . Delineating the process of viral assembly from replication is technically challenging, especially since both processes would very likely Induces formation of autophagosome-like double-membrane liposomes [112] Summary of Interactions between proteins from positive strand RNA viruses and host autophagy machinery.

cord-276437-5gkdotvt	EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Recent studies also showed that, during the epidemic, the EBOV isolates from early in the outbreak with amino acid substitutions in the GP protein possessed increased tropism for human cells, indicating human adaptation of Ebola virus during human-to-human transmission [19] [20] [21] . In a single patient, genome sequences obtained from samples during earlier stages of the acute infection phase possessed Ts at the 13 TNC positions, whereas Cs were found from samples collected during the recovery process. Our data indicate that short stretches of TNC substitutions are part of the convergent evolution during the infection process of EVD patients, shedding light on the dynamic intra-host genomic variation of EBOV during the 2013-2016 epidemic.

cord-276587-ynionj5r	Uncontrolled viral spread throughout the CNS parenchyma of mGFAPcre IFNAR fl/fl mice not only was associated with increased astrocyte infection but also affected neurons and microglia, despite overall elevated and sustained levels of mRNAs for IFN-␤ and IFN-␣ genes and ISGs. IFN-␥, a crucial mediator of MHV control in the CNS, was not impaired, despite reduced T cell CNS infiltration. To evaluate the kinetics of MHV A59 replication relative to Ifn␣/␤ and Ifn␥ mRNA levels in the CNS, brains from uninfected and infected wild-type (wt) C57BL/6 mice were harvested out to day 21 p.i. Virus replication was monitored by expression of viral RNA encoding the N protein (A59 N), which is present on genomic and all subgenomic RNAs (33) . Under the assumption that viral mRNA levels reflect similar replication in both glial populations, these data support microglia as superior initiators of IFN-␤ production relative to astrocytes following MHV A59 infection in vivo; these findings are consistent with results from primary neonatal cell cultures (18, 29) .

cord-276907-b855tj7x	Fortunately, at the current time, development of a norovirus vaccine that may offer efficacy in the context of low and middle income countries is proceeding with investment from the private sector, however an assessment of vaccine programmatic suitability and applicability to prequalification is needed, prior to Phase III trials to ensure the vaccine is appropriate for use in LMICs, assuming it is demonstrated to offer coverage over circulating genotypes within LMICs. Rotavirus is the leading cause of severe diarrhea among all children below 5 years of age worldwide, causing 20-40% of severe diarrheal hospitalisations, and is associated with significant mortality, with the latest mortality estimates at 215,000 deaths in 2013 [24] .

cord-277010-2iecsho0	title: Clinical characteristics and viral etiologies of outpatients with acute respiratory infections in Huzhou of China: a retrospective study Similarly, the positive rate of cases with a single virus infection was highest in the young children (65.5%) and lowest in adults of 18-60 years of age (38.5%). The proportion of respiratory viruses notably differed across different age groups; the virus positive rate was the highest in young children under 5 years but was lowest in adults (18~60 years) in this study. Therefore, all positive RhV and/or EV specimens and 10 FluA virus specimens with random selection were identified Table 2 Age distribution of viruses from outpatients with ARIs ARIs, acute respiratory infections by sequencing assay, respectively, and among them, four RhV positive and 3 EV positive specimens were not sequenced due to low viral load in the specimens. In summary, this study provides important epidemiologic data regarding the clinical characteristics, viral spectrum, age distribution and seasonality of viruses in outpatients with ARIs in Huzhou, China.

cord-277187-rcxjjxw3	Porcine enteric alphacoronavirus (PEAV) was first detected by our team via genomic analysis of samples collected from a diarrhea-outbreak swine herds routinely vaccinated with porcine epidemic diarrhea virus (PEDV) vaccine in a farm in Guangdong, China in February 2017 (Gong et al., 2017) . The clinical symptoms caused by PEAV in newborn piglets are similar to that by other porcine enteric pathogens such as PEDV and transmissible gastroenteritis virus (TGEV), which include vomiting, diarrhea, dehydration, and mortality rate as high as 90% (Gong et al., 2017; Zhou et al., 2018b) . To develop a live-attenuated vaccine for PEAV, we generated candidates via serial cell passage of the parental PEAV GDS04 strain and evaluated the pathogenicity of PEAV P15, P67 and P100 in 5-day-old newborn piglets. To generate an attenuated PEAV vaccine candidate, PEAV GDS04 was passaged regularly to a total of 100 passages in Vero cells and the selected passages including P15, P67 and P100 were characterized by sequencing and analyzing the complete genome (Fig. 1) .

cord-277265-p8pns7r9	However, utilizing the principles of ELISA and PCR, several serological and molecular technologies have been developed to achieve higher sensitivity, rapid, and point-of-care (POC) detection such as lateral flow assays, biosensors, loop-mediated isothermal amplification, recombinase polymerase amplification, and molecular platforms for field-level detection of animal pathogens. Since then, biotechnological applications have been making significant contributions in the development of novel powerful diagnostic assays for the efficient diagnosis and control of animal infectious diseases. Presently, molecular detection-based methods such as polymerase chain reaction (PCR) or its variants, and serological methods such as enzyme-linked immunosorbent assay (ELISA), are being used worldwide for the accurate diagnosis of many animal diseases. Although, yet not been adopted for animal disease diagnosis, but novel platforms such as smartphonebased diagnosis (which expands nucleic acid-based detection assays toward POCD) like RT-LAMP and fluorescent lateral flow immunoassay (already developed for Zika virus and Dengue virus) provide exciting opportunities for veterinary diagnostics in the near future (Rong et al., 2019) .

cord-277424-9aimvogs	In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. Further deiminated proteins identified in llama serum and serumderived EVs by F95 enrichment and LCeMS/MS analysis included key proteins of camelid innate and adaptive immunity, nuclear proteins, as well as proteins involved in metabolic function. Deimination protein candidates identified here in llama serum and EVs, which are involved in immune, nuclear and metabolic functions, are further discussed below, including where appropriate in a comparative context with relevant human diseases. As a structurally analogous immunoglobulin in shark, new antigen receptor (NAR) (Greenberg et al., 1995; Barelle et al., 2009; Flajnik and Dooley, 2009; De Silva et al., 2019) was recently also found to be deiminated (Criscitiello et al., 2019) , our current finding may provide novel insights into function of these immune proteins and be useful for refinement in therapeutic nanobody development.

cord-277455-r69j2tnw	title: Small-cell Lung Cancer Presenting as Fatal Pulmonary Hemorrhage We report a case of a 63-year-old man presenting with rapid-onset refractory severe thrombocytopenia, development of massive hemoptysis, and death from respiratory failure. SCLC differs from non-small-cell lung cancer in its rapid tumor doubling time, high growth fraction, early development of widespread metastasis, and better response to platinum doublets chemotherapy. Hematologic abnormalities such as anemia, leukopenia, and thrombocytopenia are reported to be occasionally accompanied by bone marrow metastasis or paraneoplastic phenomenon [5, 6] . Herein, we report an SCLC patient who presented with rapid-onset, refractory severe thrombocytopenia and development of fatal pulmonary hemorrhage. To our knowledge, this is the first report describing an SCLC patient presenting with fatal pulmonary hemorrhage due to refractory thrombocytopenia. Bone marrow involvement in small cell lung cancer: prognostic significance and correlation with hematological and biochemical parameters Is bone marrow examination in small-cell lung cancer really necessary?

cord-278747-3bhg9t6l	The administration of Ellagic acid, Kaempferol, and Quercetin as combined drug via the novel drug delivery systems will be a valuable therapeutic choice for the treatment of recent diseases attacking the public health including cancer, multidrug-resistant bacterial infections, diabetes mellitus, and chronic inflammatory systemic disease. They include the ligand-based virtual screening that is based on the searching for the compounds having the highest probability in pharmacological activity [10] and molecular docking that relies on the energy-based scoring function to identify ligand-target complex lowest energy [11] . Neostigmine (turquoise) as a control According to the results of pharmacodynamics, pharmacokinetics, safety, and drug-likeness predictions collectively, Ellagic acid, Kaempferol, and Quercetin were the best A. nilotica''s phytochemical constituents that contribute to the therapeutic activities; consequently, we recommend the use of Ellagic acid, Kaempferol, and Quercetin as a combined drug via the novel drug delivery systems for the treatment of recent diseases attacking the public health including cancer, multidrug-resistant bacterial infections, diabetes mellitus, and chronic inflammatory systemic diseases.

cord-279503-w4tn03w0	In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl(2)) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This assay could be highly reliable for MERS-CoV diagnosis as we have followed WHO updated recommendations for infectious disease laboratory testing, which targets the two regions on MERS-CoV considered for potential preclinical screening and high sensitivity 20 The developed assay platform was able to detect the target DNA through optical properties of the gold nanoparticles such as color changes with the naked eye and spectral shifts on UV− vis wavelength. We proposed a colorimetric assay using disulfide bonds formed by hybridizing with thiolated probes and a target; this method inhibited the aggregation of AuNPs by salt and limits the color change for diagnosis of MERS.

cord-279764-vcrbzzhu	We show that, as predicted, in co-infections, the blood-feeding nematode Haemonchus contortus suppresses aspects of the sheep immune response, thereby facilitating the establishment and/or survival of the nematode Trichostrongylus colubriformis; and that the T. We show that, as predicted, in co-infections, the blood-feeding nematode Haemonchus contortus suppresses aspects of the sheep immune response, thereby facilitating the establishment and/or survival of the nematode Trichostrongylus colubriformis; and that the T. This meta-analysis demonstrated that macroparasite-microparasite co-infection would normally result in increased numbers of microparasites owing to helminth-induced impairment of the anti-microparasite immune response, but that such effects would be moderated where resource competition was also present. colubriformis (comparing them to sheep mono-infected with each species, and with uninfected controls), by measuring nematode intensity and the host immune response. contortus infection, we analysed both the number of arrested L4-stage larvae in the host tissues along with adult worms (see the electronic supplementary material, S3 for mean and s.d. of raw counts through time).

cord-279784-o80x8nj7	title: Characterization and pathogenicity of Vero cell-attenuated porcine epidemic diarrhea virus CT strain METHODS: In this study, the highly virulent epidemic virus strain CT was serially passaged in Vero cells for up to 120 generations (P120). Previous studies conducted at Fig. 1 Biological characteristics of porcine epidemic diarrhea virus strains after 10, 64, or 120 passages. A newly isolated Chinese virulent genotype GIIb porcine epidemic diarrhea virus strain: biological characteristics, pathogenicity and immune protective effects as an inactivated vaccine candidate Oral efficacy of Vero cell attenuated porcine epidemic diarrhea virus DR13 strain Attenuation of an original US porcine epidemic diarrhea virus strain PC22A via serial cell culture passage Comparative genomic analysis of classical and variant virulent parental/attenuated strains of porcine epidemic diarrhea virus Preparation and characterization of an attenuated porcine epidemic diarrhea virus strain by serial passaging

cord-279794-hn5vmic0	Molecular clock analysis showed that divergence of the GII‐c subgroup spike gene occurred in April 2010, suggesting that the subgroup originated from recombination events before the PEDV re‐emergence outbreaks. Consistent with our previous research (Wang, Fang, & Xiao, 2016a) , the phylogenetic tree indicated that the complete PEDV genomes evolved into two separate genogroups, GI (classical) and GII (variant), as presented in Figure 1a . Genetic variation of nucleocapsid genes of porcine epidemic diarrhea virus field strains in China Detection and molecular diversity of spike gene of porcine epidemic diarrhea virus in China Genome sequencing and analysis of a novel recombinant porcine epidemic diarrhea virus strain from Henan, China Complete genome sequence of a recombinant porcine epidemic diarrhea virus strain Evolutionary and epidemiological analyses based on spike genes of porcine epidemic diarrhea virus circulating in Thailand

cord-280059-i72ayr02	However, during the last decade, swine producers in the United States (US) and other countries have voluntarily begun to share data for the control and elimination of specific infectious diseases, such as the porcine reproductive and respiratory syndrome virus (PRRSv). Here, we provide evidence of a national program for voluntary sharing of disease status data that has helped the implementation of surveillance activities that, ultimately, allowed the generation of critically important scientific information to better support disease control activities. Additional pages are shared with the project participants referring only to their own systems, and including incidence and prevalence graphs for both PRRSv and PEDv. Since its inception in 2011, the MSHMP has played a critical role in providing data that scientists translated into science-driven solutions to help the US swine industry mitigating PRRSv impact.

cord-280184-91d8i6ix	Surfaces with anti-adhesive properties, with incorporated antimicrobial substances or modified with biological active metals are some of the strategies recently proposed. This review intends to summarize the problems associated with contaminated surfaces and their importance on infection spreading, and to present some of the strategies developed to prevent this public health problem, namely some already being commercialized. This review considered English-language articles retrieved from PubMed database literature searches, bibliographies from published articles, and infection-control books and chapters, in a total of 205 references published between 2000 and 2018, considering the following criteria: the most recent studies performed on microbiological analysis on different surfaces reporting samplings performed on food contact surfaces, public spaces and hospital surfaces, where microorganisms occur naturally. All those antimicrobial substances are loaded to the surface either by immobilization or by incorporation on the bulk material; recent studies on the application of each type of loading strategy are summarized next.

cord-280374-yj0r4rwt	title: Hepatic sinusoidal-obstruction syndrome and busulfan-induced lung injury in a post-autologous stem cell transplant recipient He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. In our case other bacterial infections typically seen in an immunocompromised child are also unlikely in view of sterile cultures, complete absence of fever and normal Creactive protein (CRP).Though this clinical presentation can be caused by infection with PCJ, it is an uncommon infection. The non-infective etiologies causing respiratory symptoms in a post-transplant setting can be pulmonary GvHD, Idiopathic pneumonia syndrome (IPS), Bronchiolitis obliterans syndrome (BOS), Cryptogenic organising pneumonia (COP) and SOS. The final diagnosis is neuroblastoma stage IV, day + 68 post auto-SCT (Bu-Mel) with pneumonitis, ARDS and multi-organ failure; likely etiology being fungal pneumonia or CMV pneumonia and hepatitis secondary to ischemia with underlying SOS. Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation

cord-280442-jtvez46y	To evaluate this novel detection method, PCR assays (including conventional RT-PCR, qRT-PCR and nRT-PCR) and reverse-transcription LAMP (RT-LAMP) monitored by electrophoresis were also conducted and the specificity and sensitivity of the assays were compared with those of the mRT-LAMP-LFD assay. A total of 13 IBV strains, 7 NDV strains, and the PCR and LAMP target sequences of 6 NDV and 1 turkey coronavirus strains (TCoV) synthesized by Sangon Biotech (Shanghai, China) Co, as well as 6 other avian virus strains, were used for the determination of the specificities of RT-PCR and RT-LAMP assays. Statistical significance difference studies showed that the mean detection rates of mRT-LAMP-LFD were significantly higher than that of conventional RT-PCR assays when detecting IBV or NDV alone (P < 0.05). The mean IBV and NDV detection rates of different samples, detected by mRT-LAMP-LFD, were both 95%, and were significantly higher than those detected by conventional RT-PCR and qRT-PCR (P < 0.05, Figure 6B) .

cord-280941-ds6x0yym	The receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) was fused with the RNA-interaction domain (RID) and bacterioferritin, and expressed in Escherichia coli in a soluble form. The concentration of the ion Fe(2+), salt, and fusion linker also contributed to the assembly in vitro, and the stability of the NPs. The kinetic "pace-keeping" role of chaperna in the super molecular assembly of antigen monomers holds promise for the development and delivery of NPs and virus-like particles as recombinant vaccines and for serological detection of viral infections. Taken together, the results confirmed the immunologically relevant conformation of the MERS-CoV RBD displayed on the hybrid ferritin particles, and the crucial role of RNA in controlling the kinetic pathway for the assembly of viral antigen monomers into stable NPs. To evaluate the immunogenicity of ferritin-based NPs, BALB/c mice (n = 5) were immunized with RBD, RBD-FR, and RBD-[SSG]-FR NPs antigens.

cord-280957-cdd6ngf1	An MDCK-based cell line expressing human BST-2 was generated to study human-derived A/Puerto Rico/8/36 (H1N1; PR8) as well as two low pathogenic avian influenza viruses (subtypes H4N6 and H6N1). While this result reflects the ability of influenza A viruses in general to mediate host shut-off (Rivas et al., 2016) , it also suggests a difference in mRNA down-regulation that may be associated with decreased levels of BST-2. We report here that, contrary to our initial hypothesis that low pathogenic avian influenza viruses incapable of transmission to human hosts would be strongly restricted by human BST-2, H4N6 and H6N1 viruses grew to robust titers in MDCK cells constitutively expressing BST-2 and appeared completely resistant to its antiviral activity. We identified the PA segment as a species-specific determinant of sensitivity to BST-2, with those of low pathogenic avian influenza viruses exhibiting the ability to down-regulate human BST-2 in both transfection and infection contexts.

cord-281259-1wptx49j	title: Pneumocystis jirovecii pneumonia as an initial manifestation of hyper-IgM syndrome in an infant: A case report Human immunodeficiency virus infection, malignancy, solid organ or hematopoietic cell transplantation, and primary immune deficiency compose the risk factors for Pneumocystis pneumonia (PCP) in children, and PCP can be an initial clinical manifestation of primary immune deficiency. [9] [10] [11] [12] Especially, 43% of infants diagnosed with X-linked HIGM syndrome before 1 year of age initially presented with PCP. However, pediatricians should consider that PCP can be an initial clinical presentation of PID, [4] [5] [6] and therefore, PCP should be suspected in infants with severe interstitial pneumonia accompanying normal breathing sounds when common viral and bacterial pathogens are not identified, even though the infants may show no evidence of immune deficiency. In conclusion, we report an infant who presented with severe interstitial pneumonia and was diagnosed with PCP as the initial manifestation of underlying HIGM syndrome. Pneumocystis jiroveci pneumonia revealing de novo mutation causing X-linked hyper-IgM syndrome in an infant male.

cord-281403-yl7jdarm	Select results were: less than half of respondents (44%) stated that their office had been involved in handling a suspected or confirmed highly infectious remains case and responses indicated medical examiners. Survey questions included: demographic information (e.g. title, population served, state), personal protective equipment (PPE) worn in different infectious scenarios, procedures performed in different infectious scenarios, duration of training received, biosafety level (BSL) capabilities, and jurisdictional handling of highly infectious remains. Slightly more than half of respondents (56%; 61/108) stated their office staff had received training on donning and doffing PPE in suspected or confirmed cases of highly infectious remains; nearly one-third (32%) (18/56) reported the amount of cumulative training in hours per person, on average per year, was 1 h or less while 29% (16/56) spent between 1 and 2 h of training. 3. This survey, with respondents from nearly every U.S. state, revealed current levels of Medical Examiner/ Coroner training and education to address suspected or confirmed highly infectious remains.

cord-281437-cb3u1s7s	The science of epidemiology has described patterns of disease in human populations, investigated the causes of those diseases, evaluated attempts to control them 7 and has been the foundation for public health responses to epidemic infections for over 100 years. The vulnerability of populations to outbreaks of zoonotic diseases such as Ebola, Middle East respiratory syndrome (MERS) and Nipah has increased, the rise and spread of drug-resistant infections, marked shifts in the ecology of known vectors (for example, the expanding range of Aedes mosquitoes) and massive amplification of transmission through globally connected, high-density urban areas (particularly relevant to Ebola, dengue, influenza and severe acute respiratory syndrome-related coronavirus SARS-CoV). Preparing for epidemics, therefore, requires global health, economic and political systems to be integrated just as much as infectious disease epidemiology, translational research and development, and community engagement.

cord-281741-wzsrqc7p	To investigate the quantitative relationships between epidemic characteristics (e.g., cumulative incidence, onset week, and duration) and socioeconomic factors, including Urban ratio, PopDensity, PGDP, Income, Hospital, Hos-bed, Doctor, College, MidSchool, PriSchool, CollegeStu, MidSchoolStu, PriSchoolStu, and Pig, as well as the network structure parameters of the city vertices calculated above and to quantify the contribution of road transportation and the spatial distance to the spread of the influenza virus, we used spatial autoregressive models [33] performed in MATLAB. To investigate the quantitative relationships between epidemic characteristics (e.g., cumulative incidence, onset week, and duration) and socioeconomic factors, including Urban ratio, PopDensity, PGDP, Income, Hospital, Hos-bed, Doctor, College, MidSchool, PriSchool, CollegeStu, MidSchoolStu, PriSchoolStu, and Pig, as well as the network structure parameters of the city vertices calculated above and to quantify the contribution of road transportation and the spatial distance to the spread of the influenza virus, we used spatial autoregressive models [33] performed in MATLAB.

cord-281760-34wuttqw	Considering the fast development of IgY technology, this work aims to review its applications in human and animal health, in addition to increasing the potential use of these antibodies among researchers and consequently promoting the reduced use of non-invasive procedures on animals. extracted IgY from hens immunized with the recombinant protein FanC, from enterotoxigenic Escherichia coli (ETEC) and these antibodies bound specifically to FanC in ELISA, Western blot and Dot-blotting [59] , demanding, thus, more investigations to evaluate its viability as a potential immunotherapeutic compound. Anti-DENV2 IgY produced in goose was able to neutralize the virus in vitro and in vivo without binding to Fcγ receptors on myeloid cells and generating ADE (antibody dependent enhancement) in mice [57] . Hen egg yolk antibodies (IgY), production and use for passive immunization against bacterial enteric infections in chicken: a review Preventive effect of anti-VacA egg yolk immunoglobulin (IgY) on Helicobacter pylori-infected mice

cord-282062-h9smg0w9	We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal samples from cats with diarrhea using consensus primers matching those of circovirus and cyclovirus. Feline cyclovirus was identified by next-generation sequencing analysis in which the viral gene was detected in a pooled fecal sample collected from 4-5 healthy cats. In this study, we performed nested PCR using Circoviridae family consensus primers and detected novel CRESS DNA viruses in several cats with diarrhea symptoms. However, we concluded that FeSCV is a circular DNA virus based on the following: 1) No Giardia intestinalis was detected in the fecal test, and 2) the complete genome of FeSCV was amplified using the rolling-circle amplification and inverse PCR assays. We detected a novel CRESS DNA virus, FeSCV, in fecal samples from cats. Although it was detected using consensus primers of circovirus and cyclovirus, FeSCV was phylogenetically positioned in a clade different from that of these viruses.

cord-282204-j1slaefb	de; Oliveira, Renato A.S.; Durães-Carvalho, Ricardo; Lopes, Thaísa R.R.; Silva, Daisy E.A.; Gil, Laura H.V.G. title: A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control Laboratory tests for specific diagnosis of CHIKV infection are based on virus isolation, viral RNA detection and serology (Johnson et al., 2016) . Anti-CHIKV candidates that have been already tested in humans and/or animals include inactivated-, attenuated-, virus like particle-(VLP), DNA-and chimeric vaccines (Eckels et al., 1970; Levitt et al., 1986; Muthumani et al., 2008; Wang et al., 2008; Tiwari et al., 2009; Sharma et al., 2012 Akahata et al., 2010 Plante et al., 2011; Wang et al., 2011; Gorchakov et al., 2012; Brandler et al., 2013; Chang et al., 2014; García-Arriaza et al., 2014; Tretyakova et al., 2014; van den Doel et al., 2014; Erasmus et al., 2017) .

cord-282251-r4on3lpr	Within the span of 20 years, high-throughput technologies further advanced to include feats in protein engineering such as proteolysis-targeting chimeras (PROTACs) derived from the ubiquitination pathway (Zhou, Bogacki, McReynolds, & Howley, 2000) , streamlined phage display approaches that include Ub variants (UbV) to target protein-protein interactions in the UPS (Brown et al., 2016; Ernst et al., 2013; Ernst & Sidhu, 2013; Gabrielsen et al., 2017; Ordureau et al., 2018; Zhang et al., 2016; Zhang et al., 2017; Zhang et al., 2017; Zhang & Sidhu, 2018) and cell-based pharmacological HTS assays to enhance oncolytic virus cancer-cell-killing efficiency through viral sensitizer screens (Bourgeois-Daigneault et al., 2016; Diallo et al., 2010) (Fig. 2) .

cord-282322-ywwqnw74	Our previous study in chickens has shown that inhalation of a non-adjuvanted dry powder influenza vaccine formulation during normal breathing results in partial protection against lethal influenza challenge. Upon passive inhalation of dry influenza vaccine formulations in an optimized set-up, BLP and Advax/BLP adjuvanted formulations induced significantly higher systemic immune responses than the non-adjuvanted formulation. In a previous study, we have shown that pulmonary immunization by dispersion of a dry powder influenza vaccine directly at the syrinx of chickens (active administration) was able to completely protect these animals against lethal viral challenge [11] . For this, we initially tested whether (a) BLP or Advax could be co-formulated with influenza vaccine into dry powder formulations that are suitable for pulmonary immunization; (b) the adjuvants have the potential to boost systemic and mucosal immune responses to influenza; (c) passive administration with either non-adjuvanted or adjuvanted influenza formulations would protect chickens against a lethal HPAIV challenge.

cord-282342-5158g9kb	The following items were evaluated: ONFH incidence; patient demographic and background factors, including gender, age, BMI, and ABO and HLA incompatibility; duration of preoperative dialysis; type of renal graft (living/cadaveric donor); preoperative immunosuppressant use, including calcium inhibitors (cyclosporine A/tacrolimus) administered initially or at the time of hospital discharge; concomitant basiliximab administration; steroid administration at 2, 4, 6, and 8 weeks after RT, as prednisolone (PSL), methylprednisolone (MPSL), and total steroid doses (converted to PSL-equivalent doses); postoperative renal function, including delayed graft function (DGF), blood urea nitrogen (BUN) and creatinine (Cr) levels at 8 weeks after RT, and acute transplant rejection; and duration of hospitalization. Regardless of the increase in risk factors for RT such as older age and increased number of ABO/HLAincompatible transplants among patients, decreases in steroid administration and improvements in postoperative renal function have been observed in the Recent group.

cord-282466-r2sjv9ih	Porcine epidemic diarrhoea (PED) is a highly contagious and devastating enteric disease of pigs caused by porcine epidemic diarrhoea virus (PEDV), an enveloped, single-stranded RNA virus belonging to the Alphacoronavirus genus of the Coronaviridae family. Heavy economic losses in the pig-farming industry were sustained in the USA between 2013 and 2015 when PEDV spread very quickly and resulted in epidemics. The purpose of this review is a description of the current status of porcine epidemic diarrhoea in European pigs and the risk presented by the introduction of PEDV to Poland in comparison to the epidemics in the USA. Pathogenesis comparison between the United States porcine epidemic diarrhoea virus prototype and S-INDEL-variant strains in conventional neonatal piglets Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States Characterizing the rapid spread of porcine epidemic diarrhea virus (PEDV) through an animal food manufacturing facility

cord-282507-swxs5pr1	The second part of the review is related to phase I-III clinical trials of QS-21, mostly formulated in ASs, to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases, e.g. malaria, herpes zoster, tuberculosis, AIDS and therapeutic vaccines against cancer and Alzheimer''s disease. They can act on one or more of the following targets to increase response to Ags: (1) sustaining release at the injection site (depot effect), (2) transient secretion of cytokines and chemokines, (3) recruitement of various immune cells (neutrophils, monocytes, eosinophils, macrophages and Dendritic Cells (DCs) at the injection site leading to a local immune-competent environment, (4) expression by the recruited APCs of various Pathogen Recognition Receptors (PRRs) both on their surface (Toll-like receptors, TLRs, C-type lectin receptors, CLRs), and intracellularly (Nucleotide Oligomerization Domain (NOD)-like receptors (NLRs) and Retinoic Inducible Gene-1 (RIG)-like receptors (RLRs)), which are recognized and/or activated by adjuvants, (5) maturation and activation of recruited APCs which up-regulate the expression of Major Histocompatibility Complex (MHC)-I and/or MHC-II and activation of co-stimulatory signals CD40, CD80/86, (6) increased capacity of APCs for Ag processing and presentation by MHC, (7) migration of the mature APCs to the draining lymph nodes (dLNs) to interact with Ag-specific B or T lymphocytes (through receptor-ligand interactions, MHC-T cell receptor (MHC-TCR), CD40-CD40L, CD80/86-CD28) which are activated to produce potent Ab-secreting B cells and/or effector CD8 + T cell responses (Awate et al., 2013) .

cord-282533-w6kl74c8	METHODS: Nasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. CONCLUSIONS: FilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3429-6) contains supplementary material, which is available to authorized users. The aim of this study was to evaluate the application of FilmArray RP for the detection of respiratory organisms, and to provide information about the seasonality and prevalence of these organisms in pediatric patients with RTIs in a large children''s hospital in China.

cord-282547-ehr9aaix	7 Recently, two proposed hemostatic mechanisms have opened the door in the understanding of ARDS from molecular pathogenesis associated with endotheliopathy that promotes inflammation and coagulation disorder in sepsis and other critical illnesses [8] [9] [10] [11] ; one is "two-activation theory of the endothelium" in which endothelial pathogenesis activates inflammatory pathway and microthrombotic pathway and the other is a novel "two-path unifying theory" of hemostasis in which hemostasis initiates thrombogenesis and promotes microthrombogenesis, leading to vascular microthrombotic disease (VMTD). ARDS indicates acute respiratory distress syndrome; DIT, disseminated intravascular thrombosis; EA-VMTD, endotheliopathy-associated vascular microthrombotic disease; ECs, endothelial cells; HC, hepatic coagulopathy; MAHA/aMAHA, microangiopathic hemolytic anemia/atypical microangiopathic hemolytic anemia; MODS: multi-organ dysfunction syndrome; MOF, multi-organ failure; TMA, thrombotic microangiopathy; SIRS, systemic inflammatory response syndrome; TTP, thrombotic thrombocytopenic purpura; ULVWF, unusually large von Willebrand factor multimers activates ULVWF path, but TF path is not activated if subendothelial tissue (SET)/extravascular tissue (EVT) illustrated in Figure 2 is not compromised.

cord-283497-75qejr8o	In the present study, we aimed to (a) investigate the effect of Hz in the activation of human MO toward M2 phenotype, (b) examine the signaling pathways involved in the process, and (c) explore the potential of antimalarial drugschloroquine (CHQ) and artemisinin (ART)-in reversion of Hz-driven activation of MO. Wortmannin effectively reduced the level of IL-1β, IL-6, and IL-10 in supernatants of MO fed with Hz, signifying the role of PI3K-AKT pathway in inhibiting M2-like phenotype (Supporting Information Figure S8c ). Antimalarial drugs-artemisinin and chloroquine-partially reverse the Hz-induced M2-like phenotype activated p38 MAPK, PI3K-AKT, and NF-κB pathways and pharmacological inhibitors for these pathways dramatically down-regulated the expression and secretion of IL-10, thus, over-riding the induction triggered by Hz exposure. Hz released after schizont rupture is readily ingested by circulating MO in blood; activates PI3K-AKT, NF-κB, and p38 MAPK pathways resulting in increased expression of M2 markers; and drives the MO toward M2 (M2a and M2b)-like phenotype.

cord-283881-yhed5s98	To bridge this gap, we determined the polarity of infection, replication kinetics, and cell tropism of HPeV1 and HPeV3 in the well-differentiated human airway epithelial (HAE) model. Given that integrins and heparan sulfate have been reported to be expressed at the basolateral surface of polarized epithelium (Erlinger, 1995; Esclatine et al., 2001; Lütschg et al., 2011) , and that HPeV1 has been detected in respiratory patient samples more often than HPeV3 (Harvala et al., 2008) , we hypothesized that HPeV replication efficiency would differ depending on the inoculation site and the HPeV genotype. Furthermore, we speculated that differences in the airway epithelium host response may contribute to the distinct clinical outcomes and performed transcriptome analyses to compare the HAE gene expression profiles induced by HPeV1 and HPeV3 infection. To investigate HPeV replication in the human airway epithelium, we inoculated well-differentiated nasal HAE cultures, established from four individual donors, with HPeV1 and HPeV3 either from the apical or the basolateral surface (Figure 1 ).

cord-284060-6eonuc8x	Formulas are derived for the sensitivity indices for variations in model parameters of the disease-free reproduction number R d f and for the infected populations in the endemic equilibrium state. The modifications introduced in our analysis include: (1) the existence of an immunization program, (2) changes in the total population due to births and deaths, (3) the derivation of generalized reproduction numbers for disease-free states and endemic equilibrium states, (4) a sensitivity analysis of the effect of variations in parameter values on the reproduction numbers for disease-free states and on the infected populations of the endemic equilibrium state, and (5) a derivation of a simple formula for the critical immunization level required to prevent spread of the disease in an initially disease-free population. We have also derived formulas for sensitivity indices of the disease-free and basic reproduction numbers, and the endemic equilibrium populations for changes in the values of model parameters.

cord-284112-jobd5s4l	title: Possible Old Drugs for Repositioning in COVID-19 Treatment: Combating Cytokine Storms from Haloperidol to Anti-interleukin Agents Until recently, haloperidol was the most commonly used agent in the prevention or treatment of delirium that developed in intensive care units (9, 10) . (11) reported that haloperidol decreased mortality of patients on mechanical ventilation and hypothesized that this was due to its effect on lowering cytokine levels and, therefore, aided in preventing a cytokine storm associated with severe disease. However, we recommend that haloperidol be considered as an option to treat patients who develop agitation during the treatment process or agitation/delirium during the intensive care treatment process and continue to be administered routinely until proven otherwise. In addition to clinical studies (NCT04330638) related to the use of anti-IL agents such as anakinra, siltuximab, and tocilizumab in combating cytokine storms, studies are also being conducted with old drugs (NCT04304313) such as sildenafil, used indirectly outside of their indications.

cord-284484-oak1lfmi	title: Enablers of, and barriers to, optimal glove and mask use for routine care in the emergency department: an ethnographic study of Australian clinicians While it is difficult to plan in advance for such a rare event, staff who are competent in the principles and practice of routine infection prevention and control (IPC) and PPE use are more likely to be better protected from the start and more prepared to implement high-level precautions rapidly and safely. An important enabler of optimal glove and mask use was the professional responsibility some clinicians felt towards protecting patients from infections. ''It''s an autopilot thing, as soon as they go and get a new patient, straightaway grab a set of gloves and start doing what they need to do.'' (Registered Nurse [RN] 4) While glove use was almost automatic for the participants from the department, clinicians reported making a conscious decision to wear a mask. Enablers of, and barriers to, optimal glove and mask use for routine care in the emergency department: an ethnographic study of Australian clinicians

cord-284549-edliu3it	In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. In this study, we uncovered that HCV nonstructural NS2 protein possessed a potent in vitro VSR activity that suppressed the RNAi induced by short hairpin RNA (shRNA) and siRNA in mammalian cells. Our results showed that the reversal effect of EGFP silencing could be observed at 48 hpt (Fig. 2C) , indicating that the VSR activity was dependent on the expression level of HCV NS2 protein. To investigate whether HCV NS2 can inhibit this step, small RNAs harvested from HEK293T cells co-expressing EGFP-specific shRNA together with NS2 were subjected to Northern blotting with a DIG-labeled RNA probe targeting EGFP siRNA produced from shRNA by Dicer.

cord-284608-ba7wq52t	title: Alpha, Beta, gamma human PapillomaViruses (HPV) detection with a different sets of primers in oropharyngeal swabs, anal and cervical samples BACKGROUND: Recent studies have shown a 13-fold increase of oropharyngeal cancer in the presence of HPV, while α-HPV detection seems to be rare in oral cavity in comparison to anal or cervical district, many novel β and γ types have been isolated in this anatomical site suggesting a wide tropism range. METHODS: We analysed the presence of HPV DNA in oropharyngeal (n = 124), anal (n = 186), cervical specimens (n = 43) from HIV positive and negative patients using FAP59/64 and MY09/11 primers. In this study, we analyzed the presence of HPV DNA in oral, anal, and cervical specimens collected from HIV positive and HIV negative individuals, living in the same geographic area (regione Lazio) by using MY09/11 [20, 21] FAP59/64 primers [22] .

cord-284630-l9ghggu7	BACKGROUND: Canine parvovirus type 2 (CPV-2) was first identified in the late 1970s; it causes intestinal hemorrhage with severe bloody diarrhea in kennels and dog shelters worldwide. METHODS: Rectal swabs were collected from 260 dogs with suspected CPV-2 infection from northern, central, and southern Vietnam from November 2016 to February 2018. Canine parvovirus type 2 (CPV-2) is one of the most dangerous enteropathogens, causing fatal disease in dogs and puppies worldwide [1] . Thus, in the present study, we investigated the genotype prevalence and distribution of CPV-2 from naturally infected dogs in three regions of Vietnam using a SimpleP-robe® real-time polymerase chain reaction (PCR) assay. Interestingly, all vaccinated dogs were identified as having CPV-2c infection using the SimpleProbe® real-time PCR assay. Similar to other Asian countries [17] [18] [19] [20] [21] [22] , the CPV-2c variant appears to be the most prevalent genotype in the dog population in all regions of Vietnam.

cord-284760-i1lspg8i	In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats. Thus, this study aimed to investigate hepatoprotective activities of nicotinamide, vitamin B2, and vitamin C, separately or in combination, against thioacetamide-induced liver damage, hyperlipidemia and oxidative stress in rats. In the present data, TAA administration resulted in a significant reduction in the Table 3 Effect of Nicotinamide, Vitamin b2 and Vitamin C on hepatic MDA (nmol/mg), GSH (μmol/g tissue), catalase (U/g tissue), SOD (U/g tissue), NO (nmol/g,Hydroxyproline (Ug/g tissue) and plasma TNF-α (Pg/ml) plasma levels of a total protein that might be indicative of injury in the hepatocytes and excessive destruction of proteins including antioxidant enzymes and cellular reducing powers including SH-protein bond production or alterations in RNA sequences in the target tissues.

cord-284777-z7bd3a91	Three reverse transcription recombinase polymerase amplification assays with lateral flow dipsticks (RT-RPA-LFD) were developed for identification of the matrix and hemagglutinin (HA) genes to detect influenza A virus and distinguish subtypes H1 and H3. More recently, nucleic acid amplification tests (NAATs), such as reverse transcription polymerase chain reaction (RT-PCR) [12] [13] [14] [15] , real-time RT-PCR [16, 17] , and reverse transcription loop-mediated isothermal amplification (RT-LAMP) [18, 19] , have been used for rapid and sensitive diagnosis or subtyping of IAVs. Nevertheless, these methods require expensive equipment and/or skilled technicians, making them inappropriate for use in developing countries. In order to comprehensively evaluate the performance of RT-RPA-LFD, 28 positive throat swab specimens by matrix real-time RT-PCR were tested by RIDTs (Rapid influenza A virus antigen test kits, Guangzhou Wondfo Biotechnology Co., Ltd, China).

cord-285027-40ciukd7	We assessed symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population in Sierra Leone after over a year of outbreak response. ► To the best of our knowledge, the assessment was the first national survey that examined the impact of the devastating Ebola epidemic on populationlevel mental health using globally validated scales, and conducted after more than a year of ongoing transmission of Ebola in the country. 25 26 Known risk factors for anxiety, depression and PTSDincluding experience with ill individuals, perceptions of threat, high levels of mortality, food and resource insecurity, stigma and discrimination, and intolerance of uncertainty-may have been experienced by people in Sierra Leone during the Ebola epidemic. Table 4 presents multivariate analyses of the associations between Ebola experience and perceived Ebola threat and symptoms of anxiety and depression and PTSD, adjusting for gender, age, region and education levels.

cord-285121-3cjr1rol	In this review, we advocate the development of a novel approach, namely combination therapy by incorporating both phytochemicals and repositioned drugs to target CSCs. We cover select dietary phytochemicals (curcumin, resveratrol, EGCG, genistein) and repurposed drugs (metformin, niclosamide, thioridazine, chloroquine). For CSC targeting, we recommend four dietary phytochemicals (curcumin, resveratrol, EGCG, genistein) and four repurposed drugs (metformin, niclosamide, thioridazine, chloroquine). Furthermore, five (curcumin, resveratrol, EGCG, genistein, metformin) are listed by an international task force of 180 clinicians and scientists of "The Halifax Project", with dedicated objective to "explore the concept of a low-toxicity ''broad-spectrum'' therapeutic approach that could simultaneously target many key pathways and mechanisms" for cancer treatment [1] . EGCG works in combination with other phytochemicals and conventional drugs to enhance anti-cancer effects, targeting bulk cancer cells and CSCs [69] . We found that thioridazine and curcumin may act synergistically in inhibiting spheroids from ovarian cancer cells, with the combination more effective than either compound alone.

cord-285935-5rsk6g7l	Cyclic peptides (CP) that had been developed to abrogate interaction of p6Gag and TSG101 and inhibited viral release of HIV Virus like particles (VLPs) [76] were tested for their activity against HEV [77] . The compounds RBV and mycophenolic acid (MPA), both of which target enzymes involved in nucleotide synthesis, are either already used as treatment against HEV or have been reported for their potential to inhibit the virus. So far, the antiviral activity against HEV of only four drugs (Sofosbuvir, pegIFN-α, Ribavirin and silvestrol) was approved in experimental settings beyond in vitro cell culture systems. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus infection Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo

cord-286136-gm6w590s	Some studies show that essential oils'' and extracts'' antimicrobial activity can be further potentiated in combinations with antibiotics (beta-lactams, fluorochinolones, aminoglycosides, polymyxins), antivirals (acyclovir), and extracts of other plants (e.g. Annona senegalensis; Psidium guajava). camaldulensis plant extracts (PEx) and essential oils (EOs) and its constituents possess numerous other beneficial effects. Summarizing the available data on antimicrobial properties of Eucalyptus camaldulensis essential oil and extracts, it is obvious that this plant is a valuable source of phytotherapeutics. Chemical composition of 8 eucalyptus species'' essential oils and the evaluation of their antibacterial, antifungal and antiviral activities Antiviral -antimicrobial and schistosomicidal activities of Eucalyptus camaldulensis essential oils Chemical composition and in vitro evaluation of the antimicrobial and antioxidant activities of essential oils extracted from seven Eucalyptus species Chemical compositions and antimicrobial activity of leaves Eucalyptus camaldulensis essential oils from four syrian samples Evaluation of antimicrobial activity of Eucalyptus camaldulensis essential oil against the growth of drug-resistant bacteria

cord-286303-wo6356vq	In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We therefore selected RF with the 20-fold cross-validation scheme, having maximum mean balanced accuracy and MCC and minimum standard deviation on both measures, to perform the Fig. 2 The effect of top 20 motifs in the high (a) and low (b) mTLR9 activity group of ODNs in the dataset. Our RF model predicted 545 of these 6000 random ODNs to be of high activity and we selected the top 100 for chemical synthesis, and then experimental tested them for mTLR9 activity using the RAW-Blue reporter cell line that expresses mTLR. The test dataset used to evaluate the performance of a model was composed of 46 ODNs (23 each from the two groups of high and low mTLR9 activity).

cord-286337-qk90xb3a	While the effects of these alterations on risk of secondary bacterial pneumonia have not been studied, potential mechanisms by which these changes might modulate susceptibility to secondary bacterial infections include alterations in the nature and magnitude of the immune response in the host (microbiome on host effects) and facilitating growth of pathogens in the absence of normal commensals (inter-microbial effects). Given the effects of viruses on enhancing bacterial adherence to the epithelium (86) (87) (88) , it is perhaps not surprising that multiple studies of human subjects as well as in animal models have shown that viral infections are associated with increased colonization by potentially pathogenic bacteria (known as "pathobionts"). Another study of patients with 2009 pandemic H1N1 influenza infection revealed that the predominant phyla of the upper respiratory tract (nasal and nasopharyngeal samples) in patients harboring pandemic H1N1 were Actinobacteria, Firmicutes, and Proteobacteria although normal controls were not included; however, the authors suggested that flu is associated with an expansion of Proteobacteria (109) which is generally less abundant in healthy hosts.

cord-286607-5i406twr	Kawasaki syndrome (KS) is a necrotizing vasculitis of smalland medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. The microbiota, a microbial community of trillions of microorganisms and at least 1,000 different bacterial species, some eukaryotic fungi and viruses, and which covers every surface of the human body, plays a contributory role in many infections, immune-mediated disorders, rheumatologic diseases, and disorders of the nervous system.

cord-286719-1xjmlwqr	The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. These techniques represent the majority of molecular techniques applied in virus detection and include various types of target amplification techniques (e.g., PCR, loop-mediated isothermal amplification (LAMP), transcription-mediated amplification, and nucleic acid sequence-based amplification), signal amplification techniques (e.g., branched DNA and hybrid capture), and probe amplification techniques (e.g., ligase chain reaction and strand-displacement amplification). [70] developed an impedimetric electrochemical assay for the detection of AIV M gene sequences based on measuring changes in the impedimetric behavior of the electrode when the target DNA hybridizes with the capture DNA probes immobilized onto its surface and is subsequently labeled by AuNPs via streptavidin/ biotin interaction (Fig. 12C) .

cord-286794-adbxzgvs	title: Identification and complete genome characterization of human enterovirus 117 from a child with pneumonia in China In this study, human enterovirus C117 (EV-C117) was detected in a 3-month-old boy diagnosed with pneumonia in China. Here, we report the identification and complete genomic sequence of EV-117 in a child with pneumonia in China, which may provide more information for understanding EV-C117 infection. Using multiple primers (Table 1) , we determined the full-length viral genome sequence of the strain detected in patient CQ6747 (GenBank accession no. Conversely, all genome regions of CQ6747 showed less similarity to other EV-C strains (including EV-C104, EV-C105, EV-C109, and EV-C118) ( Table 2) . Complete genomic sequencing shows that polioviruses and members of human enterovirus species C are closely related in the noncapsid coding region Complete genome sequence of a novel human enterovirus C (HEV-C117) identified in a child with communityacquired pneumonia Respiratory infection with enterovirus genotype C117, China and Mongolia

cord-286843-8qh1pblc	Univariate and multivariate logistic regression showed that serum procalcitonin, APACHE II severity score and mixed viral-bacterial infection were associated with increased risk of hospital mortality. Postulated prohibitive factors against the routine performance of viral diagnostics tests in patients with severe CAP may include a lack of clear clinical guidelines, perceived low cost-effectiveness and the paucity of effective anti-viral therapies for respiratory viruses other than influenza. Our primary hypothesis was that respiratory viruses were important causative pathogens in severe CAP and was associated with increased mortality when present with bacterial pathogens in mixed viral-bacterial co-infections. performed a prospective observational study on physician practices in the use of respiratory virus diagnostics demonstrating that despite clinical guideline recommendations on testing of respiratory viruses during influenza season, less than half of patients admitted to the intensive care unit with pneumonia were tested for viral pathogens [14] .

cord-287131-svtdfeop	Screening of 533 bats for influenza A viruses showed subtype HL18NL11 in intestines of 2 great fruit-eating bats (Artibeus lituratus). Genomic characterizations revealed conservation of viral genes across different host species, countries, and sampling years, suggesting a conserved cellular receptor and wide-ranging occurrence of bat influenza A viruses. The segmented influenza A genome facilitates reassortment events in birds or intermediate hosts, such as swine and horses, leading to emergence of new variants potentially capable of causing zoonotic infections (2) . All critical amino acid residues associated with influenza A virus replication and entry (4,5) were conserved between the Brazil and the Peru HL18NL11 strains, including the HA monobasic cleavage site motif PIKETR/GLF (5) . Phylogenetic analyses confirmed the close genetic relationship between Peru and Brazil HL18NL11 variants across all 8 segments (Figure 2 ; Appendix Table 2 ), suggesting lack of reassortment events according to the available data.

cord-287853-cob7ur35	As illustrated in the following section and in Table 1 , mass spectrometry-based techniques have been used to perform the structural characterization, glycosylation profiling and antigen quantitation during the development of the HIV, influenza, Dengue, Ebola, Meningococcal, and other vaccines. The review also highlights that mass spectrometry-based methods such as glycan analysis has been used to analyze a specific envelope glycoproteins (Env) and has broad applicability to any other glycoprotein-based vaccines. 91 To improve on the conventional approaches for absolute quantitation of GP1 in Ebola virus-like particles (eVLPs), an isotope dilution full-scan liquid chromatography-high-resolution mass spectrometry method was developed using an UltiMate 3000 HPLC and an Development of a liquid chromatography high resolution mass spectrometry method for the quantitation of viral envelope glycoprotein in Ebola virus-like particle vaccine preparations Development and application of a reversed-phase high-performance liquid chromatographic method for quantitation and characterization of a Chikungunya virus-like particle vaccine

cord-287884-qxk1wfk8	Some of these technologies are Big Data Analytics, Internet of Things (IoT), Sensor networks (RFID, Location based Services), Artificial Intelligence (AI), Robotics, Blockchain, Mobile digital Platforms (Digital Streets, towns and villages), Clouds (Fog and Dew) computing, Social Networks and Business, Virtual reality. Accordingly, things (technologies, devices and tools) used together in internet based applications to generate data to provide assistance and services to the users from anywhere, at any time. IoT is providing some amazing applications in tandem with wearable devices, sensor networks, Fog computing, and other technologies to improve some the critical facets of our lives like healthcare management, service delivery, and business improvements. Some of the key devices and associated technologies to IoT include RFID Tags [25] , Internet, computers, cameras, RFID, Mobile Devices, coloured lights, RFIDs, Sensors, Sensor networks, Drones, Cloud, Fog and Dew. Blockchain is usually associated with Cryptocurrencies like Bitcoin (Currently, there are over one and a half thousand cryptocurrencies and the numbers are still rising).

cord-288093-012ipcdr	Moreover, high-throughput studies have identified additional non-coding RNAs that are likely processed by Dicer [9] as well as several pre-miRNA binding proteins that may regulate its cleavage activity [10] [11] [12] . The structure and activity of the purified Dicer were assessed by size-exclusion chromatography coupled to multi-angle light-scattering and refractive index (SEC-MALS/RI), negative stain transmission electron microscopy (TEM), binding assay and steady-state kinetics. Our kinetic analysis for Dicer cleavage of the pre-let-7a-1 substrate were performed under strict steady state conditions and reveals k cat and K M values that are much higher than previously reported. Moreover, SEC -MALS/RI analysis of a purified Dicer sample stored for 6 months at − 80°C in sucrose/DDM-containing buffer shows that the purified protein remains almost exclusively monomeric ( ≥ 94%), indicating that the protein is intact after long-term storage (Additional file 1: Figure S1 ).

cord-288332-y15g1yak	PURPOSE: Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. METHODS: Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Nasopharyngeal aspirates from all patients were obtained within 48 hours of admission for multiplex RT-PCR assay to detect the following 15 common respiratory viruses: influenza virus A and B (IFA, IFB), respiratory syncytial virus A and B (RSV A, RSV B), parainfluenza virus 1-4 (PIV 1, PIV 2, PIV 3, PIV 4), human coronavirus 229E and OC43 (hCV-229E, hCV-OC43), human rhinovirus (hRV), human enterovirus (hEV), adenovirus (AdV), human bocavirus (hBV), and human metapneumovirus (hMPV).

cord-288687-2dz8bu73	In this study, a total of 138 blood specimens collected from Bactrian camels from Zhangye City in Gansu Province and Yili and Aksu in Xinjiang Province, China, were examined for the presence of Borrelia spp. Phylogenetic tree of the 5S-23S rRNA gene sequences of Borrelia species obtained in the present study and those deposited in GenBank from different countries; accession numbers are shown after isolate names. Phylogenetic tree of the 5S-23S rRNA gene sequences of Borrelia species obtained in the present study and those deposited in GenBank from different countries; accession numbers are shown after isolate names. Phylogenetic tree of the flaB gene sequences of Borrelia species obtained in the present study and those deposited in GenBank from different countries; accession numbers are shown after isolate names. Phylogenetic tree of the OspA gene sequences of Borrelia species obtained in the present study and those deposited in GenBank from different countries; accession numbers are shown after isolate names.

cord-288879-rj03dsib	While the mechanisms for the function and toxicity of extended polyQ segments (or the nucleic regions that encode them) in eukaryotic proteins continue to be actively studied [16] , there has been little exploration of their occurrence and possible roles, even in neurovirulent viruses. At the start of this work, the ViPR database [29] , which allows rapid access to the published sequences of over 75,000 viral genomes or genome segments, was used to determine which RNA and DNA viruses contain polyQ repeats. As discussed below, the longest repeats were found in DNA virus proteins that function in enhancing transmissibility (cowpox ATI) or contribute to viral latency (herpes viruses). Under growth conditions allowing the virus to resume lytic growth, where the enzyme activity is required to ensure efficient replication, the region Fig. 2 Soluble polyQ segments (of cell or viral origin) may prevent beclin-1-induced autophagy, which depends on the DNA binding ability of the polyQ segment of wt-ataxin-3 (based on [2, 67] ).

cord-289026-v09m2fzw	Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Based on the results above, recombinant pAPN ectodomain was obtained as dimers, and PEDV S1 or S1t protein existed as monomers, which showed similar natures of mammalian APN [43] and other coronavirus S proteins [48] [49] [50] as previously reported. In the current study, three canonical assays were carried out to characterize the interaction between pAPN ectodomain and PEDV S1 or S1t protein since these functional target proteins were successfully prepared. Identification and comparison of receptor binding characteristics of the spike protein of two porcine epidemic diarrhea virus strains

cord-289096-wuegn0jg	Gao 1,3,4, * Infections with bat-origin coronaviruses have caused severe illness in humans by ''host jump''. The host range expansion of coronaviruses (CoVs) from wildlife to humans via genetic recombination and/or mutations on the receptor-binding domain in the spike (S) gene is well established and results in several diseases with high fatality rates, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [ [4] . Thus, pigs are regarded as mixing vessels for IAVs. However, pigs were not known to be susceptible to bat-origin coronaviruses until recently, when two independent groups reported the detection of novel swine enteric alphacoronaviruses (SeACoVs) distinct from known swine coronaviruses (with one group successfully isolating live virus). The isolation of SeACoV from ill piglets expands our knowledge of the host range of bat-origin coronaviruses, and potentially poses a threat to public health.

cord-289186-reyx10zo	The objective of this study was to compare the effect of non-GMO Saccharomyces cerevisiae fermentation products (SCFP) with that of a halofuginone treatment against Cryptosporidium parvum infection in pre-weaned calves on a commercial dairy farm. It was reported recently that 4-week feeding of neonatal Cryptosporidium-infected calves with Saccharomyces cerevisiae fermentation products resulted in significantly less fragmented and atrophied villi of the lower small intestines in comparison to untreated controls, suggesting a preventive effect of these products against the infection (Vázquez Flores et al., 2016) . Almost all study calves, regardless of the treatment group, shed Cryptosporidium oocysts (98.4%) and were positive for coproantigen (99.2%) at least once during their first 3 weeks of life (Table 1 ). It was, therefore, not surprising that the serum total protein concentration was not correlated with the intensity of Cryptosporidium infection (measured by AUC values of oocyst shedding or coproantigen scores) or the number of days with diarrhea in this study.

cord-289205-or60zzjs	Terms analysis indicated that emergency medicine, public health, disaster preparedness, natural disasters, medicine, and management were the research hotspots, whereas Hurricane Katrina, mechanical ventilation, occupational medicine, intensive care, and European journals represented the frontiers of disaster medicine research. Overall, our analysis revealed that disaster medicine studies are closely related to other medical fields and provides researchers and policy-makers in this area with new insight into the hotspots and dynamic directions. Therefore, in this study, a scientometric analysis was conducted on disaster medicine to estimate the productivity of specific journals, countries, institutions, authors, and research areas, and to identify research hotspots and trends in this field. Disaster Medicine and Public Health Preparedness also had the greatest number of total citations (n = 151), again followed by Academic Emergency Medicine (n = 134) and American Journal of Preventive Medicine (n = 127) ( Table 1 in the online data supplement).

cord-289321-ahl46ql9	Differential visualization of drug-resistant and -susceptible RNA genomes within cells revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are cis-dominant, ensuring their direct selection from complex environments. Our goal was to screen the HCV-encoded viral proteins that are current targets of antiviral compounds to determine the intracellular dominance relationships between drug-resistant and drug-susceptible genomes. To test whether susceptibility to NS5A inhibitors was dominant in the context of viral infections, we analyzed U, S, S + R and R cell populations by flow cytometry as previously performed for the NS3/4A inhibitor in Figure 3 . To test whether exogenously expressed drug-susceptible NS5A proteins could co-assemble with drug-resistant NS5A, we utilized the previously described HCV plasmid that expresses HA-tagged and GFP-tagged NS5A within the same polyprotein but does not support genome replication ( Figure 5A) . Failure of NS5A proteins to mix during infection is a likely explanation for the cis-dominance of drug resistance observed in cultured cells (Figure 4) .

cord-289413-mbrw85og	RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. This study reports the selection by phage display and characterization of 5 different human scFv antibodies binding to an active form of the Zaire EBOV VP35 [24, 25] . In a competitive assay, ELISA plates coated with VP35 or with the control antigen GO were blocked; they were then incubated with purified scFv-expressing phage both in the absence and in the presence of the competitor soluble non-phage-fused scFv at the maximum concentration of 500 μg/ml.

cord-289584-rbp7p8s9	So far, six coronaviruses have been identified from pigs, which include porcine epidemic diarrhoea virus (PEDV), porcine respiratory coronavirus (PRCV), SADS-CoV and transmissible gastroenteritis virus (TGEV) that all belong to the Alphacoronavirus genus, as well as one betacoronavirus, porcine hemagglutinating encephalomyelitis virus (PHEV) and one deltacoronavirus, porcine deltacoronavirus (PDCoV) (Lin, Saif, Marthaler, & Wang, 2016; Wesley, Woods, & Cheung, 1991; Woo et al., 2010) . Our results also indicated that both the complete genomes, N genes and S genes of all SADS-CoV strains shared the highest nucleotides identifies with those corresponding sequences of four bat coronavirus HKU2 strains. In this work, The phylogenetic trees of full length genomes and S genes of SADS-CoV sequences showed that the SADS-CoV branch clustered with these four HKU2 strains, which is same to previous results (Gong et al., 2017; Pan et al., 2017; Zhou et al., 2018) .

cord-289861-i6bfuvq1	title: CSF neopterin, a useful biomarker in children presenting with influenza associated encephalopathy? Severe neurological complications from seasonal influenza, including influenza-associated encephalopathy/encephalitis (IAE), cause considerable morbidity and mortality in healthy children, and those with pre-existing neurological disease. We identified children aged 0e14 years, with evidence of influenza and associated severe neurological disease including status epilepticus or moderate to severe encephalopathy, admitted to two paediatric hospitals which comprise the Sydney Children''s Hospital Network, the largest paediatric network in Australia. In this case series we observed two groups of children who presented with severe influenza related neurological disease. Further studies of IAE are required to evaluate whether significant elevations of CSF neopterin, particularly in combination with diffusion restriction and other MRI changes, could predict short and long-term outcome. Given the severity of influenza associated neurological complications, we recommend a "treat and test" approach to the use of oseltamivir in children presenting with acute encephalopathy/encephalitis during the influenza season.

cord-290253-hxxizipk	Susceptibility to infection is known to vary with temperature, due to within individual physiological changes in factors such as the host immune response, metabolic rate or behavioural adaptations [22] [23] [24] [25] . However, if the host phylogeny also explains much of the variation in thermal tolerance, then phylogenetic patterns in virus susceptibility could be due to differences between species'' natural thermal optima and the chosen assay temperatures. We infected 45 species of Drosophilidae with Drosophila C Virus (DCV; Dicistroviridae) at three different temperatures and measured how viral load changes with temperature. We also examine how proxies for thermal optima and cellular function (thermal tolerances and basal metabolic rate) relate to virus susceptibility across temperatures, as increasing temperatures may have broad effects on both host and parasite [43] [44] [45] . To investigate the effect of temperature on virus host shifts we quantified viral load in 12,827 flies over 396 biological replicates, from 45 species of Drosophilidae at three temperatures ( Fig 1) .

cord-290558-6ceqdzgc	Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. The aim of this study was to investigate the role of different respiratory viruses in the severity of outcomes among patients admitted to an adult tertiary teaching hospital in Perth, Western Australia. This study is one of the few to undertake a detailed comparison of admissions and clinical outcomes of the individual influenza virus types and subtypes and the non-influenza viruses in hospitalised adults. Previous research has shown that for patients infected with respiratory viruses other than influenza who are admitted to hospital, the outcomes can be just as severe as for those with influenza, with similar rates of ICU admission, ventilation and death [13] .

cord-290833-m0wodqr3	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.

cord-290861-5bxvenue	Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). After the most stable reference genes were identified, a selection of genes previously associated with nociception in rodent models, and of interest to the authors, were examined using qPCR in the same samples to allow us to start characterizing the neurobiological signature of pain associated with DJD in cats. After a set of stable reference genes were identified for each tissue type, 13 genes associated with pain in rodents were selected (based on current knowledge of genes involved in pain states (Foulkes and Wood, 2008) and their expression levels compared in the DRG from DJD-affected and healthy samples.

cord-291041-3mqs7mj1	Bioinformatics'' analysis revealed that saliva reflects the involvement of different pathways in PVE such as catalytic activity and binding, and indicates antimicrobial humoral response as a pathway with a major role in the development of the disease. Of the 90 differentially expressed proteins between survival and control groups, the proteins most down-regulated in the survival group were cathelicidin antimicrobial peptide (CAMP), rho-GDP dissociation inhibitor beta (ARHGDIB), apolipoprotein A-1 (APO-A1), neutrophil elastase (ELANE), matrix metalloproteinase-9 (MMP9), EF-hand domain containing protein D2 (EFHD2), CD177 antigen (CD177), plastin-2 (LCP1), retinol binding protein 4 (RBP4), and maltase-glucoamylase intestinal (MGAM). Overall changes in protein expression in saliva from dogs with parvovirosis obtained in this study by high-resolution quantitative proteomic analysis suggested alterations in coagulation and inflammation systems, which are closely related pathways since the activation of one mechanism may lead to the activation of the other [30] . The two most down-regulated proteins in the dogs with parvovirosis that survived, cathelicidin antimicrobial peptide (CAMP) and Rho-GDP dissociation inhibitor beta (ARHGDIB), have protective role against infections and are involved in the inflammatory response.

cord-291295-7og5umiq	Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitin-specific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. Conversely, ectopic CYPA overexpression in the EBV-positive cell lines resulted in an increase in the EBNA1 expression levels detected by WB and qRT-PCR (Figures 3D,E) . EBNA1 protein expression was restored in the C2089-shCYPA cells transfected with the wild-type CYPA expression plasmid ( Figure 4B ). As shown in Figure 4D , CYPA interference (shCYPA) reduced the EBNA1 binding to oriP DNA by approximately 50% compared to that of the control (shNC) in HEK293 cells (P < 0.05). (F) CsA and elevated CYPA on EBNA1-oriP-mediated transcription activity in the luciferase reporter assay in HEK293 cells.

cord-291704-z6e7pmk8	title: Development and characterization of a new cell line derived from European eel Anguilla anguilla kidney A new cell line derived from the kidney of European eel, Anguilla anguilla, has been established and characterized. As an amino acid-rich nutrient medium forming a CO 2 -free system, L-15 has been used for successful application on fish cell lines and made CO 2 incubators unnecessary, which in turn significantly improved the stability and convenience of cell culture (Leibovitz, 1963 (Leibovitz, , 1977 . In this study, the expression of CYP450 showed a significantly long-term upregulation after poly (I: C) induction, indicating the potential of EK cell line for toxicological and pharmacological analysis of aquatic pollutants. To define the responses of this cell line to immune stimulations, the changes of the expression of interferon regulatory factor-7 (irf7, GenBank accession no.

cord-291742-donflx7w	We joined the Johns Hopkins Armstrong Institute Comprehensive Unit-Based Safety Program for Mechanically Ventilated Patients and Ventilator-Associated Pneumonia (CUSP 4 MVP-VAP) project in October 2015 with the objective of improving the care delivery process and reducing the mortality of our mechanically ventilated patients. The implementation of each care process bundle element, along with the Confusion Assessment Method for the ICU (CAM-ICU) score and the maximum level of mobility for that day were recorded on a standard data collection form and entered into the Johns Hopkins Armstrong Institute database, which generated a compliance rate for our hospital. In our study the implementation of the multifaceted CUSP 4-MVP VAP approach resulted in an increase in SAT (51.5%-76.9%, P = .0008) and SBT (54.2%-72.2%, P = .02) compliance; an increase in the number of mechanically ventilated patients without sedation (36.1%-50.9%, P = .06); and a decrease in IVACs (4.2-3.5 per 1,000 MV days), PVAP (2.1-1.7 per 1,000 MV days), ICU mortality rates (45.3%-19.1%, P = .045), and VAE mortality rates (33.3%-8.3%, P < .37).

cord-291754-1zxztadu	In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. To compare the in vitro replication of the rescued virus rYN and its parental strain YN on CEK cells, 200 μl PBS containing 10 3.0 TCID 50 of rYN or YN virus were inoculated onto the CEK cells in 24-well plates, and 200 μl supernatants from three wells from each group were harvested at the time points of 6, 12, 24, 36, 48, and 60 hpi for a real-time PCR detection assay for IBV N gene as described above. Collectively, these results demonstrate the successful rescue of the pathogenic IBV strain YN from cloned cDNA by using electroporation of full-length IBV in vitro transcripts into N-protein expressing cells and subsequent virus amplification in the allantoic cavities of ECE.

cord-291860-dw1sfzqx	Herein, were studied the performance of an in-house mNGS protocol for routine diagnostics of viral respiratory infections with potential for automated pan-pathogen detection. Herein, were studied the performance of an in-house mNGS protocol for routine diagnostics of viral respiratory infections with potential for automated pan-pathogen detection. Clinical sensitivity was analyzed using the optimized procedure, which in short consisted of total nucleic acid extraction, including internal controls (1:100 dilution); the adapted New England Biolabs Next library preparation protocol, including fragmentation with zinc, for combined RNA and DNA detection (see Library Preparation); and sequencing of 10 million reads (Illumina NextSeq 500). The Centrifuge default settings, with NCBI''s nucleotide database and assignment of sequence reads to a maximum of five labels per sequence, resulted in various spurious classifications ( Figure 4) [eg, Lassa virus ( Figure 5 ), evidently highly unlikely to be present in patient samples from the Netherlands with respiratory complaints].

cord-292033-zkwiag7a	Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. CONCLUSIONS: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection. Furthermore, the ability of FPV and CPV to persist in the peripheral blood mononuclear cells (PBMC) of cats irrespective of the presence of neutralising antibodies [13] [14] [15] [16] [17] and the presence of parvoviral DNA in the bone marrow of healthy cats [18] , suggests that parvovirus may persist long term in the tissues of cats post-infection without causing clinical signs.

cord-292199-pl4d19w2	Modeling suggests that both STV inactivation and virus degradation have to be taken into account to achieve good agreement of simulations and experimental data for longer RTs. Together, the high DIP titers obtained, and the successful simulation of the experimental data showed that the combination of continuous bioreactors and mathematical models can enable studies regarding DIP dynamics over extended time periods and allow large scale manufacturing of DIP-based antivirals. Modeling suggests that both STV inactivation and virus degradation have to be taken into account to achieve good agreement of simulations and experimental data for longer RTs. Together, the high DIP titers obtained, and the successful simulation of the experimental data showed that the combination of continuous bioreactors and mathematical models can enable studies regarding DIP dynamics over extended time periods and allow large scale manufacturing of DIP-based antivirals.

cord-292623-mxdlii77	So, the major objective of the current study is to examine the researches in which fuzzy logic techniques have been applied in infectious diseases so to determining its trends and methods, through the processes of conducting a Systematic Literature Review (SLR). In this methodical review, the studies related to the employment of the fuzzy logic techniques in an infectious disease were assessed, and depending on the acquired outcomes, we can notice an interest amongst the researchers regarding this specific field of research. 40 studies were scrutinized and the main conclusions can be briefed as follows: (1) the key application field of the fuzzy logic in an infectious disease was related to dengue fever, hepatitis and tuberculosis, (2) amongst the fuzzy logic techniques fuzzy inference system, rule-based fuzzy logic, ANFIS and fuzzy cognitive map are commonly used in many studies, and (3) the major performance evaluation indicators such as the sensitivity, specificity, and the accuracy the ROC curve is employed.

cord-292830-gcfx1095	Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. Here, we hypothesised that some of the identified safe-in-human BSAs could possess novel antiviral activities and, therefore, could be used for treatment of many different viral infections. Fig. 1 shows BSAs and other approved antiviral drugs linked to viral and host targets through viruses they inhibit. Thus, we tested several known BSA agents against (−)ssRNA, (+) ssRNA, ssRNA-RT and dsDNA viruses and identified novel activities for dalbavancin against EV1, ezetimibe against ZIKV and HIV-1, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against RVFV. We identified novel antiviral activities for dalbavancin (against EV1), ezetimibe (against HIV-1 and ZIKV), azacitidine, cyclosporine, minocycline, oritavancin and ritonavir (against RVFV) (Fig. 4) .

cord-293525-c7nwygl1	An EriCoV-specific BRYT-Green(®) real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Characterisation of these Erinaceus coronavirus (EriCoV) nucleotide sequences revealed high nucleotide identity to MERS-CoV [3] , the cause of an acute respiratory syndrome in humans with high case fatality rates [5, 6] . Many animal species seem to have the capacity for coronavirus infection in the absence of apparent disease, including bats [15] , aquatic birds [16] and rabbits when inoculated with MERS-CoV [17] . Whole genome sequencing was performed on RNA extracted from one faecal sample collected in 2014 (R618/14) which was identified as EriCoV-positive by real-time RT-PCR. The highest proportion of EriCoV-positive hedgehog samples were submitted from the South of England (34/217, 16%); however, BLR showed no significant association (P = 0.678) between EriCoV infection status and wider region when other factors including age and year were included.

cord-293562-69nnyq8p	We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R 0 < 1. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R 0 < 1. Since the only way to control the disease is to isolate patients who have been infected with the Zika virus, we included a new population compartment consisting of hospitalized individuals.

cord-293583-qec57cid	The FilmArray Respiratory Panel (RP) was first introduced as a syndromic multiplex molecular test in 2011 for the detection of 15 viruses; additional viral analytes and bacteria were made available with a software update in 2012 after FDA clearance for these new indications. To this end, BioFire Diagnostics has updated the FilmArray RP product again by adding new assays to broaden the test''s detection capabilities (particularly for adenoviruses), modifying a subset of assays to reflect newly available genetic sequences of currently included analytes, improving chemistry to enhance sensitivity overall, and for the inclusion of new analytes. MERS-CoV was not circulating in the United States during the time of the study; therefore, all specimens were assumed to be negative, and no comparator testing was performed for this analyte. Additional discrepant analysis for these specimens included retesting with the FilmArray RP2, a combination of PCR assays as described above, and any available NCH LDT results for adenovirus.

cord-293867-c4wnr5xe	Besides the wide biological activity spectrum of imidazo[2,1-b] thiazole derivatives, also the compounds bearing hydrazide, acyl-hydrazone and spirothiazolidinone moiety, have been reported in the literature with their various effects such as antibacterial [21] , antifungal [22] , antitubercular [23] , antiviral [24] , anticonvulsant [25] and antidepressant [26] . In this study, we further explored the scaffold containing the imidazo [2,1-b] thiazole ring as the aromatic moiety, that is linked by an amide to a spirothiazolidinone ring system as the aliphatic cyclic moiety and from this point forward, novel derivatives were synthesized (Table 1) , and broadly evaluated for their antiviral and antimycobacterial activity (Fig. 2) . General procedure for the synthesis of 6-(4-bromophenyl)-N 2 -(substituted/non-substituted cycloalkylidene)imidazo[2,1-b]thiazole-3-acetohydrazides (4a-d) 0,005 mol of 3 was boiled in a water bath under reflux with 30 mL of ethanol until a clear solution was obtained.

cord-294021-x8avmtef	Subsequently, in early 2014, PDCoV was reported from the United States of America (USA) and Canada, and it caused heavy economic losses to the swine industry due to the presentation of a clinical enteric disease Song et al., 2015; Wang et al., 2014) . The authors note that PDCoV infections are common in pigs and that coinfections are frequent, especially with the porcine epidemic diarrhoea virus and rotavirus C (Hu et al., 2015; Marthaler, Raymond, et al., 2014; Song et al., 2015) . The most common coinfection was PDCoV/PEDV, found in 54.1% of the total deltacoronavirus-positive cases (46/85), a result that coincides with that reported by other authors (Song et al., 2015; Zhang, 2016 Figure 1 ). Newly emerged porcine deltacoronavirus associated with diarrhoea in swine in China: Identification, prevalence and full-length genome sequence analysis First report and phylogenetic analysis of porcine deltacoronavirus in Mexico

cord-294264-itz43cf6	authors: Ni, Qingyong; Wang, Yu; Weldon, Ariana; Xie, Meng; Xu, Huailiang; Yao, Yongfang; Zhang, Mingwang; Li, Ying; Li, Yan; Zeng, Bo; Nekaris, K.A.I. title: Conservation implications of primate trade in China over 18 years based on web news reports of confiscations For certain native primate species in China, few individuals were traded internationally based on the CITES Trade Database, whilst rescuing or confiscating news reports revealed that they were frequently traded in domestic areas. In spite of potential bias in search results caused by search engine algorithms and manual filtering, and lack of the firsthand data from authorities, zoos or wildlife rescue centres, we expect that this study could facilitate the initial steps to raise public awareness on primate trade in China, especially for slow lorises.

cord-294312-ju6vuywm	While in fact, today''s treatment regimen is typically only four vaccinations (five for immunocompromised individuals) in the arm, plus a dose of humane rabies immune globulin (HRIG). A viral disease of the central nervous system, rabies transmits between animals, including humans, when saliva containing the virus enters an opening in the skin. Usually, the rabies virus enters through the bite of a rabid animal, but transmission can also occur when infected saliva enters through mucous membranes or a break in the skin. According to the Centers for Disease Control and Prevention (CDC), the first clinical signs and symptoms of rabies may be very similar to those of the flu including general weakness or discomfort, fever, or headache. For the rabies virus to get to the salivary glands, it has to travel first from the site of entry (usually a bite wound) through the animal''s nervous system, then to the brain.

cord-295171-vx4cypf7	Subsequently, the antiviral efficacy of mizoribine was further evaluated at various intervals post-FMDV infection, we found that the viral 2B mRNA and protein expressions were continuously inhibited at different time points (0, 2, 4, and 8 h) after treatment with 75 µM mizoribine; however, no significant differences were observed between 16 h post-infection (hpi) and the control group ( Figure 4 ). Subsequently, the antiviral efficacy of mizoribine was further evaluated at various intervals post-FMDV infection, we found that the viral 2B mRNA and protein expressions were continuously inhibited at different time points (0, 2, 4, and 8 h) after treatment with 75 µM mizoribine; however, no significant differences were observed between 16 h post-infection (hpi) and the control group ( Figure 4 ).

cord-295455-km0qcmlh	The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Originally described as ADP-ribose-1 00 -phosphatases, both cellular and viral macrodomains enzymatically remove mono-and poly-ADP-ribose from proteins, supporting the notion that protein ADP-ribosylation is a component of the antiviral response. It was unclear how these mutations affected this protein, as neither mutant affected PAR binding and it was unknown whether alphaviruses'' macrodomains had de-ADP-ribosylating activity. Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites The conserved macrodomains of the nonstructural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosylhydrolases

cord-295491-zlah6u5s	The aim of this study was to test two commercially available reaction mixtures in a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect feline Coronavirus (FCoV) in body cavity effusions of cats with and without FIP, in order to minimize the time from sampling to obtaining results. The aim of this study was to test specificity and sensitivity of two commercially available reaction mixtures in a reverse transcription LAMP (RT-LAMP) to detect FCoV in body cavity effusions of cats with and without FIP, and to minimize the time from sampling to obtaining results. The FIP group (n = 34) included cats with a definitive diagnosis of FIP by one or more methods: All effusions of cats with FIP tested positive for FCoV by RT-PCR by a commercial laboratory, and in 26/34 samples putative disease-causing mutations could be detected.

cord-295575-zgta5ah8	The purpose of this literature review was to specifically examine asthma outcomes related to environmental exposures to microbial products, pertaining to endotoxin from bacteria-(1,3)-β-D-glucan and ergosterol from fungus, and common viruses associated with worsening asthma morbidity (rhinovirus, respiratory syncytial virus (RSV), enterovirus, and the influenza virus) during infancy, and to assess the risk of asthma development later in childhood [15] [16] [17] [18] (see Table 1 ). conducted a prospective longitudinal study examining whether early exposure to microbial products in dust was associated with allergy and asthma later in childhood for children in suburban areas using the following three birth cohort studies for children born between 1996 and 1999: [24••] , dust samples were collected from children''s mattresses, bedroom floors, and living room floors; and showed no association between endotoxin nor the fungal membrane lipid ergosterol in the development of asthma with exposure from birth to 7 years of age.

cord-295640-mhfu0e9r	Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. Previously, we expressed a fusion protein of NP and M2e (NM2e) in Escherichia coli and showed that immunization with NM2e formulated with aluminum hydroxide gel protected mice from a lethal challenge with heterologous influenza virus . BALB/c mice were immunized with the recombinant viruses to measure NP-and M2e-specific humoral and cellular immune responses as well as protective effect against lethal challenge with a heterologous influenza virus. Mice immunized with the recombinant vaccinia virus RVJ-NPM2e and RVJ-M2eNP showed strong antibody responses against NP, with lower titers of antibodies against M2e (Fig. 3A) . The recombinant vaccinia virus expressing 4M2e and full-length NP fusion antigen induced strong cross-protection (92%) against a lethal heterosubtypic PR8 challenge at 20 MLD 50 and thus regarded as the optimal one among the four constructs.

cord-295661-v3q1spmm	intracellularis antigen is detectable in mouse enteroids, indicating susceptibility to infection, mouse enteroids fail to replicate the cellular proliferation and gene expression changes observed in proliferative enteropathy. Wnt3a protein, which regulates the signaling pathways related to the cellular proliferation in the intestinal crypt compartment [33] , was removed from the enteroid culture media at least 3 days before infection to enable cells to better differentiate. intracellularis infection induces changes in the proliferation and differentiation of enteroid epithelial cells, as observed in the swine intestine, we evaluated expression of Ki-67, Sox9 and Muc2 in enteroids harvested at 1, 3 and 7 dpi relative to expression in enteroids at 0 dpi. intracellularis antigen stained by immunohistochemistry is observed as small bacilli in the cytoplasm of cell cultures [5, 47, 48] and in the apical cytoplasm of intestinal epithelial cells of naturally and experimentally-infected pigs.

cord-295718-nt2n9p5v	title: Bronchoalveolar lavage to evaluate new pulmonary infiltrates in allogeneic hematopoietic stem cell transplant recipients: impact on antimicrobial optimization Bronchoscopy with targeted bronchoalveolar lavage (BAL) is often used in AHSCT patients with suspected lower respiratory tract infection (LRTI) to help guide management. Bronchoscopy with bronchoalveolar lavage (BAL) is an important diagnostic tool to evaluate AHSCT recipients with new pulmonary infiltrates or without clinical response to empiric therapy [1, 2] . This study aims to determine how Aspergillus galactomannan antigen (AGA) and multiplex PCR added to traditional BAL testing affects antimicrobial treatment in AHSCT recipients with new pulmonary infiltrates. BAL was positive for infectious etiologies in 63%, mostly with elevated AGA (17/54), followed by multiplex PCR (13/54), positive bacterial (8/54), fungal (4/54) and AFB culture (1/54). BAL remained necessary to detect coinfections, as 9/13 patients with a positive multiplex PCR also had a positive bacterial culture (n¼2) or elevated AGA (n¼7) ( Table I) .

cord-295878-pd9elo4l	Based on the location-based network, we simulate influenza transmission dynamics and evaluate the efficacy of different vaccination strategies according to the identified geo-social interaction patterns. Second, the design of control strategies based on individualbased networks (e.g., vaccinate the individual with a large number of contacts) is challenging because it is infeasible to keep track of all social contacts of infections (Cohen, Havlin, & Ben-Avraham 2003; Gómez-Gardenes, Echenique, & Moreno 2006; Holme 2004 ), but the information to estimate population flows among locations based on intra-and inter-community travelers is widely available in the existing census data and travel survey reports (Mao & Bian 2010) . Thus, location-based human interaction network models are required to easily represent explicitly spatial dynamics of the disease transmission and design control strategies to target certain critical locations first rather than prioritizing individuals.

cord-296032-e58jd3ac	Methods A panel of 19 serological tests was run on patient serum samples after treatment with Triton X-100 1%, 0.1%, and 0.1% + heat inactivation at 60°C for 1 h. Inactivation tests were indeed performed on EBOV and herpes simplex virus type 1 (HSV-1) in 0.98%, 9.8%, or 98% serum, and viral inactivation by Triton X-100 only succeeded in medium with less than 10% serum, suggesting that some factors in serum interfere with detergent effects. Patient serum samples received for routine serological testing were chemically inactivated with Triton X-100 at a final concentration of 0.1% or 1% and compared with PBS-treated controls by several ELISA-based serological assays (Table 1) . In contrast, thermal inactivation by incubation of serum samples at 60 C for 1 h yielded aberrant serological test results with a mean bias of 17.5 ± 66.4%, which further increased to 37.9 ± 79.8% when combined with Triton X-100 0.1% (Table 1, Figs.

cord-296256-ipe92w4y	title: Prevalence, clinical outcomes and rainfall association of acute respiratory infection by human metapneumovirus in children in Bogotá, Colombia Human metapneumovirus (HMPV) has recently been described as a cause of severe acute respiratory infection and its prevalence and clinical behavior in children at moderate altitudes is unknown. RESULTS: Out of a total of 14,760 discharged patients, multiplex RT-PCR was performed on 502 and a virus was detected in 420 children with acute respiratory infection (ARI). CONCLUSIONS: Human metapneumovirus was the fifth most frequently isolated virus in children with ARI, had similar clinical behavior and severity to other viruses but a higher rate of viral coinfection. The data was taken from the institutional electronic charts of children who were hospitalized for acute respiratory infections and who received multiplex RT-PCR (FilmArray® BioMériux), the analyte used in this technique for HMPV detection was Type 16, A1 IA10-2003 Zeptometrix 0810161CF.

cord-296487-m4xba78g	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). Specifically, we aimed to determine hospital bedcapacity for isolation, public health workforce capacity for contact tracing and health care worker (HCW) personal protective equipment (PPE) requirements under different attack scenarios. We estimated number of hospital beds needed to control the epidemic, PPE requirements for clinical HCWs and public health workers required for contact tracing, under different scenarios. The number of hospital beds needed for case isolation was then modelled under different scenarios based on variation of response time (T), the percentage of infected cases isolated each day and how many contacts were traced. The number of contacts needed to be traced and managed was estimated based on attack size, time to response (T) and the percentage of infected cases isolated each day.

cord-296890-08kqtw8s	Specimens were examined at our collaborating institutions with a panel of molecular assays for viral pathogens including influenza A (IAV), IBV, ICV, and IDV, human adenovirus (AdV), human enterovirus (EV), human coronavirus (CoV), respiratory syncytial virus subtype A (RSV-A) or RSV-B, and parainfluenza virus (PIV) types 1–4. One study of respiratory samples collected from children living in Kuala Lumpur under 5 years of age between 1982 and 2008 found that 26.4% of the samples were positive by immunofluorescence assays and viral cultures for viral pathogens, with a prevalence of 18.6% for respiratory syncytial virus (RSV), 3.5% for parainfluenza viruses (PIVs), 2.9% for influenza viruses, and 1.37% for adenovirus [10] . The overall objective of this study was to examine the viral etiology of and risk factors for pneumonia among patients admitted to Sibu and Kapit Hospitals between June 2017 and May 2018 and, in doing so, to assist Malaysian collaborators with setting up sustainable real-time molecular assays for viral respiratory pathogens.

cord-296921-0trs364m	An electrochemical flexible biosensor composed of gold (Au), molybdenum disulfide nanoparticles (MoS(2) NPs), and Au (Au/MoS(2)/Au nanolayer) on the polyethylene terephthalate (PET) substrate is developed to detect envelope glycoprotein GP120 (gp120), the surface protein of HIV-1. The current increase of the Au/MoS 2 /Au nanolayer on the PET substrate compared to conventional bare gold electrode was due to the large surface area and the efficient electron transfer by MoS 2 NPs. Nanomaterials 2019, 9, x FOR PEER REVIEW 6 of 12 The reduction and oxidation peak currents of the Au/MoS 2 /Au nanolayer on the PET substrate derived from the redox generator were 1.13 mA and −1.17 mA, respectively, which were much higher than those peaks of the bare gold electrodes with 0.96 mA and −1.01 mA due to the large surface area and effective electron transfer of the synthesized MoS 2 NPs. The fabricated biosensor showed highly sensitive detection of gp120 with a detection limit of 0.066 pg/mL, which was more sensitive than previously reported electrochemical HIV biosensors.

cord-296992-2vp35fwv	We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. Since 2009, INSIGHT has undertaken 2 cohort studies-1 outpatient (FLU002) and 1 inpatient (FLU003)-specifically to address gaps in clinical research on the emerging influenza pandemic, including factors linked to disease progression and severe outcomes [24] . To underscore the importance of having baseline data, we compared the estimated pH1N1 clinical severity to that of seasonal influenza types and subtypes and noninfluenza respiratory patients in the post-pandemic period (2012) (2013) (2014) (2015) . Our analysis combining data from inpatient and outpatient INSIGHT cohorts demonstrates how preestablished global research networks could immediately begin rigorous studies to estimate the CFR, a key parameter of clinical severity of an emerging pandemic.

cord-297265-pwq5gir9	Three recent Science articles (Chen et al., 2018; Gootenberg et al., 2018; Myhrvold et al., 2018) describe the use of CRISPR-Cas technology to develop point-of-care diagnostics that directly detect viruses from clinical samples. Three recent Science articles (Chen et al., 2018; Gootenberg et al., 2018; Myhrvold et al., 2018) describe the use of CRISPR-Cas technology to develop point-of-care diagnostics that directly detect viruses from clinical samples. In three papers published in Science (Chen et al., 2018; Gootenberg et al., 2018; Myhrvold et al., 2018) , two groups report the use of CRISPR-Cas-based technology for the development of molecular diagnostic assays, with a focus on infectious diseases. After collection of clinical samples in a point-of-care setting, such as the patient bedside, medical office, hospital ward, or in the field, the CAS12a-or CAS13-based assay can be performed directly from the sample in under 2 hr, without the need for a separate DNA or RNA extraction step.

cord-297283-o1oauxex	This study aimed to determine the frequency and intensity of neonatal diarrhea and the incidence of RVA and attempted to monitor the G and P genotypes present in the RVA strains circulating in a high milk yield cattle herd vaccinated with RVA G6P[5] strain. The aim of this study was to determine the frequency and intensity of neonatal diarrhea and the incidence of RVA and to identify the RVA G and P genotypes circulating in dairy calves born from cows that are regularly vaccinated with the RVA G6P[5] strain in a high milk yield dairy cattle herd. Other longitudinal studies that have been conducted in Brazil to determine the level of RVA infection in calves born from vaccinated dairy cows had percentages of RVA-positive diarrheic fecal samples that were 5.7% (49/850) (Coura et al., 2015) and 3.9% (11/281) (Rocha et al., 2017) .

cord-297469-26d8o1xk	gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected cells were treated with different concentrations (12.5-200 µg/mL) of ursolic acid (UA) and sulfadiazine (SF) at 37 • C for 24 h, respectively; their survival rates were inhibited a dose-dependent manner. We evaluated the effect of ROS and NO production induced by ursolic acid in immune cells infected with T. We evaluated the effect of ROS and NO production induced by ursolic acid in immune cells infected with T.

cord-297669-22fctxk4	The virus was thought to attach to CD169 to be taken up into the cells; however, genome-edited pigs lacking CD169 were not resistant to PRRSV infection (Prather et al., 2013) . Chicken somatic cell lines have been edited to introduce changes to this gene-conferring resistance to avian leucosis virus in vitro (Lee et al., 2017) . However, as the example for avian influenza shows, host genes play an important role in other steps of the pathogen replication cycle and also provide editing targets for disease resilience or resistance. Genome editing allows integration of the disease-resistance trait into a wider selection of pigs, ensuring genetic variability and maintenance of desirable traits. (D) Resistance genes may be identified in laboratory research but not in highly bred lines, making integration into those productive animals only possible using genome editing. She employs genome editing and genetic selection to generate animals genetically resistant to viral disease.

cord-298032-3zlu8g8y	An earlier study showed that a 22mer PPMO targeting the translation start site region of EBOV VP35 positive-sense RNA exhibited sequence-specific, time-and dose-dependent inhibition of EBOV replication in cultured cells (Enterlein et al., 2006) . However, PPMO targeting conserved internal ribosome entry site (IRES) sequences have been shown to be highly effective in protecting cultured cells against infection by human rhinovirus type 14, coxsackievirus type B2, and poliovirus type 1 (PV1) (Stone et al., 2008) , with reduction of PV1 titers by up to 6 log10. In this study, virus replication in MDCK cells was significantly inhibited by three PPMO targeting either the translation start site region of PB1 or NP mRNA or the 3 -terminal region of NP viral RNA (vRNA). Inhibition of influenza virus infection in human airway cell cultures by an antisense peptide-conjugated morpholino oligomer targeting the hemagglutinin-activating protease TMPRSS2

cord-298166-045evk7g	As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Methods describing the effect of CLR01 on pseudotyped lentiviral particles (2.3.), Ebola virus infection (2.4.), the detection of ZIKV infection by a colorimetric MTT assay (2.5.) or by cell-based ZIKV immunodetection assay (2.6.), flow cytometry (2.7.) and confocal microscopy (2.8.) as well as the RNA release assay (2.9.) and the antiviral activity of CLR01 in body fluids (2.10) can be found in the supplement.

cord-298776-tjw45t3f	During the 7th MENA-ISN meeting, representatives from 8 countries presented their influenza surveillance, vaccination coverage and actions achieved and provided a list of country objectives for the upcoming 3 years. Annual vaccination campaigns in the MENA region target primarily specific high-risk groups i.e. pregnant women; individuals >6 months with underlying chronic diseases, elderly, residents of long-term care facilities, children aged 6-59 months and health care providers. MENA-ISN support the WHO initiative in building laboratory capacity and surveillance in the region and urge the governments to give high priority to the establishment and continued support for influenza surveillance systems; identify the needs of countries for establishing or improving existing surveillance networks; disseminate surveillance and disease burden data through publications and develop actions to increase vaccination coverage rates in health care professionals (HCPs), pregnant women, people at risk, elderly and children. Each country representative summarized their current situation of influenza surveillance, influenza vaccination coverage and actions achieved, and provided a list of country objectives for the upcoming 3 years.

cord-298805-ntpm68cg	Therefore, in order to overcome the limitations, many researchers have focused on the development of new immunological and molecular based rapid assays that could enable early diagnosis of infection and accurate identification of fungal pathogens causing superficial and invasive infection. Therefore, in order to overcome the limitations, many researchers have focused on the development of new immunological and molecular based rapid assays that could enable early diagnosis of infection and accurate identification of fungal pathogens causing superficial and invasive infection. As for the use of GM in diagnosis of invasive aspergilosis, recently published data suggest that detection of this Aspergillus Ag in blood and parallel PCR diagnostics provide very high sensitivity of 99% with specificity of 64% which influence 100% negative predictive value in high risk patients and enable the consideration of no-existing invasive aspergillosis in these patients and no need for antifungal therapy.

cord-299310-ukn6hm5x	ABSTRACT We determined if feeding and lying behavior, recorded by automatic calf feeding systems (ACFS) and accelerometers, could be used to detect changes in behavior before onset of neonatal calf diarrhea (NCD) or in response to disbudding pain in dairy calves. Feeding (milk consumption and the number of rewarded and unrewarded visits to the feeder) and lying behavior during the 5 d leading up to calves displaying clinical signs of NCD were analyzed. Information on feeding and lying behavior collected from ACFS and accelerometers could potentially be measured remotely on-farm and used by producers as a tool to help detect NCD early so that strategies could be promptly implemented to reduce the negative effects of this disease on calf health and production. Therefore, the objectives of our study were to determine if behav-ioral data collected from ACFS and accelerometer data loggers could be used to detect changes in behavior before the onset of NCD or in response to disbudding pain in dairy calves.

cord-299345-2i48ld8d	Pairwise identity analysis of the whole genome sequences revealed that PEDV/Belgorod/dom/2008 is an intermediate between PEDV and transmissible gastroenteritis virus (TGEV) strains. Based on the phylogenetic analysis of the M gene, the PEDV/Belgorod/ dom/2008 isolate belongs to the same clade as other virulent Russian PEDV strains, indicating a high degree of sequence homogeneity in the M gene (Fig. 3a) isolate is genetically distinct and does not belong to any group (Fig. 3b ). The identification of recombinant regions in PEDV/Belgorod/dom/2008 can be useful for further analysis of evolutionary variability, epidemiology, and development of a new diagnostic gene-based assay for porcine epidemic diarrhea virus. 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 Genome sequencing and analysis of a novel recombinant porcine epidemic diarrhea virus strain from Henan, China

cord-299379-ch7a39d6	title: Epidemiology of human respiratory viruses in children with acute respiratory tract infection in a 3-year hospital-based survey in Northern Italy() The viral etiology of ARTIs was investigated over 3 years (October 2012–September 2015) in 2575 children in Parma, Italy, using indirect immunofluorescent staining of respiratory samples for viral antigens, cell culture, and molecular assays. The simultaneous use of different diagnostic tools allowed us to identify a putative viral etiology in half the children examined and to provide an estimate of the epidemiology and seasonality of respiratory viruses associated with ARTIs. Acute respiratory tract infections (ARTIs) are a persistent public health problem (Lu et al., 2013) . This three-year (October 2012-September 2015) hospital-based survey in Parma (Northern Italy) aimed to determine the prevalence of respiratory virus infections, their seasonality, and any patterns of mixed infections in children with ARTIs by using indirect immunofluorescent staining of respiratory samples for viral antigens, cell culture, and molecular assays.

cord-299421-xn17j7a6	Analysis of swine cases confirmed a strong positive association between isolation of I 4, [5] ,12:i:-and lesions of enteric salmonellosis and suggested a similar pathogenic potential as that for Salmonella Typhimurium. Analysis of swine cases confirmed a strong positive association between isolation of I 4, [5] ,12:i:-and lesions of enteric salmonellosis and suggested a similar pathogenic potential as that for Salmonella Typhimurium. To determine the association between the presence of Salmonella I 4, [5] ,12:i:-and lesions consistent with enteric salmonellosis, we also reviewed 40 additional cases that met the previously stated inclusion criteria but from which neither Salmonella I 4, [5] ,12:i:-nor Salmonella Typhimurium were isolated; we randomly selected these cases from an Excel (Microsoft, https://www.microsoft. A review of case data for clinical submissions to the ISU-VDL confirmed a statistically significant positive association between histologic lesions consistent with enteric salmonellosis and isolation of Salmonella I 4, [5] ,12:i:-(odds ratio 10.53, 95% CI 4.45-24.88; p<0.0001) (Table) .

cord-299585-fkg8d6ym	title: Development of a triplex real-time RT-PCR assay for detection and differentiation of three US genotypes of porcine hemagglutinating encephalomyelitis virus In the present study, we report the development of a triplex real-time RT-PCR assay for detection and differentiation of three PHEV genotypes, 1, 2, and 3. The triplex real-time RT-PCR provides a rapid and sensitive method to detect and differentiate all three US genotypes of PHEV from clinical samples. Porcine hemagglutinating encephalomyelitis virus (PHEV) is one of six known porcine coronaviruses (CoVs) causing diseases in pigs (Gong et al., 2017; Wang and Zhang, 2016) . The triplex rRT-PCR developed in the present study will fulfill this purpose and can be used to monitor PHEV of different genetic genotypes and differentiate between them. The detection limit of the triplex rRT-PCR assay was determined by testing 10-fold serially diluted positive PHEV RNAs (15SW1362 and 15SW25049) and plasmid DNAs (pCR 2.1-15SW1582-N, pCR 2.1-15SW1362-NS2, and pCR 2.1-15SW25049-NS2) in duplicate.

cord-300019-8vxqr3mc	We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Although influenza virus (Flu) is the most widely recognized viral infection associated with respiratory illness, >25 viruses have been linked to pneumonia, causing a substantial disease burden in adults and elderly individuals. Therefore, we aimed to conduct a similar systematic review to identify all case-control studies since 1996 investigating the potential role of respiratory viruses in the etiology of ARIs in older adults aged ≥65 years.

cord-300083-qm27uw8r	authors: Weerasuriya, A.U.; Hu, Z.Z.; Zhang, X.L.; Tse, K.T.; Li, S.; Chan, P.W. title: New inflow boundary conditions for modeling twisted wind profiles in CFD simulation for evaluating the pedestrian-level wind field near an isolated building The new inflow boundary condition derived based on the horizontal homogeneous assumption, specifies a vertical profile of lateral wind speeds at the inlet boundary to sustain the twist effect in the empty computational domain. The proposed boundary conditions are used to simulate the PLW fields near three isolated buildings with different Height-to-Width ratio using two CFD codes; OpenFOAM, and FLUENT. Although plenty of studies have been conducted to provide inlet boundary conditions in the simulation of the atmospheric boundary layer flow, no systematic investigations, to the best knowledge of the authors, have been carried out to show the sustainability of the twisted wind profiles in the CFD computational domain.

cord-300379-db79kb5c	To quantify the ability of ATA to prevent ZIKV-induced apoptosis, tissue culture supernatants from ZIKV-infected Vero and A549 cells were harvested at 24, 48, and 72 h p.i. to measure the level of apoptotic signal as determined by caspase 3 and 7 activities ( Figure 5B) . ZIKV-infected cells showed FIGURE 4 | Aurintricarboxylic acid inhibition of ZIKV replication: Vero (A) and A549 (B) cells (24-well plate format, 2.5 × 10 5 cells/well, triplicates) were infected (MOI 0.1) with Paraiba/2015. In this study, we demonstrated that ATA (Figure 1 ) has limited toxicity (Figure 2) and an effective and dose-dependent antiviral activity against ZIKV infection (Figures 3, 4) in both monkey kidney epithelial Vero and human alveolar A549 cells. Notably, ATA can prevent ZIKV-induced CPE and apoptosis in both cell lines ( Figure 5 ) and has broad anti-viral activity against representative ZIKV strains from the African (Uganda/1947 and Nigeria/1968) and the Asian/American (Puerto Rico/2015 and French Polynesia/2013) lineages (Figure 6) .

cord-300436-beb8k075	Because TfR1 is distributed widely along the surface epithelium of newborns with anemia, and intestinal epithelial cells of newborn piglets are targets of TGEV, it is possible that TfR1 is the as yet uncharacterized 200 kDa protein that mediates TGEV infection. To test this hypothesis, we used cultured porcine intestinal columnar epithelial cells (IPEC-J2), derived from the neonatal piglet mid-jejunum [39, 40] , as a model to characterize the interaction between TfR1 and TGEV in vitro. At 24 h p.i., western blotting showed that expression of TGEV-N protein was significantly lower in IPEC-J2 cells that had been pre-incubated with anti-TfR1 Ab (Fig. 3b and c) . c and d TGEV (MOI 5) was pre-incubated with the precipitated TfR1 protein for 2 h at 37°C before cells were infected. e and f IPEC-J2 cells infected with TGEV (MOI 5) were pre-incubated with TfR1-Out (200 ng/mL) for 1 h at 37°C, and cell lysates were harvested for western blotting.

cord-300459-tu2xrt9x	We previously reported on a panel of monoclonal antibodies (mAbs) derived from the longitudinal samples of a ZIKV-convalescent individual and characterized their neutralizing activities, epitope specificities, and development timeline over the course of infection . Here, we use the mouse models of ZIKV infection and microcephaly to analyze the in vivo protective activities of six human mAbs and compare the findings with our reported in vitro neutralization activity, as measured by plaque reduction neutralization test (PRNT). mAbs that target DIII with potent neutralizing activity have also been isolated by other groups, derived from either infected humans or mice, and have been shown to be effective in various models of ZIKV pathogenesis (Fernandez et al., 2017; Magnani et al., 2017; Robbiani et al., 2017; Stettler et al., 2016; Wang et al., 2017b; Zhao et al., 2016) .

cord-300552-xpo5zsub	Methods: This study examines fugitively-emitted aerosol emissions when nebulising albuterol sulphate, as a tracer aerosol, using two commercially available nebulisers in combination with an open or valved facemask or using a mouthpiece with and without a filter on the exhalation port. Time-varying fugitively-emitted aerosol concentrations and size distributions during nebulisation were recorded using aerodynamic particle sizers at two distances relative to the simulated patient. This study highlights the potential secondary inhalation exposure to fugitive emissions for caregivers and other bystanders during a standard nebuliser treatment. To the best of the authors'' knowledge, this is the first study that quantifies time-series aerosol concentrations and the size distribution of fugitive emissions that result from standard nebuliser treatment. The findings confirm a potential exposure risk to caregivers and other bystanders to medical aerosols and highlight that variations in patient interfaces (facemask and mouthpiece) and aerosol generators (VMN and JN) influence fugitively-emitted aerosol concentrations.

cord-301285-p83ondy8	To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Due to the error-prone nature of the RNA-dependent RNApolymerase (RdRp), RNA virus replication is characterized by a high mutation rate that results in increased genetic diversity of progeny viruses (Domingo et al. When compared with unpassaged, wild-type (wt) viruses, fidelity mutants have similar growth kinetics in vitro, but are attenuated in vivo due to the alteration of diversity produced during replication, which hampers the ability of the virus to overcome bottlenecks in the host (Pfeiffer and Kirkegaard 2005; Vignuzzi et al. The 4x mutant, while exhibiting phenotypic similarities with other altered fidelity mutants, had no significant difference in virus diversity compared with the TC-83 parent after one cell culture passage.

cord-301382-zlr4nwc2	title: Sero-prevalence, cross-species infection and serological determinants of prevalence of Bovine Coronavirus in Cattle, Sheep and Goats in Ghana Cattle, goats and sheep are dominant livestock species in sub-Saharan Africa, with sometimes limited information on the prevalence of major infectious diseases. Here we established BCoV serology based on a recombinant immunofluorescence assay for cattle, goats and sheep, and studied the seroprevalence of BCoV in these species in four different locations in the Greater Accra, Volta, Upper East, and Northern provinces of Ghana. This study evaluated the sero-prevalence of BCoV infection and assessed its associated risk factors among cattle, sheep, and goats in Ghana. Univariate and multivariate logistic regression analysis were performed to determine the possible factors associated with BCoV sero-positivity for cattle, sheep, and goats. Antibody titers against bovine coronavirus and shedding of the virus via the respiratory tract in feedlot cattle

cord-301649-iipyg7ab	In a cohort of 360 allogeneic HSCT recipients, they reported that having a >1% relative gut abundance of BPG bacteria is associated with 5-fold less future development of lower respiratory viral infections. We report that having a >1% relative abundance of BPG bacteria is associated with less risk for development of respiratory viral infections in kidney transplant recipients, which provides further support for the findings from the Haak et al study. 11 Among the Paired Abx Group, 6 subjects had anaerobic antibiotic coverage and all 6 had a significant decrease in the relative gut abundance of BPG bacteria from post-transplant week 1 to post-transplant week 4 (median 9.9% vs 1.9%, respectively, P = .03, Wilcoxon signed-rank test; Figure 2E ). Box and whisker plot with the relative gut abundance of BPG bacteria on the yaxis and the fecal specimen post-transplant week on the x-axis for the 6 subjects in the Paired Abx Group who received antibiotics with anaerobic coverage.

cord-301767-1jv20em8	Primarily, pathogens may contaminate produce ''on-field'' via various routes including; atmospheric deposition, uptake from contaminated soils and groundwater (Harris et al., 2003; Lynch et al., 2009; Mei Soon et al., 2012) , use of raw (or poorly treated) manure and compost, exposure to contaminated water (irrigation or flooding), transfer by insects, or by fecal contamination generated by livestock or wild Table 1 The most commonly implicated etiological agents in fresh produce borne illnesses (Brackett, 1994; Buck et al., 2003; Heaton and Jones, 2008; Jung et al., 2014; Callej on et al., 2015) . Epidemiological investigations of food poisoning outbreaks, experimental studies examining pathogen contamination of fruits and vegetables as well as observations of increased incidence of disease in areas practicing wastewater irrigation with little or no wastewater treatment indicate that contaminated irrigation water might indeed be a source of foodborne pathogens on fresh produce (Norman and Kabler, 1953; Hern andez et al., 1997; Steele and Odumeru, 2004) .

cord-301810-vtgdqart	Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). At 5 days following challenge with IBV GA98, vaccinated/challenged birds had significantly lower RNA loads compared to positive controls at all collection times and in all tissue samples, with the exception of cecal tonsil at 24 WOA (Table 1 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ).

cord-301856-71syce4n	With the burst of next-generation sequencing and the development of cutting-edge technologies such as transcriptomics, proteomics, and systems biology, we are starting to witness the great impact of evolutionary processes on human immunity and how the interactions between microorganisms and humans that took place millennia ago might play a fundamental role not only in the response against modern pathogenic threats, but also in the emergence of autoimmune and inflammatory diseases observed in modern populations worldwide. Specific genetic variants selected throughout different periods of human history may have influenced immune responses of present-day populations against pathogenic microorganisms and may have played a role in the development of certain inflammatory and autoimmune diseases. Patients with African ancestry present a higher frequency of MTB-related genetic variants than individuals from other populations, including variants in the gene encoding for Toll-like receptor 6 (TLR6), mediating cellular responses to bacterial Malaria is one of the greatest causes of morbidity and mortality in the history of humanity.

cord-302155-hksmt48i	Despite the importance of NiV as an emerging disease with the potential for pandemic, no vaccines, or therapeutics are currently approved for human or livestock use. Vaccine efficacy studies in animal models aim to identify specific vaccine-induced correlates of protection including neutralizing antibodies or cell-mediated responses (53) . On the other hand, pigs have been used successfully as models to study many human infectious diseases (57) (58) (59) (60) (61) (62) (63) , including NiV infection (64) . There is also a growing appreciation that pigs provide a superior animal model for influenza A virus infection and immunity and should play a more prominent role as a model for human influenza vaccine development (65) . The use of non-human animal models is crucial for vaccine development against diseases such as NiV since efficacy testing in humans is impossible. Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia

cord-302226-0rhgmtbo	title: Spectrum of respiratory viral infections in liver disease patients with cirrhosis admitted in critical care unit BACKGROUND: Clinical significance of respiratory viruses (RVs) as an etiology of pneumonia in liver disease patients with cirrhosis is usually underestimated. Therefore, the aim of this study was to evaluate the spectrum of RVs in cirrhotic patients with pneumonia admitted in critical care units (CCUs) and its impact on the clinical outcome of cirrhotic patients. [7, 8, 14] The current study has found that respiratory viral infections other than influenza virus infection are also an important etiology of pneumonia in liver disease patients with cirrhosis admitted in CCUs. Transmission dynamics and seasonal distribution of RVs are key importance in understanding and limiting burden of morbidity and mortality of pneumonia patients in CCUs.

cord-302239-2sxy3spd	In this paper, we tried to show that the theory of planned behavior provides a useful conceptual framework for SI when facing a pandemic risk, and a regression method with Chinese provincial (Guangdong Province) data was applied to investigate how attitude (ATT), subjective norms (SN), and perceived behavioral control (PBC) influence SI when facing a pandemic emergency. Risk perception has been widely established as a significant predictor of engagement in preventive health behaviors, including SI [21] ; those who report being unfamiliar with the term "pandemic influenza," male respondents, and employed people who are not able to work from home have been found to be less willing to comply [22] . Using Chinese provincial (Guangdong Province) data, we investigated how ATT, SN, and PBC influence the willingness of self-isolate when facing a pandemic emergency.

cord-302355-3se1wp8o	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] .

cord-302401-oyhzn2kc	Here, we cloned the duck KPNA4 (duKPNA4) gene and analyzed its involvement in type I IFN expression as well as antiviral response against Japanese encephalitis virus (JEV). We therefore cloned the duKPNA4 gene and analyzed its role in type I IFN expression as well as the antiviral response against JEV in primary duck embryo fibroblasts (DEFs). To analyze whether duKPNA4 might be involved in type I IFN expression, we transfected DEFs with plasmid for expression of duKPNA4-HA at different doses in the presence and absence of poly(I:C) stimulation, and detected the expression of interferon-α (IFN-α) and interferon-β (IFN-β) at the mRNA level by qRT-PCR and at the protein level by ELISA. Together, these data indicated that duKPNA4 resulted in nuclear translocation of duIRF7 and facilitated type I IFN expression during JEV infection, thereby implying its involvement in the type I IFN-mediated antiviral response.

cord-302784-jkjdglns	title: Management of hospitalized drug sensitive pulmonary tuberculosis patients during the Hajj mass gathering: A cross sectional study This study documents the management of drug-sensitive TB patients during Hajj and explores the compliance of healthcare providers with the KSA TB management guidelines in the Ministry of Health (MOH) hospitals in Makkah during the mass gathering. The management of TB patients was documented using a specifically designed data collection form which included patients'' demographics data, underlying health conditions and TB risk factors as well as clinical data including various aspects of TB management such as patients'' screening, infection prevention and control (IPC), TB diagnosis and treatment and case notification and outcome. The result showed high level of compliance with the assessed TB management guidelines indices for systematic screening of TB suspects as well as IPC and surveillance, but low compliance scores were obtained for prompt TB diagnosis and use of standardized treatment regimen for drug-susceptible TB.

cord-303186-2hxlx1j2	In this study, we generated a cold-adapted live attenuated vaccine candidate (Aram-P29-CA) by short-term passage of a virulent PEDV isolate at successively lower temperatures in Vero cells. In this study, we sought to create a cold-adapted attenuated G2b PEDV low-passage strain by progressively decreasing growth temperatures to 32°C in Vero cells and then attempted to evaluate its protective efficacy on neonatal piglets against virulent PEDV challenge. Overall, the quantities of viruses in the feces of animals of group 2 significantly declined compared to those in group 1, with wide Ct ranges of 34.46-24.34 ( Efficacy of cold-adapted attenuated PEDV vaccine All animals in the parental Aram-P5-infected group were necropsied upon death at 4 or 5 DPI, while piglets in the remaining groups were euthanized at the end of the study for postmortem examinations (Fig. 7) .

cord-303265-v6ci69n0	Topics covered include molecular mechanisms of genetic variation, with emphasis on high mutation rates, Darwinian principles acting on viruses, quasispecies dynamics and its implications, consequences for virus-host interactions, fitness as a relevant parameter, experimental model systems in cell culture, ex-vivo and in vivo, long-term virus evolution, the current situation of antiviral strategies to confront quasispecies swarms, and conceptual extensions of quasispecies to nonviral systems. With regard to the concepts of genome stability versus variation addressed in this book, it is helpful to divide viruses into four groups, depending on whether it is DNA or RNA the type of genetic material, which acts as a replicative intermediate in the infected cell (bottom gray shaded boxes in Fig. 1.1 ). They were selected for replicability, stability, and evolvability with trade-offs 1.4 Origin of life: a brief historical account and current views (acquisition of benefits for one of the three traits at some cost for another trait) likely play a role at this stage (see Chapter 4 for trade-offs in virus evolution).

cord-303393-9zs3qqo4	AIM: This study aimed to isolate some of the currently circulating infectious bronchitis virus (IBV) strains from some broiler chicken farms in Al-Hasa and to do some molecular characteristics of these strains. MATERIALS AND METHODS: We collected 300 tissue specimens, including the trachea, bronchi, lungs, and kidneys from some four commercial chicken farms showing respiratory manifestations. We used three tissue suspensions (trachea, lungs, and kidneys) from three specimens representing three different IBV outbreaks in some chicken farms from Al-Hasa region. Some of these farms were reporting IBV outbreaks based on Figure-4: Phylogenetic analysis based on the partial S1 gene for the circulating infectious bronchitis virus (IBV) strains from some chicken farms in Al-Hasa region 2015-2016. Table-5: Pairwise distance analysis of partial S1 gene for the circulating IBV strains in some chicken farms in Al-Hasa region

cord-303557-bbbq6ylr	METHODS: A cross-sectional questionnaire survey was utilized to gauge information regarding capacity of hospitals to deal with infectious diseases in the context of climate change among 611 clinical professionals whose roles pertained to infectious disease diagnosis, treatment and management in Anhui Province of China. The majority of participants suggested that effective prevention and control measures, more interdisciplinary collaborations, more funding in rural areas for health care, and improved access to facilities enabling online reporting of infectious diseases, were extremely important strategies in building capacity to curb the population health impact of emerging and re-emerging infectious diseases due to climate change in China. The study employs a cross-sectional questionnaire survey among clinical professionals to explore China''s capacity of hospitals to deal with infectious diseases in the context of climate change. Further, the study explores participants'' views on capacity building in the hospital sector to curb potential emerging and re-emerging infectious diseases due to climate change in China.

cord-304023-s22wi0t0	METHODS: Influenza surveillance based on a primary care sentinel surveillance, virological indicators systematic sampling of ILI attended and severe influenza confirmed cases (SHLCI) admitted to hospital. CONCLUSIONS: 2017–2018 influenza season was an unusual epidemic season with an early onset, great predominance of influenza B (Yamagata strain) virus with a high hospitalization rate of severe cases among elderly stressing the need to upgrade vaccine uptake in this age group. 4 The 2017-2018 influenza season presented a predominant circulation of influenza virus type B during the first epidemic weeks with a high rate of severe influenza hospitalizations, especially among the elderly. The aim of this work is to describe the 2017-2018 influenza season according to the PIDIRAC Sentinel Influenza Surveillance System and how it affected elderly population in Catalonia despite moderate vaccine coverage among this age group.

cord-304057-d2r92nji	title: Sero‐prevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia A primary sero‐prevalence study of MERS‐CoV preexisting neutralizing antibodies in Dromedary camel serum was conducted in Tabuk, western north region of KSA, in order to assess the seopositivity of these animals and to explain their possible role in the transmission of the infection to Human. 11, 16, 17 Results have shown that a high number (85%) of dromedary camels from the different farms of Tabuk Riyadh and screened by ELISA test showed that 74% of the animals were found to have antibodies to MERS-CoV. 7 In the same study, 264 archived serum samples collected from dromedary camels from 1992 to 2010 in Riyadh and Kharj were also analyzed by ELISA and showed a high seroprevalence (92%) of MERS-CoV neutralizing antibodies. Middle East respiratory syndrome coronavirus neutralizing serum antibodies in dromedary camels: a comparative serological study Seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in

cord-304066-rirbdhz3	Specifically, in a murine model, CMV airway infection and inhaled environmental antigen of poor intrinsic allergenic potential were found to sensitize for allergic airway disease (AAD) only when combined. Upon airway re-exposure to the inhaled antigen, Th-2 cells secrete interleukins (IL-4, IL-5, IL-9, and IL-25) known to induce goblet cell metaplasia, the lead histopathological manifestation of AAD that is characterized by thickening of airway epithelia and increased numbers of mucus-producing goblet cells, resulting in enhanced mucus secretion and airflow obstruction. As airway exposure to environmental antigens at the time of primary airway infection after hCMV transmission is a realistic scenario of medical interest, recent work modeled this scenario in the mouse with the aim to investigate a possible virus-allergen interplay [17] . Upon co-exposure of airway mucosa to inhaled antigen/low potency allergen, represented by OVA in the specific case, and mCMV, the virus activates MHC-II + CD11c + dendritic cells (DC) that localize to the mucosa, specifically DC of the CD11b + subset of conventional B220 low Ly6c low DC, briefly CD11b + cDC.

cord-304277-aek6mvdw	We initially suspected these patients of having influenza-associated pneumonia and cryptogenic organizing pneumonia, respectively, and performed bronchoalveolar lavage, but only human parainfluenza virus-1 infection was detected by multiplex polymerase chain reaction testing. We recently experienced two cases of pneumonia in which HPIV-1 was isolated from bronchoalveolar lavage (BAL) fluid and confirmed by a multiplex polymerase chain reaction (PCR) test (Fast Track Diagnostics Resp 21 Kit, Silema, Malta), which detects the following respiratory pathogens: influenza A and B viruses; coronaviruses NL63, 229E, OC43, and HKU1; human parainfluenza viruses 1, 2, 3, and 4; human metapneumovirus A/B; rhinovirus; respiratory syncytial virus A/B; adenovirus; enterovirus; human parechovirus; bocavirus; and Mycoplasma pneumoniae. However, previous reports that investigated virus infections in patients with pneumonia used nasopharyngeal or oropharyngeal swabs to detect viruses, which raises the possibility of upper respiratory tract infection by HPIV. Furthermore, these studies include mixed viral and bacterial infections, and the clinical characteristics of the immunocompetent patients with primary HPIV pneumonia are not fully known.

cord-304488-t2jm1n77	We will then discuss the autoimmune phenotype of schizophrenia in terms of risk factors for disease including the role of infection, a peripheral and central inflammatory state, gut dysbioses and the presence of autoantibodies. We will integrate our discussion with mechanisms that contribute to relevant CNS pathologies, including behavioral indices such as severity of psychiatric symptoms and cognitive deficits and biochemical indices such as complement pathway dysfunction and autoimmune-related neurotransmitter receptor hypofunction. In most cases, the source of this inflammation in these studies is not known, but it is evident in the form of pro-and anti-inflammatory cytokine dysregulation, disrupted tryptophan and kynurenine metabolism, exposure to microbial pathogens and antigens, food hypersensitivities, complement activation, post-mortem pathologies and brain imaging.

cord-304635-z5vmhopa	title: Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner However, based on the structures of a series of MHC I molecules, such as human HLA-B*2705 (Madden et al., 1991) , rhesus macaque Mamu-A*02 , and mouse H-2K d (Mitaksov and Fremont, 2006; Zhou et al., 2004) , there is a salt bridge positioned over the peptides formed by opposite charged residues from the α1 and α2 helices of MHC I, respectively. Herein, by determining the crystal structures of human MHC I HLA-B*4001 complexed with a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N)-derived T-cell epitope (Oh et al., 2011) and mouse MHC I H-2K d bound to an immunodominant T-cell epitope from human hepatitis B virus (HBV) core antigen (HBc) (Li et al., 2005) , we clearly demonstrated the molecular features of MHC I molecules with two different salt bridges formed by the residues pairs Arg62-Glu163 and Arg66-Glu163, respectively.

cord-304807-j2k1oel2	The properties of the viral formulation, such as successful inactivation, preservation of hemagglutinin (HA) binding ability, fusion capacity and the potential to stimulate a Toll-like receptor 7 (TLR7) reporter cell line were then assessed and compared to the properties of the untreated virus. Hemagglutination and fusion ability were highly affected by those treatments that conferred higher inactivation, with BPL-treated virus binding and fusing at a lower degree compared to FA-inactivated samples. Our aim was to compare the effects of these procedures on the key properties, namely residual infectivity, receptor binding, fusion, and Toll-like receptor 7 (TLR7) mediated activation of innate immune mechanisms, and to determine whether these effects are similar for different virus strains. Previous studies show that BPL is capable of complete inactivation of influenza virus; however, the effectivity might vary depending on the incubation time and temperature.

cord-304876-txaoz7oh	42 Viral polymerase: An important molecular target for antiviral therapy Nucleoside analogs represent one of the dominant classes of antiviral agents due to their widespread use against the common chronic infections caused by human immunodeficiency virus (HIV), hepatitis B virus, and herpesviruses. 43 After being metabolized by host kinases to their triphosphate form, antiviral nucleotides compete with natural nucleoside triphosphates (NTPs) to bind to the active site of viral polymerases and alter DNA or RNA synthesis. 122 However, the results summarized here indicate that nucleoside analogs targeting the viral RNA polymerase of rhinovirus, EV71, and other enteroviruses have the potential to be efficacious in preclinical animal models, providing a rationale to conduct human studies with safer molecules sharing the same mode of action. Structure and functional analysis of the RNA-and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein

cord-305141-ri8dy54e	Aims: To determine the seroprevalence of canine respiratory coronavirus (CRCoV) in New Zealand dogs, and to explore associations with age, sex, breed, month, and geographical region of sampling and reported presence of clinical signs suggestive of respiratory disease. Logistic regression analysis was used to determine associations between seroprevalence of CRCoV and breed category, age, sex, sampling month, region, and reported health status of dogs. The aim of the present study was to investigate the epidemiology of CRCoV in a large sample of dogs in New Zealand, to explore the associations between seroprevalence for CRCoV and age, sex, breed, month, and geographical region of sampling, as well as the reported presence of clinical signs suggestive of respiratory disease. Independent variables included the dog-related variables of age (≤2, 3-6, 7-10, ≥11 years), sex (female/male), breed group (pet dogs, working dogs, non-descript dogs), health status (healthy/not healthy), and presence of respiratory signs (yes/no), as well as the samplingrelated variables of month of sampling (March to December 2014) and geographical region (Auckland, Hawkes Bay, Manawatu, Marlborough/Canterbury, Nelson/Tasman, Northland, Otago, Taranaki, Waikato, Wellington).

cord-305156-w6iqeayr	PEDV genome was also detected by RT-qPCR in the sperm-rich fraction of semen (6.94 × 10(3) and 4.73 × 10(3) genomic copies/mL) from the two boars infected with the S-InDel PEDV strain but only once at 7DPI. The PEDV positive semen (S-non-InDel and S-InDel) sampled during a previous trial and in this boar trial were inoculated to six SPF weaned pigs. S-non-InDel PEDV strain shedding has recently been evidenced in the different fractions of semen (seminal and sperm-rich fractions) and in gelatin plug of specific pathogen free (SPF) boars experimentally inoculated (Gallien et al., 2018b) . PEDV RNA was also detected in the seminal fraction of semen and in gelatin plug in S-non-InDel PEDV inoculated boars contrasting to the observations from the present study. During the second trial, no shedding was detected in feces of SPF weaned pigs inoculated with S-InDel and S-non-InDel RT-qPCR PEDV positive semen except for pig #5 at 18 DPI.

cord-305399-98sqovwb	A simple and accurate reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay was developed and evaluated for the detection of porcine pegivirus (PPgV). The results indicated that RT-LAMP assay developed in this study could be a highly specific, sensitive, and cost-effective alternative for a rapid detection of PPgV in field settings. The final volume of 25 μl reaction mixtures for RT-LAMP was prepared, which contained 1 μl of Bst DNA polymerase (NEB, USA) (8000 U/ml), 2.5 μl of 10 × Isothermal Amplification Buffer, 5 μl of Betaine (5 M), 1 μl of MgSO 4 (100 mM), 5 μl of dNTP (2.5 mM), 2 μl of each inner primers FIP and BIP (10 μmol), 0.25 μl of each outer primers F3 and B3 (10 μmol), 0.25 μl of each loop primers LF and LB (10 μmol), 1.25 μl of AMV reverse transcriptase (TaKaRa, China) (40 U/μl), 2 μl of RNA template, and the sterile distilled water was set as a negative control template.

cord-305512-p5qchjva	Query BLASTn of the obtained partial sequences of the fragments from these 5 specimens further confirmed these results with >97% sequence identity with at least 1 or 2 mismatches to multiple influenza A viruses subtypes (Supplementary Table S1 ). Query BLASTn of these 5 contigs returned closely related viruses that belonged mostly to human and swine influenza A H1N1 strains isolated between 2009 and 2019 from different countries (Supplementary Table S2 ). We provide the first molecular evidence of influenza A virus circulation in dromedary camels imported from 2 African countries (Sudan and Djibouti) but not in local camels from Saudi Arabia. Our data as well as previous reports suggest that influenza A virus could cause a sustained infection in these animals, highlighting the need for enhanced field surveillance for influenzas viruses as well as other pathogen in dromedary camels to help implementing better preventative one-health plans and programs.

cord-305602-yzc4bosn	This higher than expected connectivity suggests that the direct interactions of viral proteins with host factors allow the access of the virus to cellular complexes. For example, in a TAP-MS experiment were mapped 3787 complex associations between 54 viral proteins from different viruses and 1079 host proteins (Rozenblatt-Rosen et al., 2012) , highlighting the high degree of connectivity of the interacting proteins. As discussed above, some of the host factors predicted, by the combined transcriptional profiling and in silico analyses, to interact with host proteins implicated in direct binary contacts with influenza proteins (Y2H interactors) were demonstrated to influence viral replication in functional screenings (Shapira et al., 2009 ). Most of the small molecules interfering with PPIs bind directly to the implicated surfaces of interactions (orthosteric modulators) by targeting hot spot residues or by molecular mimicry of elements of secondary structures (Arkin et al., 2014; Basse et al., 2016; Fry, 2006; Wells & McClendon, 2007; Yin & Hamilton, 2005) .

cord-305936-tdswzj7r	Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. We analyzed particularly the most predominant variants (AH1N1 and AH3N2) on excess of mortality in the adults and elderly of different age groups in a region with marked seasonality of respiratory diseases in Brazil. Among adults (24-59 years), we observe a large excess of deaths rates during the 2009 pandemic (953 obits), which correspond to 7.1 excess deaths from all causes, and 99 excess mortality from respiratory diseases associated with viral infection in every 100,000 individuals of the age group. Although the elderly are the most vulnerable group to viral respiratory infections, we found relative small excess of deaths in years of circulating AH1N1 pre pandemic (2002 and 2008) .

cord-306004-amv0los1	Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. MERS-CoV infection in these animals merely causes mild upper respiratory tract infection [17, 18] , but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species [19] [20] [21] [22] . Given the fact that experimental in vivo infection studies and DPP4 expression analysis in different animal species revealed that dromedary camels are not the only animals in which MERS-CoV has an upper respiratory tract tropism [17, 18, 83, 84] , it is then relevant to question whether other animals can potentially spread MERS-CoV as well.

cord-306450-sh2mrhoq	The aim of this study was to investigate the respiratory viruses in children admitted to a university hospital with acute respiratory tract infection during the last 8 years by a multiplex polymerase chain reaction (PCR) assay. where coinfections were the most frequent cause of the respiratory infections in the studied group and followed by RV/EV and influenza A/B, respectively ( Figure 1B ). In our study, the age relation was significant for RSV and HMPV which were detected in 89% (260 of 292) and 81% (84 of 104) of children under 5 years, respectively. Similar to RSV, HMPV infections were frequently seen in winter and spring months as it was the case in our study while 90% of the HMPV cases were detected between January and April. Epidemiologic analysis of respiratory viral infections mainly in hospitalized children and adults in Midwest University Medical Center after the implementation of a 14-virus multiplex nucleic acid amplification test

cord-306533-lvm11o4r	DUBs interact with some of the key molecules in the IFN signaling pathway, which include, but are not limited to, RIG-I, stimulator of interferon genes (STING), tumor necrosis factor receptor-associated factors (TRAFs), interferon regulatory factor are summarized in Table 1 . A study conducted using human kidney mesangial cells (MC) showed slightly different results: silencing CYLD in MC cells and stimulating them with poly IC increased the toll-like receptor 3 (TLR3)-induced activation of RIG-I and MDA5 [26] ; however, the level of mRNA of RIG-I and MDA5 actually decreased [26] . However, when USP18 -/-MEF cells with either WT USP18 or DUB activity-mutated USP18 were induced with HSV-1, HCMV or cytosolic DNA, Ifnb, Ifna4, Tnf, IL-6 or Cxcl1 genes increased in expression, indicating that the deubiquitinating activity of USP18 is not responsible for this phenomenon [41] . In a study by Malakhova et al., USP18 inhibited IFN-induced gene activation by affecting JAK-STAT signaling pathway in 293 T cells [44] .

cord-306656-cbtf2y2f	Pyogranulomatous inflammation has been extensively described in cats, in particular in cases of feline infectious peritonitis and also associated with Mycobacteria, Actinomyces, Nocardia, Rhodococcus and fungal infections. In this case series we describe the clinical presentation, histopathology and outcome of three cases of feline idiopathic sterile steroid‐responsive pyogranuloma with different presentation and different locations of the lesion, but with the common feature of having a mass with no superficial skin involvement. We describe the clinical presentation and outcome of three cases of feline idiopathic sterile pyogranuloma with different presentation and locations, but with the common picture of a mass with no superficial skin involvement. The 16s rRNA PCR for Mycobacteria species in fresh, frozen or even in paraffin-embedded tissue sample is considered a very sensitive and specific test for diagnosis of lepromatosis/mycobacteriosis in cats compared to histopathology and ZN staining, so the possibility of a false negative is unlikely (Hughes et al.

cord-306707-dde4nlhh	Emerging and reemerging infectious diseases are largely preventable, and yet with their profound impact and increasing prevalence, they remain a threat to global health, which must be addressed. The SDGs posit that through increased surveillance and allocating more resources and funding to this health issue, diagnostic and treatment programs will be improved, and the epidemic of emerging and reemerging infectious diseases will once again begin to decline. Therefore, a global network of specialist and experts is key in designing future responses to EIDs. The introduction of vaccines led to the eradication of major infectious disease such as Smallpox and Measles that plagued earlier centuries as leading causes of death. In view of the disproportionate global burden of infectious diseases where some regions are more prone relative to others, a key consideration in eradicating EIDs may be the reallocation of resources, including expertise and clinical technology to areas that are most impacted.

cord-307046-ko3bdvo0	Complete genome sequences are now available for many of the archived isolates, allowing more accurate taxonomic assignments, analysis of their phylogenetic and evolutionary relationships with other viruses, and evaluation of the potential risks they may present to humans and wild or domestic animal populations. Scientists in these field laboratories were involved in the detection and investigation of human diseases in their respective geographic regions, surveying human and animal populations for serologic evidence of past viral infection, and searching for viruses in a wide variety of arthropods, mammals, birds, reptiles, and amphibians [2] . The family contains several serious human pathogens, including dengue, yellow fever, Zika, Japanese encephalitis, West Nile, and tick-borne encephalitis viruses (all arboviruses in the genus Flavivirus) and the hepatitis C virus (a member of the genus Hepacivirus).

cord-307543-piust0s6	title: Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study OBJECTIVES: To assess the nurses'' hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in smalland medium-sized hospitals after Middle East Respiratory Syndrome outbreak. The questionnaire included 4 domains: (A) HH knowledge, (B) HH perceptions, (C) HH attitudes and role models, and (D) participant demographics and hospital characteristics. The attitudes and role models domain (C) was adapted from Hand Hygiene Knowledge and Performance a previous study [8] . The regression model for performance was calculated as Y4 =18.302+0.247X41 (perceptions)+0.232X42 (attitudes)+ 0.875X42 (role model); the coefficients were statistically signifiIn terms of infection control infrastructure [16] , ICDs and ICNs were not fully allocated across the hospitals analysed in this study. Consistently with previous studies [13, 21, 22, 25] , our participants'' self-reported HH performance rate of self was positively correlated with their scores for perceptions, attitudes, and role models.

cord-307547-7n3f3wrz	Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (K(i) in the micromolar range). Elimination of the cyclic peptide fragments from the structure of Actinomycin D/X 2 allowed the resulting Actinocin to penetrate much further into the active sites of the studied metallopeptidases and to act as a classical competitive ligand by interacting with the metal ions (Figures 5 and 6 ). Actinomycin D is a long-known drug that was developed as an anticancer agent years before apoptosis and other cell death mechanisms and cancer progression were elucidated. Blocking the activity of MetAP2 and APN with Actinomycin D or its analogs seems to be promising for the development of new generations of potent anticancer agents that would be implicated in different mechanisms of action and directed against multiple molecular targets.

cord-308261-hxlebas8	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.

cord-308884-erofmh39	authors: Yang, Seung Won; Jang, Yo Han; Kwon, Soon Bin; Lee, Yoon Jae; Chae, Wonil; Byun, Young Ho; Kim, Paul; Park, Chan; Lee, Young Jae; Kim, Choon Kang; Kim, Young Seok; Choi, Seong Il; Seong, Baik Lin It should be noted that specificity of the antibody response to a reporter protein relative to the RID docking protein was not appreciably different regardless of the origin of an RID and the animal species to be immunized (compare Fig. 5A with 5D for eGFP and Fig. 5B with 5F for the HAgD), probably as a result of high homology (;80%) in an amino acid sequence between the murine and rabbit counterparts. D) ELISA data showing that according to the number of boosts, high-titer antibodies in serum samples from mice (n = 5) immunized with mRID-HAgD (20 mg/mouse) bound to the PR8 (H1N1) virus (10 4 PFU/well).

cord-309127-kxivgxbg	title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 In line with these observations, high amounts of MERS-CoV antigen were detected within the respiratory epithelium of the nasal turbinates of mock-vaccinated dromedaries at 4 dpi by immunohistochemistry in areas SciEntiFic REpORTS | (2018) 8:9778 | DOI:10.1038/s41598-018-28109-2 with most severe lesions ( Fig. 2A) . To finally elucidate the histogenesis of cells staining positive for MERS-CoV nucleocapsid antigen within the lamina propria of the nasal turbinates of mock-vaccinated dromedaries, additional double immunofluorescence labeling was performed. Since DPP4 was only detectable within the apical brush border of the surface epithelium and submucosal glands, but not on the surface of inflammatory cells within lamina propria and submucosa of the nasal turbinates by immunofluorescence, dromedary and human lymphoid tissue were stained for comparison and control.

cord-309518-seonrtn3	BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. [9] [10] [11] [12] While NIV may initially avoid the need for intubation and invasive mechanical ventilation (MV) , several studies have reported high failure rates and the need for invasive ventilation among patients with severe acute respiratory distress syndrome (ARDS) and an association with increased mortality. 12 In a recent analysis from the LUNG SAFE study on unselected patients with ARDS, NIV was associated with higher intensive care unit (ICU) mortality in patients with the ratio of partial pressure of oxygen to the fraction of inspired oxygen (PaO 2 /FiO 2 ) lower than 150 mm Hg. 12 The role of NIV in AHRF secondary to viral respiratory infections is unclear.

cord-309565-8syjr6k8	A long-term animal experiment involving inoculation with bovine coronavirus (BCoV) was conducted to verify its persistent infection in cattle. Until the end of the experiment (1,085, 700 and 280 days, respectively), viral RNAs were detected sporadically by RT-PCR and nested PCR from plasma, nasal discharge, and feces. Samples of nasal discharge, feces, plasma, and sera were collected daily until 10 days post inoculation (dpi), followed by weekly collection until 141 dpi and then twice-weekly collection until the end of the experiment (1,085 dpi). The virus in the digestive tract might have been quickly inactivated and excreted; therefore, viral RNAs were not detected from nasal discharge and feces at 421 dpi, 10 days after the onset. This study showed that the BCoV RNA was long-lasting, having been detected from the nasal discharge of cattle that had been maintained in an isolated room of a high-containment facility to prevent virus intrusion from outside.

cord-309663-h06876ok	In this manuscript, we describe the rationale, major steps, timeline, stakeholders, and important events that lead to the assembling of a true integrated multi-institutional and interdisciplinary team that worked toward and accomplished the ambitious goal of developing a ZTB roadmap that was published in English, Spanish, and French (13) (14) (15) to address the global challenges regarding the prevention, surveillance, diagnosis, and treatment of zoonotic TB (ZTB), globally. For this reason, as countries move toward detecting the 3 million TB cases estimated to be missed annually, and in light of the endorsed WHO "END TB" strategy, the Tripartite, The Union and the key organizations concerned with human and animal health, agriculture and TB joined forces to develop a Zoonotic TB Road Map outlining medium-and long-term milestones to globally address the prevention, surveillance, diagnostic, and treatment challenges faced by persons with ZTB.

cord-310055-9qj8d2f7	Cryptosporidiosis is a worldwide infection caused by the protozoan Cryptosporidium, a parasite that infects many species of vertebrates, including humans, causing acute gastroenteritis, abdominal pain, and diarrhea [1] . Cryptosporidiosis is transmitted primarily through the fecal-oral route, i.e., by ingesting viable oocysts of animal and/or human origin, emitted with feces that contaminated food or water [2, 3] . 9-10 μm in diameter), another coccidian protozoan parasite that infects the intestine of humans causing acute diarrhea, much attention should be given when evaluating stool samples since the oocysts of both parasites are autofluorescent and acid-fast ( Figure 2 ) [46, 47] . In addition to the above described methods, watery or mushy stools can be examined for the laboratory diagnosis of cryptosporidiosis using different techniques such as the enzyme-linked immunosorbent assay (ELISA) and immunochromatographic test, which have good sensitivity and specificity for detection of Cryptosporidium antigens [51] [52] [53] .

cord-310095-1pxki8y8	title: Detection and clinical characteristics analysis of respiratory viruses in hospitalized children with acute respiratory tract infections by a GeXP‐based multiplex‐PCR assay BACKGROUND: The information regarding viral epidemiology and clinical characteristics in hospitalized children with acute respiratory tract infection (ARTI) in central Fujian is limited. Thus, to better understand the information about the epidemiology of the pathogens in pediatric hospitalized patients with ARTI and provide effective prevention strategies, we aimed in this study to investigate the epidemiology of respiratory viruses via a GeXP-based multiplex-PCR assay in children under 15 years of age in pediatrics. 10 In this study, we used GeXP-based multiplex-PCR assay to detect 11 kinds of virus, as well as mycoplasma pneumonia and chlamydia pneumoniae in 386 samples from hospitalized children with acute respiratory tract infection over a period of 1 year. In summary, the GeXP-based multiplex-PCR assay allows us to quickly detect multiple respiratory infections caused by viruses.

cord-310182-muybvyqa	Most previous economic studies on global influenza pandemics have focused on income losses, through reductions in the size of the labour force and productivity, increases in absenteeism and, importantly, as the result of individual and social measures that interrupt transmission, but disrupt economic activity. 2, 27 Beyond influenza, the value of mortality risks has been included in estimating the costs of vaccine-preventable diseases 28 and in evaluating the economic burdens posed by rheumatic heart disease. Given the uncertain nature of an influenza pandemic, in terms of both when it may occur and how large the mortality risks will be, we applied an expected-loss framework that accounts for the uncertainty over a long period of time. 46, 48 As in many previous attempts to estimate the economic losses associated with a pandemic, many previous attempts to estimate the social costs of carbon have focused on national income accounts, without any explicit valuation of the increases in mortality resulting from climate change.

cord-310240-otf9ruvj	METHODS: ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively. CONCLUSION: We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support. Although this treatment was omitted in recent sepsis guidelines due to a lack of supporting evidence in high-quality trials [8] , several studies, including one meta-analysis, describe beneficial effects of immunoglobulins in acute pneumonia induced by drug-resistant bacterial infections [9] [10] [11] . Based on these data, we treated patients with ARDS requiring ECMO therapy with IgM-enriched immunoglobulins immediately after intensive care unit (ICU) admission. The purpose of this analysis was to systematically investigate the potential effect of IgM-enriched immunoglobulins on the outcomes of ARDS patients requiring ECMO therapy.

cord-310563-71940dh7	From the 673 amino acids of FyuA protein, a region from 1 to 492 was selected for containing more linear epitopes and the processing scores obtained were significant for MHC class I and class II binding. These OMPs are not always conserved in different genus of bacteria but their lies a probability of presence of some conserved peptide sequence in these OMPs. In this study we have taken into account the proteins which have proved to be potential vaccine candidates on the basis of invivo research work on animal models. Protein sequences of Yersiniabactin receptor of Escherichia coli UMN026 and Flagellin of Stenotrophomonas maltophilia were analyzed for the presence of linear epitopes using Bepipred portal of IEDB server. Amino acid sequences of both the proteins were analyzed for the presence of linear epitopes using the Bepipred prediction tool of IEDB server. Similarly, for Flagellin protein results in Fig. 3(A) show that 1353 significant peptide allele interactions were predicted by the server and among these, 1168 interactions were from the selected region (Supplementary information SI.2.).

cord-311176-dlwph5za	The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. METHODS: We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. In this retrospective cohort study, we found that ECMO rescue therapy was associated with lower in-hospital mortality, better oxygenation, and fewer organ failures compared to historical control (usual care) in patients with severe MERS-CoV. described the use of ECMO in two patients with acute respiratory failure secondary to MERS-CoV infection in France, where both patients developed severe hypoxia and increasing oxygen requirements, leading to mechanical ventilation and ECMO use. Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study

cord-311795-kvv3fx2n	An important area of infection prevention and control (IPC) is the optimal use of personal protective equipment (PPE) by healthcare workers (HCWs), including masks for protection against respiratory pathogens. An important area of infection prevention and control (IPC) is the optimal use of personal protective equipment (PPE) by healthcare workers (HCWs), including masks for protection against respiratory pathogens. Respiratory infectious diseases are transmitted via contact, droplet and/or airborne modes, necessitating healthcare worker (HCW) use of surgical masks or respirators and other personal protective equipment (PPE) together with appropriate hand hygiene. During periods of high-risk for respiratory infectious disease, such as the annual influenza season or a novel influenza pandemic, health departments have, and may, encourage or mandate the use of a protective respiratory mask by the general public to minimise the transmission from symptomatic people to others [49] .

cord-312001-8p7scli8	Consequently, animal cells have evolved devoted pathways which (1) sense and recognize pathogen-associated molecular patterns (PAMPs) and, more particularly, virus-associated molecular signatures; (2) initiate signaling cascades stemming from the site of detection, translocating the information to the nucleus; and (3) induce a transcriptional program that confers an antiviral state to the host ( Figure 1 ). While the cytosolic recognition of viral RNA is almost exclusively mediated by RLRs, several proteins have been proposed to play a role in DNA sensing and triggering innate immune responses, such as the DNA-dependent activator of IFN-regulatory factors (DAI), DDX41, RNA polymerase III, IFI16 and DNA-PK [62] [63] [64] [65] [66] [67] . Although the pathway leading to the transcriptional activation of Vago is still poorly understood in insects, these studies established that DExD/H-box helicase containing proteins, like Dicer and RLRs, may represent an evolutionarily conserved set of viral nucleic acid sensors that direct antiviral responses in animals [159] .

cord-312206-0pkbbb99	In this present study, we developed a detection system of microbes from porcine respiratory by using TaqMan real-time PCR (referred to as Dempo-PCR) to screen a broad range of pathogens associated with porcine respiratory diseases in a single run. We selected 17 porcine respiratory pathogens (Actinobacillus pleuropneumoniae, Boldetella bronchiseptica, Haemophilus parasuis, Pasteurella multocida, Pasteurella multocida toxin, Streptococcus suis, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma hyosynovie, porcine circovirus 2, pseudorabies virus, porcine cytomegalovirus, swine influenza A virus, porcine reproductive and respiratory virus US strain, EU strain, porcine respiratory coronavirus and porcine hemagglutinating encephalomyelitis virus) as detection targets and designed novel specific primer-probe sets for seven of them. A total of 30 lung samples from swine showing respiratory symptoms on six farms were tested by the Dempo-PCR to validate the assay''s clinical performance. The objective of this study is to develop a system based on TaqMan real-time PCR that can detect 17 pathogens, including viruses and bacteria, associated with porcine respiratory diseases in one run.

cord-312603-ear9cyri	In this paper, we consider the problem of identifying and tracking communities in graphs that change over time – dynamic community detection – and present a framework based on Riemannian geometry to aid in this task. We describe the basics of our framework in the "Riemannian geometry and dynamic graphs" section, show how it can be applied to dynamic clustering in "A Riemannian framework for dynamic community detection" section, and compare the Riemannian methods with an entry-wise linear approach on synthetic and real network data in the "Computational experiments" section. A geodesic interpolation trajectory has a constant velocity, produces an eigenvalue product that varies linearly between endpoints that are connected graphs, and can be extrapolated indefinitely without leaving the manifold of positive-semidefinite manifolds (with constant nullspace dimension).

cord-312738-p5macofk	To overcome the barriers identified in this study a multifaceted intervention is needed that includes teaching young children good hand hygiene habits, PCPs prompting parents and young children to practice hand hygiene when coming for an RTI consultation, reassuring parents that effective hand hygiene practice will not lead to abnormal psychological behaviour in their children, and community health promotion education campaigns. Data for this research were derived from a larger mixed methods qualitative study exploring PCPs and parents'' views, knowledge and attitudes towards their hand hygiene practice and reducing RTI transmission in children < 5 years of age. All participants consented to up to an hour interview or focus group to explore their views, knowledge and attitudes towards management of respiratory tract infections, including prevention strategies such as influenza vaccination and hand hygiene in children < 5 years of age.

cord-312772-fxc4zwr3	Previous studies of community-acquired pneumonia (CAP) have reported varying incidences of Gram-negative bacilli (GNB). In this prospective study we estimate the prevalence of GNB in patients admitted to hospital for CAP, identify their risk factors and clinical predictors and assess CAP-related mortality in Cambodia, a low-income country in Southeast Asia. On admission the following investigations were performed on all patients: chest X-ray, collection of blood and non-induced sputum for microbiological cultures and consecutive samples for direct sputum examination for acid-fast bacilli (AFB) and nasopharyngeal swab for polymerase chain reaction tests for 18 viral respiratory pathogens, including human metapneumovirus; respiratory syncytial virus (RSV); human bocavirus; influenza A and B viruses; coronaviruses OC43, 229E, HKU-1, NL63 and SARS; parainfluenza viruses 1-4; adenoviruses; rhinovirus and enteroviruses. In this prospective observational study from two provincial hospitals in Cambodia, 8.6% of all patients with CAP had infection caused by GNB.

cord-312959-07sn6d9r	RESULTS: Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions. Toward finding a safe and effective hygiene agent against viruses, we evaluated the durability of antiviral effects of green tea extract (GTE) as a powder type and a solution type over extended periods at various temperature conditions using human influenza A/H1N1 virus. The results showed that 0.05% and 0.1% GTE solutions, stored at 4°C and 25°C as long as 56 days, maintained potent viral inactivating activities, completely removing the viral plaque-forming ability of 10 6 PFU of the viruses (Fig. 2a & b) . Based on the previous report that ascorbic acid stabilized green tea catechins [35] , we examined the effects of the addition of common food preservatives such as ascorbic acid, citric acid, and sodium benzoate on the viral inactivating activity of GTE.

cord-313062-lpxmmbpy	PURPOSE: To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. CONCLUSION: Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months. The aim of this study is to compare the frequency and disease severity of influenza and RSV infections among children < 24 months hospitalized with respiratory symptoms during the peaks of five influenza seasons. In the province of Quebec, Canada, a prospective surveillance study with virologic assessment for influenza and other respiratory viruses was conducted during the peak weeks of influenza circulation among patients admitted for acute respiratory symptoms to four acute-care hospitals since 2012-2013. In conclusion, even during the peak weeks of influenza, more than half of hospitalizations for respiratory infections in children < 2 years of age was due to RSV, with a clinical course more severe than influenza notably among infants < 3 months.

cord-313337-8w6bxqx4	In order to establish models for the study of human nasal pathogens, it is important to understand the parallelisms and differences that exist among the olfactory systems and NALT of different species at the cellular, molecular and functional level. In this review, we summarize the main differences in the anatomical organization of NALT and the nasal immune responses in different vertebrate groups as a way to identify species that are more or less suitable for the investigation of specific Finally, several human nasal diseases appear to originate from members of the nasal microbiome, which harbors numerous pathobionts including S. The study of nasal immune responses in birds is extensive, not as models of human disease, but rather due to the important threatening pathogens that infect the respiratory tract of birds including avian influenza virus, infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) (de Geus et al., 2012) .

cord-313777-eydkfqi2	This paper proposes a relative space-based GIS data model of moving objects (RSMO) to construct, operate and analyze moving objects'' relationships and introduces two algorithms (relationship querying and relative relationship dynamic pattern matching) to derive and analyze the dynamic relationships of moving objects. It''s better computational performance of the proposed model when analyzing the relative relationships of moving objects than the absolute methods in a famous commercial GIS software based on this experimental results. Therefore, the motivation of this paper is to create a relative space-based GIS data model of moving objects and propose some basic GIS operators for analyzing moving objects, which changes the analysis of current absolute space-based GIS models and facilitates the efficient computation of real-time relative relationship dynamics, such as the surrounding dynamics and motion trends of crowds near moving objects.

cord-313869-3x2qf3yu	Based on the ability of cellular automata to model complex problems, this paper considered that, in real society, population mobility is caused by economic development, living environment, education level, and other factors, and that population density, sex ratio, and age structure of area also have some influence on the spread of infectious diseases. In order to study and analyze the influence of population density on infectious disease spread, each individual is mapped into a cell in the cellular automata model. Without considering other factors, this paper focused on the influence of three factors, namely, population density, individual heterogeneity, and mobility on infectious disease spread, and the SLIRDS model based on cellular automata was constructed. Without considering other factors, this paper focused on the influence of three factors, namely, population density, individual heterogeneity, and mobility on infectious disease spread, and the SLIRDS model based on cellular automata was constructed.

cord-314340-ltx4w9zh	During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). Indeed, 5 µM of AA treatment could inhibit histone H3 acetylation as demonstrated by the reduced levels of H3K9ac relative to the control, but AA increased the levels of H3K9ac in the context of virus infection in comparison to the mock treated but infected cells ( Figure 3E ,F).

cord-314415-yr0uxok2	In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The result showed that Bo-Circo-like virus CH is clustered into a independent branch with seven reported strains of proposed family Kirkoviridae and eight CRESS-DNA virus strains recently submitted to GenBank database; Bo-Circo-like virus CH is more closely related to Po-Circo-like virus and shows significant genetic differences with viruses in the families Circoviridae, Nanoviridae, Geminiviridae Genomoviridae, Bacilladnaviridae and Smacoviridae (Fig. 3) . The sequence alignments included strain Bo-Circo-like virus CH in this study, representative members of the Circoviridae, Geminiviridae, Nanoviridae, Genomoviridae, Bacilladnaviridae and Smacoviridae families, the proposed new genera of krikoviruses, and still unassigned novel CRESS-DNA viruses with the best BLASTp matchs in GenBank database. The sequence alignments included five Bo-Circo-like virus strains detected in this study and seven reported strains of the proposed family Kirkoviridae.

cord-314460-dbrp4vxc	We conducted a review of the literature to evaluate the processes and procedures utilized for safe AE high-level containment transport (AE-HLCT) of patients with HHCDs. Methods A literature search was performed in PubMed/MEDLINE (from 1966 through January 2019). A literature search was performed in PubMed/MEDLINE (from 1966 through January 2019) with the following terms: 1) "aeromedical isolation," 2) "aeromedical evacuation" OR "transportation of patients" OR "air ambulance" OR "HEMS" OR "Helicopter" AND "ebola" OR "lassa" OR "viral hemorrhagic" OR "highly infectious" OR "highly hazardous" OR "contagious" OR "communicable" OR "Middle East respiratory syndrome (MERS)" OR "SARS" OR "smallpox", and 3) "mobile" OR "transport" AND "high-level isolation" OR "high containment". Biselli et al 22 noted training includes personal protective equipment (PPE), patient management on ground and inflight, and equipment decontamination, whereas Christopher and Eitzen, 17 24 which detailed a 2006 Royal Air Force mission, remarked on the benefit of in-flight, just-in-time training that occurred on the flight to the patient, while also stating that the mission resulted in routine air transport isolator exercises.

cord-314567-purplsjn	HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. As studies using the whole virus do not allow for the elucidation of the specific molecular mechanisms in which each protein is implicated, in this work, we focused on a single viral protein, showing that in CD4 + T cells, HCV core protein mostly localizes in the nucleus and specifically in the nucleolus where it is greatly enriched.

cord-314841-b5l6epy3	Analysis of the host transcriptional response during respiratory viral infection using in-vitro, animal models and natural and experimental human challenge have furthered the understanding of the mechanisms and predictors of severe disease and may identify potential therapeutic targets to prevent and ameliorate illness. In addition to sensitive and rapid diagnostic testing, new molecular techniques allow an understanding of viral evolution, mechanisms and predictors of severe disease, interrogation of vaccine responses, improved bacterial and viral diagnostics and associations of viral infections with non-respiratory medical events. A number of candidate genes influencing respiratory virus susceptibility have been identified in animal and human studies and involve host virus interactions, innate immune signaling, interferon related pathways and cytokine responses (Table 1) [49] [50] [51] [69] [70] [71] [72] [73] [74] [75] . In addition, two compartments, the respiratory epithelium and blood can be sampled in human studies and interrogated using different viruses or viral strains to develop gene signatures for prognosis, as indicators of severity and to identify potential therapeutic targets.

cord-314867-qg3hl5ft	Bavachin and bavachinin showed good anti-MERS-CoV activities of 2.9 and 7.9 μM respectively by phenotypic cellular screening with vero cell. Total 12 compounds of bavachinin derivatives in four core structures were evaluated to figure out their anti-MERS-CoV activity and cell-cytotoxicity by cellular phenotypic screening method as shown in Table 1 . The further alkylations of phenolic OH of 1a with isopropyl and benzyl group decreased the anti-MERS activities (Entry 3 and 4 in Table 1 ). Interestingly, O-isopropyl Note and O-benzyl derivatives (2c and 2d, respectively) showed similar activity with 2a (non-substituted) better than 2b (Omethylated), but the cytotoxicity for vero cell also increased. As a conclusion, a series of 2-phenylchroman-4-one derivatives were synthesized for the chemical modifications of bavachin, and they exhibited anti-MERS activities in vero cell. We expect the study on bavachin derivatives can contribute to the development of anti-MERS drug.

cord-314915-b6aqwubh	Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. In the context of our work on the camelid immunogenome, the objective of this study was to characterize the genomic content of NKC and LRC with special focus on genes encoding natural killer cell receptors for MHC class I ligands in the two domestic camel species, C. dromedarius NCBI reference genome by tblastn algorithm of NCBI''s BLAST ®1 for orthologous protein sequences to killer-cell lectin-like receptors recently identified in cattle as KLR genes (Schwartz et al., 2017) . The general organization of the two genomic regions, the natural killer complex (NKC) and the leukocyte receptor complex (LRC), containing genes and gene families encoding the NK cell receptors annotated based on the dromedary genome assembly CamDro2, was established and is represented in Figure 1 .

cord-315355-a25ba7dz	The four SpDCoV strains identified in this study share a slightly higher identity (94.4-94.6% and 96.0-96.4%) to a sparrow CoV strain HKU17-6124 than to PDCoV strains (93.4-93.6% and 95.3-95.8%) in their ORF1ab and N proteins, respectively ( Fig. 1b and Supplementary Table S2 ). In contrast, the four SpDCoV strains share a significantly lower identity to sparrow CoV HKU17 (58.2-58.6%) than to three PDCoV strains (82.7-87.7%) in their S protein (Fig. 1b and Supplementary Table S2 ). In addition, they share a relatively lower identity (90.7-91.5% and 93.5-95.5%) to sparrow CoV HKU17 than the PDCoV strains (94.9-95.8% and 96.1-98.1%) in their E and M proteins, respectively (Supplementary Table S2 ). These findings were also confirmed by phylogenetic tree analysis of amino-acid sequences in which the four SpDCoV strains clustered together and were closely related to PDCoV and sparrow CoV HKU17 strains in ORF1ab, E, M, and N trees ( Fig. 1c and Supplementary Figure S1 ).

cord-317254-6q4nzv9d	title: Learning from recent outbreaks to strengthen risk communication capacity for the next influenza pandemic in the Western Pacific Region This article discusses the lessons learnt in risk communication during the response to recent outbreaks in the World Health Organization''s Western Pacific Region. 15 Countries are encouraged to learn from recent outbreaks and emergencies and to invest in their internal capacity for risk communication as per the Asia Pacific Strategy for Emerging Diseases and Public Health Emergencies (APSED III). Ten years after SARS, China proactively informed the public and international community about human cases of avian influenza (H7N9), demonstrating the benefit of timely and transparent risk communication. 10 While social media was used to listen to the public following the discovery of human cases of H7N9, the response to an outbreak of influenza-associated severe acute respiratory infections (SARI) in Fiji in 2016 showed that more traditional means of communication still have a place in effective risk communication.

cord-317389-trvleobp	title: Rapid multiplex microfiber-based immunoassay for anti-MERS-CoV antibody detection The bulk of this robust antibody immunoassay platform could be installed into a compact syringe-driven cassette device, which could perform multiplex antibody immunoassay for antibodies specifically against Middle East respiratory syndrome coronavirus (MERS-CoV) with rapid preparation amounting to a total of 5 min, as well as high sensitivity and specificity for the MERS-CoV down to 200 μg/mL. In addition to the previously established fluorescently-linked immunosorbent assay (FLISA) microfiber platform [28, 37] , the microfiber mats were pre-patterned with O 2 plasma to create multiple hydrophilic zones with different antigens, and thus creating a multiplex detection system. Rapid immunoassay testing using the cassette platform were performed in following steps: (1) antigen immobilization, (2) blocking, and (3) antibody capture. The 8-layered 10 wt% ESPS fiber mat samples were treated by O 2 plasma spot treatment for different time lengths, then tested for protein adsorption to the surface.

cord-317455-6qx0v28w	Turkey coronavirus, originally identified in the USA in the 1970s as one of the agents responsible for an acute enteritis named bluecomb (Panigrahy, Naqi, & Hall, 1973; Ritchie, Deshmukh, Larsen, & Pomeroy, 1973) and since with a multifactorial disease known as poult enteritis complex of turkeys (PEC) , has now been detected in most areas where turkeys are farmed Cavanagh et al., 2001; Dea & Tijssen, 1988; Domańska-Blicharz, Seroka, Lisowska, Tomczyk, & Minta, 2010; Martin, Vinco, Cordioli, & Lavazza, 2002; Maurel et al., 2009; Teixeira et al., 2007) , although TCoVs isolated in Europe have been shown to have a different genetic lineage to those isolated in the USA (Brown et al., 2016; Maurel et al., 2011) . At 1-day post-inoculation (dpi), two SPF turkey contacts were introduced into groups 1-4 as sentinels to demonstrate horizontal transmission of infectious virus. They were housed in a negative pressure room, under the same rearing conditions as in Exp 2, with three 11-day-old SPF turkeys introduced as contact-birds at 1 dpi to demonstrate horizontal transmission.

cord-317587-rrx2r4n2	title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs. Infectious bronchitis (IB) is one of the major viral diseases affecting the poultry industry globally. Our results indicated that there was a remarkable change in genetic diversity, dominant genotypes, and selection pressure of IBV strains in southern China over the past decade compared with the previous period of 1985-2007. Molecular characterization of major structural protein genes of avian coronavirus infectious bronchitis virus isolates in southern China

cord-317688-mr851682	Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in September 2012 [1] . The first patient (index case) with MERS-CoV infection was a 68-year-old Korean man returning from the Middle East. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea Clinical implications of 5 cases of Middle East respiratory syndrome coronavirus infection in a South Korean outbreak Renal complications and their prognosis in Korean patients with Middle East respiratory syndrome-coronavirus from the central MERS-CoV designated hospital Successful treatment of suspected organizing pneumonia in a patient with Middle East respiratory syndrome coronavirus infection: a case report

cord-318181-xxc7vdnt	A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. Nineteen predictive variables were included: age, sex, fever (temperature !38 C), one composite respiratory symptom (the presence of cough, bloody cough, shortness of breath, or chest pain), one composite gastrointestinal symptoms (the presence of diarrhea, vomiting, or nausea), seven MERS-CoV potential risk factors (contact with sick patients or camels, severe illness (defined according to the patient''s clinical status, ''yes/no'', which is based on clinical judgment), diabetes, lung disease, liver disease, renal disease, and heart disease), and seven laboratory measurements (white blood cell (WBC) count (Â10 9 /l), platelets (Â10 9 /l), creatinine (mmol/l), bilirubin (mmol/l), alanine aminotransferase (ALT; U/l), aspartate aminotransferase (AST; U/l), and albumin (g/ l)).

cord-318229-29cgwivt	An outbreak case is a patient with a positive RSV laboratory testing in samples from the upper or lower respiratory tract and a definite or possible nosocomial onset. Considering bed and room occupancy on the ward during the outbreak, direct patient to patient transmission (e.g. via droplets or contaminated surfaces) in cases 1 and 2 as well as 3 and 4 seemed epidemiologically possible as each pair was accommodated in the same room before samples were tested positive for RSV. Overlying sequence information from different quasispecies detected in the samples are highlighted in a box measures, in particular single room accommodation for contact patients (quarantine), suspension of all social activities, and surgical masks for all HCWs and visitors at any time, addressed the postulated RSV transmission pathways during this outbreak. Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward

cord-318238-56x5q7f6	METHODS: A total of 682 infants suffering from bronchiolitis, categorized based on the final clinical outcome as mild or severe, were genotyped for IL28B SNPs rs12979860 and rs8099917. CONCLUSION: SNPs rs12979860 and rs8099917 correlate with the severity of bronchiolitis and display a sex bias, where GG rs8099917 and TT rs12979860 genotypes are associated with a mild disease in girls but not in boys. Results revealed no correlation between the severity of bronchiolitis and viral coinfection but being homozygotes for the minor allele (G) for SNP rs8099917 linked with a mild bronchiolitis among hospitalized patients (OR: 0.55 (95% CI: 0.32-0.95), p = 1; Table 3 ). No differences were observed in sex distribution, gestational age, birth weight, type of delivery, nutritional status, maternal pregnancy diseases, and personal history of atopy ( Fig. 3 Correlation between clinical severity of global bronchiolitis or RSV bronchiolitis and IL28B SNPs rs12979860 and rs8099917.

cord-318340-hptjqmrl	We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. If a case is reported to the PUE system, the local center for disease control and prevention (CDC) will conduct a field investigation, collect respiratory specimens and send them to a national influenza surveillance network laboratory for testing of avian influenza viruses and, if associated with clusters of respiratory disease or relevant travel history, testing of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). For patients with illnesses meeting the PUE case definition, the surveillance officer used a standard questionnaire to collect information from the hospital information system related to demographics and, if available, epidemiological risk factors, including exposures to poultry, patients with similar symptoms, and travel history.

cord-318495-1w74wf02	The demonstration of hotspots for the generation of copyback DVGs from respiratory syncytial virus (RSV) and the identification of specific nucleotides that determine where copy-back DVGs rejoin further demonstrate that the generation of copy-back DVGs is not completely random, but instead that specific sequences encoded in the viral genome direct or facilitate their formation 50 in some infections, DVG generation is not a completely stochastic process and, instead, virus-encoded sequences favour the production and/or amplification of predominant DVGs. It remains to be determined whether conservation is a property of certain DVG types and which specific sequences and/or RNA structures lead to DVG generation in these conditions. Persistent infection with infectious pancreatic necrosis virus mediated by defective-interfering (DI) virus particles in a cell line showing strong interference but little DI replication I Interferon-inducing defective-interfering particles as mediators of cell sparing: possible role in persistent infection by vesicular stomatitis virus

cord-318683-1yxurnev	• Personal protective equipment should be improved to become more user friendly • Improved surge capacity (the ability to rapidly gear up the health system to cope with a sudden, large increase in patients with a serious, contagious disease) is required, particularly in peripheral areas • The capacity of general and reference laboratories should be increased, to keep developing faster, more reliable diagnostic tests • New and improved vaccines (pre-exposure and post-exposure) and treatment regimens should be developed • Clinical and environmental surveillance needs to increase • Syndromic surveillance systems can be maintained to register suspicious or confirmed cases reported by physicians, and the data can be used to improve risk communication programmes and to monitor the progress of an outbreak • An adequate stockpile of vaccines and medications should be maintained, both nationally and internationally • To improve preparedness for natural and bioterrorist outbreaks, international cooperation should include joint exercises involving multiple countries and constant improvement in the exchange of information on potential bioterrorism threats and management

cord-318731-vlszl0i8	title: Molecular characterization of HLJ-073, a recombinant canine coronavirus strain from China with an ORF3abc deletion Interestingly, sequence analysis suggested that HLJ-073 contained a 350-nt deletion in ORF3abc compared with reference CCoV isolates, resulting in the loss of portions of ORF3a and ORF3c and the complete loss of ORF3b. This is the first report of the isolation of strain HLJ-073 in China, and this virus has biological characteristics that are different from those of other reported CCoVs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04296-9) contains supplementary material, which is available to authorized users. In the present study, we report the emergence and molecular characterization of an, FCoV-like recombinant CCoV-HLJ-073, which was isolated from a fecal sample from a dead dog that exhibited enteritis. We isolated a canine coronavirus with a deletion in the ORF3abc region from a dead dog in China.

cord-318826-l922zqci	In large free stall dairies, it is increasingly common to encounter Salmonella infection as an endemic challenge with clinical presentations that are highly variable, ranging from the classic textbook description of reproductive losses and enteric disease in adult cattle through to lower impact problems with fevers of unknown origin, little to no diarrhea, and only modest consequences in terms of appetite and milk yield reduction. 29 Hence, if one is merely trying to obtain a yes or no answer or identify and track specific serovars, or antimicrobial susceptibility patterns over time, composite fecal samples are typically collected from areas on dairy operations where manure accumulates from a majority of adult animals, such as holding pens, alleyways, and lagoons. Prompt diagnosis, treatment, and isolation are important during an outbreak in adult cattle and environmental sampling to include bulk tank milk and high-risk housing areas should now be considered a routine part of disease prevention and surveillance.

cord-318872-0e5zjaz1	BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. The incubation period was reported to be 6.83-7 days in South Korea [4, 5] , but 5.5 in a study using data from multiple areas [6] and 5.2 in Saudi Arabia [7] . Although one study from Saudi Arabia reported longer than 17 days from onset to death [36] , Sha et al., comparing data between the Middle East and South Korea, reported similar periods of 11.5 and 11 days, respectively [29] . Mortality of MERS patients was found to be 20.4% in South Korea based on a report including all cases [27] , but most studies from Saudi Arabia reported higher rates, from 22 to 69.2% [7, 22, 33, [37] [38] [39] . Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea

cord-319031-9ubzr2f8	

cord-319399-r5hgfsxz	title: Japanese encephalitis virus: A multi-epitope loaded peptide vaccine formulation using reverse vaccinology approach The predicted epitopes identified in five proteins selected in this study could be promising for formulating a peptide vaccine against JEV and hence, could prevent the spread of JEV in affected individuals. In this study, the potential epitopes for peptide vaccine formulation were identified in five proteins of JEV namely E, prM, NS1, NS3 and NS5. In a study, the probable epitopes were identified from E6 protein of hrHPVs and these epitopes were reported to possess competence in preparing successful peptide vaccine against hrHPVs. Based on in silico approach, it was suggested Table 2a Immunogenicity (Ig) and number of aliphatic amino acids in T-cell epitopes of JEV (Hopp & Woods approach, 1981 The present study suggested that a multi-epitope-based peptide vaccine against JEV could be developed by combining the promising Bcell and T-cell epitopes found in E, prM, NS1, NS3 and NS5 proteins.

cord-319651-u7yrcto7	OBJECTIVES: It was supposed to analyze status and affecting factors in water and food-borne communicable disease by screening entrants with diarrhea symptom at the point of entry in Korea METHODS: Symptomatic travelers with water and food-borne communicable diseases who entered Korea were diagnosed by a health declaration and detection of causative agents in water and food using laboratory tests. The rate of detection of causative agents of communicable disease pathogens in travelers from Southeast Asia entering Korea was 70.2%, which was higher than people arriving from East Asia and Central Asia (57.5%; p < 0.001). CONCLUSION: The positive ratio of causative agents of water and food-borne communicable diseases was high among travelers that had entered Korea from July to September, with a high number among entrants from Southeast Asia. Using data from the quarantine information system in KCDC, this study surveyed the health status of travelers entered Korea who were quarantined during 2013 to 2017 because they had symptoms of communicable disease.

cord-319729-6lzjhn8j	title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. To assess innate immune responses in astrocytes, cells were infected with DRV or B2c at an MOI of 0.1 and the expression of several proteins involved in the MAVS signaling pathway, namely, RIG-I, p-IRF7, STAT1 and IFIT1 (ISG56), was measured by Western blot.

cord-319871-qnijw08y	title: Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms S. aureus expresses a wide repertoire of surface proteins that recognize cellular adhesive molecules and it is therefore able to adhere to and internalize into lung epithelial cells, which protects the bacteria from the host immune system and facilitate chronic infection [20] . A recent prospective study investigated the differences in the nasopharyngeal microbiome during acute respiratory tract infections due to human rhinovirus or RSV in 135 infants aged less than 6 months [38] . Several potential mechanisms through which rhinovirus increases susceptibility to bacterial infection have been demonstrated in vitro in epithelial cells of the upper and lower airways. aureus carriage and non-influenza respiratory virus infections, as well as deeper insights into mechanisms of interactions between these different pathogens.

cord-319942-ava86u8y	We aimed to evaluate the prevalence of Human Rhinovirus (HRV) infection in the acute attack of wheezy chest which began after a respiratory illness. A prospective study including children aged 2 months to 5 years presenting to the emergency department (ED) of Cairo University Children Hospitals, with an acute wheezy episode (signs of respiratory distress and expiratory wheezes on auscultation and/or hyperinflation of the chest on chest radiograph) either for the first time or recurrent wheeze defined as >2 reports of wheezing in the first 3 years of life. 5 Jartti and colleagues, 2004 studied 161 children hospitalized with acute expiratory wheezing and the presence of Rhinovirus, RSV, Coronavirus, Metapneumovirus and Enterovirus RNAs were detected in the nasal secretions. 6 Another study done on 626 hospitalized children admitted with acute expiratory wheezes, viruses were detected in the nasopharyngeal aspirates by PCR.

cord-320053-uceukiie	Abstract It is generally accepted that moderate amounts of exercise improve immune system functions and hence reduce the risk of infection whereas athletes engaged in regular prolonged and/or intensive training have a higher than "normal" incidence of minor infections, especially of the upper respiratory tract (URT, e.g., common cold and influenza). In contrast to animal research, human studies (attempting to discern the effects of prolonged exercise/intense training on URTI) have mainly involved monitoring athletes following heavy exertion (i.e., relied on natural exposure to pathogens) but only a limited number of these have verified that symptoms are due to infectious agents (pathogens) (Spence et al., 2007; Schwellnus et al., 2010; Hanstock et al., 2016) .

cord-320107-wels9wt7	Resolution of respiratory virus infection requires not only the elimination of the Keywords ► lung transplantation ► community-acquired respiratory viruses ► ribavirin ► bronchiolitis obliterns syndrome The incidence of community-acquired respiratory viruses (CARVs) is $15 cases per 100 patient-years after lung transplantation (LTx). The incidence of community-acquired respiratory viruses (CARVs) is $15 cases per 100 patient-years after lung transplantation (LTx). 8 In contrast to the nonimmunosuppressed host, CARV infection usually leads to more severe illness in the lung transplanted recipient with a higher incidence of respiratory failure. ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study

cord-320325-sjab8zsk	Using purified KSHV SOX protein, we reconstituted the cleavage reaction in vitro and reveal that SOX displays robust, sequence-specific RNA binding to residues proximal to the cleavage site, which must be presented in a particular structural context. Using an RNA substrate that is efficiently cleaved by SOX in cells, we revealed that specific RNA sequences within and outside of the cleavage site significantly contribute to SOX binding efficiency and target processing. Given that both substrates contain the requisite unpaired bulge at the predicted cleavage site (see Figure 2A and Supplementary Figure S2 ), these observations suggest that additional sequence or structural features impact SOX targeting efficiency on individual RNAs. Two SOX point mutants, P176S and F179A, located in an unstructured region of the protein that bridges domains I and II have been shown to be selectively required for its endonucleolytic processing of RNA substrates (Supplementary Figure S3A and S3B) (8, 21) .

cord-320508-egw7bvzf	The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The hypothesis presented here is that annexin V''s therapeutic administration in Ebola can prevent its Th1 cell generated inflammatory cytokine storm, stop the cascade generated hemorrhagic consumptive coagulopathy and prevent macrophage and dendritic cell infection.

cord-320559-up1q3k6q	Porcine epidemic diarrhea virus (PEDV) is the highly contagious, causative agent of an economically important acute enteric disease in pigs of all ages. In total, 838 blood samples from sows from 267 farms and 101 samples from wild boars were collected from May till November 2014 and tested for antibodies against PEDV by ELISA. The number of required blood samples from animals and farms to estimate the seroprevalence of PEDV in Dutch sow herds was calculated based on the following assumptions: PEDV is highly contagious and no vaccination against this virus was carried out in the Netherlands. For the detection of PEDV antibodies in serum samples an in-house indirect ELISA based on the viral spike (S) protein S1-part of the G2b strain GDU (Non-S-INDEL, GenBank KU985230.1) was used, similar as the ELISA previously described (Gerber et al., 2014) .

cord-320583-te8fv3gq	In adult HMPV encephalitis cases influenza-like symptoms or respiratory infection (bronchiolitis, bronchitis or interstitial pneumonia) were reported in all, though in our and Tan''s case the patient was admitted because of other complaints, and respiratory tract infection was only revealed by chest radiography [1, 3, 4] . In Fok''s case the patient was treated with a 5 days course of methylprednisolone because of no clinical improvement was noticed and autoimmune encephalitis/cerebral vasculitis was suspected [3] . In patients with suspected viral encephalitis, HMPV may be considered as the causative agent, and testing for HMPV in nasopharyngeal aspirate and CSF is then required. Adult human metapneumovirus encephalitis: a case report highlighting challenges in clinical management and functional outcome Human metapneumovirus in the cerebrospinal fluid of a patient with acute encephalitis Encephalitis-associated human metapneumovirus pneumonia in Adult Cerebrospinal fluid findings in an adult with human metapneumovirus-associated encephalitis

cord-320674-skmxrkhf	In a future-oriented approach, technological opportunities for convergence are suggested by predicting potential technological knowledge flows (TKFs) between heterogeneous fields. To solve the research questions, a new approach to exploring the TOD for technological convergence is proposed by means of link prediction in patent-citation networks and TKF networks, as well as by investigation of knowledge flow properties and technological knowledge themes. Although existing studies have proposed the TOD methods for convergence based on patent citation analysis, they offered insufficient implications because they suggested patent pairs as potential technological opportunities. Link prediction is utilized to identify a potential link in a TKF network based on patent citation information because this research aims to anticipate the future converging technological opportunity. This research proposes a systematic method to investigate the current TKF between heterogeneous fields by using patent analysis and to identify technological opportunities for convergence by predicting the potential TKF.

cord-320921-eumuid3r	Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Besides dromedary camels, other animal species, i.e. llamas, alpacas, and pigs have been shown to be susceptible and develop upper respiratory tract infection upon experimental intranasal MERS-CoV inoculation [9] [10] [11] . We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ).

cord-320950-x02zp349	A systematic review and meta-analysis (Huang et al., 2018) of studies on the accuracy of FA-RP, Nanosphere Verigene RV+ test (Hologic, 2018; Luminex, 2018) Gen-Probe Prodesse assays (Hologic, 2018) in the detection of IV A, IV B virus, RSV, hMPV, and AV showed that all of these assays had high diagnostic accuracy, with an area under the receiver operating characteristic curve (AUROC) equal to or >0.98 for all tested viruses. In a study involving 46 children aged 6-36 months with bocavirus infection, it was shown that in 22% of cases, the virus persisted in the respiratory secretions for more than 30 days, despite the rapid disappearance of clinical manifestations (Wagner et al., 2016) . In conclusion, multiplex platforms, despite significantly increasing the possibility to detect which pathogens are present in the respiratory secretions of a child with a respiratory infection, do not offer any advantage in comparison to tradition diagnostic tests regarding the identification of the true etiologic agent of the disease.

cord-320979-25ytt84j	Secondary endpoints reported in this interim analysis include (1) proportion of participants alive; (2) attainment of motor milestones as assessed by World Health Organization (WHO) criteria; (3) attainment of motor milestones by Hammersmith Infant Neurologic Examination, Section 2 (HINE-2); (4) change from baseline in the Children''s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale; (5) change from baseline in growth parameters: weight for age/length, head circumference, chest circumference, head-to-chest circumference ratio, and arm circumference; and (6) proportion of participants developing clinically manifested SMA at 13 and 24 months of age as defined by any of the following conditions: (a) age-adjusted weight < 5th percentile or decrease of ≥2 major weight growth curve percentiles (3rd, 5th, 10th, 25th, or 50th) compared with baseline, or a percutaneous gastric tube placement for nutritional support at 13 or 24 months of age; (b) failure to achieve sitting without support, standing with assistance, and hands-and-knees crawling at age 13 months; or (c) failure to achieve the milestones defined at age 13 months and failure to achieve walking with assistance, standing alone, and walking alone at age 24 months.

cord-321080-pgxxkfc0	We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. As shown in Figure 2 and Table 1 , combining HR2P-M2 and m336 resulted in strong synergistic inhibitory activity against MERS-CoV pseudovirus infection with CI values of 0.13-0.20 for 50-90% inhibition, including potency enhancement of 12.9-to 18.9-fold for m336 and 8.4-to 12.9-fold for HR2P-M2.

cord-321564-6950p8i9	BST2 is a component of innate immune response in the form of restricted enveloped virion release, and many viruses have evolved specific antagonists to counteract BST2 antiviral activity: HIV-1 Vpu, HIV-2 Env, simian immunodeficiency virus (SIV) Nef and Env, Ebola and Sendai virus GP, Kaposi''s sarcoma-associated herpesvirus K5, and influenza virus neuraminidase are all capable of antagonizing BST2. 23 We also found that the SARS-CoV spike (S) protein is capable of downmodulating BST2, thus mitigating the BST2-mediated restriction of virus-like particle (VLP) release, and suggesting that SARS-CoV and other enveloped viruses are capable of evolving additional anti-BST2 factors. BST2, bone marrow stromal antigen 2; SARS-CoV, severe acute respiratory syndrome coronavirus SARS-CoV virion release is mitigated by SARS-CoV S, it is possible that a number of enveloped viruses have developed supplementary anti-BST2 factors over time-note that in addition to Vpu, HIV-1 Nef is capable of overcoming BST2 restrictions on virus release under certain conditions.

cord-322201-5laifjgz	To explore the action of nano-silver on emerging Bacillus megaterium MTCC 7192 and re-emerging Pseudomonas aeruginosa MTCC 741 pathogenic bacteria, the study includes an analysis of the bacterial membrane damage through Scanning Electron Microscope (SEM) as well as alternation of zeta potential and intracellular leakages. The comparative antibacterial activities of nano-silver and broad spectrum antibiotics was effectively accessed against emerging pathogens Bacillus megaterium MTCC 7192 and re-emerging pathogens Pseudomonas aeruginosa MTCC 741 using agar well diffusion assay method [13] . Samples from bacterial cultures (Bacillus megaterium MTCC 7192 and Pseudomonas aeruginosa MTCC 741), mixed with 100 μg/ml of nano-silver, were collected at 3 h and pre-fixed with 2.5% glutaraldehyde for 30 min; these were then washed two times in the same buffer and post-fixed for 2 h in 1% osmium tetroxide. The inhibition zones of nano-silver obtained in this study indicated that a nano-silver has potential to control emerging and re-emerging multidrug-resistant pathogens compared to tested antibiotics.

cord-322395-xeq4yix4	We investigate the dynamics of a wild-type viral strain which generates mutant strains differing in phenotypic properties for infectivity, virulence and mutation rates. We study, by means of a mathematical model and bifurcation analysis, conditions under which the wild-type and mutant viruses, which compete for the same host cells, can coexist. Consequently, the bifurcation diagram in figure 3b shows that for mutant-type infection rates given by a m , 0.86, the coexistence state v 3 is stable whereas the virus-free state v 1 is unstable. As predicted from linear stability analysis, the Hopf bifurcation curve associated with the wt-free state v 2 does not depend on the infection rate of the wt virus a w and thus appears as a straight line given by a m ¼ 1.55.

cord-322629-kv83ekg0	title: Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route Feline infectious peritonitis virus (FIPV) causes a severe, immune-mediated disease called FIP in domestic and wild cats. In this study, when cats passively immunized with anti-FIPV-I KU-2 antibodies were orally inoculated with FIPV-I KU-2, FIP was caused at a 50% probability, i.e., FIPV not causing FIP through oral infection caused FIP by inducing antibody-dependent enhancement. Based on the findings of this study, type I FIPV which orally infected cats may cause FIP depending on the condition. In this study, we investigated whether oral inoculation with FIPV-I KU-2 causes FIP in cats passively immunized with anti-FIPV-I KU-2 antibodies. Mutation of neutralizing/antibody-dependent enhancing epitope on spike protein and 7b gene of feline infectious peritonitis virus: influences of viral replication in monocytes/macrophages and virulence in cats

cord-322649-c99lszcu	title: Rapid and Sensitive Recombinase Polymerase Amplification Combined With Lateral Flow Strip for Detecting African Swine Fever Virus In this study, we developed a rapid test that combines recombinase polymerase amplification (RPA) of the ASFV p72 gene with lateral flow detection (LFD). Results showed that the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD) for ASFV was 150 copies per reaction within 10 min at 38°C. A dilution range of 10 0 to 10 5 copies per reaction of pMD19-p72 recombinant plasmid was used to evaluate the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD), and the amplicons were evaluated through agarose gel electrophoresis. The sensitivity results showed that the detection limit of the ASFV RPA-LFD assay was 10 2 copies per reaction of the recombinant plasmid pMD19-p72. Development of a TaqMan PCR assay with internal amplification control for the detection of African swine fever virus A recombinase polymerase amplification-based assay for rapid detection of African swine fever virus

cord-322747-1e8qah7d	However, PCVs have been occasionally isolated from non-porcine animals, including ruminants (such as cattle, goats, wild chamois, and roe deers), rodents (such as NMRI mice, BALB/c mice, Black C57 mice, ICR mice, Mus musculus, and Rattus rattus), canines (such as dogs, minks, foxes, and raccoon dogs), insects (such as flies, mosquitoes, and ticks), and shellfish. Moreover, PCVs are frequently reported in biological products, including human vaccines, animal vaccines, porcine-derived commercial pepsin products, and many cell lines. Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus Viral replication and lesions in BALB/c mice experimentally inoculated with porcine circovirus isolated from a pig with postweaning multisystemic wasting disease Molecular detection and genome characterization of porcine circovirus type 2 in rats captured on commercial swine farms Detection of porcine circovirus type 2 (PCV2) in mosquitoes from pig farms by PCR

cord-323066-tvguutak	METHODS: A retrospective chart review of all children <2 years old diagnosed with bronchiolitis at the University Medical Centre Ljubljana between May 2014 and April 2015, who were treated as outpatients (paediatric emergency department, PED group) or as inpatients in the standard hospital setting (WARD group) or in the paediatric intensive care unit (PICU group). 10 The objective of our study was to ascertain demographic characteristics, clinical findings and presumptive aetiologic agents (respiratory viruses demonstrated in nasopharyngeal swab) associated with bronchiolitis severity defined as length of hospitalization for >24 hours. Electronic medical records of patients included in the study were reviewed, and statistical analysis was performed for the following clinical and laboratory data: gender, chronological age at admission, prematurity (defined as birth before 37 weeks of gestation), birthweight, history of allergies, number of previous bronchiolitis episodes, clinical manifestations of bronchiolitis using the Wang Respiratory Score, 9 comorbidities (chronic lung disease, congenital heart disease, immune deficiency or neuromuscular diseases), body temperature at admission, treatment with bronchodilators, antibiotics or supplemental oxygen and respiratory virus detected in the nasopharyngeal swab.

cord-323125-qtlevnbt	BACKGROUND: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. METHODS: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. In this investigation, we use serological detection of MERS-CoV antibodies to evaluate if asymptomatic or mildly ill case patients had detectable MERS-CoV antibodies, estimate transmission rates from known cases to their household contacts, and identify potential risk factors. For each MERS-CoV case identified in the investigation, clinical information, including symptoms, was collected using the International Severe Acute Respiratory and Emerging Infection Consortium form, which was filled out in real time by healthcare providers and subsequently verified by retrospective chart review.

cord-323261-1of5ertf	Considering the low priority of health policies since the economic reform, the limitation of the "third sector" activity permitted in authoritarian China, together with the political sensitivity of the HIV/AIDS problem in the country, this article aims to explain the proliferation of HIV/AIDS-focused NGOs in China with the usage of the securitization framework in the field of international relations (IR). Based on the discourse analysis of the official documents and newspaper articles, it is argued that Chinese national leaders followed suit the international move (i.e. UNSC Resolution 1308) to securitize HIV/AIDS in the country, framing HIV/ AIDS as a threat with social, political, economic, and security implications. Along with the weakening of international securitization efforts and the rise of Chinese government''s involvement in managing NGOs in the post-Global Fund era, the continuous proliferation of NGOs is further complicated by the fragmented nature of HIV/AIDS-focused civil society groups in China.

cord-323455-26xi2lqf	This study was performed to evaluate the proportion of adult community-acquired pneumonia (CAP) cases attributable to Streptococcus pneumoniae among Hajj pilgrims in 2016. METHODS: Adult subjects hospitalized with X-ray-confirmed CAP were enrolled prospectively from all general hospitals designated to treat Hajj pilgrims in the holy cities of Mecca and Medina. RESULTS: From August 23 to September 23, 2016, a total of 266 patients with CAP were enrolled in the study, 70.6% of whom were admitted to hospitals in Mecca; 53% of the cases were admitted after the peak of Hajj. pneumoniae among adult Hajj pilgrims in 2016, using the urine antigen test as well as standard culture-based tests, in order to determine the clinical burden of disease associated with Hajj and inform vaccination policy-making. General pattern of community-acquired pneumonia (CAP) case admissions to hospitals during the study period. It was aimed to systematically enroll all hospitalized X-ray-confirmed CAP cases among Hajj pilgrims during the study period.

cord-323700-5awng7h1	The aim of the study here presented was to establish differences in viral detection and species sampled from different sinonasal sites, in an effort to validate and standardise viral collection techniques, and facilitate further investigation of the sinonasal virome. All DNA extracts first underwent an endogenous retrovirus 3 (ERV3) assay (present as two copies per human diploid cell) in order to confirm respiratory sample collection quality. Nasal swab samples and real-time polymerase chain reaction assays in community-based, longitudinal studies of respiratory viruses: the importance of sample integrity and quality control High rates of detection of respiratory viruses in the nasal washes and mucosae of patients with chronic rhinosinusitis Detection of herpesviruses 1-6 and community-acquired respiratory viruses in patients with chronic rhinosinusitis with nasal polyposis Real-time RT-PCR detection of 12 respiratory viral infections in four triplex reactions Real-time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients

cord-323856-yr3zfxz3	Of note, resistance to colistin (CST) had been detected at relatively low levels for years in commensal isolates, but prevalence was sometimes high for pathogenic strains (Kempf et al., 2016) , and after a publication on the emerging mcr-1 gene in China (Liu et al., 2016) , it soon appeared that this gene was also present in many other countries, particularly in pig E. In addition, fecal samples collected on Days 2, 9 and 17 were inoculated, after thawing, onto the Chromagar Orientation ™ agar medium (i2a, Montpellier, France) supplemented with colistin (8 mg/L) and vancomycin (8 mg/L) (CAO-CV) as previously described (Mourand et al., 2018) to detect colistin-resistant rifampicin-susceptible E. Considering only isolates obtained without enrichment, for group G2, 52 out of 53 isolates shared the characteristics of inoculated strain 12-246 M, and one isolate obtained on Day 14, without enrichment, belonged to PGG A, had the ERIC and PFGE profiles and the antimicrobial susceptibility of 12-246 M, including resistance to colistin, although it was negative for the mcr-1 gene.

cord-323987-gh1m05gi	RIDTs with digital readout systems showed many similarities to conventional assays like small sample volume (less than 150 µL) and short analysis time (around 15 min) but exhibited much better sensitivities, even one order of magnitude lower limits of detection (LODs). Among methods mentioned, general diagnostic tests for influenza base on virus culture (conventional and shellvial), detection of viral nucleic acid (PCR) or antigens (by neuraminidase enzymatic activity, fluorescent antibody or enzyme/optical immunoassay) and serologic tests. Main trends for influenza virus detection are: (I) modifications of traditional ''gold star'' methods like PCR, RIDTs, ELISA what results in analysis time shortening, costs lowering, LOD and limit of quantification (LOQ) improvement, (II) conjugating of traditional methods and creating new platforms, micro-biochips and others, (III) introducing known solutions to new ones, like smartphone-based analysis control with results data insertion into Google Maps, (IV) reuse of the functions of known devices, like glucometer, smartphone cameras, (V) the most common used detection methods: spectral/optical, electrical, (VI) and entirely new approaches.

cord-324395-v5uiuhih	RESULTS: Here, we present Glycosylator, a Python framework for the identification, modeling and modification of glycans in protein structure that can be used directly in a Python script through its application programming interface (API) or through its graphical user interface (GUI). The GUI provides a straightforward two-dimensional (2D) rendering of a glycoprotein that allows for a quick visual inspection of the glycosylation state of all the sequons on a protein structure. Finally, Glycan Reader recognizes most types of glycans and their chemical modifications found in the Protein Data Bank (PDB), which are all available in the CHARMM force field [22] . The Glycosylator framework is composed of 7 classes, several of which can be employed as standalone instances for other applications in molecular modeling (Additional file 1: Figure S1 in the Supporting Information (SI) section). A Molecule can be instantiated directly with a 3D structure (PDB) or using a MoleculeBuilder instance and the topology information provided for the CHARMM force field [22] .

cord-324432-k0g3r1lw	PATIENTS/METHODS: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. The community cohort was derived from the Mobile Surveillance for Acute Respiratory Infections (ARIs) and Influenza-like Illness (ILI) in the Community (MoSAIC) study, a 5-year community-based surveillance ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV-4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults. epidemiology, parainfluenza, respiratory, seasonality, viruses F I G U R E 1 Flowcharts depicting the overall number of respiratory viral panel (RVP) tests ordered which yielded the final number of human parainfluenza virus (HPIV) types in the community cohort (1A) and in hospitalized patients (1B) study in New York City (NYC) that includes 250 households annually.

cord-324530-tac1unnp	title: Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis CASE SUMMARY: This report describes a cat with chronic, progressive, non-painful, non-lateralizing multifocal neurologic clinical signs associated with feline infectious peritonitis (FIP). Molecular analysis of the coronavirus spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the central nervous system (ie, brain and spinal cord). RELEVANCE AND NOVEL INFORMATION: This case report describes an early presentation of a cat with primarily neurologic FIP, with molecular characterization of the virus within various tissues. 18 Molecular analysis of the viral spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the CNS (ie, brain and spinal cord). This case report describes a young cat with neurologic FIP in which detailed clinical and molecular characterization of the associated FCoV infection was performed.

cord-324674-yd7idp90	ADP/P2Y 13 -mediated protection against viral infection operates by suppressing the expression of exchange protein activated by cAMP 1 (EPAC1), which is an alternative key intracellular sensor for cAMP. To our surprise, the RNA replication of VSV in ADP-treated RAW264.7 cells was reduced significantly in a time-( Figure 2D ) and concentration-( Figure 2E ) dependent manner. To explore the key receptors involved in ADP-mediated antiviral activities, we detected the expression of P2Y 1 , P2Y 12 , and P2Y 13 after VSV infection. ADP/P2Y 13 restricts viral replication by inhibiting cAMP signaling Type I IFN plays pivotal roles in fighting against the invaded virus, so we tested whether it was involved in ADP/P2Y 13mediated antiviral activities. As shown in Figure 7A , when infected RAW264.7 cells with VSV, NDV, and HSV-1, RNA expression of EPAC1 was increased significantly.

cord-325052-7vlxa0i7	However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. While approval of vaccines for diseases caused by such pathogens would Clinical and Experimental Immunology REvIEw ARtIClE Series Editor: E Diane williamson make a significant impact on disease outbreaks, taking niche vaccines into clinical development, including Phase III clinical trials for efficacy, requires a large investment in time and money. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or an alternative status in the United States, Canada and European Union (EU) making use of a considerable number of alternative regulatory mechanisms that are available prior to licensing, so that the products are deployable at the first indications of a disease outbreak.

cord-325112-7ie23c7f	Using SARS and the International Health Regulations (IHR) as a starting point, this article examines negotiated information orders in global public health governance and the irregularities in the supply of data that underlie them. Negotiated information orders within and among the organizations in a field (here, e.g., the World Health Organization, member states, government agencies, and international non‐governmental organizations) spell out relationships among different categories of knowledge and non‐knowledge – what is known, acknowledged to be known, and available for use in decision making versus what might be known but cannot be acknowledged or officially used. Thus although the long silence of the Chinese government was not technically a violation of the IHR, it nevertheless appeared dishonest and inappropriate to the international community, undermining rather than supporting emerging cooperative norms and in fact harming global public health by allowing the new disease to spread beyond China''s borders.

cord-325302-c4f58lsx	title: An Alumina Ceramic Total Talar Prosthesis for Avascular Necrosis of the Talus Arthroplasty using a customized total talar prosthesis designed using the computed tomography image of contralateral talus has the potential advantages of weightbearing in the earlier postoperative phase, prevention of lower extremity discrepancy, and maintenance of joint function. Radiographic staging of osteonecrosis was developed by Ficat and Arlet 17 and was modified for the ankle by Mont and Colleagues 18 Stage 1 is defined as no radiographic findings, stage 2 is defined as cystic lesion and/or sclerotic change in the talus, stage 3 is defined as crescent sign or collapse in the subchondral bone, and stage 4 is defined as joint space narrowing. Sclerotic change in the talar body would be observed even in cases without severe collapse in the talus (Fig. 1) . Alumina ceramic talar body prosthesis for idiopathic aseptic necrosis of the talus

cord-325525-d1hsguds	À l''inverse, des pathologies, comme la maladie de Glässer, sont encore susceptibles d''engendrer d''importantes pertes économiques dans des élevages à haut niveau sanitaire. En 2018, six maladies et infections à déclaration obligatoire (encéphalite à virus Nipah, gastro-entérite transmissible, cysticercose, peste porcine classique et africaine, syndrome dysgénésique et respiratoire) ont été recensées par l''Organisation mondiale de la santé animale pour les suidés 1 . Peste porcine ✦ Causée par un virus de la famille des Flaviridae, la peste porcine classique n''est actuellement plus présente en France tant dans les cheptels porcins domestiques que sauvages. Aucun traitement spécifique n''est disponible et la vaccination préventive des cheptels porcins n''est plus autorisée dans l''Union européenne depuis 1988 suite à la mise en place d''un programme d''éradication de la maladie. Cette affection, pour laquelle il n''existe ni traitement ni vaccin, résulte d''une infection par des entérovirus de la famille des Picornaviridae.

cord-325574-4zf9qtlh	MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans. By reviewing changes involving humans and camels over the past 30 years in Qatar, this study sought to identify the key drivers of the emergence and spread of MERS-CoV. The main themes that were covered during the interviews included: (changes in) people''s living conditions; customs and purposes of camel ownership; cultural habits related to camels; educational level and personal behaviors of camel owners and workers; camel movement; demographic distribution of camels in Qatar; camel farming practices: feeding, grazing, and slaughter.

cord-325679-4lfpy84d	To investigate the presence and genetic variability of FeKoV in northeast China, 197 fecal samples were collected from 105 cats with obvious diarrhea and 92 asymptomatic cats in Shenyang, Jinzhou, Changchun, Jilin and Harbin regions, Northeast China, and viruses were detected by RT-PCR with universal primers targeting all kobuviruses. By genetic analysis based on partial 3D gene, all kobuvirus-positive samples were more closely related to previous FeKoV strains with high identities of 90.5%–97.8% and 96.6%–100% at the nucleotide and amino acid levels. Additionally, phylogenetic analysis based on the complete VP1 gene indicated that all FeKoV strains identified in this study were placed into a cluster, which separated from other reference strains previously reported, and three identical amino acid substitutions were present at the C-terminal of the VP1 protein for these FeKoV strains. The genetic analysis based on the partial RdRp gene indicated that FeKoV strains shared higher nucleotide (81.2%-82.1%) and amino acid identities (91.4%-92.1%) with CaKoV strains previously reported (Kapoor et al.

cord-326558-6tss9ydx	CONCLUSIONS: In this work, we presented VirBin, a new contig binning tool for distinguishing contigs from different viral haplotypes with high sequence similarity. These methods usually estimate the bin number by aligning metagenomic data to a pre-established marker gene database, and then assign assembled contigs to different bins using sequence composition information and read coverage levels. We evaluate the haplotype number estimation and clustering performance of VirBin on both simulated and mock HIV quasispecies sequencing data. It uses bowtie2 to map reads to a set of universal genes and infers the within-species strains abundances by Fig. 3 The recall and precision of contig binning results by MaxBin. X-axis represents each haplotype, in decreasing order of relative abundance. Although abundance-based clustering has been used for contig binning from multiple samples [15, 19] , existing tools are not designed Fig. 7 The pipeline of VirBin to tackle key challenges of distinguishing contigs of different haplotypes.

cord-327202-2um6jmhk	The conundrum of dual use research of concern was crystallized by the so-called "gain-of-function" type of experiments in which avian influenza viruses were endowed with new properties in the laboratory such as increased virulence and the capacity for mammalian transmission. The major outcome of the great GOF controversy of 2012 is that it defined and crystallized some of the issues of dual-use research in biology by providing clear examples of experiments that were of great scientific value while also raising biosecurity and biosafety concerns. Consequently, when faced with GOF papers containing information that could conceivably be used to enhance the pathogenicity or transmissibility of a virus, editors and journals have almost always opted for full publication, usually requiring more details from the authors about biosafety and biosecurity methods, and often publishing an accompanying editorial emphasizing the scientifically useful aspects of the research [for examples, see Dermody et al.

cord-327660-p1b07b4t	The current RdRp tree topology combined with gene gain-loss reconstruction suggests the following evolutionary scenario for branch 1 ( Fig. 2A) : a levivirus-like ancestor that, like the extant members of the Leviviridae, possessed a capsid protein unrelated to SJR-CP (19, 52) gave rise to naked eukaryotic RNA replicons known as "mitoviruses" and "narnaviruses." These replicons consist of a single RdRp gene (Fig. 2B ) and replicate in mitochondria and in the cytosol of the host cells of fungal and invertebrate hosts, respectively (the latter hosts were identified in metaviromic holobiont analyses) (14, 53) . This genome architecture could hint at an ancestral flavivirus genome that was assembled from genes borrowed from preexisting viruses, one of which possessed a divergent "tombus-like virus" RdRp. Although the origins of branch 3 are murky, major trends in its subsequent evolution clearly included lineage-specific gene capture, starting with helicases and CapEs in the ancestors of the major lineages and followed by diverse genes in smaller groups (Fig. 4B) .

cord-328000-i9tzr13z	Three different strategies were employed for development of SARS-CoV mouse models: (i) different mouse species (or subspecies) were challenged with wildtype human SARS-CoV isolates in order to find a model that allows for replication and reflects severe respiratory disease symptoms observed in infected human patients; (ii) mice were genetically engineered to modify the host receptor, which facilitated productive SARS-CoV replication and pathogenesis; and (iii) adaptive evolution of wild-type SARS-CoV to a chosen mouse species was done to enhance pathogenesis, and associated clinical phenotypes in vivo. To adapt SARS-CoV to cause severe acute respiratory disease in mouse lungs, 6-week-old female BALB/c mice were intra-nasally infected with the clinical Urbani isolate (Roberts et al. Virus infection studies in CC mouse lines, including SARS-CoV, have led to mapping of high and low host response alleles as they relate to development of clinical signs of disease following viral pathogenesis (Bottomly et al.

cord-328086-ji2emajn	BACKGROUND: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). Clinical disease and viral load in children infected with respiratory syncytial virus or human metapneumovirus Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection High viral load of human bocavirus correlates with duration of wheezing in children with severe lower respiratory tract infection High prevalence of human bocavirus detected in young children with severe acute lower respiratory tract disease by use of a standard PCR protocol and a novel real-time PCR protocol Clinical significance of different virus load of human bocavirus in patients with lower respiratory tract infection

cord-328525-80xk3gln	Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. To strengthen our existing infection control measures in hematology and oncology, we subsequently implemented a systematic influenza and RSV screening of patients lacking respiratory symptoms on a pediatric and an adult hemato-oncological ward as a prophylactic infection control measure in the following winter (2016/2017). To extend our existing standard infection control measures, we introduced a prophylactic screening program for asymptomatic patients targeting RSV and influenza on an adult and a pediatric hemato-oncological ward.

cord-328661-spxgox52	The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong. Since 1990, however, DENV1 has been mainly isolated from the infected cases, and its continued existence in Guangdong Province indicated that endemic infectious agents of dengue may be circulating locally. With the epidemiological data since 2005 supplied by the Guangdong Provincial CDC, we studied phylogenetics, molecular characteristics, and epidemiology to strengthen the foundational research of DENV1 for the prevention of large-scale dengue epidemics, providing preventive and control measures of DF with important evidence. Based on representative strains of the E gene in lineages of the 2014 outbreak, as well as the molecular evolution database, we analyzed molecular characterization and possibility of local circulation for DENV1 since 2005 in Guangdong.

cord-328940-8vtcochx	By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota. Our computational analysis of similar GC content transitions across whole HAdV-D genomes showed comparable patterns of GC/AT transition at predicted recombination hot spots around hypervariable gene segments in the three major capsid genes-the same segments that constitute the molecular identity of each virus (14, 19, (41) (42) (43) -including the region containing Chi AD immediately 5= to penton base HVL2 (see Fig. S1 and Table S1 in the supplemental material).

cord-328979-xfze12ah	Collecting specimens within a short time from the onset of symptoms still maximizes the likelihood of accurate and timely identification of viruses associated with a respiratory illness for studies of transmission and vaccine effectiveness. While respiratory virus infections in general could be studied, the primary objective was to estimate the effectiveness of influenza vaccines using a cohort design for comparison with studies using the testnegative design (TND). With additional funding, we have expanded on these original aims by collecting blood specimens for studies of antibody-mediated Households 328 213 321 232 340 227 Participants 1441 943 1426 1049 1431 996 Influenza-positive individuals 125 32 111 50 202 38 Influenza-positive specimens 130 32 117 52 210 40 Strain A c 86 23 69 48 166 30 H1N1pdm09 27 1 3 47 0 28 H3N2 59 22 66 1 immunity, extending ARI surveillance year-round, and incorporating laboratory testing for other respiratory viruses.

cord-329227-sqetz7h6	The amounts of PEDV S proteins in the ERGIC, in other organelles, or on the cell surface are likely regulated by two nearby motifs in its cytoplasmic tail (CT): a tyrosine-based motif, Yxx⌽ (x is any residue and ⌽ is a bulky hydrophobic residue: F, M, I, L, or V), and an ER retrieval signal (ERRS), KVHVQ (10) (11) (12) (13) , as well as other viral and cellular proteins. One study demonstrated that a single amino acid substitution in this motif (KVHVQ to KVRVQ) weakens the intracellular retention function of the S proteins of the 10th passage of a murine-adapted PEDV variant, MK-P10 (18) , resulting in enhanced syncytium formation in Vero cells. In this study, we evaluated the phenotypes of transiently expressed S mutants containing mutations or deletions in these two motifs in mammalian cells and the virulence of three representative recombinant PEDVs in gnotobiotic piglets.

cord-329429-ur8g68vp	Within the gamma-CoVs the main representative is avian coronavirus, a taxonomic name which includes the highly contagious infectious bronchitis viruses (IBVs) in chickens and similar viruses infecting other domestic birds such as turkeys, guinea fowls, or quails. The methods adopted in monitoring studies of CoVs in different avian species are mainly based on detection of conservative regions within the viral replicase, nucleocapsid genes, and 3''UTR or 5''UTR. The purpose of this review is to summarise recent discoveries in the areas of epidemiology and diagnosis of CoVs in avian species and to understand the role of wild birds in the virus distribution. This taxonomic name includes IBV which causes a highly contagious disease of chickens, and genetically similar viruses isolated from other domestic galliformes: turkey coronavirus (TCoV), responsible for turkey enteritis, and the more recently detected guinea fowl coronavirus (GfCoV), the aetiological factor of fulminating disease in this species (2, 6, 27) .

cord-329459-k55ldc3m	OBJECTIVE: To analyze the correlations between the incidence of rubella and meteorological factors over the same period and previous periods including 1, 2, 3 and 4 year ago (defined according to Chinese medicine Yunqi theory of "pestilence occurring after 3 years") and establish the rubella-meteorological forecast models for Beijing area, China. METHODS: Data regarding the incidence of rubella between 1990 and 2004 from Beijing Center for Disease Control and Prevention, and the meteorological variables including daily average temperatures, daily average wind speeds, average precipitations, average relative humidity, average vapor pressures and average low cloud covers between 1986 and 2004 were collected from the Beijing Meteorological Observatory. We also found that average temperature and average relative humidity, especially in the current year, were selected as vital meteorological factors because they made the largest contributions to the rubella-meteorological forecasting models, as indicated in the back propagation artificial neural network analysis.

cord-329555-y3cp5wza	Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. Here, we report simultaneous outbreaks of respiratory disease in two nearby chimpanzee communities in Uganda, caused by two distinct negative-sense RNA viruses of human origin. Human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3) was detected in 5 of 14 individuals (35.7%) from Kanyawara chimpanzees exhibiting clinical signs during, but not before, the outbreak period (Fisher''s exact P = 0.0005). For example, HRV3 can cause upper respiratory disease and predispose chimpanzees to invasive pneumococcal infection [44] , and the bacterium Streptococcus pneumoniae co-occurs with human metapneumoviruses and respiratory syncytial viruses in both wild and in captive apes [9, 22] .

cord-329760-mcfxye4f	Using this sequence information, we constructed a CHIKV-pseudotyped lenti-virus expressing the structural polyprotein of the Korean CHIKV isolate (CHIKVpseudo) and dual reporter genes of green fluorescence protein and luciferase. Validation and comparisons of PBNA results with those from conventional PRNT indicate that the PBNA using CHIKVpseudo may be a safe, rapid, and reliable neutralization assay for evaluating the neutralizing activity of anti-sera against CHIKV. To produce CHIKVpseudo, HEK293T cells were transfected with pCMV2-FLAG-CHIKVst, psPAX2 (a gift from Dr. Seungmin Hwang, The University of Chicago, IL, USA), and Luc2P pLVX-IRES-ZsGreen1, which is able to express two reporter genes, luciferase and GFP (a gift from Dr. Nam-Hyuk Cho, Seoul National University, South Korea). Here, we adopted the strategy of expressing the entire structural polyprotein of CHIKV to generate the pseudotyped virus form of KNIH/2009/77 (CHIKVpseudo) for the enhanced infectivity compared to a virion expressing either an individual E1 or E2 protein (Hu et al., 2014) .

cord-329866-io9fvy58	With the aim to contribute to fill this diagnostic gap, a total of 61 effusions from cats with suspected effusive FIP were collected intra-vitam for detection of feline coronavirus (FCoV) antibodies and RNA by means of indirect immunofluorescence (IIF) assay and real-time RT-PCR (qRT-PCR), respectively. Fifty-one (48 ascitic and 3 pleuric fluids) of the 61 tested samples had FCoV antibody (Table 2 and Fig. 1 ), although only 37 positive effusions contained antibody levels ≥ 1:1600, which are considered highly suggestive of FIP diagnosis (Hartmann et al., 2003) . A recent paper (Meli et al., 2013) has investigated the agreement between FCoV antibody titres and RNA detection in the effusions of 13 cats with confirmed FIP, showing a correlation between high amounts of virus and lower signals in IIF assay, likely due to the fact that antibodies bound to viral antigens of the effusions are not able to bind to the antigens of the FCoV-infected cells used in serological tests.

cord-330025-6vql2u75	title: The molecular structure of 4-methylpyridine-N-oxide: Gas-phase electron diffraction and quantum chemical calculations Abstract The molecular structure of 4-methylpiridine-N-oxide, 4-MePyO, has been studied by gas-phase electron diffraction monitored by mass spectrometry (GED/MS) and quantum chemical (DFT) calculations. The quantum chemical study of the substituent effect on the properties of pyridine-N-oxides has been performed for ten compounds with different substituents [18] . The comparative analysis of structural data obtained by different methods suggests that the molecular parameters of N-oxides obtained by GED [15] look rather strange. The discrepancies in molecular structure of substituted N-oxides according to GED and other methods motivated us to perform a new gas-electron diffraction study of 4-methylpyridine-N-oxide. According to quantum chemical calculations the insertion of the methyl group in para e position to the PyO has no significant effect on the structural parameters of the pyridine ring, excluding only the ipso-angle : C2C1C5, which changes from 120.6 in PyO to 115.9 in 4-MePyO (B3LYP/cc-pVTZ).

cord-330296-706hf4qw	Abstract The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry (Gould et al., 2012) . In fact, besides the EVAg, we are unaware of any non-profit organization that is concerned with facilitating reliable access globally to viruses and associated reagents from individual virus collections for research and/or diagnostic laboratories, teaching centres or industries involved in the production of diagnostic reagents, pharmaceuticals and vaccines solely for the benefit of science, in a safe and carefully regulated manner.

cord-330503-w1m1ci4i	Advance data transfer and management techniques have made improvements in disease diagnostic and have been a critical role in national health planning and efficient record keeping. In particular, the medical profession has undergone substantial changes through the capabilities of database management, which has given rise to the Healthcare Information Systems (HIS). According to [1] , many programs are developed with the help of AI to perform specific tasks which make use of many activities including medical diagnostic, time sharing, interactive interpreters, graphical user interfaces and the computer mouse, rapid development environments, the linked listdata structure, automatic storage management, symbolic, functional, dynamic, and object-oriented programming. Thus the first phase of the usage of information technology and systems in hospital and healthcare management was to transform paper based records to database systems. AI, Robots, VR, AR, MR, IoMT, ubiquitous medical services, and big data analytics are all directly or indirectly related to IT. Medical internet of things and big data in healthcare

cord-330772-i7cfmw9x	The in vitro toxicity and antiviral ability of the surfactin-like peptide in the BLFP crude extract against PEDV were evaluated using the Vero cells. To study the antiviral activity of BLFP crude extract against PEDV, the biosurfactants were added at different time points during the viral infection. No statically significant difference in the average daily gain was noted among all groups each week BLFP crude extract with PEDV-infected cells during the whole study. Similarly, extracellular viral RNA levels in PEDV-infected cells cultured with biosurfactants were significantly lower than those without BLFP crude extract 24 and 48 HPI (Fig. 8b) . b Extracellular viral RNA levels in the supernatants of PEDV-infected Vero cells treated with or without BLFP crude extract were determined by real-time reverse transcription (RT)-PCR. d Intracellular viral RNA levels in the supernatants of PEDV-infected Vero cells treated with or without BLFP crude extract were determined by real-time RT-PCR.

cord-330819-vfagxsdz	Using enhanced hospital based surveillance of childhood ARI we identify seasonal patterns in hospitalizations as a proxy for transmission and explore the relationship of hospitalizations associated with virus detection with rainfall, temperature, and dew point, to try and identify contributing factors to observed seasonality. To examine the relationship between monthly average rain, temperature, and dew point and incidence hospitalized childhood ARI infections, we estimated the cross-wavelet transform between the z-standardized time series (we subtracted the mean of the time series and divided by the standard deviation) of weather and viral detections (Cazelles et al., 2008) . We evaluated seasonal patterns and associations with weather of hospitalizations for several respiratory viruses using three lines of evidence: 1) Poisson regression examining the relative incidence across months of virus detections adjusted for weather covariates, 2) cross-wavelet transforms of hospitalizations with viral detections, and 3) a sensitivity analysis with a logistic regression model finding odds ratio of hospitalizations with viral detections and weather variables.

cord-330942-x238hq9b	The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Recent studies however, suggest that hRV may be a clinically significant pathogen with the potential to cause serious pulmonary disease in HCT recipients (Campbell et al., 2015; Seo et al., 2015 Seo et al., , 2017 Versluys et al., 2017) with risk of progression to LRTI of 9-24% (Shah et al., 2012; Campbell et al., 2015; Fisher et al., 2017) and hRV related mortality of 4-33% (Shah et al., 2012; Campbell et al., 2015; Fisher et al., 2017) . In 2016 a joint working group in the UK (Dignan et al., 2016) has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with hematological malignancies or those undergoing hematopoietic stem cell transplantation.

cord-331255-t85yioyl	Feeding 11 billion people will require substantial increases in crop and animal production that will expand agricultural use of antibiotics, water, pesticides and fertilizer, and contact rates between humans and both wild and domestic animals, all with consequences for the emergence and spread of infectious agents. Meeting the United Nations'' Sustainable Development Goal, to "eradicate hunger" (https://sustainabledevelopment.un.org/) for this expanding human population will necessitate a large increase in food supplies, with major changes to agricultural production and distribution systems, infrastructure and social protection programmes 6 (Fig. 3) . As livestock and aquaculture production expand to address growing food demands, it is likely that current antibiotics and anthelmintics will become less effective because of evolved resistance, and thus infectious diseases of domesticated animals and humans will be more difficult to treat 75 .

cord-331641-u27ohm5p	In this study, we devised a Direct-LAMP procedure, amplifying nucleic acids with various samples (including whole blood, dried blood spot, buccal swab and saliva) without DNA purification, which is essential for conventional nucleic acid detection methods. To evaluate the performance of the Direct-LAMP, a serial dilution of the target concentrations of whole blood sample and saliva sample with two different genotypes (wild type and homozygous mutation which confirmed by sequencing) of MTHFR C677T and ALDH2 Glu504Lys, respectively, were used to determine the detection limit. Here, we have established a rapid, easy-to-use and accurate SNP detection platform using Direct-LAMP, which enables us to use whole blood, dried blood spot, buccal swab or saliva as samples for genotyping without DNA purification. In this study, we presented a Direct-LAMP for SNP detection by using whole blood, dried blood spot, buccal swab or saliva as samples without DNA purification.

cord-331827-amg309uz	BACKGROUND: Human metapneumovirus (hMPV) is a recently detected virus, which can cause mild to severe respiratory tract infections. MATERIALS/METHODS: Between January 2012 and November 2017, patients who had hMPV detected in nasopharyngeal or bronchoalveolar lavage by molecular respiratory pathogen tests were evaluated. Lower respiratory system infection (LRTI) was diagnosed in 44 patients with clinical findings, and in 31 patients out of 44 the radiological findings supported the diagnosis. Our study demonstrates the radiologic findings of hMPV infections in patients with LRSI (Figures 3 and 4) . In a recent review for radiologic imaging of viral agents that may cause pneumonia, the general radiologic findings of hMPV infections were followed as bilateral centrilobular nodules, GGO, and multilobar infiltrations; however, there was no information about nodular consolidation. In addition, they noted that the radiologic findings of hMPV infections were most commonly reported in patients with hematologic malignancy, but there were limited data on immunocompetent patients. Clinical characterization of human metapneumovirus infection among patients with cancer

cord-331835-nuhrd92z	title: The role of the hotel industry in the response to emerging epidemics: a case study of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong METHODS: This case study focuses on the epidemic outbreaks of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong, and the subsequent guidelines published by the health authority in relation to the hotel industry in Hong Kong which provide the backbone for discussion. This case study will use the example of the Metropole Hotel in Hong Kong in the international spread of Severe Acute Respiratory Syndrome (SARS) in 2003, and the effect of the government mandated quarantine of the Metropark Hotel during the swine flu 2009 in Hong Kong. After the SARS outbreak in Hong Kong the health authority established the Guidelines for Hotels in Preventing Severe Acute Respiratory Syndrome (SARS) [24] 

cord-332042-bqtflk7r	Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. The CIRN SOS Network comprises 15 to 45 acute care (depending on the year) hospitals across Canada, and influenza testing is performed using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) methods derived from the World Health Organization (WHO) [12] [13] [14] . While WHO-based real-time RT-PCRs methods are often viewed as the reference standard for influenza virus detection, diagnostic laboratories and surveillance studies often test for other viral aetiologies of respiratory illness [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] . This study''s strengths include prospectively collected specimens from a defined patient population (adults hospitalized with acute respiratory illness), comparison of results against reference methods for influenza A and B detection, and analyses performed on influenza viruses characterized by subtyping or lineage determination.

cord-332747-u46xryoo	To determine which aspects of the HCV replication cycle are limited by lipin1 silencing, single cycle infection experiments were conducted by inoculating control and lipin1-deficient cell cultures at MOI 10 with genotype 2a D183 virus. Once cultures reached >95% of HCV-positive cells, they were transduced with lentiviral vectors expressing control, HCV RNA-targeting or LPIN1-specific shRNAs. At day 7 post-transduction, cells were split and samples of the cells and supernatants were collected 24 hours later to determine infectious virus production rate by infectivity titration HCV (C) and RNA levels by RT-qPCR (D). This reduced abundance is illustrated by a significant reduction in the fraction of cells displaying vesicular structures in lipin1-deficient cell cultures (Fig 7H) despite comparable transfection efficiency and viral protein expression levels, indicating that lipin1 may be required in a critical step leading to formation of the HCV-induced vesicular compartment.

cord-333423-jhm7u8ka	Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. The type I IFN-activated ISGF3 transcription complex containing tyrosine-phosphorylated STAT1 and STAT2 associated with IRF9 is rapidly translocated to the nucleus FIG 3 PRRSV nsp11 inhibits ISGF3-induced ISRE promoter activity. This provided further support for the notion that the ability of PRRSV nsp11 to block type I IFN signaling is independent of its endoribonuclease activity and cell cytotoxicity, because these three mutants had similar effects with respect to inhibiting the formation and nuclear translocation of ISGF3 compared with WT nsp11.

cord-333639-usgpe1cz	title: Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects We focus on the choice of the macromolecular backbone as a carrier for the conjugated drug and analyze blood coagulation, binding to albumin, albumin aggregation, inhibitory activity on polymerases, and cytotoxicity for polymers differed by their anionic charge (carboxylates, phosphates and phosphonates, sulfonates). As a result, we identify polymers and macromolecular prodrugs that are devoid of blood anti-coagulation activity but are strong as inhibitors of polymerases and efficacious as delivery vehicles for ribavirinthus being attractive for the development of broad-spectrum antiviral agents. This observation echoes our recent findings on the apparent unique pairing of negative character and hydrophobicity of the polymer backbone that renders PEAA an efficacious inhibitor of e.g. hepatitis C virus intracellular replication [55] and a lead polymer with broad-spectrum antiviral activity [21] . Polyanionic macromolecular prodrugs of ribavirin: antiviral agents with a broad Spectrum of activity

cord-333801-4pjdutgg	Various study designs, including, but not limited to experimental, quasi-experimental, observational, qualitative, and mixed method designs, have been used in pharmacy practice research. The choice of a study design to answer a research question in pharmacy practice research is driven by several factors, including the type of the research question or the research hypothesis, expertise of the investigator, availability of data, and funding opportunities. Traditionally, core quantitative approaches used in pharmacy practice research include nonexperiments, quasi-experimental designs, and true experimental designs such as prospective randomized controlled intervention trials. In pharmacoepidemiology and other areas of pharmacy practice, researchers are often interested in measuring the relationships between exposure to a drug and its efficacy, toxicity, or other outcomes of interest using observational study designs. In the following section, interpretative frameworks and philosophical orientations, methodologies, data collection and analysis methods, approaches to ensure rigor, and ethical considerations in qualitative research are briefly discussed (Cohen et al., 2013; Creswell, 2013) .

cord-333882-zrdsr3nh	title: Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study We report the safety of a fully human polyclonal IgG antibody (SAB-301) produced from the hyperimmune plasma of transchromosomic cattle immunised with a MERS coronavirus vaccine. We recruited healthy participants aged 18–60 years who had normal laboratory parameters at enrolment, a body-mass index of 19–32 kg/m2, and a creatinine clearance of 70 mL/min or more, and who did not have any chronic medical problems that required daily oral medications, a positive rheumatoid factor (≥15 IU/mL), IgA deficiency (<7 mg/dL), or history of allergy to intravenous immunoglobulin or human blood products. One novel alternative method of manufacturing neutralising intravenous antibodies of consistently high affinity and avidity is to use the hyperimmune plasma of transchromosomic cattle, which produce highly potent and antigen-specific, fully human polyclonal IgG de novo, and which mount a robust antibody immune response after vaccination. SAB-301 is a novel anti-MERS-CoV intravenous immunoglobulin manufactured from the hyperimmune plasma of transchromosomic cattle that produce fully human polyclonal IgG.

cord-334027-xhfmio7k	No demonstrable pathologic effects noted during infection of three bat species [big brown bats (Eptesicus fuscus), little brown bats (Myotis lucifigus) and Mexican free-tailed bats (Tadarida brasiliensie mexicana) with various strains of JBEV or St. Louis encephalitis virus (SLEV) [69] . While experimental data demonstrated that some bat species can sustain JBEV infections and support mosquito-borne transmission of this virus, the epidemiological significance of these observations in the field remains unclear. To truly elucidate the role of bats as reservoirs for arboviruses, field surveillance studies documenting natural infection and transmission dynamics among vector and vertebrate species must be supplemented with experimental infections to characterize viremia profiles and infectiousness to vectors, virus-induced pathology, and immune kinetics following infection. The isolation of Marburg virus from Egyptian rousette bats in Uganda in addition to experimental infections demonstrating viremia and shedding in the absence of overt pathology support the role of this bat species as the reservoir for Marburg virus [6, 7, 208] .

cord-334039-7nwq4vxk	BACKGROUND: Mounting evidence suggests that holding multiple concurrent jobs in public and private (dual practice) is common among health workers in lowas well as high-income countries. Its specific objectives are (1) to map out the existing literature on the subject, determining its prevalence and distribution across geographies, publication types (e.g. peer-reviewed, grey), and specific topics addressed; (2) summarise the evidence, perspectives, and specific contents addressed; and (3) propose an agenda to advance research and development activities to first identify and then mitigate any pervasive effects of nurses'' dual practices to UHC, based on the scoping review results. The evidence available suggests that the consequences of this phenomenon are not negligible, particularly for the health of those nurses ending up working longer hours and hospital shifts because of their multiple commitments [39, 51] , but also for the organisation of public and private health services facing a more ''casual'' and less-committed kind of workforce [21] .

cord-334109-9gv92yfh	key: cord-334109-9gv92yfh authors: Cho, Hae-Wol title: Enemy at the Gate date: 2019-08-17 journal: Osong Public Health Res Perspect DOI: 10.24171/j.phrp.2019.10.4.01 sha: doc_id: 334109 cord_uid: 9gv92yfh nan individuals at a higher risk of transmitting WFB communicable diseases as they may have come from areas where the population is living in a high-density, poor, social environment. In addition, medical care may be minimal, and access to safe drinking water and clean food may be limited. Providing improved essential information on good personal hygiene practices to international travelers from/to Korea maybe a simple and effective measure for minimizing the possibility of spreading WFB communicable diseases. World Health Organization. Guidelines for drinking-water quality World Health Organization [Internet]. Foodborne diseases Foodborne and Waterborne Diseases Joint external evaluation of IHR cope capacities of the Republic of Korea Mission report Risk of Water and Food-Borne Communicable Diseases in Travelers Entering Korea

cord-335614-qh98622y	These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout. The results of PCA and OPLA-DA analysis showed that there was an obvious separation between the content of the Con and Dis groups, revealing significant changes in the concentrations of metabolites in the kidney induced by NIBV infection. In addition, the transcriptomic analysis showed that NIBV infection also activated the RIG-I-like receptor signalling pathway (Figure 3f , signal 2), which included the transcriptional upregulation of genes such as MDA5, IPS-1, TRAF3, and IκB. In the present study, the ABCG2 mRNA was downregulated in the model group chicken kidneys, partially explaining the significantly increased uric acid levels caused by NIBV infection.

cord-335644-gt1ey9wz	This study is devoted to addressing this knowledge gap by cross-comparisons of field measurements, wind tunnel tests, and large-eddy simulations (LES) under neutral and unstable conditions. When thermal conditions, specifically unstable stratification, are considered in ventilation, there will be additional challenges: First, a larger model domain is required to catch the larger turbulent structures in unstable simulations than in the neutral condition, while the grid size has to be kept small to sufficiently resolve the street-level air flows [19] . The objective of this study is to demonstrate the knowledge gap between current practices and reality by comparing wind tunnel test results, field measurements, and a pair of LES experiments in Hong Kong, and to propose possible adaptations for future AVA practices based on the comparative results and knowledge of atmospheric boundaries under various conditions. In this case study, we cross-compare pedestrian-level VR taken from field measurements, wind tunnel tests, and a pair of LES experiments in a high-density area of Hong Kong.

cord-336308-5ymjmbz2	The honeybee colony with its elaborate social organization and large repertoire of diseases provides an ideal setting to explore how the structure of the contact network contributes to the transmission of a disease. The early growth rate of an infectious process and the final epidemic size are lower in these networks compared with the mass-action model, largely because of the quick depletion of the local environment of susceptible individuals around an infected individual. This social contact network in the colony is therefore highly structured and nonrandom, leading to a pool of individuals that is heterogeneous with respect to its probability of contacting, manifesting, and transmitting an infection, presenting an invading pathogen with the challenge of negotiating this complex landscape (Fig. 2) . It is important to note here that the structure of the social network in the colony is an emergent property that arises from individual behavior, which can be altered by simple pathophysiological mechanisms arising from a disease.

cord-336441-m6pur6td	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.

cord-336986-rmxin1da	Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. Abstract: Eight differentc ompounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/oro ther hemorrhagic fever virus (HFV) infections.T hey can be considered as either (i)adenine analogues (3-deazaneplanocin A, galidesivir,G S-6620 andr emdesivir) or (ii)guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). [26] It wasa lso found active against other emerging viruses such as respiratory syncytial virus (RSV) and hepatitis Cv irus (HCV),a nd the presence of the 1''-cyano group in remdesivir wasf ound to be critical in providing selectivity toward the viral (RNA) polymerases.

cord-337747-7sb03moe	title: Molecular detection of respiratory pathogens among children aged younger than 5 years hospitalized with febrile acute respiratory infections: A prospective hospital‐based observational study in Niamey, Niger This study aims to describe viral and bacterial infections among children aged younger than 5 years hospitalized with febrile ARI at two hospitals in Niamey, Niger''s capital city, and the reported clinical procedures. 14 This study aims to describe the viral and bacterial infections among children aged younger than 5 years hospitalized with febrile ARI at two national hospitals of Niamey, the capital city of Niger, and the reported clinical procedures. In this 1-year prospective study, both viral and bacterial pathogens were detected in high proportion among hospitalized children aged younger than 5 years with febrile ARI in Niamey, Niger. Viral and bacterial etiology of severe acute respiratory illness among children < 5 years of age without influenza in Niger

cord-338907-5l6rsa94	title: The association between blood eosinophil percent and bacterial infection in acute exacerbation of chronic obstructive pulmonary disease Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. 3 The global initiatives for chronic obstructive lung disease (GOLD) guideline recommend the use of antibiotics when a bacterial infection is suspected in events of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study was the first to analyze whether bacterial infections can be differentiated based on the eosinophil percent of 2% in AECOPD patients in Korea. Although these studies were not conducted for COPD patients, it was reported that respiratory viral infections showed various cytokines and eosinophil activation depending on the type of virus. 31 In this study, patients with diseases that could affect eosinophil were initially excluded and the use of inhaled corticosteroids or oral steroid was analyzed using univariate and multivariate analysis.

cord-338942-q4neat3x	Isothermal deoxyribonucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), exhibit characteristics ideal for point-of-care (POC) applications, since their instrumentation is simpler in comparison with the standard method of polymerase chain reaction. Nucleic acids amplification methods are primarily required to be performed, as the original number of either DNA or ribonucleic acid (RNA) copies in the clinical sample is insufficient for their direct detection. A microfluidic disk-based LAMP chip, integrating sample preparation and detection, was developed [44] (Fig. 2B ). Loop-mediated isothermal amplification integrated on microfluidic chips for point-of-care quantitative detection of pathogens An integrated rotary microfluidic system with DNA extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-ofcare pathogen diagnostics An integrated microfluidic loop-mediated-isothermal-amplification system for rapid sample pre-treatment and detection of viruses Development and application of a loop-mediated isothermal amplification method on rapid detection Escherichia coli O157 strains from food samples

cord-339080-lw45xd9m	title: Integrating the resources of Korean disaster management research via the Johari window Descriptive content analysis was used to compare resources with the viewpoints of Korean-speaking researchers and English-speaking researchers using the Johari window. If the Korean research field fails to assess or use the networks of all disaster management research resources, it may not smoothly suggest appropriate alternatives not only for decision-makers but also for disaster victims. Descriptive content analysis was the methodology used for this study, as it has been considered as one of the most effective tools in analyzing the important features of Korean disaster management research resources and evaluating not only the tangible effects of research resources but also their intangible effects (FenRIAM, 2019; Vo, 2013) . Using impact assessment, this article assesses (or evaluates) how the Korean field of disaster management research has been doing with its resources and what the field should do to improve the current situation and establish appropriate alternatives.

cord-339120-38rsfs0d	authors: Yan, Nan; Tang, Cheng; Kan, Ruici; Feng, Fan; Yue, Hua. title: Genome analysis of a G9P[23] group A rotavirus isolated from a dog with diarrhea in China In this study, an RVA strain designated RVA/Dog-tc/CHN/SCCD-A/2017/G9P[23] was isolated in cell culture from a pet dog stool sample with acute diarrhea, and its whole genome was sequenced. The sequence closest to the NSP4 gene of RVA/Dog-tc/ CHN/SCCD-A/2017/G9P [23] was that of human strain R479 which was previously shown to be of porcine rotavirus origin (Wang et al., 2010) . On the other hand, the sequence closest to the VP1 gene of SCCD-A was that of strain LL3354 which was reported to be the result of a porcine rotavirus having transmitted to a human, but the phylogenetic tree for the VP1 genes showed that strains SCCD-A and LL3354 clustered together in an independent group that was distinct from any of the previously established lineages (Fig. 1) .

cord-339235-8xslz4bs	title: Molecular detection and phylogenetic properties of isolated infectious bronchitis viruses from broilers in Ahvaz, southwest Iran, based on partial sequences of spike gene A phylogenetic tree (Fig. 2) , based on the hypervariable region of S1 gene sequences of four IBV isolates from the present study and other strains of IBV retrieved from GenBank, was generated. Infectious bronchitis virus is one of the main pathogens of commercial and backyard chickens with several serotypes and genotypes circulating in the world. Genotyping of Avian infectious bronchitis viruses in Iran (2015-2017) reveals domination of IS-1494 like virus Molecular characterization of infectious bronchitis viruses isolated from broiler chicken farms in Iran The pathogenesis of a new variant genotype and QX-like infectious bronchitis virus isolated from chickens in Thailand Isolation and molecular characterization of Sul/01/09 avian infectious bronchitis virus, indicates the emergence of a new genotype in the Middle East

cord-339327-4422s317	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] .

cord-339871-jso21mbx	To investigate the diversity of PEDVs responsible for the ongoing outbreaks in South Korea, in this study, we determined the full-length sequences of the S proteins of field isolates and complete genome sequences of representative strains identified throughout 2017. Based on the S gene sequences, therefore, PEDV can be genetically separated into two genogroup clusters, genogroup 1 (G1, classical and recombinant: low-pathogenic) and genogroup 2 (G2, field epizootic or panzootic: high-pathogenic), which are further divided into subgroups 1a and F I G U R E 1 Phylogenetic analysis based on nucleotide sequences of the spike genes (a) and full-length genomes (b) of porcine epidemic diarrhoea virus strains. Molecular characterization and phylogenetic analysis of membrane protein genes of porcine epidemic diarrhea virus isolates in China Full-genome sequence analysis of a variant strain of porcine epidemic diarrhea virus in South Korea Genomic and antigenic characterization of Porcine epidemic diarrhoea virus strains isolated from South Korea

cord-339931-e2ylkonb	We aimed to evaluate the treatments, particularly the role of corticosteroids, in patients with late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are several therapeutic methods for LOHC, including ensuring appropriate hydration, hematological homeostasis (maintaining high platelet counts, appropriate red cell counts, and levels of clotting factors), pain relief, catheterization for cystoscopic clot extraction, continuous bladder irrigation with normal saline for prevention of clots and bladder tamponade, anti-infection (particularly antiviral), hyperbaric oxygen, estrogen, clotting factors, and keratinocyte growth factor therapies [5] . However, for the patients having concurrent grade II to IV acute GVHD and refractory LOHC, systemic corticosteroid therapy should be added immediately with the use of empirical antiviral therapies or anti-CMV therapy (Fig. 1) . For patients showing unsatisfactory response to anti-infection therapies, additional corticosteroid therapy may help to achieve CR, particularly for those with severe LOHC. Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versushost disease

cord-340152-b4vg33ap	The aim of this study was to evaluate the effect of the oral administration of chestnut tannins (Castanea sativa Mill.) in order to reduce the duration of calf neonatal diarrhea. Administration of tannins in calves with diarrhea seemed to shorten the DDE in T by almost 4 days compared to C, suggesting an effective astringent action of chestnut tannins in the calf, as already reported in humans. The aim of the present study was to evaluate the effect of oral administration of chestnut tannins (Castanea sativa) in the treatment of calf neonatal diarrhea. Data concerning the weight at birth and at the third week of life, the age of diarrhea onset and the T0 fecal scores (T0-FS) recorded for both groups were assessed for normal distribution by the Shapiro-Wilk normality test and then a Mann-Whitney test was applied in order to verify differences between the two groups at the inclusion time [28] .

cord-340280-m1j6v33y	OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)‐related respiratory viruses in the United Arab Emirates (UAE). 1, 5, 9 Contrary to the accumulating knowledge of ARIs in temperate regions, epidemiological research on acute respiratory viral illness in tropical and subtropical areas is limited, although the epidemiological diversity, according to local climate and latitude, has been well studied. 14 Our study was designed to describe the molecular epidemiology of ARI-related respiratory viruses, including the seasonality of the viruses in the northern UAE for over 2 years. 2, 24, 25 FLU was the most common respiratory virus in all age groups, and the positivity rate was 20.0%, which is similar to previous data reported from studies in Oman. 7,34 However, our data suggest that in the UAE, like in other temperate countries, a diverse set of respiratory viruses contribute to the ARI cases that compel patients to visit medical facilities, because of their severity.

cord-340501-bcaerchf	In this chapter, we will discuss the current state-of-the-art of activity-based probes, reporter substrates, and other relevant tools based on Ub as recognition element, to study the enzymes involved in the complex system of ubiquitination. state-of-the-art of activity-based probes, reporter substrates, and other relevant tools based on Ub as recognition element, to study the enzymes involved in the complex system of ubiquitination. A panel of all seven isopeptide-linked diUb probes can be constructed and used to covalently capture the active site cysteine of the DUB showing its reactivity and preference toward certain linkage types. Unraveling the complexity of this, highly sophisticated system is aided greatly by the development of (activity-based) probes reporting on the dynamics and structural mechanisms used by activating enzymes, ligases, and proteases counteracting the buildup of (poly)-ubiquitinated substrates.

cord-340629-1fle5fpz	In infants, prior to the introduction of rotavirus vaccines, RVAs could be detected in up to 50%-60% of all childhood hospitalisations due to acute gastroenteritis each year, were estimated to cause 138 million cases of gastroenteritis annually, and 527,000 deaths in children o5 years of age living in developing countries. Recent emerging epidemic and pandemic virus infections that cause severe disease in humans and that are associated with food production, preparation and food contamination include the coronavirus, severe acute respiratory syndrome (SARS-CoV), Nipah virus, Ebola virus and some of the highly pathogenic influenza virus strains, such as the H5N1 subtype. Infections by Severe Acute Respiratory Syndrome (SARS) virus, Nipah virus (NiV), H5N1 virus, Hepatitis A virus (HAV), Hepatitis E virus (HEV), Adenovirus, Astrovirus, Norovirus (NoV) and Rotavirus (RVA) in humans and animals are detected by nucleic acid amplification tests and serologic tests.

cord-340781-z348xbn0	Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 .

cord-340791-jcsfbxgu	Airports have developed in response to the overall traffic growth, providing infrastructure and services to their airline customers. In addition to providing access to the global air transport system thus supporting connectivity, they also generate direct, indirect, and induced economic activities and employment (McGraw, 2017) . It needs to be noted, however, that other industries certainly do generate employment, attract additional businesses (including air traffic/airports) and prompt multiplier effects as well. For the airlines, airports are instrumental for offering their product by providing the required infrastructure to operate aircraft and service their customers being passengers and cargo shippers. The airline business requires adequate airport access as well as facilities and services at competitive fees and charges, plus a growth perspective for future development. In order to address the airlines'' demand for adequate capacity and facilities to operate their business, airports provide the required infrastructure and offer a range of services.

cord-340956-1t3o24u5	Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both the swine H1N1 (odds ratio [OR] 19.16, 95% confidence interval [CI] 3.55–358.65) and swine H3N2 (OR 2.97, 95% CI 1.16–8.01) viruses, compared to unexposed and non-CAFO swine workers with less intense swine exposure. Conversely, higher odds of seroconversion against swine H3N2 virus were observed among the unexposed (OR 2.27, 95% CI 1.43-3.60) and CAFO-exposed (OR 1.98, 95% CI 1.11-3.42), when compared to the non-CAFO swine workers; the unexposed participants had higher geometric mean MN titers, compared to the other 2 groups, for all time points (Table 3) . In this report, we present the first 24 months of data from a 5-year prospective, cohort study of IAV among participants exposed and unexposed to swine in China.

cord-341272-mw6ujjrk	The relevance of individual genetic variations to Pseudomonas aeruginosa infection is emerging in several respiratory illnesses of different etiologies including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or bronchiectasis. Studies with different inbred mouse strains support the contribution of the host genetic background to predispose the animals to chronic infection and different degrees of disease severity due to a different immunoreactivity to pathogens (Table 1 ). Recently, we exploited the agar-beads mouse model of long-term chronic lung infection, refined and characterized in C57Bl/6NCrl , in five phylogenetically different inbred strains of mice to identify deviant disease phenotypes and to dissect the cell-mediated immunity . Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response The host genetic background defines diverse immune-reactivity and susceptibility to chronic Pseudomonas aeruginosa respiratory infection

cord-341907-vql8e2j3	Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Nevertheless, when coating the ELISA plate with a ZIKV full-length E protein without hFc, significantly high-titer IgG antibodies were induced, particularly in the Alum and MPL-adjuvanted EDIII ( Figure 2C ), suggesting that fusion of hFc to the EDIII subunit vaccine did not affect the generation of ZIKV-specific IgG antibodies. Nevertheless, when coating the ELISA plate with a ZIKV full-length E protein without hFc, significantly high-titer IgG antibodies were induced, particularly in the Alum and MPL-adjuvanted EDIII ( Figure 2C ), suggesting that fusion of hFc to the EDIII subunit vaccine did not affect the generation of ZIKV-specific IgG antibodies.

cord-342124-jdv17u86	title: Viral networks and detection of potential zoonotic viruses in bats and rodents: A worldwide analysis To address this gap in knowledge, we compared the associative capacity of the host–virus networks in rodents and bats with the identification of those viruses with zoonotic potential. (2015) analyse viral networks between rodents and bats at global scale identifying several ecology factors to explain virus-host associations. The parameter "betweenness" can be used to Impacts • The analysis of virus and host networks (rodents and bats) allows us to measure the potential risk of zoonotic diseases. • Measuring network connectivity can be a useful tool for identifying hosts and viruses of potential importance in the transmission dynamic of zoonotic diseases. Therefore, in this study we aimed to compare and recognize the differences in the associative capacity of the host-virus networks in rodents and bats worldwide, as well as to identify the viruses that may shift across species, including humans, suggesting zoonotic potential.

cord-342242-cynpob7b	Based on the analysis of B11-Fc and G3-Fc clones'' circulation time in the serum (presence of antibodies 14 days after injection), we decided to conduct an experiment on the survival of these mice, which previously received a single injection of the VHHs with the Fc fragment, with a repeated administration of only the lethal toxin dose 14 days after the original administration. Overall, we obtained numerous clones after two rounds of biopanning; we selected 15 clones for initial analysis based on their CDR3s, chose two clones (B11 and G3) with the best pre-mixed results in phage form in vivo, produced them in protein form, and modified their structure and characteristics by dimerization via a (Gly4Ser) 3 linker and fusion to a human IgG Fc fragment to enhance their protective activity.

cord-342782-xty16m8w	Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. The three salicylanilide anthelmintic drugs showed a dose-dependent anti-HAdV activity against both HAdV5 and HAdV16, with 100% inhibition of plaques formation at 1.25, 5 and 2.5 μM for NIC, OXY and RAF, respectively ( Fig. 2a,b) . The CC 50 values for these molecules were in all cases significantly higher than the IC 50 concentrations required for inhibition in our antiviral activity and mechanistic assays for both 293β5 cells (Table 1 ) and A549 cells (22.9 ± 9.8 µM, 76.1 ± 14.4 µM and 80.6 ± 34.7 µM for NIC, OXY and RAF, respectively). The aim of this study was to evaluate the anti-HAdV activity of NIC, a salicylanilide anthelmintic drug of human use to set the basis for its further experimental and clinical development as a potential new treatment for HAdV infections.

cord-342923-prgorr3d	title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection. Previous studies have demonstrated hnRNP A1 could interact with N proteins of SARS Coronavirus and mouse hepatitis virus (MHV) [14, 19] . Our previous work has proved that hnRNP A1 underwent different regulations in jejunum tissues of piglets infected with PEDV virulent strain and its attenuated strain [20] . The beads were then washed with IP lysis buffer five times and boiled in sample buffer, and the proteins were subjected to SDS-PAGE, followed by immunoblotting analysis with anti-Flag PAb or anti-hnRNP A1 PAb. CCL-81 cells grown on coverslips were infected with PEDV YN144 strain, YN13 strain and CV777 strain, respectively, at a multiplicity of infection (MOI) 0.001.

cord-343107-oj1re34k	Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. The 7D10 antibody recognizes the NTD of MERS-CoV S glycoprotein and neutralizes the infectivity of pseudotyped and live virus with a potency comparable to those of the most active RBD-targeting antibodies. The NTD N222Q mutation also dramatically reduced the binding and neutralization by 7D10, but did not dramatically affect the cell infection of pseudotyped MERS-CoV ( Supplementary Fig. 11) . A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein

cord-343145-ptkw0csu	title: The politics and ethics of hospital infection prevention and control: a qualitative case study of senior clinicians'' perceptions of professional and cultural factors that influence doctors'' attitudes and practices in a large Australian hospital METHODS: This qualitative case study involved in-depth interviews with senior clinicians and clinician-managers/directors (16 doctors and 10 nurses) from a broad range of specialties, in a large Australian tertiary hospital, to explore their perceptions of professional and cultural factors that influence doctors'' IPC practices, using thematic analysis of data. RESULTS: Professional/clinical autonomy; leadership and role modelling; uncertainty about the importance of HAIs and doctors'' responsibilities for preventing them; and lack of clarity about senior consultants'' obligations emerged as major themes. CONCLUSIONS: Failure of healthcare and professional organisations to address doctors'' poor IPC practices and unprofessional behaviour, more generally, threatens patient safety and staff morale and undermines efforts to minimise the risks of dangerous nosocomial infection.

cord-343206-9tqivs5f	A mass mortality event involving Chaerephon plicatus and Taphozous theobaldi bats occurred during a heat wave in April 2016 in Cambodia. Systematic documentation of bat die-offs related to extreme weather events is necessary to improve understanding of the effect of changing weather patterns on bat populations and the ecosystem services they provide. Although the effects of climate change on wildlife populations is increasingly documented (FAO 2012) , there is still much to learn about the responses of particular species to extreme temperature events, and the potential consequences for their populations and the ecosystem services they support. Systematically documenting mass mortality events is important to understand how bat populations could be affected by a changing environment and climate (Welbergen et al. As such, this report contributes to documenting how changes in land-use and weather patterns influence bat population resilience and health.

cord-343390-y903mxcj	title: Bovine respiratory syncytial virus seroprevalence and risk factors in non-vaccinated dairy cattle herds in Brazil This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. Due to this, the current study aimed to determine antibody prevalence against BRSV and investigate some risk factors associated with BRSV seroprevalence in herds of an important milk producing region in São Paulo State, Brazil. Bovine respiratory syncytial virus seroprevalence and risk factors in endemic dairy cattle herds Prevalence of and risk factors for bovine respiratory syncytial virus (BRSV) infection in non-vaccinated dairy and dual-purpose cattle herds in Ecuador

cord-343596-w9rw2wak	Red blood cell invasion requires a co-ordinated series of protein/protein interactions, protease cleavage events, intracellular signals, organelle release and engagement of an actin-myosin motor, which provide many potential targets for drug development. In this review, we discuss red blood cell invasion as a drug target and highlight a number of approaches for developing antimalarials with invasion inhibitory activity to use in future combination therapies. One leading drug target involved in signalling during RBC invasion is calcium dependent protein kinase 1 (CDPK1), a parasite kinase not present in the human host (Harper and Harmon 2005) that has key roles in microneme secretion, activation of the actin-myosin motor and other processes required for RBC invasion (Fig. 2b-e) (Green et al. Suramin and suramin analogues inhibit merozoite surface protein-1 secondary processing and erythrocyte invasion by the malaria parasite Plasmodium falciparum

cord-343780-084lq92r	title: Detection, sequence analysis, and antibody prevalence of porcine deltacoronavirus in Taiwan To investigate if PDCoV is also present in Taiwan, three swine coronaviruses—PDCoV, porcine epidemic diarrhea virus (PEDV), and transmissible gastroenteritis coronavirus (TGEV)—were tested using real-time reverse transcription polymerase chain reaction (rRT-PCR) in 172 rectal swab samples from piglets exhibiting diarrhea between January 2016 and May 2017 on 68 pig farms in Taiwan. Currently, there are at least three members of the family Coronaviridae that can cause diarrhea in pigs: transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine deltacoronavirus (PDCoV) [8] . Based on the real-time RT-PCR (rRT-PCR) detection results, the percentage of pig farms that were positive for at least of one of the coronaviruses was 25% for PDCoV (17/68), 22.1% for PEDV (15/68), and 2.9% for TGEV (2/68). Phylogeny analysis of PDCoV-N genes showed that PDCoVs found in Taiwan were highly similar in their nucleotide sequences to isolates from the United States, mainland China, and other countries (Fig. 1) .

cord-344184-ac2bhtdj	title: The effect of cow udder score on subsequent calf performance in the Nebraska Sandhills However, beef cows with poor udder conformation may decrease production by decreased calf BW at weaning and increased labor costs, leading producers to cull females with mammary problems. The objective of this study was to evaluate the effect of beef cow udder score within two calving seasons on preweaning and postweaning progeny performance. Models included the effect of treatment, cow age, calving season, and calf sex for all appropriate data. Moreover, Hennessy and Arthur (2004) evaluated the effect of high and low preweaning growth on calf efficiency in the feedlot, reporting no differences in ADG between the two groups. However, steer calves suckling GOOD udder cows did have heavier carcass weights after the finishing period. Effects of intramammary infection and parity on calf weaning weight and milk quality in beef cows

cord-344227-rdlinzrn	As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Mice deficient in C3 (C3 -/-), the central protein of the complement signaling pathway, were protected from SARS-CoV-induced weight loss and had reduced pathology, improved respiratory function, and lower levels of inflammatory cytokines/chemokines in the lung and periphery. Immunohistochemical staining revealed that SARS-CoV MA15 infection induced complement deposition in the lung (Fig. 4) , similar to that associated with pathogenesis in Ross River virus-infected mice (41) and some influenza virus infections (34) , and it is likely that complement deposition contributes to pulmonary disease and inflammatory cell recruitment.

cord-344309-6c2wttxg	title: Development and application of an indirect ELISA for the detection of antibodies to porcine epidemic diarrhea virus based on a recombinant spike protein In this study, an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant truncated spike (S) protein of PEDV was developed and validated. This indirect ELISA was compared to indirect immunoinfluscent assay (IFA), and the overall coincidence rate was 96.74% based on testing 368 clinical serum samples with different PEDV antibody levels. Finally, the S1 indirect ELISA was applied to detect serum antibodies of 3304 field samples collected from different pig farms in eastern China, and it presented an overall substantial agreement on the PEDV infection status. Therefore, this study selected a gene fragment within the S1 subunit as a coating antigen to develop an indirect enzyme-linked immunosorbent assay (ELISA) method for the detection of PEDV antibodies. Detection of antibodies against porcine epidemic diarrhea virus in serum and colostrum by indirect ELISA

cord-345044-2fez1gu0	The present paper reports a 3‐year cross‐sectional hospital‐based study aimed at detecting and quantifying HAdV DNA and mRNA of the HAdV hexon gene in adenoid and palatine tonsil tissues and nasopharyngeal secretions (NPS) from patients with adenotonsillar hypertrophy or recurrent adenotonsillitis. Although this study indicates that a significant proportion (~85%) of individuals with chronic adenotonsillar diseases have persistent nonproductive HAdV infection, including those by HAdV C, B, and E, epithelial and subepithelial cells in tonsils seem to be critical for HAdV C production and shedding in NPS in some patients, since viral antigen was detected in these regions by immunohistochemistry in four patients, all of which were also positive for HAdV mRNA detection. This was a cross-sectional study that evaluated the presence of HAdV in different samples of tissues and secretions from the upper respiratory tract of children with obstructive sleep apnea (OSA) or recurrent tonsillitis, comparing the results with control patients.

cord-345045-nlui9d6e	Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. In 2015, 8515 ID physicians were practicing in the United States [5] , often combining clinical care with work as educators, epidemiologists, public health leaders, antimicrobial stewardship or infection prevention and control directors, researchers, administrators, and policymakers. Further, the work of ID physicians provides broader public protection against infectious threats through community and healthcare facility-based infection control and prevention activities, surveillance, outbreak response, and other public health activities.

cord-345312-i7soyabu	OBJECTIVE: To determine whether rapid polymerase chain reaction (PCR) testing for influenza and respiratory syncytial viruses (RSV) in emergency departments (EDs) is associated with better patient and laboratory outcomes than standard multiplex PCR testing. Rapid PCR tests were expected to facilitate timely and appropriate initiation of treatment, improve outbreak prevention and infection control measures, and expedite the assessment of patients in EDs. In this study, we analysed routinely collected data to determine whether rapid PCR testing for influenza and RSV infections in EDs is associated with improved patient and laboratory outcomes. Other studies have also reported that hospital admission numbers were significantly lower when rapid influenza virus testing was used in EDs. An analysis of outcomes for more than 300 adults at a tertiary care centre in New York found that early diagnosis of respiratory infections was associated with significantly fewer hospitalisations of influenza-positive patients.

cord-346054-k84rcpav	Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. The analysis of IgG reactivity to structural and non-structural proteins and to recombinant fragments and synthetic peptides spanning VP1, VP2, and VP3 from RV89 is shown in Supplementary Fig. 2a for all 120 children and in Supplementary Fig. 2b for those children (n = 41) who had shown increases of RV89-specific antibody responses in follow-up serum samples taken after recovery. Based on our previous observations that antibody increases specific for the N-terminal portion of VP1 can be detected in serum samples obtained from subjects after RV infection 36 , the PreDicta chip was equipped with a VP1 peptide set which should allow detecting species-specific immune responses at high resolution ( Fig. 1 ).

cord-346586-fxxceffl	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] .

cord-346697-ixho9t5g	For virus screening, we captured 86 Asian house shrews at 7 districts in Shenzhen city, Guangdong province, China from 2013 to 2015 (Table S1 in Supporting Information). SmHCVs were detected out at five sites in Shenzhen city, while more than two thirds positive samples came from the Bao''an and Figure 1 Sequence analysis, pathogenesis, and viral RNA detection of novel hepaciviruses in Asian house shrews. The phylogenetic tree based on obtained genome sequences (NS3 to NS5B region) showed these hepacivirus strains detected in Asian house shrews formed an independent branch ( Figure 1A) . In this study, highly diverse hepacivirus (SmHCV) sequences were detected in Asian house shrews. The viral RNA could be detected in samples collected from 2013 to 2015, suggesting that these SmHCVs had a wide distribution in Shenzhen city and had been circulated for a long time in Asian house shrews.

cord-346726-u7dhbmht	We aimed to describe the potential benefit of new rapid molecular respiratory tests (MRT) in decreasing inappropriate antibiotic use among the inpatients presenting with influenza-like illness (ILI). It is time to increase the awareness about the viral etiology in respiratory tract infections (RTIs) and implement MRT in clinical practice. In adults, influenza virus, rhinovirus, adenovirus, respiratory syncytial virus (RSV), human coronavirus, and parainfluenza virus cause infections with considerable morbidity and mortality [1, 3] , and in infants, RSV is the most common reason for RTIs among hospitalized patients [4] . In this study, we aimed to describe the viral etiology in influenza-like illness (ILI) in children and adults and to show the benefit of new rapid molecular respiratory tests (MRT) in decreasing inappropriate antibiotic use. By using molecular rapid tests (MRT) in our hospital, inappropriate antibiotic use and also duration of inappropriate antibiotic use after the detection of virus was significantly decreased among inpatients.

cord-346777-zmmnn9b2	title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. These results demonstrate that the MERS-CoV-S protein pseudotyped VSV particle-based neutralization assay would serve as a safe, reliable and highly specific alternative method to detect MERS-CoV neutralizing antibodies to be used for future sero-epidemiological studies. A laboratory-confirmed SARS-CoV patient serum sample and a panel of human sera with confirmed high neutralizing antibody titres to human coronaviruses 229E, HKU1, OC43 and NL63 were used in this study to evaluate the VSV-MERS-CoV-S particle-based neutralization assay for potential cross-neutralization.

cord-347465-yu6oj30v	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.

cord-347889-lpd1olqq	Our work demonstrates that when the Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a accessory gene is expressed in yeast it causes a slow-growth phenotype. We also demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in cells. We demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in mammalian cells. Our work demonstrates the utility of yeast for identifying novel interactions between viral proteins and eukaryotic cells and defines SIRT1 as a proviral factor for MERS-CoV replication. (B) Yeast cells transformed with a Gal-inducible plasmid to express MERS-CoV ORF4a or a vector control were cultured for 2 days in media containing 2% raffinose to reach saturation. We have demonstrated that SIRT1 is a proviral cellular protein for MERS-CoV replication and that yeast cells represent a powerful tool to identify previously unknown virus-host interactions.

cord-348063-5yd7hr5e	In this study, turbulent Schmidt number (Sc(t)) was modified as a function of turbulent kinematic viscosity rather than a constant value to better simulate dispersion of airborne contaminant in two typical enclosed spaces: an aircraft cabin and an office room. Fig. 2 shows comparison of experimental data from particle image velocimetry (PIV) measurement [29] with simulated airflow patterns in CS4 of the aircraft cabin ( Fig. 1 (a) ) by three turbulence models. Fig. 3 shows comparison of predicted airflow velocities with experimental data [22] at poles V1 to V3 for the office room ( Fig. 1 (b) ) by different turbulence models. In this paper, a method to modify Sc t as a function of turbulent kinematic viscosity based on airflow vortex structures was introduced to better simulate dispersion of airborne contaminant in two typical enclosed spaces: an aircraft cabin and an office room.

cord-348131-pkovyjo6	The mRNA level of RNase L did not change upon IFN treatment in RoNi/7 cells, indicating that, similarly to the human RNASEL gene, bat RNASEL is not an ISG ( Fig. 2A) , consistent with the lack of an ISRE in its promoter region (data not shown). Upon infection with SINV, degradation of rRNA, as assessed by Bioanalyzer, was detected in wild-type (WT) and bOAS1-KO and bOAS2-KO cells but not in bOAS3-KO and bRNase L-KO cells (Fig. 6C) , indicating that the activation of RNase L during SINV infection in RoNi/7 cells is dependent on bOAS3 expression, similar to our previous findings in human cells. bOASL2 shares high sequence similarity with mouse OASL2 (see Fig. S2 in the supplemental material), suggesting that Activation of Bat RNase L Depends on OAS3 but Not MAVS ® like the mouse protein, bOASL2 may have catalytic activity.

cord-348409-oxjd263z	Areas covered: The architectural traits of filamentous viruses and their derivatives, IAVs, facilitate the display of specific antigenic peptides which induce antibody production to prevent or curtail infection. The creation of Random Peptide Libraries (RPL), where random oligopeptides are fused to major capsid proteins (gp3 or gp8) and displayed on individual inovirus clones creating a random variety of IAVs which can be used for vaccine design via epitope mapping using monoclonal or polyclonal antibodies. Through this breakthrough technology which was the subject matter of the Nobel Prize in Chemistry 2018 (see ''Expert Commentary'' below), inovriuses displaying oligopeptides mimicking antigens (or specific epitopes of an antigen) can be used to vaccinate hosts thus inducing the desired antibody production. Unlike previous studies, which used a single specific peptide fused to a inovirus, four different antigenic peptides were displayed by inoviruses in a cocktail of recombinant IAVs. The induction of a cellular response completely vaccinated 1/3 of the pigs in the study and reduced the number of cysticerci in all other pigs [61] .

cord-348660-qnbgywgy	Following optimization of the ELISA protocol, 18 test sera were obtained from broiler chickens exposed to natural wild-type IBV infection, 18 test sera from broiler chickens vaccinated with a live-attenuated commercial IBV vaccine, and sera obtained at different time-points from chicks immunized with recombinant IBV N protein (described above) were analyzed to detect IBV N-specific antibodies. To assess the reliability of the performance of our in-house indirect IBV N ELISA, a panel of sera was obtained from chickens naturally infected with local wild-type IBV strains, chickens vaccinated with live-attenuated commercial IBV vaccine, and chickens immunized with recombinant IBV N protein (expressed in a baculovirus expression system). This represents the first study in Turkey that expressed recombinant IBV N protein in baculovirus and examined its reactivity against antisera obtained from Turkish chickens for potential use as antigen Fig. 5 Detection of IBV N specific antibodies in sera obtained from naturally infected chicken (a) and vaccinated chickens (b) using an in-house IBV-N ELISA and a commercial ELISA.

cord-348819-gq7lp931	The second set of manuscripts focuses on in-depth analysis of each of the factors affecting cross-species transmission: infection dynamics in reservoir hosts, pathogen survival in the environment, recipient host exposure, dose -response relationships and establishment of infection in recipient hosts. The authors show how modelling cross-species transmission as a percolation process, in which pathogens move from infected reservoirs to recipient hosts along a graph representing various spillover pathways [18, 19] , reveals first principles for how such datasets will behave and how common statistical tools can produce misleading inferences and poor predictions. This inclusive approach to confronting epidemiological models with longitudinal data in poorly understood reservoir host systems holds promise for elucidating spatio-temporal risk of pathogen spillover. Through several case studies (e.g. Lyme disease [63] , Hendra virus [64] , Plasmodium knowlesi [65] ), the authors further demonstrate how ecologically focused research has facilitated predicting spillover of particular pathogens in space and time and facilitated design of intervention strategies.

cord-349011-kxhpdvri	Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O''Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. The "Viral Subversion of Host Cell Processes" session also included presentations from the following trainees: Nichole McMullen (Dalhousie University) who reported the unconventional egress mechanisms of non-enveloped reoviruses, Justine Sitz (Université Laval) who described interactions between a human papillomavirus protein and a host DNA repair-specific E3 ubiquitin ligase, and Quentin Osseman (Université de Montréal) who described interactions between respiratory syncytial virus (RSV) and the host autophagy pathway.

cord-349042-u9svz7pf	The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. Examination of expression profiles of single live cells has shown that linear aRNA amplification neither results in occurs after synthesis of double-stranded cDNA, when T7 RNA polymerase is added and aRNA is transcribed from the cDNA template. 45 developed a method to facilitate aRNA detection of antibody-antigen interactions by covalently attaching a double-stranded cDNA that contains a T7 RNA polymerase promoter in front of a reporter sequence to a specific antibody.

cord-349279-wbb7h2zu	The rates of infection and community epidemiology of respiratory viruses in healthy children needs further definition to assist interpretation of molecular diagnostic assays in this population. The most commonly detected viruses in samples collected during ARI were HRV (52.8%), HCoV (11.0%), parainfluenza virus (PIF) (6.0%), IFV (4.5%), RSV (3.8%), and HMPV (3.5%). Detection of any virus and codetection of viruses were both significantly associated with swabs collected during ARI episodes. While their corresponding risk ratios are not considered significant, the number of detections of these viruses is relatively small, and a larger analysis would be required to rule out the clinical significance of detecting HRV-B, AdV and HBoV in ARIs. The effect of viral coinfection on respiratory disease severity in children has not been well established. New molecular virus detection methods and their clinical value in lower respiratory tract infections in children Viruses associated with acute respiratory infection in a community-based cohort of healthy New Zealand children

cord-350019-4nlbu54e	Using this extensively studied biological system, we identified the first example of a TLR-stimulated lncRNA, lincRNA-Cox2, which was capable of positively and negatively regulating distinct types of innate immune genes [42] [43] [44] [45] [46] . The majority of lncRNAs studied in immunity were initially identified following RNA-sequencing to examine their expression profiles in specific cell lines or tissues during inflammatory activation. Hence future studies may opt to target TF binding sites, secondary structure and/or polyadenylation sites as a way to more finely dissect the functional portions of lncRNAs. The ease in which Cas9 can be targeted to specific genomic regions sparked the development of a modified (catalytically inactivated) version of the protein fused to the KRAB (Krüppel associated box) chromatin-silencing domain termed CRISPRi [174, 175] (Fig. 3C) . Genome-wide screening for functional long noncoding RNAs in human cells by Cas9 targeting of splice sites

cord-350201-tluc2ck7	The impetus for the current study was the identification of a virus related to avian paramyxovirus type 1 (APMV-1) from a fatal human case of unknown cause in the Netherlands by viral metagenomics analysis [8] . In this study, we fully characterized the Dutch clinical isolate of APMV-1-like virus, determined its phylogenetic relationship to other APMV-1 strains, and correlated presence of this virus with lesions in tissues obtained from the patient at autopsy. Domestic pigeons were inoculated intratracheally with the Dutch clinical virus isolate to determine infectivity and transmissibility, clinical signs, and pathological changes (Supplementary Methods). This is consistent with the New York case, where evidence of PPMV-1 infection in feces and urine also suggested extrarespiratory Pigeon Paramyxovirus-Linked Pneumonia • JID 2018:218 (1 October) • 1041 Table 1 spread [11] . It is relevant for these PPMV-1 cases that the risk of 2 pigeon-associated diseases-chlamydiosis and cryptococcosis-was largely a function of the immune status of patients, rather than contact with infected birds [32, 33] .

cord-350389-6o9t2am7	RESULTS: We used sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) after in gel digestion of the proteins and quantitative real-time PCR (qRT-PCR) and showed that the levels of two MUPs, odorant-binding protein 3 (OBP3) (i.e. PGCL4) and MUP13 (i.e. PGCL1), in urine and their mRNAs in liver were higher in males than in females and were suppressed by orchidectomy and restored by testosterone treatment (T treatment). In the current study, we analysed MUPs in Lewis rats using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative real-time PCR (qRT-PCR), isoelectric focusing electrophoresis (IEF), In gel digestion and nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS), and then generated rMUPs. We further examined the activity of rMUPs by testing whether these proteins elicited behavioural and neuronal responses in female rats.

cord-350565-mejd7blb	We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. Although serosurveys have bolstered recent efforts to understand the geographic range and clinical spectrum of EBOV and Zika virus infections (47, 48) , the enhancement of dengue hemorrhagic fever risk by prior exposure (49) , and the role of immunologic history in influenza susceptibility and vaccine response (50) , there remain few examples of public health programs undertaking serological studies for routine surveillance, at least in civilian populations (51) .

cord-350836-1enteev7	RIG-I (Retinoic acid-inducible gene I) and MDA5 (Melanoma Differentiation-Associated protein 5), collectively known as the RIG-I-like receptors (RLRs), are key protein sensors of the pathogen-associated molecular patterns (PAMPs) in the form of viral double-stranded RNA (dsRNA) motifs to induce expression of type 1 interferons (IFN1) (IFNα and IFNβ) and other pro-inflammatory cytokines during the early stage of viral infection. For the former, siRNA-mediated knock-down (110, 111) , cellular knockout (112) and inhibition by viral protein (109, (113) (114) (115) (116) conditions for TRIM25 in multiple cell types have been shown to change RIG-I cellular localization (110) and to negatively affect RIG-I K63 ubiquitination, association with MAVS and IFN signaling [when the constitutively active RIG-I CARD domain was overexpressed (109, (112) (113) (114) (115) (116) or during viral infection (109, 111, 114) ].

cord-350964-0jtfc271	In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Nucleic acid that was extracted from liver samples of 157 bats (29 species; Table S1 ) and 470 rodents (six species) was screened for pegivirus and human hepatitis B, C, E viruses and their homologues ( Table 1 ) by nested and semi-nested PCR assays with degenerate primers.

cord-351046-yq7287k9	There is a broad differential for a patient with respiratory failure, and careful physical examination and history are imperative to reduce morbidity and prevent mortality. There is a broad differential for a patient with respiratory failure, and careful physical examination and history are imperative to reduce morbidity and prevent mortality. The initial vital signs on his third ED presentation were as follows: temperature 36.7°C, heart rate 130 beats per minute, respiratory rate 30 breaths per minute, pulse oximetry 99%, and blood pressure of 113/81 mm Hg. On examination, the patient was awake and calm in his mother''s arms with no acute distress. The differential for a patient presenting to the ED with acute respiratory distress is broad and includes infection, ingestion, trauma, envenomation, muscular disorders, and autoimmune etiologies. Scorpion envenomation often presents with respiratory distress along with increased drooling, abnormal eye movements, muscle twitching, and agitation. 13, 14 The treatment for myasthenia gravis begins with respiratory support including intubation or noninvasive ventilation.

cord-351413-3nfukrfl	title: Spatiotemporal Clustering of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Incidence in Saudi Arabia, 2012–2019 We analyzed the spatiotemporal clustering of the MERS-CoV incidence in Saudi Arabia between 2012 and 2019 at the city level by using Kulldorff''s spatial scan statistics via SaTScan 9.6 [39] . The results of the spatiotemporal cluster analysis of MERS-CoV infection, using years and months as the time aggregates from 2012 to 2019, showed significant most likely and secondary clusters in Saudi Arabia (Table 3; Table 4 and Figure 5 ; Figure 6 ). Wadi The results of the spatiotemporal cluster analysis of MERS-CoV infection, using years and months as the time aggregates from 2012 to 2019, showed significant most likely and secondary clusters in Saudi Arabia (Table 3; Table 4 and Figure 5 ; Figure 6 ). Community case clusters of middle east respiratory syndrome Coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: A descriptive genomic study

cord-351525-306syrrn	title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. As a brief summary of the results, 21 of the 24 cell lines showed significant susceptibility to SADS-CoV infection, defined by efficient viral replication, antigen expression, and the appearance of cytopathic effect (CPE). As some cells did not display CPE after SADS-CoV infection, all cell lines were subsequently tested for viral M protein expression by immunofluorescence assay (IFA) Fig. 1) , revealing the same range as seen by CPE in the different cell lines (data not shown).

cord-351760-698voi9y	The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. In vivo study demonstrated that prophylaxis with m336 reduced virus titers in the lung of rabbits infected with MERS-CoV [15] , and m336 also provided transgenic mice expressing human DPP4 with full prophylactic and therapeutic protection from MERS-CoV [16] . A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection Passive Transfer of a Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV

cord-351932-dn60t7qa	As reported by Jesus et al., 2016 , diosgenin (3-β-hydroxy-5spirostene) is the primary furostanol saponin found in several plants, including Dioscorea species, and is described as a promising bioactive compound with several medicinal properties, i.e. hypolipidemic, antioxidant, anti-inflammatory, hypoglycaemic, and antiproliferative activities (5) . A new furostanol glycoside namely 26-O-β -D-glucopyranosyl-3β,26-dihydroxy-20,22-seco-25(R)-furost-5en-20,22-dione-3-O-α-L-rhamnopyranosyl-(1→4)-α -L-rhamnopyranosyl-(1→4)-[ α -L -r h a m n o p y r a n o s y l -( 1 → 2 ) ] -β -Dglucopyranoside was isolated from the methanolic extract of the rhizome of Dioscorea cayenensis growing in Cameroon, together with the known spirostanol saponins described as methyl protodioscin, asperoside and prosapogenin A of dioscin (12) . Concerning the phytochemical profile, twelve cyclic diarylheptanoids were isolated from the rhizomes of Dioscorea nipponica (20) , among which two new cyclic diarylheptanoids, diosniponol A and B; moreover, as reported by the same authors, these compounds were evaluated for their effects on nitric oxide production without cell toxicity in lipopolysaccharide-activated BV-2 cells.

cord-352231-awkkper2	In 1987, Garfield listed the "top 100" best cited articles ever published in JAMA and named them "citation classics" [8] , and these classics represent the highest impact work in a given field [9] . We analyzed the papers according to number of citations, publication year, authors, journal impact factor, country of origin, and article type (basic science, observational study, interventional clinical trial, and review) [21] . We also observed the lack of papers on brucellosis in animal health and for this we suggest two explanations: (a) journals in the categories of agriculture and food sciences receive fewer citations than those in basic and clinical sciences as evidenced by the impact factor in these categories. Despite these limitations, the study provides a picture for the main cited articles in brucellosis research publications since the discovery of Brucella 130 years ago.

cord-352807-1yhxnvoh	manillensis had an overall preference toward C-endings and indicated that codon usage patterns are mediated by differential expression, GC content, and biological function. In general, mutation pressure tends to shuffle A/U and G/C pairs to cause nucleotide composition bias, selection constraints lead to preferences for codons that maximise protein production efficiency in highly expressed genes, and genetic drift eliminates codon changes across generations as a result of immigration and emigration at the population level. It would be of great value to generate more reliable coding sequences for new gene discovery; furthermore, the genetic processes revealed by their codon usage patterns will further contribute to determining the effects of long-term evolution on the genetically diversified and unique physiological behaviour of medical leeches. Their codon usage patterns, which were calculated as GC12/GC3 ratios and ENC values, were compared to the average values obtained from all CDSs to measure the effects of different evolutionary states of anticoagulant-related mechanisms.

cord-352837-a29d5dkv	Given the technical and bioinformatic advances as well as the declining laboratory costs, the application of deep sequencing to identify etiologic agents in clinical samples has been approached in different pathologies, including those caused by community-acquired respiratory viruses (CARVs). With these caveats in mind, and given the significant global burden of viral respiratory tract disease in the very young and the very old [10] [11] [12] oropharyngeal (NP/OP) samples of SARI cases were identified through a national surveillance study conducted by the Uganda Virus Research Institute from 2010 through 2015. Taken together, this report from resource-limiting settings is also of relevance for resource-rich countries and raises the question about how to best expand current first-or second-line testing for respiratory viral pathogens including CMV, parvovirus B19, and measles, and how to move to more deep sequencing virome analysis and comprehensive metagenomics in the near future.

cord-353185-aapg75af	Building the value of China-Africa "One Health" strategy partnerships, frameworks and capacity development and implementation through leveraging on current and innovative China-Africa health initiatives, but also, mobilizing efforts on climatic changes and disasters mitigation and lifestyle adaptations strategies against emerging and current infectious diseases threats are essential to establish epidemic surveillance-response system under the concept of global collaborative coordination and lasting financing mechanisms. Africa CDC focus on strategic priority areas and innovative programs aiming at improving evidence-based decision making and practice in event-based capacity development for surveillance, disease prediction, and improved functional clinical and public health laboratory networks and actions in minimizing health inequalities, and promoting quality care delivery, public health emergency preparedness and response best practices in achieving regional [1, 4, 10] .

cord-353325-41ke6vor	Among various wind tunnel measurement techniques, use of Irwin probe is simple and accurate compared to hot-wire anemometry and it can be installed at numerous locations for simultaneous measurement of pedestrian level wind speed. Presence of tall building in the urban area tends to deflect the upper-level high-speed wind to the ground, which creates conditions that could be unpleasant or even dangerous to pedestrians. The last section presents different studies related to the actual urban environment, which comprises the effect of building design parameters and general guidelines for the urban planning in response to pedestrian comfort. To obtain design related contribution for the assessment of pedestrian level wind environment, generally field measurement on the real urban environment, wind tunnel testing on the scaled model of the urban area and CFD simulation are employed. The present study reviews the different wind comfort criterion for pedestrians and measurement techniques to evaluate these wind speeds.

cord-353553-adaow2w7	Recientemente, las recomendaciones de la European Respiratory Society and European Society for Clinical Microbiology and Infections Diseases 7 , aconsejan el ingreso en la UCI ante la presencia de al menos dos de las siguientes circunstancias: presión arterial sistólica menor de 90 mm Hg, presencia de insuficiencia respiratoria con PaO 2 /FIO 2 < 250 o la afectación de 2 o más lóbulos en la radiografía de tórax, o bien uno de los siguientes: necesidad de ventilación mecánica o necesidad de vasopresores durante más de 4 horas (shock séptico), con un nivel de recomendación A3. Se define bacteriemia o fungemia relacionada con el catéter como el aislamiento del mismo microorganismo en los hemocultivos extraídos por punción en una vena periférica y en el cultivo cuantitativo o semicuantitativo de la punta del CVC retirado, en un paciente con clínica de sepsis, y sin otro foco de infección aparente.

cord-353554-98uzivsk	title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. 64 The virus-receptor interaction was reported to be a principal determinant of viral host 65 range, tissue tropism and cross-species infection [11, 16, 22] . However, we found the viral receptor tended not to interact with each 248 other ( Figure S3D 270 Since the virus has to compete with other proteins for binding to the receptor, proteins (Table S5) .

cord-354664-mzzvmyea	While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. Last updated in 2007, the joint Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) guidelines for CAP recommend empiric combination therapy with a beta-lactam plus macrolide or monotherapy with a respiratory fluoroquinolone (e.g., moxifloxacin) for adult patients hospitalized with CAP in a non-ICU setting [21] . The body of evidence used to support current IDSA/ATS guideline recommendations that advocate for combination therapy with a beta-lactam plus macrolide in the management of hospitalized adult patients with CAP originates from a series of large, retrospective cohort studies that showed improved clinical outcomes in patients treated with combination therapy. Based on the findings of these large observational studies, many clinical practice guidelines recommend combination therapy with a beta-lactam plus macrolide or monotherapy with a respiratory fluoroquinolone as first-line therapy for hospitalized adult patients with CAP.

cord-354700-bdpp3qmf	I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. I will discuss how a target-agnostic approach based on highthroughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host-pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response.

cord-354783-2iqjjema	Several strategies for containing the spread of misinformation in temporal networks have been proposed [59] [60] [61] [62] . [60] examined epidemic spreading on activity driven temporal networks and developed mean-field based theoretical approaches for three different control strategies, i.e., random, targeted, and egocentric. At time step t each spreader i transmits with probability λ the misinformation to ignorant neighbors in network G(t). In an effective containing strategy the misinformation spreading dynamics is suppressed for a given fixed fraction f of immunized nodes, i.e., the objective function is The most used strategy for containing the spread of misinformation is randomly immunizing a fraction of f nodes [66] . An effective containing strategy with a fraction of immunized node f and a small outbreak threshold λ c greatly decreases the final misinformation outbreak size R. As in Fig. 6 , the HC strategy most effectively contains the misinformation spreading on temporal networks irrespective of the values of λ.

cord-354816-so3v11fy	Through correlation analysis, regression modelling and Sobel test, it is found that: i) occupant health is significantly affected by neighborhood building height, building density and cleanliness; ii) the relationships between neighborhood environment and occupant health are significantly mediated by indoor environment, in terms of visual and acoustic comfort; and iii) neighborhood greenspace affects occupant health indirectly through influencing indoor air quality. To measure the mediating effects of indoor environment (i.e., thermal comfort, indoor air quality, ventilation, visual comfort and acoustic comfort) on the relationships between neighborhood environment (i.e., neighborhood building height, neighborhood building density, neighborhood greenspace and neighborhood cleanliness) and occupant health, the classic Sobel test is adopted [2] . The results of this study indicates that health of occupants are directly affected by neighborhood building density, neighborhood building height and neighborhood cleanliness, and these effects are significantly mediated by occupants'' acoustic and visual comforts in the indoor environment.

cord-354904-7gq2e6f0	We used spherical gold nanoparticles (average diameter, 15 nm) as a platform for the antigen for swine transmissible gastroenteritis virus (TGEV). The literature data demonstrate that immunization of animals with the TGEV antigen coupled to gold nanoparticles (GNPs) not only activates antigen-presenting cells but also increases the proliferative activity of splenic lymphoid (antibody-forming) cells. Immunization with the TGEV antigen conjugated to GNPs as a carrier activates the respiratory activity of lymphoid cells and peritoneal macrophages, which is directly related to their transforming activity and to the activation of antibody generation. After the virus''s nucleic acid was inactivated with ribonuclease, the resultant antigen (a mixture of viral capsid proteins) was used for conjugation with GNPs and for subsequent animal immunization. A study of the respiratory activity of splenic lymphoid cells (Fig. 5) showed that after immunization with the conjugate, the activity increased 2.2-fold, as compared to the control, whereas after immunization with TGEV antigen alone, it did not change much.

cord-355465-qjtifwhd	title: Molecular characterization of US-like and Asian non-S INDEL strains of porcine epidemic diarrhea virus (PEDV) that circulated in Japan during 2013–2016 and PEDVs collected from recurrent outbreaks RESULTS: Phylogenetic analysis based on S gene sequences revealed that all the recent field PEDVs were genetically distinct from the classical Japanese strains, and were classified into three genotypes: North American (NA), S INDEL, and Asian non-S INDEL. Another subclade, designated as PED-J2, including 14 Japanese strains collected in Miyazaki were also clustered into a segregated branch as shown in Fig. 1 The sequence data revealed that S genes from the Japanese field PEDVs are of 4152-4161 nt long, and encode proteins with 1381-1386 aa residues. 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

cord-355535-01h8yyqj	The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. A standardized form was used for data extraction, including the main characteristics (author, year of publication, sample size, age, definition of exacerbation, quality, detection method, study design and season), primary outcome (the prevalence of viral infection during asthma exacerbations), and secondary outcomes (the prevalence of viruses in different strata). We also did a subgroup analysis to assess the weight of viral infection on asthma exacerbations with respect to geographic region, population, type of respiratory tract secretion examined, and detection method. Because difference in the geographic regions, age, study population, type of respiratory tract secretion, and detection method significantly confound the determination of the prevalence of individual viruses, heterogeneity was not assessed in this study.

cord-355570-27wwgdtp	The following gene expression signatures were studied: (1) oviduct markers (estrogen receptor 1, ovalbumin, and SPINK7 ovomucoid), (2) epithelial markers (keratin 5, keratin 14, and occludin) and (3) stem-like/progenitor markers (CD44 glycoprotein, LGR5, Musashi-1, and sex determining region Y-box 9, Nanog homebox, OCT4/cPOUV gene encoding transcription factor POU5F3). In this paper, we have made initial attempts to confirm progenitor molecular signatures in oviducts of laying hen (Gallus gallus domesticus) and quail (Coturnix japonica), both in tissue and in cultured oviduct epithelial cells (in vitro assay). Those panels were comprised of oviduct (ESR1, OVAL, and OVM), epithelial (KRT5, KRT14, and OCLN), and stem-like/progenitor (LGR5, MSI1, SOX9, NANOG, and OCT4/cPOUV) gene expression signatures. In this study, we have characterized the expression of oviduct, epithelial, and stem/progenitor markers in the oviduct tissue and cell culture of two avian species, the hen and the quail.

cord-355991-4zu69e0y	The epidemiological and clinical presentations of outbreaks of neonatal mortality associated with enteritis and the detection of TGEV started in the gestation units. When TGEV enters in a naïve herds, an epizootic form characterized by a 100% mortality of pre-weaning piglets due to diarrhea and dehydration is normally observed [1, 14] . In this study, although all cases were selected using clinical features and epidemiological information, the histological evaluation consistently showed lesions compatible with viral infection. The application of IHC and ISH-RNA on archived paraffin blocks from cases of neonatal diarrhea with high morbidity and mortality allowed retrospective identification of TGEV infection. During the period when the sows showed gastro-enteric clinical signs, 2-to 4-day-old piglets presented vomiting (75-80%) and diarrhea (90%), and the mortality rate of suckling pigs reached 90%. Emergence of porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences

cord-356007-6b0w36l9	OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. Of these 10 available HCP, 9 reported prolonged, close contact with an unrecognized patient case before implementation of MERS-CoV IPC measures and with limited PPE use ( Table 3 ). Among the 10 interviewed HCP cases, the time from first positive MERS-CoV result to serum collection was 55-61 days, and 1 was seropositive: a 32-year-old female who had reported headache, muscle aches, and productive cough. Among them, 9 HCP (33%) tested rRT-PCR positive for MERS-CoV; 5 reported contact with index patient B before At hospital B, 34 of 50 MERS-CoV rRT-PCR-negative HCP contacts of cases (68%) were interviewed and provided serum. One was seropositive, a physician who had close, prolonged contact with index B after isolation and while wearing recommended PPE; however, he had previously tested rRT-PCR positive for MERS-CoV in 2013.

cord-356048-nku844kt	RECENT FINDINGS: In the context of Hajj, one of the largest religious MGs at Mecca, Saudi Arabia, respiratory tract infections are the leading cause of infectious diseases in pilgrims with a prevalence of 50–93%. In this review, we summarize recent findings in the field of infectious diseases associated with international MGs. The Hajj (Table 1) The Hajj, an annual Muslim pilgrimage to Mecca, Saudi Arabia, is one of the largest religious MGs in the world with about two million pilgrims from 185 countries [4] . The predominance of bacterial pathogens in Hajj-related gastrointestinal infections poses a major risk to public health through the potential emergence and transmission of antimicrobial-resistant bacteria [53] . (Table 1) Although numerous gastrointestinal and respiratory outbreaks have been documented at large-scale open-air festivals, particularly music festivals, with thousands of participants, these events are probably neglected, in terms of public health attention, as well as surveillance and prevention of infectious disease strategies, compared to other categories of MGs [78] .

cord-356094-sbtigcfr	perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. The results of adaptation and replication in CEK cells, such as CPE, reverse transcription polymerase chain reaction (RT-PCR), and IBV growth curve determined by tissue culture infective dose (TCID 50 ) at different time were tested. The relative mRNA expression level of IBV-N gene was detected by qRT-PCR and the virus titer of IBV was determined by TCID 50 to analyze the antiviral effect of HPE, HPW and SEE (Figure 3) . FIgUre 8 | The effects of Hypericum perforatum ethyl acetate (HPE) on infectious bronchitis virus (IBV) messenger ribonucleic acid (mRNA) expression levels of trachea (A) and kidney (B).

cord-356242-tydil7d7	title: Estimating the impact of violent events on transmission in Ebola virus disease outbreak, Democratic Republic of the Congo, 2018–2019 Here, we use spatial and temporal trends of EVD case counts to compare transmission rates between health zones that have versus have not experienced recent violent events during the outbreak. Since 1976, 10 of the over 34 reported Ebola virus disease (EVD) outbreaks have been in the Democratic Republic of the Congo (DRC) (World Health Organization Regional Office for Africa, 2018; Anon, 2019) . Our time series regression found an effect of violent events on estimated R across both symptom onset data and case report data, across all plausible levels of inter-region transmission (Fig. 3) , and lagged follow-up periods of 14 or more days.