msword_compared_abstracts.txt

v1only_Compared_abstracts_2020-07-27.docx 


Main 
document 
changes 
and 
comments 
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published_pubmed_ 


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determine 
which 


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reveal 
asymmetric 
transmission 
patterns 
between 


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drive 


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in 


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may 


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, 


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is 


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are 


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-

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to 


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likely 


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A 



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" 


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. 
The 
degree 
of 


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.: 


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remains 
uncertain. 


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is 
well-supported 
by 
meta-analytic 
studies, 
but 
population-based 
estimates 
remain 
scarce. 


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for 
population-level 


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of 


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associated 
with 


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related 
to 


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Here, 
we 
used 
an 


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Using 


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range 
of 


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tasks 


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assessment 
criteria 



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assessments 


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to 
investigate 
whether 
there 
are 


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, 
this 
study 
investigated 
population-level 


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ing 


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. 


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.: 


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a 


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( 


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cognitive 
functioning 
[ 


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) 


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-

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) 


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]) 


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-


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s 


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, 


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Classification 
of 


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was 


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classifications 
were 


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(CIDI-SF). 


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. 


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explored 


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investigated 


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i) 
recurrent 
MDD, 
(ii 
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a) 
recurrence, 
(b 
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MDD 


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d 


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. 


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. 


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.: 


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β 


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ß 


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q 


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PFDR 


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∙ 


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× 


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significant 


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, 


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β≥ 



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ß= 


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Analysis 
within 
the 
lifetime 
MDD 
group 
indicated 
that 


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Clinical 
characteristics 
revealed 
differential 
profiles 
of 
cognitive 
impairment 
among 


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with 


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; 
those 
who 
reported 


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had 
significantly 
lower 
g-factor 
(β 
= 
-0.14, 
P 
= 
1.5∙10-2), 
with 
greatest 
impairments 
in 


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and 
use 
of 
psychotropic 
medication 
performed 
worse 
on 
cognitive 
tests. 
Severe 
psychosocial 
impairment 
and 


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(β 


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showed 
the 
strongest 
association 
(ß 


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q 


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PFDR 


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∙10-5). 
Other 
clinical 
characteristics 
showed 
differential 
profiles 
of 
cognitive 
impairment 
across 
cognitive 
domains. 
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× 
10-5). 


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. 
These 
findings 
reveal 
a 
modest 
negative 
association 


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.: 
Findings 
describe 
small 
but 
robust 
associations 


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lower 


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. 


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within 
a 
population-based 
sample. 
Overall 
effects 
were 
of 
modest 
effect 
size, 
suggesting 
limited 
clinical 
relevance. 
However, 
deficits 
within 


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showed 
greater 
deficits 


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were 
more 
pronounced 


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MDD 


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clinical 


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with 
greatest 
effects 
relating 
to 


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particularly 
severe 


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. 


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." 


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Both 
genetic 
and 
environmental 
factors 
influence 
the 
etiology 
of 



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) 
is 


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), 


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irreversible 


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worldwide. 
Previous 
genetic 
and 
epidemiological 
studies 
have 
shown 
that 
the 
AMD 
progression 
are 
affected 
by 
genetic 
variants 
and 
environmental 
factors. 


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. 


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mainly 
diagnosed 


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primarily 
measured 


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color 
fundus 


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and 
recent 
studies 
have 
shown 
the 
success 
of 


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of 
the 
fundus 
of 
the 
retina 
and 
recently 
developed 


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in 
predicting 


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can 
successfully 
predict 


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the 
studies 


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these 
methods 



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utilized 


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used 


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s 


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The 
Age-Related 
Eye 
Disease 
Study 
(AREDS), 
a 
large-scale 
clinical 
trial 
from 
the 
National 
Eye 
Institute, 
includes 
massive 
genome-wide 
genotyping 
data, 
longitudinal 
color 
fundus 
photographs, 
and 
disease 
severity 
assessment 
over 
a 
period 
of 
12 
years, 
providing 
an 
unprecedented 
opportunity 
to 
investigate 
prediction 
models 
for 
AMD 
progression. 
In 
this 
report, 
we 
jointly 
used 


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Here 
we 
used 
both 


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dynamically 


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whether 


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as 
having 


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had 


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(e.g., 
whether 
the 
time 
to 
progression 
to 
late 
AMD 
for 
the 
eye 
exceeds 
3 
years 
from 
the 
current 
visit) 


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(CNN). 


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. 


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color 



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centered 
on 
the 
macula 


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and 
52 
AMD-associated 
genetic 
variants 


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with 
corresponding 
genotypes 
and 


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from 
the 
Age-Related 
Eye 
Disease 
Study, 
which 
provided 
disease 
severity 


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and 
fundus 
images 


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. 
The 
first 
part 
of 
this 
model 
was 
derived 
from 
a 
CNN 
to 
extract 
features. 


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over 
a 
period 
of 
12 
years. 


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the 
color 


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photos 


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images 


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-

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-

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-

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(AUC) 



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CI: 


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confidence 
interval 


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-

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– 


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AUC 


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averaged 
area 
under 
the 
receiver 
operating 
characteristic 
curve 
value 


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CI: 


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confidence 
interval 


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-

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– 


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We 
have 
validated 
our 
results 
in 
an 
independent 
dataset 
of 
200 
Caucasians 
extracted 
from 
UK 
Biobank 
and 
the 
results 
showed 
an 
AUC 
of 
0.9 
(95%CI: 
0.85-0.94) 
for 
predicting 
whether 
the 
eye 
progresses 
to 
late 
AMD 
exceeding 
the 
3 
years. 


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(MF)/multicentric 
(MC) 


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but 
are 
clearly 
separated 
with 
no 
intervening 
in 
situ 
or 
invasive 
disease. 
It 


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and 


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the 
prevalence 
of 


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prevalence 


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/multicentricity 


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a 
cohort 
of 


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mutant 
patients 


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mutation 
carriers 
with 
breast 
cancer 
from 
Northern 
Ireland 


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-

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-

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91 


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), 
(120 


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-91, 


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), 
with 


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-120) 
and 


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, 


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/multicentricity 


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%, 


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% 


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, 


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= 


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= 


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multifocal 


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MF/MC 


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= 


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= 


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), 


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) 
and 


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= 


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= 


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), 
and 
were 
more 


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). 
These 
observations 
are 


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younger 
at 
diagnosis 
compared 
with 
those 
with 
unifocal 
tumours 
(p=0.039). 


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driven 
by 
the 
higher 
BRCA2 
mutation 
prevalence 
observed 
within 
this 
cohort. 
The 


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multifocal 


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MF/MC 


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-

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-

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OR 


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odds 
ratio 


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to 


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– 


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= 


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= 


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BRCA2 
carriers 
show 
much 
greater 
multifocality 
than 
those 
carrying 
BRCA1. 
Multifocal 
tumours 
are 
strongly 


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These 
findings 
were 
subsequently 
validated 
in 
a 
second, 
large 
independent 
cohort 
of 
patients 
with 
BRCA 
-

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with 


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breast 
cancers 
from 
a 
UK-wide 
multicentre 
study. 
This 
confirmed 
a 
significantly 
higher 
prevalence 
of 
MF/MC 
tumours 
amongst 
BRCA2 
mutation 
carriers 
compared 
with 
BRCA1 
mutation 
carriers. 
This 
has 
important 
implications 
for 
clinicians 
involved 
in 
the 
treatment 
of 
BRCA2 
-associated 
breast 
cancer, 
both 
in 
the 
diagnostic 
process, 
in 
ensuring 
that 
tumour 
focality 
is 
adequately 
assessed 
to 
facilitate 
treatment 
decision-making, 
and 
for 
breast 
surgeons, 
particularly 
if 
breast 
conserving 
surgery 
is 


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both 
BRCA2 
mutant 
and 
oestrogen 
receptor 
positive 


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considered 
as 
a 
treatment 
option 
for 
these 
patients 


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" 


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: 


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-

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– 


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: 


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-


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– 


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: 


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in 


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with 
those 
of 


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: 


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GWAS 


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Genome-wide 
association 
study 


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. 


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." 


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Purpose: 
Spinal 


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"PurposeSpinal 


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functional 


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but 
retention 
of 
the 
paralogous 
SMN2 
gene 


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genetic 



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its 
paralog 


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by 
standard 
NGS-based 
pipelines 
has 
been 


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is 


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historically. 
Preconception 


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. 


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of 
potential 
parents 


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SMN1 


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of 
SMN1 


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. 
Methods: 
We 


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and 
Genomics.MethodsWe 


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novel 
informatics 


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whole-

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W 


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. 
This 
algorithm 
calculates 
the 
CNs 
of 
SMN1 
and 
SMN2 
using 



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by 
analyzing 


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and 
SMN2. 
Results: 
We 


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/2.ResultsWe 


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a 
total 
of 


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sequenced 
to 
high 
depths 
(>30x) 
across 
five 
ethnic 
populations. 
Across 
these 
samples 
we 


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, 


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a 
total 
of 
251 
(1317) 


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1568 


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whole 
gene 


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SMN1 
gains 
or 


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12:08:00 
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(gains) 
of 
SMN1 


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6241 
(374) 


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12:08:00 
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6615 


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SMN2 
gains 
or 



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(gains) 
of 
SMN2. 
We 


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, 
and 


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we 
validated 


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99.8% 
of 


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CN 
calls 
and 
showed 
that 
all 
(48/48) 


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98% 
(47/48) 


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99.7% 


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those 
measured 


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orthogonal 
methods, 


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digital 
PCR. 
Conclusion: 
This 
WGS-based 


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a 
recall 
of 
100% 
for 
SMA 
and 
97.8% 
for 
carriers, 
and 
a 
precision 
of 
100% 
for 
both 
SMA 
and 
carriers.ConclusionThis 


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-

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also 


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carrier 



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for 
carrier 
status 


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large-scale 
WGS 


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GS 


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. 


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." 


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and 
enduring 


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disease 
course. 


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courses. 


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disease 


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-

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– 


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-

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(GE) 
– 


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an 



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s 


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a 


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s 


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multi-site 
longitudinal 


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it 
was 
possible 
to 


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we 
could 


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will 


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would 


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Importantly, 


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classification 
based 
on 


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m 


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f 


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s 


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t 



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, 


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BOLD 
activity 


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activation 
estimates 


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were 
obtained 
from 
the 
same 
data 
and 


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predict 
clinical 
trajectories 
with 


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allow 
for 


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classification 


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publishedabstracts 
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the 


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12:08:00 
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generative 
embedding 


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12:08:00 
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GE 


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dynamic 


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trial-by-trial 


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the 


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. 
Given 
the 
limited 
sample 
size 



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our 
study, 


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trial-by-trial 
stimuli. 


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present 
results 
are 
preliminary 
but 
may 
serve 
as 
proof-of-concept, 
illustrating 
the 
potential 
of 
GE 
for 
obtaining 
clinical 
predictions 
that 
are 
interpretable 
in 
terms 
of 
network 
mechanisms. 


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a 
mechanistically 
informed 
generative 
model 
of 
a 
neuronal 
circuit 
underlying 


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publishedabstracts 
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12:08:00 
PM 


abnormal 
dynamic 
changes 
of 
connections 
involved 
in 


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perception 
may 
have 
predictive 
utility 
for 
distinguishing 
disease 
courses 
in 
MDD 
patients 


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processing 
might 
be 
associated 
with 
higher 
risk 
of 
developing 
a 
less 
favorable 
clinical 
course 


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publishedabstracts 
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12:08:00 
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Background 


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publishedabstracts 
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-

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publishedabstracts 
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Methods 


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publishedabstracts 
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women 


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cases 


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publishedabstracts 
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to 


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publishedabstracts 
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– 



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publishedabstracts 
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<U+2009> 


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publishedabstracts 
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population 


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publishedabstracts 
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three 
hospitals 


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a 
population-based 
case–control 
study 


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9: 
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publishedabstracts 
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from 
2013 
to 
2015 


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9: 
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publishedabstracts 
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Results 


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publishedabstracts 
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<U+2009> 


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<U+2009> 


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publishedabstracts 
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, 


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<U+2009> 


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publishedabstracts 
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greater 
or 
equal 
to 


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publishedabstracts 
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12:08:00 
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= 


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publishedabstracts 
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<U+2009> 


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publishedabstracts 
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to 



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publishedabstracts 
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– 


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publishedabstracts 
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to 


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– 


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publishedabstracts 
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greater 
or 
equal 
to 


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12:08:00 
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= 


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publishedabstracts 
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<U+2009> 


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Pheterogeneity 


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p 
-heterogeneity 


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Conclusion 


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Differences 
in 
reproductive 
patterns 
and 
subtype 
heterogeneity 
are 
consistent 
with 
racial 
disparities 
in 
subtype 
distributions. 


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" 


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of 
geographic 
areas 
in 
analyses 
of 
health 
inequalities 
between 
places. 


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. 


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subdomains 
and 
indicators 
that 
are 
used 
to 
calculate 
the 
IMD 
score. 



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domains 
of 
deprivation. 


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subdomains 
and 
indicators 


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domains 


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This 
could 
offer 
insights 
into 
areas 
that 
face 
similar 
challenges. 


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sub-

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-

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Recent 


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represented 
local 
authorities 
that 
were: 
(i) 
Most 
deprived, 
predominantly 
urban; 
(ii) 
Least 
deprived, 
predominantly 
rural; 
(iii) 
Less 
deprived, 
rural; 
(iv) 
Deprived, 
high 
crime, 
high 
barriers 
to 
housing; 
and 
(v) 
Deprived, 
low 
education, 
poor 
employment, 
poor 
health. 


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only 
partially 
reflect 
different 
levels 
of 
overall 
deprivation. 
In 
particular, 
two 
clusters 
share 
similar 
overall 
IMD 
scores 
but 
have 
contrasting 
patterns 
of 
deprivation. 


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These 
methods 
can 
be 
used 
to 
draw 
on 
the 
richer 
set 
of 
information 
contained 
in 
the 
IMD 
subdomains 
and 


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This 
approach 


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identify 


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distinguish 
between 



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underlying 


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IMD 


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overall 
deprivation 


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. 


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." 


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Importance: 


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"Background 


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, 
suicidal 
ideation 


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-related 
behaviours, 
characterised 
as 
ideation, 
plans, 


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and 
suicide 
related 
death. 


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. 


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has 


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could 
have 


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Objective: 



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Aims 


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(MR) 


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Design: 


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Method 


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in 
the 
UK 
Biobank, 


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estimated 
observational 


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calculated 
observed 


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using 
data 
from 
the 
UK 
Biobank 
cohort. 


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. 


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conducted 
MR 
using 
both 
individual 
level 
and 
summary 
level 
methods. 
MR 
uses 


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used 
Mendelian 
randomisation 
to 
explore 
the 
relationship 
between 
smoking 
and 
suicide 
attempts 
and 
ideation, 
using 


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instrumental 
variables 


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instruments 


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Setting: 
The 
observational 
analysis 
and 
individual 
level 
MR 
were 
conducted 
using 
the 
UK 
Biobank, 
a 
cohort 
study 
that 
recruited 
from 
study 
centres 
across 
the 
UK 
between 
2006 
and 
2010. 
Summary 
level 
MR 
analyses 
used 
summary 
data 
from 
previously 
published 
genome-wide 
association 
studies 
conducted 
in 
individuals 
of 
European 
ancestry. 
Participants: 
337,053 
individuals 
from 
the 
UK 
Biobank 
aged 
from 
39 
to 
70 
years 
at 
recruitment 
(mean 
= 
56.91 
years, 
SD 
= 
7.99 
years) 
and 
54% 
of 
the 
sample 
were 
female. 
Exposures: 
Smoking 
initiation, 
smoking 
heaviness, 
smoking 
cessation 
and 
lifetime 
smoking. 
Main 
Outcome(s) 
and 
Measure(s): 
Suicidal 
ideation 
and 
suicide 
attempts. 


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: 


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and 


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, 


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behaviour 


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ideation 
and 
attempts 


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al 


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e 


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OR 
= 


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odds 
ratio, 


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, 


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; 


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= 



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to 


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– 


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, 
p< 


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;P< 


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MR 


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Mendelian 
randomisation 


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SNP 


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-nucleotide 
polymorphism 


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. 


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(odds 
ratio 
for 
lifetime 
smoking 
on 
suicidal 
ideation, 
0.050; 
95% 
CI 
-0.027 
to 
0.127; 
odds 
ratio 
on 
suicide 
attempts, 
0.053; 
95% 
CI, 
-0.003 
to 
0.110). 


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, 


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behaviours. 
Conclusions 
and 
relevance: 


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ideation 
or 
attempts. 
Conclusions 
This 
was 
the 
first 
Mendelian 
randomisation 
study 
to 
explore 
the 
effect 
of 
smoking 
on 
suicidal 
ideation 
and 
attempts. 



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strong 
evidence 
for 
a 
causal 
effect 
of 
smoking 
behaviour 
on 
suicidal 
behaviour. 
Our 
evidence 
suggests 
that 
further 
research 
is 
needed 
into 
alternative 
risk 
factors 
for 
suicide 
which 
might 
make 
better 
intervention 
targets. 


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clear 
evidence 
for 
a 
causal 
effect." 


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Background: 
The 


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"BackgroundThe 


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pre-hospital 


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prehospital 


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develops 
and 


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predicting 


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generating 
risk 
scores 
based 
on 


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based 
on 


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using 


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Methods: 
Dispatch 


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MethodsDispatch 


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to 


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– 


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Model 
predictions 
were 
used 
to 
generate 


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which 


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generated 
based 
on 
the 
models 
and 


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System 


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Scores 


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scores 


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similar 
but 


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Results: 
A 


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ResultsA 


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-

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– 


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s 


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to 


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– 


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scores 


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to 


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– 


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71 
to 


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70– 


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80 


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79 


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to 


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– 


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scores 


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scores. 


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.ConclusionsMachine 
learning-based 
risk 
scores 
outperformed 
a 
widely-used 
rule-based 
triage 
algorithm 
and 
human 
prioritization 
decisions 
in 
predicting 
hospital 
outcomes. 
Performance 
was 
robust 
in 
a 
prospectively 
gathered 
dataset, 
and 
scores 
demonstrated 
adequate 
calibration. 
Future 
research 
should 
explore 
the 
robustness 
of 
these 
methods 
when 
applied 
to 
other 
settings, 
establish 
appropriate 
outcome 



measures 
for 
use 
in 
determining 
the 
need 
for 
prehospital 
care, 
and 
investigate 
the 
clinical 
impact 
of 
interventions 
based 
on 
these 
methods." 


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performed 


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available 


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3 


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9 


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. 
Response 
to 
the 
first 
pharmacological 
treatment 


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after 
quality 
control. 
Antidepressant 
response 


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, 
considering 
rare 
variants 
only 
and 
rare 
+ 
common 
variants. 
Gene-

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. 
Gene-based 


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After 
quality 
control 
1209 
subjects 
were 
included. 


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, 


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Genetic 
models 
showed 


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was 
observed 
in 
the 
testing 
sample 
which 
was 


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and 
they 
were 



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factors. 
Some 
models 
were 
replicated, 
with 
a 
weaker 


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predictors, 
but 
they 
were 
not 
significantly 
better 
than 
clinical 
predictors 
alone. 
Replication 
results 
were 
driven 
by 
clinical 
factors, 
except 
for 
a 
model 
developed 
in 
subjects 
treated 
with 
serotonergic 
antidepressants, 
which 
showed 
a 
clear 
improvement 
in 


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, 
in 
STAR*D 
and 
GENDEP 
when 
considering 
also 
clinical 
factors 
and 
in 


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at 


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in 
STAR*D 


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Introduction: 
Diabetes 


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"BackgroundDiabetes 


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(DM) 


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and 
financially 
costly. 


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that 
can 
impose 
a 
substantial 
economic 
burden. 


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(DPN) 


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a 


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and 
frequent 
cause 


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microvascular 
complication 


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DM 
that 
increases 
the 
potential 
for 


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. 
Despite 
its 
serious 
complications,limited 
evidence 


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due 
to 
ulceration 
and 
amputation. 
Though 
there 


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available 
on 
the 
magnitude 


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a 
significant 
amount 


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diabetic 
peripheral 
neuropathy 
among 
patient 
with 
diabetes 
mellitus. 


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variation 
in 
the 
primary 
studies 
on 
DM 
regarding 
the 
prevalence 
of 
DPN 
in 
Africa. 


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the 
objective 
of 


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, 


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systematic 
review 
and 
meta-analysis 


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study 


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aimed 


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pooled 


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overall 


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diabetic 
peripheral 
neuropathy 
among 


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DPN 
in 
DM 


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with 
diabetes 
mellitus 


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Methods: 
PubMed 


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MethodsPubMed, 


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, 


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Africa 
journal 
online 


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, 
African 
Journals 
OnLine, 


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afro 
library 


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African 
Library, 


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the 


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s 


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the 


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’s 


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diabetes 
mellitus 


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. 
All 
statistical 


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in 
Africa. 
The 
meta-

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done 


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performed 


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the 


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™ 


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for 
windows. 
Results: 
Twenty 


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.ResultsTwenty 


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comprises 
of 


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includes 


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, 


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-

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– 


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, 


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magnitude 


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prevalence 


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in 
DM 
patients 


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at 


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Conclusion: 
This 


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ConclusionThis 


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diabetic 
peripheral 
neuropathy 


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DPN 


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-

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s 


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strategy 
depending 
on 
their 


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strategies, 
which 
are 
specific 
to 
the 


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context. 
Furthermore 


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. 


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study 


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. 
Key 
word: 
diabetic 
peripheral 
neuropathy 
diabetes 
mellitus 
Systematic 
review 
Meta-analysis 
Ethiopia. 


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." 


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" 


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Epstein–Barr 
virus 
( 


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) 


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‘ 


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’ 


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‘ 


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’ 


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‘ 


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’ 


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‘ 


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’ 


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‘ 


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’ 


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‘ 


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’ 


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A 
total 
of 


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attributable 
proportion 
due 
to 
interaction 
( 


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PM 


)<U+2009>=<U+2009> 


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1x10 


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publishedabstracts 
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U+2009><<U+2009>1<U+2009>×<U+2009>10 


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; 
RERI 
3.84, 
p<5x10-3; 
S 
1.68, 
p=0.06). 


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). 


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infectious 
mononucleosis 
( 


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) 


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odds 
ratio 
( 


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) 


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<U+2009>=<U+2009> 


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<U+2009>=<U+2009> 


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s 


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. 


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." 


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" 


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Recent 
years 
have 
seen 
a 
growing 
interest 
in 
the 
therapeutic 
use 
of 
psychedelic 
substances 
for 
the 
treatment 
of 
anxiety 
and 
depression 
in 
patients 
with 
affective 
and 
mood 
disorders. 


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how 
brain 
networks 
supporting 
perceptual 
and 
higher-order 
cognitive 
and 
emotional 
functions 
are 
affected 
during 


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. 


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on 
large-scale 
brain 
networks' 
functional 
organization. 


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on 



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about 


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the 


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onetoa 
few 


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24 
hours 


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one 


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1 


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one 


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1 


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i 


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ï 


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intra-and 
inter-network 


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maps 


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, 


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using 
a 
seed-to-whole 
brain 
connectivity 
approach, 
and 
statistically 



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, 
and 


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functional 


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subsequently 


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scores 
of 
the 


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scores 


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session. 


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effects. 


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functional 
connectivity 
in 
the 


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of 


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connectivity 
within 


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and 


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, 


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functional 
connectivity 
in 
the 


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of 



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connectivity 
within 


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one 


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, 
and 
increased 
connectivity 
between 
the 
salience 
and 
default 
mode 
networks 
1 


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. 
No 
connectivity 
changes 
between 
groups 
were 
found 
in 


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compared 
to 
placebo. 
Connectivity 
of 


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. 
Subacute 
increased 
connectivity 
of 
the 


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did 
not 
differ 
between 
groups. 


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connectivity 
increases 


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positively 


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assessed 
during 
the 
acute 
effects 
of 
ayahuasca, 
while 


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, 


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connectivity 
of 
the 


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connectivity 


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negatively 



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. 


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, 
and 
increased 
salience 
default 
mode 
network 
connectivity 
correlated 
with 
altered 
affect 
scores. 


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known 
to 


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that 


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processes. 


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functions." 


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reduced 


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is 
associated 
with 
lower 


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' 


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’ 


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RA 
increased 
the 


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Adjusted 
odds 
ratios 
(AORs) 
were 
estimated 
using 
the 
Cochran-Mantel-Haenszel 
(CMH) 
method 
and 
presented 
with 
95% 
confidence 
intervals 
(CIs) 
and 
p-values. 
RA 
was 
associated 
with 
a 
higher 


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-

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– 



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-

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– 


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-

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– 


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), 


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), 


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-

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– 


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-

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– 


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' 


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’ 


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-

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– 



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reduced 
by 
treatment 


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lower 
among 
patients 
treated 


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-

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– 


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-

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– 


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and 


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or 


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-

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– 


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was 


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reduced 


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associated 
with 
a 
lower 


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Alzheimer's 
disease 



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AD 


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-

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– 


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further 


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lower 


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reduction 


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achieved 


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found 


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reduced 
the 


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were 
associated 
with 
lower 


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-

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– 


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-

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– 



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" 


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. 


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. 


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-

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– 


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IgG1


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immunoglobulin 
G1– 


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publishedabstracts 
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a 


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(1 


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publishedabstracts 
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er 


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publishedabstracts 
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us 


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b 


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(2 


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publishedabstracts 
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er 



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publishedabstracts 
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us 


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. 


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n 


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publishedabstracts 
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al 


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publishedabstracts 
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. 


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publishedabstracts 
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IgG 


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immunoglobulin 
G 


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-

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. 
Clinicaltrials.gov 
identifier 
NCT02837705. 


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." 


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" 


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Glucocorticoid 
(GC) 
administration 
is 
an 
effective 
therapy 
commonly 
used 
in 
the 
treatment 
of 
autoimmune 
and 
inflammatory 
diseases. 
However, 
the 
use 


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Patients 
with 
type 
2 
diabetes 
mellitus 
(T2DM) 
are 
at 
risk 
for 
a 
variety 
of 
severe 
debilitating 
effects. 
One 


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PM 


GC 
can 
give 
rise 
to 



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the 
most 


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. 
The 
main 
detrimental 
side 
effect 
of 
GC 
therapy 
is 
significant 
bone 
loss, 
resulting 
in 
glucocorticoidinduced 
osteoporosis 
(GIOP). 


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experienced 
by 
patients 
with 
T2DM 
are 
skeletal 
diseases 
caused 
by 
changes 
in 
the 
bone 
microenvironment. 
As 
a 
result, 
patients 
with 
T2DM 
are 
at 
risk 
for 
higher 
prevalence 
of 
fragility 
fractures. 


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preventing 
and 
managing 
GIOP; 
however, 


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counteracting 
this 
effect. 
Some 
antidiabetic 
medications, 
such 
as 
metformin, 
have 
been 
shown 
to 
have 
a 
positive 
effect 
on 
bone 
health 


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clearly 
defined 
guidelines, 
it 
can 
be 
very 
difficult 
for 
physicians 
to 
choose 


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optimal 
therapy 
for 
their 
patients. 


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PM 


addition 
of 
additional 
drugs 
into 
patients’ 
treatment 
plans. 
Chinese 
randomised 
controlled 
trial 
(RCT) 
studies 
have 
also 
proposed 
antiosteoporotic 
pharmacotherapies 
as 
a 
viable 
alternative 
treatment 
strategy. 


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regarding 
this 
topic 


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two-part 


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patient 


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all 
available 
GIOP 
treatments 


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antidiabetics 
(part 
I) 
and 
antiosteoporotic 
(part 
II) 
pharmacotherapies 



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PM 


decrease 
fracture 
incidences, 


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12:08:00 
PM 


decrease 
fracture 
incidences 
among 


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12:08:00 
PM 


improve 
indications 
of 
bone 
turnover 
markers 
(BTMs) 
in 


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12:08:00 
PM 


undergoing 
GC 
treatments. 


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19: 
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12:08:00 
PM 


with 
T2DM. 


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PM 


MEDLINE, 
EMBASE 


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publishedabstracts 
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PM 


Medical 
Literature 
Analysis 
and 
Retrieval 
System 
Online, 
Excerpta 
Medica 
Database 


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PM 


CINAHL, 
CENTRAL 


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PM 


Cumulative 
Index 
to 
Nursing 
and 
Allied 
Health 
Literature, 
Cochrane 
Central 
Register 
of 
Controlled 
Trials 


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PM 


CNKI, 
CQVIP 


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19: 
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publishedabstracts 
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12:08:00 
PM 


China 
National 
Knowledge 
Infrastructure, 
Chongqing 
VIP 
Information 


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PM 


randomized 
controlled 
trials 
( 


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PM 


) 


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, 



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RCTs 
that 
evaluate 
different 
antiresorptive 
regimens 
taken 
by 


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12:08:00 
PM 


We 
will 
include 


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PM 


undergoing 
GC 
therapy 
during 
the 


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PM 


with 
T2DM 
who 
have 
taken 
antidiabetics 
(part 
I) 
or 
antiosteoporotic 
(part 
II) 
therapies 
with 
relevant 
outcome 
measures 
in 
our 


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or 
had 
taken 
GC 
for 
at 
least 
3 
months 
in 
the 
year 
prior 
to 
study 
commencement 
with 
lumbar 
spine 
BMD, 
femoral 
neck 
BMD, 
total 
hip 
BMD, 
vertebral 
fracture 
incidences 
and/or 
non-vertebral 
fracture 
incidences 
as 
outcomes 
will 
be 
selected 


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(ROB) 


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CINeMA 


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Confidence 
in 
Network 
Meta-Analysis 


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PM 


GRADE 


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Grading 
of 
Recommendations 
Assessment, 
Development 
and 
Evaluation 


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changes 
in 


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results 
as 


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and 
BTMs 
in 
either 



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PM 


or 
standardised 


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differences 
(WMDs) 
and 
standardized 
mean 
differences 
(SMDs), 


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difference, 


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odds 
ratios 


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ORs 


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(SUCRA) 


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ion 


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e 


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al 


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s 


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two-part 


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a 


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s 


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publishedabstracts 
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GIOP. 



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PM 


T2DM 
bone 
disease. 


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19: 
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publishedabstracts 
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PM 


an 


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s 


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PM 


antidiabetic 
medications 
and 
antiosteoporotic 


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12:08:00 
PM 


for 
maintaining 
bone 
health 


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19: 
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publishedabstracts 
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12:08:00 
PM 


reducing 
incidences 
of 
bone 
loss 
and 
fractures 
associated 


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19: 
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PM 


patients 


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GIOP. 
Systematic 
Review 
Registration 
International 
Prospective 
Register 
for 
Systematic 
Reviews 
(PROSPERO): 
CRD42019127073 


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T2DM." 


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Background: 
Disability 


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20: 
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"BackgroundDisability 


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Methods: 
Estimates 
of 
DALYs 


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MethodsDALY 
estimates 


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-


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– 


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DALY 


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of 
DALYs 


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ASR 
of 
DALYs 


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DALY 
ASRs 


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across 


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for 


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s 


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Results: 
The 


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ResultsThe 


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As 
expected, 


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All-cause 
DALY 


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absolute 


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publishedabstracts 
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Conclusion: 
Disease 



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ConclusionDisease 


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ASR 
of 
DALYs 


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PM 


DALY 
ASRs 


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ASR 
of 
DALYs 


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DALY 
ASRs 


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, 


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, 


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reflect 


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guide 


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disease 
patterns. 


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PM 


priority 
setting 
by 
avoiding 
large 
disparities 
occurring 
between 
crude 
and 
age-standardised 
results 
sets, 
which 
could 
potentially 
confuse 
non-technical 
audiences." 


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" 


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21: 
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: 


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publishedabstracts 
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, 


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using 
microelectrode 
recordings 
(MERs) 


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iii 


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3 


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Nineteen 


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19 


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pre-surgical 
3 
tesla 


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21: 
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presurgical 
3T 


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-

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patients 


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microelectrode 
recordings 
(MERs) 
from 
the 
thalamus. 



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thalamic 
MERs. 


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-

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, 


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and 


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, 


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-

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-

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, 


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-

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-

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%


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cohort 


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LGS 


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DBS 
undertaken 
in 



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undergoing 
CM-DBS 
reported 


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with 
LGS 


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3 
tesla 


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3T 


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Intraoperative 


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, 


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; 


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, 


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inter-patient 


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interpatient 


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, 


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. 


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." 


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" 



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: 


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: 


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, 


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: 


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-

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– 


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publishedabstracts 
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utes 


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-

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– 


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utes 


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-

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– 


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utes 


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-


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– 


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publishedabstracts 
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utes 


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-

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– 


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utes 


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-

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– 


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publishedabstracts 
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utes 


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utes 


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utes 


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, 


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utes 


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utes 


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utes 



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utes 


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: 


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. 


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." 


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(ICP) 


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(TBI). 


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. 


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(HTS) 


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(SOS) 


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(HTS) 


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TBI. 


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traumatic 
brain 
injury. 


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(ICP) 


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TBI 



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traumatic 
brain 
injury 


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HTS 


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hypertonic 
saline 


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-

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ICP. 


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intracranial 
pressure. 


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(GOS-E) 


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6 


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six 


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"Purpose: 


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phenotypes 


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disorders 


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major 
indications 


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a 
frequent 
indication 



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children 
undergoing 


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However, 
up 
to 
50% 


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Fifty 
percent 


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, 
however, 


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periodic 


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Here 
we 
show 


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can 
boost 
diagnostic 
yield 
in 
neuromuscular 
diseases, 
but 
its 
utility 
in 
neurodevelopmental 
disorders 
is 
hampered 
out 
of 
concern 
for 
sourcing 
relevant 
tissue 
for 
RNA 
analysis. 
Here 
we 
show 


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on 


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-

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is 
highly 
suitable 
for 
neurodevelopmental 
Mendelian 
gene 
testing 
and 
demonstrate 
the 
utility 
of 
this 
approach 
in 
suspected 
cases 
of 
Cornelia 
de 
Lange 
syndrome 
(CdLS). 
Methods: 
Genotype-Tissue 
Expression 
project 
transcriptome 
data 
for 
LCL, 
blood, 
and 
brain 
were 
assessed 
for 
neurodevelopmental 
Mendelian 
gene 
expression. 
Detection 
of 
abnormal 
splicing 
and 
pathogenic 
variants 
in 
these 
genes 
was 
performed 
with 
a 
novel 
RNA-seq 
diagnostic 
pipeline 
and 
using 
a 
validation 
CdLS-LCL 
cohort 
(n 
= 
10) 
and 
test 
cohort 
of 
patients 
who 
carry 
a 
clinical 
diagnosis 
of 
CdLS 
but 
negative 
genetic 
testing 
(n 
= 
5). 
Results: 
LCLs 


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the 
transcriptional 
repertoire 


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isoform 
diversity 



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Mendelian 
genes, 
enabling 
testing 
of 
over 
1000 
genetic 
syndromes. 
LCLs 
also 
showed 
a 


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genes 
and 
express 


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increase 
in 
the 
number 
of 
genes 
causing 
neurodevelopmental 
phenotypes 
when 


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more 
of 
these 
genes 


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to 
whole 


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with 


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) 
indicating 
a 
more 
robust 
testing 
landscape. 
We 
applied 
an 
RNA-seq 
diagnostic 
pipeline 
on 
LCLs 
from 
patients 
with 
Cornelia 
de 
Lange 
syndrome 
(CdLS), 
a 
rare 
multisystem 
neurodevelopment 
disorder 
and 
found 
100% 
sensitivity 
for 
detection 
of 
abnormal 
splicing 
and 


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). 
This 
enables 
testing 
of 
more 
than 
1000 
genetic 
syndromes. 
The 
RNA-seq 
pipeline 
had 


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all 


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. 
Application 
of 
the 
pipeline 
on 
unsolved 
cases 
of 
CdLS 


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and 


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novel 
diagnoses 
such 
as 


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splicing 


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splice 
products 
in 
NIPBL 


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NIPBL 


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BRD4 


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BRD4. 
This 
work 
demonstrates 
that 


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ANKRD11. 
Conclusion: 
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broad, 


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robust 


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and/ 


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, 


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. 


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." 


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-

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– 


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C. 


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Clostridium 


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, 


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outcome 


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Importance: 


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"Background.: 


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where 


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and 


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Objective: 
Develop 
a 


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The 
aim 
of 
the 
current 
study 
was 
to 
test 
the 
ability 
of 


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method 
predicting 
the 
diagnosis 
of 


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models 
applied 
to 
electronic 
medical 
records 
(EMRs) 
to 
predict 


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early 


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offspring 


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life, 


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, 
using 
parental 
electronic 
medical 
records 
(EMR) 
available 
before 
childbirth 
Design: 
Prognostic 
study 
of 


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. 
Methods.: 
We 
used 


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within 


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from 


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including 
EMR 
information 


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the 


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), 


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) 


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through 


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and 


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The 
complete 
EMR 
record 
of 
the 
parents 
was 
used 
to 
develop 
various 
ML 
models 
to 
predict 
the 
risk 
of 
having 
a 
child 
with 
ASD. 
Main 
outcomes 
and 
measures: 


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parental 


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, 


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until 
offspring's 
birth 



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machine 
learning 


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ML 


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-

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, 


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the 
area 
under 
the 
receiver 
operating 
characteristic 
curve 
(AUC; 


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-

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s 


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) 


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, 


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[ 


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). 


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]). 


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: 


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.: 



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, 
achieving 
an 


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. 
The 


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performance 
across 
all 
models 
had 


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-

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s 


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9 


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28.63 


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29.93 


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62 


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18 


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96.05 


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positive 
predictive 
value 


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PPV 


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43.35 


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Conclusion 
and 
relevance: 


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Conclusions.: 
We 
conclude 
that 


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. 


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as 
well 
as 
reveal 
previously 
unknown 
features 
to 
be 
associated 
with 
ASD-risk. 


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. 


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." 


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E 


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Ae 


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' 


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’ 



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‘ 


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’ 


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-

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a 


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' 


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’ 


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' 


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’ 


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' 


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’ 


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Background: 


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"BackgroundExisting 
physical 
activity 
guidelines 
predominantly 
focus 
on 
healthy 
age-stratified 
target 
groups. 


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-

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– 



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Methods: 
The 


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MethodsThe 


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and 
using 
a 
three-phased 
process 


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. 


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, 
and 


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identified, 
and 
a 
content 
analysis 
was 
conducted 
on 
these 
recommendations. 


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analysed. 


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the 
findings 
of 
the 
content 
analysis 
were 
summarised, 
and 


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. 
The 
seven 
recommendations 
were 


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and 


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noncommunicable 
diseases 
( 


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). 


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. 



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Results: 
The 


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ResultsThe 


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should 


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minutes 


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min 


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minutes 


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min 


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Conclusion: 
The 


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ConclusionThe 


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. 


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." 


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" 


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. 


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: 



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. 
Forty-four 


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:A 
total 
of 
44 


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9y6m 


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9 
years 
6 
months 


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1y10m 


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1 
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at 


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(T2) 


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(T2), 


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> 


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; 
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a 


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s 


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. 
Trial 
registration: 
Registered 
at 
ClinicalTrials.gov 
on 
22nd 
August 
2017 
(Identifier: 
NCT03256357). 


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." 


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Background: 


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Methods: 


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Results: 



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The 
functional 
analysis 
by 


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, 


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. 
Conclusions: 
In 
this 
study, 
a 
molecular 
classification 
of 
anal 
squamous 
cell 
carcinoma 
using 
high-
throughput 
proteomics 
and 
whole-exome 
sequencing 
data 
was 
proposed. 
Moreover, 
differences 
between 
the 
two 
established 
groups 
suggested 
some 
possible 
therapies. 


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" 


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lower 
economic 
status 


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high 
epidemic 
vulnerability 


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in 


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' 


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’s 


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. 


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." 


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Understanding 
exposures 


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"Background 
and 
ObjectiveUnderstanding 
pharmacokinetic 
disposition 


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{beta}


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β


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ethodsM 


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twelve 


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12 


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patients 


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Results 


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= 


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= 


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(CrCL) 


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= 


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= 


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CrCL 


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creatinine 
clearance 


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-

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The 


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ConclusionThe 


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. 


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." 


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Objectives: 
We 


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"ObjectivesWe 


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Design: 
Prospective 


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DesignProspective 


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participants: 
Adults 


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participantsAdults 


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Methods: 
We 


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MethodsWe 


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Results: 
We 


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ResultsWe 


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-

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– 


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-

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– 


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-

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– 


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Conclusion: 
Even 


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ConclusionEven 


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. 


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." 


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"Background: 


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International 
Classification 
of 
Diseases, 
10th 
revision 
( 


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) 


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an 


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-

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-

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To 
solve 


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Objective: 
The 
objective 
of 


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issue, 
we 


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study 
was 
to 


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-

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Methods: 


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" 


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" 


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2,973 


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2973 


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; 


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, 


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; 


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, 


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-

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-

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; 


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, 


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a 
convolutional 
neural 
network-based 
architecture 
[ 


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). 


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]). 


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Results: 


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AUC-ROC 


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area 
under 
the 
receiver 
operating 
characteristic 
curve 


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an 


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-

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72. 
ConvNet's 
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70. 
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Conclusions: 


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. 


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." 


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" 


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one 
of 


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study 
of 


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studies 
of 
men 
who 
have 
sex 
with 
men 
( 


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) 


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(U.S.): 


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: 


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estimating 
and 
simulating 


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parameterizing 


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analytic 


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the 
study 


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this 
paper 


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length 


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age 


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(" 


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(“ 


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"), 


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”), 


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for 
all 
partnership 
types 


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. 


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." 


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DNA 


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"BackgroundDNA 


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Here 


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ResultsHere 


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= 


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{beta}=7.9x10-3 


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β 
= 
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= 


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body 
mass 
index 
( 


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, 


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), 


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, 


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= 


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but 
it 
was 


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or 


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a 


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the 


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after 
correction 
for 
multiple 
testing 


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= 


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= 


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=[ 


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=[ 


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= 


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These 


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ConclusionsThese 


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. 


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." 


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’ 


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Area 
under 
the 
Curve 
( 


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) 


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82 


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83 


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82 


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83 


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79 


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" 


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s: 


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IgG 


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immunoglobulin 
(Ig) 
G 


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, 


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and 


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five 


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5 


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: 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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re-coded 


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recoded 


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five 


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5 


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, 


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five 


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one 


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five 


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one 


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and 
1 


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three 


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3 


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CBA-

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-CBA 


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two 
enzyme-linked 
immunosorbent 
assays 
(ELISA, 


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2 
ELISAs 
( 


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: 


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four 


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%) 


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%), 


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inter-assay 


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interassay 


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: 


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s 


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very 
good 
agreement 
for 


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four 


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3 


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a 


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comparison 
of 
aquaporin-4 
antibody 


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for 
other 
autoantigens. 


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. 


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. 


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." 


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Background: 
Madagascar 
has 
one 
of 
the 
highest 
rates 
of 
stunting 
and 
at-risk 
child 
development 
in 
the 
world:50 


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"Background50 


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), 
supported 
by 
the 
World 
Bank, 


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) 


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PIVOT, 
a 
health 
care 
NGO 
operating 
in 
collaboration 
with 
the 
MOH, 
conducts 
a 
longitudinal 
study, 
the 
IHOPE, 
to 
assess 
the 
population 
level 
impact 
of 
their 
collaborative 
health 
system 
strengthening 
activities 
on 
the 
rural 
district 
of 
Ifanadiana 
in 
southeastern 
Madagascar. 


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to 


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of 


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children 
ages 


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years 
old 


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year 
olds 


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the 
rural 
district 
of 


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district 



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in 
southeastern 
Madagascar 


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Methods: 
The 
household 
survey 


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MethodsThe 


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a 
one 


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the 
2016 


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IHOPE 


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in 
2016, 
at 
the 
time 
of 
the 
initiation 
of 
PNAN 
III. 


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(a 
population-representative 
cohort 
study 
begun 
in 
2014). 
We 
interviewed 


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to 


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– 


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were 
interviewed, 


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Multiple 
Indicator 
Cluster 
Survey 
( 


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) 


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We 
analyzed 



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were 
analyzed 


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. 
We 
assessed 


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for 


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-

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for 
delayed 
development 
compared 
to 


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-for-delay 
vs. 


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-

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-

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-

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< 


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> 


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the 
international 
normed 
population 
and 


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, 
respectively. 


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. 



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(maternal 
age, 
education 
level, 
household 
wealth, 
number 
of 
other 
children 
under 
5 
in 
the 
house), 


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, 


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(reading, 
singing, 
playing 
with 
child), 


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, 


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(number 
and 
type 
of 
childrens 
books 
or 
toys, 
whether 
child 
was 
left 
alone 
or 
in 
the 
care 
of 
another 
child 
<10 
years), 
and 


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, 
and 
selected 


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(wasting, 
stunting, 
underweight, 
ill 
in 
last 
4 
weeks, 
vaccination 
status). 
We 
included 


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factors. 


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in 
univariable 
analysis 


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an 


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< 


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in 


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were 
included 


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. 
We 
constructed 
the 



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; 


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using 


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used 


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on 
generalized 
linear 
models 


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Results: 
Of 


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ResultsOf 


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(40%) 


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were 
considered 


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had 


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compared 
to 
their 


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than 


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50.5% 
of 
the 


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This 
was 
driven 
mostly 
by 
the 
literacy/numeracy 
domain, 
with 
only 
7% 
of 
children 
considered 
developmentally 
on 
track 
in 
that 
domain. 
50.5% 
of 



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and 
19.0% 
had 
severe 
stunting. 


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. 
76 
(17.6%) 
had 
> 
= 
4 
stimulation 
activities 
in 
past 
3 
days. 


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5 


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13 


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09 


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21 


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07 


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being 
at 
risk 
for 
delay 
based 
on 
ECDI 
z 
scores 
<-1 
compared 
to 


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increased 
delay 
vs. 


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Factors 
associated 
with 
lower 
risk 
for 
delay 
included 
having 
some 
adult 
play 
with 
the 
child 
and 
greater 


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. 
Adolescent 
motherhood 
(OR. 
4.09 
(1.40, 
11.87)) 
decreased 
children’s 
development 
vs. 
peers. 


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. 
Factors 
associated 
with 
low 
development 
compared 
to 
peers 
included: 
under 
age 
5 
in 
the 
household, 
having 
a 
teenaged 
mother 
(age 
<20 
years--OR3.89 
(1.32, 
11.48)), 
and 
having 
an 
adult 
who 
recently 
took 
the 
child 
outside. 
Factors 
associated 
with 
less 
developmental 
risk 
included 
increased 
number 
of 
developmentally 
stimulating 
activities 
by 
someone 
other 
than 
a 
parent(OR 
0.28(0.16, 
0.50)), 
and 
primary 
child 
toys 
are 
found 
objects 
rather 
than 
store 
bought 
or 
homemade 



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reduced 
odds 
of 
delay 
for 
both 
outcomes 


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(95%CI 
= 
0.76 
(0.63, 
0.91) 
& 
0.27 
( 


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33 
( 


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15, 


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.14, 
0.73)). 
Discussion: 
In 
this 
setting 
of 
high 
malnutrition, 
stunting 
in 
children 
is 
not 


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48) 
respectively). 
Stunting 
was 
not 
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lower-

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delay 
risk 
(1.36 
(0.85, 
2.15) 
or 
low 


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compared 
to 
their 
peers, 


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(0.92 
(0.48, 
1.78)) 


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adjusting 


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controlling 


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Families 
with 
teenaged 
mothers 
are 


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ConclusionsIn 
this 
setting 
of 
high 
child 
malnutrition, 
stunting 
is 
not 
independently 
associated 
with 
developmental 
risk. 
A 
low 
proportion 
of 
children 
receive 
developmentally 
supportive 
stimulation 
from 
adults, 
but 
non-parent 
adults 
provide 


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likely 
to 
have 
children 
with 
lower-development. 


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stimulation 
in 
general 
than 
either 
mother 
or 
father. 
Stimulation 
from 


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adult 
involvement 
seems 
very 
relevant 
to 
child 
development 
in 
this 
setting. 
Further 
research 
in 
the 
IHOPE 
longitudinal 
study 
may 
help 
to 
clarify 
direction 
of 
association. 
Interventions 
targeting 
adolescent 
girls 
before 
they 
become 
parents 
may 
be 
of 
particular 
utility 
in 
this 
setting. 


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adults 
is 
associated 
with 
lower 
odds 
of 
delay." 


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Abstract 
Background: 
Malnutrition 


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"BackgroundMalnutrition 


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under 
nutrition 


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undernutrition 


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mal 


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u 


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dern 


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mal 


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u 


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dern 


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Methods: 
A 


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MethodsA 


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, 


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was 


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were 


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Binary 


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Bivariate 


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multiple 
variable 


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multivariate 


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was 
done 


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analysis 
were 
performed 


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malnutrition. 
Results: 
Data 


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undernutrition.ResultsData 


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1062 


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under 
nutrition 


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undernutrition 


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) 
was 
(36.8%) 
(95% 
CI: 
33.8%-39.8%) 
and 


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kg/m2) 
and 
overweight 
or 
obesity 
were 
34% 
and 
9%, 
respectively. 


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which 
severe 
malnutrition 
accounts 
9.7%. 
Overweight 
and 
obese 
was 
8.6%. 
Malnutrition 


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undernourished 
patients, 
severely 
malnourished 
patients 
(BMI<16 
kg/m2) 
accounted 
of 
9%. 
Undernutrition 


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= 


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= 


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4


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– 


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798), 
patients 



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79), 
patients 
with 
no 
access 
to 
water 
supply 
(AOR 
= 
1.69, 
95% 
CI, 
1.16–2.47) 
and 
patients 


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AIDS 
staging 


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stage 


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= 


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= 


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3 


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0 


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392-3.693 


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33–2.97 


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= 


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= 


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667



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74– 


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943), 


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07). 
Moreover, 
the 
odds 
of 
undernutrition 
was 
more 
likely 
among 


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= 


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= 


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463


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38– 


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837 


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47 


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=4.677 


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= 
3.6 


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761-12.419 


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55–8.35 


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= 



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= 


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833-4.165). 
Conclusion: 
Both 
under 
nutrition 


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66–3.51), 
respectively.ConclusionBoth 
undernutrition 


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are 


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or 
obesity 
were 


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Mal 


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U 


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dern 


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. 


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." 


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Abstract 
Background: 
Concern 


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"BackgroundConcern 



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(HT) 


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Methods: 
We 


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MethodsWe 


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HT 


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heart 
transplantation 


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Results: 
For 


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ResultsIn 


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mortality 
(n 
= 
506,543) 


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HF 


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readmission 
(n 
= 
526,309) 


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<0.2% 
of 


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1,166 
and 
1,016 


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and 
<0.1% 
received 
HT 
in 
either 
cohort. 


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while 
3 
and 
2 
had 
a 
heart 
transplantation, 
respectively. 
In 
the 
HF 
mortality 
(n 
= 
1,015,335) 
and 
readmission 
(n 
= 
1,254,124) 
cohorts, 
789 
and 
931 
received 
an 
LVAD, 
while 
212 
and 
202 
received 
a 
heart 
transplantation, 
respectively. 


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> 


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≥ 


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>1 
HT 


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≥1 
heart 
transplantation 


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> 


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≥ 


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HT 


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heart 
transplantation 


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< 


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≤ 


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HT 


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heart 
transplantation 


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Conclusion: 
Hospitals 



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ConclusionHospitals 


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> 


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≥ 


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> 


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≥ 


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HT 


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heart 
transplantation 
typically 


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a 
trend 
toward 


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on 
average 


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HT 


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heart 
transplantation 


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. 


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." 


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Background: 



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, 


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Objective: 


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. 
Study 
Design: 


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, 


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) 


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; 


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( 


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μ 


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({Sigma}androgen 


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(Σandrogen 


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g 


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μg 


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-

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–20 



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’s 


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Results: 


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g 


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μg 


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({Sigma}androgen 


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(Σandrogen 


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g 


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μg 


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Conclusion: 


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" 


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DIDCs 


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s 


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DIDCs 


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s 



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DIDCs 


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s 


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DIDC 


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' 


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’ 


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participated 
in 


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completed 


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cold 
pressor 
test. 


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CPT. 


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to 


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with 


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Objectives: 


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"Background: 
In 
England, 
national 
safety 
guidance 
recommends 
that 
ciclosporin, 
tacrolimus 
and 
diltiazem 
are 
prescribed 
by 
brand 
name 
due 
to 
their 
narrow 
therapeutic 
windows 
and, 
in 
the 
case 
of 
tacrolimus, 
to 
reduce 
the 
chance 
of 
organ 
transplantation 
rejection. 
Various 
small 
studies 
have 
shown 



that 
changes 
to 
electronic 
health 
records 
(EHR) 
interface 
can 
affect 
prescribing 
choices. 
Objective: 
Our 
objectives 
were 


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and 


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Design: 


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Methods: 
We 
carried 
out 


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. 
Setting: 


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using 


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: 


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were 


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Main 
outcome 
measures: 


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s 


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. 


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." 


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Background 
Intranasal 


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"BackgroundIntranasal 



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“ 


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” 


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, 


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Methods 
Using 


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MethodsUsing 


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four 


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4 


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four 


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4 


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hours 


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h 


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four 


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one 



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Results 
No 


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ResultsNo 


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u 


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s 


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one 


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1 


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one 


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1 


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“ 


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” 


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Conclusions 
While 


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ConclusionsWhile 


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Trial 
registrationThe 
trial 
was 
registered 
with 
the 
European 
Clinical 
Trial 
Registry 
(Eudract 
2014-00058645) 
on 
January 
22, 
2014 
(https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE)." 



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" 


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(US). 


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. 


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based 


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the 
basis 
of 


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testing 


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a 


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( 


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(= 


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y/o 
or 
older 


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years 
old 


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$) 


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dollars) 


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the 



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the 


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in 


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of 


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The 


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' 


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. 


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." 


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" 


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, 


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addressed 
barriers 
to 
its 


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evaluated 
predictive 
factors 
of 
its 
acceptance 
and 
subsequent 


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United 
States. 


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USA. 


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patients' 



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utilization 


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use 


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mHealth 


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-

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to 


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Only 


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utilization 


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acceptability 


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; 


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p<0.01 


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CI95% 
1.25-5.88 


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older 


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> 
80 
years 
of 
age 


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; 



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p< 


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CI95% 
0.01


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23 


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utilization 


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acceptability 


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; 


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p<0.01). 


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CI95% 
10.13-6748.71). 


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the 


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that 
factors 
such 
as 
age, 
educational 
achievement, 
and 


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mobile 
technology 
is 
the 
predominant 
determinant 


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internet 
are 
significant 
predictors 


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utilization 



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acceptability 
of 
a 
mHealth 
application 
among 
cancer 
patients 


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. 


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." 


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Background 
Stereotactic 
radiosurgery 
is 
a 
form 
of 
radiotherapy 
that 
is 
performed 
in 
a 
single 
session 
and 
focuses 
high-dose 
ionizing 
radiation 
beams 
from 
a 
collimated 
radiation 
source 
to 
a 
small, 
localized 
area 
of 
the 
body. 


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"Background: 


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-

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[ 


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), 


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]), 


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, 


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: 


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the 
use 
of 
CyberKnife, 
a 
frameless 
image-guided 
linear 
accelerator 
stereotactic 
radiosurgery 
system, 
in 
conjunction 
with 
CardioPlan, 
a 
cardiac 
specific 
radiotherapy 
planning 
software, 
to 
treat 
patients 
with 
scar-related 
VT 


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STAR 



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: 


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, 


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scar-related 


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based 


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basis 
of 
the 


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al 


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pre-procedural 


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preprocedural 


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delineated 
with 
the 
aid 
of 
CardioPlan 


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: 


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% 
male, 


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% 
men; 
mean 
age 


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old, 


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; 



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% 


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% 
with 


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, 


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; 


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% 


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%) 
with 
refractory 
VT 


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%) 


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between 
January 
and 
June 
2018 


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two 


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2 


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necrosis 
or 
other 
radiation 


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: 


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ventricular 


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, 



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. 


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." 


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" 


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, 


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-

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, 


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A 
total 
of 


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-

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., 


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, 


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-

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one 


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, 



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-

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81mm 


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81 
mm 


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inter-lesion 


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interlesion 


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6mm 


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6 
mm 


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. 


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=0 


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= 


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. 


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=0 


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= 


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s 



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inter-lesion 


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interlesion 


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. 


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." 


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Objective: 
To 


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"ObjectiveTo 


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-

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-

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-

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-

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Methods: 
Tremor 


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MethodsTremor 


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-

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-


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Results: 
PSA 


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ResultsPSA 


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= 


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= 


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-

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= 


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= 


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< 


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< 


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= 


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= 


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Conclusions: 
Differences 


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ConclusionsDifferences 


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. 



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." 


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accurate 


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ac-curate 


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interactions 


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in-teractions 


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, 


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promotes 


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pro-motes 


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, 


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replication 


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repli-cation 


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dependent 


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depen-dent 


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-


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-

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d 


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, 


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RNAPII 


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Pol 
II 


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RNAPII 


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the 
Pol 
II 


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-

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By 


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In 


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, 


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d 


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s 


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, 



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" 


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= 


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= 


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= 


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= 


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. 


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." 


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" 


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The 
impact 


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Since 
the 
incidence 


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on 
the 
rise 


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rising 


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so 
that, 
it 
is 
predictable 


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one 
may 
expect 



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household’s 


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related 
to 
the 
disease 


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further 


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near 


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Yet 
the 
cost 
associated 
with 
the 
disease 
is 
not 
known. 


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and 
identify 
associated 
factors 


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Institution 


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An 
institution-

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design 


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conducted 


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employed 
to 
conduct 
the 
study 


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July 
1-30, 


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13 
August 
to 
2 
September 


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aged 
18 
years 
and 
older 



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treatment 
and 
whose 
age 
was 
greater 
than 
eighteen 
years 
old 


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follow-up 


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up 


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analysis 
was 
conducted 


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analyses 
were 
performed 


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es 


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Overall, 


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A 
total 
of 
349 
patients 
participated 
in 
the 
study. 


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-

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– 


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share 


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constitute 


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total 


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$ 



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US$ 


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-

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– 


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accounted 
of 
a 


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comprised 


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%) 


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%), 


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total 


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$ 


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$ 


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-

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– 


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In 
this 
study, 
the 
primary 


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family 
size 
(4– 
6 
and 
> 
6), 



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, 


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(≥ 
10 
km), 


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a 


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the 


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were 


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(stage 
two) 
of 
patients 
were 
identified 
as 
the 


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illness 
of 


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. 


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illnesses. 


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with 


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to 


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mean 


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the 
patients 
letting 


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households, 
exposing 



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Therefore, 
due 
attention 
should 
be 
given 
by 


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Hence, 


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should 
give 
due 
attention 


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financial 
hardships. 
Key 
words: 
Illness, 
total 
cost, 
direct 
cost, 
indirect 
cost, 
Region, 
Ethiopia. 


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catastrophic 
health 
expenditures." 


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non-absorbing 


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nonabsorbing 


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due 
to 


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because 
of 


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due 
to 


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because 
of 


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" 


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autism 
spectrum 
disorder 
(ASD) 


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ASD 



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’s 


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. 


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." 


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Fusion 
with, 
and 
subsequent 
entry 
into, 
the 
host 
cell 
is 
one 
of 
the 
critical 
steps 
in 
the 
life 
cycle 
of 
enveloped 
viruses. 
For 


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) 
is 
a 
major 
emerging 
zoonotic 
infectious 
disease. 
Since 
its 
first 
outbreak 
in 
2012, 
the 
virus 
has 
repeatedly 
transmitted 
from 
camels 
to 
humans 
with 
2,468 
confirmed 
cases, 
causing 
851 
deaths. 
To 
date, 
there 
are 
no 
efficacious 
drugs 
and 
vaccines 
against 
MERS-CoV, 
increasing 
its 
potential 
to 
cause 
a 
public 
health 
emergency. 
A 
critical 
step 
in 
the 
life 
cycle 
of 
MERS-CoV 
is 
the 
fusion 
with 


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), 


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host 
cell 
with 
its 


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as 


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is 
the 


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the 


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protein 


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the 
process 
of 


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ions 



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s 


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for 


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in 


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s 


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, 


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substituting 


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screening 
a 
mutant 
array 
in 
which 


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were 
substituted 


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. 


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(A). 


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the 
mutants 


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their 


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pseudoparticle 
(PP) 


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pseudo-particles 
(PPs) 
on 



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without 
and 
with 


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in 
modulating 


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+. 


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+ 
environments. 
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wild-type 
( 


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) 


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s 


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two 


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2 


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Subsequent 


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(ESR) 
experiments 


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titration 


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that 


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an 
approximate 
1:1 



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binds 
one 


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to 


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+, 


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+ 
ratio, 
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an 
1:2 


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which 
binds 
two. 
Our 
data 
suggests 
that 
there 
are 


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to 
Ca2+ 
ratio, 
suggesting 


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-

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and 
that 
the 
number 
of 
Ca2+ 
ions 
interacting 
with 
the 
FP 
has 
implications 
on 
the 
fusion 
dynamics 
of 
the 
virus 


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ies 


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y 


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o 


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ø 


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mapping 



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segregating 


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' 


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’ 


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=2,417 


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= 
2417 


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Organization's 


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Organization′s 


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[&le;]


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≤− 


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-

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– 


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-

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– 


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" 



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aims 
to 
analyse 
basic 


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analyses 
full 


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to 
estimate 


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estimates 


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data 
from 


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2016 


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2016. 


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dataset. 


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Basic 


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Full 


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doses 
DPT 


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dose 
DTP3 


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s 


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vaccine 



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(MCV1), 
3-dose 
pneumococcal 
(PCV3), 
and 
2-dose 
rotavirus 
vaccines 


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) 


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), 


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assessed 


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estimated 


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inequalities. 


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inequities, 
and 


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estimated 


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assessed 


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basic 


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full 


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geographic, 


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, 


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National 



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Full 
vaccination 


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for 
basic 
vaccinations 


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39.7% 


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33.3% 
[29.4-37.2] 


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between 
between 
53.2% 
(DTP3) 
and 


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from 
49.1% 
[45.1-53.1] 
for 
PCV3 
to 


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( 


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[65.5-72.8] 
for 


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). 


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. 


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present 
for 
all 
vaccines. 


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pronounced 
with 
concentration 
indices 
of 
0.30 
and 
0.23 
respectively. 


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from 
richer 
households, 
urban 
regions, 
primary 
maternal 
education 
and 
male 


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in 
Addis 
Ababa 
and 
Dire 
Dawa 
were 
seven 
times 
more 
likely 
to 
have 
full 
vaccination 
compared 
to 
children 
living 
in 
the 
Afar 
region. 
Children 
in 
female



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associated 
with 
higher 
vaccination 
coverage. 
The 
Ethiopia 
Mini 
Demographic 
and 
Health 
Survey 
2019 
reports 
national 
coverage 
for 
basic 
vaccinations 
at 
43.3% 
with 
single 
vaccination 
coverage 
ranging 
between 
57.8% 
(measles) 
and 
74.2% 
(BCG). 
Conclusions 


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49% 
less 
likely 
to 
have 
full 
vaccination.Conclusion 


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has 
improved 
from 
2016 
to 
2019, 
but 
remains 
below 
the 
coverage 
goals 
of 
the 
EPI. 
Low 
vaccination 
coverage 
is 
associated 
with 


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in 
Ethiopia 
has 
a 
pro-advantaged 
regressive 
distribution 
with 
respect 
to 
both 
household 
wealth 
and 
maternal 
education. 
Children 
from 


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, 


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-

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. 


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had 
lower 
full 
vaccination 
coverage. 


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approaches 
are 
necessary 
to 


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programmes 
to 
reach 
under-immunised 
children 
in 
these 
subpopulations 
will 


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among 
these 
population 
subgroups 


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equitable 
uptake 
of 
vaccines 


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equity 
outcomes 



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. 
Keywords: 
Immunisation 
coverage, 
vaccine 
equity, 
Ethiopia, 
Demographic 
and 
Health 
Survey 


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." 


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Purpose: 
To 


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"PurposeTo 


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LSD's). 
Methods: 
Assessment 


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LSDs).MethodsAssessment 


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Results: 
Between 


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ResultsBetween 


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= 


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= 


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= 


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= 


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= 


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= 



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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 



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' 


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-

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– 


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= 


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= 


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Conclusions: 
The 


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ConclusionsThe 
drug 


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for 
LSDs 


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into 
diversified 


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, 
with 
increased 
focus 
on 
diverse 


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molecules 


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-molecule 
targets 


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" 


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“ 



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"


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”– 


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. 


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." 


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s 


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s 


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" 


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“ 


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" 


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” 


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(NHANES) 


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(CSHA) 


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and 


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also 



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s 


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-

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– 


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polar 


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For 
host 
and 
parasite 
communities 
in 
the 
Southern 
Ocean, 
investigations 
of 
many 
major 
groups 
of 
parasites 
have 
largely 
been 
limited 
to 
taxonomic 
and 
phylogenetic 
studies, 
creating 
an 
urgent 
need 
for 
the 
collection 
of 
baseline 
ecological 
data 
if 
we 
are 
to 
detect 
changes 
in 
host-parasite 
interactions 
in 
the 
future. 


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Antarcticas 
South 


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the 
southern 


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and 
intensity 
of 
three 
leech 
species 
(Trulliobdella 
bacilliformis, 
Trulliobdella 
capitis, 
and 
Nototheniobdella 
sawyeri) 
on 
the 
host 
fish 
species 
Chaenocephalus 
aceratus, 
Champsocephalus 
gunnari, 
and 
Chionodraco 
rastrospinosus. 
Additionally, 
we 
characterize 
spatial 
patterns 
of 
relative 
abundances 
of 
each 
leech 
species 
across 
the 
Elephant 
and 
South 
Orkney 
Islands 


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, 
intensity, 
spatial 
patterns 
of 
relative 
abundances 


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(i.e., 
post-cyclic) 


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-

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– 


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" 


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' 


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’ 


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' 


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’ 


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({+/-} 


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(± 


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percent 


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% 


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negatively 


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. 


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." 


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"Factor 
VIII 
(FVIII) 
is 
the 
coagulation 
factor 
deficient 
in 


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which 


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an 
X-linked 
bleeding 
disorder 
caused 
by 
deficiency 
of 
factor 
VIII 
(FVIII), 


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-

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. 


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from 
mammalian 
host 
cells. 


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, 


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, 


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in 
the 
ER 


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lumen 


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chaperones 


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chaperone 
families 


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co-chaperones, 


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cochaperones, 
immunoglobulin 
binding 
protein 
( 


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) 


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CANX/CRT 


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calnexin/calreticulin 


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{beta}


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β


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, 


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folding 


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aggregation 


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Key 
Points-FVIII 
forms 
amyloid 
aggregates 
in 
the 
ER 
that 
are 
dissolved 
in 
a 
chaperone-and 
glucose-
dependent 
manner 
to 
produce 
secreted 
active 
FVIII. 
-A 
short 
amino 
acid 
sequence 
in 
the 
A1 
domain 
causes 
{beta} 
sheet 
polymerization 
and 
ER 
chaperone 
BiP 
binding 
to 
this 
site 
prevents 
aggregation." 


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-

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, 


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datasets 


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data 
sets 


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: 


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cases 
with 



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cases 


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controls 


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control 
subjects 


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robust 


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" 


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, 


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virus 


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human 
coronavirus 


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[HCoV-229E] 


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Middle 
East 
respiratory 
syndrome 
CoV 
[ 


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). 


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]). 


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ImportanceNo 
antivirals 
are 
approved 
for 
the 
treatment 
of 
bunyavirus 
infection. 
The 
ability 
to 
rapidly 
screen 
compounds 
and 
identify 
novel 
antivirals 
is 
one 
means 
to 
accelerate 
drug 
discovery 
for 
viruses 
with 
no 
approved 
treatments. 
We 
used 
this 
approach 
to 
screen 
hundreds 
of 
compounds 
against 
La 
Crosse 
virus, 
an 
emerging 
bunyavirus 
that 
causes 
significant 
disease, 
including 
encephalitis. 
We 
identified 
several 
known 
and 
previously 
unidentified 
antivirals. 
We 
focused 
on 
a 
potassium 
ionophore, 
valinomycin, 
due 
to 
its 
promising 
in 
vitro 
antiviral 
activity. 
We 
demonstrate 
that 
valinomycin, 
as 
well 
as 



a 
selection 
of 
other 
ionophores, 
exhibits 
activity 
against 
La 
Crosse 
virus 
as 
well 
as 
several 
other 
distantly 
related 
bunyaviruses. 
We 
finally 
observe 
that 
valinomycin 
has 
activity 
against 
a 
wide 
array 
of 
human 
viral 
pathogens, 
suggesting 
that 
disrupting 
potassium 
ion 
homeostasis 
with 
valinomycin 
may 
be 
a 
potent 
host 
pathway 
to 
target 
to 
quell 
virus 
infection." 


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SARS 


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18 
years 
ago, 
a 
large 
number 
of 


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of 


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(SARS) 
18 
years 
ago, 
a 
large 
number 
of 
SARS-

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s 


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,2,3, 


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indicated 


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have 
shown 


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of 
those 


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,6, 


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ov 



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w 


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2019


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-2019) 


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), 


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, 


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which 


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from 


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on 
12 


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12th, 


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s 


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d 


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2,794 



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-

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with 
three 
fatal 
cases 


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including 
80 
deaths 


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26 


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20th, 


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the 


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an 


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They 


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The 
sequences 


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to 
each 
other 


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5 


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f 


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t 



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it 
was 
found 


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we 
show 


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2019


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-2019 


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-

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The 


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domains 


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The 


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In 
addition, 
2019


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-2019 


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was 
then 


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, 
which 
can 


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could 


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Importantly 



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Notably 


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have 


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this 
novel 
CoV 


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2019-nCoV 


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, 


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—angiotensin 
converting 
enzyme 
II 
( 


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, 


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)— 


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novel 


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, 


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2019-nCoV 


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SARS-CoV-2 


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, 



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2019-nCoV 


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SARS-CoV-2 


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Importance: 
Understanding 
the 
mechanisms 
of 
primary 
resistance 
to 
immune 
checkpoint 
blockade 
therapy 
is 
of 
paramount 
importance 
for 
treatment 
selection. 


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"Introduction 


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co-mutated 


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comutated 


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nonsquamous 


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non-squamous 


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, 


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(NSQ 
NSCLC), 


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. 


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(ICB). 


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immune 
checkpoint 
blockade 


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ICB 



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Objective: 


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The 
objective 
of 
this 
study 
was 


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er 


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us 


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across 
different 
treatment 
classes 
in 
nonsquamous 
non-small 
cell 
lung 
cancer. 
Design: 
A 
retrospective, 


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in 
NSQ 
NSCLC.Methods 
Patients 
diagnosed 
with 
stage 
IIIB, 
IIIC, 
IVA 
or 
IVB 
NSQ 
NSCLC 
from 
a 


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, 
from 
January 
1, 
2011, 
through 
December 
31, 
2018. 
Setting: 
Multicenter, 
including 
academic 
and 
community 
practices. 
Participants: 
Patients 
diagnosed 
with 
stage 
IIIB, 
IIIC, 
IVA, 
or 
IVB 
nonsquamous 
non-small 
cell 
lung 
cancer 
who 
initiated 
first-line 
treatment 
within 
90 
days 
after 
diagnosis. 
Main 
Outcomes 
and 
Measures: 


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were 
retrospectively 
assessed. 


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(rwPFS) 


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(OS) 
were 


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: 


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z 


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s 



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with 
advanced, 
nonsquamous 
non-small 
cell 
lung 
cancer 
(mean 
age 
at 
advanced 
diagnosis, 
66.3 
years 
[SD 
10.3], 
54.4% 
female, 
80.1% 
with 
a 
history 
of 
smoking), 


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/ 


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(PD-1)/ 


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(PD-L1) 


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= 


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= 


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immune 
checkpoint. 


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ICB 
cohorts. 
There 
was 
no 
observable 
interaction 
between 
STK11 
mutations 
and 
anti-PD-1/anti-PD-L1 
treatment 
on 
rwPFS 
(HR, 
1.05; 
95% 
CI 
0.76 
to 
1.44; 
p=0.785) 
or 
OS 
(HR, 
1.13; 
95% 
CI 
0.76 
to 
1.67; 
p=0.540). 
Similarly, 
there 
was 
no 
observable 
interaction 
between 
KEAP1 
mutations 
and 
treatment 
on 
rwPFS 
(HR, 
0.93; 
95% 
CI 
0.67 
to 
1.28; 
p=0.653) 
or 
OS 
(HR, 
0.98; 
95% 
CI 
0.66 
to 
1.45; 
p=0.913).Conclusion 
Our 
results 
show 
that 
STK11-KEAP1 
mutations 
are 
prognostic, 
not 
predictive, 
biomarkers 
for 
anti-PD1/
anti-PD-L1 
therapy." 


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Backgrounds 
There 
has 
been 


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BackgroundsAn 
ongoing 
outbreak 
of 


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outbreak 


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hit 
a 
major 
city 


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since 


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, 
Wuhan, 


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, 


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which 
spreads 
internationally. 
This 
is 
the 
first 
study 
to 
quantify 


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subsequently 
reached 
other 
provinces/regions 
of 
China 
and 
other 
countries. 
We 
present 
estimates 
of 


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Methods 
Accounting 


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MethodsAccounting 


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21 


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24 


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Findings 
The 


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FindingsThe 


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3.30 


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–2.55 


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3.58 


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2.89– 


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16-7.10 


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39 


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0 


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8 


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With 
rising 
report 


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We 
demonstrated 
that 
changes 
in 
reporting 


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, 
the 
mean 
R0 
is 
likely 
to 
be 
below 
5 
but 
above 
3.Conclusion 
The 


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substantially 
affect 
estimates 
of 
R0.ConclusionThe 


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3.30 
(95%CI: 
2.73-3.96) 
to 
5.47 
(95%CI: 
4.16-7.10), 


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2.24 
to 
3.58, 


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is 


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a 
worldwide 


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a 


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the 


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, 
the 


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-

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-

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, 


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s 


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-

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-

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and 


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, 


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of 
2019-nCoV, 
and 
12 


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whole 
genome 


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five 


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SARS, 
2 


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the 
severe 
acute 
respiratory 
syndrome, 
two 


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MERS 


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Middle 
East 
respiratory 
syndrome, 


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5 


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five 


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-

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-

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FUBAR 


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Fast 
unconstrained 
Bayesian 
approximation 


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s 


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ve 


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while 


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, 
whereas 


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modelling 
helped 
to 
explain 


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modeling 
revealed 


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. 


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-

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-

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-

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S 


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Spike 
Glycoprotein 


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s 


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2019nCoV 
could 
be 
considered 
a 
coronavirus 


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the 
new 
2019-nCoV 
is 


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n 


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or 
another 
host 
where 
mutations 
conferred 
upon 
it 
the 


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after 
mutation 
conferring 


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830 


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24,500 


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26 


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492 


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24 
January 


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5 
February 


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other 


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24 


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not 
yet 


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only 


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evidence 
of 
sustained 


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limited 


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, 


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early 


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37. 


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41 
(credible 
interval 
[0.27, 
0.55]). 


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005. 


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012 
(credible 
interval 
[0, 
0.099]). 


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large 


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e 


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i 


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an 


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persons 
infected 
with 
the 


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2019-nCoV) 
provides 


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COVID-19) 
infections 
from 
the 
epicenter 
of 
Wuhan, 
China, 
has 
provided 


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newly 


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recently 


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Migration 
events 
put 
travelers 
at 
risk 
of 
infection 
for 
the 
duration 
of 
their 
exposure 
to 
an 
area 
where 
transmission 
is 
known 
to 
occur. 


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event-date 


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of 


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from 


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of 
2019-nCoV 
where 
event 
dates 
for 
cases 
have 
been 
shared 


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inv 


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m 


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g 


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interpretation 
of 


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2019-nCoV 


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COVID-19 



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s 


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two 
to 
nine 


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2–14 


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, 


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the 
median 
incubation 
period 
is 
4


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has 
a 
mean 
of 
around 


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Weibull 


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best-fit 
lognormal 


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, 
which 
was 
the 
best 
fit 
model. 


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. 


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di 


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hospitalization 


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hospital 
admission 
(for 
treatment 
and/or 
isolation) 


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–4 



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. 


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without 
truncation 
and 
at 
5–9 
days 
when 
right 
truncated. 


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estimate 
of 
the 


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isolation 
and 


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nine 


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14 


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We 
also 
note 
that 


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.8 


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(17 
days 
with 
right 
truncation) 


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COVID-19 


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of 
this 
novel 
virus 


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BackgroundA 


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Background: 
A 


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MethodsPutative 



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Methods: 
Putative 



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ResultsOur 



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Results: 
Our 



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-


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_ 



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5 



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5' 



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3 



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3' 



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-


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_ 



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3' 



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ConclusionsThe 




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Conclusions: 
The 


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Currently, 


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( 


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causes 


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) 
is 
causing 


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that 
started 


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Little 
is 
known 
about 
its 
epidemiological 
characteristics. 


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34 


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88 


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in 
the 
early 
outbreak 
phase 


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5.8 
( 
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6. 


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.6 
-7.9, 
95% 
CI) 


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, 



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(95% 
credible 
interval: 
5.6–7.7), 


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2. 


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3 


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1 


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should 


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to 


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2019-nCoV 


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for 
2019-nCoV 


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durations 
for 


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durations 


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11,900 


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-

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-

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Therefore, 


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These 
results 
suggest 
that 


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has 


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may 
have 


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., 


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. 


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indicating 


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implying 


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An 


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"BackgroundAn 


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the 
novel 


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severe 
acute 
respiratory 
syndrome 



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2019-nCoV 


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2 
(SARS-CoV-2) 


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7818 


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95 
333 
confirmed 


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30th 
January 


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March 
5, 


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early 


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is 
crucial 
for 


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and 


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likely 


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and 


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is 
crucial 
for 
assessing 
the 


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We 


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Combining 
a 
mathematical 
model 
of 
severe 
SARS-CoV-2 
transmission 
with 
four 
datasets 
from 
within 
and 
outside 
Wuhan, 
we 
estimated 
how 
transmission 
in 
Wuhan 
varied 
between 
December, 
2019, 
and 



February, 
2020. 
We 
used 
these 
estimates 
to 
assess 
the 
potential 
for 
sustained 
human-to-human 
transmission 
to 
occur 
in 
locations 
outside 
Wuhan 
if 
cases 
were 
introduced.MethodsWe 


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of 
coronavirus 
disease 


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-nCoV 


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(COVID-19) 


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exported 


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international 


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originating 


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that 
originated 


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and 
the 
likely 
prevalence 
of 
symptomatic 
cases 
in 
the 
city 
as 
of 
23rd 


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during 


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, 
2020, 
and 
February, 


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would 


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might 


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To 
estimate 
the 
early 
dynamics 
of 
transmission 
in 
Wuhan, 
we 
fitted 
a 
stochastic 
transmission 
dynamic 
model 
to 
multiple 
publicly 
available 
datasets 
on 
cases 
in 
Wuhan 
and 
internationally 
exported 
cases 
from 
Wuhan. 
The 
four 
datasets 
we 
fitted 
to 
were: 
daily 
number 
of 
new 
internationally 
exported 
cases 
(or 
lack 



thereof), 
by 
date 
of 
onset, 
as 
of 
Jan 
26, 
2020; 
daily 
number 
of 
new 
cases 
in 
Wuhan 
with 
no 
market 
exposure, 
by 
date 
of 
onset, 
between 
Dec 
1, 
2019, 
and 
Jan 
1, 
2020; 
daily 
number 
of 
new 
cases 
in 
China, 
by 
date 
of 
onset, 
between 
Dec 
29, 
2019, 
and 
Jan 
23, 
2020; 
and 
proportion 
of 
infected 
passengers 
on 
evacuation 
flights 
between 
Jan 
29, 
2020, 
and 
Feb 
4, 
2020. 


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used 
an 
additional 
two 
datasets 
for 
comparison 
with 
model 
outputs: 
daily 
number 
of 
new 
exported 
cases 
from 
Wuhan 
(or 
lack 
thereof) 
in 
countries 
with 
high 
connectivity 
to 
Wuhan 
(ie, 
top 
20 
most 
at-risk 
countries), 
by 
date 
of 
confirmation, 
as 
of 
Feb 
10, 
2020; 
and 
data 
on 
new 
confirmed 
cases 
reported 
in 
Wuhan 
between 
Jan 
16, 
2020, 
and 
Feb 
11, 
2020.FindingsWe 


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daily 


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, 
R, 
fluctuated 
between 
1.6-2.9 
from 
mid-December 
to 
mid-January 
2020. 
We 
found 
that 
the 
US, 
Australia 
and 
France 
had 
more 
confirmed 
cases 
with 
travel 
history 
to 
Wuhan 
than 
the 
model 
predicted, 
and 
estimated 
that 
there 
were 
29,500 
(14,300-85,700) 
prevalent 
symptomatic 
cases 
in 
Wuhan 
on 
23rd 
January 
2020, 
when 


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(Rt) 
in 
Wuhan 
declined 
from 
2∙35 
(95% 
CI 
1∙15–4∙77) 
1 
week 
before 


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. 


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on 
Jan 
23, 
2020, 
to 
1∙05 
(0∙41–2∙39) 
1 
week 
after. 


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R 


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Rt, 
assuming 
SARS-like 
variation 


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as 


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to 


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in 
early 
January 



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more 
than 
three 


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at 
least 
four 
independently 


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Our 


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InterpretationOur 


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2019-nCoV 
has 
substantial 
potential 
for 
ongoing 
human-to-human 


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COVID-19 


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, 
and 
exported 
cases 
from 


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probably 
declined 
in 


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may 
have 
increased 
prior 
to 
travel 
restrictions 
being 
introduced 
on 
23rd 


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during 
late 


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, 


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. 


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, 
coinciding 
with 
the 
introduction 
of 
travel 
control 
measures. 


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with 
similar 
transmission 
potential 
to 
Wuhan 
before 
these 
control 
measures 



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may 
still 
cause 


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might 
lead 
to 


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. 


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." 


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"Summary 


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-

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the 


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severe 
acute 
respiratory 
syndrome 
(SARS)-related 


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2019-nCoV 


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SARS-CoV-2 


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2,000 


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2000 


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-

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one 
minute 



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1 
min 


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ten 


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2019-nCoV 


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SARS-CoV-2 


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. 
AvailabilityAvailable 
online: 
https://www.genomedetective.com/app/typingtool/cov 
* 
Contactkoen@emweb.be 
and 
deoliveira@ukzn.ac.za 
Supplementary 
informationSupplementary 
data 
is 
available 
online." 


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to 
stop 
the 
COVID-19 
disease. 


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a 


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-

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-

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in 
order 


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SARS. 


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severe 
acute 
respiratory 
syndrome. 


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identified 
specific 
BCoV 


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confirm 
high 
sequence 
similarity 
(>99%) 
between 
all 
sequenced 
2019-nCoVs 


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which 
appear 
to 
be 


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available, 
with 


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relative 
to 
the 
new 
virus, 
with 
protein 


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BCoV 
sequence 
sharing 
96.2% 


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, 
confirming 
the 
notion 


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91.1%, 
providing 
further 
evidence 
for 
a 


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a 


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-

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-

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We 
also 
detected 
low 
variability 
within 


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Despite 


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available 


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low 
heterogeneity 
of 
the 


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-

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-

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specimens 
sequenced 
so 
far, 
despite 
a 
few 
hyper-variable 


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genomes, 
we 
could 
identify 
at 
least 
two 
hypervariable 


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, 
one 
of 
which 
is 
responsible 
for 
a 
Serine/Leucine 
variation 
in 
the 
viral 
ORF8-encoded 
protein 


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model 
anti-viral 


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be 
considered 
for 
antiviral 


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on 


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deriving 
from 
previous 
anti-coronavirus 
approaches 


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the 
2019 


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COVID-19 
outbreak 
caused 
by 
a 


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(2019-nCoV) 
outbreak. 
Since 
the 
first 
reported 
case 
in 
the 
Wuhan 
city 
of 
China, 
2019-nCoV 
has 
spread 
to 
other 
cities 
in 
China 
as 
well 
as 
to 
multiple 
countries 
across 
four 
continents. 


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, 
Severe 
Acute 
Respiratory 
Syndrome 
Coronavirus 
2 
(SARS-CoV-2). 



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ov 


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w 


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2019-nCoV 


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SARS-CoV-2 


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2019-nCoV 


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SARS-CoV-2 


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SARS-CoV, 
which 
caused 


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Severe 
Acute 
Respiratory 
Syndrome 
coronavirus 
(SARS-CoV), 


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outbreak 
in 
2003, 


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2019-nCoV 


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SARS-CoV-2 


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2019-nCoV 



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SARS-CoV-2 


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29 
January 


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21 
February 


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2019-nCoV 


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this 
novel 
virus 


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2019-nCoV. 


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SARS-CoV-2. 


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s 


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of 


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and 


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, 


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, 
and 


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. 


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Background: 
Since 



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"BACKGROUNDSince 


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acute 
respiratory 
disease 
(ARD) 
due 
to 
2019 
novel 


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when 


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( 


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disease 


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-nCoV 


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(Covid-19 


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. 
We 
sought 
to 
delineate 


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, 
data 
have 
been 
needed 
on 


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these 
cases. 
Methods: 
We 


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the 
affected 
patients.METHODSWe 


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the 


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on 
1,099 


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regarding 
1099 



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2019-nCoV 
ARD 


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Covid-19 


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30 


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/provincial 


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, 
autonomous 
regions, 
and 


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in 
mainland 
China 


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th 


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Results: 


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primary 
composite 
end 
point 
was 
admission 
to 
an 
intensive 
care 
unit 
(ICU), 
the 
use 
of 
mechanical 
ventilation, 
or 
death.RESULTSThe 


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of 
the 
patients 


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, 
and 


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; 



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90% 


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9% 
of 
the 
patients 


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females. 


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female. 
The 
primary 
composite 
end 
point 
occurred 
in 
67 
patients 
(6.1%), 
including 
5.0% 
who 
were 
admitted 
to 
the 
ICU, 
2.3% 
who 
underwent 
invasive 
mechanical 
ventilation, 
and 
1.4% 
who 
died. 


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18 


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9 


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the 


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history 
of 


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, 
whereas 
31.30 


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. 
Among 
nonresidents 
of 
Wuhan, 
72.3 


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been 
to 
Wuhan 
and 
71.80% 


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contact 
with 
residents 
of 
Wuhan, 
including 
31.3% 
who 


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contacted 
with 
people 
from 
Wuhan. 
Fever 
(87.9%) 
and 
cough 
(67.7%) 
were 


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visited 
the 
city. 



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. 


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were 
fever 
(43.8% 
on 
admission 
and 
88.7% 
during 
hospitalization) 
and 
cough 
(67.8%). 


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is 


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was 


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. 


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(3.8%). 


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3.0 


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4 


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interquartile 


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0 


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2 


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24.0 
days 
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typical 
radiological 



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most 
common 
radiologic 


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50.00%). 
Significantly 
more 


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CT) 
(56.4%). 
No 
radiographic 
or 
CT 
abnormality 
was 
found 
in 
157 
of 
877 
patients 
(17.9%) 
with 
nonsevere 
disease 
and 
in 
5 
of 
173 
patients 
(2.9%) 
with 


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cases 
were 
diagnosed 
by 
symptoms 
plus 
reverse-transcriptase 
polymerase-chain-reaction 


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disease. 
Lymphocytopenia 
was 
present 
in 
83.2% 
of 
the 
patients 
on 
admission.CONCLUSIONSDuring 
the 
first 
2 
months 
of 
the 
current 
outbreak, 
Covid-19 
spread 
rapidly 
throughout 
China 
and 
caused 
varying 
degrees 
of 
illness. 
Patients 
often 
presented 


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fever, 
and 
many 
did 
not 
have 


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al 


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than 
non-severe 
cases 
(23.87% 
vs. 
5.20%, 
P<0.001). 
Lymphopenia 
was 
observed 
in 
82.1% 
of 
patients. 
55 
patients 
(5.00%) 
were 
admitted 
to 
intensive 
care 
unit 
and 
15 
(1.36%) 
succumbed. 
Severe 
pneumonia 
was 
independently 
associated 
with 
either 
the 
admission 
to 
intensive 
care 
unit, 
mechanical 
ventilation, 
or 
death 
in 
multivariate 
competing-risk 
model 
(sub-distribution 
hazards 
ratio, 
9.80; 
95% 
confidence 
interval, 
4.06 
to 
23.67). 
Conclusions: 
The 
2019-nCoV 
epidemic 
spreads 
rapidly 
by 
human-to-human 
transmission. 
Normal 
radiologic 
findings 
are 
present 
among 
some 
patients 
with 
2019-nCoV 
infection. 
The 
disease 
severity 
(including 
oxygen 
saturation, 
respiratory 
rate, 
blood 
leukocyte/lymphocyte 
count 
and 
chest 
X-ray/CT 
manifestations) 
predict 
poor 
clinical 
outcomes. 


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. 
(Funded 
by 
the 
National 
Health 
Commission 
of 
China 
and 
others.)" 


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" 


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a 
syndrome 
associated 
with 



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= 


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= 


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= 


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= 


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= 


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= 


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= 


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= 


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syndromes 


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syndromes 


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= 


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= 


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. 


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." 



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Background 
To 
analyse 
the 
impact 
of 
the 
Novel 
Coronavirus 
Pneumonia 
(NCP 


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"BackgroundA 
novel 
coronavirus 
disease 
(COVID-19 


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due 
to 
the 
severe 
respiratory 
syndrome 
coronavirus 
(SARS-CoV-2) 
infection 
occurred 
in 
China 
in 
late 
December 
2019. 
Facemask 
wearing 
with 
proper 
hand 
hygiene 
is 
considered 
an 
effective 
measure 
to 
prevent 
SARS-CoV-2 
transmission, 
but 
facemask 
wearing 
has 
become 
a 
social 
concern 
due 
to 
the 
global 
facemask 
shortage. 
China 
is 
the 
major 
facemask 
producer 
in 
the 
world, 
contributing 
to 
50% 
of 
global 
production. 
However, 
a 
universal 
facemask 
wearing 
policy 
would 
put 
an 
enormous 
burden 


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shortage 
in 
China 
and 
provide 
insight 
into 
the 
development 
of 
emergency 
plans 
for 
future 
infectious 
disease 
outbreaks. 
Methods 


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supply.MethodsWe 
performed 
a 


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concerning 
facemasks 


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shortage 
analysis 
using 


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shortage 
analyses 


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and 
the 
Center 
for 
Disease 
Control 
and 
Prevention 
(CDC) 
of 
the 
Peoples 
Republic 
of 
China. 
Findings 
Supplies 
of 
facemasks 
in 
the 
whole 
of 
China 
would 
have 
been 
sufficient 
for 
both 
the 
healthcare 
workers 
and 
the 
general 
population 
if 
the 
NCP 
outbreak 
only 
occurred 
in 
Hubei 
province. 
However, 
if 
the 
outbreak 
occurred 
in 
both 
Hubei 
and 
Guangdong 
provinces, 
facemask 
supplies 
in 
the 
whole 
of 
China 
could 
last 
for 
34 
days 
if 
no 
alternative 
public 
health 
intervention 
was 
introduced. 
There 
would 
be 
a 
shortage 
of 
480 
million 
facemasks 
by 
mid-February 
2020. 
If 
the 
outbreak 
occurred 
in 
the 
whole 
of 
China, 
facemask 
supplies 
could 
only 
last 
for 
16 
days 
and 
the 
shortage 
would 
considerably 
worsen, 
with 
a 
shortage 
of 
11.5 
billion 
facemasks 
by 
mid-February 
2020. 
Interpretation 
In 
light 
of 
the 
novel 
coronavirus 
outbreak 
in 
China, 
insufficient 
medical 
resources 
(e.g., 
shortage 
of 
facemasks) 
can 
considerably 
compromise 
the 
efficacy 
of 
public 
health 
measures. 
An 
effective 
public 
health 
intervention 
should 
also 
consider 
the 
adequacy 
and 
affordability 
of 
existing 
medical 
resources. 
Global 
collaboration 
should 
be 
strengthened 
to 
prevent 
the 
development 
of 
a 
global 
pandemic 
from 
a 
regional 
epidemic 
via 
easing 
the 
medical 
resources 
crisis 
in 
the 
affected 
countries. 



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the 
Centre 
for 
Disease 
Control 
and 
Prevention 
(CDC), 
and 
General 
Administration 
of 
Customs 
(GAC) 
of 
the 
People's 
Republic 
of 
China. 
Three 
scenarios 
with 
respect 
to 
wearing 
facemasks 
were 
considered: 
(1) 
a 
universal 
facemask 
wearing 
policy 
implementation 
in 
all 
regions 
of 
mainland 
China; 
(2) 
a 
universal 
facemask 
wearing 
policy 
implementation 
only 
in 
the 
epicentre 
(Hubei 
province, 
China); 
and 
(3) 
no 
implementation 
of 
a 
universal 
facemask 
wearing 
policy.FindingsRegardless 
of 
different 
universal 
facemask 
wearing 
policy 
scenarios, 
facemask 
shortage 
would 
occur 
but 
eventually 
end 
during 
our 
prediction 
period 
(from 
20 
Jan 
2020 
to 
30 
Jun 
2020). 
The 
duration 
of 
the 
facemask 
shortage 
described 
in 
the 
scenarios 
of 
a 
country-wide 
universal 
facemask 
wearing 
policy, 
a 
universal 
facemask 
wearing 
policy 
in 
the 
epicentre, 
and 
no 
universal 
facemask 
wearing 
policy 
were 
132, 
seven, 
and 
four 
days, 
respectively. 
During 
the 
prediction 
period, 
the 
largest 
daily 
facemask 
shortages 
were 
predicted 
to 
be 
589∙5, 
49∙3, 
and 
37∙5 
million 
in 
each 
of 
the 
three 
scenarios, 
respectively. 
In 
any 
scenario, 
an 
N95 
mask 
shortage 
was 
predicted 
to 
occur 
on 
24 
January 
2020 
with 
a 
daily 
facemask 
shortage 
of 
2∙2 
million.InterpretationImplementing 
a 
universal 
facemask 
wearing 
policy 
in 
the 
whole 
of 
China 
could 
lead 
to 
severe 
facemask 
shortage. 
Without 
effective 
public 
communication, 
a 
universal 
facemask 
wearing 
policy 
could 
result 
in 
societal 
panic 
and 
subsequently, 
increase 
the 
nationwide 
and 
worldwide 
demand 
for 
facemasks. 
These 
increased 
demands 
could 
cause 
a 
facemask 
shortage 
for 
healthcare 
workers 
and 
reduce 
the 
effectiveness 
of 
outbreak 
control 
in 
the 
affected 
regions, 
eventually 
leading 
to 
a 
pandemic. 
To 
fight 
novel 
infectious 
disease 
outbreaks, 
such 
as 
COVID-19, 
governments 
should 
monitor 
domestic 
facemask 
supplies 
and 
give 
priority 
to 
healthcare 
workers. 
The 
risk 
of 
asymptomatic 
transmission 
and 
facemask 
shortages 
should 
be 
carefully 
evaluated 
before 
introducing 
a 
universal 
facemask 
wearing 
policy 
in 
high-risk 
regions. 
Public 
health 
measures 
aimed 
at 
improving 
hand 
hygiene 
and 
effective 
public 
communication 
should 
be 
considered 
along 
with 
the 
facemask 
policy." 


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novel 


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( 


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disease-

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nCoV) 
infected 
pneumonia 
(NCIP 


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(COVID-19 


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(WHO, 
CDC, 
ECDC, 
NHC 
and 
DXY) 


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, 
China 


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, 
i.e. 


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. 
In 
particular, 
we 
provide 
an 
estimation 
of 
the 
case 
fatality 
and 
case 
recovery 
ratios, 
along 
with 
their 
90% 
confidence 
intervals 
as 
the 
outbreak 
evolves. 
On 
the 
basis 
of 
a 
Susceptible-Infectious-Recovered-
Dead 
(SIDR) 
model, 
we 
provide 
estimations 
of 


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) 


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), 


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per 
day 


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, 
recovery 
and 


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rates, 
along 
with 
their 
90% 
confidence 
intervals 


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and 
recovery 
rates. 
By 
calibrating 
the 
parameters 
of 
the 
SIRD 
model 
to 
the 
reported 
data, 
we 
also 
attempt 
to 
forecast 
the 
evolution 
of 
the 
outbreak 
at 
the 
epicenter 
three 
weeks 
ahead, 
i.e. 
until 
February 
29 


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which 
can 
be 
considered 
only 
as 
a 
subset 
of 
the 
actual 
numbers 
of 
infected 
and 
recovered 
cases 
in 
the 
total 
population, 


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second 


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five 


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twenty 



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eight 


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forty 


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. 
Our 
computations 
and 
analysis 
were 


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, 
leaving 
the 
number 
of 
deaths 
unchanged. 


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a 
mean 
field 
Susceptible-Infected-Recovered-Dead 
(SIRD) 
model. 


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the 
reported 
data, 
the 
expected 
value 
of 
R0 
as 
computed 
considering 
the 
period 
from 
the 
11th 
of 
January 
until 
the 
18th 
of 
January, 
using 
the 
official 
counts 
of 
confirmed 
cases 
was 
found 
to 
be 
∼4.6, 
while 
the 
one 
computed 
under 
the 
second 
scenario 
was 
found 
to 
be 
∼3.2. 


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2.5, 
while 
the 
one 
computed 
by 
the 
official 
counts 
of 
the 
confirmed 
cases 
from 
the 
11th 
of 
January 
until 
the 
18th 
of 
January 
was 
found 
to 
be 
4.6. 
Furthermore, 
on 
the 
estimated 
parameters 
from 
both 
scenarios, 
we 
provide 
tentative 
three-week 
forecasts 
of 
the 
evolution 
of 
the 
outbreak 
at 
the 
epicenter 


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∼2.6 
based 
on 
confirmed 
cases 
and 
∼2 
based 
on 
the 
second 
scenario 


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simulations 
suggest 
that 
the 


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will 
surpass 
68,000 
(as 
a 
lower 
bound) 
and 


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an 
upper 



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a 
lower 


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current 


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the 
up 
to 
the 
10th 
of 
February 
reported 


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and 
estimations 
on 
the 
official 
count 
of 
infected 
people 
in 
the 
population 


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7,000 


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2,700 
(as 
a 
lower 
bound) 


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; 
however, 


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. 


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mortality 
rate 


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case 
fatality 
ratio 
from 
January 
26 


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also 
a 
high 
underestimation 
of 
the 
number 
of 
infected 
and 
recovered 
people 
in 
the 
population, 
which 
will 
hopefully 
lower 
the 
death 
toll. 


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mainly 
because 
of 
the 
fact 
that 
the 
actual 
cumulative 
numbers 
of 
infected 
and 
recovered 
cases 
in 
the 
population 
most 
likely 
are 
much 
higher 
than 
the 
reported 
ones. 
Thus, 
in 
a 
scenario 
where 
we 
have 
taken 
twenty 
times 
the 
confirmed 
number 
of 
infected 
and 
forty 
times 
the 
confirmed 
number 
of 
recovered 
cases, 
the 
case 
fatality 
ratio 
is 
around 
∼0.15% 
in 
the 
total 
population. 
Importantly, 
based 
on 
this 
scenario, 
simulations 
suggest 
a 
slow 
down 
of 
the 
outbreak 
in 
Hubei 
at 
the 
end 
of 
February. 


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beta 


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urgently 
needed 


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(MCM) 


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, 


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[A]


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-angstrom-

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-EM 


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–electron 
microscopy 


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show 


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provide 


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protein 


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angiotensin-converting 
enzyme 
2 
( 


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) 


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does 
severe 
acute 
respiratory 
syndrome 
( 


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-

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)


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, 


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2019


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-2019 


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that 


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virus 


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atomic-resolution 


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the 


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MCMs 


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medical 
countermeasures 


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over 
45 


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more 
than 
100 


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PCR 


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more 
than 
1,000 


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4000 


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Feb 
12, 


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10 
March 


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Imported 
cases 
and 
small 
transmission 
clusters 
have 


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The 
outbreak 
has 


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reported 
globally. 
Early 
data 
suggest 
the 
virus 
transmits 
readily 
and 


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declared 


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cannot 
be 
ruled 
out 


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by 
the 
WHO 
on 
Mar 
11, 
2020. 
Here, 
we 
explore 
how 
seasonal 
variation 
in 
transmissibility 
could 
modulate 
a 
SARS-CoV-2 
pandemic 


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). 
We 
use 


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) 
and 
we 
parameterise 
our 
model 
for 
SARS-CoV-2 
using 



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to 
explore 
the 
effect 
of 
seasonal 
variation 
in 
transmissibility 
on 
a 
potential 
SARS-CoV-2 
pandemic. 
A 
model 
allowing 


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. 
The 
model 
allows 


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of 
SARS-CoV-2 
spread 
shows 
how 
a 
pandemic 
could 
unfold 
in 
2020-2022. 


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. 


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small 


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early 
2020 
in 


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and 
a 
larger 
peak 


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A 
smaller 
range 
of 
parameters 
suggests 
a 
peak 
in 
the 
first 
half 
of 
2020 
or 
two 
peaks 
of 
similar 
magnitude. 


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beyond 


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across 
the 
world 


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ov 


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w 


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provisionally 
termed 
2019-nCoV 


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SARS-CoV-21 


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likely 


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probable 


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2019-nCoV 


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SARS-CoV-2 


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facilitating 


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that 
may 
have 
facilitated 


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, 


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2019-nCoV 


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SARS-CoV-2


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Malayan 


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-

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CoVs 


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coronaviruses 


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2019-nCoV 


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SARS-CoV-2


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very 
closely 
related 
to 
2019-nCoV 


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that 
exhibits 
strong 
similarity 


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. 


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to 
SARS-CoV-2. 


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2019-nCoV 


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SARS-CoV-2 


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intermediate 


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for 
this 
novel 
human 
virus 


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in 
the 
emergence 
of 
new 
coronaviruses 


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’s 


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(PD) 


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(DLB). 
The 
majority 
of 
patients 
with 
isolated 
rapid 
eye 
movement 
sleep 
behavior 
disorder 
(iRBD) 
develop 
PD 
or 
DLB 
later 
in 
life, 
suggesting 
that 
iRBD 
is 
a 
prodromal 
phase 
of 
these 
two 
conditions. 


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. 


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, 


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iRBD. 


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isolated 
rapid 
eye 
movement 
sleep 
behavior 
disorder 
(iRBD). 


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1,287 
controls 
from 
European 
descent. 
Logistic 
regression 
adjusted 
for 
sex 
and 
age 
showed 
no 
significant 
associations 
with 
two 
common 
variants 
and 
iRBD 
(rs1050239 
and 
rs8164). 
The 
frequency 
of 
all 
rare 
nonsynonymous 
SMPD1 
variants 
(minor 
allele 
frequency 
<1%) 
was 
found 
to 
be 
twice 
as 
high 
in 
cases 
than 
in 
controls 
(1.46% 
vs. 
0.70%, 
Fisher's 
exact 
test 
p=0.09) 
but 
there 
was 
no 
statistically 
significant 
burden 
(p=0.64). 


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1287 
controls 
from 
European 
descent. 


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Background: 
The 


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"BackgroundThe 


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Method: 
Peripheral 


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MethodsPeripheral 


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Findings: 
Of 



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FindingsOf 


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[0∙6 
(0∙6-0∙8)] 


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[4∙7 
(3∙6-5∙8)] 


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. 


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[1.1 
(0∙8-1∙4); 
2∙0 
(1∙5-2∙9)]. 


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lymphocyte 
ratio 
(NLR) 
(AUC=0∙93) 
and 
neutrophil-to-

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(AUC 
=0∙94) 


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the 
most 


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s 


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Conclusion: 
The 


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InterpretationThe 


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and 
NLR 


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FundingThe 
National 
Natural 
Science 
Foundation 
of 
China, 
the 
National 
Science 
and 
Technology 
Major 
Project, 
the 
Health 
Commission 
of 
Hubei 
Province, 
Huazhong 
University 
of 
Science 
and 
Technology, 
and 
the 
Medical 
Faculty 
of 
the 
University 
of 
Duisburg-Essen 
and 
Stiftung 
Universitaetsmedizin, 
Hospital 
Essen, 
Germany." 



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" 


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2019-nCoV 


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SARS-CoV-2 


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2019-nCov 


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SARS-CoV-2 


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2019-nCoV 


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SARS-CoV-2 


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" 


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“ 


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" 


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” 


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. 


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." 


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Since 
December, 
2019, 
an 



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The 


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pneumonia 
caused 
by 
the 
new 


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a 
novel 


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(2019-nCoV) 
has 
hit 
the 
city 
of 
Wuhan 
in 
the 
Hubei 
Province. 
With 
the 
continuous 
development 
of 
the 
epidemic, 
it 
has 
become 
a 
national 


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, 
which 
was 
later 
formally 
named 
the 
severe 
acute 
respiratory 
coronavirus 
2 
(SARS-CoV-2), 
has 
caused 
a 
worldwide 


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and 
calls 
for 
urgent 
antiviral 
treatments 
or 
vaccines. 
The 
spike 
protein 
on 
the 
coronavirus 
envelope 
is 
critical 
for 
host 
cell 
infection 
and 
virus 
vitality. 


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. 


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2019-nCoV 


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SARS-CoV-2 


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human 


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attaches 
host 
cells 
though 


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infects 
humans 
through 


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receptor 
binding 
domain 
(RBD) 
domain 



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protein 


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the 
angiotensin-converting 
enzyme 
II 
( 


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). 
However, 
the 


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. 
Here, 
we 
have 
systematically 
studied 
the 


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2019-nCoV 
binding 
to 
human 
ACE2 
and 
evolution 
of 
2019-nCoV 
remain 
unclear. 
In 
this 
study, 
we 
have 
extensively 
studied 
the 
RBD-ACE2 
complex, 
spike 
protein, 
and 
free 
RBD 
systems 
of 
2019-nCoV 
and 
SARS-CoV 
using 


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human 
infection 
with 
SARS-CoV-2 
and 
SARS-CoV 
by 


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molecular 
dynamics 
( 


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) 


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shown 


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found 


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the 
RBD-ACE2 
binding 
free 
energy 
for 
2019-nCoV 
is 
significantly 
lower 


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SARS-CoV-2 
binds 
ACE2 
with 
a 
higher 
affinity 


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SARS-CoV, 
which 
may 
partly 
explain 


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for 
SARS-CoV, 
which 
is 
consistent 
with 
the 
fact 
that 
2019-nCoV 


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SARS-CoV-2 


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2019-nCoV 
shows 


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SARS-CoV-2 
has 


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2019-nCoV 


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SARS-CoV-2 


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able 
to 


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may 


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may 
also 
provide 


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provides 


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2019-nCoV 


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SARS-CoV-2 


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are 
thought 
to 


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that 
are 
known 
to 
have 
a 
higher 
body-temperature 
than 
humans. 
It 
was 


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. 
Our 
computation 


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revealed 


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suggested 


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of 
2019-nCoV 


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-ACE2 
binding 
for 
SARS-CoV-2 


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flexible 
especially 
near 
the 
binding 
site 
and 
thus 
will 
have 
a 
higher 
entropy 
penalty 
upon 
binding 
ACE2, 
compared 
to 
the 
RBD 
of 
SARS-CoV. 
That 
means 
that 
2019-nCoV 
will 
be 
much 
more 


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in 
terms 
of 
human 
infection 


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that 
for 


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With 
the 
rising 
temperature, 
2019-nCoV 


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Thus, 
it 


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to 


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that 
SARS-CoV-2 
would 


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, 
and 
get 
controlled 
more 
easily. 
The 
present 


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when 
the 
temperature 
rises. 
These 



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are 
expected 
to 


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would 


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helpful 


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beneficial 


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control 
as 
well 
as 


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and 


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/ 


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2019-nCoV. 


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SARS-CoV-2. 


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As 
a 
novel 
coronavirus 
(COVID-19) 
continues 
to 
emerge 
throughout 
China 
and 
threaten 


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We 
estimate 


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globe, 
its 
transmission 
characteristics 
remain 
uncertain. 
Here, 
we 
analyze 
the 


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distribution 
of 


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-the 
time 
period 
between 
the 
onset 
of 
symptoms 
in 
an 
index 
(infector) 
case 
and 
the 
onset 
of 
symptoms 
in 
a 
secondary 
(infectee) 
case-of 



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for 


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infector-infectee 
pairs 
with 


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COVID-19 


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of 
coronavirus 
disease 


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by 
health 
departments 
in 
18 
Chinese 
provinces 
between 
January 
21, 
2020, 
and 


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in 
China 
as 
of 


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reported 
serial 
intervals 
range 
from 
-11 
days 
to 
20 
days, 
with 
a 


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of 


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interval 
was 


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confidence 
interval: 


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CI 


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-

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– 


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), 
a 
standard 
deviation 
of 



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days), 
SD 


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confidence 
interval: 


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-

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– 


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), 
and 


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days); 


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1 


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6 


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case 


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indicating 
pre-symptomatic 


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indicated 
presymptomatic 


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recent 


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a 
novel 
coronavirus 
associated 
with 
an 
ongoing 
outbreak 
of 
pneumonia 
(Covid-2019) 



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SARS-CoV-2 
has 


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>90,000 


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of 
more 
than 
72,000 
people 


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claimed 
over 
1,800 
lives. 


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>3,000 
deaths. 


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glycoprotein 
trimers 


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glycoproteins 


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the 
humoral 
immune 
response. 


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antibodies. 


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here 


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mediates 
entry 
in 
VeroE6 


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uses 
ACE2 
to 
enter 


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in 
BHK 
cells 
transiently 
transfected 
with 
human 
ACE2, 
establishing 
ACE2 
as 
a 
functional 
receptor 
for 
this 
novel 
coronavirus. 
We 
further 
demonstrate 


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which 
correlates 



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correlating 


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other 


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a 


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electron 
microscopy 
structure 


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EM 
structures 


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demonstrating 
spontaneous 
opening 
of 
the 
receptor-binding 
domain, 
and 


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sera 


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antibodies 


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-

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target 


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thereby 


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Background 


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Methods 


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Findings 



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As 
a 
result, 


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before 


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while 


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and 


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, 


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five 


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5 


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seven 


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7 


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seven 


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7 


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= 


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= 


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Interpretation 



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Overall, 


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"Potential 
transmissibility 
of 
asymptomatic 
2019 
Novel 
Coronavirus 
infection 
and 
a 
substantial 
asymptomatic 
ratio 
have 
been 
reported 
in 
clinical 
studies. 
Employing 
a 
statistical 
modeling 
analysis, 
we 
derived 
a 
delay-adjusted 
asymptomatic 
ratio 
of 
the 
positive 
2019-nCoV 
infections 
onboard 
the 
Princess 
Cruises 
ship 
along 
with 
the 
timeline 
of 
infections. 
We 
estimated 
the 
percentage 
of 
cases 
that 
are 
asymptomatic 
to 
be 
34.6% 
(95% 
CrI: 
29.4%-39.8%), 
with 
most 
of 
the 
infections 
occurring 
before 
the 
start 
of 
the 
2-week 
quarantine.Competing 
Interest 
StatementThe 
authors 
have 
declared 
no 
competing 
interest.Funding 
StatementKM 
acknowledges 
support 
from 
the 
Japan 
Society 
for 
the 
Promotion 
of 
Science 
(JSPS) 
KAKENHI 
Grant 
Number 
18K17368 
and 
from 
the 
Leading 
Initiative 
for 
Excellent 
Young 
Researchers 
from 
the 
Ministry 
of 
Education, 
Culture, 
Sport, 
Science 
& 
Technology 
of 
Japan. 
KK 
acknowledges 
support 
from 
the 
JSPS 
KAKENHI 
Grant 
Number 
18K19336 
and 
19H05330. 
AZ 
acknowledges 
supports 
from 
the 
Oxford 
Martin 
School 
Programme 
on 
Pandemic 
Genomics. 
GC 
acknowledges 
support 
from 
NSF 
grant 
1414374 
as 
part 
of 
the 
joint 
NSF-NIH-USDA 
Ecology 
and 
Evolution 
of 
Infectious 
Diseases 
program" 


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On 
5 
February 
2020, 
in 
Yokohama, 
Japan, 
a 
cruise 
ship 
hosting 
3,711 
people 
underwent 
a 
2week 
quarantine 
after 
a 
former 
passenger 
was 
found 
with 
COVID-19 
post-disembarking. 
As 
at 
20 
February, 
634 
persons 
on 
board 
tested 
positive 
for 
the 
causative 
virus. 
We 
conducted 
statistical 
modelling 
to 
derive 
the 
delay-adjusted 
asymptomatic 
proportion 
of 
infections, 
along 
with 
the 
infections’ 
timeline. 
The 
estimated 
asymptomatic 
proportion 
was 
17.9% 
(95% 
credible 
interval 
(CrI): 
15.5–20.2%). 
Most 
infections 
occurred 
before 
the 
quarantine 
start. 


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Abstract 
Background: 


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Objectives 


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) 


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)


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Diagnostic 
test 



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Laboratory-

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on 


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diagnostic 
tests 
utilized 


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ion 


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ase 


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assay 
(qRT 


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(RT 


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was 
the 
main 
means 
of 
confirmation, 
and 
sample 
collection 
was 
mostly 


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on 


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swabs, 
which 
was 
easy 


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samples. 
This 
study 
evaluated 
the 
diagnostic 
value 


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miss 
the 
diagnosis. 
It 
is 
necessary 


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analyzing 
throat 
and 
sputum 
samples 
in 
order 


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seek 
specimen 
types 
with 
higher 



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improve 
accuracy 
and 


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and 
accuracy. 


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. 


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: 


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qRT 


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the 
RT 


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: 


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qRT 


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the 
RT 


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= 


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= 


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: 


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a 


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we 



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those 
from 


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. 


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-

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– 


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– 


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– 


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– 


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-

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– 


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OBJECTIVE 
To 
reveal 
more 
data 
on 
the 
epidemiologic 
and 


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"BackgroundRecent 
studies 
have 
focused 
on 
initial 



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and 
epidemiological 


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the 


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) 


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), 
which 
is 
the 
mainly 
revealing 
situation 
in 
Wuhan, 
Hubei.AimThis 
study 
aims 
to 
reveal 
more 
data 
on 
the 
epidemiological 
and 
clinical 
characteristics 
of 
COVID-19 


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from 
five 
hospitals 
in 
east 
of 


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province 


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DESIGN 


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DesignThis 
study 
was 
a 


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SETTING 
Five 
hospitals 
in 
east 
of 
Zhejiang 
province, 
China. 
PARTICIPANTS 
88 


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MethodsEighty-eight 


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3 


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three 


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ly 



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hospital. 


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five 
hospitals 
in 
Zhejiang 
province, 
China. 


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MAIN 
OUTCOME 
MEASURES 
A 
team 
of 
physicians 
who 
had 
been 
treating 
these 
patients 
extracted 
and 
recorded 
the 
exposure 
history, 
clinical 
symptoms, 
chest 
computed 
tomography 


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Results 


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laboratory 
findings 
from 
medical 
records 
and 
sent 
the 
data 
to 
the 
working 
group 
in 
Ningbo 
to 
review 
and 
calculate. 
RESULTS 
Of 


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discussionOf 


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pneumonia 


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while 
3 


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, 
three 


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cases 


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-

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ly 


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COVID-19 
pneumonia 
cases. 


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. 


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– 


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, 


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s 


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8 


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eight 


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cases 


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patients 


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and 


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cases 


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patients 


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confirmed 
aircraft 
transmission 


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diagnosed 
after 
having 
flown 
together 
in 
the 
same 
flight 
with 
no 
passenger 
that 
could 
later 
be 
identified 
as 
the 
source 
of 
infection 



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IQR, 


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interquartile 
range 


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– 


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the 


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the 


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– 


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, 
and 
27.47% 
cases 
showed 
unilateral 
pneumonia. 
CONCLUSION 
Social 


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.ConclusionsSocial 


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travel 
by 
airplane 


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flying 
alongside 
with 
persons 
already 
infected 
with 
COVID-19 


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COVID-19 
patients 
get 
transmitted 
and 
could 
be 
rapidly 
diagnosed 


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people 
got 
infected 
with 



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. 


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." 


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An 
outbreak 
of 
COVID-19 
developed 
aboard 
the 
Princess 
Cruises 
Ship 
during 
January–February 


2020. 


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how 


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varied 
over 
the 
course 


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COVID-19 


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aboard 
the 
Princess 
Cruises 
Ship, 
January-February 
2020. 
Probably 
due 
to 


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. 
Our 
estimate 
of 


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enhanced 
quarantine 
control, 
overall 


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mean 
reproduction 
number 
in 
the 
confined 
setting 
reached 
values 
as 
high 
as 
~11, 
which 
is 
higher 
than 
mean 
estimates 
reported 
from 
community-level 
transmission 
dynamics 
in 
China 
and 
Singapore 
(approximate 
range: 
1.1–7). 
Our 
findings 
suggest 
that 


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stage, 
but 
it 
exhibited 
fluctuations 
around 


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phase 
after 
the 
Japanese 
government 
implemented 
an 
enhanced 
quarantine 
control. 
Most 
recent 
estimates 
of 
Rt 
reached 
values 
largely 
below 


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which 
suggests 



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indicating 
that 


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very 
low 
probability 
of 
observing 


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outbreaks 
of 
the 
disease 


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outbreak 
of 
the 
novel 
coronavirus 
was 
unlikely 
to 
occur 
aboard 
the 
Diamond 
Princess 
Ship 


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BACKGROUND: 
A 
recent 
outbreak 
of 


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"Background 
& 
AimsSome 
patients 
with 


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occurs 
mainly 
in 
China, 
with 
rapidly 
increasing 
the 
number 
of 
cases 
(namely 
COVID-19). 


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have 


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functions 
are 
frequently 
present 
in 
these 
patients, 
here 


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function. 


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clinical 


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some 


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the 


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METHODS: 
In 
this 



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MethodsWe 
performed 
a 


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, 
we 
included 
all 


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of 
148 
consecutive 
patients 
with 


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cases 
in 


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(73 
female, 
75 
male; 
mean 
age, 
50 
years) 
at 
the 


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to 


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through 


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The 


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Patient 


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up 


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A 
total 
of 
148 
cases 


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Patients 


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, 


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the 



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hospital 


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FINDINGS: 
Of 
148 
confirmed 
SARS-CoV-2-infected 
patients, 
49.3% 
were 
females 
and 
50.7% 
were 
males. 
The 
median 
age 
was 
50.5 
years 
(interquartile 
range, 
36-64). 
Patients 
had 
clinical 
manifestations 
of 
fever 
(70.1%), 
cough 
(45.3%), 
expectoration 
(26.7%) 
at 
admission. 
75 
patients 
(50.7%) 
showed 


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functions 
at 
admission, 
characterized 
by 
an 


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function 
was 
defined 
as 


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of具体那些升高 
alt, 
ast, 
GGT, 
AKP等. 
Patients 
(n 
= 
75) 
who 
had 
elevated 
liver 
function 
index 
were 
more 
likely 
to 
have 
a 
moderate-high 
degree 
fever 
(44% 
vs 
27.4%; 
p 
= 
0.035) 


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levels 
of 
alanine 
and 
aspartate 
aminotransferase, 
gamma 
glutamyltransferase, 
alkaline 
phosphatase, 


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significantly 
present 
in 
male 
patients 
(62.67% 
vs 
38.36%; 
p 
= 
0.005). 
The 
numbers 
of 
CD4+ 
and 
CD8+ 
T 
cells 
were 
significantly 
lower 
in 


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total 
bilirubin.ResultsFifty-five 
patients 
(37.2%) 
had 
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group 
than 
those 
in 
normal 
liver 
function 
group. 
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at 
hospital 
admission; 
14.5% 
of 
these 
patients 
had 
high 
fever 
(14.5%), 
compared 
with 
4.3% 
of 
patients 
with 
normal 
liver 
function 
(P 
= 
.027). 
Patients 
with 
abnormal 
liver 
function 
were 
more 
likely 
to 
be 
male, 
and 
had 
higher 
levels 
of 
procalcitonin 
and 
C-reactive 
protein. 


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in 
prehospital 
medications 


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normal 
and 
abnormal 
liver 
function 



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, 
while 
the 
utilization 
rate 
of 


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in 
medications 
taken 
before 
hospitalization; 
a 
significantly 
higher 
proportion 
of 
patients 
with 
abnormal 
liver 
function 
(57.8%) 
had 
received 


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was 
significantly 
higher 
in 
patients 
with 
emerging 
liver 
injury 
than 
that 
in 


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compared 
to 


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functions. 
Importantly, 
the 
emerging 


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function 
(31.3%). 
Patients 
with 


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functions 
after 
admission 
caused 
a 
prolonged 
length 
of 
stay. 
INTERPRETATION: 


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function 
had 
longer 
mean 
hospital 
stays 
(15.09 
± 
4.79 
days) 
than 
patients 
with 
normal 
liver 
function 


(12.76 
± 
4.14 
days) 
(P 
= 
.021).ConclusionsMore 
than 
one 
third 
of 
patients 
admitted 
to 
the 
hospital 
with 
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may 
cause 
the 


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infection 
have 
abnormal 


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damage 


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, 


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the 
Lopinavir/ritonavir 


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this 
is 
associated 
with 
longer 
hospital 
stay. 
A 
significantly 
higher 
proportion 
of 
patients 
with 
abnormal 
liver 
function 
had 
received 
lopinavir/ritonavir 
after 
admission; 
these 
drugs 


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applied 
carefully 
for 
the 
treatment 
of 
COVID-19. 


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given 
with 
caution." 


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Background: 


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The 
Coronavirus 
Disease 
2019 
( 


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PM 


) 


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the 


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COVID-19 
has 
now 
been 
declared 
a 
pandemic 
and 


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of 


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for 


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United 
States 
( 


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) 


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high, 
at 
the 
time 
of 
survey 
administration 
the 
risk 
of 
infection 
in 
the 
US 
was 


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, 



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. 


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Methods 
and 
Findings: 


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the 


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The 


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the 


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Conclusion: 


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" 


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new 


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identified 


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, 
known 


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2019 
novel 


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severe 
acute 
respiratory 
syndrome 


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(COVID-19) 


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2 
(SARS-CoV-2), 



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a 


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-

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– 


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that 
commenced 
in 
Wuhan1


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of 
coronavirus 
disease 
2019 
(COVID-19)1,2,3, 


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, 


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is 


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are 


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therapeutics 


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therapeutic 
agents 
for 
the 
treatment 
of 
this 
disease, 


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In 
order 


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Here 
we 
describe 
the 
results 
of 
a 
programme 
that 
aimed 


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we 
initiated 
a 
program 
of 
combined 


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by 
combining 



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, 


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to 
identify 
new 


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. 
This 
programme 
focused 
on 
identifying 


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the 
COVID-19 


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). 


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) 
of 
SARS-CoV-2: 


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coronavirus 


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, 
which 
plays 


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of 
coronaviruses 
and 
has 


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this 
virus5 


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SARS-CoV-25 


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Here, 


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, 


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( 



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, 


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) 


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, 


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subsequently 


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then 


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COVID-19 


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of 
SARS-CoV-2 


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Next, 


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over 


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more 
than 


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— 


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, 


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— 


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Seven 



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Six 


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inhibit 


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compounds 
inhibited 


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with 
IC50 


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, 
showing 
half-maximal 
inhibitory 
concentration 


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ranging 


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that 
ranged 


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48 


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67 


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16.62 
μM. 
Ebselen, 
thiadiazolidinone-8 
(TDZD-8) 
and 
N3 


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21.4 
μM. 
One 
of 
these 
compounds 
(ebselen) 
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strong 


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promising 


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this 



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our 


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and 
establishes 
a 
new 
paradigm 
for 


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which 
can 
lead 
to 


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where 


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for 
which 


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. 


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." 


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The 


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"BackgroundThe 


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over 


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in 


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in 


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over 


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a 



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case 
numbers 


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number 
of 
confirmed 
cases 


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intervention 


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from 
multiple 


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of 
implemented 


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We 


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MethodsWe 


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Susceptible, 
Un-quanrantined 
infected, 
Quarantined 
infected, 
Confirmed 
infected 
(SUQC) 


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SUQC 


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adequately 
characterizes 


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characterize 


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model 


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parameterize 


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intervention 
effects 
of 



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by 
artificial 


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The 


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ResultsThe 


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ed 


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ions 


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i 


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ou 


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ve 


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> 


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> 


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ve 


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d 


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< 



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< 


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the 
effectiveness 
of 


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that 


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in 
inhibiting 


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are 
effective 
in 
preventing 
the 
spread 
of 


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estimated 
by 
our 
model 


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significantly 


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substantially 


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0.1914 


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that 


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( 


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) 


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(0.1914), 


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0.2189 



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that 


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( 


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(0.2189 


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increases 


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it 
jumps 


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Feb 
12th 


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February 
12 


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diagnosis 


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evidence 


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. 


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in 
new 
diagnosis 
guidelines. 


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un-quarantined 


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number 
of 
unquarantined 


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individuals 



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cases 


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as 
high 
as 


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estimated 
to 
be 


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r 


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lin 


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a 


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es 


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th 


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recent 


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as 
of 
February 
21, 
2020 


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s 


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of 


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in 


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are 



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is 


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-

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of 


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around 
mid 
March 
for 


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( 


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) 
around 
mid-March 


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of 


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before 
early 
March 
2020 
for 


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before 
March 
2020. 


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. 


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of 
the 
whole 
country 


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estimated 
to 
be 


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in 
China 


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We 



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Note 
that 
the 
estimates 
are 
from 
a 
deterministic 
ODE 
model 
and 
should 
be 
interpreted 
with 
some 
uncertainty.ConclusionsWe 


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e 


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at 


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early 


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-

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counties 
in 
a 


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countries 
at 


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, 
Italy 


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. 


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." 


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Since 


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"ObjectivesSince 


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identified 
individual 


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case 



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infection 


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identified 


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, 


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confirmed 


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. 
As 
of 
Feb 
26, 
2020, 
1,261 


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, 
resulting 
in 
6284 


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of 
COVID-19 


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12 


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42 


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were 
confirmed 
in 


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as 
of 
Mar 
6, 
2020. 
To 
examine 
the 
growth 
rate 
of 
the 
outbreak, 
we 
present 
the 
first 
study 
to 
report 
the 
reproduction 
number 
of 
COVID-19 
in 


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Using 
the 
incidence 
data 


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MethodsThe 
daily 
confirmed 
cases 


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, 
we 
estimate 



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in 
South 
Korea 
were 
extracted 
from 
publicly 
available 
sources. 
By 
using 
the 
empirical 
reporting 
delay 
distribution 
and 
simulating 
the 
generalized 
growth 
model, 
we 
estimated 
the 
effective 
reproduction 
number 
based 
on 
the 
discretized 
probability 
distribution 
of 
the 
generation 
interval.ResultsWe 
identified 
four 
major 
clusters 
and 
estimated 


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–1.6). 
In 
addition, 
the 
intrinsic 
growth 
rate 
was 
estimated 
at 
0.6 
(95% 
CI: 
0.6, 
0.7), 
and 
the 
scaling 
of 
growth 
parameter 
was 
estimated 
at 
0.8 
(95% 
CI: 
0.7, 
0.8), 
indicating 
sub-exponential 
growth 
dynamics 
of 
COVID-19. 
The 
crude 
case 
fatality 
rate 
is 
higher 
among 
males 
( 


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6), 
which 
indicates 


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1%) 
compared 
to 
females 
(0.4%) 
and 
increases 
with 
older 
age.ConclusionsOur 
results 
indicate 
an 
early 


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of 
COVID-19 
in 
South 
Korea 


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. 


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." 


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Thousands 


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As 


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April 
3, 
2020, 
more 
than 
1,000,000 


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in 
China 
along 
with 
many 
other 
countries 


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around 
the 
world 



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∼ 


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~ 


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ACE2 


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, 
suggesting 
the 
potential 
capacity 
for 
the 
infection 
of 
SARS-CoV-2 
to 
the 
fetus 
through 


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. 
And 
thus, 
both 


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and 
the 
placenta 
dysfunction/abortion 
caused 
by 
SARS-CoV-2 
need 
to 
be 
further 
carefully 
investigated 
in 
clinical 
practice 


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were 
dispersed 
for 


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was 
sent 
to 


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(VT) 


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(GP) 


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(i.e., 
234 
front-line 
nurses 
and 
292 
non-front-line 
nurses) 


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VT 


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vicarious 
traumatization 


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Front-line 
nurses 
are 
engaged 
in 
the 
process 
of 
providing 
care 
for 
patients 
with 
COVID-19. 
The 


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VT 
scores 
slightly 
increased 
across 
periods 
of 
aiding 
COVID-19 
control, 
although 
no 
statistical 
difference 
was 
noted 
(P 
= 
0.083). 
However, 
the 
study 
found 
lower 
scores 
for 
VT 
in 
nurses 
[median 
= 
69; 
interquartile 
range 
(IQR) 
= 
56-85] 
than 
those 
of 
the 
GP 
(median 
= 
75.5; 
IQR 
= 
62-88.3) 
(P 
= 
0.017). 
In 
addition, 
the 
VT 


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vicarious 
traumatization 


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(FLNs; 
median 
= 
64; 
IQR 
= 
52-75), 


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nFLNs; 
median 
= 
75.5; 
IQR 
= 
63-92) 
( 


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VT 


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vicarious 
traumatization 


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GP 


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general 
public 


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FLNs 


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front-line 
nurses 


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). 


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); 


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with 
those 



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to 
the 
scores 


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nFLNs 


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non-front-line 
nurses 


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Importantly, 
nFLNs 
are 
more 
likely 
to 
suffer 
from 
VT, 
which 
might 
be 
related 
to 
two 
factors, 
namely, 
gender 
[odds 
ratio 
(OR) 
= 
3.1717; 
95% 
confidence 
interval 
(CI) 
= 
4.247-18.808; 
P 
= 
0.002] 
and 
fertility 
[OR 
= 
2.072; 
95%CI 
= 
0.626-24.533; 
P 
= 
0.039]. 


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nFLNs 


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non-front-line 
nurses 


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GP 


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general 
public 


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VT 


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vicarious 
traumatization 


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GP 


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general 
public 


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Clinical 
assessment 



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"BackgroundAssessment 


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-

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-

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-

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the 
outbreak 
of 


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-

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-

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respiratory 


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infectious 
diseases 


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infection 


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in 
the 
UK 
and 
elsewhere 


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s 


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We 



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ObjectivesWe 


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our 
case 


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a 


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, 
reviewed 
by 
Infectious 
Diseases 
Consultants 


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assessed 


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Infectious 
Diseases 


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Infection 


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We 
prospectively 
evaluated 
our 
service 
between 
the 
29th 
Jan 


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MethodsBetween 
29 
January 


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24th 
Feb 


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24 
February 


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. 


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, 


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have 



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and 
subsequent 
diagnosis 


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well 


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Final 


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ResultsPatients 
assessed 
were 
aged 
from 
0 
to 
76 
years; 
36/68 
were 
female. 
Peaks 
of 
clinical 
assessments 
coincided 
with 
updates 
to 
the 
case 
definition 
for 
suspected 
COVID-19. 


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-

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-

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-

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-

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(COVID-19), 


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, 


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RSV, 


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-

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, 


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and 



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9/68 
were 
treated 
with 


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Nine 
of 
sixty-eight 
received 


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to 
a 
negative 
pressure 
room 
of 
whom 


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, 


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/68 
were 
admitted 
solely 


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an 


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self-

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at 
home 


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either 


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similar 


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more 
likely 
to 
have 
fever 
or 
raised 
respiratory 
rate 
compared 


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, 
with 
modestly 
more 
fever 
and 
shortness 
of 
breath 
in 
the 
clinically 
admitted 
/ 
antimicrobial 
group. 
The 
most 
commonly 
prescribed 
antimicrobials 
were 
doxycycline, 
moxifloxacin 
and 
oseltamivir. 
The 


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.ConclusionsThe 


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, 



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a 


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to 
manage 


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, 


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able 


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the 
proportion 
of 


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Extensions 
of 
the 
epidemiological 
criteria 
for 
the 
case 
definition 
of 
suspected 
COVID-19 
lead 
to 
increased 
screening 
intensity; 
strategies 
must 
be 
in 
place 
to 
accommodate 
this 
in 
time 
for 
forthcoming 
changes 
as 
the 
epidemic 
develops." 


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the 


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virus 


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SARS-CoV-2 


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Using 
the 
same 
method 
we 
also 
estimate 
the 
basic 
reproductive 
number 
of 
MERS 
virus 
is 
8.16 
which 
is 
higher 
than 
SARS-CoV-2. 


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and 


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. 
Moreover, 


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and 
immunity 
effect 
of 
patients 



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coronavirus 
disease 
2019 
( 


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) 


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has 


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are 
underway 
currently 


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were 
undertaken 


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have 


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d 


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on 


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in 


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to 


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well 


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well 


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Following 


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After 



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a 


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we 


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of 


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have 


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Summary 
Background 
The 


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"BackgroundThe 


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Methods 
A 


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MethodsA 


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confirmed 


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= 


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= 


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period 


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using 
immunoassays. 


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. 



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disease 


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and 
severity 
of 
disease 


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Findings 
Among 


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ResultsAmong 


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% 
(161/173), 


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%, 


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(143/173) 


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% 
(112/173), 


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%, 


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Twelve 


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The 
reason 
for 
the 
negative 
antibody 
findings 
in 
12 


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who 
had 
not 
seroconverted 
were 
those 
only 


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might 
due 
to 
the 
lack 
of 


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early 



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later 


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were 
collected. 


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. 


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median 


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sequentially 
appeared 


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time 


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, 
with 
a 
median 
time 
of 


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were 
day-

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day-

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day-

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days, 
respectively. 


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, 
separately. 


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in 
the 
first 
7 
days 
of 
illness 


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within 
1-week 
since 
onset 



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then 


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%, 


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% 
(Ab), 


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(IgM) 


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for 
Ab, 
IgM 
and 


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( 


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respectively 


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) 


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-

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the 
positive 
rate 
of 


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detectability 


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-

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s 


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to 



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-

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patients 


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< 


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< 


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= 


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= 


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= 


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= 


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Interpretation 
The 


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ConclusionsThe 


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. 


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." 


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1, 



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s 


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d 


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novel 
coronavirus 
disease 
( 


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) 


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and 


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, 


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, 


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ve 


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d 


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We 
used 


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In 
this 
study, 


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numbers 
of 


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to 


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imported 
into 



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ern 


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and 
estimated 
16533 
(95% 
CI: 
5925, 
35538) 


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were 
used 
to 
estimate 
the 
number 
of 


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. 
It 
was 
estimated 
that 
the 
total 
number 
of 
cases 
in 
Iran 
was 
16 
533 
(95% 
confidence 
interval: 
5925–35 
538) 


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25 


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25, 
2020 


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the 


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(SARS-CoV-2) 


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-

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-CoVs 


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Middle 
East 
Respiratory 
Syndrome 
coronavirus 
( 


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-

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-

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), 



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-

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-

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-

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, 


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-

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the 


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two 


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-


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-

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s 


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from 
SARS-CoV-2 
-a 
virus 
causing 
current 
world-wide 
epidemics. 


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. 


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this 
structure 


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these 
structures 


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models 
of 
Nsp15 


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homologs 


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-

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coronavirus 
disease 
( 


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) 


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1. 


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%( 



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.6% 
(95% 
confidence 
interval 
(CI): 


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89–6 


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%) 


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) 


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2 


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1 


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95% 
CI: 


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75%-5. 


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38– 


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%). 


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.6), 
respectively. 


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onboard 


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on 
board 



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using 


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from 


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data 


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estimate 


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estimated 
CFR 
and 


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and 
CFR 


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0.5% 
(95% 
CI: 
0.2


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%) 
and 
1.1 


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-2.4%) 


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–2.7) 
and 
0.6% 
(95% 
CI: 
0.2–1.3), 


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" 


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vulvo-vaginal 


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vulvovaginal 


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non-clinical 



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nonclinical 


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non-symptomatic, 
pre-menopausal 


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nonsymptomatic, 
premenopausal 


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mid-stream 


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midstream 


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peri-urethral 


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periurethral 


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three 


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3 


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the 


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the 


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IMPORTANCE 
Following 
the 
discovery 
of 
the 
collective 
human 
urinary 
microbiota, 
important 
knowledge 
gaps 
remain, 
including 
the 
stability 
and 
variability 
of 
this 
microbial 
niche 
over 
time. 
Initial 
urinary 
studies 
preferentially 
utilized 
samples 
obtained 
by 
transurethral 
catheterization 
to 
minimize 
contributions 
from 
vulvovaginal 
microbes. 
However, 
catheterization 
has 
the 
potential 
to 
alter 
the 
urinary 
microbiota; 
therefore, 
voided 
specimens 
are 
preferred 
for 
longitudinal 
studies. 
In 
this 
report, 
we 
describe 
microbial 
findings 
obtained 
by 
daily 
assessment 
over 
3 
months 
in 
a 
small 
cohort 
of 
adult 
women. 
We 
found 
that, 
similarly 
to 
vaginal 
microbiotas, 
lower 
urinary 
tract 
(LUT) 
microbiotas 
are 
dynamic, 
with 
changes 
relating 
to 
several 
factors, 
particularly 
menstruation 
and 
vaginal 
intercourse. 
Our 
study 
results 
show 
that 
LUT 



microbiotas 
are 
both 
dynamic 
and 
resilient. 
They 
also 
offer 
novel 
opportunities 
to 
target 
LUT 
microbiotas 
by 
preventative 
or 
therapeutic 
means, 
through 
risk 
and/or 
protective 
factor 
modification." 


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The 


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"BackgroundThe 


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the 


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yet 


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the 


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is 
yet 
to 
be 
clear. 
Herein 


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remains 
unclear.MethodsTo 
obtain 
the 
structural 
information 
of 
the 
SARS-CoV-2 
nucleocapsid 
protein 


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. 
Although 
overall 
structure 
is 
similar 
with 


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using 
X-ray 
crystallography 
technology. 
To 
explored 
the 
interaction 
mechanism, 
we 
complemented 
functional 
studies 
by 
in 
vitro 
surface 
plasmon 
resonance 
analysis 
and 
biolayer 
interferometry 
assays.ResultsAlthough 
the 
overall 
structure 
is 
similar 
to 


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Complemented 
by 
in 
vitro 
binding 
studies, 
our 


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ConclusionsOur 


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the 


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. 



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." 


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The 


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"BackgroundThe 


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was 
dominate 
in 


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is 
a 
common 
condition 
among 


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process. 


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hospitalized 
patients 
with 
COVID-19. 


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severe 


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The 


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MethodsThe 


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pneumonia 


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Results 
found 
that 
patients 
with 
higher 


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The 
primary 
outcome 
was 
in-hospital 
death 
defined 
as 
the 
case 
fatality 
rate. 
Research 
information 
and 
following-up 
data 
were 
obtained 
from 
their 
medical 
records.ResultsThe 
best 
cut-off 
value 
of 


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(above 


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for 
predicting 
in-hospital 
death 
was 


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pg/mL) 
level 


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pg/mL 
with 
the 
sensitivity 
for 
100% 
and 
the 
specificity 
for 
66.67%. 
Patients 
with 
high 
NT-proBNP 
values 
(> 
88.64 
pg/mL) 


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more 
risks 
of 
in-hospital 
death. 


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a 
significantly 
increased 
risk 
of 
death 
during 
the 
days 
of 
following-up 
compared 
with 
those 
with 
low 
values 
(≤88.64 
pg/mL). 


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i 


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me 


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g 


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t 


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cofounders 
in 
separate 
modes, 
NT-proBNP 
presented 
as 


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risk 
factors, 
NT-proBNP 
was 
independently 
correlated 
with 
in-hospital 
death.ConclusionNT-proBNP 
might 
be 


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of 


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for 



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. 


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." 


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Mobile 
phone 
apps 
implementing 
algorithmic 
contact 
tracing 
can 
speed 
up 
the 
process 
of 
tracing 
newly 
diagnosed 
individuals, 
spreading 
information 
instantaneously 
back 
through 
a 
past 
contact 
network 
to 
inform 
them 
that 
they 
are 
at 
risk 
of 
being 
infected, 
and 
thus 
allow 
them 
to 
take 
appropriate 
social 
distancing 
and 
testing 
measures. 
The 
aim 
of 
non-pharmaceutical 
infection 
prevention 
is 
to 
move 
a 
population 
towards 
herd 
protection, 
a 
state 
where 
a 
population 
maintains 
R0<1, 
thus 
making 
it 
impossible 
for 
a 
pathogen 
to 
cause 
an 
epidemic. 
Here, 
we 
address 
epidemiological 
issues 
that 
affect 
the 
feasibility 
of 
an 
algorithmic 
approach 
to 
instantaneous 
contact 
tracing; 
ethical 
and 
implementation 
issues 
are 
addressed 
separately. 
First 
we 
quantify 
the 
parameters 
of 
COVID-19 
in 
a 
framework 
that 
is 
consistent 
with 
the 
renewal 
equation 
formulation 
of 
epidemic 
spread. 
Second, 
we 
use 
an 
analytical 
solution 
to 
application 
of 
first-degree 
contact 
tracing 
in 
the 
renewal 
equation 
model 
to 
explore 
combinations 
of 
efficacy 
that 
can 
induce 
herd 
protection 
(R0<1). 
With 
the 
emergence 
of 
the 
novel 
viral 
pathogen 
SARS-CoV-2, 
of 
clear 
potential 
for 
a 
global 
pandemic 
with 
high 
fatality 
rates 
and 
incapacitated 
health 
systems, 
the 
question 
of 
prevention 
has 
critical 
priority. 
We 
come 
to 
the 
conclusion 
that 
isolating 
symptomatic 
cases 
and 
tracing 
their 
contacts 
in 
a 
classical 
manner 
is 
not 
sufficiently 
fast 
to 
stop 
the 
spread 
of 
the 
epidemic 
and 
needs 
to 
be 
accompanied 
by 
measures 
of 
social 
distancing 
that 
are 
disruptive 
to 
a 
wide 
number 
of 
people. 
We 
show 
that 
first-degree 
instantaneous 
contact 
tracing, 
informing 
users 
when 
they 
can 
move 
safely 
or 
when 
to 
seek 
medical 
help 
and 
avoid 
vulnerable 
individuals, 
has 
the 
potential 
to 
stop 
the 
spread 
of 
the 
epidemic 
if 
used 
by 
a 
sufficiently 
large 
number 
of 
people 
with 
reasonable 
fidelity. 


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"INTRODUCTIONCoronavirus 
disease 
2019 
(COVID-19), 
caused 
by 
severe 
acute 
respiratory 
syndrome– 
coronavirus 
2 
(SARS-CoV-2), 
has 
clear 
potential 
for 
a 
long-lasting 
global 
pandemic, 
high 
fatality 
rates, 
and 
incapacitated 
health 
systems. 
Until 
vaccines 
are 
widely 
available, 
the 
only 
available 
infection 
prevention 
approaches 
are 
case 
isolation, 
contact 
tracing 
and 
quarantine, 
physical 
distancing, 
decontamination, 
and 
hygiene 
measures. 
To 
implement 
the 
right 
measures 
at 
the 
right 
time, 
it 
is 
of 
crucial 
importance 
to 
understand 
the 
routes 
and 
timings 
of 
transmission.RATIONALEWe 
used 
key 
parameters 
of 
epidemic 
spread 
to 
estimate 
the 
contribution 
of 
different 
transmission 
routes 
with 
a 
renewal 
equation 
formulation, 
and 
analytically 
determined 
the 
speed 
and 
scale 
for 
effective 
identification 
and 
contact 
tracing 
required 
to 
stop 
the 
epidemic.RESULTSWe 
developed 
a 
mathematical 
model 
for 
infectiousness 
to 
estimate 
the 
basic 
reproductive 
number 
R0 
and 
to 
quantify 
the 
contribution 
of 
different 
transmission 
routes. 
To 
parameterize 
the 
model, 
we 
analyzed 
40 
well-characterized 
source-recipient 
pairs 
and 
estimated 
the 
distribution 
of 
generation 
times 
(time 
from 
infection 
to 
onward 
transmission). 
The 
distribution 
had 
a 
median 
of 
5.0 
days 
and 
standard 
deviation 
of 
1.9 
days. 
We 
used 
published 
parameters 
for 
the 
incubation 
time 
distribution 
(median 
5.2 
days) 
and 
the 
epidemic 
doubling 
time 
(5.0 
days) 
from 
the 
early 
epidemic 
data 
in 
China.The 
model 
estimated 
R0 
= 
2.0 
in 
the 
early 
stages 
of 
the 
epidemic 
in 
China. 
The 
contributions 
to 
R0 
included 
46% 
from 
presymptomatic 
individuals 
(before 
showing 
symptoms), 
38% 
from 
symptomatic 
individuals, 
10% 
from 
asymptomatic 
individuals 
(who 
never 
show 
symptoms), 
and 
6% 
from 
environmentally 
mediated 
transmission 
via 
contamination. 
Results 
on 
the 
last 
two 
routes 
are 
speculative. 
According 
to 
these 
estimates, 
presymptomatic 
transmissions 
alone 
are 
almost 
sufficient 
to 
sustain 
epidemic 



growth.To 
estimate 
the 
requirements 
for 
successful 
contact 
tracing, 
we 
determined 
the 
combination 
of 
two 
key 
parameters 
needed 
to 
reduce 
R0 
to 
less 
than 
1: 
the 
proportion 
of 
cases 
who 
need 
to 
be 
isolated, 
and 
the 
proportion 
of 
their 
contacts 
who 
need 
to 
be 
quarantined. 
For 
a 
3-day 
delay 
in 
notification 
assumed 
for 
manual 
contact 
tracing, 
no 
parameter 
combination 
leads 
to 
epidemic 
control. 
Immediate 
notification 
through 
a 
contact-
tracing 
mobile 
phone 
app 
could, 
however, 
be 
sufficient 
to 
stop 
the 
epidemic 
if 
used 
by 
a 
sufficiently 
high 
proportion 
of 
the 
population.We 
propose 
an 
app, 
based 
on 
existing 
technology, 
that 
allows 
instant 
contact 
tracing. 
Proximity 
events 
between 
two 
phones 
running 
the 
app 
are 
recorded. 
Upon 
an 
individual’s 
COVID-19 
diagnosis, 
contacts 
are 
instantly, 
automatically, 
and 
anonymously 
notified 
of 
their 
risk 
and 
asked 
to 
self-isolate. 
Practical 
and 
logistical 
factors 
(e.g., 
uptake, 
coverage, 
R0 
in 
a 
given 
population) 
will 
determine 
whether 
an 
app 
is 
sufficient 
to 
control 
viral 
spread 
on 
its 
own, 
or 
whether 
additional 
measures 
to 
reduce 
R0 
(e.g., 
physical 
distancing) 
are 
required. 
The 
performance 
of 
the 
app 
in 
scenarios 
with 
higher 
values 
of 
R0 
can 
be 
explored 
at 
https://bdi-
pathogens.shinyapps.io/covid-19-transmission-routes/.CONCLUSIONGiven 
the 
infectiousness 
of 
SARS-CoV-2 
and 
the 
high 
proportion 
of 
transmissions 
from 
presymptomatic 
individuals, 
controlling 
the 
epidemic 
by 
manual 
contact 
tracing 
is 
infeasible. 
The 
use 
of 
a 
contact-tracing 
app 
that 
builds 
a 
memory 
of 
proximity 
contacts 
and 
immediately 
notifies 
contacts 
of 
positive 
cases 
would 
be 
sufficient 
to 
stop 
the 
epidemic 
if 
used 
by 
enough 
people, 
in 
particular 
when 
combined 
with 
other 
measures 
such 
as 
physical 
distancing. 
An 
intervention 
of 
this 
kind 
raises 
ethical 
questions 
regarding 
access, 
transparency, 
the 
protection 
and 
use 
of 
personal 
data, 
and 
the 
sharing 
of 
knowledge 
with 
other 
countries. 
Careful 
oversight 
by 
an 
inclusive 
advisory 
body 
is 
required." 


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Epidemics 
of 


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The 


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pandemic 


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have 
more 
than 
100 


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has 
>2,000 


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Diagnosis 
of 


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performed 
by 


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diagnosed 
using 
quantitative 


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q 



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quantitative 


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q 


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its 


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their 


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Here, 


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reverse 
transcription 
loop-mediated 
isothermal 
amplification 
( 


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) 


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severe 
acute 
respiratory 
syndrome 
coronavirus 
2 
( 


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, 


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), 


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reported 


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We 
also 
adapted 


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was 
adapted 


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our 



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this 


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so 
that 
the 
tests 
potentially 
performed 
in 


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to 
enable 


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confirmed 


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defined 


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used 


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established 


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-

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– 


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a 
superior 


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superior 


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compared 


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the 


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the 



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the 


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We 
then 


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Here 
we 


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derived 
from 
EK1 


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the 


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that 
of 


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the 
original 


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and 


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inhibiting 


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inhibited 
the 


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4 


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examined 


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the 



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other 


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virus 
(CHIK) 
and 
Middle 
Eastern 
Respiratory 
Syndrome 
Coronavirus 
(MERS-CoV). 


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Background 
The 


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"BackgroundThe 


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Methods 
We 


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MethodsWe 


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Results 
During 


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ResultsDuring 


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two 
(10.5 


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three 
(16.7 


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Conclusion 
Severe 


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ConclusionSevere 


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. 


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." 



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Background 
What 
are 
the 
health 
and 
wellbeing 
conditions 
of 
people 
during 
the 
COVID-19 
outbreak 
in 
China? 
The 
epidemiological 
reports 
now 
focus 
on 
the 
confirmed 
COVID-19 
cases, 
and 
we 
aim 
to 


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We 


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public 
health 
emergencies 
into 


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confinement 
to 
contain 


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Methods 
One 
month 
into 
the 
outbreak, 


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/ 


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– 


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sampled 


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surveyed 


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on 
the 
eight 
dimensions 
of 
health 
(SF12), 
distress 
(K6), 
and 
life 
satisfaction 


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in 
China 


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densities 


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rates 


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confirmed 



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confirmed 
cases. 
The 
participants 
also 
reported 


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cases 
on 


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work 
status, 
whether 
they 
had 
chronic 
health 
issues, 
the 
number 
of 
hours 
they 
exercised 
per 
day 
in 
the 
past 
week. 
Findings 
In 
general, 
life 
of 
normal 
adults 
was 
severely 
disrupted. 
33% 
of 
the 
participants 
had 
not 
left 
their 
home 
at 
all 
during 
the 
one-month 
period 
due 
to 
the 
restrictive 
measures 
to 
contain 
COVID19 
in 
China. 


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health 
conditions, 
distress 
and 
life 
satisfaction. 


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the 


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; 


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, 


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; 


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, 


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suspended 


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stopped 


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suspended 


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stopped 



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mental 
and 
physical 


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by 
SF12 


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(K6). 


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. 


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the 


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individuals 
location 


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an 
individual's 
home 
city 


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moderated 
by 
the 


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contingent 
upon 
individuals’ 


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exercising 
hour 
of 
each 
individual. 
Interpretation 


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their 
hours 
of 
exercise. 


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findings 
support 


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evidence 
supports 


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a 



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in 


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f 


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epistemologically. 
We 
need 
to 
support 


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, 


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for 


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suspended 


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stopped 


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also 


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people 
who 
are 
usually 


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physically 


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, 
as 
indicated 
by 
more 
exercises, 


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people 


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pe 


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ep 



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a 


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due 
to 


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during 


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thinking 
of 


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considering 


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restrictive 


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be 


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We 
report 
that 


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"• 


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rates 
outside 
Hubei 


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Wuhan 
are 
nearly 
constant. 
•COVID-19 


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Wuhan 
and 


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Province, 
China 



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grow 


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decays 
(R2>0.93) 
and 
grows 
(R2>0.95), 
respectively. 
A 
great 
number 
of 
newly 
supplied 
medical 
resources 
( 


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. 
•Over 
40,000 
aided 


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and 


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help 
Hubei 
to 
effectively 
treat 
patients. 
•Newly 
supplied 


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) 
enabled 
overwhelming 


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allow 
over 
38,000 


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in 
Wuhan 


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effectively. 
This 
may 
help 
other 
countries 
to 
deal 
with 
the 
coming 
COVID-19 
outbreaks. 


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in 
hospitals." 


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ar 


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ar 


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-

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– 


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-

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– 


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-

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ar 


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ic 


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consistencies 


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concordance 


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with 


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and 


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were 
100% 
and 
97.1% 
in 
IgM 
and 
IgG 
strips, 
respectively 


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showed 
Cohen's 
kappa 
value 
of 
0.93, 
which 
represented 
the 
almost 
perfect 
agreement 
between 
two 
types 
of 
samples 


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In 
March 
2020, 
Coronavirus 
Disease 
2019 
originating 
from 
Wuhan, 
China, 
has 
become 
pandemic. 
Based 
on 
epidemic 
data 
from 
China 
we 


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We 


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and 
constrained 


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-Infected-

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–Exposed– 


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-Excluded 
(SIIE) 


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–Removed 


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. 


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of 
the 
spread 
of 
COVID-19. 


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characterized 
by 


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parametrised 


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three 
parameters: 


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by 
the 


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t, 
and 
two 
rate 
parameters: 



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rC 


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,ß 


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rE. 
These 
two 
rates 
control 


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, 
<U+03B3>. 
The 
rates 
depend 
on 
nontherapeutic 
interventions 
and 
determine 
the 
basic 
reproduction 
number, 
R0 
= 
ß/<U+03B3>, 
and, 
together 
with 
t, 


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β 
describing 
epidemic 
growth 


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its 


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the 


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during 
which 
the 
number 
of 
excluded 
(confirmed) 
individuals 
grows 
as 
E 
= 
E0 
exp(α,t) 
with 
α 
= 
lnβ. 
The 
rates 
can 
be 
modified 
by 
non-therapeutic 
interventions: 
rC 
can 
be 
reduced 
by 
quarantine, 
while 
rE 
can 
be 
increased 
by 
efficient 
testing, 
enabling 
isolation 
of 
infectious 
individuals. 
In 
order 
to 
contain 
exponential 
epidemic 
growth, 
quotient 
rC/rE 
has 
to 
be 
reduced 
to 
1. 
Based 
on 
the 
model, 
we 
estimate 
that 
the 
quarantine 
imposed 
in 
China 
on 
January 
23, 
2020 
resulted 
in 
about 
50-fold 


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<U+03B8>. 
Initial 
R0 
determines 
the 


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this 
quotient, 
allowing 
to 
terminate 
the 
exponential 
growth 
phase 
and 
enter 
the 
phase 


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ß 
required 
to 
contain 
the 
spread 


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exponential 
regression 


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the 
epidemic. 
We 
demonstrate 
that 
introduction 



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daily 
new 
cases. 
In 
contrast, 
quarantine 
imposed 
in 
northern, 
most 
affected, 
Italian 
provinces 
on 
February 
21 
resulted 
in 
about 
3-fold 
reduction 


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a 
cascade 


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rC/rE 
and 
corresponding 
decrease 


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multiple 
exposed 
states 
enables 
the 
model 
to 
reproduce 
the 
distributions 


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β 
from 
about 
1.5 
to 
about 
1.2; 
further 
5-fold 
reduction 
is 
necessary 
to 
terminate 
exponential 
growth. 
Even 
higher 
reduction 
should 
take 
place 
in 
France, 
Germany 


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the 
incubation 
period 


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Spain 
for 
which 
β 
> 
1.3 
(as 
of 
March 
10, 
2020). 
Considering 
longer-term 
dynamics 
in 
the 
case 
when 
the 
initial 
exponential 
growth 
is 
not 
contained 
by 
quarantine, 
we 
analyzed 
a 


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the 
serialinterval 
reported 
by 
epidemiologists. 
Using 
the 
model, 
we 
consider 
a 
hypothetical 


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rE 


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ß 
is 
modulated 
solely 
by 
anticipated 
changes 
of 
social 
behaviours: 
first, 
ß 


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the 


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a 


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which 
convinces 



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, 
pressuring 


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self-

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themselves. 
In 
such 
case, 


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, 
and 
then, 
over 
longer 
time 
scale, 
ß 
increases 
as 
people 
gradually 
accept 
the 
risk. 
In 
this 
scenario, 


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growth 


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spread 


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plateau 
and 


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decrease 
over 
years. 
This 
scenario, 


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regression, 
which, 


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, 
produce, 


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distribute 


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deploy 


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or 
atleast 
limit 
daily 
cases 
to 
a 
manageable 
number 


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" 



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The 
behavior 
of 


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Given 


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general 
public 
will 
likely 
have 
an 
important 
bearing 
on 


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extensive 
time 
needed 
to 
conduct 
a 
nationally 
representative 
household 
survey 
and 


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course 
of 
the 
coronavirus 
disease 
2019 
(Covid-19) 
epidemic. 
Human 
behavior 
is 
influenced 
by 
people's 


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commonly 
low 
response 
rate 
of 
phone 
surveys, 
rapid 
online 
surveys 
may 
be 
a 
promising 
method 
to 
assess 
and 
track 


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. 


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among 
the 
general 
public 
during 
fast-moving 
infectious 
disease 
outbreaks. 


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This 
study 
aimed 
to 
apply 
rapid 
online 
surveying 


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coronavirus 
disease 
2019 
( 


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) 


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(US) 


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(UK). 
Design: 
Cross-sectional 
online 
survey 
conducted 


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.Methods: 
An 
online 
questionnaire 
was 
administered 
to 
3000 
adults 
residing 
in 
the 
United 
States 
and 
3000 
adults 
residing 
in 
the 
United 
Kingdom 
who 
had 
registered 
with 
Prolific 
Academic 
to 
participate 
in 
online 
research. 
Prolific 
Academic 
established 
strata 
by 
age 
(18-27, 
28-37, 
38-47, 
48-57, 
or 
≥58 
years), 
sex 
(male 
or 
female), 
and 
ethnicity 
(white, 
black 
or 
African 
American, 
Asian 
or 
Asian 
Indian, 
mixed, 
or 
“other”), 
as 
well 
as 
all 
permutations 
of 
these 
strata. 
The 
number 
of 
participants 
who 
could 
enroll 
in 
each 
of 
these 
strata 
was 
calculated 
to 
reflect 
the 
distribution 
in 
the 
US 
and 
UK 
general 
population. 
Enrollment 
into 
the 
survey 
within 
each 
stratum 
was 
on 
a 
first-come, 
first-served 
basis. 
Participants 
completed 
the 
questionnaire 


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rd 


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3rd 


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2, 


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Setting: 
Online. 
Participants: 


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Results: 


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sample 


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total 


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3,000 


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2986 
and 
2988 


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United 
States 
and 
the 
United 
Kingdom, 
respectively, 
completed 
the 
questionnaire. 
Of 
those, 
64.4% 
(1924/2986) 
of 


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participants 



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3,000 
adults 
residing 
in 
the 


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51.5% 
(1540/2988) 
of 


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who 
were 
representative 
of 
the 
general 
population 
by 
age, 
sex, 
ethnicity, 


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participants 
had 
a 
tertiary 


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, 
and 


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degree, 
67.5% 
(2015/2986) 
of 
US 
participants 
had 
a 
total 


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. 
Measurements: 
Response 
to 
21 
survey 
questions. 
Results: 
2,987 
of 
3,000 
US 
and 
2,978 
of 
3,000 
UK 
adults 
completed 
the 
questionnaire 
(response 
rate 
of 
99.4%). 
The 


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between 
US 
$20,000 
and 
US 
$99,999, 
and 
74.4% 
(2223/2988) 
of 
UK 
participants 
had 
a 
total 
household 
income 
between 
£15,000 
and 
£74,999. 
US 
and 
UK 
participants’ 


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by 
participants 


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Covid-19 
was 
4 


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severe 
acute 
respiratory 
syndrome 
coronavirus 
2 
(SARS-CoV-2) 
was 
5 


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: 


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%


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%-15.0%) 
and 
3.0% 
(IQR 
2.0%


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%). 


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%), 
respectively. 


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33 


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37 


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: 
32 


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36.1%-39 


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% 
-35.0 


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US 
participants 
and 
29.7% 
(95% 
CI 
28.1%-31.4%) 
of 
UK 


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" 


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“ 


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" 


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” 


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. 
27 


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, 
and 
25 


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: 
26.5% 
-28.7 


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24.1%-27.2 


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US 
participants 
and 
29.6% 
(95% 
CI 
28.0%-31.3%) 
of 
UK 


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was 


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In 
addition, 
29.7% 
(95% 
CI: 
28.1% 
-31.3%) 
of 
US 
participants 
and 
40.7% 
(95% 
CI: 
39.0% 
-42.5%) 
of 
UK 
participants 
stated 
that 
if 
they 
were 
an 
Uber 
driver, 
they 
would 
at 
least 
sometimes 
refuse 
rides 
to 
passengers 
with 
East 
Asian-sounding 
names 
to 
reduce 
their 
risk 


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Around 
half 
(53.8%, 
95% 
CI 
52.1%-55.6%) 


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infection. 
46.6 


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US 
participants 
and 
39.1 


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: 
45.3% 
-47.8 


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37.4%-40.9 


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UK 


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from 
Covid-19. 
Limitation: 
While 
participants 
were 
representative 


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when 
infected 
with 
SARS-CoV-2.Conclusions: 
The 
distribution 



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the 
UK 
and 
US 
adult 
population 


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participants 


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age, 
sex, 
ethnicity, 


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total 


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, 


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, 
they 
may 
not 
be 
representative 
by 
other 
(unobserved) 
characteristics. 
Conclusion: 
These 


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followed 
approximately 
that 
of 
the 
US 
and 
UK 
general 
population. 
The 


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can 


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from 
this 
online 
survey 
could 


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More 
broadly, 


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' 


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’ 


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of 
Covid-19 
over 
time. 
Primary 
funding 
source: 
National 
Center 
for 
Advancing 
Translational 
Sciences 


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during 
rapidly 
moving 
infectious 
disease 
outbreaks." 



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" 


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coronavirus 
disease 
2019 
( 


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, 
which 
is 


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) 


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severe 
acute 
respiratory 
syndrome–coronavirus 
2 
( 


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virus, 
continues 
to 
spread 
globally 


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) 
has 
now 
become 
a 
pandemic 


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epitopes 
on 


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antigenicity 
of 


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In 
this 
study, 
we 
have 


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We 
therefore 


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the 
receptor-binding 
domain 
(RBD) 
of 
the 
SARS-CoV-2 
spike 
(S) 
protein 
in 
complex 
with 


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. 


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, 
in 
complex 
with 
the 
receptor 
binding 
domain 
(RBD) 
of 
the 
SARS-CoV-2 
spike 
(S) 
protein 
at 
3.1-angstrom 
resolution. 



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, 
distal 
from 
the 
receptor 
binding 
site, 


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s 


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ep 


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op 


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by 
CR3022 


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"" 


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“ 


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"" 


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” 


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. 
Overall, 
this 
study 
provides 
structural 


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slightly 
rotated. 
These 
results 
provide 


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s 


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the 
antigenicity 


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antibody 
recognition 



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ONE 
SENTENCE 
SUMMARYStructural 
study 
of 
a 
cross-reactive 
SARS 
antibody 
reveals 
a 
conserved 
epitope 
on 
the 
SARS-CoV-2 
receptor-binding 
domain." 


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within 
3%. 


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quite 
small. 


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the 


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, 


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the 


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severe 
acute 
respiratory 
syndrome 
coronavirus 
2 
( 


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-

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-

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) 


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coronavirus 
disease 
2019 
( 


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) 


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, 


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both 


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the 
social 
connectedness 
of 
older 
and 
younger 
generations 


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intergenerational 
interactions 


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nowcasting. 


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forecasting 
of 
hospitalization 
and 
critical 
care 
needs. 


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th 


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10, 
of 



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10th, 


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who 


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contacted 


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contact 
with 


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COVID19, 
13 


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COVID-19. 
There 


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found 
to 
have 
COVID19, 


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13 
individuals 
who 
contracted 
COVID-19 


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in 
a 


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to 


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– 


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Of 


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There 
were 


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of 
which 



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had 
infections 


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individuals 
developed 
COVID-19 


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in 
a 


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% 


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73 
to 


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7– 


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COVID19 


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COVID-19 


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13 


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12th 


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were 
identified, 
resulting 


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have 
been 
recorded, 
giving 
a 


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coexisting 
medical 
conditions 


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comorbidities 



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a 
higher 


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for 


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of 
a 


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s 


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of 
COVID-19 


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from 


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in 


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, 
with 
elevated 
age-stratified 
case 
fatality. 


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. 


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COVID19 
outbreak, 


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the 
COVID-19 
outbreaks, 
and 
may 


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to 


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patients 
with 


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patients 



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s 


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– 


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(95% 
confidence 
interval, 
25–69%) 


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transmission 
could 
occur 
before 
first 
symptoms 
of 


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secondary 
cases 
were 
infected 
during 


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. 


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cases’ 
presymptomatic 
stage, 
in 
settings 
with 
substantial 
household 
clustering, 
active 
case 
finding 
and 
quarantine 
outside 
the 
home. 


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pre-symptomatic 


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presymptomatic 


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, 


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and 



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Background: 


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Methods: 
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Two 
hundred 
fourteen 


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' 


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’ 


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18 


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18 


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26 


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26, 


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, 


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severe 
acute 
respiratory 
syndrome 
coronavirus 
2 
( 


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) 


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Results: 


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, 



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to 


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Conclusions: 


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, 


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., 
so 


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can 


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could 


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Background 
Chloroquine 


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"BackgroundChloroquine 


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COV-19 


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SARS-CoV-2 


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COV-19 


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infected 
by 
this 
virus. 


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. 



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methods 


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methodsFrench 
Confirmed 
COVID-19 


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from 
early 
March 
to 
March 
16th, 


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nasal 


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nasopharyngeal 


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. 


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in 
a 
hospital 
setting. 


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, 


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s 


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Day-6 


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Day6-post 
inclusion 


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Results 


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ResultsSix 
patients 
were 
asymptomatic, 
22 
had 
upper 
respiratory 
tract 
infection 
symptoms 
and 
eight 
had 
lower 
respiratory 
tract 
infection 
symptoms. 


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D6-post 
inclusion 


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than 
reported 


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than 
reported 


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Conclusion 
: 
Hydroxychloroquine 


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ConclusionDespite 
its 
small 
sample 
size 
our 
survey 
shows 
that 
hydroxychloroquine 
treatment 


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COVID-19 


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with 
COVID-19 


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. 


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." 


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Objectives: 
The 
January 
2020 


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"ObjectivesThe 
December 
2019 


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‘ 


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’ 


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Study 
designThe 



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: 


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is 
a 


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Methods: 
We 


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MethodsWe 


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Results: 
We 


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ResultsWe 


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papers 


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articles 


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Conclusions: 
People 


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ConclusionsPeople 


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. 


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." 


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(CoV) 


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human 
coronaviruses 



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CoVs 


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UK. 


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United 
Kingdom. 


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, 


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, 


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, 


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" 


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severe 
acute 
respiratory 
syndrome 
coronavirus 
2 
( 


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, 


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), 


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Whereas 


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Although 


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important 


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needed 



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, 


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al 


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Here, 


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al 


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the 


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-

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protein-specific, 


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SARS-CoV-2 


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of 
SARS-CoV-2 


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d 


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-

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individuals 


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persons 


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, 
as 
revealed 



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sensitive 
and 
specific 
in-house 
ELISAs. 


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2 
weeks 
after 
disease 
onset. 


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while 


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, 
and 


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two, 
with 


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2 
assays; 
the 


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showing 


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ELISA 
showed 


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here 


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the 


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al 


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, 


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. 


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." 



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" 


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the 


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March 
29 


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April 
15 


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time-dependent 
mortality 


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timedependent 
death 


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Findings: 


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Results: 
Based 
on 
our 
predictions 
of 
Iran 
about 
29000 
people 
will 
be 
infected 
from 
March 
25 
to 
April 
15, 
2020. 


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12 


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one 
week 
(15.03.2020 


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3 
days 
(March 
25 



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03.21. 


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March 
27, 


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03.18. 


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March 
25, 


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7 


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26 


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5 


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. 


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." 


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more 
than 
200 


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nearly 
1,280 


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nearly 
9 


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is 
thought 
to 
have 
originated 
from 
an 
animal 
reservoir, 
and 



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In 
the 
wake 


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Because 


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a 
global 
pandemic 


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this, 


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origin 
and 
spread 
of 
a 
novel 
infectious 
disease 


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SARS-CoV-2 
hACE2 
interaction 


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r 


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th 


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r 


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, 


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h 


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coronaviruses 


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beta 


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coronavirus 



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SARS-CoV-2 


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-

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variants 
of 
the 


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SARS-related 


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We 
probe 
how 


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" 


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A 


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] 


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-

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, 


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], 



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-

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genes 


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the 
disease 
caused 
by 



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coronavirus 


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execute 


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performed 


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all 
known 


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145 


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d 


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is 


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was 


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presented 


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was 
represented 


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that 


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1). 


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M. 
Lin, 
H.-T. 
Tseng, 
J. 
A. 
Trejaut, 
H.-L. 
Lee, 
et 
al., 
BMC 
Med 
Genet 
4:9, 
2003, 
https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). 
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that 



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-

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ed 


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. 


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." 


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" 


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: 


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prediction 


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that 
aim 
to 
predict 
either 
(i) 
presence 
of 
existing 


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for 
diagnosing 
coronavirus 
disease 
2019 
( 


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) 
in 
patients 
with 
suspected 


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or 
(ii) 
future 
complications 
in 
individuals 
already 
diagnosed 


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for 
prognosis 
of 
patients 


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. 
Any 
models 
to 
identify 
subjects 
at 
risk 
for 
COVID-19 


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, 
and 
for 
detecting 
people 


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were 
also 
included. 


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at 
increased 
risk 
of 
becoming 
infected 
with 
covid-19 
or 
being 
admitted 
to 
hospital 
with 
the 
disease. 


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: 
Rapid 


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Living 


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of 
prediction 
models 
for 
diagnosis 
or 
prognosis 
of 
COVID-19 
infection. 


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. 


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: 


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, 
EMBASE 
via 


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and 
Embase 
through 


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, 


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until 
13th 
March 


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up 
to 
7 
April 


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: 


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Two 
authors 
independently 
screened 
titles 
and 
abstracts. 


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: 
Data 
from 
included 
studies 
were 



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At 
least 
two 
authors 
independently 


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independently 
by 
at 
least 
two 
authors 
based 
on 


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data 
using 


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(critical 
appraisal 
and 
data 
extraction 
for 
systematic 
reviews 
of 
prediction 
modelling 
studies) 


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, 
and 


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; 


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. 
Data 
were 
extracted 
on 
various 
domains 
including 
the 
participants, 
predictors, 
outcomes, 
data 
analysis, 
and 


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( 


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performance. 


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risk 
of 
bias 
assessment 
tool). 


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: 
1916 


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4909 


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. 
Of 
these, 
15 


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, 
and 
51 


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for 
data 
extraction 
and 
critical 
appraisal. 
We 


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. 
The 
review 


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to 
predict 


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for 
predicting 


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a 


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outcomes 


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nine 


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to 
detect 
COVID-19 
infection 
in 
symptomatic 
individuals 
(seven 
of 
which 
were 
deep 
learning 
models 
for 
COVID-19 
diagnosis 
utilising 
computed 
tomography 
(CT) 
results 


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for 
detecting 
covid-19 
(34 
were 
based 
on 
medical 
imaging 


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seven 


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progression 
to 
severe 
disease, 



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None 


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The 
most 
frequently 
reported 
predictors 


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the 
15 
studies 
used 
data 
on 


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presence 
of 


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cases 
outside 
of 
China. 
Predictors 


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in 
more 
than 
one 
of 
the 
19 
models 
were: 


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body 
temperature, 
signs 
and 
symptoms, 


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comorbidities, 
C-reactive 
protein, 
lymphocyte 
markers 
(percentage 
or 
neutrophil-to-lymphocyte 
ratio), 
lactate 
dehydrogenase, 


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blood 
pressure, 
and 
creatinine. 
The 
most 
frequently 
reported 
predictors 
of 
severe 
prognosis 
in 
patients 
with 
covid19 
included 
age 


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CT 
images. 
Reported 
C-

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computed 
tomography 
scans. 
C 


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for 
the 
prediction 
models 


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those 


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prediction 
models 



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(reported 
for 
all 
3 
general 
population 
models), 


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, 


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65 


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> 


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more 
than 


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those 
for 
diagnosis 
(reported 
for 
5 
of 
the 
9 


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), 


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, 


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85 


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98 
in 
those 
for 
prognosis 
(reported 
for 
4 
of 
the 
7 


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99 
in 


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). 


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. 



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studies 


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models 


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or 
unclear 


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and 
poor 
statistical 
analysis, 
including 


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. 
Reporting 
quality 
varied 
substantially 
between 
studies. 
A 


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, 
and 
vague 
reporting. 
Most 
reports 
did 
not 
include 
any 


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and 


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or 


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was 
absent 
in 
almost 
all 
reports 


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the 
model 


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: 
COVID-19 
related 


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diagnosis 
and 
prognosis 


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covid-19 


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through 
publications 
and 
preprint 
reports, 
aiming 


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in 


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at 


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where 
this 
is 
needed 


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when 
they 
are 


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. 
Many 


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needed. 
This 
review 
indicates 
that 
proposed 


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we 


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a 


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and 
all 
appraised 
as 


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, 
at 


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. 
We 
call 
for 


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, 
and 
their 
reported 
performance 
is 
probably 
optimistic. 
Hence, 
we 
do 
not 
recommend 
any 
of 
these 
reported 
prediction 
models 
to 
be 
used 
in 
current 
practice. 


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the 


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well 
documented 


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worldwide 
to 
support 
collaborative 
efforts 
in 
building 



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and 
collaboration 
are 
urgently 
needed 
to 
develop 


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rigously 
developed 
and 
validated 
COVID-19 
related 


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rigorous 


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. 


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, 
and 
validate 
promising 
ones. 


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current 
studies 


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included 
models 


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as 
candidate 
predictors 


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potential 
inclusion 
in 


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We 
also 
stress 
the 
need 
to 
adhere 
to 
methodological 
standards 
when 
developing 
and 
evaluating 
COVID-19 
related 
predictions 
models, 
as 


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Methodological 
guidance 
should 
be 
followed 
because 


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may 


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could 


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when 
used 
to 
guide 



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in 
guiding 


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about 
COVID-19 
in 
the 
current 
pandemic. 


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. 
Finally, 
studies 
should 
adhere 
to 
the 
TRIPOD 
(transparent 
reporting 
of 
a 
multivariable 
prediction 
model 
for 
individual 
prognosis 
or 
diagnosis) 
reporting 
guideline." 


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Objective: 
The 


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"ObjectiveThe 


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is 


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was 


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with 


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from 
those 
of 


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chest 


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pulmonary 


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the 


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COVID-19 


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Methods: 
Adult 



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MethodsAdult 
patients 


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patients 


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of 
COVID-19 


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within 
14 
days 


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s 


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-

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-

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within 
14 
days 
of 
symptom 
onset 


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the 


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the 


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data 
of 


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the 


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non-confirmed 


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nonconfirmed 



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Results: 
A 


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ResultsA 


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, 


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cases 


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testing 


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cases 


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testing 


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the 


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opacity 
(GGO), 


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opacities 
(GGOs), 
the 


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, 


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and 


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were 


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s 



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s 


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, 
of 
which 
were 


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among 
the 
positive 
patients, 
found 
in 


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cases 


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cases 


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patients 


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%) 


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%), 


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presented 


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all 


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<0 


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< 


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) 


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), 



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s 


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is 
around 


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was 
approximately 


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Conclusions: 
The 


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ConclusionsThe 


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of 
GGO 


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with 
GGOs 


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which 
alerts 


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alerting 


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prompt 


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promptly 


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the 
end 
of 


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ends. 


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." 



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-and 


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-/ 


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the 


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standard 


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-

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– 


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-

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s 


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the 


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-

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– 


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-

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s 


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" 



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coronavirus 
disease 
2019 
( 


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) 


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of 
high 
importance 


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highly 
important 


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is 


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(ARDS), 


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, 


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ICU 


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intensive 
care 
unit 


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a 
link 


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an 
association 


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. 


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." 


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" 



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some 


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a 
few 
coronavirus 
disease 
( 


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) 


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and 
soon 
the 
disease 
broke 
out 


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in 
Wuhan, 
Hubei, 
China. 
Soon 
after, 
increasing 
numbers 
of 
cases 
were 
detected 
in 
other 
parts 
of 
China, 
eventually 
leading 
to 
a 
disease 
outbreak 
in 
China 


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.| 


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, 
such 
as 
its 
pathogenesis, 
spread, 
prevention, 
and 
containment.Objective: 
The 
aim 
of 
this 
study 
was 
to 
collect 
media 
reports 
on 
COVID-19 
and 
investigate 
the 
patterns 
of 
media-directed 
health 
communications 
as 
well 
as 
the 
role 
of 
the 
media 
in 
this 
ongoing 
COVID-19 
crisis 
in 
China. 


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Huike 


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WiseSearch 


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related 


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the 


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, 


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1st 



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to 


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and 


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th 


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The 
data 
were 


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We 
then 


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by 


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the 
data 
using 


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using 


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with 
evidence 
of 


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(LDA) 


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the 


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a 


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then 



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two-dimensional 


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a 
2D 


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| 
Findings 


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Results 


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duplicates, 


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duplications 
and 
irrelevant 
reports, 
our 
search 
identified 


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were 
identified 


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our 


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the 


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obtained 
their 
names 


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generated 
the 
topics’ 
themes 


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main 


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most 


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and 



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/ 


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or 


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/ 


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and 


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6%, 


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57% 
(n=2538), 


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6%, 


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08% 
(n=1258), 
and 


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8% 


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79% 
(n=919) 


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, 


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| 
Interpretation: 
The 
Chinese 


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Conclusions: 
Topic 
modeling 
of 
news 
articles 
can 
produce 
useful 
information 
about 
the 
significance 
of 


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for 
early 
health 
communication. 
Comparing 
the 
number 
of 
articles 
for 
each 
day 
and 
the 
outbreak 
development, 
we 
noted 
that 
mass 
media 



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lag 


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in 
China 
lagged 


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development 
of 


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outbreak 
development. 


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. 


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rather 


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global 


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worldwide 


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also 


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s 


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. 


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among 
others. 


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should 
address 


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addresses 



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' 


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’ 


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. 


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." 


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if 


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is 


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s 


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-

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– 


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{degrees} 


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° 


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{degrees} 


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° 


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{degrees} 



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° 


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fic 


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NF{kappa}B 


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NFκB 


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periprotein 
space 


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'periprotein 
space' 


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" 


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: 
SARS-CoV 


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Severe 
acute 
respiratory 
syndrome 
coronavirus 


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(SARS-CoV-2) 


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cause 


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causative 
agent 
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the 


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coronavirus 
disease 
2019 
( 



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that 
has 
been 


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), 
which 
was 


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WHO 
in 


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World 
Health 
Organization 
on 
11th 
March 


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COVID-19 


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for 
COVID-19 


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in 
each 
country, 
and 


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between 
countries, 


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therapeutic 
for 
COVID-19. 
Aims 
of 
the 
study: 
this 
review 
aimed 
to 


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treatment 
to 
date.AimTo 


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COVID-19 


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with 
COVID-19 


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the 


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: 



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the 


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electronic 
databases 
( 


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). 


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. 


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, 


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1st 


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1 
st, 


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26th 


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26 
th, 


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, 


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and 


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s 


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design 


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: 
As 
of 
March 
26, 
2020, 
of 
the 
initial 
manuscripts 



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Four 
hundred 
and 
forty-nine 
articles 
were 


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(n=449) 
articles. 
Forty-one 


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in 
the 
literature 
search; 
of 
these, 
41 


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, 
of 
which 


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in 
this 
review. 
These 
were 


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( 


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( 


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and 


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The 
most 
common 
mentioned 
and 


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Corticosteroid 
treatment 
was 


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medicine 
in 
this 
systematic 
review 
was 
corticosteroids 


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most 
frequently 


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: 


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up 



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the 
therapeutics 


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medication 


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in 
COVID-19 


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to 
treat 
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. 


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with 
COVID-19. 


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forty-one 
research 
articles 
on 
COVID-19 
and 
therapeutics 
were 
found 


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41 
studies 
were 


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to 
be 
included 


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for 
inclusion 


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of 
which 
were 


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, 
corticosteroid 
therapy 
was 
found 
to 
be 
the 


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. 
Corticosteroid 
treatment 
was 
reported 


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used 
medicine 



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frequently 


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these 
studies. 


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the 
literature." 


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. 


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-emotional, 
physical 
and 
mental 
exhaustion 
due 
to 
excessive 
and 
prolonged 
stress. 


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the 


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working 
adults’ 


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ir 


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would 


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may 


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carrying 


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with 


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to 


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for 



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Background. 
The 
Coronavirus 
disease 
19 
(COVID-19) 
pandemic 
has 
led 


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"With 
respect 


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widespread 
concerns 
about 
the 
risk 
of 
infection 
in 
patients 
with 


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observations 
by 
Monti 
et 
al,1 
a 
survey 
featuring 
31 
questions 
related 
to 


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RD) 
receiving 
disease 
modifying 
ant-rheumatic 
drugs 
(DMARDs) 
and 
other 
immunosuppressants 
(IS). 
Methods. 
A 
SurveyMonkey 
based 
electronic 
survey 


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RDs) 
during 
the 
covid-19 
pandemic 


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conducted 
amongst 


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administered 
to 


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to 
understand 
the 
need 
for 
changes 
in 
prevailing 
practices. 
Results. 
Of 
the 
861 
invitees, 
221 
responded. 
In 
the 
wake 
of 
the 
pandemic, 
47.5% 
would 
reduce 
biological 
DMARDs 
(bDMARDs) 
while 
only 
12.2% 
would 
reduce 
the 
use 
of 
conventional 
synthetic 
DMARDs. 
64.2% 
were 
likely 
to 
defer 
change 
in 
IS, 
the 
reluctance 
being 
most 


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.Of 
861 
invitees, 
221 
(25.7%; 
92.7% 
adult 
rheumatologists, 
52.2% 
academicians) 
responded. 
Most 
perceived 
the 
need 
for 
a 
change 
in 
the 
management 
of 
RDs 
(online 
supplementary 
files). 
Almost 
half 
(47.5%) 
reduced 
the 
usage 
of 
biological 
disease 
modifyinig 
anti 
rheumatic 
drugs 
(bDMARDs), 
whereas 
only 
12.2% 
did 
so 
for 
csDMARDs 
(figure 
1). 
Of 
the 
respondents, 
66.5% 
were 
more 
inclined 
to 
initiate 
hydroxychloroquine 
(HCQ) 
in 
patients 
with 
borderline 
indications, 
whereas 
14% 
disagreed 


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this 
approach. 
Nearly 
two-thirds 
(64.2%) 
were 
less 
inclined 
to 
change 
the 
major 
immunosuppressant 
(IS) 
for 
impending 
flare, 
with 
58.3% 
deferring 


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58.3%) 


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RTX), 


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closely 


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(53.3%), 
anti-tumor 


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, 
antitumour 


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factor 
alpha 
agents 
(52.4%) 
and 


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factors 
(anti-TNFs), 


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34.39%). 
Hydroxychloroquine 


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JAKinibs) 
and 
other 
bDMARDs. 
An 
earlier 
taper 
of 
glucocorticoids 


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the 


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choice 
(81.9%) 
for 
the 
treatment 
of 
COVID-19 
followed 
by 
protease 
inhibitors 
(22.1%) 
and 
intravenous 
immunoglobulin 
(8.1%). 
Chloroquine 


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by 
57.9% 
in 
inactive 
disease. 
There 


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less 
preferred 
(19%). 
More 
than 
two-thirds 
(70.5%) 
believed 
that 
COVID-19 
might 
trigger 
macrophage 
activation 
syndrome. 
Social 
distancing 
(98.1%) 
and 
hand 
hygiene 
(74.6%) 
were 
recommended 
by 
majority. 
62.8% 
would 
avoid 
touch 
for 
clinical 
examination 
whenever 
feasible. 
Conclusion. 
Most 
rheumatologists 
perceived 
the 
need 
to 
change 
treatment 
of 
RDs 
during 
the 
COVID-19 
pandemic; 
reduce 
immunosuppression 
and 
defer 
the 
usage 
of 
rituximab 
and 
bDMARDs. 



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lack 
of 
consensus 
on 
continuing 
IS 
infusions." 


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Importance 
The 
United 
States 
is 
experiencing 
an 
acute 
shortage 
of 
reagents 
important 
for 
performance 
of 
assays 
for 
the 
detection 
of 
severe 
acute 
respiratory 
syndrome 
coronavirus 
2 
(SARS-CoV-2), 
the 
causative 
agent 
of 
COVID-19 
in 
clinical 
specimens. 
Objective 
To 
determine 
whether 
saving 
in 
reagents 
for 
detection 
of 
SARS 
CoV-2 
can 
be 
accomplished 
using 
the 


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"ObjectivesTo 
establish 
the 


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in 
a 
public 
health 
laboratory. 
Design 
The 


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for 
the 
detection 
of 
SARS-CoV-2.MethodsThe 


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specimen 


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to 
be 
five 
specimens 


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Parameters 
affecting 
the 
optimal 
pool 
size 
of 
5 
specimens 
were: 
prevalence 
rate 
of 
5%, 
a 
lower 
limit 
of 
detection 
of 
1 
to 
3 
RNA 
copies 
per 
microliter, 
sensitivity 
and 
specificity 
of 
100%, 
two-stage 
pooling 
algorithm, 
and 
a 
range 
of 
pool 
sizes 
of 
3 
to 
10 
samples. 


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From 
this 
analysis, 
25 


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microliter 


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μL 


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each 
confirmed 


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one 
SARS-CoV-2 
positive 



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positive 
patient 


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microliter 


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μL 


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microliter 


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μL 


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then 


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subsequently 


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subsequently 


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with 


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using 


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CDC 


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that 
was 
developed 
by 
the 
CDC 
and 
used 
according 
to 
the 
instructions 
of 
manufacturer. 
Setting 
Studies 
were 
conducted 
in 
the 
Nebraska 
Public 
Health 
Laboratory 
with 
samples 
collected 
from 


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. 
Positive 
pools 
were 
consequently 
split 
into 


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patients 
throughout 
the 
state. 
Participants 
A 
total 
of 
21 
SARS 
CoV-2 
confirmed 
positive 
samples 
and 
84 
SARS 
CoV-2 
confirmed 
negative 
samples 
were 
used 
to 
create 
21 
pools. 
The 
positive 
specimens 
were 
selected 
for 
Ct 
values 
indicating 
a 
relatively 
low 
amount 
of 
viral 
RNA. 
The 


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specimens 
and 
tested 
by 
extraction 
and 
PCR. 
This 


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then 


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also 


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community 


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. 
Results 
Following 
extraction 
and 
RT-PCR 
amplification, 
all 
21 


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grouped 
into 
12 
pools.ResultsAll 
25 


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characterized 
as 
SARS-CoV-2 
RNA 
detected 


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positive 


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cycle 
threshold 
( 


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) 


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samples. 


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individual 
specimens. 


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community 


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, 
grouped 
in 
12-pools, 


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two 


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2 


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two 
detected 


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2 
individual 


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testing 


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with 


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while 
using 
22 
extractions/PCR 
tests, 


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total 


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savings 


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Conclusion 
and 
Relevance 


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ConclusionsWhen 
the 
incidence 
rate 
of 
SARS-CoV-2 
infection 
is 
10% 
or 
less, 


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may 


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will 


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% 
when 
the 
positive 
laboratory 
test 
rate 
is 
10% 
or 
less. 


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%." 


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-


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-

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-and 
collision-

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a 


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-

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"Background: 


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Results: 


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Results 
were 


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We 


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compared 


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compare 
our 
results 


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In 
conclusion, 


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Conclusion: 


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. 



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." 


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To 


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"With 
emerging 
resistance 
to 
frontline 
treatments, 
it 
is 
vital 
that 
new 
drugs 
are 
identified 
to 
target 
Plasmodium 
falciparum. 
One 
of 
the 
most 
critical 
processes 
during 
parasites 
asexual 
lifecycle 
is 
the 
invasion 
and 
subsequent 
egress 
of 
red 
blood 
cells 
(RBCs). 
Many 
unique 
parasite 
ligands, 
receptors 
and 
enzymes 
are 
employed 
during 
egress 
and 
invasion 
that 
are 
essential 
for 
parasite 
proliferation 
and 
survival, 
therefore 
making 
these 
processes 
druggable 
targets. 
To 


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in 
the 
asexual 
blood 
stage 
of 
Plasmodium 
falciparum 


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(MMV) 


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. 
This 


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, 
a 
400 


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comprises 
of 
400 
drugs 


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{micro}M 


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μM 


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, 


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greater 


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significant 



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.\n\nImportancePlasmodium 
falciparum 
causes 
the 
most 
severe 
form 
of 
malaria 
and 
with 
emerging 
resistance 
to 
frontline 
treatments, 
there 
is 
the 
need 
to 
identify 
new 
drug 
targets 
in 
the 
parasite. 
One 
of 
the 
most 
critical 
processes 
during 
the 
asexual 
blood 
stage 
in 
the 
parasites 
lifecycle 
is 
the 
egress 
from 
old 
red 
blood 
cells 
(RBCs) 
and 
subsequent 
invasion 
of 
new 
RBCs. 
Many 
unique 
parasite 
ligands, 
receptors 
and 
enzymes 
are 
employed 
during 
egress 
and 
invasion 
that 
are 
essential 
for 
parasite 
proliferation 
and 
survival, 
therefore 
making 
these 
processes 
druggable 
targets. 
Identifying 
novel 
compounds 
that 
inhibit 
these 
essential 
processes 
would 
further 
their 
development 
into 
possible 
antimalarials 
that 
would 
be 
highly 
effective 
at 
killing 
asexual 
RBC 
stage 
parasites 
when 
used 
in 
combination 
with 
drugs 
that 
target 
the 
intraerythrocytic 
growth 
phase. 
These 
compounds 
potentially 
may 
also 
be 
used 
as 
novel 
tools 
to 
study 
the 
complex 
biology 
of 
parasites 
to 
gain 
further 
insight 
into 
the 
mechanisms 
behind 
egress 
and 
invasion. 


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." 


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An 
actin 
mesh 
fills 
both 
mouse 
and 
fly 
oocytes. 


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actin 
nucleators 
Spire 
and 
Cappuccino 
synergize 
to 
promote 
actin 
assembly, 
but 
the 
mechanism 
of 
their 
synergy 
is 
controversial. 
Together 
these 
proteins 
promote 
the 
formation 
of 
actin 


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, 
which 


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built 
by 
a 


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mechanism 
and 
used 
to 
establish 


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structures 
that 
regulate 
the 
establishment 
of 
oocyte 


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Two 
actin 
nucleators, 
Spire 
and 
Cappuccino, 
collaborate 
to 
build 
actin 
filaments 
that 
connect 
vesicles 
and 
the 
cortex. 


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oogenesis 
and 
for 


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; 
however, 
we 
understand 
little 
about 
why 
the 


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. 
This 
synergy 
is 
proposed 
to 
be 
driven 
by 
elongation 
and 
the 
formation 
of 
a 
ternary 
complex 
at 
filament 
barbed 
ends, 
or 
by 
nucleation 
and 


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is 
necessary. 


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at 
filament 
pointed 
ends. 


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. 


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and 
added 
Cappuccino 
and 
actin. 
Barbed 
ends, 
protected 
by 
Cappuccino, 
grow 
away 
from 
the 
beads 
while 
pointed 
ends 
are 
retained, 
as 
expected 
for 
nucleation-driven 
synergy. 


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increased 
nucleation 
is 
a 
major 
part 
of 
synergy 
and 
that 


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alone 
binds 
both 


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is 
sufficient 
to 
bind 


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-

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ends 


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retain 


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-

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. 



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near 
beads 
and 


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’ 


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Partial 


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Loss 
of 
barbed-end 
binding 
increases 
nucleation 
by 
Spire 
and 
synergy 
with 
Cappuccino 
in 
bulk 
pyrene 
assays 
and 
on 
beads. 
Importantly, 
genetic 


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of 
fertility 


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a 


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the 


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Spires 


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oogenesis. 
Thus, 
increased 
nucleation 
is 
a 
critical 
element 
of 
synergy 
both 
in 
vitro 
and 


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function, 
but 
that 
it 
may 
play 
a 
role 
under 
normal 
circumstances. 
We 
propose 
that 
Spire 
stimulates 
nucleation 
by 
Cappuccino 
in 
a 
manner 
similar 
to 
the 
collaboration 
between 
APC 
and 
mDia1.\n\nSummaryActin 
nucleators 
Cappuccino 
and 
Spire 
collaborate 
to 
build 
an 
actin 
mesh 
in 
oocytes. 
Data 
demonstrate 
that 
the 
collaboration 
leads 
to 
synergistic 
actin 
nucleation, 
as 
opposed 
to 
elongation. 
Further, 
Spire 
binds 
both 
ends 
of 
polar, 
actin 
filaments, 
resolving 
a 
long-outstanding 
question 


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Summary 


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" 


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. 
To 


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, 
and 
unifying 
database 
content 
across 
metagenome 
profiling 
tools 
can 
be 
cumbersome. 
To 


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.\n\nAvailability 
and 
implementationSource 
code 
available 
for 
download 
at 
https://github.com/leylabmpi/Struo. 
Custom 
GTDB 
databases 
available 
at 
http://ftp.tue.mpg.de/ebio/projects/struo/\n\nContactnicholas.youngblut@tuebingen.mpg.de 


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." 


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{+/-} 


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± 


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{+/-} 


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± 


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{+/-} 


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± 


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{+/-} 


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± 


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{+/-} 


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± 



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{+/-} 


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± 


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{+/-} 


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± 


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{+/-} 


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± 


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{+/-} 


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± 


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-

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– 


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{middle 
dot} 


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∙ 


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– 



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Compared 
to 
both 
REC 
and 
CON, 


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-

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– 


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-

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– 


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[&le;] 


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≤ 


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-

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– 


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-

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– 


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-

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– 


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anaerobic 



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3-minute 
cycling 


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-

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– 


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[&le;] 


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≤ 


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) 
compared 
to 
both 
REC 
and 
CON. 


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). 


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BackgroundAnswering 
the 
question 
how 
conserved 
patterning 
systems 
are 
across 
evolutionary 
lineages 
requires 
a 
broad 
taxon 
sampling. 
Phoronid 


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"BackgroundPhoronids, 
rhynchonelliform 
and 
linguliform 
brachiopods 
show 
striking 
similarities 
in 
their 
embryonic 
fate 
maps, 
in 
particular 
in 
their 
axis 
specification 
and 
regionalization. 
However, 
although 
brachiopod 


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previously 


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using 
fate 
mapping 
and 
morphogenesis, 
yet 


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in 
detail 
and 
demonstrated 
embryonic 
patterning 
as 
a 
causal 
factor 
of 
the 
gastrulation 
mode 
(protostomy 
vs 
deuterostomy), 


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still 



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. 


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in 
phoronids. 
To 
understand 
whether 
phoronids 
display 
underlying 
embryonic 
molecular 
mechanisms 
similar 
to 
those 
of 
brachiopods, 


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the 
evolutionarily 
conserved 


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dur 


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g 


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development 
of 
the 
protostomic 


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.\n\nResultsThe 


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.ResultsThe 


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Surprisingly, 
brachyury, 
an 
evolutionary 
conserved 
transcription 
factor 
often 
associated 
with 
gastrulation 
movements 
and 
patterning 
of 
the 
mouth 
and 
hindgut, 
seems 
to 
be 
unrelated 
with 
gastrulation 
and 
mouth 
patterning 
in 
phoronids. 
Furthermore, 
six3/6, 


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Furthermore, 
six3/6, 
usually 


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.\n\nConclusionsOur 


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. 
Surprisingly, 
brachyury, 
a 
transcription 
factor 
often 
associated 
with 
gastrulation 
movements 
and 
mouth 
and 
hindgut 
development, 
seems 
not 
to 
be 
involved 
with 
these 
patterning 
events 
in 
phoronids.ConclusionsOur 
description 
and 


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ies 



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y 


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that 
of 


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. 


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, 
which 
is 
likely 
related 
to 
their 
shared 
protostomic 
mode 
of 
development. 


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P 


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Ph 


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also 


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also 


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. 


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." 


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" 


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bacterial 


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in 
Bacteria 


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, 
especially 
global 
regulators, 



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, 
especially 
at 
microevolutionary 
scales 


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sequence 
diversity 


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genetic 
variation 


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on 
thousands 


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from 
a 
large 
collection 


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clinical 
and 
environmental 


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Escherichia 
coli 


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of 
E 
coli. 
We 
found 
that 


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. 


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in 
sequence 


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, 
and 
that 
their 
diversity 
was 
constrained 
by 
their 
regulatory 
roles. 
Over 
longer 
time-scales, 
the 
conservation 
of 
TFs, 
other 
than 
global 
regulators 
(GR), 
was 
low 


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species. 
Over 
very 
short 
time-scales 
represented 
by 
lab 


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natural 
isolates, 
with 
TFs 
of 
large 
regulons 
being 
more 
conserved. 
In 
contrast, 
TFs 
showed 
higher 
mutation 
frequency 
in 
adaptive 
laboratory 


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studies, 
we 
confirmed 
an 
excess 
of 
beneficial 
mutations 
in 
TFs. 
TFs 
accumulated 
mutations 
much 
faster 
than 
TGs 
in 
the 
first 
10,000 
generations 
of 
a 


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experiments. 
However, 
over 


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laboratory 


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experiment. 
However, 
as 


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spanning 
60 
000 
generations, 
mutation 
frequency 
in 
TFs 
gradually 
declined 
after 
a 
rapid 
initial 
burst. 
Extrapolating 
the 
dynamics 
of 
genetic 
variation 
from 
long-term 
laboratory 


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proceeded, 
mutations 
appeared 
in 
TFs 
at 
rates 
similar 


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or 
lower 
than 
those 
in 
TGs. 
Our 
results 
suggest 


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natural 
populations, 
we 
propose 


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gene 


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." 


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. 


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AimBiotic 


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"Aim 
Biotic 


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, 



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-

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.\n\nLocationSwitzerland\n\nMethodsIn 


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. 
Location 
Switzerland. 
Methods 
In 


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multi-species 


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multispecies 


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' 


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.\n\nResultsOur 


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. 
Results 
Our 


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-

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, 


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to 


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with 


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-

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-


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-

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— 


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defense 
tradeoff 


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defence 
trade-off 


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tradeoff 


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trade-off 


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-

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or 
never 
evolved 


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.\n\nMain 
conclusionsOur 


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. 
Main 
conclusions 
Our 


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, 


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-

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. 


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." 



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ObjectiveRates 


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"Rates 


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-

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– 


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.\n\nMethodsTo 
evaluate 
the 
expression 
of 
C2cd5, 
we 
first 
used 
in 
situ 
hybridization 
and 
RNAscope 
technology 
in 
combination 
with 
electronic 
microscopy. 
For 
in 
vivo, 
we 
characterized 
the 
energy 
balance 
of 
wild 
type 
(WT) 
and 
C2CD5 
whole-body 
knockout 
(C2CD5KO) 
mice 
fed 
normal 
chow 
(NC) 
and/or 
western-diet 
(high-fat/high-sucrose/cholesterol) 
(WD). 
To 
this 
end, 
we 
performed 
comprehensive 
longitudinal 
assessment 
of 
bodyweight, 
energy 
balance 
(food 
intake, 
energy 
expenditure, 
locomotor 
activity 
using 
TSE 
metabolic 
cages), 
and 
glucose 
homeostasis. 
In 
addition, 
we 
evaluated 
the 
consequence 
of 
loss 
of 
C2CD5 
on 
feeding 
behavior 
changes 
normally 
induced 
by 
MC4R 
agonist 
(Melanotan, 
MTII) 
injection 
in 
the 
paraventricular 
hypothalamus 
(PVH). 
For 
in 
vitro 
approach, 
we 
tease 
out 
the 
role 
of 
C2CD5 
and 
its 
calcium 
sensing 
domain 
C2 
in 
MC4R 
trafficking. 
We 
focused 
on 
endocytosis 
of 
MC4R 
using 
an 
antibody 
feeding 
experiment 
(in 
a 
neuronal 
cell 
line 
-Neuro2A 
(N2A) 
stably 
expressing 
HA-MC4R-GFP; 
against 
HA-tag 
and 
analyzed 
by 
flux 
cytometry).\n\nResultsWe 
found 
that 
1) 
the 
expression 
of 
hypothalamic 
C2CD5 
is 
decreased 
in 
diet-induced 
obesity 
models 
compared 
to 
controls, 
2) 
mice 
lacking 
C2CD5 
exhibit 
an 
increase 
in 
food 
intake 
compared 
to 
WT 
mice, 
3) 
C2CD5 
interacts 
with 
endocytosis 
machinery 
in 
hypothalamus, 
4) 
loss 
of 
functional 
C2CD5 
(lacking 
C2 
domain) 
blunts 
MC4R 
endocytosis 
in 
vitro 
and 
increases 
MC4R 
at 
the 
surface 
that 
fails 
to 
respond 
to 
MC4R 
ligand, 
and, 
5) 
C2CD5KO 
mice 
exhibit 
decreased 
acute 
responses 
to 
MTII 
injection 
into 
the 
PVH.\n\nConclusionsBased 
on 
these, 
we 
conclude 
that 
hypothalamic 
C2CD5 
is 
involved 
in 
MC4R 
endocytosis 
and 
regulate 
bodyweight 
homeostasis. 
These 
studies 
suggest 
that 
C2CD5 
represents 
a 
new 
protein 
regulated 
by 
metabolic 
cues 
and 
involved 
in 
metabolic 
receptor 
endocytosis. 
C2CD5 
represent 
a 
new 
target 
and 
pathway 
that 
could 
be 
targeted 
in 
Obesity. 


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" 


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integrates 
genomics, 
transcriptomics 
and 
mass 
spectrometry 
(MS)-based 
proteomics 
to 
gain 


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promises 
new 



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. 


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by 
integrating 
genomics, 
transcriptomics 
and 
protein 
profiling 
including 
modifications 
by 
mass 
spectrometry 
(MS). 
A 
critical 
limitation 
is 
sample 
input 
requirements 
that 
exceed 
many 
sources 
of 
clinically 
important 
material. 
Here 
we 
report 


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was 
therefore 
developed 
for 
frozen 


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for 


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witha 
“ 


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and 


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” 


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workflow. 
For 
technical 
proof-of-principle, 


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. 
As 
a 
demonstration, 
we 
analyze 
core 
needle 


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-

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– 


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hours 


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h 


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the 
first 
dose 
of 


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initiating 


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were 
analyzed. 


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. 
We 
show 
greater 
suppression 
of 


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both 
ERBB2 
and 
mTOR 
target 


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, 
as 
well 
as 
mTOR 
target 
phosphosites, 
were 
significantly 
more 
suppressed 
upon 
treatment 


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suggesting 
MS-based 
pharmacodynamics 
is 
achievable. 
Furthermore, 
integrated 
analyses 
indicated 


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and 
identify 


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(false-ERBB2 
positive) 
and 


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, 


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(pseudo-ERBB2 
positive). 


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, 
and 


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features 
in 
true-ERBB2+ 
cases, 


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mechanisms 


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ov 


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re 


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were 
observed. 
Thus, 
proteogenomic 
analysis 
of 
needle 
core 
biopsies 
is 
feasible 
and 


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. 
The 


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should 
be 
investigated 


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and 
discovery 
potential 
of 
proteogenomics 
at 
biopsy-scale 
warrants 
further 
investigation 


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"Purpose 


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s 


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. 
miR-375 
may 
act 


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(MCC). 
In 
other 
cancers, 
it 
acts 


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either 


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depending 
on 
the 
cell 
context. 


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. 


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miR-375 
is 
present 
as 


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free-

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free 
in 
the 
serum 
of 
patients 
with 
advanced 
MCC 
and 
thus 


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miR-375 


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a 


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in 
patients 
with 
advanced 
MCC 


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cells 


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Methods 


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Nearly 
complete 


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in 
MCC 
cell 
lines 


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performed 


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achieved 


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miR-375 


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lipofectamine 
transfection 
or 


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in 
classical 
MCC 
cell 
lines 
WaGa 
and 
PeTa. 
Viability 
and 
both 
changes 
in 


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. 
The 
cell 
viability, 


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as 
well 
as 


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, 
and 


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determined. 
Genes 
targeted 


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not 
altered 


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miR-375 
were 
predicted 
using 
ENCORI; 
based 
on 
these 
miR-375 
regulated 


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this 
knockdown. 
miR-375 
target 
genes 
and 
related 


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by 
genes 
ontology 
(GO) 
and 
gene 
set 
enrichment 
analysis 
(GSEA). 
Expression 
of 
these 
genes 
was 
analyzed 
by 
multiplexed 
RT-qPCR 
to 
check 
the 
effect 
of 
miR-375 
knockdown 
on 
these 
signaling 
pathways.Results 
Complete 
knockdown 
of 
miR-375 
expression 
by 
antagomiRs 
was 
only 
achieved 
by 
using 
nucleofection. 
This 
knockdown 
did 
not 
affect 
cell 
growth 
pattern, 
morphology, 
or 
proliferative 
capacity. 
miR-375 
predicted 
target 
genes 
GO 
analysis 
revealed 
that 


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using 
Encyclopedia 
of 
RNA 
Interactomes 
(ENCORI) 
revealing 


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focal 
adhesion-

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epithelial 
to 
mesenchymal 
transition 
(EMT)


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were 


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by 
miR-375. 
GSEA 
of 
gene 
expression 
data 
of 
MCC 
cell 
lines 
further 
strengthened 
the 
regulation 
of 
Focal 
adhesion-related 
genes 
by 
miR-375. 
However, 
gene 
expression 
analysis 
revealed 
that 
miR-375 
knockdown 
had 



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. 
Therefore, 
their 
expression 
was 
analyzed 
by 
multiplexed 
qRT-PCR 
after 
miR-375 
knockdown, 
demonstrating 


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effect 
on 
expression 
of 
these 
pathways 
related 
genes.Conclusions 
Complete 
miR-375 
knockdown 
did 
neither 


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in 
expression. 
In 
summary, 
highly 
effective 
miR-375 
knockdown 
in 
classical 
MCC 
cell 
lines 
did 
not 
significantly 
change 
the 


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n 


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; 


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. 


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an 


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as 


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." 


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, 
thus 
suggesting 
that 
likely 
functions 
of 
miR-375 
for 
the 
intercellular 
communication 
of 
MCC 
should 
be 
addressed. 


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" 


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is 
upregulated 


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tends 
to 
present 



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and 
presents 


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, 
linearized, 
and 
aligned 


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continually 


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: 
first 
tangential 


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, 
and 
their 
orientation 
with 
respect 


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(indicating 
growth) 
and 
later 
perpendicular 
to 
the 
tumor 
boundary 
(indicating 
likely 
metastasis). 
Current 


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has 
been 
correlated 
with 
invasive 
state. 
Currently, 


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gels 
are 
the 
standard 


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tumor 
models 
are 
unable 
to 


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tumor 
cell-extracellular 
matrix 
interaction 
model. 
The 
reticular, 
dense, 
and 
isotropic 
nanofiber 
(~900 
nm-diameter, 
on 
average) 
gels 
do 
not, 
however, 


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yet 


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and 


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procedure 


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method 


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bundles 
of 


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bundles 
with 
an 


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type 
I, 
whose 


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of 


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may 
be 
varied 
between 
about 
4 
μm 
and 


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m, 
compared 
to 
the 
reticular 
dense 
collagen 
nanofiber 
([~]900 
nm-diameter, 
on 
average) 
prepared 
using 
common 
protocols. 
The 


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μm 
dependent 
upon 
diluent 
temperature 
and 
ionic 
strength. 
The 
durability 
and 


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the 


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highway 


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route 


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invasion. 


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outgrowth. 


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cancer 



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tumor 


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stroma 


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extracellular 
matrix 


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. 


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." 


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, 


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, 


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, 


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-

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a 


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down-regulation 


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downregulation 


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an 
up-regulation 


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upregulation 



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new 


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-

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new 


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" 


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(TCA) 


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STM 


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S. 
Typhimurium 
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the 


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({Delta}fumABC 


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(ΔfumABC 


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STM 
{Delta}fumABC 


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, 
S. 
Typhimurium 
ΔfumABC 


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the 


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s 



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STM 


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S. 
Typhimurium 
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, 


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restored 


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-

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-

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-

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STM, 


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S. 
Typhimurium 
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.\n\nImportanceWe 


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.IMPORTANCE 
We 


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, 


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, 


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. 



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." 


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, 


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binding 
or 
release 
of 
DNA 
during 
mitosis, 


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mutation 
of 
factors 
that 
regulate 


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dynamics 


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and 
release, 


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-differentiating 
this 
architectural 
state 
from 
normal 
mitotic 
condensation 
(requiring 
cohesins 
and 
condensins) 
and 
the 
premature 
condensation 
(requiring 
condensins) 
that 
occurs 
during 
interphase 
in 
response 
to 
nutrient 
starvation. 


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. 


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encoding 


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-

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" 


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grouping 


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population 


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. 


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." 


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d 


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d 


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ed 


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o 


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i 


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, 


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" 


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health 
and 


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Nowhere 
may 
this 
be 
as 
dramatic 
as 


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where 


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’ 


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. 
Here 
we 
show 
that 
this 
deforestation 
resulted 
in 
decreased 


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, 
which 
led 
to 
lower 


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and 
invertebrate 
abundance 
and 
diversity, 
increased 


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abundances 
and 
higher 


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, 
and 
reduced 
rates 


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. 
We 
examined 
how 
this 
deforestation 
impacted 
ecosystem 
function 
by 
comparing 
patterns 


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net 
ecosystem 
production 
(NEP), 


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(GPP), 
ecosystem 
respiration 
(Re), 
and 
the 
range 
between 
GPP 
and 
Re 
in 
remnant 
kelp 
forests, 
urchin 
barrens, 
and 
habitats 
that 
were 
in 
transition 
between 
the 
two 
habitat 
types 
at 
nine 
islands 
that 
spanned 
more 
than 
1000 
kilometers 
of 
the 
archipelago. 
Our 
results 
show 
that 
deforestation, 
on 
average, 
resulted 
in 
a 
24% 
reduction 
in 
GPP, 
a 
26% 
reduction 
in 
Re, 


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respiration 
by 
the 
ecosystem. 


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a 
24% 
reduction 
in 
the 
range 
between 
GPP 
and 
Re. 
Further, 
the 
transition 
habitats 
were 
intermediate 
to 
the 
kelp 
forests 
and 
urchin 
barrens 
for 
these 
metrics. 


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ed 


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, 


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; 


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net 
ecosystem 
production. 


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NEP. 


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patterns 
were 
consistent 
across 
nine 
islands 
spanning 
more 
than 
1000 
kilometers 
of 
the 
archipelago. 


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effects 
of 
deforestation 
on 
ecosystem 
productivity, 
however, 
were 
highly 
variable 
between 
years 
and 
among 
the 
study 
islands. 


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the 
health 
of 
coastal 
ecosystems 
and 
how 
they 
function. 
Significance 
statementWidespread 
marine 
deforestation 
results 
in 
reduced 
biodiversity 
and 
primary 
productivity 
throughout 
more 
than 
1000 
km 
of 
the 
Aleutian 
Archipelago." 


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how 
coastal 
ecosystems 
function. 


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" 


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Contrary 
to 
common 
concepts, 


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), 


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) 


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assist 


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facilitate 


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higher-order 



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structure 


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accessibility 


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samples 


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= 


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= 


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either 


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TERT 
mRNA 


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throughout 
the 
promoter 


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throughout 
the 
promoter 


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/C250T 
mutations. 
Author 
summaryPvdV 
and 
RvD 
formulated 
research 
goals 
and 
aims 
and 
supervised 
the 
overall 
progress. 
Wet-lab 
experiments, 
preparation 
of 
the 
manuscript 
and 
statistical 
analysis 
were 
performed 
by 
CS 
and 
CR. 
CS 
designed 
the 
novel 
assays. 
RN 
was 
involved 
in 
the 
experimental 
setup. 
RvD, 
NG 
and 
PvdV 
were 
responsible 
for 
funding 
acquisition. 
CR, 
RN, 
NG, 
RvD 
and 
PvdV 
critically 
reviewed 
the 
manuscript." 


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or 
C250T 
mutations. 


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(R) 


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® 



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, 


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, 


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Additionally 


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In 
addition 


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(PVP) 


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[&ge;] 


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≥ 


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-

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two 


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2 


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the 
severity 
of 


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that 


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and 
an 
ongoing 
controversy 


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is 
severe 
but 
the 
role 
of 
reactive 
astrogliosis 
not 
well 
understood 
given 
its 
implication 



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the 
roles 
of 
astrocytes 
with 
studies 
identifying 
astrocytes 
as 
associated 
both 
with 


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and 
damage 
as 
well 
as 
potentially 
having 
a 
protective 
role 


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as 
damaging 
or 
neuroprotective 


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-, 


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-alpha, 


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1{beta}, 


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1beta, 


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-{ 


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-

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} 


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" 


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progression 


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that 


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show 



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find 


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ICL 
degradation 


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the 
formation 
of 
nicks 


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single 
strand 
breaks 
( 


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) 


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cleavage 


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subsequently 


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and 


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. 
The 
spontaneous 
conversion 
of 
ICLs 
to 
DSBs 


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earlier 
determination 


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finding 


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non-homologous 


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nonhomologous 


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further 



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refine 


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. 


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