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n
d
f
u
n
ctio
n
o
f
a
b
d
o
m
in
al
s
o
f
t
tis
s
u
es
an
d
o
r
g
an
s
th
r
o
u
g
h
s
p
ec
if
ic
g
en
tle
m
a
n
eu
v
er
s
[
1
3
]
.
T
h
e
r
atio
n
a
le
b
eh
in
d
v
is
ce
r
al
m
an
ip
u
latio
n
is
to
ad
d
r
ess
r
estrictio
n
s
o
r
ad
h
esio
n
s
in
v
is
ce
r
al
tis
s
u
es
t
h
at
co
u
ld
lead
to
alter
ed
b
io
m
ec
h
an
ics
an
d
n
eu
r
o
p
h
y
s
io
lo
g
ical
f
u
n
ctio
n
s
,
co
n
tr
ib
u
tin
g
to
s
y
m
p
to
m
s
,
s
u
c
h
as p
ain
an
d
d
is
co
m
f
o
r
t
[
1
4
]
.
W
h
ile
th
er
e
is
ex
is
tin
g
ev
id
en
ce
s
u
p
p
o
r
tin
g
th
e
ef
f
ica
cy
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
in
ce
r
tain
g
ast
r
o
in
test
in
al
d
is
o
r
d
er
s
,
s
u
c
h
as
ir
r
itab
le
b
o
wel
s
y
n
d
r
o
m
e,
its
ap
p
licatio
n
in
f
u
n
ctio
n
a
l
d
y
s
p
ep
s
ia
is
less
well
estab
li
s
h
ed
[
1
5
]
.
T
h
e
r
ef
o
r
e,
a
s
y
s
tem
atic
r
ev
iew
f
o
cu
s
in
g
o
n
v
is
ce
r
al
m
an
ip
u
lati
o
n
in
ter
v
en
tio
n
s
f
o
r
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
aim
ed
to
s
y
s
tem
atica
lly
o
u
tlin
e
an
d
s
u
m
m
ar
ize
th
e
av
ailab
l
e
ev
id
en
ce
o
n
th
e
ef
f
ec
tiv
en
ess
o
f
th
is
ap
p
r
o
ac
h
in
allev
iatin
g
s
y
m
p
to
m
s
an
d
im
p
r
o
v
in
g
th
e
q
u
ality
o
f
li
f
e
o
f
p
atien
ts
with
f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia.
T
h
r
o
u
g
h
th
e
in
co
r
p
o
r
atio
n
o
f
d
iv
e
r
s
e
s
tu
d
y
d
esig
n
s
an
d
ev
id
en
ce
ty
p
es,
a
s
y
s
tem
ati
c
r
ev
iew
o
f
f
er
s
a
th
o
r
o
u
g
h
ass
ess
m
en
t
o
f
th
e
ex
is
tin
g
b
o
d
y
o
f
k
n
o
wled
g
e
r
eg
ar
d
i
n
g
v
is
ce
r
al
m
an
ip
u
latio
n
f
o
r
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia,
p
in
p
o
in
t
in
g
ev
id
e
n
ce
g
ap
s
an
d
p
o
s
s
ib
le
av
en
u
es f
o
r
f
u
r
th
er
i
n
v
esti
g
atio
n
[
1
6
]
.
T
h
e
o
b
j
e
c
t
i
v
e
o
f
a
s
y
s
t
e
m
a
t
i
c
e
v
a
l
u
a
t
i
o
n
o
f
v
i
s
c
e
r
a
l
m
a
n
i
p
u
l
a
t
i
o
n
t
h
e
r
a
p
i
e
s
f
o
r
p
a
t
i
e
n
t
s
w
i
t
h
f
u
n
c
t
i
o
n
a
l
dy
s
p
e
p
s
i
a
w
a
s
t
o
m
a
p
a
n
d
c
o
m
p
i
l
e
t
h
e
a
v
a
i
l
a
b
l
e
d
a
t
a
o
n
h
o
w
w
e
l
l
t
h
i
s
m
e
t
h
o
d
w
o
r
k
s
t
o
m
a
n
a
g
e
s
y
m
p
t
o
m
s
a
n
d
e
n
h
a
n
c
e
p
a
t
i
e
n
t
s
'
q
u
a
l
i
t
y
o
f
l
i
f
e
.
F
o
r
c
o
m
p
l
i
c
a
t
e
d
a
n
d
d
i
v
e
r
s
e
s
u
b
j
e
c
t
s
,
l
i
k
e
m
a
n
u
a
l
t
h
e
r
a
p
y
i
n
t
e
r
v
e
n
t
i
o
n
s
,
t
h
i
s
k
i
n
d
o
f
e
v
a
l
u
a
t
i
o
n
i
s
e
s
p
e
c
i
a
l
l
y
h
e
l
p
f
u
l
s
i
n
c
e
i
t
e
n
a
b
l
e
s
a
t
h
o
r
o
u
g
h
e
x
a
m
i
n
a
t
i
o
n
o
f
t
h
e
b
o
d
y
o
f
l
i
t
e
r
a
t
u
r
e
t
o
s
p
o
t
e
v
i
d
e
n
c
e
g
a
p
s
a
n
d
p
o
s
s
i
b
l
e
d
i
r
e
c
t
i
o
n
s
f
o
r
f
u
r
t
h
e
r
s
t
u
d
y
.
T
h
i
s
s
y
s
t
e
m
a
t
i
c
r
e
v
i
e
w
o
f
f
e
r
s
a
t
h
o
r
o
u
g
h
s
u
m
m
a
r
y
o
f
t
h
e
c
u
r
r
e
n
t
s
t
a
t
e
o
f
k
n
o
w
l
e
d
g
e
o
n
a
g
i
v
e
n
i
s
s
u
e
b
y
i
n
c
o
r
p
o
r
a
t
i
n
g
a
v
a
r
i
e
t
y
o
f
s
t
u
d
y
s
t
y
l
e
s
a
n
d
e
v
i
d
e
n
c
e
c
a
t
e
g
o
r
i
e
s
.
B
y
ca
r
ef
u
lly
g
ath
er
in
g
an
d
an
aly
zin
g
all
av
ailab
le
ev
id
en
ce
,
th
e
s
y
s
tem
atic
r
ev
iew
wil
l
p
r
o
v
id
e
a
f
u
ll
p
ictu
r
e
o
f
wh
at
is
k
n
o
wn
ab
o
u
t
u
s
in
g
v
is
ce
r
al
m
an
ip
u
latio
n
as
a
tr
ea
tm
en
t
f
o
r
p
eo
p
le
with
f
u
n
ctio
n
al
d
y
s
p
ep
s
i
a.
T
h
e
f
in
d
in
g
s
o
f
th
is
r
ev
iew
m
ay
also
h
av
e
im
p
o
r
tan
t
im
p
licatio
n
s
f
o
r
c
lin
ical
p
r
ac
tice
b
y
in
f
o
r
m
in
g
h
ea
lth
ca
r
e
p
r
o
f
ess
io
n
als
ab
o
u
t
th
e
p
o
ten
tial
b
e
n
ef
its
an
d
lim
itatio
n
s
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
i
n
f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia
m
an
a
g
e
m
en
t
o
f
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
.
T
h
is
s
tu
d
y
will
e
n
h
an
ce
th
e
s
tan
d
ar
d
o
f
ca
r
e
an
d
r
esu
lts
f
o
r
p
atien
ts
with
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
b
y
h
el
p
in
g
to
cr
ea
te
ev
id
en
ce
-
b
ased
g
u
id
elin
es
an
d
r
ec
o
m
m
en
d
atio
n
s
f
o
r
th
e
u
s
e
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
in
ter
v
en
tio
n
s
in
th
is
co
n
d
itio
n
'
s
m
an
ag
em
en
t.
2.
M
E
T
H
O
D
T
o
g
u
ar
a
n
tee
th
e
v
ali
d
ity
an
d
tr
u
s
two
r
th
in
ess
o
f
th
e
r
esu
lts
,
a
s
tr
ict
m
eth
o
d
o
lo
g
y
is
f
o
llo
w
ed
in
th
e
s
y
s
tem
atic
r
ev
iew
o
f
t
h
e
ef
f
e
cts
o
f
v
is
ce
r
al
m
a
n
ip
u
latio
n
i
n
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia.
Fo
llo
win
g
th
e
p
ar
ad
ig
m
cr
ea
ted
b
y
Ar
k
s
ey
an
d
O’
M
alley
[
1
7
]
,
th
is
s
y
s
tem
atic
r
ev
iew'
s
m
eth
o
d
o
lo
g
y
co
n
s
is
ts
o
f
f
iv
e
s
tep
s
:
i)
f
o
r
m
u
latin
g
th
e
r
esear
ch
q
u
es
tio
n
;
ii)
lo
ca
tin
g
p
er
tin
en
t
s
tu
d
ies;
iii)
ch
o
o
s
in
g
s
tu
d
ies;
iv
)
ch
ar
tin
g
th
e
d
ata;
an
d
v
)
c
o
m
p
ilin
g
,
s
u
m
m
ar
is
in
g
,
an
d
r
e
p
o
r
tin
g
th
e
f
in
d
in
g
s
.
A
th
o
r
o
u
g
h
ex
am
i
n
atio
n
o
f
th
e
b
o
d
y
o
f
r
esear
ch
o
n
v
is
ce
r
al
m
a
n
ip
u
latio
n
in
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
is
m
ad
e
p
o
s
s
ib
le
b
y
th
is
m
et
h
o
d
ical
a
p
p
r
o
ac
h
,
wh
ich
also
o
f
f
er
s
im
p
o
r
tan
t
i
n
s
ig
h
ts
in
to
th
e
p
o
s
s
ib
le
co
n
s
eq
u
en
ce
s
an
d
clin
ical
p
r
ac
tice
im
p
licatio
n
s
o
f
th
is
tech
n
iq
u
e
.
B
y
f
o
llo
win
g
estab
lis
h
ed
g
u
id
elin
es
an
d
p
r
o
to
co
ls
,
th
is
s
y
s
t
em
atic
r
ev
iew
aim
s
to
co
n
tr
ib
u
te
to
th
e
ev
id
en
ce
b
ase
s
u
r
r
o
u
n
d
in
g
t
h
is
tr
ea
tm
en
t m
o
d
ality
a
n
d
in
f
o
r
m
f
u
tu
r
e
r
esear
ch
in
th
e
f
ield
.
2
.
1
.
Det
er
m
ini
ng
t
he
re
s
ea
rc
h ques
t
io
n a
nd
pert
inent
lit
er
a
t
ure
T
h
e
r
esear
ch
q
u
esti
o
n
f
o
r
th
i
s
s
y
s
tem
atic
r
ev
iew
wa
s
as
:
W
h
at
is
th
e
ev
id
en
ce
f
o
r
th
e
ef
f
ec
ts
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
o
n
th
e
m
an
ag
em
en
t
o
f
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia?
T
h
e
r
esear
ch
q
u
esti
o
n
was
f
o
r
m
u
lated
to
g
u
id
e
th
e
s
ea
r
ch
f
o
r
r
elev
an
t
s
tu
d
ies
an
d
to
en
s
u
r
e
t
h
at
th
e
r
ev
iew
was
f
o
cu
s
ed
an
d
r
e
lev
an
t.
T
o
id
e
n
tify
r
elev
an
t
s
tu
d
ies,
a
s
y
s
tem
atic
s
ea
r
ch
was
co
n
d
u
cted
u
s
in
g
th
e
SC
OPUS,
Pu
b
Me
d
,
Go
o
g
le
Sch
o
la
r
s
,
an
d
Sem
an
tic
Sch
o
lar
d
atab
ases
f
o
r
ar
ticles
p
u
b
lis
h
ed
b
etwe
en
jan
u
ar
y
2
0
1
2
to
f
eb
r
u
ar
y
2
0
2
4
.
T
h
e
s
ea
r
ch
ter
m
s
in
clu
d
e
"v
is
ce
r
al
m
an
ip
u
latio
n
,
"
“v
is
ce
r
al
o
s
teo
p
ath
y
”,
“o
s
teo
p
ath
ic
m
a
n
ip
u
latio
n
”,
"f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia,
"
“g
astro
eso
p
h
ag
ea
l
r
ef
l
u
x
”,
an
d
r
elate
d
k
ey
wo
r
d
s
.
T
h
e
s
ea
r
ch
s
tr
ateg
y
was
d
esig
n
ed
to
b
e
co
m
p
r
eh
e
n
s
iv
e
an
d
in
clu
s
iv
e,
to
en
s
u
r
e
t
h
at
all
r
el
ev
an
t st
u
d
ies we
r
e
id
en
tifie
d
.
2
.
2
.
Select
ing
s
t
ud
ies
I
n
clu
s
io
n
c
r
iter
ia
wer
e
s
tu
d
ies
th
at
in
v
esti
g
ated
t
h
e
ef
f
ec
ts
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
o
n
th
e
m
an
ag
em
en
t
o
f
f
u
n
cti
o
n
al
d
y
s
p
ep
s
ia,
r
eg
ar
d
less
o
f
th
e
s
tu
d
y
d
esig
n
.
Stu
d
ies
m
u
s
t
b
e
p
u
b
lis
h
ed
in
E
n
g
lis
h
an
d
in
clu
d
e
h
u
m
an
p
a
r
ticip
an
t
s
.
Stu
d
ies
wer
e
ex
clu
d
ed
if
th
ey
f
o
cu
s
ed
o
n
o
th
er
g
astro
eso
p
h
ag
ea
l
co
n
d
itio
n
s
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
1
4
,
No
.
2
,
J
u
n
e
20
2
5
:
1
0
5
2
-
1
0
5
9
1054
o
r
d
id
n
o
t
s
p
ec
if
ically
ex
a
m
in
e
th
e
v
is
ce
r
al
m
an
ip
u
lati
o
n
in
ter
v
en
tio
n
s
.
T
wo
r
ev
ie
wer
s
in
d
ep
en
d
en
tly
ev
alu
ated
th
e
f
u
ll
-
tex
t
a
r
ticles
f
o
r
in
clu
s
io
n
in
th
is
s
y
s
tem
atic
r
ev
iew,
r
eso
lv
in
g
an
y
d
is
a
g
r
ee
m
en
ts
b
etwe
en
th
em
th
r
o
u
g
h
d
is
cu
s
s
io
n
an
d
co
n
s
en
s
u
s
.
T
wo
r
ev
iewe
r
s
i
n
d
ep
en
d
en
tly
s
cr
ee
n
e
d
th
e
titl
es
an
d
a
b
s
tr
ac
ts
o
f
all
th
e
id
en
tifie
d
s
tu
d
ies
to
d
eter
m
in
e
th
eir
elig
ib
ilit
y
f
o
r
in
cl
u
s
io
n
,
an
d
f
u
ll
-
tex
t
ar
ticles
w
er
e
o
b
tain
ed
f
o
r
all
s
tu
d
ies th
at
m
et
th
e
in
clu
s
io
n
cr
iter
ia
o
r
wer
e
u
n
s
u
r
e
o
f
th
eir
elig
ib
ilit
y
.
2
.
3
.
Cha
rt
ing
t
he
da
t
a
A
s
t
a
n
d
a
r
d
i
ze
d
d
a
t
a
e
x
t
r
a
ct
i
o
n
f
o
r
m
w
a
s
u
t
i
li
z
e
d
t
o
c
h
a
r
t
t
h
e
d
a
t
a
f
r
o
m
t
h
e
l
is
t
e
d
r
es
e
a
r
c
h
.
T
h
e
f
o
r
m
c
o
n
t
a
i
n
e
d
d
e
t
ai
ls
a
b
o
u
t
t
h
e
s
t
u
d
y
'
s
d
e
s
i
g
n
,
s
a
m
p
l
e
s
i
ze
,
i
n
te
r
v
e
n
t
i
o
n
d
o
s
a
g
e
,
r
e
p
o
r
t
e
d
r
es
u
l
ts
,
p
e
r
t
i
n
e
n
t
f
i
n
d
i
n
g
s
,
a
n
d
d
e
g
r
e
e
o
f
p
r
o
o
f
.
T
h
e
p
u
r
p
o
s
e
o
f
t
h
e
d
a
t
a
e
x
t
r
a
c
t
i
o
n
f
o
r
m
w
a
s
t
o
g
u
a
r
a
n
t
e
e
t
h
a
t
a
l
l
p
e
r
t
i
n
e
n
t
d
a
t
a
w
a
s
r
e
c
o
r
d
e
d
a
n
d
t
h
a
t
t
h
e
d
a
t
a
w
e
r
e
c
o
n
s
i
s
t
e
n
t
b
e
t
w
e
e
n
t
r
i
a
l
s
.
T
h
i
s
a
p
p
r
o
a
c
h
m
a
d
e
i
t
s
i
m
p
l
e
t
o
c
o
m
p
a
r
e
a
n
d
s
y
n
t
h
e
s
i
z
e
f
i
n
d
i
n
g
s
f
r
o
m
v
a
r
i
o
u
s
s
t
u
d
i
e
s
,
o
f
f
e
r
i
n
g
a
t
h
o
r
o
u
g
h
p
i
c
t
u
r
e
o
f
t
h
e
s
t
a
t
e
o
f
t
h
e
f
i
e
l
d
.
A
d
d
i
t
i
o
n
a
l
l
y
,
b
y
r
e
d
u
c
i
n
g
b
i
a
s
a
n
d
e
r
r
o
r
s
i
n
d
a
t
a
e
x
t
r
a
c
t
i
o
n
,
t
h
e
s
t
a
n
d
a
r
d
i
z
e
d
f
o
r
m
i
m
p
r
o
v
e
d
t
h
e
v
a
l
i
d
i
t
y
a
n
d
r
e
l
i
a
b
i
l
i
t
y
o
f
t
h
e
r
e
s
u
l
t
s
.
2
.
4
.
Co
lla
t
ing
,
s
um
ma
rizing
,
a
nd
re
po
rt
ing
re
s
ults
L
astl
y
,
th
e
s
y
s
tem
atic
r
ev
iew
co
m
p
iled
,
s
u
m
m
e
d
u
p
,
an
d
r
ep
o
r
ted
t
h
e
r
esu
lts
f
r
o
m
t
h
e
in
clu
d
ed
r
esear
ch
.
T
o
f
in
d
r
ec
u
r
r
in
g
th
e
m
es,
tr
en
d
s
,
an
d
g
ap
s
in
th
e
liter
atu
r
e,
th
e
d
ata
wer
e
co
m
b
i
n
ed
.
T
h
e
s
y
s
tem
atic
r
ev
iew'
s
f
in
d
in
g
s
ar
e
p
r
esen
ted
in
an
u
n
d
er
s
tan
d
ab
le
an
d
s
u
cc
in
ct
way
.
T
h
e
r
esu
lts
ar
e
p
r
e
s
en
ted
in
a
way
th
at
is
s
im
p
le
to
co
m
p
r
eh
e
n
d
a
n
d
in
ter
p
r
et.
Ad
d
itio
n
ally
,
th
e
r
esu
lts
ca
n
o
f
f
er
e
v
id
en
ce
-
b
ased
s
u
g
g
esti
o
n
s
f
o
r
th
e
u
s
e
o
f
v
is
ce
r
al
m
a
n
ip
u
latio
n
in
th
e
t
r
ea
tm
en
t
o
f
f
u
n
ctio
n
a
l
d
y
s
p
ep
s
ia
a
n
d
ar
e
p
r
esen
te
d
in
a
way
th
at
is
p
er
tin
en
t
to
clin
ical
p
r
ac
tice.
Acc
o
r
d
in
g
to
t
h
e
2
0
1
1
Ox
f
o
r
d
C
en
tr
e
f
o
r
E
v
i
d
en
ce
-
B
ased
Me
d
icin
e
lev
els
o
f
ev
id
en
ce
,
we
ass
ig
n
ed
ea
c
h
s
tu
d
y
a
g
r
ad
e
as sh
o
w
n
in
T
ab
le
1
.
T
ab
le
1
.
E
v
id
en
ce
lev
els f
r
o
m
th
e
Ox
f
o
r
d
ce
n
tr
e
f
o
r
e
v
id
en
ce
-
b
ased
m
ed
icin
e
Le
v
e
l
Ty
p
e
o
f
s
t
u
d
y
1
C
o
m
p
r
e
h
e
n
si
v
e
a
n
a
l
y
si
s
o
f
r
a
n
d
o
mi
se
d
t
r
i
a
l
s
2
R
a
n
d
o
m
i
z
e
d
t
r
i
a
l
3
n
o
n
-
r
a
n
d
o
m
i
z
e
d
f
o
l
l
o
w
-
u
p
r
e
se
a
r
c
h
o
r
c
o
n
t
r
o
l
g
r
o
u
p
4
S
t
u
d
y
i
n
g
c
a
s
e
s
e
r
i
e
s
a
n
d
c
a
se
-
c
o
n
t
r
o
l
5
N
o
t
a
p
p
l
i
c
a
b
l
e
2
.
5
.
Resea
rc
h f
lo
w
T
h
e
r
esear
ch
f
l
o
w
f
o
r
r
etr
iev
in
g
ar
ticles
f
r
o
m
th
e
Pu
b
Me
d
,
SC
OPUS,
Go
o
g
le
Sch
o
lar
,
Sem
an
tic
Sch
o
lar
d
atab
ases
is
ca
r
r
ied
o
u
t
u
s
in
g
id
en
tific
atio
n
,
s
cr
ee
n
in
g
,
elig
ib
ilit
y
,
an
d
in
cl
u
d
e
th
e
s
tu
d
y
tech
n
iq
u
es
.
Af
ter
th
at,
d
ata
a
n
aly
s
is
was
ca
r
r
ied
o
u
t
to
o
b
tain
r
elev
an
t
an
d
s
ig
n
if
ican
t
r
esu
lts
.
T
h
e
r
esear
ch
r
esu
lts
ar
e
th
en
co
m
p
iled
in
th
e
f
o
r
m
o
f
a
r
ep
o
r
t
o
r
s
cien
tific
ar
ticl
e
f
o
r
p
u
b
licatio
n
.
T
h
is
p
r
o
ce
s
s
en
s
u
r
es
th
at
th
e
in
f
o
r
m
atio
n
o
b
tain
ed
ca
n
b
e
ac
ce
s
s
ed
an
d
u
tili
ze
d
b
y
in
ter
ested
r
ea
d
er
s
.
T
h
e
au
to
m
a
tio
n
t
o
o
ls
u
s
ed
ar
e
g
r
ad
ep
r
o
GDT
5
wh
ich
ca
n
b
e
ac
ce
s
s
ed
th
r
o
u
g
h
th
e
s
ite
h
ttp
s
://g
d
t.g
r
ad
ep
r
o
.
o
r
g
/ap
p
.
A
to
tal
o
f
3
5
5
ar
ticles
wer
e
ex
clu
d
e
d
b
ased
o
n
th
is
a
u
to
m
atio
n
to
o
l
f
o
r
v
a
r
io
u
s
r
ea
s
o
n
s
in
clu
d
in
g
o
u
t
o
f
th
e
s
co
p
e,
n
o
t
o
p
en
ac
ce
s
s
,
ir
r
elev
an
t to
th
e
to
p
ic,
s
am
p
le
s
ize,
an
d
ty
p
e
o
f
s
tu
d
y
.
Mo
r
e
d
etails ca
n
b
e
s
ee
n
in
Fig
u
r
e
1
.
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
N
T
h
e
4
0
6
p
a
p
er
s
in
all
wer
e
r
ev
iewe
d
.
W
e
ch
o
s
e
2
6
a
b
s
tr
ac
ts
f
o
r
th
e
f
ir
s
t
s
cr
ee
n
in
g
a
f
ter
s
ca
n
n
in
g
t
h
e
titl
es
an
d
ab
s
tr
ac
ts
an
d
elim
in
atin
g
d
u
p
licates.
T
wen
ty
-
f
o
u
r
f
u
ll
-
tex
t
ar
ticles
wer
e
ch
o
s
en
an
d
v
etted
f
r
o
m
th
is
g
r
o
u
p
.
Fig
u
r
e
1
s
h
o
ws
th
at
eig
h
t
ar
ticles
s
ati
s
f
ied
all
in
clu
s
io
n
r
eq
u
ir
em
e
n
ts
.
T
wo
p
ilo
t
o
r
f
ea
s
ib
ilit
y
s
tu
d
ies,
o
n
e
p
r
o
s
p
ec
tiv
e
s
tu
d
y
,
two
r
a
n
d
o
m
is
ed
tr
ials
,
o
n
e
p
ilo
t
r
a
n
d
o
m
is
ed
tr
ial,
a
n
d
two
ca
s
e
r
e
p
o
r
ts
co
m
p
r
is
ed
th
e
eig
h
t
elig
ib
le
p
ap
e
r
s
as
p
r
esen
ted
in
T
ab
le
2
.
T
y
p
ically
,
s
am
p
le
s
izes
wer
e
s
m
all.
T
h
e
s
am
p
le
s
ize
f
o
r
f
iv
e
o
f
th
e
in
v
esti
g
atio
n
s
was
f
ewe
r
th
an
th
ir
ty
.
T
h
e
f
in
al
s
elec
tio
n
'
s
d
iv
er
s
ity
o
f
s
tu
d
y
a
p
p
r
o
ac
h
e
s
o
f
f
er
s
a
th
o
r
o
u
g
h
s
u
m
m
ar
y
o
f
t
h
e
s
tate
o
f
t
h
e
f
ield
'
s
r
esear
ch
.
No
twith
s
tan
d
in
g
th
e
m
o
d
est
s
am
p
le
s
izes,
th
e
v
ar
iety
o
f
s
tu
d
y
d
esig
n
s
d
ee
p
en
s
th
e
c
o
n
clu
s
io
n
s
an
d
en
a
b
les a
m
o
r
e
c
o
m
p
le
x
co
m
p
r
eh
en
s
io
n
o
f
th
e
to
p
ic.
T
h
e
in
itial
an
aly
s
is
o
f
th
e
in
cl
u
d
ed
s
tu
d
ies
s
u
g
g
ested
th
at
v
i
s
ce
r
al
m
an
i
p
u
latio
n
m
ay
h
av
e
p
o
ten
tial
b
en
ef
its
in
t
h
e
m
a
n
ag
em
en
t
o
f
f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia
[
1
4
]
,
[
1
9
]
–
[
2
3
]
.
Fu
n
ctio
n
al
d
y
s
p
e
p
s
ia
is
a
co
m
m
o
n
g
astro
in
test
in
al
d
is
o
r
d
er
ch
a
r
ac
ter
ized
b
y
r
ec
u
r
r
in
g
p
ai
n
o
r
d
is
co
m
f
o
r
t
in
t
h
e
u
p
p
e
r
ab
d
o
m
en
,
o
f
te
n
ac
co
m
p
an
ied
b
y
b
lo
atin
g
,
e
ar
ly
s
atiety
,
an
d
n
a
u
s
ea
,
with
o
r
with
o
u
t
g
astro
eso
p
h
a
g
ea
l
r
ef
lu
x
d
is
ea
s
e
s
y
m
p
to
m
s
[
2
4
]
,
[
2
5
]
.
T
h
e
ex
a
ct
ca
u
s
e
o
f
f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia
is
n
o
t
well
u
n
d
er
s
to
o
d
,
an
d
tr
ea
tm
en
t
o
p
tio
n
s
ar
e
lim
ited
[
2
6
]
.
T
h
ese
s
tu
d
ies
ex
am
in
ed
v
a
r
io
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Flo
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[
1
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Vis
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m
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ip
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latio
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m
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th
er
ap
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tech
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ascia,
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[
2
7
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2
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.
I
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3
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[
3
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[
3
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Vis
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ly
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ay
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elief
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p
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d
q
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ality
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[
1
6
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[
3
7
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,
[
3
8
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.
Vis
ce
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3
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ai
n
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u
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n
d
g
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p
ty
in
g
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r
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ized
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r
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esh
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2
2
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d
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[
4
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[
1
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[
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4
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[
4
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S
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[
4
4
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–
[
4
6
]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
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ce
r
al
m
an
ip
u
l
atio
n
in
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia.
T
h
is
will
h
elp
en
s
u
r
e
th
at
p
atien
ts
ar
e
well
-
in
f
o
r
m
e
d
an
d
ac
tiv
ely
i
n
v
o
lv
ed
in
th
eir
tr
ea
tm
en
t
d
ec
is
io
n
s
.
W
ith
m
o
r
e
ev
id
en
ce
-
b
ased
r
esear
ch
,
clin
ician
s
ca
n
m
ak
e
m
o
r
e
i
n
f
o
r
m
ed
r
ec
o
m
m
en
d
atio
n
s
r
eg
ar
d
in
g
t
h
e
u
s
e
o
f
v
is
ce
r
al
m
an
ip
u
la
tio
n
f
o
r
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia.
T
h
is
will u
ltima
te
l
y
lead
to
im
p
r
o
v
ed
p
atien
t o
u
tco
m
es a
n
d
s
atis
f
ac
tio
n
with
th
eir
tr
ea
tm
en
t.
I
n
th
e
m
ea
n
tim
e,
clin
ician
s
s
h
o
u
l
d
c
o
n
tin
u
e
t
o
s
tay
u
p
d
ated
o
n
th
e
latest
r
esear
ch
f
in
d
i
n
g
s
an
d
g
u
id
elin
es
r
elate
d
to
v
is
ce
r
al
m
an
ip
u
latio
n
t
o
p
r
o
v
i
d
e
th
e
b
est p
o
s
s
ib
le
ca
r
e
f
o
r
th
eir
p
atien
ts
.
A
s
y
s
tem
atic
r
ev
iew
o
f
th
e
ef
f
ec
ts
o
f
v
is
ce
r
al
m
an
i
p
u
lati
o
n
o
n
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
p
r
o
v
id
ed
a
co
m
p
r
eh
e
n
s
iv
e
o
v
e
r
v
iew
o
f
th
e
ex
is
tin
g
liter
atu
r
e
o
n
th
is
to
p
ic.
Alth
o
u
g
h
th
e
r
ev
iew
is
s
till
o
n
g
o
in
g
,
a
n
d
th
e
f
in
al
r
esu
lts
ar
e
n
o
t
a
v
ailab
le,
s
o
m
e
p
r
elim
in
ar
y
f
in
d
in
g
s
ca
n
b
e
d
is
cu
s
s
ed
b
ased
o
n
th
e
in
clu
d
ed
s
tu
d
ies
an
d
th
eir
in
itial
an
aly
s
es.
T
h
is
d
is
cu
s
s
io
n
h
ig
h
lig
h
ts
th
e
p
o
ten
tial
b
en
ef
its
an
d
lim
itatio
n
s
o
f
v
is
ce
r
al
m
an
ip
u
l
atio
n
in
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
m
an
ag
em
en
t o
f
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia.
So
m
e
s
tu
d
ies s
u
g
g
est th
at
v
is
ce
r
al
m
an
ip
u
latio
n
m
ay
im
p
r
o
v
e
s
y
m
p
to
m
s
s
u
c
h
as
b
lo
atin
g
an
d
d
is
co
m
f
o
r
t
i
n
p
atien
ts
with
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia
[
3
2
]
,
[
5
7
]
–
[
5
9
]
.
Ho
wev
e
r
,
m
o
r
e
r
esear
ch
is
n
ee
d
ed
t
o
f
u
lly
u
n
d
e
r
s
tan
d
th
e
m
ec
h
an
is
m
s
b
eh
in
d
th
ese
p
o
ten
tial
b
en
ef
its
an
d
to
d
eter
m
in
e
th
e
lo
n
g
-
ter
m
ef
f
ec
tiv
en
ess
o
f
th
is
tr
ea
t
m
en
t
ap
p
r
o
ac
h
.
T
h
e
p
r
elim
i
n
ar
y
f
in
d
in
g
s
s
u
g
g
est
th
at
v
is
ce
r
al
m
an
ip
u
latio
n
m
ay
b
e
a
p
r
o
m
is
in
g
ap
p
r
o
ac
h
f
o
r
m
an
a
g
in
g
f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia
s
y
m
p
to
m
s
.
Fu
tu
r
e
s
tu
d
ies
s
h
o
u
ld
f
o
c
u
s
o
n
lar
g
e
r
s
am
p
le
s
izes
an
d
lo
n
g
er
f
o
llo
w
-
u
p
p
er
io
d
s
to
p
r
o
v
id
e
m
o
r
e
c
o
n
clu
s
iv
e
ev
id
en
ce
o
n
its
ef
f
icac
y
.
E
x
p
l
o
r
in
g
th
e
ef
f
ec
ts
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
o
n
o
th
er
g
astro
i
n
test
in
al
co
n
d
itio
n
s
co
u
ld
p
r
o
v
id
e
v
alu
a
b
le
i
n
s
ig
h
ts
in
to
it
s
b
r
o
ad
er
th
er
ap
e
u
tic
p
o
ten
tial.
B
y
f
u
r
th
er
in
v
esti
g
atin
g
th
e
s
p
ec
if
ic
tech
n
iq
u
es
an
d
f
r
e
q
u
en
c
y
o
f
tr
ea
tm
en
t
th
at
y
ield
th
e
b
est
r
es
u
lts
,
h
ea
lth
ca
r
e
p
r
o
v
id
e
r
s
ca
n
o
p
tim
ize
th
e
u
s
e
o
f
v
is
ce
r
al
m
an
ip
u
latio
n
i
n
clin
ic
al
p
r
ac
tice.
4.
CO
NCLU
SI
O
N
T
h
e
in
itial
an
aly
s
is
o
f
th
e
in
c
lu
d
ed
s
tu
d
ies
s
u
g
g
ests
th
at
v
i
s
ce
r
al
m
an
ip
u
latio
n
m
ay
h
av
e
p
o
ten
tial
b
en
ef
its
in
th
e
m
an
ag
em
e
n
t
o
f
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia.
T
h
ese
s
tu
d
ies
ex
am
in
ed
v
ar
io
u
s
o
u
tco
m
es
r
elate
d
to
f
u
n
ctio
n
al
d
y
s
p
ep
s
ia,
s
u
ch
a
s
p
ain
in
ten
s
i
ty
,
q
u
ality
o
f
l
if
e,
an
d
g
astric
em
p
ty
in
g
.
W
h
ile
th
e
r
esu
lts
o
f
in
d
iv
id
u
al
s
tu
d
ies
v
ar
ied
,
s
o
m
e
ev
id
e
n
ce
s
u
g
g
ests
th
at
v
i
s
ce
r
al
m
an
ip
u
latio
n
m
ay
lead
to
im
p
r
o
v
e
m
en
ts
in
th
ese
o
u
tco
m
es.
So
m
e
p
o
s
s
ib
le
way
s
th
at
v
is
ce
r
al
m
a
n
ip
u
lat
io
n
ca
n
h
el
p
p
eo
p
le
with
f
u
n
c
t
io
n
al
d
y
s
p
ep
s
ia
b
y
lo
wer
in
g
g
astro
eso
p
h
ag
ea
l
r
ef
lu
x
d
is
ea
s
e,
ch
an
g
in
g
v
is
ce
r
al
h
y
p
er
s
en
s
itiv
ity
,
an
d
im
p
r
o
v
i
n
g
s
to
m
ac
h
m
o
tili
ty
.
Ho
wev
er
,
t
h
e
q
u
ality
o
f
t
h
e
in
clu
d
ed
s
tu
d
ies
v
ar
ied
an
d
t
h
e
h
eter
o
g
en
eity
o
f
th
e
s
tu
d
y
d
esig
n
s
,
in
ter
v
en
tio
n
s
,
an
d
o
u
tco
m
e
m
ea
s
u
r
es
m
ad
e
it
ch
allen
g
in
g
to
d
r
aw
d
ef
in
itiv
e
co
n
clu
s
io
n
s
.
C
o
m
p
ar
ativ
e
ef
f
ec
tiv
en
ess
r
esear
ch
is
r
eq
u
ir
ed
to
d
eter
m
in
e
th
e
r
elativ
e
b
en
ef
its
an
d
r
is
k
s
o
f
d
if
f
er
e
n
t
in
ter
v
en
tio
n
s
f
o
r
f
u
n
ctio
n
al
d
y
s
p
e
p
s
ia.
Stu
d
ies
co
m
p
a
r
in
g
v
is
ce
r
al
m
a
n
ip
u
l
atio
n
with
o
th
er
m
a
n
u
al
th
er
ap
y
tech
n
iq
u
es
o
r
co
n
v
en
tio
n
al
tr
ea
tm
en
ts
co
u
l
d
p
r
o
v
i
d
e
v
alu
a
b
le
in
s
ig
h
ts
in
to
th
e
o
p
tim
al
m
a
n
ag
em
en
t
o
f
th
is
co
n
d
itio
n
.
RE
F
E
R
E
NC
E
S
[
1
]
N
.
D
e
B
o
r
t
o
l
i
e
t
a
l
.
,
“
G
a
s
t
r
o
e
so
p
h
a
g
e
a
l
r
e
f
l
u
x
d
i
se
a
se,
f
u
n
c
t
i
o
n
a
l
d
y
s
p
e
p
s
i
a
a
n
d
i
r
r
i
t
a
b
l
e
b
o
w
e
l
sy
n
d
r
o
m
e
:
c
o
m
mo
n
o
v
e
r
l
a
p
p
i
n
g
g
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l
d
i
s
o
r
d
e
r
s,”
A
n
n
a
l
s
o
f
G
a
st
r
o
e
n
t
e
ro
l
o
g
y
,
v
o
l
.
3
1
,
n
o
.
6
,
p
p
.
6
3
9
–
6
4
8
,
2
0
1
8
,
d
o
i
:
1
0
.
2
0
5
2
4
/
a
o
g
.
2
0
1
8
.
0
3
1
4
.
[
2
]
N
.
Th
a
p
a
r
e
t
a
l
.
,
“
P
a
e
d
i
a
t
r
i
c
f
u
n
c
t
i
o
n
a
l
a
b
d
o
mi
n
a
l
p
a
i
n
d
i
s
o
r
d
e
r
s,”
N
a
t
u
re
rev
i
e
w
s
.
D
i
s
e
a
s
e
p
ri
m
e
rs
,
v
o
l
.
6
,
n
o
.
1
,
p
.
8
9
,
2
0
2
0
,
d
o
i
:
1
0
.
1
0
3
8
/
s
4
1
5
7
2
-
020
-
0
0
2
2
2
-
5.
[
3
]
Y
.
W
a
n
g
,
J.
D
.
Z.
C
h
e
n
,
a
n
d
B
.
N
o
j
k
o
v
,
“
D
i
a
g
n
o
s
t
i
c
me
t
h
o
d
s
f
o
r
e
v
a
l
u
a
t
i
o
n
o
f
g
a
s
t
r
i
c
m
o
t
i
l
i
t
y
-
a
mi
n
i
r
e
v
i
e
w
,
”
D
i
a
g
n
o
st
i
c
s
,
v
o
l
.
1
3
,
n
o
.
4
,
2
0
2
3
,
d
o
i
:
1
0
.
3
3
9
0
/
d
i
a
g
n
o
s
t
i
c
s1
3
0
4
0
8
0
3
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
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8
8
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6
I
n
t J Pu
b
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Hea
lth
Sci
,
Vo
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1
4
,
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2
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u
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20
2
5
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1058
[
4
]
M
.
D
.
P
e
r
m
a
n
a
a
n
d
K
.
R
e
n
a
l
d
i
,
“
M
a
n
a
g
e
m
e
n
t
o
f
g
a
s
t
r
i
c
mo
t
i
l
i
t
y
d
i
s
o
r
d
e
r
,
”
T
h
e
I
n
d
o
n
e
si
a
n
J
o
u
r
n
a
l
o
f
G
a
st
r
o
e
n
t
e
ro
l
o
g
y
,
H
e
p
a
t
o
l
o
g
y
,
a
n
d
D
i
g
e
s
t
i
v
e
En
d
o
sc
o
p
y
,
v
o
l
.
1
9
,
n
o
.
1
,
p
p
.
2
5
–
3
6
,
2
0
2
0
,
d
o
i
:
1
0
.
2
4
8
7
1
/
1
9
1
2
0
1
8
2
5
-
3
6
.
[
5
]
A
.
K
a
r
u
n
a
n
a
y
a
k
e
,
S
.
R
a
j
i
n
d
r
a
j
i
t
h
,
H
.
A
.
D
e
S
i
l
v
a
,
S
.
G
u
n
a
w
a
r
d
e
n
a
,
a
n
d
N
.
M
.
D
e
v
a
n
a
r
a
y
a
n
a
,
“
A
u
t
o
n
o
mi
c
f
u
n
c
t
i
o
n
s
a
n
d
g
a
st
r
i
c
mo
t
i
l
i
t
y
i
n
c
h
i
l
d
r
e
n
w
i
t
h
f
u
n
c
t
i
o
n
a
l
a
b
d
o
m
i
n
a
l
p
a
i
n
d
i
s
o
r
d
e
r
s,”
W
o
r
l
d
J
o
u
rn
a
l
o
f
G
a
st
ro
e
n
t
e
r
o
l
o
g
y
,
v
o
l
.
2
5
,
n
o
.
1
,
p
p
.
9
5
–
1
0
6
,
2
0
1
9
,
d
o
i
:
1
0
.
3
7
4
8
/
w
j
g
.
v
2
5
.
i
1
.
9
5
.
[
6
]
A
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[
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[
8
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[
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3
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L.
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1
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5
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[
1
6
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T
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[
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7
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[
1
8
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A
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