JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-13-30 (2013)

Reviewer's report
Title:Role of the ABCG8 19H risk allele in cholesterol absorption and gallstone
disease
Version: 1Date:4 December 2012
Reviewer: Nigel Bird
Reviewer's report:
This paper examines cholesterol absorption and the ileal cholesterol transporters
ABCG5 / 8 and NPC1L1 stratified by the p.D19H allele. 168 patients were
recruited from colonoscopy lists of which 34 were found to have gallstones. The
paper represents a thorough examination of these transporters with largely
negative results, which nevertheless do not detract from the value of the work.
Major Compulsory Revisions
I found that the presentation of the results made the paper difficult to follow at
times. I felt that the stratification of patients by BMI was not particularly well
justified. The WHO categorisies a BMI of less than 25 as normal weight, 25-29.9
as overweight and >30 obese but the authors stratify their patients into <25 and
>25 and also use the terms 'overweight' and 'obese' interchangeably. In the
Results section values for the BMI's are wrongly reported as BMI +/- 25.2 and +/-
26.6, Table 2 has the correct values and SEM's. These are reported as being
significant, although it is hard to reconcile this clinically.
On page 12 it is inferred that the differences in HNF1alpha expression are
different but they present a p value of 0.0564 which is not significant.The values
reported for the overweight group in Table 2 also are reported as being
significant at the 0.047 level whereas the levels of 7667 +/- 1295 versus 7274 +/-
1759 suggest otherwise. Throughout the paper I would like to see the statistical
test that was used to generate the probabilities reported explicitly. A number of
statistical tests were used and it would help the readers if they knew which test
applied to what data. It would also add to the credibility of the paper if Power
calculations could be included since the possibility of a Type II statistical error is
always a risk in these types of studies.
Minor Essential Revisions
I would like to see a Table showing the diagnoses / indications for colonoscopy
since chronic constipation is a known risk factor for the generation of gallstones.
The patients did not suffer from gallstone disease and so this term should not be
used interchangeably with gallstone carriers. Similarly, some of the patients in
the overweight group may have been obese, but not all and therefore this term
should not be used interchangeably.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-30 (2013)

Reviewer's report
Title:Role of the ABCG8 19H risk allele in cholesterol absorption and gallstone
disease
Version: 2Date:16 January 2013
Reviewer: Nigel Bird
Reviewer's report:
I have read the revised manuscript and accept that the authors have addressed
all of the points raised in the first review. I would therefore recommend
publication.
Review for 10.1186/1471-230X-13-30 (2013)

Reviewer's report
Title:Role of the ABCG8 19H risk allele in cholesterol absorption and gallstone
disease
Version: 2Date:3 February 2013
Reviewer: Markku Nissinen
Reviewer's report:
The manuscript is now acceptable for publication.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests' below.
Review for 10.1186/1471-230X-13-28 (2013)

Reviewer's report
Title:Chronic Fatigue Syndrome 5 years after giardiasis: differential diagnoses,
characteristics and natural course
Version: 2Date:17 July 2012
Reviewer: Eva Libman
Reviewer's report:
1) Goals of the study
The primary objectives of this study were to:
• Describe post infectious fatigue in the form of CFS and ICF in a group of
patients who had self-reported chronic fatigue 3 years after giardiasis
• Identify differential diagnoses
Secondary objectives were to:
• Describe the natural course of fatigue at 3 and 5 years after infection
• Identify factors associated with chronic fatigue
2) Methodology
The methods were appropriate and well-described. However, there was no
comment made on the seemingly very low participation rate (approximately
21%), raising serious questions both about representativeness of the sample and
power of the statistical analyses.
3) Interpretation/Discussion
Minor important revisions:
I would have liked the Discussion section to be related more specifically to the
goals presented in the Introduction.
More than 50% of the sample was diagnosed with CFS/ICF, however there were
also some important co-morbidities identified 3 years and 5 years post infection –
e.g. abdominal problems/IBS, asthma, allergies depression. The prevalence of
asthma and allergy was surprisingly high, but there was no commentary on this
finding. It looks as if there is also a substantial amount of depression among
those participants designated as Giardia- induced CFS/ICF, even though
depression presumably would have designated such participants to the Chronic
Fatigue Other Aetiology category. Probably because of small sample size, if is
not clear what the specific factors are that are associated with chronic fatigue
and where co-morbidities fit into the evolution of post infection fatigue. Since all
participants had the same infectious disease, it would have been interesting to
include the evolution of fatigue in those where SAHS, depression and anxiety
were diagnosed as well, rather than excluding them. These aspects should be
clarified and amplified.
Major important revision:
There is no mention of limitations in this study; the small sample size and
reasons for this should definitely be included.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests
(document refused to upload; review was copied and pasted into box)
Review for 10.1186/1471-230X-13-28 (2013)

Reviewer's report
Title:Chronic Fatigue Syndrome 5 years after giardiasis: differential diagnoses,
characteristics and natural course
Version: 2Date:17 September 2012
Reviewer: Fumiharu Togo
Reviewer's report:
Major Compulsory Revisions
What does “natural course” mean? All participants did not have any treatments
during 2 years? This effects on fatigue at 5 years.
Medical history after giardiasis should be stated. The history should be
considered for categorizing subjects. The history also effects on fatigue at 5
years.
Are there any reasons for using 15 as a cut-off point of fatigue score for selecting
participants?
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-28 (2013)

Reviewer's report
Title:Chronic Fatigue Syndrome 5 years after giardiasis: differential diagnoses,
characteristics and natural course
Version: 3Date:31 October 2012
Reviewer: Daniel Neu
Reviewer's report:
no further review required
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
no to all of the above
Review for 10.1186/1471-230X-13-28 (2013)

Reviewer's report
Title:Chronic Fatigue Syndrome 5 years after giardiasis: differential diagnoses,
characteristics and natural course
Version: 3Date:8 November 2012
Reviewer: Eva Libman
Reviewer's report:
The manuscript is more clearly written, and the authors have taken into account
most of the reviewer commentaries.
There is still some additional clarification needed:
1. The definition of CFS (p4) - diachotomized....added score..is not easily
understood (minor point)
2. Although the very low participation rate is now included as a "limitation", I think
the implications for interpretation of the data from this very small and
unrepresentative sample need to be elaborated (minor essential revision)
2, In the Discussion (p8) the authors talk about a control group. Such a group
was not mentioned previously and needs to be either elaborated in the Methods
section or otherwise clarified (major essential revision).
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-13-28 (2013)

Reviewer's report
Title:Chronic Fatigue Syndrome 5 years after giardiasis: differential diagnoses,
characteristics and natural course
Version: 3Date:19 November 2012
Reviewer: Fumiharu Togo
Reviewer's report:
Major Compulsory Revisions
Meaning of “natural course” is still uncleared. What is your definition of the term?
In the response letter, authors state "However, the study was not designed to
evaluate
effect of previous treatment, and these data are not presented." However, the
authors examined
changes of fatigue during 2 years among patients and sample size is too small to
generalize the results.
So what does this study evaluate?
In the method section, the authors also state "as an optional part of the study, the
patients were offered treatment consisting of
randomisation into two different treatment programs performed by psychiatrists.",
which is a kind
of intervention on fatigue level and effects on results of this paper.
Although, it is not clear whether patients in this study received the treatment
program,
treatment for the patients from 3 to 5 years after giardiasis should be described.
In the response letter, authors state "A cut-off of 15 was used in order to exclude
those who had
very mild self-reported fatigue between 11 and 14." Please add this in the
method section and cite
previous studies which define that scores < 15 is "very mild fatigue".
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-29 (2013)

Reviewer's report
Title:A synergistic interaction between transcription factors nuclear
factor-kappaB and signal transducers and activators of transcription 3 promotes
gastric cancer cell migration and invasion
Version: 2Date:3 January 2013
Reviewer: sergei I. grivennikov
Reviewer's report:
Authors have improved the manuscript significantly and I think it is acceptable in
its current form. I agree that in their system 'metastasis assay' will be difficult to
perform (especially within the reasonable timeframes) and therefore these
experiments should not further delay the publication of this paper
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-29 (2013)

Reviewer's report
Title:A synergistic interaction between transcription factors nuclear
factor-kappaB and signal transducers and activators of transcription 3 promotes
gastric cancer cell migration and invasion
Version: 2Date:3 January 2013
Reviewer: brendan jenkins
Reviewer's report:
Minor Compulsory Revision:
1) Page 13, 1st paragraph, line 3 - correct epithelila to epithelial
2) page 15, last paragraph, last line, "our observations contrast with a report by
Yang et al" reword this sentence as there is no evidence in this manuscript
suggesting that STAT3 does not heterodimerize with RelA. In fact double
immunofluorescence staining showed that pRelA and STAT3 co-localize in the
nucleus.
Major Compulsory Revision:
3) I still believe it is important to address how NF-kB is regulating STAT3. Were
appropriate controls, such as a known STAT3 binding partner (eg STAT1), used
for the co-immunoprecipitation experiments? It is possible that STAT3 and RelA
may not heterodimerize in human gastric cancer cells. Therefore, in addition a
simple IL-6 qPCR and immunoblot on SNU-638 cells over-expressing IkBaM, to
show a reduction in IL-6 expression levels will suffice to speculate that NF-kB
may induce STAT3 activation through IL-6.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that i have no competing interests' below
Review for 10.1186/1471-230X-13-27 (2013)

Reviewer's report
Title:Looking for Predictive Factors of Clinical Response to Adsorptive
Granulocyte and Monocyte Apheresis in Patients with Ulcerative Colitis
Version: 2Date:13 January 2013
Reviewer: Abbi Saniabadi
Reviewer's report:
MS title: Looking for Predictive Factors of Clinical Response to Adsorptive
Granulocyte and Monocyte Apheresis in Patients with Ulcerative Colitis,
by DR Yoko Yokoyama, and colleagues
In a retrospective setting, the authors have looked at the clinical and endoscopic
features of patients with active ulcerative colitis who may respond to selective
depletion of elevated myeloid lineage leucocytes, or otherwise, might be
non-responders. Basically an extracorporeal, non-pharmacologic treatment
strategy. A total of 43 patients with active colitis were treated in an outpatient
setting, each received 10 treatment sessions over 10 weeks. The authors
factored patients’ entry demographic variables into analyses by receiver
operating characteristic (ROC), and multiple logistic regression. They found that
patients with a short duration of UC and low cumulative corticosteroid dose at
entry were good responders, but the best responders were patients who received
the treatment immediately after a clinical relapse. Patients with a high cumulative
corticosteroid dose and those with extensive loss of the mucosal tissue at the
lesion sites were non-responders.
The manuscript is well written, the standard of the English language is high.
Likewise, the manuscript has sound and clinically relevant data. Therefore, I
have no hard words for the authors.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Review for 10.1186/1471-230X-13-27 (2013)

Reviewer's report
Title:Looking for Predictive Factors of Clinical Response to Adsorptive
Granulocyte and Monocyte Apheresis in Patients with Ulcerative Colitis
Version: 2Date:4 February 2013
Reviewer: yasuo suzuki
Reviewer's report:
This paper is very interesting and valuable for clinical practice of ulcerative colitis
treatment.
Cytapheresis is thought to be a good tratment for patients with active ulcerative
colitis, but a oly few paper have shown good indications for cytapheresis with
active ulerarive colitis patients.
So, the results of this paper are very important.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-25 (2013)

Reviewer's report
Title:High mortality of pneumonia in cirrhotic patients with ascites
Version: 1Date:10 September 2012
Reviewer: Masaki Kaibori
Reviewer's report:
Comments:
The manuscript "High mortality of pneumonia in cirrhotic patients with ascites"
details the effect of variable infectious diseases on the mortalities of cirrhotic
patients with ascites. The authors demonstrate that infectious diseases indeed
increased 30-day and 90-day mortalities of cirrhotic 1,294 patients with ascites.
Among variable infectious diseases, pneumonia was most related to mortalities.
It is an interesting and important study examining the impact of pneumonia or
SBP in cirrhotic patients with ascites. Why is the pneumonia related to mortality
of cirrhotic patients with ascites? Please describe the authors'
speculation in the Discussion section.
Review for 10.1186/1471-230X-13-25 (2013)

Reviewer's report
Title:High mortality of pneumonia in cirrhotic patients with ascites
Version: 2Date:27 December 2012
Reviewer: Tony Bruns
Reviewer's report:
In their revision, the authors clarify some important points raised and improved
the value of the manuscript (Points 1a, 1b).
In their point-to-point responses, the authors acknowledge that the following data
are important to interpret the results and confounders: MELD score, causes of
death, type of pneumonia (CAP, HAP, VAP), presence of SIRS, ICU-treatment,
penumonia severity scores (Points 2a-d). However, their method of data
acquisition (retrospective ICD-based study) does not allow to incorporate these
data.
Furthermore, microbiological data are not available and, therefore,
recommendations regarding prophylaxis (vaccination) or empiric treatment
cannot be drawn.
Major Compulsory Revisions
1) English grammar is poor throughout the manuscript. I would advice a
professional language editing service prior to publication.
2) Please indicate the limitations of the study (see Points 2a-d and above) in the
manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-13-21 (2013)

Reviewer's report
Title:Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor,
alleviates liver injury induced by acetaminophen overdose in mice
Version: 2Date:17 October 2012
Reviewer: Svenja Sydor
Reviewer's report:
The manuscript of Tomishima and Ishitsuka et al. concerns with the effect of the
TXA2 synthase inhibitor ozagrel within Acetaminophen/Paracetamol
(APAP)-associated liver injury.
The authors could show that ozagrel-administration ameliorates the outcome of
liver injury after APAP-intoxication explicitly. Mice with ozagrel-injection showed
increased survival rates and were protected from APAP-induced liver damage. In
vitro experiments could show that ozagrel may reduce NAPQI
(N-acetyl-p-benzoquinone imine), a reactive metabolite generated after
APAP-administration. The authors suppose that ozagrel could be applied as
efficient drug to reduce APAP-related liver injury as NAC (N-acetyl cysteine) is
still used as an effective antidote after APAP- intoxication in clinical practice.
The experiments were designed substantially including cell culture experiments
as well as a mouse model. The results are reported in a clear and well-organized
manner with established and qualitative adequate methods and exactness.
Minor comments:
- In figure 5A the definitions of the asterisks shown in this graph are not given in
figure legends which make the diagram incomprehensible. Please change the
figure legend accordingly.
Major comments:
- The authors seek to use ozagrel as effective new treatment in APAP-induced
liver injury because NAC has limited therapeutic efficacy against APAP-induced
hepatoxicity. However in vitro experiments (figure 6) show that NAC shows a
higher efficacy versus NAPQI-induced cell death. How can the authors explain
this issue? What are the advantages of ozagrel- compared to NAC-administration
after APAP-intoxication in the author`s opinion? This question should be
discussed by the authors.
- Did the authors also measure the effect of NAC on hepatic GSH depletion and
compare it to the effect of ozagrel as shown in figure 5A? This could emphasise
the opinion that ozagrel-treatment should be preferred instead of NAC-treatment.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-21 (2013)

Reviewer's report
Title:Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor,
alleviates liver injury induced by acetaminophen overdose in mice
Version: 4Date:11 December 2012
Reviewer: Thomas Schreiter
Reviewer's report:
In the revised form of the manuscript “Ozagrel hydrochloride, a selective
thromboxane A2 synthase inhibitor, alleviates liver injury induced by
acetaminophen overdose in mice” all major revisions have been addressed
properly by the authors.
Nevertheless, this reviewer found one discrepancy in the Legend of Figure 1B:
The reviewer suggested “… mice were treated with ozagrel (200mg/ml, n=5) or
saline (n=11) 30 min after APAP injection (n=16, might be omitted)… “.
The authors changed to “… mice were treated with ozagrel (200mg/ml, n=5) or
saline 30 min after APAP injection (n=11) … “. If the total number of mice was 11,
the number of saline treated mice would have been six, but there are eight data
points in the graph. This should be adjusted.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-21 (2013)

Reviewer's report
Title:Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor,
alleviates liver injury induced by acetaminophen overdose in mice
Version: 4Date:18 December 2012
Reviewer: Svenja Sydor
Reviewer's report:
The authors clarified all named issues.
There is only one minor comment: Please change # in figure legend 6 to *,
according to the asteriks (*) used in figure 6.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-13-23 (2013)

Reviewer's report
Title:Medication adherence and persistence in the treatment of Canadian
ulcerative colitis patients: analyses with the RAMQ database
Version: 2Date:25 September 2012
Reviewer: Barney Hawthorne
Reviewer's report:
This is a well-written study of adherence to mesalamine in a large population of
UC patients.
The low adherence and persistence are perhaps unsurprising.
Minor comments
1) No data on dose used, and dose frequency. This data may not be available
from the database. If not this should be made clear.
2) In the background, p.4 2nd paragraph the authors state that Mezavant
multimatrix pH-dependent and gastro-resistant coating is the reason the drug can
be taken once daily. It should be made clear that the Eudragit-S coating delays
release until the distal ileum/caecum is reached, and the hydrophilic and
lipophilic matrix core allows gradual release of drug as it passes through the
colon. The design is intended to allow more mucosal contact with the native drug
before N-acetylation, The manufacturers had the foresight to use trial designs to
demonstrate once-daily therapy was as effective as divided dose, and the same
has now been shown for most other delayed release mesalamine preparations.
This should be clarified.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-13-23 (2013)

Reviewer's report
Title:Medication adherence and persistence in the treatment of Canadian
ulcerative colitis patients: analyses with the RAMQ database
Version: 2Date:11 October 2012
Reviewer: yvette leung
Reviewer's report:
Minor essential revisions:
Did you exclude 5-ASA prescriptions for microscopic colitis?
How did you account for cesssation of therapy because the patient was given a
new presciption for another drug if 5-ASA was ineffective? Eg. initiation of imuran
or remicade
How do the results of your study add to the literature?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-13-23 (2013)

Reviewer's report
Title:Medication adherence and persistence in the treatment of Canadian
ulcerative colitis patients: analyses with the RAMQ database
Version: 3Date:17 December 2012
Reviewer: Barney Hawthorne
Reviewer's report:
No further comments.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-13-23 (2013)

Reviewer's report
Title:Medication adherence and persistence in the treatment of Canadian
ulcerative colitis patients: analyses with the RAMQ database
Version: 3Date:15 January 2013
Reviewer: yvette leung
Reviewer's report:
I have reviewed the authors' reply to my comments previously and accept their
replies
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-22 (2013)

Reviewer's report
Title:Improvement of endocytoscopic findings after per oral endoscopic
myotomy (POEM) in esophageal achalasia; Does POEM reduce the risk of
developing esophageal carcinoma?
Version: 4Date:7 November 2012
Reviewer: P. Marco Fisichella
Reviewer's report:
Nice manuscript, well written. Interesting research idea, very original. Minor flaws
in the retrospective study design. Discussion, tables and figures are appropriate.
No revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-22 (2013)

Reviewer's report
Title:Improvement of endocytoscopic findings after per oral endoscopic
myotomy (POEM) in esophageal achalasia; Does POEM reduce the risk of
developing esophageal carcinoma?
Version: 4Date:25 December 2012
Reviewer: Tsutomu Nomura
Reviewer's report:
Major Compulsory Revisions
This study aims to evaluate the effectiveness of POEM in patients with
esophageal achalasia. The authors claim that POEM is an effective and less
invasive treatment for achalasia and may reduce the risk of esophageal
carcinogenesis.
For the benefit of the reader, however, several points need clarifying and certain
statements, which are given below.
1) In discussion, page 10/33, line5-7#Inoue et al. reported that there was no
recurrence after the POEM procedure in their 17 case series of achalasia[10].
#In their report (reference No 10), the mean follow-up period was 5 months. More
long follow-up period should be needed to claim#there was no recurrence after
the POEM procedure#.
2) In discussion, page 11/33, line20-21#Expression of the Ki-67 protein is
associated with the clinical course of mucosal inflammation[25].#
#In the report (reference No 25), I could not find the description. In abstract, they
mentioned that the expression of the Ki-67 protein is associated with the clinical
course of cancer (breast and prostate), but did not mention of correlation with
mucosal inflammation.
3) In discussion, page 11/33, line21 #They suggested####
##They#are Dr. Leeuwenburgh? Dr. Scholzen?
4) The authors should discuss about the relationship between patients
characteristic (type, dilation, duration of disease etc.) and the results of
endocytoscopy, Ki67 and p53.
5) The authors should check the references.
#reference 12 #Dis Esophagus, 2011#
##Dis Esophagus,2012 Apr;25(3):235-41. doi #?
#reference 28#American journal of gastroenterology#
##Am J Gastroenterol#?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-20 (2013)

Reviewer's report
Title:Clostridium leptum group bacteria abundance and diversity in the fecal
microbiota of patients with inflammatory bowel disease: a case-control study in
India
Version: 1Date:14 October 2012
Reviewer: liping chen
Reviewer's report:
C.leptum group, which belongs to the Firmicutes phylum, can produce short
chain fatty acid exerting anti-inflammatory effect. This study explored the
characteristics of C.leptum group in Indian IBD patients by TTGE and qPCR. It is
interesting and important for us to improve our understanding about dysboisis of
bacterial subgroups in IBD patients with different geographical background.
In this study, authors draw a conclusion that total numbers of C.leptum group
bacteria and F.prausnitzii was reduced in both CD and UC patients, and were not
related with disease activity.
I think it is debatable in that author did not characterize the number of total
bacteria. The premise to compare quantity variance of bacterium (group)
between IBD and healthy controls is that total bacterial number is comparative
between IBD and healthy controls. But i have no information about it from this
study. I think it is reasonable to compare bacterium (group) in different groups
with ratio of some bacterium (group) and the number of total bacteria. I suggests
that author characterizes the number of total bacteria furtherly.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that i have no competing interests
Review for 10.1186/1471-230X-13-20 (2013)

Reviewer's report
Title:Clostridium leptum group bacteria abundance and diversity in the fecal
microbiota of patients with inflammatory bowel disease: a case-control study in
India
Version: 1Date:18 November 2012
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
Major comments:
1. The sample size of the cohorts is relatively small compared to many other
currently emerging studies on intestinal dysbiosis in IBD.
2. The focus is exclusive on C.leptum, in particular F. prausnitzii. The association
between reduced counts or diversity of this bacterial species and IBD has been
described in several previous cohorts. It would have been interesting to describe
a broader pattern of microbial dysbiosis in the IBD population from India.
Minor comments:
1. Perhaps the authors can provide a few more sentences on the ‘healthy
controls’ selected for their study. Was this from a gastroenterology practice as
well, or from a primary care general medical population?
2. In their statistical analysis, the authors refer to performing post-hoc Bonferroni
tests. This needs to be described in a little greater detail. What was the
Bonferroni adjusted p-value that represented statistical significance?
3. What medical treatments for their IBD were the patients on? Did any of the CD
patients have a history of surgical treatment of their disease? Had any patients
recently undergone a colonoscopy or colonoscopy preparation?
4. Throughout the manuscript – the authors present an overall p-value, followed
in parenthesis by p-values for the various between group comparisons. Perhaps
an easier way to present is just to describe the p-values between HC and CD,
and HC and UC. I don’t see the need for an overall between all 3-group p-values
when one is describing the subgroups anyway.
5. Was there a difference in colon counts or diversity by duration of IBD?
6. I think the authors conclusion that the changes in gut microbiome could be due
to dietary restrictions placed on IBD patients (Page 14) is somewhat speculative
and not backed up by data. In the absence of dietary information gathered as
part of their study, I would suggest excluding this speculation unless there is data
from other groups that provide objective evidence for this hypothesis.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-19 (2013)

Reviewer's report
Title:Intestinal biopsy to diagnose celiac disease is not always required:
Importance of combined antibody tests
Version: 2Date:29 July 2012
Reviewer: Jocelyn Silvester
Reviewer's report:
The authors calculated PPV and NPV for histologic findings of celiac disease in a
population with a high pre-test probability of celiac disease. Based on cut-offs
derived from this population, they then determined which combination of tests
might obviate the need for intestinal biopsy in the same population. The cut-offs
were not validated in a second population.
Minor essential revisions
1. The discussion contains contradictory statements regarding the content of
European guidelines for diagnosis of celiac disease. [second sentence first
paragraph and final paragraph]
2. Abstract – objective misspelled.
3. Table 2 - 1% and 2% are false positive and false negative rates, respectively,
not NPV of positive test and PPV of negative test.
4. Table 3 – first column header – should this be fn?
Discretionary revisions
1. The patients with celiac disease were older than the controls. Was this
difference significant?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-19 (2013)

Reviewer's report
Title:Intestinal biopsy to diagnose celiac disease is not always required:
Importance of combined antibody tests
Version: 2Date:2 October 2012
Reviewer: Julio C Bai
Reviewer's report:
I understand the manuscript deserves publication.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-13-19 (2013)

Reviewer's report
Title:Intestinal biopsy to diagnose celiac disease is not always required:
Importance of combined antibody tests
Version: 2Date:13 October 2012
Reviewer: Xavier Bossuyt
Reviewer's report:
The authors present a study in which they claim that intestinal biopsy is not
always required to diagnose celiac disease. The disease can be diagnosed
based on combined antibody tests in patients with a high pretest probability.
Major comments
In this study, the prevelance of celiac disease was >50%. This is higher than the
prevalence of celiac disease in consecutive samples submitted to a routine
clinical laboratory for testing for celiac disease (and probably than the prevalence
of celiac disease in consecutive patients that undergo small bowel biopsy
because of suspicion of celiac disease).
Predictive values depend on the prevalence. Thus, the predictive values
presented in this paper were calculated for a high prevalence (pre-test
probability), and, therefore, may not be representative for settings in which the
prevalence is lower. This should be discussed. For example, the positive
predictive value would be 87% if the pretest probability was 7% (based on data in
Table 2).
Are the patients and controls consecutive patients that presented to the
gastroenterolgist? Given the importance of the pre-test probability (see above), it
woud be good if the authors could give a more detailed description of the clinical
presentation of the patients and controls. Particularly, how would the authors
estimate the pre-test probability for celiac disease in an individual patient? For
example, the authors mention iron deficiency. Is iron deficiency a condition that is
associated with a high (>50%) pretest probability for celiac disease?
A concern is that there might be a selection bias in this study. If the patients that
underwent biopsy were selected based on a positive serological test, then there
is a selection bias. This should be discussed.
Discretionary
There is a recently published report on the combination of tests for celiac disase:
Vermeersch P, Geboes K, Mariën G, Hoffman I, Hiele M, Bossuyt X. Serological
diagnosis of celiac disease: comparative analysis of different strategies. Clin
Chim Acta. 2012;413:1761-7
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no financial conflicts of interest.
Review for 10.1186/1471-230X-13-19 (2013)

Reviewer's report
Title:Intestinal biopsy to diagnose celiac disease is not always required:
Importance of combined antibody tests
Version: 3Date:1 December 2012
Reviewer: Jocelyn Silvester
Reviewer's report:
The authors have responded to most concerns raised during previous review.
However, concerns regarding the limited generalisability of definition of cutoffs
within the population studied without validation in a separate population have not
been addressed in the discussion nor have the analyses been presented using
the manufacturer recommended cut-offs for the tests.
In implementing these changes, a description of methods has been added to the
discussion and a description of results has been incorporated in methods.
This paper is substantially similar to that by Vermeersch et al published in Clinica
chem acta in November 2012 (ref 13), with the paper under review including
anti-deamidated gliadin peptide IgA antibodies which were not analysed by
Vermeersch et al. While the methodology of the Vermeersch et al paper has
been cited, its relation to the work presented has not been included in the
discussion.
Major essential revisions
1. Address the use of test cut-offs defined within the study population and the
relationship to generalisability of results and/or include analysis using both the
self-defined and the manufacturer recommended cut-offs for the assays used.
2. Include consideration of the relation between the results in this study and that
reported by Vermeersch et al. In the discussion
3. Ensure that methodology, results and discussion are well-defined and material
is reported in the appropriate section.
Minor essential revisions
1. The reference for methodology for positive and negative likelihood ratios
should be amended as the current reference is inappropriate.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-19 (2013)

Reviewer's report
Title:Intestinal biopsy to diagnose celiac disease is not always required:
Importance of combined antibody tests
Version: 3Date:5 December 2012
Reviewer: Xavier Bossuyt
Reviewer's report:
Minor revision.
In the discussion, the authors could compare the likelihood ratios obtained in
reference 13 with the likelihood ratios obtained in their study. This can be done
for some conditions (e.g. at the level of a single test and the combinations of two
tests).
There are some spelling errors in the text that should be corrected.
Review for 10.1186/1471-230X-13-18 (2013)

Reviewer's report
Title:Physiologic and Laboratory Correlates of Depression, Anxiety, and Poor
Sleep in Liver Cirrhosis
Version: 2Date:17 June 2012
Reviewer: Grace Wong
Reviewer's report:
This study demonstrated some interesting phenomenon concerning the
relationship between the psychological and physiological aspects among cirrhotic
patients. The sample size was reasonable.
Major Compulsory Revisions
1. The investigators had done a lot of work, but there was only about one page in
the Result section. I am sure the authors may make more good use of their work
and observation. I would suggest some sub-sections under the Result part, e.g.
Patients, Psychological analysis, Heart rate variability, Correlation between
psychological and physiological parameters etc. Under each sub-section the
authors may describe more in details about their findings.
2. I think the important and novel findings of this study was not well illustrated in
Table 1 and 2. Instead of comparing patients of different CP class, it may be
better to compare patients with or without psychological distress.
3. If AST was correlated with psychological distress, how about ALT? Why there
was a difference between these two markers?
4. As the authors concluded that AST is an important mediator of inflammatory
process which was found correlated with psychological distress, was this
postulation supported by the similar correlation between necroinflammation and
psychological distress? How many patients had liver biopsy done? What were
the results of liver biopsy, in particulars the necroinflammation index.
Minor Essential Revisions
1. This is a relatively short paper, but surprising the number of reference is as so
high (63 references in total). It would be more appropriate to select
representative papers as references, such as 1 or 2 references from [4-8], [9-16],
[17-24], [25-29] etc.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-18 (2013)

Reviewer's report
Title:Physiologic and Laboratory Correlates of Depression, Anxiety, and Poor
Sleep in Liver Cirrhosis
Version: 2Date:8 August 2012
Reviewer: Charmaine Stewart
Reviewer's report:
The aims of the study were not well stated.
The clinical relevance has not been demonstrated by the study.
Major Revisions: Please identify the questions that are being addressed by this
study and the end-points. Better defined population, were these patients
hospitalized or were they inpatients; did they have renal insufficency?
The authors found ST elevation to be significantly correlated with HAMD and
PSQI scores and concluded that AST was a marker of direct liver damage and
psychological stress. This conclusion is difficult to reach with such limited data.
Furthermore, the patients with Child class C had significantly higher bilirubin
levels raising the possibility of acute on chronic liver disease, a stressful
physiological state that could result in more profound hyperdynamic circulation
and hence a higher heart rate.
The clinical relevance of the findings are minimal.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-13-18 (2013)

Reviewer's report
Title:Physiologic and Laboratory Correlates of Depression, Anxiety, and Poor
Sleep in Liver Cirrhosis
Version: 3Date:19 September 2012
Reviewer: Grace Wong
Reviewer's report:
I greatly appreciate the effort of authors on improving the manuscript. I believe it
is now ready for publication.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-17 (2013)

Reviewer's report
Title:Co-culture of primary human tumor hepatocytes from patients with
hepatocellular carcinoma with autologous peripheral blood mononuclear cells:
Study of their in vitro immunological interactions.
Version: 1Date:3 August 2012
Reviewer: Frank Tacke
Reviewer's report:
This manuscript describes the culture of primary parenchymal cells from normal
human liver and HCC specimens. Furthermore, the authors conducted
co-cultures with autologous PBMCs.
1. Although I acknowledge the technical value of the culture of primary
parenchymal human liver cells, I believe the work is preliminary at present. The
FACS plots are not convincing at all, and the MHC-II expression of the
“hepatocytes” indicates that there might be “contamination” by other cells. The
authors only mention negative staining for CD14 or CD3, but this should be
shown. The quality of the presented FACS data is rather poor (likely due to the
low numbers of cells retrieved from human tissue), but this makes the data
difficult to interpret. I think it is important to show that (a) no cell doublets were
measured (FSC-W), and (b) all “hepatocytes” stain negative for CD45
(leukocytes), endothelial and HSC markers. Furthermore, immunohistochemistry
for typical KC and HSC markers (e.g., CD68, decorin) should be performed.
2. The co-culture experiments are, to my opinion, difficult to interpret. The
co-staining of CD8 and HLA-DR is not convincing, because the compensation
appears not appropriate. How should CD8+ cells and hepatocytes/HCC cells
“communicate”? Why do both populations upregulate MHC-II? I strongly doubt
that these observations are truly relevant. More functional assays would be
needed to confirm that these observations are not artefacts, but related to
pathogenically relevant mechanisms.
3. Co-cultures of hepatocytes / tumor cells with defined immune cell
subpopulations (e.g., isolated by MACS) are needed to identify and delineate the
interactions.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.