JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-13-175 (2013)

Reviewer's report
Title:Abnormal fecal microbiota community and functions in patients with
hepatitis B liver cirrhosis as revealed by a metagenomic approach
Version:4Date:11 December 2013
Reviewer: Isabella Inden
Reviewer's report:
Major compulsatory revisions
1. There is no correlation between the different viral load and the and microbiota
community and functions, but there is a correlation between patient and control
group. The definition of the control group is only done by HBV-DNA and cirrhosis
yes or no. Anti-HBc is completly ignored.
2. The relevance of the article and for the management is still poor- if there is no
difference in microbiota community between the different cirrhotic causes, so the
importance of the results are still circumstantial.
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.
Review for 10.1186/1471-230X-13-173 (2013)

Reviewer's report
Title:Correlation between the methylation of SULF2 and WRN promoter and the
irinotecan chemosensitivity in gastric cancer
Version: 3Date:16 June 2013
Reviewer: Gyeong Hoon Kang
Reviewer's report:
The authors analyzed 102 gastric cancer tissue samples for their methylation
status in SULF2 and WRN and correlated with drug sensitivity using histoculture
drug response assay. Specific comments are as follows.
Major compulsatory revisions
1. The authors did not perform the MethyLight technology which utilizes an
oligonucleotide probe with fluorescence reporter dye and quencher dye. The
authors performed SYBR Green methylation-specific PCR (MSP) but did not
quantify SULF2 and WRN methylation levels. The authors should have
performed quantitative analysis of WRN or SULF2 methylation, using MethyLight,
pyrosequencing, or COBRA. MSP is inconsistent in detection of low level of
methylation and the presence of methylation by MSP does not tell us whether
50% of tumor DNA alleles are methylated or 0.1% of tumor DNA alleles are
methylated. With 0.1% methylation, we cannot expect methylation-associated
inactivation of gene expression in all tumor cells.
2. The authors demonstrated that there was an increase in the inhibition rate in
association with SULF2 methylation or both SULF2 and WRN methylation.
However, it cannot be excluded that the increased response may not be specific
to CPT-11. Thus, the authors should perform HDRA with other chemotherapeutic
drugs, e.g. 5-FU or oxaliplatin.
Minor Essential Revisions
1. It cannot be accepted that gastric cancer has an overall 5 year survival of 10%
(the first paragraph of “Introdcution” section). If this corresponds to China, please
provide references.
2. And it might be not true that gastric cancer is the fourth most common cancer
in Japan (the first paragraph of “Introdcution” section).
Discretionary Revisions
1. It would be better if the authors perform RT-PCR for SULF2 and WRN and
correlate expression of the gene with methylation status.
2. Please add a brief, general description of the study subjects at the beginning
of the results section: Distribution of sex, age and tumor location (antral, body,
upper third), etc.
3. “#2 test was used to assess the association between methylation and patient
characteristics” should be moved from “Results” section to “Data analysis”
paragraph.
4. It would be better for the authors to provide percentage values after number of
cases in parenthesis throughout Table 1.
5. The authors should give percentage values of the inhibition rates for SULF2
and WRN methylation and unmethylation groups.
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-13-173 (2013)

Reviewer's report
Title:Correlation between the methylation of SULF2 and WRN promoter and the
irinotecan chemosensitivity in gastric cancer
Version: 4Date:20 September 2013
Reviewer: Gyeong Hoon Kang
Reviewer's report:
Minor Essential Revisions.
1. Why did the authors use 1997 AJCC staging rather than 2003 AJCC staging
for the gastrectomy samples which were from 2009 to 2011?
2. The authors should delete "MethyLight" in the sentence "The
fluorescence-based real-time PCR assay, MethyLight, was used in the detection
of methylated DNA." becuase the authors did not perform the MethyLight
technology.
Level of interest: An article of importance in its field
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-13-173 (2013)

Reviewer's report
Title:Correlation between the methylation of SULF2 and WRN promoter and the
irinotecan chemosensitivity in gastric cancer
Version: 4Date:23 September 2013
Reviewer: Mathewos Tessema
Reviewer's report:
The revised manuscript addressed most of the comments raised in the previous
review. However, despite the authors’ best effort, the manuscript remains poorly
written. Also, a critical experiment that was recommended to significantly improve
the conclusion and impact of the manuscript is left as a future plan. Thus, I
recommend the following before it is considered for publication.
1. Evaluate expression of ISG15, compare its level between sensitive and
resistant groups, and discussion the results in comparison with previous studies.
2. Use professional help to improve the language.
3. New figure 3 is taken without any modification from a published article. Since
the paper is already cited, its inclusion seems unnecessary and may require
permission from the previous publisher.
Level of interest: An article of importance in its field
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-13-171 (2013)

Reviewer's report
Title:A retrospective study of acute pancreatitis in patients with hemorrhagic
fever with renal syndrome
Version: 2Date:1 May 2013
Reviewer: SUDEEP KHANNA
Reviewer's report:
English needs some revision
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-13-171 (2013)

Reviewer's report
Title:A retrospective study of acute pancreatitis in patients with hemorrhagic
fever with renal syndrome
Version: 2Date:13 May 2013
Reviewer: Rakesh Kochhar
Reviewer's report:
Major compulsory revisions
The authors describe 6 patients of henorrhagic fever with renal failure who were
deemed to have acute pancreatitis.I am not sure they have made a case for
cause and effect . Even the diagnosis of pancreatitis was questionable in 2
patients with normal enzymes (pain, per se is a common occurrence in HFRF).
Secondly they have not excluded other causes of pancreatitis. There is no
description of alcohol intake or offending drugs. One patient atleast, had gall
stones.
Thirdly autopsy studies with demonstration of the offending agent would actually
clinch the issue. I admit that is not an easy thing to do.
Why can not the 6 patients be having vascular congestion in pancreas as well in
conjunction with other organs. Aren't the authors reading too much in the edema
of the gland ?
Lastly the report conveys a mistaken idea that these patients need to be treated
FOR pancreatitis. I believe the treatment of patients with or wyhout elevated
amylase/lipase will remain the same.
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 declare that I have no competing interests.
Review for 10.1186/1471-230X-13-171 (2013)

Reviewer's report
Title:A retrospective study of acute pancreatitis in patients with hemorrhagic
fever with renal syndrome
Version: 3Date:1 October 2013
Reviewer: Rakesh Kochhar
Reviewer's report:
Major comments: The authors have explained that other etiologies of acute
pancreatitis were excluded. And they argue that presence of pain and imaging
findings despite normal enzymes are good enough to diagnose acute
pancreatitis. One could debate that; though. the authors should discuss this fact
(normal enzymes) in their discussion.
They also need to suggest the possible pathogenesis of acute pancreatitis in the
viral hemorrhagic fever. And discuss why should occurrence of pancreatitis in
their patients be linked to Hanta virus.
The conclusion of " In addition, when HFRS patients present with abdominal
pain, pancreatic enzyme levels should be detected and imaging analyses should
be conducted to assess the function and morphology of the pancreas to detect
the complications of AP " needs to be modified becauase one cannot say that all
patients of abdominal pain(65%) with Hanta virus infection should have a CT
scan. And they should also discuss the implications of diagnosing AP in the
hemorrhagic fever patients.
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.
Review for 10.1186/1471-230X-13-172 (2013)

Reviewer's report
Title:Allopurinol use in pregnancy in three women with inflammatory bowel
disease: safety and outcomes: a case series.
Version: 1Date:13 August 2013
Reviewer: Nanne K de Boer
Reviewer's report:
Major revisions:
NONE
Minor revisions:
1. The largest series of cases describing allopurinol during pregnancy has been
published this year, this important paper must be discussed (Hoeltzenbein, PLOS
one 2013), given its message.
2. The second autoimmune disease, next to IBD, in which allopurinol and
low-dose thiopurines has been used is autoimmune hepatitis. Perhaps the
authors can mention this in their manuscript, just to be complete.
3. Patient 2 displays a normal TPMT activity and has low/normal 6TGN and
6MMP levels (when looking at the ratio it is elevated), but was this patient not
underdosed? Why not increase the dosage first? Perhaps the authors can
explain.
4. May I suggest to outline in the discussion part, how (dedicated) physicians
should monitor their pregnant patients during pregnancy? Should the newborn be
checked for possible toxicity? A practical advice for the clinician!
5. The most important message from the Jharap-paper (Gut 2013) was that the
unborn child was exposed intrauterine to the pharmacologically active 6TGN
metabolite, possibly explaing the high rate of anemia in the newborns (and low
platelets). Perhaps the authors can comment on this, taking in account the
alteration in thiopurine metabolism by adding allopurinol.
6. The landmark paper on the clinical use of allopurinol-thiopurine combination is
written by Chocair (Lancet 1993), this paper should be mentioned.
7. There are quite a lot of review/meta-analysis being used as references, may I
suggest to provide original papers and for example the ECCO statement on this
topic.
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-13-172 (2013)

Reviewer's report
Title:Allopurinol use in pregnancy in three women with inflammatory bowel
disease: safety and outcomes: a case series.
Version: 1Date:25 August 2013
Reviewer: John K Triantafillidis
Reviewer's report:
MINOR ESSENTIAL REVISIONS
Allopurinol and azathioprine have been categorized by the FDA as C and D
respectively. Therefore, even though the risk (at least for azathioprine) seems
minimal, combination use of these drugs in pregnant women with IBD must be
applied only after full explanation of the possible risks and benefits. This must be
repeatedly emphasized in the text.
We also suggest that authors should mention the results of a recent description
(Hoeltzenbein M, Stieler K, Panse M, Wacker E, Schaefer C. Allopurinol Use
during Pregnancy - Outcome of 31 Prospectively Ascertained Cases and a
Phenotype Possibly Indicative for Teratogenicity. PLoS One. 2013 Jun
19;8(6):e66637. Print 2013.) According to this, among 31 prospectively
ascertained pregnancies with allopurinol exposure there was one child with
severe malformations. The authors recommend caution with allopurinol treatment
in the first trimester, until further data are available.
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-13-172 (2013)

Reviewer's report
Title:Allopurinol use in pregnancy in three women with inflammatory bowel
disease: safety and outcomes: a case series.
Version:2Date:31 October 2013
Reviewer: Nanne K de Boer
Reviewer's report:
I have no additional remarks.
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-13-170 (2013)

Reviewer's report
Title:Validation of intraluminal and intraperitoneal microdialysis in ischemic small
intestine - Clinical feasibility of equilibration dialysis.
Version: 1Date:29 May 2013
Reviewer: Erik Solligard
Reviewer's report:
The role of the intestine in organ failure is a interesting field of research. To
detect intestinal hypoperfusion is difficult, and the development of useful tools for
monitoring the intestine is important. Microdialysis may be such a tool, and one
question being asked for several years is should one monitor inside or outside of
the intestinal lumen.The aim and background of the study comparing the luminal
vs the serosal side of the intestine is relevant and appropriate. As they state,
there are plentuful of experimental studies, but scarse with clinical studies.
But, I'm more reluctant to the second aim of the study, at least how it is
presented in this manuscript; "a pilot material with peri- and post-operative
monitoring of the intestinal region with equilibration dialysis".
Major Compulsory revisions
The equilibration dialysis part of the paper is interesting. The method is described
earlier, and several studies has been performed. But in this paper this section is
not well designed, nor well written.
The principle of the method is not described, the placement of the sacs are not
possible to reproduce based on your description, and you do not describe the
method of colection of the samples etc. The number of patients is small.
The study is not designed to answer your questions about the usefullness of this
method in clinical monitoring.
My request is to take out this topic from the paper, redesign the study and
publish as a separate paper.
Minor Essential Revisions
The total gut ischemia model ex vivo is not well described in the methods
section. Please describe the surgical methods in brief, the handling of the
intestinal specimen, placement of the probes etc. An illustration could do good. in
the Microdialysis - ex vivo validation, you only describe the technical parts om the
technique. What about recovery?
Discretionary revisions
Did you use the best ten minute fraction in each interval or did you make any
mean values of the whole interval? Please describe.
Table 1; what is "n"? It is not readable.
Figure 2 is then not relevant.
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-13-170 (2013)

Reviewer's report
Title:Validation of intraluminal and intraperitoneal microdialysis in ischemic small
intestine
Version:2Date:28 November 2013
Reviewer: Norbert Cibicek
Reviewer's report:
My comments were summarized in the previous report. Almost all of them were
addressed by the authors, many (but not all) of them in a satisfactory (or correct)
manner and contributed to the increased quality of the paper.
To account for and defend my positions in detail in the rest of the comments and
pointing out all the remaining imperfections found in the present manuscript
would be inadequately time consuming. I know it is details, but nevertheless
wonder why the authors did not take the time to correct all minor spelling errors
(e.g. "spesificity" or "charasteristics") in the tables and/or captions.
I must, however, answer one question posed by the authors regarding data
interpretation. As a clinical biochemist whose primary focus is on clinical data
interpretation, I was not arguing against the difference in the trends observed in
the L/P and L/G ratios (I think I am quite aware of the biochemistry of these
simple metabolites) but rather their variability... Regarding the "specificity" of
glycerol - I was just citing their own article. Glycerol can by no means be
considered a "specific indicator of gut epithelial damage", even though it was
documented to correlate with cell damage in a number of papers. For example,
serum AST is routinely used as an indicator of (and in numerous studies also
correlates with) hepatal tissue damage, but cannot be considered a
"liver-specific" indicator, since it is found in many other tissues including skeletal
or cardiac muscle and its increased serum catalytic concentration can be
observed even following sample haemolysis. Compare this issue with e.g.
oncomarkers on one hand and e.g. cardiac troponine on the other.
Such argumentation and explanation of individual points could go on and on...
Since my previous comments will be published along with the article, I can see
no point in continuing a lengthy discussion and will now opt for publishing the
article. The authors may (and will) get the important feedback by the peers in the
field.
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-13-170 (2013)

Reviewer's report
Title:Validation of intraluminal and intraperitoneal microdialysis in ischemic small
intestine
Version:2Date:2 December 2013
Reviewer: Erik Solligard
Reviewer's report:
Dear Editor
I find the authors answers and changes in the manuscript in very good
accordance with the proposed changes, so I will recomend this paper for
publication in its present form.
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-13-168 (2013)

Reviewer's report
Title:Autoimmune Pancreatitis - A Comparative Description Highlighting North
American Experiences In Diagnosis And Management
Version: 1Date:13 December 2012
Reviewer: Terumi Kamisawa
Reviewer's report:
Similar papers about AIP have been published already. However, this study
appears to be important as there are few reports about AIP from Canada.
There is a major issue in Methods of this study.
Major compulsory revisions:
As international consensus diagnostic criteria for AIP are pulished, comparison of
old diagnostic criteria is not necessary. The materials should be focused on
patients diagnosed as Type 1 and type 2 AIP according to international criteria.
If authors want to analyze patients with only IgG4-related sclerosing cholangitis,
they should use diagnostic criteria of IgG4-related sclerosing cholangitis (JHPBS
2012).
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-13-168 (2013)

Reviewer's report
Title:Autoimmune Pancreatitis - A Comparative Description Highlighting North
American Experiences In Diagnosis And Management
Version: 1Date:17 December 2012
Reviewer: Myung-Hwan Kim
Reviewer's report:
1. The authors performed a study to review presentation and outcomes of
patients with AIP, and to report the applicability of diagnostic criteria in Canadian
patients.
First of all, there is no new discovery about AIP patients except they are
Canadian patients. Regarding AIP patients in North America, many studies have
already been published from Mayo, MGH, Pittsburgh, and so on. A simple report
of clinical features from one center may contribute minimally to current
knowledge. There are already many studies from a variety of nations, and even
international multicenter study exists (Pancreas 2011;46:809).
2. Regarding applicability of diagnostic criteria, it was already reported from
North American population by Pittsburgh group (Am J Gastroenterogy
2009;104:2295). Moreover, revised HISORt criteria (2009) and international
consensus criteria for AIP (2011) were already published. In this study, the
authors only used HISORt (2006), Japan Pancreas Society (2006), Korean
(2007) Criteria.
3. I’m not sure that all patients included for this study are really AIP because their
proportion of positive response to steroid therapy is too low, when compared with
reported response rate (>95%). Especially, their patient with PSC and elevated
IgG4 (Table 3) should be differentiated from IgG4-related sclerosing cholangitis.
Only elevation of serum IgG4 cannot diagnose IgG4-related sclerosing
cholangitis (Gastroenterology 2008;134:706).
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-13-168 (2013)

Reviewer's report
Title:Autoimmune Pancreatitis - A Comparative Description Highlighting North
American Experiences In Diagnosis And Management
Version: 1Date:17 December 2012
Reviewer: Raffaele Pezzilli
Reviewer's report:
The authors aimed to compare the various proposed criteria in assessing the
diagnosis of autoimmune pancreatitis. We should thank the authors for their
efforts but we have some concerns.
1. The study is retrospective and many clinical features in some patients have
been missed to definitively assess the diagnosis of autoimmune pancreatitis.
2. A number of patients were treated with steroids without a histological
diagnosis and this may explain why the Korean criteria has a sensitivity better
than the others criteria.
3. The authors should include in their comparative analysis also the new criteria
for the diagnosis of autoimmune pancreatitis Shimosegawa T, Chari ST, Frulloni
L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Klöppel G, Lerch MM, Löhr
M, Notohara K, Okazaki K, Schneider A, Zhang L; International Association of
Pancreatology. International consensus diagnostic criteria for autoimmune
pancreatitis: guidelines of the International Association of Pancreatology.
Pancreas. 2011 Apr;40(3):352-8.
4. The statistical analysis is poor and a appropriate statistic should be added in
comparing the various criteria utilized for assessing the diagnosis of autoimmune
pancreatitis.
5. There are many percentages that have been missed: For example, on page 8
“Pre-treatment serology” “36/55 patients had serum IgG4 levels accessible to our
review.” the percentage should be added (65.5%).
6. Please do not initiate the period with arabical number.
Level of interest: An article of limited interest
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-13-168 (2013)

Reviewer's report
Title:IgG4 Related Disease - A Retrospective Descriptive Study Highlighting
Canadian Experiences In Diagnosis And Management
Version: 2Date:16 February 2013
Reviewer: Raffaele Pezzilli
Reviewer's report:
I have no further comments
Level of interest: An article of limited interest
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-13-168 (2013)

Reviewer's report
Title:IgG4 Related Disease - A Retrospective Descriptive Study Highlighting
Canadian Experiences In Diagnosis And Management
Version: 2Date:16 February 2013
Reviewer: Siddharth Singh
Reviewer's report:
Discretionary Revisions:
Several key concerns raised by this reviewer have been acknowledged and/or
addressed. However, the discussion continues to be superficial and not very
helpful for the community gastroenterologist:
- The key findings of this descriptive study should be compared and contrasted to
current findings in the literature. For example, why do the authors feel the
response to corticosteroids was poor in this series?
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-13-168 (2013)

Reviewer's report
Title:IgG4 Related Disease - A Retrospective Descriptive Study Highlighting
Canadian Experiences In Diagnosis And Management
Version: 2Date:21 February 2013
Reviewer: Terumi Kamisawa
Reviewer's report:
Regrettably, The authors could not revise the manuscript according to reviewers'
comments.
Review for 10.1186/1471-230X-13-168 (2013)

Reviewer's report
Title:IgG4 Related Disease - A Retrospective Descriptive Study Highlighting
Canadian Experiences In Diagnosis And Management
Version: 2Date:4 March 2013
Reviewer: Myung-Hwan Kim
Reviewer's report:
The revision is improved. The authors satisfactorily replied to my questions.
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-13-169 (2013)

Reviewer's report
Title:Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in
mice
Version: 1Date:18 February 2013
Reviewer: Manlio Vinciguerra
Reviewer's report:
The paper "Role of serotonin in fatt acid-induced non-alcoholic fatty liver disease
in mice" by Ritze et al. demonstrates that a diet rich in saturated or
monounsaturated fatty acids promote NAFLD in mice, through a dysfunction of
the intestinal permeability and of therein serotonin system.
The manuscript, although not very innovative, is well designed and data are
convincing. However it suffers of several pitfalls that need to be addressed.
Revisions
1) the authors talk recurrently of "energy consumption"? However, it looks like
that in their studies they measured food intake, which is the correct expression.
How this was measured? Energy consumption in the differently FA-fed groups
should be assessed with the aid of metabolic cages. It is possible that although
food consumption is the same, energy expenditure varies, and this has an effect
on NAFLD. Similarly, what is the weight of these mice, and the liver weight to
body weight ratio? These would be very interesting data.
2) Line 65. A reference is missing.
3) Line 75. Define better the "translocation hypothesis"
4) 5-HT has a well defined role in hepatic stellate cells (HSC) activation and
fibrosis. Do the authors observe some different degree of fibrosis in their 3
experimental dietary groups. Please discuss the role of 5-HT on HSC function in
the models presented.
5) References 21 and 22 are somewhat old and published on minor Journals. Do
the authors have better references.
6) histologies in Figure 1: the control panel has a background staining completely
different than the experimental conditions. It is odd and it should be changed with
a better image.
7) A western blot for MyD88 would be required to support Fig. 2B
8) Figure 2F is not commented. When something is shown in a Figure, it should
be commented.
9) Line 180. Define SERT.
10) Line 195. Reference 28 has nothing to do to what it is described (intestinal
permeability , gut endotoxin).
11) Line 198. Show the data not shown.
12) Line 200 and 201. Show the data not shown.
13) Line 216. "...unclear". This statement could be better supported with a recent
reference. For instance: PMID: 22658146.
14) Line 224. When comparing their study to the published [31] one, it would be
useful to state quantitatively in what the different PUFA that was intaken by the
animals consisted of (% of energy from which nutrient, FA etc).
15) Line 272. Substitute "to be published" with "of the manuscript".
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-13-169 (2013)

Reviewer's report
Title:Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in
mice
Version: 4Date:15 August 2013
Reviewer: Manlio Vinciguerra
Reviewer's report:
None.
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-13-169 (2013)

Reviewer's report
Title:Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in
mice
Version: 4Date:19 August 2013
Reviewer: Bernhard Watzl
Reviewer's report:
The revised version has improved significantly and the authors have addressed
most of the reviewer's comments.
Some points still could be improved.
Lines 106 ff: Please indicate how many mice were used for the second
experiment.
Line 153: "...receiving a 6% fat diet". This is not in line with the information given
in Table 1 (11 %).
Lines 154-155: "...the means of the combined high-fat groups were calculated". I
do not think that this is correct because it ignores a potential impact of the fat
quality.
Line 168: "...fat quality had a pronounced effect" (see above).
Line 156ff: I still think that a two-way ANOVA would be correct. Is the outcome of
the analysis different between a one-way and a two-way ANOVA?
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.
Review for 10.1186/1471-230X-13-169 (2013)

Reviewer's report
Title:Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in
mice
Version:5Date:14 November 2013
Reviewer: Bernhard Watzl
Reviewer's report:
no further comment
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-13-165 (2013)

Reviewer's report
Title:Effects of Interleukin-4 or Interleukin-10 Gene Therapy on
Trinitrobenzenesulfonic Acid-Induced Mouse Colitis
Version: 1Date:18 July 2013
Reviewer: Chien-Yun Hsiang
Reviewer's report:
This manuscript reports the effects of IL-4 or IL-10 gene therapy on
TNBS-induced mouse colitis. Authors find that intraperitoneal injection of plasmid
DNA carrying IL-4 or IL-10 gene is useful in the control of TNBS-induced murine
colitis. However, their combination has less effect on the TNBS-induced colitis.
Finding a way to control IBD is an important issue. This work suggests the
potential usage of IL-4 or IL-10 on the improvement of TNBS-induced colitis.
However, there are some questions needed to be addressed.
1. There are many studies reporting the usage of IL-4 or IL-10 protein on the
treatment of TNBS-induced colitis. Therefore, authors should emphasize the
novelity of this manuscript.
2. The effects of IL-4 or IL-10 on the improvement of TNBS-induced colitis are
controversial. Some reports show that administration of these cytokines is
effective but others don't. The detail mechanisms of IL-4 or IL-10 on the colitis
should be further analyzed.
3. Authors find that combination of IL-4 and IL-10 has less effect on colitis.
Recent study reports that IL-4 induces a suppressive IL-10-producing CD8+ T
cell population. Authors should further elucidate why combinatory therapy shows
less effect.
4. In this manuscript, plasmid DNA carrying IL-4 or IL-10 gene is injected
intraperitoneally and RT-PCR data show that IL-4 and IL-10 RNAs are detectable
in the colon. How do these plasmid DNAs be delivered to colon, uptaken by
colon cells, and expressed in colon? What kinds of cells in the colon are
responsible for the expression of exogenous IL-4 or IL-10 gene? Authors should
elucidate the kinds of cells expressing IL-4 or IL-10 by IHC or other assays.
Additionally, the delivery of plasmid DNA to colon is another question needed to
be analyzed.
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-13-165 (2013)

Reviewer's report
Title:Effects of Interleukin-4 or Interleukin-10 Gene Therapy on
Trinitrobenzenesulfonic Acid-Induced Murine Colitis
Version: 2Date:16 October 2013
Reviewer: Fermin Sanchez de Medina
Reviewer's report:
The inclusion of the new data requested and the toning down of claims about the
combinaiton data have improved the manuscript in my opinion.
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-13-165 (2013)

Reviewer's report
Title:Effects of Interleukin-4 or Interleukin-10 Gene Therapy on
Trinitrobenzenesulfonic Acid-Induced Murine Colitis
Version:2Date:29 October 2013
Reviewer: Chien-Yun Hsiang
Reviewer's report:
Authors have revised the manuscript according to reviewers' comments.
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-13-166 (2013)

Reviewer's report
Title:A nationwide population-based study of the inflammatory bowel diseases
between 1998 and 2008 in Taiwan
Version: 1Date:25 August 2013
Reviewer: Siew Ng
Reviewer's report:
By using a nationwide registration system in Taiwan, the authors have shown the
incidence and prevalence of IBD in Taiwan and further demonstrated a rise in
incidence and prevalence from 1998 to 2008. These are one of the first few data
nationwide emerging from Taiwan and showed consistent trend with that of
studies from Korea, Japan and Hong Kong. Unlike in the West, there are very
few countries in Asia with the exception of Japan and Taiwan that have
nationwide registry system. These data are important and will contribute to our
knowledge on the epidemiology of IBD in Asia, which until recently have been
lacking.
Major Compulsory Revisions
None
Minor Essential Revisions
Although their data are timely, the paper will carry more weight if they were to
discuss their data in context of the recently published large scale
population-based epidemiologic study across nine countries in Asia-Pacific
showing geographic variability in disease incidence even within Asia (Ng et al.
Gastroenterology 2013). Taiwan appeared to have disease incidence that is
lower than Hong Kong, some parts of Mainland China, and Macau, relatively
similar to that of Malaysia and Sri Lanka, but higher than that of Thailand and
Indonesia. One may speculate that different degree of
urbanization/socioeconomic status may play a part to the variation. UC is also
more common in Taiwan.
I think it would be worth discussing the magnitude of this incomplete capture, ie
the true patient load versus registered patient number, is there anyway of having
an estimation of the proportion not registered relative to this study.
Do the data represent crude annual incidence or age-standardized incidence
based on WHO criteria?
Are disease phenotypes captured within the registry – it would be interesting to
compare disease behaviour and severity with other Asian countries and the
West. Especially since the authors have shown a higher standardized mortality
rate compared with the general population for Crohn’s disease and the
West/Japan. It is useful to speculate more on what could be the potential cause,
eg patients with co-morbidities and older age have increased mortality.
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-13-166 (2013)

Reviewer's report
Title:A nationwide population-based study of the inflammatory bowel diseases
between 1998 and 2008 in Taiwan
Version:1Date:18 October 2013
Reviewer: Parakkal Deepak
Reviewer's report:
This is a well written manuscript that highlights an important epidemiological
phenomenon of increasing incidence and prevalence of IBD in Asia in a
population level study. The authors have also made a good attempt at comparing
their findings to what’s known in contemporary literature.
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.
Declaration of competing interests:
None
Review for 10.1186/1471-230X-13-164 (2013)

Reviewer's report
Title:Low Helicobacter pylori primary resistance to clarithromycin in gastric
biopsy specimens from dyspeptic patients of a city in the interior of Sao Paulo,
Brazil
Version: 1Date:3 October 2013
Reviewer: Guillermo Ignacio Perez-Perez
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:
No conflict of interest
Review for 10.1186/1471-230X-13-167 (2013)

Reviewer's report
Title:Combination therapy of infliximab and thalidomide for refractory
entero-Behcet's disease: a case report
Version: 3Date:6 October 2013
Reviewer: Harry Xia Xia
Reviewer's report:
This case report presents a case with refractory entero-Behcet’s disease which
was successfully treated with combination of infliximab and thalidomide. The
report adds new knowledge or experience in the management of the disease.
The manuscript is generally fairly written; some minor modifications are needed.
Minor Essential comments:
1. Abstract: Case presentation needs to be more detailed. For example, the
demographic and clinical information should be described. The term
“gastrointestinal Behcet’s disease” needs to be mentioned in the main text, and
may be removed in the Abstract, even if defined in the main text.
2. Introduction: Specific data and supporting references should be provided for
“along the ancient Silk Route”, and “with severe morbidity and considerable
mortality”. Suggest moving and incorporating the data and references described
in the Discussion to the Introduction.
3. Case presentation”: You mentioned in one place that “PET/CT found multiple
and flake concentration around the jejunum and ileum”, but later that “PET/CT
did not reveal abnormal concentrations nor increased metabolism, ….”. This is
unclear to me. Please clarify.
4. Table 1 actually is a figure.
5. Discussion should focus on the diagnosis and treatment of the disease, based
on your successful case, such as lesions to be learnt, experience to be shared
and recommendation.
6. Use abbreviations correctly. No abbreviations are needed for those terms that
are not to be used later in the main text.
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-13-167 (2013)

Reviewer's report
Title:Combination therapy of infliximab and thalidomide for refractory
entero-Behcet's disease: a case report
Version: 3Date:6 October 2013
Reviewer: Antonio Di Sabatino
Reviewer's report:
In this paper the Authors describe the case of a 23-year-old male patient affected
by recurrent abdominal pain, who underwent both gastroscopy and double
balloon enteroscopy which revealed duodenal and jejunal ulcers. On the basis of
endoscopic and clinical features (abdominal symptoms associated to recurrent
oral and genital ulcers) the patient was diagnosed as affected by Behcet’s
disease and treated with a combination of two TNF-alpha inhibitors, i.e.
thalidomide and infliximab, with clinical and endoscopic improvement. The
authors conclude that combination therapy with thalidomide and infliximab seems
to be effective in refractory entero-Behcet’s disease.
The description of the case suffers from a number of limitations. My major
concern regards the diagnosis, since on the basis of jejunal ulcers refractory
celiac disease and ulcerative jejunoileitis should have been excluded. Indeed,
celiac antibodies, such as anti-transglutaminase and anti-endomysial, have not
been included among the serum antibody panel, and there is no histologic
information concerning the degree of villous flattening and intraepithelial
lymphocyte infiltration both at duodenal and jejunal level. Based on the
localization of intestinal ulcers (jejunum) the esclusion of celiac disease and its
complications is mandatory, as Behcet’s ulcers are mainly located in the
ileocecal tract. Moreover, though rare, the association of Behcet’s disease and
celiac disease has been already reported in literature. The clinical improvement
observed could be explained by the fact that refractory celiac disease has been
shown to respond to anti-TNF treatment.
Minor points:
- Page 5, line 11: How “the possibility of intestinal lymphoma was excluded”? No
investigation have been done to esclude an enteropathy-associated T-cell
lymphoma (entero-TC or entero-RM).
- Page 6, line 7: The use of CDAI does not make sense in this case. It is even
low appropriate to assess efficacy of anti-TNFs in Crohn’s disease (endoscopic
scores evaluating mucosal healing are more accurate).
- The language should be improved.
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-13-162 (2013)

Reviewer's report
Title:Pyoderma gangrenosum in refractory celiac disease: a case report
Version: 1Date:9 September 2013
Reviewer: Gabrio Bassotti
Reviewer's report:
An interesting, well written report. I have only a few questions on this case:
- I wonder whether this refractory CD patients was actually a "refractory" one.
Wasd HLA typing done?
- could be possible that the villous atrophy be due to causes other than CD?
- was the patient using drugs able to mimick hiostological findings of CD?
- further histologuical assessment is needed (for histance, there was evidence of
collagenous bands?)
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-13-162 (2013)

Reviewer's report
Title:Pyoderma gangrenosum in refractory celiac disease: a case report
Version: 1Date:20 September 2013
Reviewer: Jonas Ludvigsson
Reviewer's report:
None.
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-13-162 (2013)

Reviewer's report
Title:Pyoderma gangrenosum in refractory celiac disease: a case report
Version: 1Date:29 September 2013
Reviewer: Francesco Valitutti
Reviewer's report:
In this case report by Sedda et al. a possible coexistence between refractory
celiac disease and pyoderma gangrenosum is described for the first time.
The paper can be accepted when the authors address the following criticisms.
1) since this is a single report, the sentence in the abstract "physicians should be
aware that pyoderma gangrenosum can associate with refractory celiac disease"
is not appropriate: a conclusive association is not sound, albeit the case
described. That sentence can be misleading and should be removed from the
abstract.
2) also in the abstract, the last sentence on the immunological complexity of RCD
versus pyoderma g. sounds too definite despite the paucity of data to support it.
Please remove it.
3) pyoderma gangrenosum should be included among the keywords.
4) in the background (line 5) please remove or rephrase "strictly linked to the
clinical presentation": the meaning is not clear
5) (line 17) "be called into question" should be replaced by "be questioned". The
following “Whether” should be changed with “when”.
6) (line 24) “pathologies” should be changed with “diseases” and “which
associate with” should be changed with “which might be associated to”
7) since RCD is usually a consequence of a long-standing undiagnosed or
non-compliant-to-diet celiac disease, information about dietary compliance from
1993 should be given to the reader in the case presentation
8) In the conclusion (line21) please add “case” to “this is the first (case)”. Also
state more cautiously: “to show a POSSIBLE association”. Please remove from
the conclusions statements on the complexity of the immunological response and
on the awareness of the physicians about this possible association.
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