JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-14-76 (2014)

Reviewer's report
Title:Factors Associated with Mortality Risk for Malignant Colonic Obstruction in
Elderly Patients
Version:2Date:11 February 2014
Reviewer: Preet Paul Singh
Reviewer's report:
The authors have addressed most of the points - but still ignored some others.
These 2 issues remain and should be included in the revised manuscript -
From my previous review:
2. Table 4 - what is p-vale of '0'? Please report actual p-value. Its unclear what is
the
reference category for the multivariate odds ratio? This needs to be clearly
reported.
Also the odds ratio for peritonitis is less than 1 which means having peritonitis is
protective in terms of mortality, which is clearly a mistake.
ANSWER:When pvalue is mentioned as 0, we mean p<0.01. According to the
reviewer’s comment, the odds ratio for peritonitis is less than 1 which means
having
peritonitis is protective in terms of mortality, which is clearly a mistake.Sorry for
our
negligence. We have carefully checked the statistics and we have revised
it.(page 24)
COMMENT -
- p-value has been corrected. OR for peritoninis is now correct.
- reference category for the multivariate odds ratio is still not reported in Table
4B. Please understand that the odds ration means nothing as long as we dont
understand what 2 groups are being compared.
Please address these 2 points as discussed above.
3. As all patients failed conservative management - I do not think "emergent"
surgical
intervention is still correct. Clearly the patients who developed peritonitis went
onto
emergent surgery, but not ones who were otherwise stable and did not have
resolution
of bowel obstruction at 72 hrs. Also what happened to patients who presented
with
signs of peritonitis - were they also conservatively managed or taken directly to
surgery? Patient selection is very confusing. It may be better to say, that this
study
looks at subset of patients who underwent urgent surgery for failure of medical
management of bowel obstruction.
ANSWER:We agree the reviewer’s comment opinion. According to the reviewer’s
comment, we revised it. (page 5).
COMMENT - The authors have changed that on page 5 - but the abstract and
other places in the mansucript, they are still using the term "emergent surgery".
Please make it uniform.
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-14-75 (2014)

Reviewer's report
Title:Antibiotic exposure in pregnancy and risk of coeliac disease in offspring: a
cohort study
Version:1Date:18 December 2013
Reviewer: Umberto Volta
Reviewer's report:
The present study “Antibiotic exposure in pregnancy and risk of celiac disease in
offspring” is a cohort study, aiming to investigate the association between
antibiotic exposure during pregnancy and CD in offspring. Of the 1836 children
exposed to antibiotics during pregnancy, 12 (0.7%) children developed celiac
disease in comparison with 34 (0.5%) of the 6893 unexposed children. The
Authors conclude that no statistically significant association between antibiotic
exposure during pregnancy and CD in offspring was observed.
This is a clear and very simple study with a negative result since the data
produced did not show any causal effect of antibiotic treatment during pregnancy
on the possible development of CD in offspring.
It has been demonstrated that the infant microbiota may play a role in celiac
disease development and it has been also proved that protracted antibiotic
treatment in the first 18 months of life can cause changes of intestinal microbiota
leading to an increased risk for celiac disease. Based on the results of the
present paper, antibiotic treatment during the pregnancy does not cause an
increased risk of CD in offspring.
The Authors underline in the text the limitations of their study. One of the most
important is the lack of information about the duration of antibiotic treatment and
its dosage, which obviously could have a relevant impact on microbiota changes,
so increasing the risk for celiac disease in cases with protracted and high dose
treatment.
I address a couple of questions to the Authors:
1) Did the antibiotic treatment favor an earlier appearance of celiac disease? It
could be of interest for the reader to know if the 12 children exposed to antibiotics
had an earlier onset of celiac disease compared to the 34 unexposed children.
2) Moreover, the Authors should specify if the two groups of subjects developing
celiac disease (those exposed to antibiotics and those unexposed) displayed a
different clinical presentation (classical, non classical, subclinical). It is difficult to
have this information in the cohort studies, but, if available, it should be provided
to the reader.
Level of interest: An article of importance in its field
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 interest
Review for 10.1186/1471-230X-14-75 (2014)

Reviewer's report
Title:Antibiotic exposure in pregnancy and risk of coeliac disease in offspring: a
cohort study
Version:1Date:25 January 2014
Reviewer: Patrizia Brigidi
Reviewer's report:
The paper ³Antibiotic exposure in pregnancy and risk of coeliac disease in
offspring: a cohort study² is an epidemiology-based study, investigating the
possible association between antibiotic exposure during pregnancy and the
coeliac disease onset in offspring.
The manuscript is well written, the aim and the design of the study well
described. Unfortunately, no statistically significant association between antibiotic
treatment in pregnancy and coeliac disease in offspring was found, and therefore
the interest of the results reported is limited. The discussion is rather
long-winded, if we consider the result presented, and it should be shortened.
Review for 10.1186/1471-230X-14-74 (2014)

Reviewer's report
Title:Serum trefoil factor 3 as a promising non-invasive biomarker for gastric
cancer screening: A monocentric cohort study in China
Version:10Date:22 December 2013
Reviewer: Katsunori Iijima
Reviewer's report:
The authors demonstrated the usefulness of serum TFF3 as a promising
biomarker for gastric cancer comparing that of serum pepsinogen, and concluded
that serum TFF3 measurement is a better biomarker of gastric cancer than
serum PG measurement. I admit it is a clinically important issue, but I found the
following concerns.
There have already a few studies to investigate the usefulness of serum TFF3 for
detection for gastric cancer (ref.25, 33). Compared with these previous studies,
the present study comprised much smaller cases with gastric cancer (n=183 or
192 in previous studies vs. n=72 in the present study). Inclusion of a small
number of gastric cancer patients is a major limitation of this study.
I also found that there is a serious problem for the definition of gastric atrophy
with serum PG in the present study. The authors used European assay kit
(GastroPanel) for pepsinogen measurement, but they applied the Japanese
criteria for definition of gastric atrophy (PG I <70 ng/mL and PG I/II ratio < 3.0).
However, two recent paper (Iijima K, et al. Serum biomarker tests in delineation
between patients with gastric atrophy or healthy, normal stomach. World J
Gastroenterol. 2009; 21;15:853-9. & Miki K, et al. Cautious comparison between
East and West is necessary in terms of the serum pepsinogen test. Dig Endosc.
2009;21:134-5) reported that serum PG I values in GastroPanel examination
gave exactly twice as high PG I levels as the Japanese assays, while no
differences occurred between the PG II tests. Correspondingly, the PG I/II ratio in
the GastroPanel examination was exactly twice as high as the ratio in the
Japanese tests. Therefore, the definition of gastric atrophy in the present study
was too strict because it corresponded to PG I <35, PG I/II<1.5 in employing
Japanese assay kit. I think that the maneuver well explained the too low
sensitivity (37.5%) of PG test in this study compared with previous studies using
Japanese assay kit (sensitivity 45%-77%). At the same time, specificity of the PG
test of the present study (81.1%) is relatively high compared with previous study
(68%-87%). I think the Japanese criteria of serum PG should not be applied for
the results obtained with European assay kit. I would like authors to recalculate
their results with proper definition or to discuss this issue as a limitation.
The authors enrolled 61 patients with CAG and 27 patients with CNAG. I would
like to know the details as to how the authors define CAG or CNAG. Are they
histologically defined? Where are biopsies taken? How many biopsies? What
kind of grading scale for the histological assessment?
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.
Review for 10.1186/1471-230X-14-73 (2014)

Reviewer's report
Title:KRAS mutations: variable incidences in a Brazilian cohort of 8,234
metastatic colorectal cancer patients
Version:1Date:17 January 2014
Reviewer: Iris Nagtegaal
Reviewer's report:
The current paper reports on a large number of CRC cases in which the KRAS
mutation status has been determined. This wealth of data adds to the available
literature, however, there are a number of questions and comments:
- in the introduction there is a large paragraph on ER, and relation to CRC. This
is not relevant in the introduction, so a summarised part might be replaced to the
discussion. However, since the manuscript does not investigate ER status I think
this is speculative.
- figure 1 is incomplete
- although there is a significant difference between women and men in the
frequency of KRAS mutation, this difference is rather small.
- in the part about the age distribution the authors discuss all results as if these
are significant, however, this is not the case and I think that it is not realistic to
state that an opposite results is obtained in these cases.
- at least part of the data could be gathered in figures rather than tables, which
would make it easier to see the differences.
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-14-73 (2014)

Reviewer's report
Title:KRAS mutations: variable incidences in a Brazilian cohort of 8,234
metastatic colorectal cancer patients
Version:1Date:1 February 2014
Reviewer: Grazia Palomba
Reviewer's report:
“KRAS mutations: variable incidences in a Brazilian cohort of 8,234 metastatic
colorectal cancer patients”
The aim of the study is to assess the distribution of KRAS mutations in Brazilian
metastatic colorectal cancer patients.
Major Compulsory Revisions
KRAS point mutations are highly prevalent in CRC and mostly occur in codons
12, 13, and 61. The profile of KRAS mutations was analyzed by direct
sequencing of KRAS codons 12 and 13 only. Although not frequently mutated in
CRC (5-6% of cases), codon 61 should have been analyzed (in this large
patients’ collection, more than 400 cases could have been misclassified).
More information about the distribution of mutations, according to additional
clinico-pathological characteristics of CRC patients, should be presented [mainly,
anatomical site of primary tumor (right, transverse, left colon, etc.), disease
stage, tumor grading].
The discussion about the importance of sexual hormones in the risk for CRC
should be more concise. Previous studies have indeed investigated sex-related
differences in the prognostic impact of KRAS and BRAF mutation in CRC. No
significant association was found between KRAS mutations and sex. Further
studies directly focused on the associations of hormonal factors with KRAS
mutation status in CRC are awaited.
Minor Essential Revisions
Methods: why did the authors use the semi-nested PCR for the mutational
analysis?
Results: In the first paragraph of the Results, the last sentence should be
removed (it has been repeated twice the fact that a part of samples was not
analyzed).
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-14-71 (2014)

Reviewer's report
Title:Abdominal Attacks and Treatment in Hereditary Angioedema with
C1-Inhibitor Deficiency
Version:2Date:5 March 2014
Reviewer: Marco Cicardi
Reviewer's report:
The manuscript provides a large amount of detailed data on abdominal attacks in
patients with HAE. There is a huge literature on HAE symptoms, but exclusively
or mostly based on retrospective analysis of data going back several years. The
data of this manuscript were collected within the clinical studies performed for the
development of kalbitor and despite some differences in the study designs; the
information is of high quality and based on objective measurements. Reports
based on specific analysis of subgroups of data derived from the clinical trials
provide new important knowledge. Abdominal attacks have many specific
problems, which are of particular interest for gastroenterologists frequently not
aware of the existence of this condition. Drive attention to these unusual
situations could improve clinical practice. The data in the manuscript are well
organized and described. Shortening the results section leaving part of the data
in tables and figures could improve readability. The part of the discussion that
deals with the diagnosis could be improved as detailed in the specific remarks.
Specific remarks
Discussing the diagnosis the authors state, “once it is suspected it can be
confirmed by laboratory tests” and then they discuss C4. It is not clear to me if
they refer to diagnosis of HAE in a previously not diagnosed patient arriving with
abdominal pain, or if they refer to the reduction of C4 as sign of an ongoing
attack for a patient who already has the diagnosis. Both problems are difficult to
deal for physicians. It is true that C4 identifies HAE, but it is not a test performed
in emergency. On the other hand, C4 reduces during attacks, but its level does
not identify presence or absence of the angioedema. The LevPharma trial tried to
use this parameter to mark the presence of an angioedema attack, but then they
were not able to use it and eventually had to have an external expert judging on
the presence of the symptoms. So far, no reliable marker can define abdominal
angioedema and criteria remain on clinical judgment and efficacy of specific
treatments. I suggest reviewing the paragraph and highlighting these points
The authors properly refer to side effects of long-term prophylaxis with
androgens. To be correct they should also report the paper from Gandhi, which is
based on data from an FDA register of reported side effect. This register listed 10
severe cases of thrombosis related to Cinryze over a period of 3 years of use of
this drug. These drawbacks of Cinryze need to be reported when dealing with its
use in HAE.
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:
no competing interest
Review for 10.1186/1471-230X-14-71 (2014)

Reviewer's report
Title:Abdominal Attacks and Treatment in Hereditary Angioedema with
C1-Inhibitor Deficiency
Version:2Date:9 March 2014
Reviewer: Timothy Craig
Reviewer's report:
I had the opportunity to review your manuscript titled
“Abdominal Attacks and Treatment in Hereditary Angioedema with C1-
Inhibitor Deficiency
By Eitan Rubinstein MD1, Leslie E. Stolz PhD2, Albert L. Sheffer MD3, Chris
Stevens MD2, Athos Bousvaros MD”
Thank you very much for the opportunity. Your manuscript was well written and
well thought out; however, I have a few suggestions that may help in improving
the manuscript.
Abstract- no needed changes
Introduction-
Please remove the following
“(EDEMA0,
EDEMA1®, EDEMA2®, EDEMA3®-Double Blind, EDEMA3®-Repeat Dosing,
EDEMA4®,
DX-88/19) and report the results of ecallantide (KALBITOR®, Dyax Corp.,
Burlington, MA)
treatment.”
In the last sentence, next to Gastroenterologist, please add “Surgeon and ED
Physician”.
Methods:
Well done
Results:
Should be DATA WERE
“data from EDEMA0, EDEMA1, EDEMA2 and DX-88/19 was analyzed”
Do you have data on CT scans of the abdomen? If so please include these data.
Discussions:
Although the statement ”Once the diagnosis is suspected, blood tests can
confirm the diagnosis” is true please specify that rarely are the results available
at the time of a patient presenting unless they are already diagnosed. Please add
that these will be important data to obtain in the ED for future attacks since the
treatment of HAE is unique.
Please reference the 4 “Guidelines” so that the GI community is aware of these
publications. This should include Canadian-HUNG, WAO, HAWK and the HAE_A
Please include Dr Bieddenkapp as an author. None of the authors were involved
in the EDEMA program and I am sure did not analyze these data. For this reason
please remove the line “The authors wish to thank Joseph Biedenkapp, PhD
(Dyax Corp.) for his assistance with the drafting of this manuscript.” And add him
as an author unless you are able to show he had less to do with this manuscript
than the present authors did.
Thank you for the opportunity. I enjoyed the manuscript and it is well done.
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:
no concerns
Review for 10.1186/1471-230X-14-72 (2014)

Reviewer's report
Title:Expression of energy metabolism related genes in the gastric tissue of
obese individuals with non-alcoholic fatty liver disease
Version: 1Date:16 July 2013
Reviewer: Munechika Enjoji
Reviewer's report:
Authors presented the expression profiles of energy metabolism associated
genes in gastric tissue of obese NAFLD patients and assessed the association of
the expression levels with hepatic steatosis, inflammation, fibrosis, and NASH.
This study includes novel findings which may be helpful for investigation of
NAFLD. Then, this report has potential for publication, I think. But there are some
incoherent expressions in the text. Major Compulsory Revisions are needed.
Comments
1. [Abstract: 1st line] Authors wrote “this energy balance…..”. What is the
meaning of “this”?
2. [Methods] What extent of gastric wall was included in your samples for PCR,
mucosa only, with submucosa, or entire gastric wall? Which kind of cells is
important for this study?
3. [Abstract & Discussion] Authors wrote “accumulation of the fat in the liver
parenchyma is accompanied by downregulation of genes encoding for CPE and
IL1B in the gastric mucosa of same patient”. But the data of expression levels of
these genes were not shown in different stage of fatty liver in same patient.
4. Do you have any data of patients without obesity, which may be a better
control?
5. [Methods] Please show us the definition of morbidly obese NAFLD patients.
How to select the enrolled patients?
6. [Introduction] More detailed explanation of your previous manuscript
(reference No 3) should be presented.
7. [Table 1] Patient number of advanced inflammation is 13. But the number of
steatosis with advanced inflammation (n=23) and that of NASH with advanced
inflammation (n=18) are larger than 13. In addition, the number of NASH with
advanced inflammation (n=18) are larger than that of NASH (n=15).
8. [Figures] I do not get the meaning of Figure 2. Are these figures required?
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, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-14-72 (2014)

Reviewer's report
Title:Expression of energy metabolism related genes in the gastric tissue of
obese individuals with non-alcoholic fatty liver disease
Version:1Date:17 November 2013
Reviewer: anja geerts
Reviewer's report:
Major comments:
- The place of the biopsy in the stomac tissue (antrum, fundus?,..) ? Always the
same place? Could it make a difference concerning the region of the biopsy in
the stomach tissue?
- It would be very interesting to compare these data with data on sstomach tissue
6 months to 1 year after the bariatric surgery.
- The difference in gene expressions in the stomach tissue : is this a
consequence of the steatosis of steatohepatitis? Or is it a trigger in the
development of steatotis or steatohepatitis?
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-14-70 (2014)

Reviewer's report
Title:Overexpression of SLC38A1 is associated with poorer prognosis in
Chinese patients with gastric cancer
Version: 1Date:25 July 2013
Reviewer: Sumiya Ishigami
Reviewer's report:
The author demonstrated SLC38A1 was overexpressed in gastric cancer tissues
and most likely contributes to tumor progression as independent prognostic
marker for the first time.
The patients’ number is large (more than 1000!) and the results of this study are
interesting and original. It seems to be suitable for acceptance in this journal;
however, some critical points could not be ignored.
Please resubmit after removing stage IV gastric cancer patients.
Major points
1) Overall survival in these patients is extremely poor even though 40% of the
patients were stage I or II. The author did not mention about the operation
manner and R0 surgery or not. 1074 patients may receive non-curative surgery.
Please add the information of surgery such as the tumor location, the degree of
lymph node dissection, operation manner (total, distal and proximal
gastrectomy), and anticancer treatment before and after surgery.
2) Prognostic significance cannot be evaluated using the patients receiving R1 or
R2 patients. Please remove stage IV gastric cancer patients in this study.
3) Table 1 is missing.
4) Their three previous studies using gene chip analysis really suggested an
elevated SLC38A1 mRNA expression in gastric cancer?
Review for 10.1186/1471-230X-14-70 (2014)

Reviewer's report
Title:Overexpression of SLC38A1 is associated with poorer prognosis in
Chinese patients with gastric cancer
Version: 1Date:12 August 2013
Reviewer: Rui Manuel Reis
Reviewer's report:
Overexpression of SLC38A1 is associated with poorer prognosis in Chinese
patients with gastric cancer
Jing Xie1*#, M.D., Jie-jun Wang*3, M.D., Ping Li2#, MS, Hui-feng Gao1, MS,
Jian-Xin Qian3, MS, Ling-Yan Yuan3, MS
In the present study, Jing Xie and co-authors analyzed the IHC profile of large
series of gastric cancer, and correlated with patient’s clinical-pathological
features. The authors find that SLC38A1 overexpression is an independent
prognostic factor and in vitro depletion of SLC38A1 was associated with a lower
aggressive behavior.
The study is interesting, pertinent and the overall results are important for the
scientific community. Despite of that, some issues most be answered in order to
send a rigorous and clear message of this manuscript.
Major Compulsory Revisions
- Despite the mention that demographic and clinical-pathological features of the
series herein analyzed were previously described ion other studies, it is
fundamental to show to the readers of the present study that epidemiological
data in the format of a new table 1.
- The manuscript lacks current table 1 and table 2, and without that it is
impossible to assess the text written by the authors.
- Considering the IHC analysis. The authors correctly used as a negative control,
the omission of the primary antibody. However, it is also mandatory to use a
second negative control, where the primary antibody is replaced by a universal
negative antibody from the specie, in order to evaluate the specificity of the
SLC38A1 antibody used in the study.
- In the material and methods, or results section, the authors most detailed the
semi-quantitative scoring system used for IHC evaluation.
- In the results section, a more detailed and deeper description of the SLC38A1
expression pattern must be presented. What types of cells were positive, it was
focal, diffuse, etc.
- The in vitro results are interesting, however, it is missing the behavior of the
parental cells in all the experiments.
Minor Essential Revisions
Some grammatical mistakes should be corrected. A full written re-evaluation is
suggested.
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-14-70 (2014)

Reviewer's report
Title:Overexpression of SLC38A1 is associated with poorer prognosis in Chinese
patients with gastric cancer
Version:2Date:26 October 2013
Reviewer: Rui Manuel Reis
Reviewer's report:
The authors properly addressed the issues previously raised. The submitted
replied version has some typing errors that should be corrected.
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.
Review for 10.1186/1471-230X-14-70 (2014)

Reviewer's report
Title:Overexpression of SLC38A1 is associated with poorer prognosis in Chinese
patients with gastric cancer
Version:2Date:3 November 2013
Reviewer: Sumiya Ishigami
Reviewer's report:
What is the positive control of SLC38A1? Did author always evaluate expression
of SLC38A1 under the positive and negative control? Please add in the method
section.
What was the “ thrombosis” in the tables? Is it necessary to analyze as
prognostic marker?
Previous reports suggested that PCNA and p53 were independent prognostic
markers. Why did not authors insert these factors in multivariate analysis?
Why did the authors evaluate “anemia” in the multivariate analysis?
Clinical factors which are significant for survival by univariate analysis should be
included in multivariate analysis. Please delete.
Please state why histology is selected as independent prognostic marker.
B SE Wald df Sig. Exp(B) 95.0% CI Exp(B) in table 2 is too hard to understand.
There is no discussion about significant correlation between SLC38A1 and
clinical factors (histology and PCNA).
“Survival and prognostic factors” in the discussion section.
Survival significance of SLC38A1 is very poorly described Please enrich this part.
“Molecular markers for the development and progression of gastric cancer
include p53[33], nm23 [34], CD44 [35],and p-mTOR [13]. “ is not necessary.
Please delete.
Level of interest: An article of importance 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-14-68 (2014)

Reviewer's report
Title:Mucosal gene therapy using a pseudotyped lentivirus vector encoding
murine interleukin-10 (mIL-10) suppresses the development and relapse of
experimental murine colitis
Version:2Date:11 February 2014
Reviewer: Suy Somanathan
Reviewer's report:
1) Major Compulsory Revisions
In the discussions, the authors claim the success of being able to administer two
doses of the lentiviral vector. However, even one dose was sufficient to correct
the phenotype of DSS induced colitis. Given that how can the authors claim any
contribution from the second vector administration?
Moreover, the level of IL-10 did not change after the second vector. The authors
provide an explanation that the levels of endogenous IL-10 may have gone down
to which may keep the levels of IL-10 the same.
However, what if there was a humoral immune response to the first vector
administration that blocked the second vector. In this case the authors would still
get the same level of protection, since one vector administration was sufficient to
protect, and as expected the levels of IL-10 would not change.
So either the authors have to provide evidence that the second vector
administration was successful or discuss the possibility that the second
administration could have failed.
2) Major Compulsory Revisions
Have the authors measured IL-10 levels in serum? Did they change? And what
effect if any does LVmIL-10 expression have on any other immune response in
the animal? For instance, would we expect immunity to be compromised against
a pathogen by this approach? The authors could easily measure the B or T cell
responses against some commonly available antigens after the LVmIL10
treatment. Or at least the potential for such issues should be discussed.
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-14-68 (2014)

Reviewer's report
Title:Mucosal gene therapy using a pseudotyped lentivirus vector encoding
murine interleukin-10 (mIL-10) suppresses the development and relapse of
experimental murine colitis
Version:2Date:18 February 2014
Reviewer: Roberto Calcedo
Reviewer's report:
The manuscript “Mucosal gene therapy using a pseudotyped lentivirus vector
encoding murine interleukin-10 (mIL-10) suppresses the development and
relapse of experimental murine colitis” by Matsumoto, H et al describes the use
of a lentiviral vector encoding IL-10 administered locally in a mouse model of
enterocolitis. Authors showed the treatment suppress the development and the
relapse of colitis.
Although the study is well conducted and the manuscript is well written additional
information and corrections are needed:
Major compulsory revision:
1. Methods: page 11. Authors design the study using 4 experimental groups: NC,
Mock, LV1 and LV2. Author did not include mIL-10 plasmid alone group that
would control for the levels of correction obtained only with plasmid DNA. Do
author have any data showing levels of mIL-10 using just plasmid in the gut? The
second group that is missing is the LV without mIL10, this group would control for
the LV specific CD4 T-cell response. How do authors know that the effect they
see is caused by mIL-10 and not by LV CD4 T cells changing the cytokine milieu
in the lamina propria?
2. Discussion: page 22. “In the context, it is notable that IL-10 levels were
comparable between the single dose and the double dose groups…”. It could be
that the second administration does not have an effect because of neutralizing
antibodies to LV, developed after the first LV administration, blocking gene
transfer. Do authors have any data on antibodies (sIgA) or neutralizing antibodies
to LV?
Minor compulsory revision:
1. Figure 2e. Authors added in the graph: “Pre-treatment before gene
transduction” This statement is confusing. Mice were injected with LV vector so
there is gene transfer so why this “before”?
2. Results: page 18. The cytokine data should be presented as a plot. If the
journal does not allow more figures in the manuscript, include histology pictures
(fig 5a-5h) as supplementary data.
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-14-67 (2014)

Reviewer's report
Title:Deregulated Expression of Circadian Clock Genes in Gastric Cancers
Version: 1Date:9 October 2013
Reviewer: Richard G Stevens
Reviewer's report:
This is a small study of circadian gene expression in gastric cancer. The topic is
interesting and the study appears to have been carefully conducted. Given the
small sample size it is important that the authors acknowledge this limitation and
point out that the study had low power; real differences could easily have been
missed. For example, on page 6 it is stated
“Our data demonstrated only PER2 expression was significantly upregulated (p <
0.005) and the expression of the other seven genes was not different between
cancer and noncancerous tissues (Table 2 and Figure 1).”
The authors have confused ‘not statistically significant’ with ‘not different’. In fact
from figure 1 there are differences in expression of several of the genes (not just
Per2); these differences are not statistically significant, but in a larger study might
be found to be real. Also, as the authors point out, the Per2 difference is in the
opposite direction than expected based on previous studies. The final paragraph
of the Discussion is highly speculative, but that is fine because the speculations
are reasonable.
Also, in the Introduction, the word ‘proof’ should be avoided.
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:
no competing interests
Review for 10.1186/1471-230X-14-67 (2014)

Reviewer's report
Title:Deregulated Expression of Circadian Clock Genes in Gastric Cancers
Version:2Date:1 March 2014
Reviewer: Pasquale Innominato
Reviewer's report:
The Authors have provided acceptable replies to the issues presented to them,
and the manuscript is now improved.
I have 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-14-65 (2014)

Reviewer's report
Title:Prevalence of pre-transplant electrocardiographic abnormalities and
post-transplant cardiac events in patients with liver cirrhosis
Version:2Date:11 January 2014
Reviewer: Aurore BRONDEX
Reviewer's report:
Major Compulsory Revisions
1/ Prevalence of ECG abnormalities : it seems that the studied population
(n=186) is not representative of the 234 patients with cirrhosis undergoing liver
transplantation described in this study : indeed, table 1 shows differences
concerning the etiology of cirrhosis, cardiovascular risk factors (arterial
hypertension, diabetes mellitus) and proportion of coronary investigation.
Furthermore, no data are available concerning the prevalence of CAD in these 2
groups.
2/ This study lacks data on cardiovascular risk factors (obesity and dyslipidemia
were not taken into account)and cardiovascular diseases (particularly CAD,
hypertensive cardiopathy, arrhythmias) in the studied cirrhotic patients. These
could account for ECG abnormalities, more than cirrhosis itself and more than
reported associated factors such as male gender, age, smoking, arterial
hypertension, severity and etiology of cirrhosis. To note, these patients seem to
have underwent echocardiography (cohort previously used, cf reference 13) and
testing for CAD, so data about underlying cardiopathy or CAD should be
available. In the same way, it would have been interesting to study the correlation
between "ECG positive for CAD" and diagnosed CAD, as these ECG
abnormalities are not specific.
3/ Concerning the prevalence of ECG abnormalities and the risk of cardiac
events, there are major confounding variables in this study. It seems
inappropriate to compare ECG abnormalities and outcome of a healthy cohort,
without CAD or known cardiovascular disease, without cirrhosis, not undergoing
any surgery, with ECG abnormalities and outcome of cirrhotic patients
undergoing a major surgery, whose coronary status and cardiovascular medical
past is not described (to note, litterature reports a prevalence of CAD up to 26%
in cirrhotic patients undergoing transplantation, which is a lot more than in
general and "healthy" population). Moreover, data concerning cardiovascular risk
factors in these 2 populations are not available.
4/ Concerning the relation of pre-transplant ECG abnormalities to post-transplant
cardiac morbidity and mortality : both are probably related to preexisting
cardiovascular diseases (particularly hypertensive cardiopathy, arrhythmias and
CAD) that were not taken into account in this study. Thus the relation of
pre-transplant ECG abnormalities to post-transplant cardiac morbidity and
mortality cannot be clearly established.
Minor Essential Revisions
Tables count : 5 rather than 4.
Discretionary Revisions
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-14-65 (2014)

Reviewer's report
Title:Prevalence of pre-transplant electrocardiographic abnormalities and
post-transplant cardiac events in patients with liver cirrhosis
Version:2Date:18 January 2014
Reviewer: Jorge Quiroga
Reviewer's report:
Minor essential revisions
1. Were the patients subjected to procedures after the pretransplant cardiac
work-up ?. For example, pacemaker placement, coronary artery ballooning or
stenting or cardiac resincronization?. If so, the basal EKG, that is the core of this
study is not the true pre-transplant EKG. This points needs clarification.
2. There were cardiac events during the transplant surgery?. If so, were these
events recorded and included as post-transplant cardiac complications in this
series?. Introperative time is period of special risk for these events and this ponit
needs clarification
3. The cases of post-transplant deaths due to heart disease should be detailed
and its relationship with pre-transplant EKG alterations explained. Numerical data
may be added to table 5.
4. This same group of investigators reported previously (reference 13 in this
paper) the occurrence of peri-transplant heart failure in virtually this same series
of patients (186 patients in this paper and 177 in the previous one). The previous
paper included detailed pre-transplant echocardiographic data and only few EKG
data. The decision of the author´s of spliting pre-transplant heart data in two
papers is acceptable but jeopardizes, at least in part, the global comprehension
of the impact of heart disease on post-transplant evolution. In this reviewer´s
oppinion the paper would be improved if the authors make an effort for
integrating in the discussion of this paper the information they obtained in the
previous one. Surprinsingly, the comments the authors devote to that paper in
the discussion are extremely scarce.
5. The number of patients that were finally evaluated should be mentioned in the
abstract
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-14-66 (2014)

Reviewer's report
Title:High mobility group B1 mediates gut bacterial translocation in
acetaminophen hepatotoxicity
Version: 1Date:10 August 2013
Reviewer: Li Ning
Reviewer's report:
Minor Essential Revisions
1# Results, paragraph 1: 6 hours after APAP injection, what is the glutathione
concentrations in control mice?
2# Results, paragraph 2: “published in 22” should be changed to “published in
reference 22”.
3# Discussion, paragraph 1: “serves” should be changed to “serve”.
4# Grammar and diction - please have the paper reviewed for the proper use of
the English language. Needs some language corrections before being published.
5# References: Please follow the guidelines of the BMC Gastroenterology
reference style, and check all the reference listed.
6# The legends of Figures should be shortened and simplifed. Do not copy all
words from the Methods section.
7# What did the red words in author’s PDF manuscript mean?
8# What was the assession standards for BrdU and PCNA staining?
9# The methods of BrdU and PCNA staining should be shortened
10# The Statistical software and its version should mentioned in the Statistical
methods section.\\
11# Significance p value in the Results section should be italic.
12# "Minor issues not for publication" because of some minor comments.
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'
Review for 10.1186/1471-230X-14-66 (2014)

Reviewer's report
Title:HMGB1 neutralization is associated with bacterial translocation during
APAP hepatotoxicity
Version:2Date:12 November 2013
Reviewer: Li Ning
Reviewer's report:
Accept without revision
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.
Review for 10.1186/1471-230X-14-66 (2014)

Reviewer's report
Title:HMGB1 neutralization is associated with bacterial translocation during
APAP hepatotoxicity
Version:2Date:24 November 2013
Reviewer: Carol R Gardner
Reviewer's report:
Major Compulsory Revisions:
Results:
Liver Injury:
This section is a discussion of previously reported data and some of the data that
has also been reported on page 13 of the manuscript. Either combine this section
with the BrdU staining section or include the ALT/AST data with the prior section
on bioactivation and call it "liver injury". There is also no mention in the materials
and methods on how the authors determined the percentage of the necrotic
areas within the liver sections.
Bacterial translocations to MLN and the liver:
The first sentence makes no sense: it reads: "Bacterial translocation was
measured in our published APAP toxicity studies (data not published) and the
results showed that: when i.p. injected into mice....." Please correct.
Discussion:
In general, the discussion is difficult to read and the sentence structure is poor.
The authors were asked to address the possibility that the proliferating
macrophages within the livers at 48 h could be either pro- or anti-inflammatory.
Their response to the reviewer was that they were confused and simply put the
statement in the discussion without a reference or context. Current literature
recognizes the existence of multiple populations of macrophages (classically
activated-M1 and alternatively activated-M2) which can be present at different
stages during the course of toxic events. This is what needs to be addressed in
view of the fact that macrophages are proliferating and/or migrating into the liver.
The 2nd sentence in the paragraph on gut permeability does not make sense.
Figure 4: The backgrounds don't match and the background on 4E is so bright it
obscures the area of interest.
Minor Essential Revisions:
Figure 3: The X-axis labels are spaced to closely and difficult to read.
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-14-66 (2014)

Reviewer's report
Title:HMGB1 neutralization is associated with bacterial translocation during
APAP hepatotoxicity
Version:2Date:31 December 2013
Reviewer: Daniel J Antoine
Reviewer's report:
I have no further comments - the authors responses to my initial critique are
appreciated. I would recommend accept without further comments to my original
review.
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.
Review for 10.1186/1471-230X-14-64 (2014)

Reviewer's report
Title:Discussing the influence of electrode location in the result of esophageal
prolonged pH monitoring
Version: 2Date:28 August 2013
Reviewer: Hendrik Manner
Reviewer's report:
Dear authors,
thank you very much for making the changes.
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:
no competing interests
Review for 10.1186/1471-230X-14-64 (2014)

Reviewer's report
Title:Discussing the influence of electrode location in the result of esophageal
prolonged pH monitoring
Version:3Date:24 January 2014
Reviewer: mate knabe
Reviewer's report:
In the revised version of the manuscript the authors have answered all points
sufficiently
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:
No competing interest exists
Review for 10.1186/1471-230X-14-63 (2014)

Reviewer's report
Title:A Descriptive Study of Colorectal Function in Adults with Prader-Willi
Syndrome: High Prevalence of Constipation
Version: 3Date:26 March 2013
Reviewer: Oliver Schwandner
Reviewer's report:
No major or minor revisions needed
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:
No competing interests.