JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-12-16 (2012)

Reviewer's report
Title:Involvement of a periodontal pathogen, Porphyromonas gingivalis on the
pathogenesis of non-alcoholic fatty liver disease.
Version: 3Date:17 December 2011
Reviewer: Frank Tacke
Reviewer's report:
The authors have addressed most of my concerns and improved the manuscript.
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 interests.
Review for 10.1186/1471-230X-12-16 (2012)

Reviewer's report
Title:Involvement of a periodontal pathogen, Porphyromonas gingivalis on the
pathogenesis of non-alcoholic fatty liver disease.
Version: 3Date:19 December 2011
Reviewer: Richard Blumberg
Reviewer's report:
n/a
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-12-16 (2012)

Reviewer's report
Title:Involvement of a periodontal pathogen, Porphyromonas gingivalis on the
pathogenesis of non-alcoholic fatty liver disease.
Version: 3Date:13 January 2012
Reviewer: Lawrence J Saubermann
Reviewer's report:
I have no further concerns or 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-12-14 (2012)

Reviewer's report
Title:Diagnostic Accuracy of the Aspartate Aminotransferase-to-Platelet Ratio
Index for the Prediction of Hepatitis B-Related Fibrosis: A leading Meta-Analysis.
Version: 2Date:1 November 2011
Reviewer: Valentina Medici
Reviewer's report:
Jin et al conducted a meta-analysis on the diagnostic accuracy of the aspartate
aminotransferase to platelet ratio index for the prediction of fibrosis in chronic
hepatitis B. The authors initially identified 16 studies and included 9 studies in the
final analysis. A total of 1,798 patients were included. About 53% of patients
presented significant fibrosis and cirrhosis.
The study mirrors the cited meta-analysis on chronic hepatitis C and AST to
platelets ratio as predictor of significant fibrosis in terms of statistical methods
and results presentation. However, this is the first time that this analysis is
performed in chronic hepatitis B and there are limited data on the application of
the ratio for chronic hepatitis B. Overall the study is well written and reaches
meaningful conclusions that have clinical relevance.
Major critiques
1) was there any assessment of the liver biopsies quality? Was the number of
portal tracts considered in the selection of the studies?
2) the authors should state the date range from were the studies were selected
3) the authors should present the flow diagram of studies inclusion and exclusion
4) the authors did not report the quantitative assessment of publications bias
Minor critiques
1) the meaning of the abbreviation APRI should be explained both in the abstract
and in the background
2) the number of patients included in the prediction of cirrhosis should be stated
3) the manuscript will require a revision of the English language.
For example,
a) background: “APRI has developed well in chronic hepatitis C”
b) discussion: “non-invasion markers”
c) discussion: “a plausibility of our review is that using meta-regression to test
heterogeneity...”
d) abstract and conclusions: “can also not reduce the number of liver biopsy”
Level of interest: An article of importance in its field
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.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-14 (2012)

Reviewer's report
Title:Diagnostic Accuracy of the Aspartate Aminotransferase-to-Platelet Ratio
Index for the Prediction of Hepatitis B-Related Fibrosis: A leading Meta-Analysis.
Version: 3Date:7 December 2011
Reviewer: Valentina Medici
Reviewer's report:
The authors have properly addressed my comments.
One minor correction of the English language: :APRI may not be a good tool of
predicting hepatitis B-related significant fibrosis and cirrhosis and can also not
reduce the number of liver biopsies among CHB patients".
Level of interest: An article of importance in its field
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.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-15 (2012)

Reviewer's report
Title:Diagnostic Accuracy of Cyst Fluid Amphiregulin in Pancreatic Cysts
Version: 1Date:18 September 2011
Reviewer: Christopher Halloran
Reviewer's report:
This is a retrospective, but small study of analysis of pancreatic cyst fluid using
amphiregulin (AREG). The motivation was to use this novel biomarker to
differentiate between non-mucinous, benign mucinous and malignant mucinous
cysts. This is an important topic and the authors should be congratulated on their
endeavours in this field.
Major Revisions / Questions to be answered
It is unclear whether AREG use was investigated as a biomarker for
dysplasia/malignancy or for mucinous/non-mucinous lesions as suggested in the
abstract.
It would be helpful to know whether the pre-operative diagnoses differed from the
post operative histology and what the indications for surgery were.
This study attempts to differentiate between benign mucinous lesions and
mucinous lesions, which have dysplastic or malignant cells. However the
“benign” group contains 9 BD-IPMN, 3 MD-IPMN and 3 MCN. Practically
MD-IPMN and MCD should be treated as pre-malignant cysts and should be
resected regardless; therefore this use of tumour markers in these cases does
help.
Furthermore 3 cases of high-grade dysplasia were found in the MD-IPMN, which
were classified as “benign tumours”. Therefore was the analysis performed
between the benign cysts and the malignant cyst groups? in which case there
was bias or between those that were histologically benign with those of
dysplasia/malignancy? Hence I am not sure what the authors point is exactly –
clarification is required.
Looking at these data it is clear that MD-IPMN and MCD have a higher median
AREG and should never have been included in the grouping. These data are
summarized in table 3 that only have 9 patients not the 12 stated – where are the
rest. Overall this is VERY confusing as it is unclear exactly which patients were
compared.
As the data pertaing to which patients were used in the accuracy testing and
ROC curve are unclear I am hesitant to accept these findings without
qualification.
Overall the use of AREG performs no better than CEA in those cases where both
results are included. Obviously the small numbers and retrospective approach
hinder this study but it would be interesting to see how AREG performs along
side CEA and CA 199.9 from cyst aspirates in a prospective group of patients
presenting with non-inflammatory pancreatic cysts.
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 interests
Review for 10.1186/1471-230X-12-15 (2012)

Reviewer's report
Title:Diagnostic Accuracy of Cyst Fluid Amphiregulin in Pancreatic Cysts
Version: 1Date:30 September 2011
Reviewer: Paula Ghaneh
Reviewer's report:
This paper evaluates the use of cyst fluid amphiregulin levels in the diagnosis of
pancreatic cysts.
Comments:
1. The question is an important one as the number of patients with cystic lesions
in the pancreas is rising and tests which can differentiate benign and malignant
cysts are needed.
2. What were the inclusion criteria for the study – were all patients with cysts
considered or were there other criteria such as cyst size or suspicious features?
The authors must have had some criteria to ensure an appropriate range of
cases.
3. It is not entirely clear how the cyst fluid samples were obtained – can the
authors describe how the cyst fluid was obtained – all EUS or some at surgery?
Also how much fluid was required/harvested?
4. Was the ELISA fully validated?
5. The main drawback is the size of the patient sample and the mixed patient
population – but this is probably acceptable for a pilot feasibility study – did the
authors perform a sample size calculation for this study?
6. What was the sensitivity/specificity of CEA for this cohort of patients?
7. The authors should stress that this test needs further validation in larger
prospective series.
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-12-15 (2012)

Reviewer's report
Title:Diagnostic Accuracy of Cyst Fluid Amphiregulin in Pancreatic Cysts
Version: 1Date:5 October 2011
Reviewer: Mike Larvin
Reviewer's report:
This study is a potentially useful addition to the thorny issue of pancreatic cyst
fluid diagnosis. I enjoyed reading this paper.
Minor essential revisions and queries:
It is self-evident that if 2-8% of the population have a pancreatic cyst and half are
potentially malignant, then cystadenocarcinomas would be beginning to dominate
the known incidence of pancreas cancers. Was this an error?
Methods: Could the authors confirm whether 2 freeze-thaw cycles is deleterious
to the detection of AREG in their own lab?
Results: This study adds useful information to existing methods, allowing for
sample size as the authors acknowledge.
EUS is becoming a gold standard for pre-operative diagnosis of pancreatic cystic
lesions, but in the absence of malignant cells marker elevations are not always
helpful. Further studies appear justified and it may be that AREG has a
diagnostic role alongside CEA and imaging findings.
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, Michael Larvin MD, have no competing interests.
Review for 10.1186/1471-230X-12-15 (2012)

Reviewer's report
Title:Diagnostic Accuracy of Cyst Fluid Amphiregulin in Pancreatic Cysts
Version: 2Date:5 January 2012
Reviewer: Christopher Halloran
Reviewer's report:
I think all my issues have been addressed and providing the other reviewers are
happy this can be published
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-12-15 (2012)

Reviewer's report
Title:Diagnostic Accuracy of Cyst Fluid Amphiregulin in Pancreatic Cysts
Version: 2Date:6 January 2012
Reviewer: Mike Larvin
Reviewer's report:
I have read the responses to my queries and that of the other two reviewers and
reviewed the new manuscript.
I believe that the responses have led to greater clarity, and that the new
manuscript is acceptable.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-12-13 (2012)

Reviewer's report
Title:Chronic fatigue syndrome after Giardia enteritis: clinical characteristics,
disability and long-term sickness absence.
Version: 1Date:23 April 2011
Reviewer: Peter White
Reviewer's report:
The authors describe a case series of 96 patients referred and admitted to a
clinic complaining of fatigue, who had laboratory confirmed giardiasis some two
years previously. On this basis, they conclude that a proportion of these patients
are the only ones of a much large incident cohort (n > 1200) who have chronic
fatigue syndrome and that giardiasis was the cause.
Major Compulsory Revisions
How many of the original inception cohort were not admitted for clinical
assessment – over 1100? Only those referred were assessed. It is difficult to
conclude anything about causation from this. It is not possible to state accurately
the prevalence of CFS (4.6%) on the basis of examining a referred selected
small sample of the original cohort. We do not know the prevalence of CFS in
those not assessed.
How were life events and psychiatric history assessed? Were standardised
measures used? If not, data may not be reliable or valid.
The threshold for clinical depression and anxiety on the Hospital Anxiety
Depression sub-scales is 11+, not 15. These figures need recalculating.
The 1994 CDC criteria for defining CFS have been superseded by the
international (CDC) criteria (Reeves WC et al, 2003).
Minor Essential Revisions
Please give the range of FSS in methods.
Discretionary Revisions
Abstract: Please give percentage figures to nearest integer for those improving or
depressed, et cetera. A decimal point percentage figure lacks meaning with a
denomimator of only 58.
1. Is the question posed by the authors well defined?
Yes
2. Are the methods appropriate and well described?
No. The study of prevalence of a condition in an inception cohort requires
examination of either the whole cohort or a random selection of the original
cohort, not a selected sample referred to a clinic. Relying on population norms,
sometimes from different countries is not a reliable way to examine a control
group. There is no assessment of whether patients were fatigued before onset of
giardiasis, so no relationship to giardiasis can be interpreted. Similarly, a
significant proportion developed their fatigue some months after infection, casting
doubt on the relationship between fatigue and the infection.
3. Are the data sound?
Yes, in so far as they describe a case series.
I would advise rewriting as a case series, but not making conclusions about the
relationship to giardiasis, and outlining the limitations of such a design.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have done consultative work for the UK Department for Work and Pensions and
a re-insurance company.
Review for 10.1186/1471-230X-12-13 (2012)

Reviewer's report
Title:Chronic fatigue syndrome after Giardia enteritis: clinical characteristics,
disability and long-term sickness absence.
Version: 3Date:16 June 2011
Reviewer: Peter White
Reviewer's report:
I have read the revised report, but I am afraid to say there are still major
methodological problems with this report.
1. The authors use the denominator of 1262 patients, when the real denominator
is 96.
2. The authors say they used the Reeves et al criteria for diagnosing CFS, but
this recommends using a standardised psychiatric interview, which they did not
do. A HADS scale does not, for instance, measure recent history of psychiatric
disorders, which is necessary to make a CDC diagnosis of CFS. The authors
continue to use the wrong threshold for judgement of clinical depression and
anxiety of 15. The original authors of the HADS clearly state it is 8-10 for
borderline and 10+ for clinically significant mood disorders on the two sub-scales.
With this standard of measurement, not complying with CDC criteria, I cannot be
confident that the 56 patients did have CFS.
3. Their main aim is to describe the phenotype of CFS after giardiasis, but they
make no empirical analysis of the phenotype.
4. The relationship between giardiasis and CFS cannot be assumed to be
causative when there is a delay in development of CFS after infection of months.
5. The fundamental problem is that the authors explicitly interpret their data as
though it was an epidemiological study of the relationship between giardiasis and
CFS, when it is not. The authors overintrepret what is essentially a case series of
patients who have been referred to a hospital for fatigue some time after
contracting giardiasis.
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 advise the UK government and a re-insurance company about disability related
to medically unexplained symptoms and mental health.
Review for 10.1186/1471-230X-12-12 (2012)

Reviewer's report
Title:"Drop in" gastroscopy outpatient clinic - experience after 9 months
Version: 1Date:25 October 2011
Reviewer: Oyvind Bjertnaes
Reviewer's report:
I enjoyed reading about this project, and appreciated the inclusion of patient
evaluation and the triangulation of different perspectives. However, the project
mostly seems to be a quality improvement project, with questionable scientific
value. I wonder if the study might be better suited as a quality improvement
report in another journal. If so, the SQUIRE guidelines could be useful for the
authors
(http://www.squire-statement.org/assets/pdfs/SQUIRE_guidelines_table.pdf ).
Major Compulsory Revisions:
First, the Background lacks references to and discussion of relevant scientific
literature. It is difficult to understand why this quality improvement initiative was
chosen and what gap in the literature this study is trying to fill. Furthermore, the
Background is restricted to Norway, which will be a serious limitation for
international readers. Second, the Methods lack documentation of and reflexion
on the quality of the applied study methods including survey methodological
issues and psychometric issues. Patient satisfaction studies have been criticized
for having to little focus on reliability and validity (see for instance Sitzia J. How
valid and reliable are patient satisfaction data? An analysis of 195 studies. Int J
Qual Health Care. 1999 Aug;11(4):319-28), and this criticism is relevant for the
current study. Third, the Results should include a table with results for questions
in all three materials. Fourth, the Discussion does not discuss main findings in
relation to relevant scientific literature. Furthermore, study limitations and
external validity are hardly mentioned in the Discussion. Fifth, questionnaires
with question formulations and response scales should be included in
appendices.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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-12-12 (2012)

Reviewer's report
Title:"Drop in" gastroscopy outpatient clinic - experience after 9 months
Version: 1Date:29 October 2011
Reviewer: Anthony Catto-Smith
Reviewer's report:
this paper describes a clinical audit of an interesting approach to the provision of
endoscopic services. The methodology and analyses are sound with no specific
criticisms to offer. The only area of concern that I had was with table 2 which was
a bit difficult to understand. it wasn't clear what the data referred to in terms of
the numbers in brackets and the denominator numbers. This needs to clarified in
the table legend
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-12-11 (2012)

Reviewer's report
Title:Long-term effects of treatment and response in patients with chronic
hepatitis C on quality of life
Version: 2Date:9 September 2011
Reviewer: Bart van Hoek
Reviewer's report:
This manuscript provides important data on HRQOL in HCV treatment. It needs a
legend to the figures. No other 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-12-11 (2012)

Reviewer's report
Title:Long-term effects of treatment and response in patients with chronic
hepatitis C on quality of life
Version: 2Date:22 November 2011
Reviewer: GEORGE ABOUDA
Reviewer's report:
The paper is written in good English, the research question is of clinical
relevance, this has been addressed carefully and clearly within the substance of
the literature.
Few comments
1- There are many abbreviations within the text; the authors may do with
reducing it when possible.
2- Many variables are mentioned and these are not shown in comparative table
before and after treatment.
3- There are few questions raised in the results but the authors are not
discussing it , such as why the cirrhotics are doing better than non cirrhotics,
reason of the high drop put rate while it is mentioned in methodology that
questionnaires were given 6 weeks from start of treatment, how did the authors
overcome the country differences ( cultural and social ) is it by the multivariate
analysis and logistic regression .
Level of interest: An article of importance in its field
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-12-10 (2012)

Reviewer's report
Title:Serological Assessment of gastric mucosal Atrophy in gastric Cancer.
Version: 1Date:31 October 2011
Reviewer: Lars Engstrand
Reviewer's report:
The ms is well written and addresses questions and answers to scientists and
physicians in this field. There is a need for screening programs that include
evaluation of markers such as H. pylori and serological characterization of the
gastric mucosa i.e. preneoplastic conditions. Such approaches have been
discussed and presented before and this study adds information to the field by
evaluating the use of potential biomarkers and a possible association to specific
gastric cancer characteristics. Some minor comments and questions should be
addressed:
1. Data assessment page 6: The reason for excluding mixed type tumors is not
clear. Clarify "for statistical reasons".
2. Assessment of serum parameters page 8. Add a reference to justify that
patients with positive CagA-status are classified as H. pylori positive. An
exclusive Cag A antibody response has been suggested as a serological scar i.e.
an indication of past H. pylori infection and consequently the definition should be
modified in the text.
3. All figures should be presented in a supplement. The results are clear in the
text and the figures does not add any substantial information in the ms as it is
presented now.
4. It would be of interest for gastroenterologists to get some advise or clinical
impact based on the current findings in this study. How should we approach
patients with diffuse type cancers for example? Is a combination of endoscopy
and serological screening the best option and if so, should we apply such
strategies in both high and low risk populations?
3.
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-12-10 (2012)

Reviewer's report
Title:Serological Assessment of gastric mucosal Atrophy in gastric Cancer.
Version: 1Date:18 November 2011
Reviewer: Mario D'Elios
Reviewer's report:
The article by Bornschein et al is well written. The question posed by the authors
is well defined. The methods are appropriate and well described.
The data sound well. The manuscript adhere to the relevant standards for
reporting and data deposition. The discussion and conclusions are well balanced
and adequately supported by the data. The authors clearly acknowledge any
work upon which they are building. The title and abstract accurately convey what
has been found.
It will be useful for readers to include the discussion of PMID:15242679.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-9 (2012)

Reviewer's report
Title:Luteolin decreases IGF-II production and down-regulates insulin-like
growth factor-I receptor signaling in HT-29 human colon cancer cells
Version: 1Date:25 July 2011
Reviewer: Thomas THS Haarmann-Stemmann
Reviewer's report:
In this study Lim et al. investigated the effect of luteolin exposure on insulin-like
growth factor receptor signaling in a human colon cancer cell line. The authors
observed that luteolin decreases IGF-II expression and damps IGF-IR signaling
and conclude that this may lead to induction of cell-cycle arrest and programmed
cell death in their test system. The manuscript is nicely arranged and the
introduction provides the necessary background information. The presentation
and discussion of the results is ok, but can be enhanced (see below). In my point
of view, one important experiment is missing.
The majority of the described effects of luteolin on IGF/IGF-R signal transduction
were previously demonstrated in other test systems, e.g. prostate cancer cells.
However, I think the article by Lim et al. is still of interest for scientist working on
the field.
Listed below are several points which should be addressed by the authors before
I can recommend the publication of this article in BMC Gastroenetreology:
- Discretionary Revisions
0) In figures 3 and 4 the densitometry of the single bands is given in numbers
above the respective gel picture. I think the effects will become more visible if the
authors just add the respective column diagrams (as done for the other figures)
1) Luteolin is known to bind to certain cellular receptors, e.g. the aryl
hydrocarbon receptor. Therefore it would be interesting to know, if the
luteolin-mediated inhibition of IGF-II secretion (figure 1) occurs on transcriptional
or post-transcriptional level? I strongly recommend to figure this out by adding an
experiment using cycloheximide and actinomycin D, respectively.
- Minor Essential Revisions
2) The solvent for luteolin is missing and should be added. Did the authors
include the respective solvent controls in their experiments?
3) The sequences of the oligonucleotides used for PCR are missing and should
be added.
- Major Compulsory Revisions
4) The analysis of the effect of luteolin on ERK1/2 phosphorylation stands
isolated in the manuscript. The authors discuss that the luteolin-mediated
inhibition of ERK1/2 phosphorylation probably leads to inactivation of cdc25c in
their test system. This would be indeed an important finding since the activation
status of cdc25c represents an important link between the current article and the
previously published results of the group. Therefore, the authors should add an
experiment where they examine cdc25c phosphorylation in absence/presence of
luteolin.
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-12-9 (2012)

Reviewer's report
Title:Luteolin decreases IGF-II production and down-regulates insulin-like
growth factor-I receptor signaling in HT-29 human colon cancer cells
Version: 1Date:28 July 2011
Reviewer: Jing Fang
Reviewer's report:
Lim et al demonstrated in the manuscript that luteolin dose-dependently
decreased IGF-II secretion and the expression of IGF-IR precursor protein of
colon cancer HT-29 cells. They found that luteolin decreased IGF-I-induced
tyrosine phosphorylation of IGF-IR and association of p85 with IGF-IR. Moreover,
they reported that luteolin decreased IGF-I-stimulated PI3K/AKT and ERK1/2
signaling. The authors concluded that luteolin down-regulated the activation of
PI3K/Akt and ERK1/2 pathway via decreasing IGF-IR signaling in HT-29 cells,
which may be one of the mechanisms responsible for the luteolin-induced
apoptosis and cell cycle arrest. Generally, the study is quite primarily. It has been
reported that luteolin inhibited IGF-1/IGF-1R signaling and its downstream
targets AKT and ERK (Carcinogenesis vol.28 no.3 pp.713–723, 2007).
Therefore, the novelty of the current work is limited.
Major comments
The authors showed that luteolin inhibited IGF-1/IGF-1R signaling. However, it is
not clear whether or not this inhibition plays a major role in the luteolin-induced
repression of cell proliferation and cell apoptosis.
1. Does the inhibition of IGF/IGF-1R signaling lead to suppression of proliferation
or apoptosis of HT29? Does neutralization of IGF-II results in repression of
proliferation of HT29 cells?
2. Does luteolin inhibit IGF-1/IGF-1R signaling in other colon cancer cells, such
as HCT116 or SW480?
3. The authors determined the effects of luteolin on expression of IGF-II of HT29
cells (Fig. 1). The cells were incubated in serum-free medium for 24 h, followed
by a treatment of luteolin for another 24 h. It is not clear why the cells were
incubated in serum-free medium. What was the status of the cells after luteolin
treatment under the experimental condition? Was the downregulation of
expression of IGF-II due to inhibition of cell proliferation or due to cell apoptosis?
Minor:
1. The inhibition of IGF-1R mRNA level is minor (Fig. 3B). It is suggested to
perform Real-time PCR to determine the IGF-1R mRNA levels.
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-12-9 (2012)

Reviewer's report
Title:Luteolin decreases IGF-II production and down-regulates insulin-like
growth factor-I receptor signaling in HT-29 human colon cancer cells
Version: 1Date:29 July 2011
Reviewer: Sang Woon Choi
Reviewer's report:
Major Compulsory Revisions
1) Page 2: The method section of the abstract needs to be changed. Authors just
listed the names of method and did not address what they measured.
2) Page 12, Line 4: ‘IGF-1 stimulated the association of the p58 regulatory….’
What is ‘the association’? Please make it clear.
3) The conclusion section includes only a brief summary of the results. The
statement of significance of the results or the future perspectives could be
needed.
Minor Essential Revisions
1) Page 2: The method section of the abstract: What does MTT stands for? If the
method is just a routine one for cell culture work, it doesn’t need to be here.
Discretionary Revisions
1) Does HT-29 cell also increase the synthesis of IGF-I? If so, can it also be
inhibited by luteolin?
2) Would it be reasonable to test if IGF II stimulated HT-29 cell growth also does
not abrogate the luteolin-induced growth inhibition?
3) Authors used only one cancer cell line. It is curious whether or not luteolin also
inhibits normal cell’s IGF-IR signaling. If so, too much luteolin could be bad for
the normal cells, even though it is good to inhibit the cancer cell growth?
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-12-8 (2012)

Reviewer's report
Title:Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: a
retrospective multicenter chart review study
Version: 1Date:5 April 2011
Reviewer: Rodrigo Machado
Reviewer's report:
Minor essential revisions
1. Inconclusive results should be defined. Also, a reference should be provided
for the reference values (the previous validation study).
2. Results. If data in table 2 was analyzed using p for trend (degree of freedom =
1), it should be stated.
3. Conclusions are different in the text and in the abstract - in the text there is no
statement suggesting shortening the test to 10-13 min (Text: the test required
less than 10 min). Both are not exact. The mean duration was 10.24 min with SD
of 2.43 in Germany, for instance - it means that 2.5% have a duration larger than
15 min (as noted, max was over 20).
4. In order to further clarify this point, authors could state the proportion of tests
that would be inconclusive or false negative with the test lasting up to a given
time (such as 10 or 13 min).
5. References 14 and 15 are 7 and 8. Also, journals abbreviations should be
corrected (ref 2, 13). Also, ref 20 - the term "pylori" is lacking.
Discretionary revisions
1. Basic demographic data could be included to describe the study population
(gender, age distribution - at least min and max).
2. Advantages of shortening the test should be discussed as well as study
limitations.
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-12-8 (2012)

Reviewer's report
Title:Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: a
retrospective multicenter chart review study
Version: 1Date:28 June 2011
Reviewer: Luigi Gatta
Reviewer's report:
The aim of this study was to evaluate the duration of the time needed for
diagnosing Helicobacter pylori by the BreathID system.
The main drawback of this study was the lacking of a gold standard to evaluate
the performance of the BreathID system: the same device tested is used as gold
standard to diagnose the infection. Unfortunately this is a retrospective study,
and therefore It is not clear if this bias can be removed.
It would be worth also discussing more in detail the "test duration" and the "test
duration until diagnosis". Why did the test take on average 12.97 min. to be
performed in Italy and 15.10 in Germany? Was this due to difference of the
patients (e.g. PUD vs. NUD patients)?
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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-12-8 (2012)

Reviewer's report
Title:Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: a
retrospective multicenter chart review study
Version: 4Date:9 January 2012
Reviewer: Michael Fried
Reviewer's report:
I have reviewed the manuscript and would recommend to accept it for publication
in BMC Gastroenterology. I do not share the concerns of reviewer 2: The
comparison of this relatively new technology to standard infrared spectrometry
have already been performed and published. Furthermore it is not the goal of the
study to validate BreathID for the detection of HP infection but to explore if this
test would diminish the length of the measurement period. The authors
convincingly demonstrate that BreathID, probably by providing continuous 13C
data can distinctly shorten the measurement time to detect HP in patients. The
authors acknowledge that the high dose of citric acid may have also played a role
to achieve this effect. The findings are important and though this is an
retrospective and not comparative study relevant.
Review for 10.1186/1471-230X-12-7 (2012)

Reviewer's report
Title:Factors Linked to Severe Thrombocytopenia During Antiviral Therapy in
Patients with Chronic Hepatitis C and Pretreatment Low Platelet Counts
Version: 1Date:1 July 2011
Reviewer: Seyed-Moayed Alavian
Reviewer's report:
There are some comments for improvement the manuscript.
1- Thrombocytopenia is one of the extrahepatic manifestations of HCV infection
(Ref: Khattab MA, Eslam M, Alavian SM. Hepatitis C Virus as a Multifaceted
Disease: A Simple and Updated Approach for Extrahepatic Manifestations of
Hepatitis C Virus Infection. Hepat Mon. 2010; 10(4):258-69.) and a variety of
pathogenic mechanisms that are implicated in this abnormal finding are portal
hypertension and hypersplenism in the cirrhosis stage, autoimmune reaction to
platelets, and direct infection of platelet and megakaryocytes by HCV infection.
The authors should differentiate between these mechanisms especially the
existence of cirrhosis or not in their study group. The autoimmune reaction can
exaggerated more the thrombocytopenia.
2- I would lie to understand about the kind of study, retrospective or prospective?
3- It is important to differentiate between the kind of peginterferon,
thrombocytopenia is more common with peg 2a than 2b (Ref: Alavian SM,
Behnava B, Tabatabaei SH. The Comparative Efficacy and Safety of
Peginterferon Alpha-2a vs. 2b for the Treatment of Chronic HCV Infection: A
Meta-Analysis. Hepat Mon. 2010;10(2):121-31.)
4- The authors found that “low albumin (P=0.020), low Hgb level (P=0.026), low
platelet count (P=0.001), genotype non-1 (P=0.033), and rate of platelet decline
at week 2 (P<0.001) were significantly correlated with the development of severe
thrombocytopenia by univariate analysis (Table 2)), I think it means the existence
of cirrhosis before therapy and they should discuss it in the discussion part.
Level of interest: An article of importance in its field
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.
Declaration of competing interests:
No Competing interest
Review for 10.1186/1471-230X-12-7 (2012)

Reviewer's report
Title:Factors Linked to Severe Thrombocytopenia During Antiviral Therapy in
Patients with Chronic Hepatitis C and Pretreatment Low Platelet Counts
Version: 2Date:25 August 2011
Reviewer: Edoardo Giovanni Giannini
Reviewer's report:
The Authors have revised the paper following the suggestions, and the updated
version in improved in many points. I still have some minor queries.
Minor Essential Revisions.
- Page 6, 2nd line from the bottom: "...in whom liver biopsy was performed".
- Page 7, line 11. It is unlikely that "newly developed thrombocytopenia" was
categorised "deterioration" as the absence of thrombocytopenia was an
exclusion criteria of the study.
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:
Conflict of Interests Statement:
Edoardo G. Giannini received travel and lectures grant from
Merck/Schering-Plough, Hoffman-LaRoche, and GlaxoSmithKline.
Review for 10.1186/1471-230X-12-7 (2012)

Reviewer's report
Title:Factors Linked to Severe Thrombocytopenia During Antiviral Therapy in
Patients with Chronic Hepatitis C and Pretreatment Low Platelet Counts
Version: 2Date:9 September 2011
Reviewer: Seyed-Moayed Alavian
Reviewer's report:
After review the rivsed file, it can publish.
Level of interest: An article of importance in its field
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-12-6 (2012)

Reviewer's report
Title:GDNF protects apoptosis in enteric glia: Evidence for an autocrine loop
Version: 2Date:26 May 2011
Reviewer: Alexandre B M da Silveira
Reviewer's report:
Discretionary Revisions
- Figure 1 and 3 should present the augment or scale bars of all pictures.
- Figures 4 and 5 should be done without grids and all columns must have the
standard derivation.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-6 (2012)

Reviewer's report
Title:GDNF protects apoptosis in enteric glia: Evidence for an autocrine loop
Version: 2Date:14 June 2011
Reviewer: Bindu Chandrasekharan
Reviewer's report:
The authors Steinkamp et al in their article ‘ GDNF protects apoptosis in enteric
glia: Evidence for an autocrine loop’ aims to unravel the role of a neurotrophin-
glial derived neurotrophic factor (GDNF) in the regulation of enteric glial
apoptosis. The authors observed GDNF and apoptosis marker (caspase3/7) in
the biopsy specimens of Crohn’s disease patients by immunofluorescence. In
vitro studies on enteric glial cultures (EGC) revealed that the combination of
IFN-# and TNF-# induced apoptosis, but addition of GDNF to the culture does
not affect the amount of apoptosis. However, neutralization of GDNF in the EGC
cultures dramatically increased apoptosis in these cells. The authors claim that
as enteric glia produce high amounts of GDNF during inflammation, their results
suggest an autocrine apoptosis protection loop in these cells in CD.
The manuscript needs following revisions before publication.
Major compulsory revisons
1. The authors have shown GFAP/ Caspase-3/7 merge staining and GFAP/
GDNF merge staining in biopsies. It would be interesting to check if GDNF
positive tissue is positive for caspase-3/7 and this result would add to the
conclusions.
2. Have authors looked at expression of GDNF receptors (GFR and Ret) in the
Crohn’s patient biopsies-is there an upregulation?
3. The authors demonstrated that addition of anti-GDNF antibody increases the
extent of apoptosis induced by a combination of TNF and IFN. Is this true for
other cytokines like IL-1B or IL-6 on glial apoptosis. The authors could try a
combination of pro-inflammatory cytokines (TNF+ IL-6 + IL-1B) and validate their
result with anti-GDNF antibody.
4. The enteric glial cell apoptosis has been demonstrated by caspase3/7
staining, have authors looked at glial cell proliferation in the biopsies staining and
in vitro cultures by Ki 67 or BrDU staining. This would help assess if increased
apoptosis is related to decrease in cellular proliferation or an effect of GDNF in
itself.
Minor revision
5. The conclusion part of the manuscript seems to reiterate the results, authors
could cite more relevant references and compare and discuss their results.
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-12-6 (2012)

Reviewer's report
Title:GDNF protects enteric glia from apoptosis: Evidence for an autocrine loop
Version: 4Date:9 August 2011
Reviewer: Alexandre B M da Silveira
Reviewer's report:
No revision is needed
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-6 (2012)

Reviewer's report
Title:GDNF protects enteric glia from apoptosis: Evidence for an autocrine loop
Version: 4Date:12 August 2011
Reviewer: Bindu Chandrasekharan
Reviewer's report:
The authors Steinkamp et al in their article ‘GDNF protects apoptosis in enteric
glia: Evidence for an autocrine loop’ aims to unravel the role of a neurotrophin
glial derived neurotrophic factor (GDNF) in the regulation of enteric glial
apoptosis.
The authors have now performed additional experiments and included the new
data in the manuscript. They have also revised the discussion as suggested.
However one of the comments raised (comment no.4) has not been pursued as
the authors feel that it is beyond the scope of their manuscript. Otherwise I feel
that they have addressed all my concerns and the manuscript can be accepted
for publication in the current revised form.
Discretionary revision
1. The authors may include the statement that other cytokines like IL-6, IL-1B
had no effects on apoptosis in the results section (where they mention effects of
TNF-IFY), currently this is included as a part of the discussion in the manuscript.
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-12-4 (2012)

Reviewer's report
Title:High-dose clevudine impairs mitochondrial function and glucose-stimulated
insulin secretion in INS-1E cells
Version: 4Date:13 December 2011
Reviewer: Nazzareno Capitanio
Reviewer's report:
Authors have modified the manuscript so that it now strengthens their original
results. Therefore, I recommend the revised submission to be accepted without
further changes.
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-12-4 (2012)

Reviewer's report
Title:High-dose clevudine impairs mitochondrial function and glucose-stimulated
insulin secretion in INS-1E cells
Version: 4Date:14 December 2011
Reviewer: Bernard Fromenty
Reviewer's report:
NA
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-12-5 (2012)

Reviewer's report
Title:Value of fecal calprotectin in the evaluation of patients with abdominal
discomfort: an observational study
Version: 2Date:28 September 2011
Reviewer: Yinghong Wang
Reviewer's report:
COMMENTS FOR THE AUTHOR:
This is an observational prospective study of the diagnostic value of fecal
calprotectin based on the analysis of association between fecal calprotectin and
upper or lower endoscopy findings. It is a large series of 575 patients enrolled.
The data show that higher fecal calprotectin values before the endoscopy could
reliably predict the significant organic abnormalities in the GI tract. The predictive
value is less well in the upper GI tract than in the colon.
1. Authors mentioned 136 patients had both EGD and colonoscopy, among
them, 106 patients had negative initial endoscopy evaluation. What was the
indication for repeat evaluation in 53 patients? What was the initial calprotectin
level of these specific group of 106 patients?
2. Was there a change in the calprotectin level between the initial and follow up
endoscopy? What is the time gap between the two endoscopy evaluations?
3. Can the authors speculate what will be an appropriate evaluation option, EGD
vs colonoscopy or both for a patient with abdominal discomfort based on an
elevated fecal calprotectin level?
4. Is there any data on the level of fecal calprotectin post treatment for these
significant GI diseases e.g. esophagitis, gastritis, ulcers, etc in the follow up?
Can fecal calprotectin level be used to monitor the disease activity in the non-IBD
patients?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.