JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02516-2 (2022)

Title: The 30-day hospital readmission and mortality after surgery in colorectal cancer patients
Version: 3 Date: 13 May 2022
Reviewer's report:
This manuscript addresses the major concern of readmissions after colorectal surgery. The
authors utilized data from the Ministry of National Guard-Health Affairs Cancer Registry to
determine significant predictors of readmission, reasons for readmission, and assessed survival
rates.
Major Comments
1) The t-test is not appropriate for heavily skewed data. Was the appropriateness of the t-test
assessed? LOS and operation time are likely skewed.
2) A very large number of otherwise eligible patients were missing a discharge date for their
index admission and were thus excluded. Do you have an explanation for why so many patients
were missing discharge dates? I’m concerned these patients may be systematically different
from those whose discharge date was present, potentially skewing the results. Were there any
other variables included with similarly large percent missingness?
3) First paragraph of the results section: “Compared to non-readmitted patients, readmitted
patients were less likely to have regional stage (55.10% vs. 63.52%; P-value=0.03) but more
likely to have a distant metastasis (34.69 vs. 17.26; P-value=0.03).” This is not the correct
interpretation of the p-value of 0.03 from the chi-square test. Please correct. The p-value quoted
simply states that there is a significant association between readmission and stage, the p-value
does not directly compare the proportions in the two situations listed.
4) What was the justification for splitting table 3 based on tumor location? It would be interesting
to see this same analysis done with surgery approach and type.
5) 49 patients were readmitted, thus your multivariable model should have no more than 5 terms
included. The model presented has 12 thus is overfit and cannot be generalized to the overall
population. A forward stepwise approach would be more appropriate capping the terms at 5.
Further, treating Age, BMI, and LOS as continuous variables would be best to avoid loss of
power.
6) What statistical methods were used for the survival analysis? These should be addressed in
the statistical methods section.
Minor Comments
1) Last sentence of second paragraph of the introduction as the period in the wrong place.
2) “Multivariable” is the correct term to use throughout as opposed to “Multivariate”.
3) In Table 1 the total column should have a “% or SD” as opposed to only “%”.
4) Please be consistent in reporting percentages, use either 1 or 2 decimal places throughout; the
% symbol is also sporadically missing.
Review for 10.1186/s12876-022-02516-2 (2022)

Title: The 30-day hospital readmission and mortality after surgery in colorectal cancer patients
Version: 3 Date: 13 Jun 2022
Reviewer's report:
Authors reported that no prior studies assess the colorectal cancer rate  of hospital readimissions
among the Saudi population. The authors stated that Saudi peoples experienced CRC at late
stages with low survival rate and the rate of readmission after surgery is unknown. Following
datas from the Ministry of National Guard- Health Affairs Cancer Registry, the present study
aims to assess and clarify these issues. Identifying the rate of readmission and its predictors will
contribute to the development of interventions that should reduce readmission, hospitalization
costs and improve cancer patient outcomes
This is a retrospective cohort study that uses data from a Saudi national registry and it was
approved by King Abdullah international medical research center. Statistical analysis was well
conducted.
Compared to non-readmitted patients, readmitted patients were less likely to have regional stage
(55.10% vs. 63.52%; P-value=0.03) but more likely to have a distant metastasis (34.69 vs.
17.26; P-value=0.03). In the univariate analysis, there was a positive association between age
and readmission and females had higher odds of readmission than males, but both did not reach
a significance level.
The authors found that 13.76% of CRC patients were readmitted within 30-day of index
hospitalization, a finding that is slightly higher than previous studies. Gastrointestinal, urinary
tract and surgical site infection were the most frequent causes of readmission. Metastatic disease
is a reknowned factor that could affect the readmission rate.….
The high rate of open surgery (about 70%) can affect the high rate of readmissions for infections
(surgical site infection or gastrointestinal infection)? I think that optimizing and developing
a minimally invasive surgery program could be an effective resource of containing costs and
readmissions.
Review for 10.1186/s12876-022-02516-2 (2022)

Title: The 30-day hospital readmission and mortality after surgery in colorectal cancer patients
Version: 4 Date: 11 Jul 2022
Reviewer's report:
The term "Multivariate" should be updated to "Multivariable" in Table 4 to reflect the analysis
done.  The authors have otherwise addressed all of my comments.
Review for 10.1186/s12876-022-02468-7 (2022)

Title: Risk factors for portal hypertensive gastropathy
Version: 3 Date: 22 Jun 2022
Reviewer's report:
Thank you for the manuscript entitled “Risk factors of portal hypertension gastropathy.” I found
it very interesting and clear. Here are my comments:
1. The grading of severity of PHG has an important role on this study as you mentioned in
Discussion that the diagnose often fluctuates. How many physicians made decisions on the
grading of the same patient? How long did the physicians work on the endoscopy or hepatology?
When the grading of the same patient had inter-observer difference, what the grading would
see as?
2. The first paragraph of Results, especially a few sentences of the end of it, is hard to understand.
Please rewrite it.
3. In Discussion and Conclusion, you mentioned “relieving the degree of varices may reduce
the occurrence/severity of PHG.” Is there any theory that might support this idea other than the
result of this paper?
4. There are some typos: as in 31th or Spearmamn.
Review for 10.1186/s12876-022-02532-2 (2022)

Title: Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is
associated with immunotherapy efficacy and survival in colorectal cancer
Version: 1 Date: 29 Jun 2022
Reviewer's report:
The authors have conducted a detailed database-based analysis of the relationship between
colorectal cancer SELENBP1 expression and the cancer microenvironment and have derived
solid results. The research is very clear and easy to understand.
1) The authors should include a clearer picture of Fig. 2b, which clearly shows that the expression
level of SELENBP1 is decreased in the tumor area.
2) For Fig. 2c-f, the authors show immunohistological staining of normal and tumor. Can you
show that the degree of SELENBP1 expression in tumors correlates with prognosis, based on
the results of immunohistological staining at your institution?
3) For Fig. 3b, if the AUC is less than 0.5, can you show the predictive endpoints in reverse?
4) It is a very important finding that SELENBP1 is associated with immune infiltration and
efficacy of immunotherapy. However,   what is shown in Fig. 9i alone is not a sufficient evidence
for a favorable antitumor effect of SELENBP1 expression on immune checkpoint inhibitors. We
do not question the overall results of the authors' study, but a figure should be included at the
end that supplements and reinforces the validity of the results presented in the database. Various
analyses have been performed, but as a result, there is a lack of new scientific knowledge for
the reader to gain.
Review for 10.1186/s12876-022-02532-2 (2022)

Title: Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is
associated with immunotherapy efficacy and survival in colorectal cancer
Version: 4 Date: 10 Aug 2022
Reviewer's report:
The authors carefully and vigorously considered my suggested and therefore improved
significantly the manuscript.
One question remains to be answered:
9) The manuscript results are extensively based on bioinformatic analysis, please
provide R code in github for the analysis.
Reply:
Thank you for your detailed comments. We've provided the R code on Github at
zczhuchenghc@163.com.
I wasnt able to find R code on Github using author suggested link or account.
This is important for other scientists to test and to repeat the current results. Please provide
working Github link for R code.
Review for 10.1186/s12876-022-02532-2 (2022)

Title: Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is
associated with immunotherapy efficacy and survival in colorectal cancer
Version: 5 Date: 03 Oct 2022
Reviewer's report:
The manuscript has been much improved and is in nice condition.
I think this manuscript will be acceptable now.
Review for 10.1186/s12876-022-02510-8 (2022)

Title: A 9#gene expression signature to predict stage development in resectable stomach
adenocarcinoma
Version: 6 Date: 02 Jul 2022
Reviewer's report:
At present, this research lacks novelty, and  all data was collected through public database.
Therefore,  I suggest a major revision for this manuscript in order to make this manuscript meet
criteria for publication.
Firstly, the authors should polish their manuscript because of appearance of some grammar
mistakes.
Secondly, the authors should compare their own model with previous signatures to show this
model better.
Finally, the authors should conduct the experimental analysis on the 9 genes at the level of
protein to strength their findings.
Review for 10.1186/s12876-022-02510-8 (2022)

Title: A 9#gene expression signature to predict stage development in resectable stomach
adenocarcinoma
Version: 6 Date: 19 Jul 2022
Reviewer's report:
Liu et al. identified a 9-gene signature to predict cancer stage in STAD. Different datasets and
methods were used to validate the results. Overall, manuscript is well written and analysis is
rigorous. I have few concerns that should be addressed in the manuscript.
(1) Please elaborate abbreviations on their first appearance in the manuscript, Example: AJCC,
TNM.
(2) “There are chances to link the gene expression profile.” Incomplete statement.
(3) There are some sentences which are not clear. Ex: Considerable understaging still occurs “.
Authors are advised to proofread the manuscript with native English speaker.
(4) Introduction lacks detailed information on association of genes with STAD prognosis/
survival. There are numerous studies which used gene signatures to predict prognosis or survival.
Authors must provide clear and detail information on what are the previous studies that identified
gene signature to predict prognosis in STAD and describe the novelty and advancements of this
study.
(5) Generally, the grouping of stages would be early and later stages.
(6) “The present study aimed to perform …. based on bioinformatic algorithms”. What is
bioinformatics algorithm?
(7) In the methods, what is T stage information? What is the criteria to divide the patients into
low and high-stage groups? What about stage IV? Why stage IIb is under high-stage group while
IIa under low-stage group?
(8) Perform the gene expression difference between stage IIa and IIb. Are they significant?
(9) Why the data was split into 66.7% and 33.3% for training and validation. Usually, data is
split into 5:5 or 6:4 or 7:3 or 8:2 etc. Please define training-validation set.
Review for 10.1186/s12876-022-02520-6 (2022)

Title: Comparing Diagnostic Performance of Cantonese-Chinese version of Rome IV Criteria
and a short Reference Standard for Functional Dyspepsia in China
Version: 1 Date: 19 Aug 2022
Reviewer's report:
A. Strength
# The title cover the content of the study
# The abstract provide an accessible summary of the paper
# The introduction provide background and information relevant to the study
# The findings described by the author correlate with the results
# The results of the study are confirmatory but not novel.
# The figures and tables clear and legible.
# The manuscript is adequate for ethical issues.
B. Major issues that should be corrected are:
# A sample size of 220 subjects is not representative for Cantonese people, which have over
80 million native speakers with the prevalence of functional dyspepsia is 30%. So, you have to
justify why the sample size of 220 participants is selected in this study?
# You have divide methods in to two phases. Please combine them by replace phase one by
one short paragraph. E.g. “The English version of the Rome IV diagnostic questionnaire were
translated to Cantonese by professional medical translators, and Cantonese R4DQ-FD were pre-
tested in ten FD patients before data collection”.
# Please discuss your pertinent findings in relation to other studies findings.
C. Minor issues that should be corrected are:
# How do you classified health status as poor, very poor, good…? Please put operational
definitions in methods.
# Add China on the title.
Review for 10.1186/s12876-022-02520-6 (2022)

Title: Comparing Diagnostic Performance of Cantonese-Chinese version of Rome IV Criteria
and a short Reference Standard for Functional Dyspepsia in China
Version: 3 Date: 19 Sep 2022
Reviewer's report:
strengths:
The title cover the content of the study
The abstract provide an accessible summary of the paper
The introduction provide background and information relevant to the study
The findings described by the author correlate with the results
The results of the study are confirmatory.
The figures and tables clear and legible.
The manuscript is adequate for ethical issues.
Review for 10.1186/s12876-022-02511-7 (2022)

Title: Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment of advanced colorectal
cancer: A meta-analysis
Version: 1 Date: 28 May 2022
Reviewer's report:
Dear authors, thank you for your manuscript entitled "Efficacy and safety of anti-PD-1/PD-L1
therapy in the treatment of advanced colorectal cancer: A meta-anaylisis"
I find the quality of your manuscript good, the content clair and coherent, the linguistic style
adopted appropriate, with no major linguistic issues.
However, I will add some minor comments  to improve the quality of the manuscript:
- In the inclusion criteria (line 63): study investigating efficacy of anti PD-1/PD-L1.
However, you included also  combination studied of anti PD1 /PD-L1 + anti CTLA4.
Please specify in the inclusion criteria that combinational strategies with antiangiogenetic
treatments were admitted, since a possible impact on MSS subgroup has been highlighted and
remarked in the discussion .
- line 99 remove parenthesis OSR)
- I will add in the discussion a brief comment on toxicities with comparison with the main studies
of immunotherapy in lung and melanoma cancers (useful to clarify that they were stackable).
- Please add reference in line 169
- I suggest to read these articles and integrate them in your manuscript
El Jabbour T, et al. PD-L1 protein expression in tumour cells and immune cells in mismatch
repair protein-deficient and -proficient colorectal cancer: the foundation study using the SP142
antibody and whole section immunohistochemistry. J Clin Pathol. 2018 Jan;71(1):46-51. doi:
10.1136/jclinpath-2017-204525. Epub 2017 Jun 30. PMID: 28667193.
Valentini AM,  et al. PD-L1 expression in colorectal cancer defines three subsets of
tumor immune microenvironments. Oncotarget. 2018;9(9):8584-8596. Published 2018 Jan 12.
doi:10.18632/oncotarget.24196
- please correct by adding all the missing "t" in the PRISMA 2020 checklist.
Thank You
Dr. Claudia Parisi
Review for 10.1186/s12876-022-02511-7 (2022)

Title: Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment of advanced colorectal
cancer: A meta-analysis
Version: 1 Date: 09 Jul 2022
Reviewer:  Giulia Poli
Reviewer's report:
In mixed studies we suggest ROBINS-I and RoB 2 tools.The QUADAS-2 is to prefer in the
acuracy diagnostic methanalysis, instead of intervention metanalisys or proportion metanalisys.
In mixed studies we suggest ROBINS-I and RoB 2 tools.The QUADAS-2 is to prefer in the
acuracy diagnostic methanalysis, instead of intervention metanalisys or proportion metanalisys.
Statistical analisys: evaluation of  primary end points:
objective response rate
disease control rate
progress free survival rate
overall survival rate
Specifical outcome tools  are nedeed in a proportion metanalisys, because this is not an acuracy
diagnostic methanalysis. Those are not clearly specified in the statistical analisys report. The
between study heterogeneity is correctly described. A < or >50% I2 index is specified in the
fixed effet or a random effect model.
Forest plots: negative mesurementes are not allowed in a proportion metanalisys. Fig. 4a
presents negative mesurements; in Fig 6a some studies have a negative confidence interval.
We suggest to specifie how to measure your primary and also secondary end points.
We suggest to present in this study your Influence Analisys. (this is not important to specifie an
influence analisys on the secondary end points)
Review for 10.1186/s12876-022-02514-4 (2022)

Title: Prognostic value of long-term antidiabetic and antihypertensive therapy in postoperative
gastric cancer patients: the FIESTA study
Version: 2 Date: 24 Jul 2022
Reviewer:  Tsutomu Namikawa
Reviewer's report:
I read the manuscript “Prognostic value of long-term antidiabetic and antihypertensive therapy in
postoperative gastric cancer patients: the FIESTA study". The authors investigated the efficacy
of the long-term antihypertensive and antidiabetic therapy for the patients who underwent
gastrectomy for gastric cancer in authors’ institute. This paper had a valuable information to
treat gastric cancer; however, there were several unclear points to be revised. My comments are
as follow.
1. The authors described that patients with diabetes mellitus and hypertension had remarkably
poorer survival duration than non-hypertension and non-diabetic patients. However, Figure
1 showed that patients with hypertension had better survival duration than non-hypertension
patients. Authors should confirm this result.
2. Generally, many factors are involved in survival of patients with cancer. In this study, the
untreated diabetes mellitus group had more stage IV and underwent chemotherapy patients than
the other two group. Have you tried these results in a multivariate analysis?
3. Abbreviations should be defined at the first appearance (i.e., AMPK, PD-L1). The authors
should prepare the manuscript with close attention.
Review for 10.1186/s12876-022-02514-4 (2022)

Title: Prognostic value of long-term antidiabetic and antihypertensive therapy in postoperative
gastric cancer patients: the FIESTA study
Version: 2 Date: 01 Aug 2022
Reviewer's report:
This is a prospective cohort study evaluating hypertension and diabetes as a risk of mortality in
gastric cancer patients based on a large n. Interesting results have been obtained. I would like
you to address a few points of concern.
1.   The authors wrote in "Mortality risk estimation" section, "As presented in Figure 2, Figure
3, and TableS3, after adjusting for age, gender, tobacco and alcohol As presented in Figure 2,
Figure 3, and TableS3, after adjusting for age, gender, tobacco and alcohol, and family history of
tumor, the overall mortality risk of patients with antihypertensive and hypoglycemic therapies
was lower by 42% (HR: 0.58, 95% CI: 0.47-0.73, p<0.001) and 70% (HR: 0.30, 95% CI:
0.24-0.38, p<0.001). Are the HRs in Figure 2 and 3 adjusted hazard ratios? Please explain in
detail how you estimated the HRs in Figures 2 and 3. It appears that the results of univariate
analysis are described as the results of multivariate analysis.
2. In the Survival comparison of medications, "(HR:0.33 compared to HR: 0.71 for Cox
regression and p:0.0152)" and "(HR:0.16 compared to HR: 0.86 for Cox regression, Log-rank
test p:0.0003). What does this mean? What does this mean? Please write the results correctly
so that the reader can understand the meaning correctly. The p-values are also mixed where the
logrank test is written and where it is not.
3. What is the classification of TableS2? Please describe the Characteristic correctly.
4. Please put Tick mark and No. at risk on all KaplanMeier curves.
Review for 10.1186/s12876-022-02514-4 (2022)

Title: Prognostic value of long-term antidiabetic and antihypertensive therapy in postoperative
gastric cancer patients: the FIESTA study
Version: 3 Date: 22 Aug 2022
Reviewer:  Tsutomu Namikawa
Reviewer's report:
The author has revised the manuscript according to the suggestions.
I do not think there is much room for additional improvement in this article.
Review for 10.1186/s12876-022-02514-4 (2022)

Title: Prognostic value of long-term antidiabetic and antihypertensive therapy in postoperative
gastric cancer patients: the FIESTA study
Version: 3 Date: 31 Aug 2022
Reviewer's report:
A thoughtful response was made by the authors.
However, I would like to request one more response.
The KM curve shows a 95% confidence interval, but it is difficult to see the figure.
Please remove only the 95% confidence interval.
No other additional comments from me.
Review for 10.1186/s12876-022-02517-1 (2022)

Title: Multi-parametric Magnetic Resonance Imaging of Liver Regeneration in a Standardized
Partial Hepatectomy Rat Model
Version: 1 Date: 15 Jun 2022
Reviewer's report:
Caixin Qiu and collaborators evaluate the role of „Multi-parametric Magnetic Resonance
Imaging of Liver Regeneration in a Standardized Partial Hepatectomy Rat Model”. This is
an important study further establishing the role of small animal imaging techniques on liver
regeneration. However, several experimental aspects raise concerns.
Major issues:
1.       Lack of novelty. The main findings of the study were the following: “PH induced liver
changes that can be observed on MRI.” However, there are numerous preclinical researches,
which proved that micro-MRI is a suitable method to follow liver regeneration after various
surgical interventions (PH, PVL, ALPPS, etc).
2.       Ki67 index showed that the mitotic activity of hepatocytes reached the peak on
postoperative day 2 in the present study. According to literature data the peak of cell division
is somewhat earlier (24-30hour). Therefore, it is a need to validate the animal model used in
the current experiments and assess the possibility that technical elements accounted for this
deviation from literature results.
3.       In the pathological analysis groups the author did not measure the weight (or volume)
of the liver. By these measurements the validation of the model would be possible. In addition
these data could be compared with the volumetric alterations measured by MRI (giving some
additional information of the reliability of the used methods).
4.       The authors speculated that the significant increase in T2 values after PH results from
an increase in fat and water content of the residual liver. However, these alterations were not
analyzed completely in the pathological group. The wet, and dry weight of the liver lobes
were not measured. The wet/dry ratio of the liver was not calculated (edema formation). In
addition, to measure the fat content of the hepatocyte the authors used a simple semiquantitative
score on H&E slides. There is no information about the type/location of steatosis (macro-, or
microsteatotis/periportal, centrolobular), and the authors did not use special staining (e.g. Oil
red O).
5.       “The D value of tissues is affected by cell perimeter length, cell density, size, and
permeability, and a study showed that the cell perimeter length is the most important factor.
[…] K values are a measure of the complexity and heterogeneity of the cell microenvironment.”
However, the author did not analyze the micro-architectural alterations in regenerating liver
lobes, only measured the size of the hepatocyte on H&E stained slides (not reliable). By
immunohistochemical staining for cytokeratins - outline the cell membranes of the hepatocytes
– the determination is cell area and surface is more accurate. In addition, architectural changes of
the liver lobules and the alterations in connective tissue content could have also been evaluated.
This manuscript is not suitable for publication in the present form.
Review for 10.1186/s12876-022-02512-6 (2022)

Title: A simplified multiplex methylated DNA testing for early detection of colorectal cancer
in stool DNA
Version: 0 Date: 25 Jul 2022
Reviewer's report:
The manuscript highlights new changes introduced in a stool test ColoDefense that improves
its sensitivity for cancer detection.
A few comments/questions for the authors that need for be addressed before accepting.
1- Section 2.1.  What were the basis for selecting the subjects?  Were they symptomatic at
enrollment?
2- It is noted in Table 1 that the age median between cases and controls differ by 12 years.  This
is crucial as it is known that methylation increases with age. The authors did not address this
in the text and chose to skip over it.
I recommend that the authors show a plot of age distributions between cases and controls and
redo the analysis excluding controls that skew the age difference and show if this makes the
performance worse or stay the same.  This needs to be added to the paper.
Review for 10.1186/s12876-022-02512-6 (2022)

Title: A simplified multiplex methylated DNA testing for early detection of colorectal cancer
in stool DNA
Version: 1 Date: 16 Aug 2022
Reviewer:  Mai-britt Worm Orntoft
Reviewer's report:
Thank you for the revisioned version of the manuscript.
I think your revised manuscript has improved compared to the original version.
Best of luck with you validation of you test in a an actual screening cohort. I predict that the
loss of specificity will prove an obstacle for actual implementation, as your supplemental table
3 clearly showed, that with a control group more similar to the cases, specificity dropped below
90%.  The iFOBT test have a specificity above 95%, as I recall.
A side-by-side comparison of your test and the iFOBT test would be most interesting.
Best regards.
Review for 10.1186/s12876-022-02503-7 (2022)

Title: Translation and Evaluation of the Simplified Chinese Version of the Rating Form of IBD
Patient Concerns
Version: 2 Date: 18 Jun 2022
Reviewer's report:
In general, in this article, the authors made  a significant evidence-based  effort  to translate into
Chinese and validate the US-version of the Rating form of IBD patient concerns. We believe
that their venture adds to  existing literature and widens  horizons for research collaboration.
However, through our in-depth reading we came across several shortcomings  that need to be
resolved  in order for the manuscript to be considered for publication.
All our suggestions are summarized below:
1) In the selection criteria, the authors stated that they included patients with DEFINITE IBD.
This is not accurate. Please clarify. Was it histologically confirmed?
2)In the exclusion criteria the authors did not take into consideration co-existent diseases
and neuropsychiatric disorders that can affect the results of the study. Please discuss under
limitations
3) Recall period was set up to 14 days. It is too short to eliminate recall bias. Please justify how
it affects results and discuss under limitations?
4) As a measure of clinical activity the authors used QMS questionnaire which is solely used
in china. Why they did not use activity indices such as partial mayo, harvey-bradshaw? Please
justify. In addition the authors discussed in the section of limitations that they have not included
endoscopic and biochemical parameters. If they had used the abovementioned clinical indices
the abovementioned limitation would have been addressed and the study results would have had
more power.
5) In the translation process, the authors did not include representatives from the target
population. This practically means that FACE VALIDITY AND CROSS-CULTURAL
ADAPTATION WERE NOT CHECKED. Please discuss under limitations
6)When the authors evaluated the structural validity of their chinese version, they found poor
fit of their own data to the examined models. Why they have confined their analysis only to
those two models? What about their own novel model? This is really important for the reader
because it may  disclose diversities of the chinese  population in comparison with non-chinese
populations
7)Since COSMIN guidance for the measurement of the properties of the questionnaire please
add results for
a) content and criterion validity
b)measurement error
c) effect sizes where appropriate
Review for 10.1186/s12876-022-02503-7 (2022)

Title: Translation and Evaluation of the Simplified Chinese Version of the Rating Form of IBD
Patient Concerns
Version: 2 Date: 07 Aug 2022
Reviewer's report:
Thank you for giving opportunity to review your work.  I think the quality of the study is good
and I have only minor questions regarding it:
1.  Please clarify, whether patients  who did not complete the second questionnaire refused to
do so or were lost to follow-up?
2. Given the size of the study and size of China as country, I think it's  not possible to generalize
the study results to whole 'mainland china' as mentioned and the scope should be reduced to a
specific region in the country.
3. Over what time frame (weeks/months) were patients included in the study?
4. Please clarify what the level of education was for those patients, who did not have higher
education.
Review for 10.1186/s12876-022-02480-x (2022)

Title: Utility of ascitic tumor markers and adenosine deaminase for differential diagnosis of
tuberculous peritonitis and peritoneal carcinomatosis
Version: 2 Date: 03 Jul 2022
Reviewer:  Mikhail Nikolaevich Reshetnikov
Reviewer's report:
The section « Patient selection and diagnosis criteria» does not indicate whether patients with
HIV infection were included in the studies.
What forms of pulmonary tuberculosis have been observed in patients with tuberculous
peritonitis?
How long did patients with pulmonary tuberculosis receive antituberculosis therapy until the
detection of tuberculous peritonitis?
It is necessary to use new works by authors on this topic. References to the works of authors
dating from the last century are not desirable.
Review for 10.1186/s12876-022-02480-x (2022)

Title: Utility of ascitic tumor markers and adenosine deaminase for differential diagnosis of
tuberculous peritonitis and peritoneal carcinomatosis
Version: 2 Date: 24 Jul 2022
Reviewer:  Anurag Sachan
Reviewer's report:
The article is constructed well with  adequate statistical analysis.
The results are consistent with available literature.
The combination with cytology  could have been explored.
Few spelling changes such as uric instead urine in table 1. Capital initial letter for uniformity
in S1.
In discussion, different cut-offs for ADA and tumor markers  in available literature should have
been compared.
Review for 10.1186/s12876-022-02497-2 (2022)

Title: Bowel Preparation Using 2-Liter Split-dose Polyethylene Glycol Regimen Plus
Lubiprostone Versus 4-Liter Split-dose Polyethylene Glycol Regimen: A Randomized
Controlled Trial
Version: 2 Date: 10 Jul 2022
Reviewer's report:
Dear all,
I have had the pleasure to read the reseach article by Sirinawasatien et al. The draft is well written
and the trial seem logically constructed. Methods and statistics are well described. The colon
cleansing regime with 2 l PEG spit dose plus prior lubiprostone is new and has not been reported
so far. Results are clearly presented, if somewhat to be expected since lubiprostine showed in
a meta-analysis from 2016 a higher rate of patients with excellent colon cleansing in different
colon cleansing regimes. Nevertheless, this is  new and importand data in this field. I have just
one little annotation for the figures 2 and 3 to please add the subject number (N) of each group
in the caption.
In summary I support the publication of the article.
Review for 10.1186/s12876-022-02497-2 (2022)

Title: Bowel Preparation Using 2-Liter Split-dose Polyethylene Glycol Regimen Plus
Lubiprostone Versus 4-Liter Split-dose Polyethylene Glycol Regimen: A Randomized
Controlled Trial
Version: 2 Date: 30 Jul 2022
Reviewer's report:
1. This is a well designed, straight forward, RCT. No methodological mistakes or concerns.
2. It would be very beneficial if the authors can subcategorize polyps detected during
colonoscopies in the two different groups based on the pathology of the polyps (adenomas versus
sessile serrated lesions versus hyper plastic polyps) and the location.
3. Moreover, it would also be helpful if the author can provide the difference in withdrawal time
between both groups as it can reflect the time needed to clean the colon.
Review for 10.1186/s12876-022-02497-2 (2022)

Title: Bowel Preparation Using 2-Liter Split-dose Polyethylene Glycol Regimen Plus
Lubiprostone Versus 4-Liter Split-dose Polyethylene Glycol Regimen: A Randomized
Controlled Trial
Version: 3 Date: 07 Sep 2022
Reviewer's report:
Dear all,
Thank you for your revision of the draft  and the point-by-point answer. I have nothing more to
add and I support the publication of the article.
Kind regards
Review for 10.1186/s12876-022-02504-6 (2022)

Title: Late Hepatitis C Virus Diagnosis Among Patients with Newly Diagnosed Hepatocellular
Carcinoma: A Case-Control Study
Version: 1 Date: 24 Jun 2022
Reviewer's report:
Chang et al. reported that elderly and patients who have DM and alcohol related disease should
receive early HCV screening.
1. Definition of the control group is unclear. Authors should define that in the text in detail.
2. How was the HBV infection status of the study patients?
3. HCC is male-dominant diseases. How was the androgen receptor in the mechanism of the
development of HCC? Authors should discuss more.
4. Similarly, authors should discuss about the association between HCC and scenescence.
Review for 10.1186/s12876-022-02504-6 (2022)

Title: Late Hepatitis C Virus Diagnosis Among Patients with Newly Diagnosed Hepatocellular
Carcinoma: A Case-Control Study
Version: 1 Date: 20 Jul 2022
Reviewer's report:
Overall this is a great study and well written manuscript which paint a good picture of HCV
infection on a national level. It is unfortunate to find out that there are still significant percentage
of late diagnosis of HCV infection. The finding of the study will promote HCV screening to
prevent the devastating HCC in the future. However, it is worth noting that Taiwan has a robust
guideline regarding screening of HCV infection. In order to further improve the early detection
of HCV infection, adherence to guideline recommended care would be crucial. Future studies
to explore the barrier to lack of adherence might be consider.
Last but not least, female physicians are more commonly associated with good outcome based on
various gender studies, ranging from female surgeon to female primary care provider. One would
wonder if there is a significant gender preference in specialty selection, which result in better
outcome among male provider as they were more likely to be internalist or gastroenterologist.
A more comprehensive analysis should be consider when we reach such a sensitive conclusion.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 0 Date: 05 May 2022
Reviewer:  Yuusaku Sugihara
Reviewer's report:
The authors evaluated the effect of UC disease duration on FC was investigated and compared
to that on FIT. The result is that Similar to FIT, FC is affected by the duration of UC, indicating
that FC may be a highly useful biomarker, especially in short-term disease.
 This report represents an effort to accomplish this, as these data will most likely prove to be
a unique resource well into the future. However, there are many similar papers#Evaluation of
mucosal healing of ulcerative colitis by a quantitative fecal immunochemical test, Nakarai et
al), and the author should devise a way to convey the problem to be solved more clearly to the
reader. In particular, it should be clearly stated in the introduction.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 0 Date: 06 Jun 2022
Reviewer's report:
Thie article written by Ishida et al. is titled "Effect of Disease Duration on Fecal biomarkers in
Ulcerative colitis". This study explored the influence of UC duration on fecal calprotectin(FC)
by calculating the correlation between FC and endoscopic scores. The article has the correct
structure, which helps to reveal all The studied issues. The presented topic is relevant.
In lines 112 to 114, the author proposed to divide the patients enrolled in cohort 1 into the group
of short and long term disease duration, and the sample size is shown in Figure 1. But the reason
for such grouping is not explained, which may confuse readers.
In lines 238 to 239, the author used receiver operating characteristic analysis(ROC analysis) to
study the predictive value of FC and FIT for mucosal healing in different groups of patients.
Still, only P values and area under the curve were listed in Table 4. Adding the Figure about
ROC Curves of FC and FIT and labelling AUC will help illustrate the point.
Endoscopy is traumatic for patients, and the evaluation results are not entirely accurate.
Therefore, it is crucial to explore new biomarkers for UC treatment. The paper is logical and
helps to reveal the problem under study.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 0 Date: 04 Jul 2022
Reviewer:  Sakuma Takahashi
Reviewer's report:
It is my pleasure to review the manuscript entitled "Effect of disease duration on fecal biomarkers
in ulcerative colitis: A prospective cohort study". However, I have several concerns that need
to be addressed before considering publication.
1) The analysis of "Cohort 1" is quite complicated and difficult to understand. The authors write
that "In the analysis of the long-term disease-duration group, the group with a disease duration
of 16 years or more was omitted because of their small sample sizes. Similarly, in the analysis
of the short-term disease-duration group, the group with a disease duration of #2 years, which
had small sample sizes, were omitted. In addition, the data for groups with disease durations of
20 and 30 years or more were evaluated since the sample sizes of groups with disease durations
of 16 to 38 years or more were small." on line 180-186, page 11-12.
These sentences may give arbitrary Impression for readers.
2) The authors write that "To avoid the effects of colonoscopic preparation or examination
on biomarkers, fecal samples for FC and FIT were collected the day before or after the
colonoscopy." on line 138-139, page 9.  I wonder FC and FIT collected the day after
the colonoscopy are influenced  colonoscopic preparation or examination, especially biopsy
procedures.
3) The authors write that "We suspect that DNA damage via this mechanism also alters
the inflammatory cytokine profile of the intestinal tract and may affect FC, which reflects
neutrophils in the intestinal tract." on line 326-328, page 20. It may be appropriate to include
references support this hypothesis.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 1 Date: 24 Jul 2022
Reviewer:  Yuusaku Sugihara
Reviewer's report:
This report represents an effort to accomplish this, as these data will most likely prove to be a
unique resource well into the future. I think this paper should be published.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 1 Date: 02 Aug 2022
Reviewer:  Sakuma Takahashi
Reviewer's report:
It is my pleasure to review the manuscript entitled "Effect of disease duration on fecal biomarkers
in ulcerative colitis: A prospective cohort study".
The manuscript has been revised well. However, I have several concerns that need to be
addressed before considering publication.
1) The authors write that "To avoid the effects of colonoscopic preparation or examination on
biomarkers, fecal samples for FC and FIT were collected the day before or after the
colonoscopy." on line 140-141, page 9.
I wonder FC and FIT collected the day after the colonoscopy are influenced colonoscopic
preparation or examination, especially biopsy procedures. We published some papers on fecal
biomaker, but we always collect fecal samples the day before the colonoscopy.
Please analyze whether the timing of fecal sampling influence the result or not.
2) The authors write that "We suspect that DNA damage via this mechanism may also alter the
inflammatory cytokine profile, like the apoptosis signal pathway due to DNA damage, in the
intestinal tract and may affect FC, which reflects neutrophils in the intestinal tract [39]." on line
330-334, page 20. I read the 39th paper of the references, but I could not find such result. I think
[39] might be wrong. 40th paper of the references might be correct.
3) The authors write that "A previous study evaluated the relationship between FC and disease
duration for CD by dividing patients into groups with disease duration less than 10 years and
ten years or longer. The authors reported that disease duration did not affect the diagnostic
usefulness of FC [40]." on line 342-345, page 20-21. I read the 40th paper of the references,
but I could not find such result. I think [40] might be wrong. 39th paper of the references might
be correct.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 1 Date: 07 Aug 2022
Reviewer's report:
The article written by Ishida et al. is titled "Effect of Disease Duration on Fecal biomarkers in
Ulcerative colitis". This study explored the influence of UC duration on fecal calprotectin(FC)
by calculating the correlation between FC and endoscopic scores. Unfortunately, this article
didn't show its contribution to ulcerative colitis clinical management. The authors pointed out
that FC is more sensitive in UC patients with short disease duration, but didn't explain its guiding
significance and the definition of "short disease duration".
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 3 Date: 06 Sep 2022
Reviewer:  Sakuma Takahashi
Reviewer's report:
It is my pleasure to review the manuscript entitled "Effect of disease duration on fecal biomarkers
in ulcerative colitis: A prospective cohort study" again.
The manuscript has been revised well.
I think this manuscript is now acceptable for publication in BMC gastroenterology.
Review for 10.1186/s12876-022-02502-8 (2022)

Title: Effect of disease duration on fecal biomarkers in ulcerative colitis: A prospective cohort
study
Version: 3 Date: 13 Sep 2022
Reviewer:  Yuusaku Sugihara
Reviewer's report:
This report represents an effort to accomplish this, as these data will most likely prove to be a
unique resource well into the future. I think this paper should be published.
Review for 10.1186/s12876-022-02500-w (2022)

Title: Association between serum uric acid-to-creatinine ratio and non-alcoholic fatty liver
disease: a cross-sectional study in Chinese non-obese people with a normal range of low-density
lipoprotein cholesterol
Version: 0 Date: 11 Jul 2022
Reviewer's report:
1. Ethnic committee approval number should be listed.
2. Missing spaces in several places (E.g.,: serum uric acid-to-creatinine (SUA/Scr)).
3. Since the level of serum uric acid was affected by kidney function, the study should distinguish
patients with impaired kidney function or normal kidney function. eGFR should be used as
covariate added the analysis.
4. The levels of serum uric acid and  LDL-C were also affected by some medicine. The study
should consider the effect of medicine on SUA/Scr.
Review for 10.1186/s12876-022-02500-w (2022)

Title: Association between serum uric acid-to-creatinine ratio and non-alcoholic fatty liver
disease: a cross-sectional study in Chinese non-obese people with a normal range of low-density
lipoprotein cholesterol
Version: 0 Date: 25 Jul 2022
Reviewer's report:
The authors tested the association between serum uric acid-to-creatinine (SUA/Scr) and
NAFLD. The study includes large sample size and data presentation is clear.  However, study
concept and aim of the study is unclear and unacceptable.
1. Manuscript is descriptive rather than hypothesis verification. The aim of the number of
statistical analyses remains unclear.
2. The authors mention about the possible use of SUA/Scr for diagnosis for NAFLD. However,
there are a number of tools such as FLI, ZJU index and HSI to predict NAFLD. ROC analysis is
missing in the present manuscript. Cut-off values of SUA/Scr was not provided and significance
of SUA/Scr in terms of the clinical implementation remains unclear.
Review for 10.1186/s12876-022-02500-w (2022)

Title: Association between serum uric acid-to-creatinine ratio and non-alcoholic fatty liver
disease: a cross-sectional study in Chinese non-obese people with a normal range of low-density
lipoprotein cholesterol
Version: 1 Date: 19 Aug 2022
Reviewer's report:
Significance in the clinical practice is limited but the showing the potential association between
UA and NAFLD.
Review for 10.1186/s12876-022-02500-w (2022)

Title: Association between serum uric acid-to-creatinine ratio and non-alcoholic fatty liver
disease: a cross-sectional study in Chinese non-obese people with a normal range of low-density
lipoprotein cholesterol
Version: 1 Date: 09 Sep 2022
Reviewer's report:
The author has made the corresponding revision according to the revision opinion,I
it conforms to the publication standard.
Review for 10.1186/s12876-022-02501-9 (2022)

Title: Clinical Characteristic and Pathogenesis of Tumor-Induced Acute Pancreatitis: A
Predictive Model
Version: 1 Date: 17 Jul 2022
Reviewer's report:
1.Tumor such as pancreatic cancer are mentioned in the background as the leading cause of
admission for AP, but no literature support is provided. Because the incidence of tumor-related
acute pancreatitis was only 2.4% in the results, it ranked low and included three causes, such as
distal bile duct (14 cases), ampulla (13 cases) and pancreas (73 cases).
2.In the methods section, the author mentions that 360 patients in the control group were
randomly selected for inclusion, but what method was used for random selection? Why not 1:3
or 1:4, please describe in detail.
3.In the epidemiology section of the results, the incidence of tumor-related AP increased
significantly in 2020 and 2021 (0.81% in 2019, 3.83% in 2020, and 2.82% in 2021), why#
4.In the epidemiology section of the results, how is diet-related AP defined (diet-related (9.5%)),
and what foods are there? Is there a cause of hypercalcemia?  What is the difference between
idiopathic AP (12.7%) and AP associated with other etiologies(0.3%)?
5.In the Baseline clinical features section, "Compared with the control group, the tumor group
was less likely to have gallstone-related episodes.", how to determine whether this AP episode
was due to tumor or gallstone.
6.9% of patients underwent EUS examination, does it mean that only 9 patients were diagnosed
by EUS-FNA, and the other 91 patients were diagnosed with tumor-related AP by surgical
pathology? How to grasp the indications for surgery? Because the early manifestations of tumor-
associated AP are not specific, imaging may not have characteristic findings.
7.How is Vascular invasion defined?