JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-023-02824-1 (2023)

Title: Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by
Multi-Omic data analysis
Version: 1 Date: 13 Apr 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors aim to show prognostic role of OSBPL3 and look
for the functionality of this gene. OSBPL3 is one of the potential drivers of MAPK/AKT
pathway and highly expressed in solid tumors. #t is related with poor prognosis in different
types of solid tumors. The authors selected CRC to show the prognostic role. They included
all stages of cancer noted major clinicopathological characteristics. However, they did not take
homogeneous stage, not noted surgery, right or left side colonic tumor, RAS and BRAF mutation
and MSI status. They outlined molecular pathways and the potential role of OSBPL3.  When
whole group analyzed, they clearly showed significant prognostic role of OSBPL3 in CRC.
In the context of oncology clinical practice, OSBPL3 must be analyzed in homogeneous stage
(You could not include stage I and 4 diseases together), and the study must include molecular
prognostic biomarkers like KRAS, BRAF, MSI, cerbb2 and treatment characteristics of the
patients. Therefore, this study produces theoretical  knowledge, but did not produce clinically
important data.
REQUESTED REVISIONS:
They have to exclude drug information, because these drugs are not used to treat CRC patients,
so any oncologist could use OSBPL3 for these drugs. Low clinical value and decrease the total
worth of the study.  Also they stated that IO agents and relation with OSBPL3 expression but
they did not include any patients treated with IO agents. They have to clear the sentences that
overstatement for the goal of this study.
ADDITIONAL REQUESTS/SUGGESTIONS:
They have to include strategies ( surgery, and chemotherapy) , patients characteristics ( right
and left colon, rectum cancer), and molecular test result KRAS, BRAF and MSI.
Review for 10.1186/s12876-023-02824-1 (2023)

Title: Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by
Multi-Omic data analysis
Version: 4 Date: 15 May 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: the authors made adequate response to each concern that raised by
reviewers. They also clearly showed the relation with OSBPL3 and Kras mutation which has
strong prognostic and predictive marker in CRC.
ADDITIONAL REQUESTS/SUGGESTIONS:
none
Review for 10.1186/s12876-023-02899-w (2023)

Title: Prevalence of Gastro-oesophageal reflux disease, and its associated risk factors among
medical students: A nation-based cross-sectional study
Version: 2 Date: 25 Jun 2023
Reviewer's report:
Dear Authors,
I found the paper interesting, mainly because it addresses an important topic and includes a very
high number of a specific population (medical students in Egypt).
However, some issues have to be taken into account and I kindly ask you to answer to them:
- The tables are not clear and are somehow misleading. I would not compare "total" vs.
"yes", meaning GERD population, but I would add the column "No GERD". In this way, the
comparison between the GERD and No-GERD population would be more meaningful and more
easy to read.
- It's difficult to figure out a real statistical differences in some of the variables, because they
are divided into >2 categories. I would keep BMI, Physical activity, analgesics and meals
dichotomous, in order to really understand in there are differences.
- All the statistically significant factors should be included in the logistic regression, for example
coffe consumption, physical activity and analgesics. Also, if you find any statistical significance
in the analysis of the BMI and number of meals when categorised in a dichotomous fashion,
these should be included in the logistic regression as well.
- The limitation paragraph should include only limitation, and not state that this is the first study
in Egypt (already underlined in the discussion.
Review for 10.1186/s12876-023-02883-4 (2023)

Title: Reply to comment on “Ultrasonographic scores for ileal Crohn’s disease assessment:
Better, worse or the same as contrast#enhanced ultrasound?
Version: 1 Date: 07 May 2023
Reviewer's report:
Your response letter to Nylund et al. is well written. However, I have some recommendations:
1) You state that endoscopy examinations were performed by an operator without experience
in ultrasound, “meaning that the operator did not have the knowledge to interpret ultrasound
findings”. I assume that the endoscopist was a certified gastroenterologist and knowledge of
ultrasound findings in GI diseases is essential for board certification in many countries. Even if
the person does not perform ultrasound exams by him or herself, I doubt that he or she cannot
interpret frequent ultrasound findings such as bowel wall thickening. Please try to find a more
plausible explanation.
2) Considering the SES-CD activity grading, you refer to a paper from 2009 (Ref. #5). Although
validation of inflammation activity scores is complicated, more recent papers have used SES-
CD in different approaches and with lower cut-offs. I would recommend acknowledging the
point of Nylund et al., that the cut-off SES-CD #7 is relatively high, and a lower value might
have also been justified.
Review for 10.1186/s12876-023-02883-4 (2023)

Title: Reply to comment on “Ultrasonographic scores for ileal Crohn’s disease assessment:
Better, worse or the same as contrast#enhanced ultrasound?
Version: 1 Date: 31 May 2023
Reviewer's report:
This retrospective study is comparatively innovative, and the authors' correspondence to
reviewers are objective. I agree to accept the paper. Look forward to verify the conclusion in
further perspective study.
Review for 10.1186/s12876-023-02882-5 (2023)

Title: Comment on “Ultrasonographic scores for ileal Crohn’s disease assessment: Better, worse
or the same as contrast#enhanced ultrasound?”
Version: 2 Date: 11 Jan 2023
Reviewer's report:
This comment is objective as there are indeed several problems in original paper. Since selective
bias is obvious in original paper, and no reproducible studies were designed, some results were
not credible.
Review for 10.1186/s12876-023-02882-5 (2023)

Title: Comment on “Ultrasonographic scores for ileal Crohn’s disease assessment: Better, worse
or the same as contrast#enhanced ultrasound?”
Version: 2 Date: 15 Jan 2023
Reviewer's report:
This is a comment on a recent retrospective study which focussed on contrast-enhanced
ultrasound in patients with inflammatory bowel disease. (Freitas et al.).
The authors address limitations of the work of Freitas et al., namely the retrospective approach
and methodology issues such as the applied cut-offs of the SES-CD score and the mode of time
intensity curve analysis.
This comment is welcome because
a) the authors are experts in the field
b) the addressed limitations have already been discussed during the review process (https://
bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-022-02326-6/peer-review)
I don't see relevant limitations in the present manuscript. However, I would recommend
discussing the issue of the algorithm used for the curve fit directly with Freitas et al. before
publishing a reproduction of their figure.
Review for 10.1186/s12876-023-02897-y (2023)

Title: Proton beam therapy for hepatocellular carcinoma with bile duct invasion
Version: 1 Date: 21 May 2023
Reviewer:  L.H. Wu
Reviewer's report:
Comments:
1.How did the authors discriminate bile duct invasion with other situations (i.e., oppression of
bile duct by tumor). Clinically, it is not surprising that bile duct invasion was found to be only
oppression of bile duct during resection in potentially resectable HCC.
2.How did the authors define central type BDI.
3.Please discuss about the influence of obstructive jaundice on the following therapies.
4.what about the combination usage of targeted therapies or immunotherapies among these
patients since the standard care of advanced HCC was not radiotherapy during the research
period.
5.it did not show typical imaging of HCC (i.e., wash-in and wash-out) in figure 4 and figure 5,
how did the authors establish the diagnosis in the absence of biopsy?
6. Several typo errors need to be corrected. (i.e., Table 2 classificaton)
7. in Table 2, it may be not appropriate to use "recurrence" since radiotherapy is not usually
deemed as radical therapy in HCC.
Review for 10.1186/s12876-023-02897-y (2023)

Title: Proton beam therapy for hepatocellular carcinoma with bile duct invasion
Version: 1 Date: 25 May 2023
Reviewer's report:
The aim of this retrospective study was to clarify the efficacy and safety of proton beam
therapy for hepatocellular carcinoma with bile duct invasion. Fifteen patients treated with proton
beam therapy were observed to have overall survival, local recurrence, progression survival
and adverse events. This study concluded that proton beam therapy was feasible with tolerable
toxicities for the treatment of hepatocellular carcinoma with bile duct invasion.
Hepatocellular carcinoma with bile duct invasion is rare, and resection has traditionally been the
primary treatment. The authors studied the efficacy and safety of treatment with the proton beam.
Major problem:
The DISCUSSION is redundant and lacks logic. Therefore, it is difficult to understand.
This study investigated the usefulness of proton beam therapy for hepatocellular carcinoma with
bile duct invasion. It would be easier to understand if we first list the problems from effectiveness
and safety in conventional treatment methods and then discuss conventional therapy and proton
beam therapy with comparison.
Miner problems:
1. Two out of 15 cases were described as recurrence-free. These recurrence-free patients had no
intrahepatic, distant, or local recurrences. However, the PFS at 3 years is 0%. Did both cases
die within 3 years without recurrence?
2. A statement is needed in the methods section regarding central vs. peripheral.
3. There are grammatical problems and spelling errors. Please proofread English by native.
Review for 10.1186/s12876-023-02897-y (2023)

Title: Proton beam therapy for hepatocellular carcinoma with bile duct invasion
Version: 2 Date: 14 Jun 2023
Reviewer:  L.H. Wu
Reviewer's report:
My comments were basically responded in a reasonable manner.  I think this manuscript is
acceptable in current manner given a minor revision.
In reply to comment #1,  The authors claimed that "In addition two radiologists
independently examined images of each patients enrolled in this study." This method may be
insufficient in a study protocol given that inconsistent opinion between two radilologists may
occur.
Review for 10.1186/s12876-023-02901-5 (2023)

Title: External Application of Mirabilite before Surgery can Reduce the Inflammatory Response
and Accelerate Recovery in Mild Acute Biliary Pancreatitis
Version: 1 Date: 27 Jun 2023
Reviewer:  Aleksandar Karamarkovic
Reviewer's report:
Interesting piece of investigation
Review for 10.1186/s12876-023-02903-3 (2023)

Title: 5-year Oncological Outcomes in Left-sided Malignant Colonic Obstruction: Stent as
Bridge to Surgery
Version: 3 Date: 28 Jun 2023
Reviewer:  Enrico Fiori
Reviewer's report:
The work does not add any additional information to the present literature. The authors, in this
retrospective study, described a small number of patients. The fact that the number of patients
with T4 tumors was significantly higher in the SEMS group than in the BTS group made the
oncological results less reliable.
Review for 10.1186/s12876-023-02903-3 (2023)

Title: 5-year Oncological Outcomes in Left-sided Malignant Colonic Obstruction: Stent as
Bridge to Surgery
Version: 3 Date: 02 Jul 2023
Reviewer's report:
This study investigates long-term oncologic outcomes of colonic stent placement as a bridge
to surgery in malignant colonic obstruction compared to upfront surgery. Presentation of 5-
year survival results is impressive, but retrospective nature and small sample size are significant
limiting factors that were also noted by the authors.
Major issues:
1. Were there any adverse events related to SEMS placement? They are mentioned in the
Methodology, but not reported in the Results section.
2. How were patients selected to receive SEMS as a bridge to surgery vs undergo upfront
surgery? Did you have reliable preoperative clinical staging results in all cases?
3. Were prognostic factors also tested in multivariate regression analysis?
Minor issues:
1. Table legends are missing in Table 1. Please clarify abbreviations.
2. What were the reasons for total colectomy?
Review for 10.1186/s12876-023-02900-6 (2023)

Title: Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of
HCC in high-risk population
Version: 0 Date: 11 Feb 2023
Reviewer:  Jin-Wook Kim
Reviewer's report:
This work assessed the diagnostic performance of methylated SEPT9 for HCC.
1. This study is case-control: screening performance cannot be deduced from this work.
2. What is the proportion of comorbid cirrhosis in HCC?
3. Liver function may affects the diagnostic performance of HCC tumor markers: present
albumin, bilirubin, prothrombin time, platelet counts data.
4. comparison of sensitivity / specificity may not be appropriate for comparing tumor marker
performances: present comparison of AUROC with p values: I guess the AUC did not seem to
differ between the markers.
5. Include AUROC comparison between AFP and AFP+mSEPT9.
6. As indicated in discussion, effect of viral markers need to be elucidated.
Review for 10.1186/s12876-023-02900-6 (2023)

Title: Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of
HCC in high-risk population
Version: 0 Date: 28 May 2023
Reviewer:  Mohamed Omran
Reviewer's report:
It’s my pleasure to be a referee to the manuscript titled “Methylated SEPT9 combined with AFP
and PIVKA-II is effective for opportunistic screening of HCC in high-risk population
In the present manuscript, the authors evaluated the prognostic value of methylated SEPT9
combined with AFP and PIVKA-II in the diagnosis of hepatocellular carcinoma (HCC).
There are so many selection and information biases that preclude it from being accepted in its
present form in the journal unless the authors review and change all the suggestions made by
the reviewers and me.
- The introduction section must be more focused on the diagnostic performance of methylated
SEPT9 combined with AFP and PIVKA-II.
All material and methods sections without reference
Information bias: Were the investigators who assessed these measures blinded by clinical data,
including if the patients had or did not have HCC?
- Clinical and routine laboratory data of HCC not present especially etiological factors
- AUROC cut-offs: How were the best cut-offs selected? Sensitive or specific?
-  Discussion section must present similar studies with details about other biomarkers' diagnostic
performances.
Review for 10.1186/s12876-023-02900-6 (2023)

Title: Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of
HCC in high-risk population
Version: 1 Date: 21 Jun 2023
Reviewer:  Jin-Wook Kim
Reviewer's report:
1. The authors claim that this work assessed "screening" performonace of serum markers in
combination  on the ground that samples were collected a prior of HCC diagnosis, but I do
not agree for the following reason:  for the screeing performances, "all control cases" (HC in
this study) should be examed who visited the institution in the same period as HCC cases were
chosen,  not 1:1 sampling (the authors should also present the selection criteria of study HC
population from the entire HC cases who visited authors' institution), regardless of prospective or
retrospective sampling. Otherwise, this study may claim "diagnostic performance of combined
markers" in the current case-control setting.
2.  Regarding the "What is the proportion of comorbid cirrhosis in HCC?",  the authors should
responsd with the percentage of cirrhosis in HCC patients "in THIS study", because many
markers are influenced by the presence/absence of cirrhosis.
3. Regarding liver function, I guess some patients were Child Pugh class B. Present the
percentages of Child Pugh class, and also add additional analysis stage-specific performance for
Child A vs B, like Fig. 3.
4. Regarding comparison of ROC, present the methods.
5. "Response: We also checked the references regarding the performance of mSEPT9, AFP and
PIVKA-II in HBV, HCV and  alcoholic HCC, and we found similar performance of the markers
in HCC with different etiology": present them in Results section.
Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 2 Date: 01 May 2023
Reviewer's report:
Comments to the Author
The article entitled ‘An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult
Patients with Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study",
reappraised the role of systemic chemotherapy for elderly with advanced biliary tract cancer. The
authors demonstrated from this large retrospective study that chemotherapy provided a survival
benefit in patients aged over 70 years old with metastatic BTC.
This study is well conducted and the manuscript is concise and reasonably well-written. The
authors should be commended. However, these are some suggestions to improve this manuscript.
1. The authors collected the data from patients with various ICD-O-3 topographical and
morphological codes. Therefore, the authors should provide the details of the patient according
to the code in Table 1 as there are many differences in the nature of disease amongst various
types of bile duct tumors.
2. Were all patients classified as ‘advanced’ in this study initially presented as advanced disease,
or classified as advanced after disease recurrence?
3. There should be more subgroup analysis according to the location of the disease other than
just gallbladder and non-gallbladder e.g. ampulla, intrahepatic cholangiocarcinoma, perihilar
cholangiocarcinoma, distal cholangiocarcinoma, etc.
4. Was there any difference in the rate of survival between each chemotherapy regimen, and
whether it is combined or monotherapy?
5. Since there is an inevitable selection bias when analyzing the benefit of chemotherapy from a
retrospective study. Besides performing propensity score matching, the authors should provide
more information on how the authors minimized the selective bias in this case.
6. Which parameters had been adjusted in propensity score matching? More discussion should
be made regarding the essential parameters affecting patients’ survival that cannot be included
in the analysis.
7. The primary outcome mentioned overall survival. What are the data on progression-free
survival and quality of life?
8. The author should provide more details on the site of metastasis, such as distant lymph node
or distant organ metastasis, as each could affect the patient’s prognosis and should be included
in the propensity score.
9. The author should provide more details on the number of lines of chemotherapy used in this
study. If the second-line chemotherapy was given, it should be mentioned.
Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 2 Date: 04 May 2023
Reviewer's report:
Thank you for your submitting the manuscript.  Tolerability significantly matters when systemic
chemotherapy undergoes for older patients, especially more than 70 years old. Your manuscript
is of importance to know and encourages physicians undergoing systemic chemotherapies for
older patients, but lack the data of what factors are leading to successful systemic chemotherapies
even in older patients over 70 years old. Randomized Phase III study of gemcitabine plus S-1
versus gemcitabine plus cisplatin in advanced biliary tract cancer, FUGA trial included older
patients less than age of 80. I believe this evidence is a kind of guideline for treating unresectable
bile duct cancer in Japan. I also reviewed that the recently published research focusing on
older patients from FUGA trial. It was well written in informative details ( Sci Rep. 2022 Jan
19;12(1):987.doi: 10.1038/s41598-021-04550-8) .
Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 2 Date: 12 May 2023
Reviewer:  Changqing Xie
Reviewer's report:
The authors Hirao T et al. presented a result from the analysis of efficacy of chemotherapy in
older adult patients with BTC based on patient's age. They used Japanese dataset with over 2600
patients included in the study. They found out older adult patients with metastatic BTC benefit
from chemotherapy especially patients whose age are less than 85 year old. This is an interesting
study and provides evidence to support chemotherapy in elderly patients with metastatic BTC.
This is also a well-designed and well written manuscript and will provide important information
in clinical practice.
Several information may need be addressed.
1) It seems like all patients were treated with chemotherapy in first line setting. Please include
some comments about the role of chemotherapy in second line setting in these population though
we have to acknowledge there is limited options even in general for metastatic BTC.
2) Please add the newly published KEYNOTE-966 data in the discussion.
Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 3 Date: 06 Jul 2023
Reviewer's report:
Comments to the Author
In the revised version of the article entitled ‘‘An Age-group Analysis on the Efficacy of
Chemotherapy in Older Adult Patients with Metastatic Biliary Tract Cancer: A Japanese Cancer
Registry Cohort Study”, The authors' response to my comments is sincere, and they have made
extensive revisions. The manuscript has been obviously enhanced.
I would like to inform you that this version is excellent. I have no more comment.
Respectfully yours,
Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 3 Date: 17 Jul 2023
Reviewer's report:
I am confident that my intentions have been effectively conveyed to the authors, and I genuinely
appreciate their diligent efforts.
Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 3 Date: 18 Jul 2023
Reviewer's report:
Thank you for giving a consideration to my suggestions.  I reviewed your amended manuscripts,
which is satisfactory to acceptance to our journal.
Review for 10.1186/s12876-023-02873-6 (2023)

Title: Comprehensive analysis of m6A regulators associated with immune infiltration in
Hepatitis B virus-related hepatocellular carcinoma
Version: 2 Date: 10 Apr 2023
Reviewer's report:
The study is very interesting and important to analyze the m6A regulators associated with
immune infiltration in Hepatitis B virus (HBV)-related hepatocellular carcinoma. The paper is
well written and well conducted. However, some deficiencies must be corrected or they cannot
be accepted for publication
1. The authors used bioinformatics methods to screen the differentially expressed m6A related
genes based on TCGA databases. However, more detail of method on data processing need to be
added, to make sure readers could repeat this work and result. The bioinformatics methods used
in this study is traditional. There should be further animal or clinical experiments to validate
the article conclusions.
2. A prognostic signature (m6A clusters) containing these m6A related genes was constructed
and significantly correlated with overall survival (OS). The reported results are interesting, but
it’s too preliminary for the mechanism in this study. It is very interesting to give more insight
into the target molecules of these m6A related genes and the mechanism by which these m6A
related genes can influence the development of Hepatitis B virus (HBV)-related hepatocellular
carcinoma.
3. The results are equivocal. In the results part, each subheading should be named with a specific
result. The correlation between the results of each part is poor.
4. The quality of the figure is poor. The gene name and GO and KEGG pathway information
in Figure 4 is not fully clear.
5. This paper attempts to establish a prognostic feature based on m6A clusters, which can be
used to predict the clinical prognosis of patients with HCC. But it was only attempted in one
compound, which could not account for the reliability of this method.
6. The authors found that the m6A related genes were significantly associated with clinical
prognosis and clinical pathological characteristics, tumor-related immune cell infiltration,
TIME, and immunotherapeutic response. It is better to further find the mechanisms by which
the m6A related genes to modulate the chemotaxis and function of immune cells in the tumor
microenvironment of HCC. There should be further animal or clinical experiments to validate
the article conclusions.
7. There are numerous spelling/grammar/formatting errors in the current version of the
manuscript. Please correct them carefully and seek help from qualified colleagues or
professional editing company if necessary.
8. If applicable, please provide full scans of the entire original gels displayed in your manuscript,
the original files for any microscopy images or flow cytometry data (.fcs) included in your
figures, and gating strategies for each flow experiment with clear labels to differentiate separate
experiments.
9. The author mentioned in the article that RT-qPCR validation has been completed. Please
provide the original RT-qPCR data and Figures. Figure 7?
10. Why should authors who did not contribute be included as co-authors?
Review for 10.1186/s12876-023-02873-6 (2023)

Title: Comprehensive analysis of m6A regulators associated with immune infiltration in
Hepatitis B virus-related hepatocellular carcinoma
Version: 2 Date: 17 Apr 2023
Reviewer's report:
This study is well-designed and the manuscript is well-written, but there are several concerns
still need to be solved before further proceeding.
1. “HBV” should be omitted in the title.
2. There are so many researches concerning the association between m6a regulators and HCC.
What is the difference between your research and before studies.
3. Authors performed the study using TCGA and GSE14520 dataset, but not both of them are
HBV-related HCC patients. Therefore, if it is appropriate to naming this title?
4. Why did not authors conduct both in vitro and in vivo experiments to further validate their
conclusions and explore specific mechanisms?
5. Authors ought to add more discussion content regarding present findings and previous reports
in the Discussion part.
6. In the Availability of data and materials part#there should be “hepatocellular carcinoma”
rather than “gastric cancer”. Also, authors should add the availability of GEO database.
Review for 10.1186/s12876-023-02873-6 (2023)

Title: Comprehensive analysis of m6A regulators associated with immune infiltration in
Hepatitis B virus-related hepatocellular carcinoma
Version: 10 Date: 04 Jul 2023
Reviewer's report:
I am glad to receive this revised version of the manuscript.The authors have revised the
manuscript thoroughly .They have not performed the experiments for validation for some
reasons, however, they have reanalyzed the existing data and conducted additional statistical
analyses,incorporated additional relevant references and conducted a comprehensive literature
review.These modifications provide further support for their research.Overall, I agree to publish
this research.
Review for 10.1186/s12876-023-02904-2 (2023)

Title: Gut Microbiota Analyses of Inflammatory Bowel Diseases from a representative Saudi
Population
Version: 2 Date: 05 Aug 2022
Reviewer's report:
Dear editor,
I feel sorry to reject a paper but I think the authors have to work on it. I provided useful feedback
for the authors. The paper lacks important methodological concepts and cannot be accepted due
to lots of bias and confounders. Consequently, It is not internally valid unfortunately.
Abstract
Introduction: please add abbreviations to Crohn’s and ulcerative colitis (UC and CD ) in the
first sentence so that you can use it later. Please correct grammar mistake in the introduction
( mediated disorders of the gastrointestinal tract are major contributors to the overarching
Inflammatory bowel diseases)
Results ( please add p values and confidence intervals to each result described).
Methods:
The first sentence should be in the introduction ( the aim of this study). Please explain the type
of study used more. Maybe reduce the introduction if you stuck with word counts.
Main manuscript
Line 97: I would use the term patients with IBD instead of IBD subjects
Line 98 add ‘at’ after internal medicine clinics instead of comma
Line 100: how does Crohns diagnosis based on endoscopy ? do you mean gastroscopy only
please clarify. Also please use ICD codes for diagnosis and add them to the method section.
Inclusion: how long patients were diagnosed with the disease? What treatment where they on?
It is important to know if they were on steroids or other immunosuppressants.
Regarding exclusion criteria: how about patients with recent infections such as gastroenteritis
or c. diff why not accounted for ? how about patients with active IBD  ?
CRP is not enough to determine activity. Stool fecal calprotectin plus a clinical score should be
used at least to exclude or control for those with active disease >
Sample size calculation was not explained.
Healthy control were not defined ? how the authors knew that they were “healthy” ?
Table 1 is lacking so many important details ( subtype of UC and CD), medications used, clinical
scores, fecal calprotectin results, medications used.
STROBE guidelines also not followed
Review for 10.1186/s12876-023-02904-2 (2023)

Title: Gut Microbiota Analyses of Inflammatory Bowel Diseases from a representative Saudi
Population
Version: 2 Date: 06 Sep 2022
Reviewer:  João Carlos Gomes-neto
Reviewer's report:
Dear authors,
I will try to be practical here, and my comments are intentionally made to help highlighting the
quality of the work and its impact. However, I understand that I may be intruding since I will be
proposing major changes in the structure of the narrative and figures.  This is not an imposition
but I suggestion in order to facilitate readability.
Here is how I would structure the new figures with the same data:
1. Alpha-diversity analysis panel
- use two metrics of alpha-diversity such as simpson and shannon indexes and plot across the
main treatment (IBD status or case/control status). You could use R face_wrap and break it apart
based on the other features such as age, sex, etc. I understand that some of these variables would
have to categorized or left as continuous for such a plotting. I would then run a glm model (alpha
metric ~ each variable) or a permanova model and retrieve the p-value and R-squared for each
variable and add to the individual plots partitioned by that corresponding variable. This panel
would exhaustively look at differences in alpha-diversity and the contribution of each variable
on the data.
2. Beta-diversity analysis panel
- this is similar to point 1, but now using Bray-curtis like you have with 2D PCAs colored by
each variable, while adding the p-value and R-squared per variable, which can be retrieved from
a permanova model.
3 - Once the diversity analysis has be done systematically, now you could use 2 approaches
to identify the genus and/or species differentiating between the major treatment (case-control
variable - IBD status)
- T.test with FDR or bonferroni correction vs the log fold change
- Random forest
4. Once you have identified the major taxa differentiating between the major treatment, now you
can seek to measure the real contribution of this taxa on predicting the outcome of interest (IBD
status), while accounting for the other factors in the model either as fixed or random effects.
If using IBD status as binary then a logistic regression model would work. That would be my
preference and each model would be stated as (ibd status ~ taxa + fixed  and/or random effect),
and the predicted probabilities could be graphically depicted.
5. Then lastly, I would explore the correlation between those taxa across treatments.
Other notes:
I don't think you would need to filter out minor taxa prior to doing the analysis, first because they
are part of the data and composition, and second, because those will not pop up as significant
anyway, but their heterogeneity may affect diversity metrics. Another thing that needs to be
clarified is if normalized or rarefied taxonomic data was used for the analysis. Maybe I missed
that point. If so, apologies.
Sincerely
Review for 10.1186/s12876-023-02904-2 (2023)

Title: Gut Microbiota Analyses of Inflammatory Bowel Diseases from a representative Saudi
Population
Version: 7 Date: 15 Mar 2023
Reviewer's report:
Overall this is a good study of the analysis of gut microbiome in this case-controlled study of
Ulcerative colitis and Crohn's disease patient cohort among the Saudi population. The paper is
well written and analyses are not exaggerated.
One aspect that could differentiate the story further, is that I am curious to know whether there
were differences in microbial genera within the ileitis and ileocolitis (N=110, i.e., about 90%
of Crohn's patients in this study); and how could that compare to other forms of inflammatory
Crohn's disease (Gastroduodenal, jejunal)? It is not clear whether these were distinct metadata
considerations.
The results section can be elaborated with data more clearly. Currently it looks like the writing
focuses more on the experimental methods.
Minor issues:
The level of statistical significance is unclear between the different genera compared in Figure
4 bar graphs.  Even if unsignificant, a comparison of the healthy Vs UC could be shown in this
figure, with all the individual OTU data shown in the scatter.
Review for 10.1186/s12876-023-02904-2 (2023)

Title: Gut Microbiota Analyses of Inflammatory Bowel Diseases from a representative Saudi
Population
Version: 7 Date: 24 Mar 2023
Reviewer's report:
Alsulaiman et al. reported the characteristics of the gut microbiota of IBD patients in Saudi. As
they described in the Introduction, few gut microbiota studies were reported in this area and
numbers of subjects (IBD patients: 219, Controls: 124) were very large, so this study is very
important in this field. However, they have to modify the manuscript prior to publication as
described below.
Major comments
1. They reported that two genera, Veillonella and Lachnoclostridium showed significant
association with CD versus controls. This is new and important in IBD study. Thus, I want
more detailed analyses about it. For example, what species are abundant in IBD or controls, or
what is the characteristics of those who have high abundances of these genera? I think that you
can specify bacteria at species-level by QIIME2. The present data look quite superficial. These
analyses will help deeper discussion.
2. In the Introduction, they described “considering the lack of microbiome studies
in Saudi populations”, but a few studies have been already reported (i.e. https://
pubmed.ncbi.nlm.nih.gov/36695274/ ). They should refer such previous reports and discussed
the difference between the present and previous ones.
3. Please check whether Supplementary figures are correct. For example, in the manuscript, they
described that sequence reads counts were shown in Fig S1, but actually FigS1 showed alpha-
diversity.
4. I felt that the explanation of Fig2 was incomplete. Please describe the result of Fig2 clearly
in the manuscript. In addition, age difference among three groups will influence the results of
gut microbiota comparison. I want to suggest that they should select the subjects in the same
age categories from three groups, and compare the microbiota of controls and patients in all the
age categories.
5. In the conclusion section, they described “we have shown that there key differences in gut
microbiota between this study and previous studies of larger Western populations”.However,
they did not present such data.
Minor comments:
Abstract,”Results”
“significant diversity” should be modified in an appropriate expression.
“observe” should be changed to “observed”.
Methods, “Study Populations”, line12:
Add “period” in the word “H. pylori”
Review for 10.1186/s12876-023-02904-2 (2023)

Title: Gut Microbiota Analyses of Inflammatory Bowel Diseases from a representative Saudi
Population
Version: 10 Date: 19 Jun 2023
Reviewer's report:
I am satisfied with all the author’s responses. Please check the following minor comments.
Minor comments:
Page2 line36: Please correct the sentence to “Crohn’s diseases and ulcerative colitis, both of
which are….”.
Page4 line92: Does “UD” mean “UC” ?
Page5 line105: “Crohn’s disease” and “ulcerative colitis” should be changed to “CD” and “UC”,
respectively.
Page5 line108: “H. pylori” should be in italic.
Review for 10.1186/s12876-023-02869-2 (2023)

Title: Risk factors for diabetic ketoacidosis in acute pancreatitis patients with type 2 diabetes
Version: 3 Date: 20 Apr 2023
Reviewer's report:
Dear editor,
I have read with interest the manuscript, and I propose to reject the manuscript. Here are some
suggestions about the manuscript
1. First of all the study population is too low.
2. The authors stated in the material-method section that the patients monitored their blood
glucose every 4 hours to observe whether DKA occurred within 48 hours after admission (self-
monitorization?). But it was not mentioned whether the patients received insulin therapy. For
example if a patient has hyperglycemia, he should receive insulin to prevent DKA development.
It is crucial to mention the therapy protocol, because it raises suspicion of ethical problems
(leaving patients without appropriate diabetes therapy).
3. Some spelling errors exist: starting a sentence with a number, “patients had a history of
drinking“, no space after numbers before brackets, some punctuation errors and so on.
4. How was poor glycemic control determined?
5. I think that the study has some important statistical errors. Median values should represent as
median (interquartile range) but the study included not a range in the brackets, just one value.
Two patients in group 1 and 3 patients in group 2 are female and the p value is <0.001 (?). The
smokers level are also different in two groups with such a low population count? Each group had
one each severe AP, and the difference was <0.001? The statistical analysis should be checked
by a statistical editor or reviewer.
6. The discussion part is also insufficient. It should include similar studies and compare
them with the present study (for example: Fu Y, Liu X, Cui B, Wang C, Liu Z, Zhao B.
Clinical Characteristics of Concomitant Diabetic Ketoacidosis in Type 2 Diabetes Patients
with Acute Pancreatitis. Diabetes Metab Syndr Obes. 2022 Jan 11;15:111-119. doi: 10.2147/
DMSO.S336619). If the authors think that they performed a different study, this should also be
mentioned.
7. More recently published references should be cited in the manuscript.
Review for 10.1186/s12876-023-02869-2 (2023)

Title: Risk factors for diabetic ketoacidosis in acute pancreatitis patients with type 2 diabetes
Version: 3 Date: 23 Apr 2023
Reviewer's report:
Despite the manuscript entitled "Risk factors for diabetic ketoacidosis in acute pancreatitis
patients with type 2 diabetes" sound scientific enough, there are few issues that must be revised
before consideration.
- Rationale of the study must be issued better in the background. Acute pancreatitis
is associated with elevation inflammatory markers (National Journal of Health Sciences
2021;6(3):90-91. DOI: 10.21089/njhs.63.0090) and cytokines (Rev Assoc Med Bras (1992).
2019 Feb;65(2):204-210. doi: 10.1590/1806-9282.65.2.204). Similarly, diabetes mellitus (Acta
Medica Mediterranea 2014;30:425-428) and its complications (Primary Care Diabetes, 2021;
15(6): 1071-1074.   DOI: 10.1016/j.pcd.2021.08.015.) are characterized with high burden of
inflammation. Hence studying diabetic ketoacidosis in acute pancreatitis patients is reasonable.
Improve the introduction section please.
- Small study cohort is the main methodological issue. However, methods were expressed well,
otherwise. Statistics are correct except lack of mentioning of the normality test that conducted
with to the study variables.
- Discussion is too short. Main aspects for a discussion were ignored. For example, authors
found serum uric acid as a risk factor for development of DKA. DKA is associated with
increased markers of inflammation. Similarly, high serum uric acid or uric acid based markers
were reported in other inflammatory conditions including hypertension (Postgraduate Medicine
2022;134(3): 297-302. DOI: 10.1080/00325481.2022.2039007), hepatic steatosis (Rev Assoc
Med Bras 2021;67(4):549-554. DOI: 10.1590/1806-9282.20201005.), thyroiditis (Rom. J.
Intern. Med. 2021;59(4):403-408. DOI: 10.2478/rjim-2021-0023.), metabolic syndrome (Rev
Assoc Med Bras 2019; 65(1):9-15.  DOI: 10.1590/1806-9282.65.1.9) and type 2 DM
(Aging Male. 2020;23(5):1098-1102. DOI: 10.1080/13685538.2019.1678126). In addition, I
recommend authors to comment on clinical usage of their findings even with few words. Finally,
single center nature could be added as another limitation.
Review for 10.1186/s12876-023-02869-2 (2023)

Title: Risk factors for diabetic ketoacidosis in acute pancreatitis patients with type 2 diabetes
Version: 7 Date: 02 Jun 2023
Reviewer's report:
I re-reviewed the manuscript's revised version. Authors responded adequately to my criticism in
previous review round. There is nothing more that require further revision. Hence, I recommend
publication.
Review for 10.1186/s12876-023-02889-y (2023)

Title: Symptoms and symptom clusters in patients newly diagnosed with Inflammatory Bowel
Disease: results from the IBSEN III Study
Version: 1 Date: 10 May 2023
Reviewer's report:
This is an interesting study aimed to examine the prevalence of symptoms and explore symptom
clusters and their possible associations with socio-demographic and clinical variables in a
prospective population-based inception cohort of patients newly diagnosed inflammatory bowel
disease.
The study was well performed and written and the aim is very interesting. I believe there are
some aspects to be clarified that would improve the quality of the study.
First of all, I believe it is necessary to clarify whether the same analyzes were carried out on
stool and blood samples in all the patients or whether only the data from available tests were
collected. It would also be necessary to specify whether the analyzes were centralized in a single
laboratory or not and which biochemical parameters were analyzed on the blood samples.
Authors should clarify the meaning of the following sentence "Fecal calprotectin values <30
and >1800 µg/g were registered as 29 and 1801 µg/g, respectively" (lines 151-152).
Although the numerical value does not change, the authors should standardize the unit of
measurement of fecal calprotectin (mg/kg or µg/g) both in the text and in Table 1. It is not clear
what the following sentence in the Table 1 legend refers to “*Fecal calprotectin values <30 and
>1800 µg/g were registered as 29 and 1801 µg/g, respectively”.
In the methods paragraph, the authors should state that the MSAS questionnaire was
electronically administered, as reported in the discussion.
Regarding the prevalence of symptoms, how do the authors explain a significantly higher
proportion of patients with dizziness among those with active disease?
Finally, I think the authors meant that no statistically significant association was found between
calprotectin # 250 mg/kg and cluster membership (line 255).