JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02571-9 (2022)

Title: Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential
markers for ulcerative colitis: a retrospective study
Version: 1 Date: 03 Jul 2022
Reviewer's report:
The manuscript is focused on a relevant issue. Please address the following suggestions:
1) The abstract presents many abbreviations without the necessary description, ex. platelet-to-
lymphocyte ratio (PLR), please correct
2) In the introduction section please connect the sentences “Although we have found several
studies in the literature indicating that NLR and PLR could be used to evaluate UC severity.
The sample size is relatively small (…)”.
3) In the methods sections please detail the Etics committee approval of the study protocol and
wether informed consent was obtained. Please detail if the parameters collected are in outpatients
or if hospitalized patients were also included
4) In the discussion section, line 4, please replace “study” for “studies”.
5) In table 2 it would be relevant to discriminate if the disease extent and treatment are similar
in both groups (active and remitted)
6) In the table legends please replace “facal” for “faecal”.
Review for 10.1186/s12876-022-02571-9 (2022)

Title: Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential
markers for ulcerative colitis: a retrospective study
Version: 4 Date: 07 Aug 2022
Reviewer's report:
My previous comments have been addressed appropriately. Congratulations on your work.
Review for 10.1186/s12876-022-02571-9 (2022)

Title: Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential
markers for ulcerative colitis: a retrospective study
Version: 4 Date: 13 Aug 2022
Reviewer's report:
The authors revised well, but the  inherent  defect of  novelty limited the value.
Review for 10.1186/s12876-022-02575-5 (2022)

Title: Hypertension and diabetes mellitus are associated with high FIB-4 index in a health
checkup examination cohort without known liver disease
Version: 1 Date: 09 Jun 2022
Reviewer's report:
Review of “Hypertension and diabetes mellitus are associated with high FIB-4 index in a health
checkup examination cohort without known liver disease”
This study investigated the background of high FIB-4 index in the apparent health people
and found that hypertension and diabetes mellitus are associated with high FIB-4 index in the
apparent health people. This study is potentially interesting; however, several problems to be
solved.
1. To add the definition of cardiovascular disease in the Method section.
2. This reviewer understands that FIB-4 index was useful for diagnose liver fibrosis in the
patients with NAFLD or fatty liver disease. How to diagnose having NAFLD or fatty liver
disease? Did the authors evaluate the NAFLD or fatty liver disease by image?
3. Or, please discuss the usefulness of FIB-4 index in the people without NAFLD or fatty liver
disease.
4. How to evaluate the lifestyle factors, especially alcohol consumption?
Review for 10.1186/s12876-022-02575-5 (2022)

Title: Hypertension and diabetes mellitus are associated with high FIB-4 index in a health
checkup examination cohort without known liver disease
Version: 1 Date: 22 Jul 2022
Reviewer's report:
In the present manuscript the authors report the results of a cross sectional study investigating the
prevalence of elevated FIB-4 in the general Japanese population as well as the factors associated
with a higher FIB-4 score. The topic is of some interest and the population is large enough for
statistical analysis to be applied properly.
I have the following comments:
- Please revise the English (e.g “the prevalence of NAFLD has increased from 17.9% in 2016
to 18.8% in 2030”, we are not in 2030 yet, so it is expected to increase)
- It seems that a high number of participants were excluded because data were lacking on
variables included in the FIB-4 evaluation. Could you provide data showing that the features of
included and excluded participants were not different?
- It is not clear to this reviewer why participants with significant alcohol consumption were not
excluded from the study, given that authors chose to apply the NAFLD definition. Please also
describe if a particular questionnaire was used to estimate the degree of alcohol consumption
- It is not clear how authors chose variables to be included in the multivariate logistic regression
model. Please specify. I also suspect that the association between hypertension, diabetes and
high FIB-4 could become not significant after adjusting for age. Could you please also include
age in the model?
- Related to the previous point authors should report Odds Ratios and not Hazard ratios, since
odds ratios are obtained from logistic regression. Did the authors convert them in HR? If so,
please describe how. It is also not clear how the OR/HR for albumin and WBC is reported. Is
it for a standard deviation increase?
- I believe the manuscript might gain in interest if these results were compared with
recent studies perfomed on the association between NAFLD and hypertension (doi: 10.1097/
MEG.0000000000002299 and doi: 10.1161/HYPERTENSIONAHA.120.15220)
Review for 10.1186/s12876-022-02575-5 (2022)

Title: Hypertension and diabetes mellitus are associated with high FIB-4 index in a health
checkup examination cohort without known liver disease
Version: 2 Date: 22 Sep 2022
Reviewer's report:
The authors revised well. This reviewer has several comments.
1. Was history of ischemic heart disease or stroke collected with a self-report questionnaire?
2. Is the Fib-4 index a useful tool for people without fatty liver?
Review for 10.1186/s12876-022-02576-4 (2022)

Title: A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy
adults in China- a cross-sectional study
Version: 1 Date: 12 Sep 2022
Reviewer's report:
Comments to authors
Congratulations to authors
Manuscript is reasonably well written but need some language editing with a native speaker.
There are similar studies trying to characterize NAFLD/MAFLD subgroups, but this study
from an Asian country with different obesity cut off and definitions for metabolic syndrome is
pertinent.
Do you have any elastography reports to compare the subgroups? FIB-4 and NFS have
limitations as compared to image-based testing for fibrosis scores and amount of hepatic
steatosis?
Drug (herbal or dietary supplements) induced hepatic steatosis is a common occurrence in many
countries, did you consider this into your patient selection and analysis. It is sometimes difficult
to get this history from patients, particularly for OTC medications/products
I assume that most patients did not have biopsy, and this is not really required for diagnosis. But
did you consider liver biopsy in any of these patients, as in some cases the etiology of elevated
transaminases is speculative
I would recommend revising the discussion session and summarize it into 3 sections- first
briefly summarizing pertinent findings in this study and explaining its clinical relevance, second,
comparing it with existing literature and third session to explain the larger clinical relevance
and applicability of the study results with a mention of limitations of the study and scope of this
study to generate further studies
Review for 10.1186/s12876-022-02576-4 (2022)

Title: A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy
adults in China- a cross-sectional study
Version: 1 Date: 05 Oct 2022
Reviewer's report:
This is an interesting study and has merit and provides new and important information. However,
there are concerns that must be addressed.
1. There is a disconnection between the abstract and the introduction. Also, the entire analysis
on MAFLD. Thus, the introduction section needs to be extensively revised to start by MAFLD
as per the abstract and refocused around this
2. “Compared with the diagnostic criteria of NAFLD, the MAFLD definition are highly
consistent.” This needs to be modified to be “Compared with the diagnostic criteria of NAFLD,
the MAFLD definition is highly consistent and has superior utility”.
3. “These criteria can identify a group of people who have not been diagnosed with NAFLD.” It
should be “These criteria can identify a group of people who have been missed with NAFLD”.
4. Reference 2 needs to be replaced by another one specifically on MAFLD (PMID: 35587339,
PMID: 35710982).
5. The discussion section needs to be abbreviated and better synthesized the data.
6. Overall, the manuscript needs extensive editing, including for English.
7. There are multiple omissions of crucial references that need to be fixed (PMID: 35248211,
PMID: 34265276, PMID: 34129272, PMID: 36070122, PMID: 35143431).
Review for 10.1186/s12876-022-02577-3 (2022)

Title: Threshold of Main Pancreatic Duct for Malignancy in Intraductal Papillary  Mucinous
Neoplasm at Head-neck and Body-tail
Version: 1 Date: 05 Aug 2022
Reviewer's report:
This manuscript titled “Threshold of main pancreatic duct for malignancy in intrapapillary
mucinous neoplasm at head-neck and body-tail” is intriguing and informative. Li et al. showed
an informative retrospective study where different threshold of MPD diameter was determined
between IPMN in the pancreatic head-neck and in the pancreatic body-tail.  Although I partially
agree with the authors’ opinions, there were some problems in this manuscript. In addition,#
think that their interpretation and method of analyses are not enough to draw these conclusions.
Therefore, I regret to inform that this manuscript is not suitable for publication of BMC
gastroenterology. My suggestions are described below:
1) In general, a retrospective study is affected by the characteristics of its population and the
study concerning surgical specimen, like this study, is influenced by surgical indication of each
institution. In this study, about 40% of patients had no high-risk stigmata and/or worrisome
features. Therefore, the authors should clearly describe their institutional indication of surgery
in the treatment of IPMN.
2) The authors performed retrospective analysis including BD-IPMN. However, most BD-IPMN
does not have dilated MPD because malignant cells and plentiful mucin are not present in the
MPD. Therefore, I think it is not reasonable to determine the threshold of MPD to discriminate
malignant IPMN from benign one using all IPMNs including BD-IPMN. Rather than that, it
would be better to determine thresholds separately, between BD-IPMN and MPD-involved
IPMNs, and between the pancreatic head-neck and body-tail, respectively.
3) In multivariate analysis, factors should be determined by univariate analysis. However, in
this study, only specific factors were included in multivariate analysis. For example, univariate
analysis in the head-neck IPMN shown in Table 3 should include the factors which have
significant statistical significance in Table 1 such as serous CEA level, the presence or absence
of mural nodule, Diabetes mellitus, and so on.
4) The authors recommended the cut-off value of MPD diameter to distinguish malignant IPMN
as 6.45 mm in the pancreatic head-neck IPMN and 7.7 mm in the pancreatic body-tail. In
addition, in cases with MPD-involved IPMNs, 8.2 mm was suggested as threshold. In practice,
these values are too minute to measure in MRI and/or CT image. They should discuss about it.
5) In Table 1 and 2, only the number of patients was filled in some cells. It is quite difficult to
understand these cells, therefore, percentage should be added in them.
6) It would be better to add tangent line in receiver operating curve in figures.
Review for 10.1186/s12876-022-02577-3 (2022)

Title: Threshold of Main Pancreatic Duct for Malignancy in Intraductal Papillary  Mucinous
Neoplasm at Head-neck and Body-tail
Version: 1 Date: 01 Oct 2022
Reviewer's report:
Interesting paper on a surgical series of IPMN. I think the main limitation is the risk of selection
bias due to the fact that all patients underwent surgery. This way all the other patients are
excluded from the analysis thus missing other potential prognostic factors.
Other comments:
1) English grammar should be improved. I recommend the authors to have their manuscript
revised by a native speaker
2) I would emphasize in the discussion the role of EUS-through the needle biopsy in the
diagnostic management of PCLs, citing the recent relevant papers PMID: 35451041  and PMID:
32014422
3) I would also quickly comment the role of EUS in general in the management of pancreatic
lesions (both cystic and solid) citing the papers PMID: 35124072  and PMID: 27356212)
Review for 10.1186/s12876-022-02577-3 (2022)

Title: Threshold of Main Pancreatic Duct for Malignancy in Intraductal Papillary  Mucinous
Neoplasm at Head-neck and Body-tail
Version: 2 Date: 26 Oct 2022
Reviewer's report:
In this manuscript titled “Threshold of main pancreatic duct for malignancy in intrapapillary
mucinous neoplasm at head-neck and body-tail”, Li et al described that different threshold of
MPD diameter was determined to discriminate malignant IPMN from benign one in both head/
neck and body/tail in the pancreas. Although I think highly of their massive efforts to revise
this manuscript, you did not adequately reply to my suggestions. Therefore, I suppose some
revisions are needed in this manuscript. My suggestions are described below:
1) Your conclusion was quite ambiguous.  To determine surgical indication in the case
with MPD-involved IPMNs in the pancreatic head and/or neck, which threshold of the main
pancreatic duct would you recommend 6.5 mm or 8.5 mm? More clear description is needed.
2) You showed threshold of the MPD is 6.5 mm and 8.5 mm to identify malignant IPMNs in all
IPMN patients and MPD-involved IPMN cases, respectively. However, in the cases with branch
duct (BD)-IPMNs, the threshold would be smaller than 6.5 mm because the MPD diameter
is generally small in BD-IPMNs. In addition, Yoshioka et al [10] showed that MPD diameter
more than 3 mm as a risk factor of pancreatic ductal adenocarcinoma in the patients with BD-
IPMN, as you described. Therefore, I concern that some patients with malignant IPMN would
be excluded from surgical treatment if you use 6.5 mm as a threshold in the patients with BD-
IPMN. Therefore, it would be better to show thresholds of the MPD also in case of BD-IPMN.
3) In multivariate analysis, factors should be determined by univariate analysis. However, in
this study, only specific factors were included in multivariate analysis. For example, univariate
analysis in Table 4 should include the factors which have significant statistical significance in
Table 2 such as extra-pancreas extension and the presence of mural nodule.
4) In Table 2, diabetes mellitus should also be analyzed.
5) In table 3 and 4, it would be better to show data of the pancreatic head-neck and those of the
body-tail in separate tables.
Review for 10.1186/s12876-022-02563-9 (2022)

Title: A risk scoring system for advanced colorectal neoplasia in high-risk participants to
improve current colorectal cancer screening in Tianjin, China
Version: 3 Date: 23 Sep 2022
Reviewer:  Ragesh B. Thandassery
Reviewer's report:
We appreciate the authors for this detailed retrospective study.  It is a significantly extensive
database, and the results are pertinent. Diet and lifestyle profoundly impact colorectal cancer,
and including these factors in the analysis will be helpful. Also, the lack of external validation
limits these risk-scoring systems.
I recommend further organizing the discussion section for further clarification of the study's
relevance for patients.
Review for 10.1186/s12876-022-02563-9 (2022)

Title: A risk scoring system for advanced colorectal neoplasia in high-risk participants to
improve current colorectal cancer screening in Tianjin, China
Version: 3 Date: 04 Oct 2022
Reviewer:  Harishankar Gopakumar
Reviewer's report:
Dear Authors,
It was with great pleasure that I read your work titled “A risk scoring system for advanced
colorectal neoplasia in high-risk participants to improve current colorectal cancer screening in
Tianjin, China”
I commend the Authors on their well-researched and relevant work in the interesting field of
colorectal cancer screening, especially in resource limited settings.
The factors that have been included in the scoring system are recognized risk factors and
implementing these will be safe, inexpensive and convenient making it appropriate for the
purpose of screening. The odds ratio and thus the weights assigned to each risk factor in the
scoring system are consistent with contemporary understanding.
There are a few concerns that I have outlined below.
Minor
#1 There have been prior studies with various proposed scoring systems including some of the
risk factors considered in this paper. I am afraid this study suffers from lack of novelty.
Overall, the success of any screening program is multifactorial and depends on adherence,
awareness and willingness to proceed to the next step in case of a positive finding.
As the authors have mentioned, one of the main hurdles with the existing CRC screening
program in the geographic location where this study was conducted, is low adherence with
follow up.
Authors of this study propose that this scoring system could promote adherence to colonoscopy
recommendation. However, it is not clear how that could be.
# 2 There seems to be some inconsistencies with definitions.
For example, lines, 147,148, 149 “ACN was defined as CRC or advanced adenoma # 10 mm in
diameter or with villous components or high-grade dysplasia”.
However, under results, the authors mention that
“Of these, 14677 (49.7%) individuals were found to have CN, including 2324 (7.9%) and 462
(1.6%) diagnosed with ACN and CRC, respectively”
Based on the proposed definition by authors above, CRC would be included in ACN
# 3 Lines 209, 210, 211. Needs correction, clarity in discussion. Authors mention that “The
proportions of LR, MR and HR were 20.4% (6012/29504), 7.1% (1288/18208) and 12.2%
(1152/9463), respectively”.  This seems to be incorrect. I compared this to the data in Table 4.
The numbers 6012, 18208 and 9463 are the number of LR, MR and HR patients based on the
proposed scoring system, while the number 29504 is the total study population. The numbers
1288 and 1152 are patients with AN. Seems like for the above calculation, for MR and HR, it
should have been 18208/29504 and 9463/29504 respectively.
Review for 10.1186/s12876-022-02527-z (2022)

Title: Triclosan Exposure Induced Disturbance of Gut Microbiota and Exaggerated
Experimental Colitis in Mice
Version: 1 Date: 10 Jun 2022
Reviewer's report:
* Please  describe the methods carefully. It is not clear what method (protein, mRNA) was used
to assess expression of p65, occludin, TLR4 and others. And what housekeeping gene/protein
was used as control. It will be important to show representative protein (western blot) bands.
* Histology methods mentions 'Liver' samples, please read the manuscript carefully. Describe
how histology score in DSS was calculated.
* Include information on how many mice were used per group and if independent experiments
were conducted.
* Please check the panel numbers in the text.
* In fig 7, cytokine levels of controls should be included to compare the changes caused by DSS.
* Do authors have data on body weights in DSS colitis?
* What is "intraepithelial neoplasia" is not clear.
* What does author mean by "non-specific colitis?" (page 11, line 7)
* The conclusions are not fully supported by the data. For instance, bacterial translocation (page
11, line 5) is not actually shown. Please modify the language to match the actual results.
* Since the casual role of TCS-induced alterations in microbiota in promoting colitis is not
shown, I suggest modifying the title (e.g. Triclosan Exposure Induced  Disturbance of Gut
Microbiota and Exaggerated Experimental Colitis in Mice).
Review for 10.1186/s12876-022-02527-z (2022)

Title: Triclosan Exposure Induced Disturbance of Gut Microbiota and Exaggerated
Experimental Colitis in Mice
Version: 7 Date: 26 Sep 2022
Reviewer's report:
In this paper, Jing et al. proposed to determine the effects of triclosan (TCS), an antibiotic heavily
used in consumer products, on intestinal inflammation and ulcerative colitis model. The authors
have addressed all my concerns, which have made this manuscript significantly clearer and with
more realistic interpretation of results.
The only thing missing still regards the unit for the panel B in Figures 1, 4, and 7. Authors
replied my previous comment saying the proteins were detected by semi-quantitative western
blot without concentration unit, but they should indicate the normalization. Please include in
the Figure "relative concentration" or include “Protein/#-actin ratio” and include in the figure
legend they have been normalized to #-actin concentration (see examples PMIDs: 28864290,
33420088, 24837592) as this information is not mentioned elsewhere.
Review for 10.1186/s12876-022-02558-6 (2022)

Title: Adverse outcomes after non-hepatic surgeries in patients with alcoholic liver diseases: a
propensity-score matched study
Version: 1 Date: 01 Mar 2022
Reviewer's report:
1. Hepatitis and cirrhosis from other etiologies affect the postoperative outcomes in the previous
study. (3, 4) Please demonstrate the underlying liver diseases in matched controlled population.
2. Liver function improves within a few months after discontinuation of alcohol. (2, 5) Therefore,
the diagnosis of alcoholic hepatitis or alcoholic liver damage 24 months before surgery might
not influence postoperative complications. Is it possible to identify patients diagnosed within
six months before surgery?
3. Liver-related complications like jaundice, hepatic coma, gastrointestinal hemorrhage, ascites
and alcohol dependence syndrome were mentioned in table 4. Please identify the ICD-9 used
to identify all terms above.
4. Intraabdominal surgery had a higher mortality rate in patients with cirrhosis. (6, 7) We
suggested further subgroup analysis comparing outcomes of patients undergoing different types
of surgery.
References
1. Eliasen M, Grønkjær M, Skov-Ettrup LS, Mikkelsen SS, Becker U, Tolstrup JS, et al.
Preoperative alcohol consumption and postoperative complications: a systematic review and
meta-analysis. 2013;258(6):930-42.
2. Northup PG, Friedman LS, Kamath PSJCG, Hepatology. AGA clinical practice update
on surgical risk assessment and perioperative management in cirrhosis: expert review.
2019;17(4):595-606.
3. Del Olmo JA, Flor-Lorente B, Flor-Civera B, Rodriguez F, Serra MA, Escudero A, et al. Risk
factors for nonhepatic surgery in patients with cirrhosis. 2003;27(6):647-52.
4. Befeler AS, Palmer DE, Hoffman M, Longo W, Solomon H, Di Bisceglie AMJAoS.
The safety of intra-abdominal surgery in patients with cirrhosis: model for end-stage
liver disease score is superior to Child-Turcotte-Pugh classification in predicting outcome.
2005;140(7):650-4.
5. Bhangui P, Laurent A, Amathieu R, Azoulay DJJoh. Assessment of risk for non-hepatic
surgery in cirrhotic patients. 2012;57(4):874-84.
6. Mansour A, Watson W, Shayani V, Pickleman JJS. Abdominal operations in patients with
cirrhosis: still a major surgical challenge. 1997;122(4):730-6.
7. Friedman LSJTotAC, Association C. Surgery in the patient with liver disease. 2010;121:192.
Review for 10.1186/s12876-022-02558-6 (2022)

Title: Adverse outcomes after non-hepatic surgeries in patients with alcoholic liver diseases: a
propensity-score matched study
Version: 3 Date: 05 Oct 2022
Reviewer's report:
Thank you very much for submitting the revised manuscript and addressing the concerns raised
in the last review.
I have no further comments.
Review for 10.1186/s12876-022-02584-4 (2022)

Title: Medication Use Among Patients with Crohn’s Disease or Ulcerative Colitis Before and
After the Initiation of Advanced Therapy
Version: 3 Date: 27 May 2022
Reviewer's report:
This is a study that retrospectively analyzed the changes in pain treatment before and after the
introduction of biologics using a health care database.
It is very important topics, but there are a lot of limitation in this study.
It is necessary that the authors should perform more precise analysis.
As the author stated, NSAIDs are indistinguishable when used, for example, for headaches. Is
it possible to set a minimum dose to focus on the regular use of NSAIDs as a pain medication
for IBD?
Steroids were included as pain medication, but isn't it used to control the inflammation of IBD?
Steroid free remission is one  of the therapeutic goal which is widely accepted, but why was the
steroid usage rate so high even after the introduction of bio? How much was amount of steroid
after initiation of bio?
There is Insufficient results and discussion regarding the use of the opioids which is th most
important medication in this topic.
Changes of opioid use after bio introduction was not described.
In general consensus, opioid use is a poor prognostic factor in IBD. Therefore, this reviewer
recommends the authors to analyze the surgical rate of opioid users.
In this survey, 36.5% of patients with UC and 41.5% of patients with CD used opioids. This
reviewer believes that this is a fairly high percentage, which this reviewer dose not think that
it is adequate for IBD management. Please analyze more detail and discuss it. For example, is
this database from IBD core-facility? Or does it include a lot of general gastroenterologists? Is
it possible to analyze them separately? The quality of management may affect to the ratio of
opioid use.
In Crohn disease, did the perianal lesion have any effect for use of pain medication?
Review for 10.1186/s12876-022-02584-4 (2022)

Title: Medication Use Among Patients with Crohn’s Disease or Ulcerative Colitis Before and
After the Initiation of Advanced Therapy
Version: 5 Date: 13 Nov 2022
Reviewer's report:
The authors adequately addressed the points of critique. They chose to analyze the influence
of modern treatment options on glucocorticoids as well as pain medication. The former having
been shown in plenty of other publications before this, the latter being very new.
There are only minor points of critique.
A) Considering, that patients might be taking analgetics for different reasons, the statistically
significant reduction in pain medication is quite remarkable and is worth mentioning in the
abstract.
B) Page 7, first sentence: "these medications [analgetics]" do not result in healing of the inflamed
intestine.
C) Page 14, Number of pain medication fills: The equations model did not show a significiant
change in pain medication fill rather than showing that there was no significant change.
Review for 10.1186/s12876-022-02562-w (2022)

Title: The profile of the key pro-inflammatory cytokines in the serum of patients with CD and
their association with the disease severity and activity
Version: 1 Date: 20 Jun 2022
Reviewer:  Gilles R. G. Monif
Reviewer's report:
This is a  classically prepared manuscript that was  developed with care.
The authors ask a simple question and then proceed to answer it  with a small, but well
constructed experimental design. The data reinforces previously published  and cited data (Br.
J. Clin. Pharmacol. 2020.86;1296-1305).
Where it suffers is attempting  to be overly inclusive in orientating the reader to Crohn's
Disease. The introduction needs to be reworked with deletion of paragraphs three on and updated
discussion of the now documented  pathogenesis of Crohn's disease .
Crohn's disease is not an autoimmune disease, but an immune-mediated disease. Most of the
authors' corresponding references date to pathogenesis are dated.
A better introduction to their data is discussion of cytokine response as a critical component
of cellular immunity to organismal challenge or  as in the case of Crohn's disease,  antigen
challenges secondary to pre-set  fixation of the immune system's pro-inflammatory response
to Mycobacterium avium subspecies paratuberculosis (Med. Hypothesis 2015. 85,878-88;
Gastrointest. Discord. 2021, 3;138-141).
In the conclusion, the authors may want to speculated on the usefulness of cytokine monitoring
as a gage of therapeutic efficacy.
Review for 10.1186/s12876-022-02562-w (2022)

Title: The profile of the key pro-inflammatory cytokines in the serum of patients with CD and
their association with the disease severity and activity
Version: 1 Date: 27 Jun 2022
Reviewer's report:
There are many limitations in this manuscript which is not suitable to be published in the current
form.
My comments are listed as follows.
1. Abbreviations must be defined upon first use, and provide the full name in both the Abstract
and the main text.
2. In Abstract, the authors did not mention the correlation results.
3. The conclusion should be concise and only summarize the most important contribution of the
research in both the Abstract and the main text.
4. In Introduction, please simplifying for readability. And focus on the relationship regrading
inflammatory and CD
5. In statistical analysis, why the authors used Student’s t-criterion test? Whether these
continuous variables were fitted the normal distribution? Otherwise, the authors should replace
by Mann-Whitney U test. Additionally, please provide a test for normal distribution.
6. why the authors used Spearman method to conduct correlation analysis?
7. Confounding factor may be in this study, the authors seemed to do not consider it, and how
to control it?
8. In Results, keeping the P value in three decimal places, for example P <0.001.
9. In Discussion, please discussed the similarities between the current results with previous
findings, and provide reasonable explanations for potential inconformity.
10. In Discussion, avoid to mention the results and use conclusion and general sentence.
11. The Conclusion should be concise and only summarize the most important contribution of
the research, please make a difference between the results and the conclusions.
Review for 10.1186/s12876-022-02562-w (2022)

Title: The profile of the key pro-inflammatory cytokines in the serum of patients with CD and
their association with the disease severity and activity
Version: 4 Date: 01 Sep 2022
Reviewer:  Gilles R. G. Monif
Reviewer's report:
A cleanly constructed manuscript.
It's limitations reside in Crohn's disease having been already well established as an immune-
mediated disease. The discussion of the demography and cost of disease, while well presented,
do little for the presentation of the research data.
Several statements need to be cleaned up: page 3 para 3 line 1-4 CD affects  a very specific
area of the gastrointestinal tract, the ileocecum (Chapter20 Doi: 10.9734/bpi/dmmr/v11/14229D
C .Emerging Trends in Disease and Health Vol.9 may help clarify the disease entity that you are
studying). Only after surgery alters the cite of primary fecal stasis does the site of the disease
move. Oral cavity involvement is a direct consequence of microbial infection  by Mycobacterium
avium subspecies paratuberculosis and the consequence of MAP's immune-mediated  disease
process (see reference 18 & 21)
Page 3, para 4 lines1-3 are best deleted .
Overall, let the data specific for itself:  A cytokine cascade is in evidence in individuals with
Crohn's disease and there is a positive correlation between their level and disease manifestation.
Review for 10.1186/s12876-022-02562-w (2022)

Title: The profile of the key pro-inflammatory cytokines in the serum of patients with CD and
their association with the disease severity and activity
Version: 4 Date: 05 Sep 2022
Reviewer's report:
The authors  did not addressed my comments appropriately and  should response my comments
by  point-to-point.
And I did not see the results of correlation in the manuscript.
Review for 10.1186/s12876-022-02562-w (2022)

Title: The profile of the key pro-inflammatory cytokines in the serum of patients with CD and
their association with the disease severity and activity
Version: 6 Date: 16 Oct 2022
Reviewer:  Gilles R. G. Monif
Reviewer's report:
The updated manuscript now reflects a better understanding of the events that combine to
produce disease.  Thank you. Given the ability of biologics to preclude cytokine/ MAP
cytotoxicity,  a positive dose clinical response correlation was to have be anticipated .
According to its FDA filing,  Humira(R) had been able to induce a temporary remission in
40% of study patients . In 60% of study patients, it was failed therapy. Dietary exclusion
of foods potentially adulterated by MAP has been shown to produce superior outcomes
to those initially achieved with a biologic (J. Crohn Colitis 11:1205-1212. 2017; World J.
Gastroenterol. 16;2484-2495.2014). What is lacking to date is a comprehensive, randomized,
blinded, comparison between MAP exclusion diet/initial antibiotic coverage and biologics.
Humira(R) and its  current re-formulation  is the globally the number one or two revenue
producing drugs.  Administering added drug will increase cost.
Review for 10.1186/s12876-022-02566-6 (2022)

Title: Association of gallbladder diseases with risk of gastrointestinal polyps
Version: 2 Date: 24 Jun 2022
Reviewer:  Juan Carlos Araya
Reviewer's report:
In recent years we have seen how gallbladder polyps have been gaining ground in clinical
practice and studies of the etiology of gallbladder carcinoma. Probably, the better skills of
our radiologists and the use of ultrasound with better technology explain this phenomenon.
However, it is not a minor fact that the understanding and better systematization of the
gallbladder polyps contribute to a better understanding of their importance and improve the
therapeutic approach algorithms. The study by Wenbin Geng and others adds a new and exciting
point of view, opening lines of exploration of unquestionable interest. Even though it is a
study that uses data that are not the traditional golden rules, it demonstrates an association
between entities commonly studied separately. In the future, we will be able to see similar
population analyses, supported by detailed histopathological data and molecular studies that
open the discussion about possible shared metabolic pathways. My recommendation is that the
article should be published, given the authors could make some changes:
1. On page 10 of the revised document, first paragraph, and first sentence, there is confusing
information when comparing single or multiple gallbladder polyps with large intestine polyps
and multiple gallbladder polyps. Either it is a bug, or it requires simplifying the comparison of
groups of cases.
2. Referring to the list of the gallbladder, large intestine, and stomach polyps, the authors, refer
to Table 3. Unfortunately, this table did not include the group of patients with stomach polyps
only. Such data is relevant and should be added.
3. In general, in gallbladder polyps, the size of 1 cm has been considered the breaking point
for deciding on immediate surgery or strict control and follow-up. As the authors do not have
information to define whether the patients with gallbladder polyps considered are neoplastic or
not, my recommendation is to discuss the reason why 0.5 cm was chosen as the division between
significant cases or, if possible, reconstruct the analysis using 1 cm as the dividing line.
4. To focus the manuscript on the most valuable contribution of the authors, I suggest that
tables 4, 6, 7, and 8 be reserved as unpublished data and accessible as complementary material,
available through the internet for those who would like to know detailed information.
5. In the final part of the presentation of the results, the distinction of colorectal polyps as
adenoma and non-adenoma appear. In my opinion, if the histology of some or all of these cases
was available, it should be stated in the material and methods section and the summary tables
of the manuscript.
6. The length of the manuscript and the clarity of the exposition seem clear.
7. The discussion is precise and raises some hypotheses that future studies could contribute to
its validation.
8. The bibliography seems appropriate.
Review for 10.1186/s12876-022-02566-6 (2022)

Title: Association of gallbladder diseases with risk of gastrointestinal polyps
Version: 5 Date: 29 Sep 2022
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?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have responded to all of the reviewer's comments. There
remain a few issues to address.
ADDITIONAL REQUESTS/SUGGESTIONS:
1. “We define gallbladder disease as gallstones and gallbladder polyps.” – in this sentence the
‘and’ should be ‘or’
2. “The colorectal polyps were located in the right colon (proximal to splenic flexure) and left
colon (splenic flexure and distal to splenic flexure).” – this should be “The colorectal polyps
were recorded as being in the right colon (proximal to splenic flexure) or left colon (splenic
flexure and distal to splenic flexure).
3. The addition of the following text helps but needs additional information as follows:
“Multivariable analysis was adjusted for those significant in the univariate analysis.”. Change
‘adjusted’ for ‘performed’. Also state how did you define significant.
4. “No correlation was found between gallbladder polyps and right-colon polyps (adjusted OR
= 1.77, 95% CI: 0.97–3.23, P = .064).” – I think it’s too strong to say there was no association.
I would say this is a borderline (or suggestive) positive association.
5. It’s unclear what a non adenoma is in the following sentence? “No correlation was found
between gallbladder polyps and colorectal non-adenoma”
6. Table 5: add ‘years’ where it says age in the table"
Review for 10.1186/s12876-022-02531-3 (2022)

Title: The association between dietary total antioxidant capacity and odds and severity of
irritable bowel syndrome among Iranian adults: a cross-sectional study
Version: 1 Date: 10 Jul 2022
Reviewer's report:
This is a cross sectional study exploring the relationship between TAC and IBS in adults. The
topic is important and the paper appears to be a good fit for this journals. I don’t have any
comments, because I follow and review the papers which are published from SEPAHAN project.
Almost of these papers have been published in high quality journals.
Review for 10.1186/s12876-022-02531-3 (2022)

Title: The association between dietary total antioxidant capacity and odds and severity of
irritable bowel syndrome among Iranian adults: a cross-sectional study
Version: 1 Date: 31 Jul 2022
Reviewer's report:
The manuscript entitled “The association between dietary total antioxidant capacity and odds
and severity of irritable bowel syndrome among Iranian adults: a cross-sectional study” is well-
design and meaningful topic. However, some revisions and clarifications especially in Abstract,
Introduction, Methods, and Results section should be considered.
Major revision
1. As a general comment, there are some writing and grammatical errors in the text, and having
an editor read through the paper would be useful to take care of this.
2. In the Results section of the Abstract and Main text, you did not report the prevalence of IBS
and its subtypes in the participants of this study!
3. Please use term "tertile" instead of "category" in all parts of the Manuscript. Using the word
"category" means that you have arbitrarily classified the participants based on dTAC.
4. Considering that your study is an epidemiological study that examines the role of a type
of dietary index (dTAC) in predicting the risk of a chronic disease (IBS), therefore, the
present study is a study in the field of prevention of chronic diseases, not in the treatment
and management of a chronic disease. In the Manuscript, especially in the Introduction and
Discussion sections, you should not discuss the role of nutritional factors in the treatment or
management of IBS, and there is no need to provide the results of studies conducted on the
nutritional management of IBS. Please focus only on studies examining the role of nutrition in
predicting IBS risk. For example, in the second paragraph of the Introduction section, lines 12
to 16, it is discussed on the nutritional management and treatment of the IBS.
5. Some sentences in the Introduction section are very general and do not have a clear
explanation. Please explain them in more detail. For example, in the sentence" Accordingly,
several studies have been conducted on the associations between dTAC and chronic disease ", at
least mention the names of chronic diseases. And dTAC has the ability to prevent these chronic
diseases according to the results of these studies?
6. Which chronic diseases and which medications could have a confounding role in your study?
You must specify
7. Can marital status be a confounding variable for your study analyses? Please explain.
8. Why did you perform sensitivity analysis based on gender and body mass index? Did you
check the interaction of these variables with total oxidant capacity in relation to the outcome of
the study? Table 1 does not show any significant difference regarding these two variables across
tertiles of dTAC! Please explain.
Review for 10.1186/s12876-022-02531-3 (2022)

Title: The association between dietary total antioxidant capacity and odds and severity of
irritable bowel syndrome among Iranian adults: a cross-sectional study
Version: 3 Date: 01 Oct 2022
Reviewer's report:
Thank you so much for the revisions and responses to the comments. The manuscript is well-
edited and revised, and no further changes are needed.
Review for 10.1186/s12876-022-02559-5 (2022)

Title: Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease
Version: 3 Date: 09 Jun 2022
Reviewer's report:
It is a very interesting study about the mucosal cytokine’s gene transcription and the response
to biological therapy in IBD patients.
I suggest improving the description of the variables in table 1. For example: "Primary/secondary"
would be Primary/secondary non-response? "Mucosal TNF" would be Mucosal TNF gene
transcription?
It would be interesting to better describe the UC and CD groups that responded to the treatment,
especially which biologics they used.
An interesting comparison would be the comparison divided by disease (UC or CD) and by drug
(anti-TNF responder versus anti-TNF non-responder), for example. I understand that this type
of analysis may be limited by the low number of patients in the sample, but the results would be
interesting to evaluate the association between the expression of cytokines in the mucosa and
the response to a certain class of medication. Please include this observations in the discussion.
An idea for future studies.
Review for 10.1186/s12876-022-02559-5 (2022)

Title: Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease
Version: 3 Date: 09 Aug 2022
Reviewer's report:
Major Comments:
The major limitation of this study is the lack clinical relevance as it is expected that individuals
with ongoing inflammation will have elevated inflammatory cytokine levels as compared to
controls or those with resolved inflammation.
It is important to note that a significant increase in TNF, IL17, and IL23 in a single time
point of inflamed mucosa does not necessarily indicate a specific “resistance mechanisms” to
biologic therapy as is interpreted in the discussion section paragraph 2. These cytokines are
markers of ongoing inflammation. The authors could better clarify exactly when biopsies were
obtained in the treatment course, but this is presumed to be after non-response was determined
as defined in criteria for non-response to biologic therapy. This study would be improved if pre-
treatment transcripts were available for the same patients as that might provide some insight
into mechanisms.
As expected, there is little difference in the cytokine transcripts in non-responders and those in
the reference groups obtained at disease onset who also have active inflammation. This suggests
that the transcripts seen may just be a result of active inflammation rather than any mechanism
of non-response.
This paper may be improved by restating conclusions to focus more on the cytokine transcripts
in inflamed vs. not inflamed mucosa as well as emphasizing the differences in treated mucosa
in remission as compared to controls.
Minor Comments:
1. In the abstract background and aims section last line “throughlevel” should be trough level.
2. Again in discussion line 3 troughlevels should have a space – trough level
Review for 10.1186/s12876-022-02528-y (2022)

Title: Overall Survival and Toxicity of Y90 Radioembolization for Hepatocellular Carcinoma
Patients in Barcelona Clinic Liver Cancer Stage C (BCLC-C)
Version: 2 Date: 13 Apr 2022
Reviewer's report:
Dear Authors, the work is about an observational study  on TARE in BCLC-C  HCC patients.
The results bring to the light, for another time, the question if in this setting it would be better
a chemotherapy  or a TARE. The results are encouranging but too limited to give some clinical
strong indications. We would need prospective and comparative trials between the more recent
chemotherapies and TARE, in terms of toxicity and OS. In the meanwhile, all studies results
could help us to identify the ideal patients to give one or another HCC therapy, but too often the
choice is oriented by local experience and local availability of therapies.
Moreover, it is not so clear from the paper,  how many treatments (i.e. procedures) for single
patient have been performed (the data could be insert in the table), and the median time in
months, to the onset of liver function worsening, in the cases  when it occurred (i.e. it could be
dependent by TARE of physiological progressive liver failure due to cirrhosis?).
Review for 10.1186/s12876-022-02528-y (2022)

Title: Overall Survival and Toxicity of Y90 Radioembolization for Hepatocellular Carcinoma
Patients in Barcelona Clinic Liver Cancer Stage C (BCLC-C)
Version: 4 Date: 17 Jun 2022
Reviewer's report:
many of the concerns remained not addressed.
Review for 10.1186/s12876-022-02528-y (2022)

Title: Overall Survival and Toxicity of Y90 Radioembolization for Hepatocellular Carcinoma
Patients in Barcelona Clinic Liver Cancer Stage C (BCLC-C)
Version: 4 Date: 01 Jul 2022
Reviewer's report:
The authors reply  consistently to our comments. Could be suitable for publication in order to
editor's priority.
Review for 10.1186/s12876-022-02528-y (2022)

Title: Overall Survival and Toxicity of Y90 Radioembolization for Hepatocellular Carcinoma
Patients in Barcelona Clinic Liver Cancer Stage C (BCLC-C)
Version: 6 Date: 22 Sep 2022
Reviewer's report:
The authors addressed the questions appropriately.
Review for 10.1186/s12876-022-02528-y (2022)

Title: Overall Survival and Toxicity of Y90 Radioembolization for Hepatocellular Carcinoma
Patients in Barcelona Clinic Liver Cancer Stage C (BCLC-C)
Version: 6 Date: 01 Oct 2022
Reviewer's report:
The authors answered properly to the questions.
Review for 10.1186/s12876-022-02473-w (2022)

Title: The Application of magnetic anchoring traction device in assisting donor liver bench
surgery in classic orthotopic liver transplantation
Version: 2 Date: 22 Apr 2022
Reviewer:  Jae Do Yang
Reviewer's report:
- The authors developed a new traction devices  during bench surgery  in LT and demonstrated
that this  effectiveness and  feasibility showed.
- This manuscriprit has a novelity and the conclusion is supported by the data.
- I think that you need to develop assessment tools of  this devices compare to control group.
- how long time duration of setting  of this devices?