JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03730-4 (2025)

Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from
a Retrospective Cohort Study
Version: 1 Date: 01 Dec 2024
Reviewer's report:
In this manuscript entitled “Effect of L-carnitine Supplementation on Muscle Cramps in Liver
Cirrhosis: Results from a Retrospective Cohort Study”, the authors examined the association
between levocarnitine supplementation and muscle cramps in patients with cirrhosis. While this
is an interesting study, there are some concerns which should be clarified.
Major comments
1. Malnutrition is important in the pathogenesis of muscle cramps in patients with liver cirrhosis
(PMID: 35861232). The authors should make an introduction regarding this point.
2. In the result section, the authors should demonstrate the baseline characteristics of the included
patients such as Child-Pugh score, MELD score, other medications, and laboratory data.
3. The molecular mechanism of levocarnitine on muscle cramps needs to be explained in the
discussion session (PMID: 31864971).
4. Levocarnitine also improves mortality in patients with cirrhosis. The authors should add a
discussion in this point (PMID: 35511698).
Review for 10.1186/s12876-025-03730-4 (2025)

Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from
a Retrospective Cohort Study
Version: 1 Date: 08 Dec 2024
Reviewer's report:
Line 98: Exclusion criteria were other secondary caused of cramps. By authors own submission
causes of cramps in cirrhosis can be AKI, dehydration, dyselectrolytemia. There is no mention
of these confounding factors in the manuscript.  Authors should have mentioned in the methods
and methodology the prevalence of such predisposing factors in the study population. Ideally
these factors should be corrected before one can comment on the effectiveness of L-carnitine.
A multivariate analysis to take care of confounding factors would have given a more accurate
results on the effectiveness of L-carnitine
Line 11: 27.8% patients in this retrospective study had cramps. The authors could have studied
the factors as to why these patients had cramps while the remaining 71% screened patients did
not have cramps to make this study more insightful. This could have been a secondary objective
of the study
Table 3: Does not explain clearly the correlation of BMI and severity of cramps. It is not clear
from the table if high BMI is protective, or low BMI is protective against cramps
Line 182, 183: There is mention of complete resolution of cramps in certain percentage of
patients. However, there is no table in the manuscript to substantiate this conclusion.
The numbers in each subgroup especially the group with daily cramps is very small hence
making it difficult to come to a conclusion
If these points could be added to the manuscript, then study will have more impact
Review for 10.1186/s12876-025-03730-4 (2025)

Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from
a Retrospective Cohort Study
Version: 2 Date: 11 Jan 2025
Reviewer's report:
Thank you for your response to the comments.
Absence of baseline data like 1.disease severity (CTP/ MELD scores) 2. Nutritional status 3.
severity of sarcopenia makes it difficult to conclude if these are potential confounding factors
for response to L carnitine supplementation.
Perhaps the authors in their conclusion can add a note that this is a pilot study and results of
this study should be validated with a well designed prospective study to avoid all biases and
confounders.
Review for 10.1186/s12876-025-03738-w (2025)

Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 2 Date: 25 Dec 2024
Reviewer:  Hawal Lateef Fateh
Reviewer's report:
Review for 10.1186/s12876-025-03738-w (2025)

Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 2 Date: 12 Jan 2025
Reviewer:  Zhaohui Tang
Reviewer's report:
This paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing
on five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes
tumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte
telomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3
variants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122
expression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the
work highlights the importance of specific genetic variants in tumor aggressiveness, contributing
to ongoing discussions on precision screening for HCC in NASH patients.
However#there are still some issues to be addressed before it’s suitable for publication:
1.Could you provide additional details on the power calculation used to determine that 48
patients would be sufficient to detect significant genetic associations?
2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135)
persist in other ethnic groups or in a larger, more diverse study cohort?
3.Although the work is significant for Sri Lankan populations, additional insight or discussion
on how these findings might translate to broader or multi-ethnic contexts could strengthen the
paper’s global relevance.
4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic
risk factors on the identified SNPs and their association with NASH-HCC?
Review for 10.1186/s12876-025-03738-w (2025)

Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 3 Date: 28 Jan 2025
Reviewer:  Hawal Lateef Fateh
Reviewer's report:
- Ensure the title reflects the study scope clearly and concisely.
- Verify if the abstract provides a structured summary (background, methods, results,
conclusion) while maintaining brevity.
- Assess if the introduction effectively justifies the research, clearly presenting the gap in the
literature and the study's objectives.
- Suggest adding more specific references or updating citations if needed.
- Verify if all experimental procedures are clearly described and reproducible.
- Suggest clarifications or elaborations on sample size justification, statistical methods, or
experimental protocols.
- Evaluate if the data presentation is clear, consistent, and free from redundancy.
- Ensure tables and figures are self-explanatory and enhance comprehension.
- Point out if any statistical analyses lack adequate description or context.
- Assess if the discussion appropriately interprets findings, acknowledges limitations, and aligns
with the objectives.
- Recommend emphasizing key findings and minimizing overgeneralization.
- Suggest grammar, spelling, and structural improvements to improve readability.
- Check adherence to journal formatting guidelines.
- Verify citation accuracy and formatting consistency.
Review for 10.1186/s12876-025-03738-w (2025)

Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 3 Date: 04 Feb 2025
Reviewer:  Zhaohui Tang
Reviewer's report:
Thank you for the author's patient and meticulous answers. However, I still have some doubts
that need to be clarified:
1. How was the study powered to detect associations for “TM6SF2” and “MBOAT7” SNPs,
given their lack of significance?
2. Were multiple testing corrections applied? If not, how might uncorrected p-values impact the
interpretation of “PNPLA3” associations?
3. Can the authors elaborate on the biological mechanisms linking “PNPLA3” rs2281135 to
miR-122 elevation and tumor nodularity?
4. Why were cirrhotic and non-cirrhotic HCC patients not stratified in analyses, given prior
evidence of SNP associations with cirrhosis?
5. Could the observed age/BMI associations with “PNPLA3” rs2281135 reflect survivorship
bias or confounding factors (e.g., comorbidities)?
6. Overrepresentation of Sinhalese individuals (47/48) limits generalizability to other ethnic
groups in Sri Lanka or globally.
Review for 10.1186/s12876-025-03685-6 (2025)

Title: Quality of life, functional impairment and healthcare experiences of patients with irritable
bowel syndrome in Norway: An online survey
Version: 4 Date: 20 Aug 2024
Reviewer:  Ewa Ma#ecka-Panas
Reviewer's report:
This is the very comprehensive report with the rarely large number of patients evaluated.The
study aim was to  determine the impact of IBS on the quality of life, functional impairment and
healthcare experiences of patients in Norway.The problem is widely known, but surprisingly
not that widely addressed.Some parts of the data provided are widely known, as  low  HRDL,
delay in medical help seeking, however economic burden of IBS was more rarely studied.My
main problem here is the IBS diagnosic criteria and the medical data of the studied group. The
statement that the patients  were diagned by medical doctor in not informative enough.It should
be specified, if this were general practicioners or gastroenterologists or other specialist.Did they
use Rome IV IBS diagnosis criteria or other diagnostics? Were there associated diseases, which
could alter the results? The Rome IV criteria are mentioned in the discussion, but this is not clear
that that was the main diagnostic criteria, which should be stated in the material section.The
statement that IBS patients are not satisfied with the medical treatment is very familiar to all
gastroenterologists, since it takes time to gain the indispensable patients confidence on one
hand , but on the other hand the MD's time is scarce everywhere.Therefore, the authors should
underline, which obtained data represent the true novelty
Review for 10.1186/s12876-025-03685-6 (2025)

Title: Quality of life, functional impairment and healthcare experiences of patients with irritable
bowel syndrome in Norway: An online survey
Version: 4 Date: 31 Jan 2025
Reviewer's report:
Thank you for this survey, which adds to our knowledge of IBS in Norway  with real-life data.
I have just a few comments:
1- I'm not convinced by the relevance of the responses from people under the age of 18, i.e.
25 persons (according to question 2) and  38 persons according to the ‘school pupil’ category
(question 4). We are not sure that they are capable of understanding and answering the questions.
If it wasn't the parents who answered for them, I suggest that these questionnaires should not
be included in the analysis.
2- You rightly excluded 327 questionnaires from the analysis because the diagnosis had not been
made by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These questionnaires
should be excluded from the analysis.
I would go further and also exclude the 158 questionnaires where people answered question
7:  "Yes, it was diagnosed by another doctor (not a GP or gastrointestinal specialist)". In my
opinion, only a GP or gastroenterologist can correctly diagnose IBS.
It would also have been better to cross this with the response ‘I haven't been diagnosed by a
doctor 249’ in question 10.
3- There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not
seen either by a GP or by the gastroenterologist according to question 7.
4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS-
D or IBS-M. Did you get this information directly from the people or did you deduce it?  In my
opinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't
meet the definition. For example, an IBS patient with constipation predominance must have hard
stools > 25% of the time and soft stools < 25% of the time.
To be correct, these should be indicated in the same way as the other symptoms (as for headache
and fatigue) in the table.
5- We do not understand how the ‘unemployed’ category is calculated.
Table 1 shows 1035 (38%) “unemployed”. In the discussion section, it says: ‘The present survey
revealed that the unemployment rate among IBS patients was 29%, which is therefore more than
8-fold that of the general population.’
I think there may be some confusion about the term “unemployed”. At times in your article it
refers to all the categories in question 4 without the ‘employed’ category, and at other times it
refers to ‘people of working age who are looking for work’.
Please clarify these points.
6- It would have been interesting to have information on income brackets or socio-professional
categories.
Review for 10.1186/s12876-025-03677-6 (2025)

Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in
liver cirrhosis
Version: 1 Date: 25 Nov 2024
Reviewer's report:
It is a worthwhile job#however there are some issues that need to be addressed.
1. Some important variables were not included in the analysis,  such as history of hepatic
encephalopathy.
2. Univariate analysis  showed that ascites was also an independent risk factor. Why was it not
included in the multivariate analysis#
3. Unreasonable use of charts: Tables 1 and 3 can be merged into one table and repeatedly
expressed in Table 1 and Figure 1.
Review for 10.1186/s12876-025-03677-6 (2025)

Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in
liver cirrhosis
Version: 2 Date: 22 Dec 2024
Reviewer:  Billy Siahaan
Reviewer's report:
Comment from reviewer :
1.Congratulation for your work , but I still confused about the method of collecting data and
method you use in this study. Could you describe more detail about “who experienced UGIB
within six months of discharge, were included in the study” , is the laboratory , fibroscan and
endoscopy were conducted  at the same time of hospitalisation ?  or all the variable were
collecting before any important treatment that may altered the result ?
2.I recommend you get additional exclusion regarding portal vein thrombosis or any non
cirrhotic condition that may have a different value from the spleen stiffness measurement and
the prognostic
3.“Of these, 99 patients had hepatitis B “ , what about the other etiology ? could you describe
and include in your baseline characteristic ? Its also important to difference between the use of
antiviral treatment because it has difference result in my opinion
4.If you had etiologies from MAFLD , I am not sure if the cholesterol level maybe altered and
could be a big bias for this research.
5. Could you describe what fibroscan type do you used especially for measurement of spleen
stiffness? Because the accuracy is different between 50 hz and 100hz ( spleen dedicated
fibroscan)
6.In this research you compare the model with other models like child pugh score. Could you
describe more detail about the method you used for get AUC from child pugh score model in
correlation with the upper gastrointestinal bleeding event
7.Did you had any record regarding the use of albumin transfusion during treatment at the
hospital? Please describe more detail especially in the variable that related to the study
Review for 10.1186/s12876-025-03677-6 (2025)

Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in
liver cirrhosis
Version: 2 Date: 24 Dec 2024
Reviewer's report:
The authors have provided a thorough explanation and revisions. It is now clear that this is a
retrospective case-control study, and all patients had no history of UGIB at baseline. This is a
critical point, as patients with a history of UGIB are at higher risk for rebleeding.
I suggest minor revision:
First, change "no previous history of gastrointestinal bleeding" to the exclusion criteria (i.e.,
"patients with a history of gastrointestinal bleeding were excluded").
Second, expand the limitations section to address the absence of data on patients’ use of non-
selective beta-blockers (NSBBs) and antiviral therapies, as these factors could influence the
outcomes.
Finally, avoid using the term “matched,” as it may raise concerns about the randomization
process and the lack of a clear 1:1 or 1:2 matching ratio. Instead, revise this description to:
"These patients were compared with 151 patients with cirrhosis hospitalized during the same
period at the same hospital, who were discharged within six months without developing UGIB."
This revised phrasing indicates that all non-UGIB patients during this period were included.
Review for 10.1186/s12876-025-03677-6 (2025)

Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in
liver cirrhosis
Version: 2 Date: 01 Jan 2025
Reviewer's report:
Univariate analysis showed significant differences in ascites, hepatic encephalogy, LS, SS, PLT,
AST, APRI, FIB-4, ALB, TBIL, Scr, FIB, TC, and PT, all above statistically significant factors
should be included in the multivariate analysis, and then the model should be constructed.
Review for 10.1186/s12876-025-03739-9 (2025)

Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice
Version: 2 Date: 24 Feb 2025
Reviewer's report:
All my concerns have been thoroughly addressed. The readability has significantly improved,
making it easier to interpret the findings in this revision. I recommend acceptance.
Review for 10.1186/s12876-025-03732-2 (2025)

Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the
ClinicalTrials.gov Database
Version: 2 Date: 23 Jan 2025
Reviewer:  Joost Boeckmans
Reviewer's report:
Hui Du and colleagues provide an overview of clinical trials in MASLD registered on
ClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain
concepts could add innovative aspects, in which I hope my input can be useful:
Major
- Introduction: in my opinion, the introduction would benefit from discussing the potential drug
targets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on
prevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two-
hit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper.
- The authors describe hepatic fat content as a frequent endpoint. What about the technique to
quantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid
reduction? Same for histology, are there already some using AI?
- Based on the search, what are the advantages of current ‘most popular’ drugs under
development over the failed compounds? Eg. Elafibranor.
- What about personalized treatment developments? Eg. Regarding PNPLA3? When did these
kinds of approaches emerge?
All in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more
detail, since this informs about new developments
Minor
- Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette
JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA.
The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis.
Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0.
Epub 2022 Jul 5. PMID: 35798021.
- Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create
some uniformity.
- Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar
- Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through
mechanisms such as metabolic and energy balance”; would be informative to add a percentage
to this number. How did the targets change throughout the time?
- Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple
concepts (cfr methods section).
- Was gender (vs sex) adequately used?
- This quite recent article reported on the same topic: PMID:38327733. What is the added value
of this paper?
Review for 10.1186/s12876-025-03732-2 (2025)

Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the
ClinicalTrials.gov Database
Version: 2 Date: 26 Jan 2025
Reviewer's report:
This study provides an overview of the MASLD/NAFLD interventional clinical trials. However,
I have concerns about the conduct and decisions that need further clarification:
Key points:
1. Please use current terminology (i.e., MASLD) consistently throughout the manuscript.
2. Provide more detailed information on the methodology, including the full search strategy,
data handling (how? who? what was done?), and statistical analysis.
3. The authors show the global distribution of MASLD clinical trials. However, it is unclear
whether this distribution includes multinational trials, leading to uncertainty as to whether
this information is accurate. For example, there are MASH trials with sites in Argentina
(NCT03053050, NCT03205150, NCT02855164, NCT03517540), which is shown as having
0 trials. Please investigate the multinational trials further or clearly state that the countries
considered are only those registered in the CT.gov database and acknowledge this as a limitation.
In addition, a table showing the number of trials for each country and their further stratification
by income level (according to the World Bank country classification) would be welcome.
4. Please clarify why phases of studies were classified as 'NA' (not applicable).
Minor points:
1. Introduction: Please provide information on the prevalence of MASLD with updated data
(PMID: 36626630).
Review for 10.1186/s12876-025-03706-4 (2025)

Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult
females: a cross-sectional, nationally representative study (NHANES 2017–2020)
Version: 2 Date: 08 Oct 2024
Reviewer's report:
We had the honor to review the manuscript on weight-adjusted waist circumference index and its
associations with liver disease (steatosis and fibrosis based on FibroScan) amongst females from
the NHANES 2017-2020 database. Although the findings are interesting and the topic deserves
further investigation the enthusiasm is limited due to the complexity of the study and lack of a
single strong story aiding the reader through this information.
Major
1. Although some other markers were investigated, it remains unclear to me if the WWI is better
in assessing the risk of steatosis and fibrosis compared to the other tests mentioned in this study.
2. Although one should always consider impact of sex on body composition and the associated
risks, I miss the comparison to the male counterpart. Is the WWI also better in males? Are there
different associations? Or can we use WWI in both female and males?
3. I am intrigued by the U shaped correlation for WWI and LSM. This seems to be in
contradiction with Table 1, where the lowers LSM was reported for Q1 and highest for Q4.
Might this due to (over)adjusting? Among the Q1, were there also more patients with clinically
relevant increased LSM?
4. Although the data is interesting, I have difficulties extracting useful conclusions for further
research and/or clinical practice. I recommend the authors to assess carefully what the main
messages would be of this paper and how the tables and figures could contribute to this message.
Minor
1. Please check for style and grammar. Some sentences are duplicate or in contradiction. For
example, the first sentence is duplicated in the data analysis section and the table legends are
sometime duplicated, especially the models, however, they are not the same models which is
confusing.
Review for 10.1186/s12876-025-03706-4 (2025)

Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult
females: a cross-sectional, nationally representative study (NHANES 2017–2020)
Version: 6 Date: 13 Jan 2025
Reviewer's report:
I endorse the changes made by the authors. They address the previously mentioned issues.
Review for 10.1186/s12876-025-03727-z (2025)

Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and
behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study
Version: 1 Date: 23 Jan 2025
Reviewer's report:
The authors confirmed the association between IBD and ARFID and examined the prevalence
of ARFID and its associated factors in a sample of around 500 individuals. They reported that
factors such as having Crohn's disease, having an active disease, having an attitude to managing
symptoms, and having a specific dietary history were associated with ARFID.
Many of the points are similar to those previously reported and there is considered to be little
new evidence. In addition, the low generalisability of the study needs to be discussed in several
respects, including the following.
First, the likelihood that participants in the study would be committed to the diet in the first place
needs to be discussed, and how patients who would not wish to participate in the study would
be treated needs to be fully discussed.
Secondly, the participants were, on average, 37.2 years old (28-46), and it should be mentioned
that most were this young. In other words, it is important to note that the elderly, who are more
prone to nutritional disorders, etc., were not considered.
It should also be mentioned that more than two-thirds of the participants have a university
education or higher. This is because interest in dietetics may be influenced by the presence of
education.
About the results:
Are the results in Table 4 univariate analyses? If they are multivariate analyses, a description
should be added to the Method statistics, and it should also be stated in Table 4 that it is a
multivariate analysis.
If a multivariate analysis has not been performed, this should be clearly stated and the Discussion
should state that the risk factors obtained in this study were univariate and independent.
A satisfactory explanation of the above points and a correction of the article is needed.
Review for 10.1186/s12876-025-03727-z (2025)

Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and
behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study
Version: 3 Date: 11 Feb 2025
Reviewer's report:
The response letter to the review was confirmed.
Unfortunately, the response letter contained only the revised sections and not the author's
opinion. However, they will not significantly affect the decision.
One point, I could not read the response about selection bias between study participants and
non-participants.
Patients who actively participate in the study and those who do not agree to participate may have
different preferences for food and diet. Therefore, we believe that the point at which selection
bias is already present at the time of participation in this study should also be mentioned as a
Limitation.
Review for 10.1186/s12876-025-03719-z (2025)

Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients
treated at hospitals in Bahir Dar city, North-west Ethiopia
Version: 3 Date: 27 Dec 2024
Reviewer's report:
Dear authors the title you are studying is crucial but I have concerns and comments for
corrections.
1. Between line numbers 4-9, please add your affiliations, emails and telephone number, p.o.
box and fax number.
2. In line 36, please give the title, which is introduction before you write the sub heading which
is background.
3. In line 106, “Materials and Methods” correct to Methods and materials.
4. In lines 107-116, merge the two subheadings and make then as study area and period and then
make the study design a separate sub heading. When writing about the study area, first write
about Bahardar city, the population and then the health service institutions.
5. In lines, 117-121, summarize in to one sentence, which is only about the study design.
6. From lines, 122-139, of the data collection procedure is not clear. It needs a through revision
and correction. Since the data collected were chart review, why COVID-19 prevention measures
were a concern and is it now a public health concern?
7. There are a lot of missing sections in the methodology such as, populations, eligibility,
sampling technique, sample size calculations, study variables, operational definitions etc.
8. I have not seen the treatment outcome.
9. In table 2, there is no need of writing the keys since there is an abbreviation sections.
10. In the associated factors table at line number 193-196, you should add the cross tabulation
in order to understand very easily.
Review for 10.1186/s12876-025-03719-z (2025)

Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients
treated at hospitals in Bahir Dar city, North-west Ethiopia
Version: 3 Date: 29 Dec 2024
Reviewer:  Tirsit Ketsela Zeleke
Reviewer's report:
Thank you for the opportunity to review this manuscript. This study focuses on the assessment of
treatment outcomes and associated factors among patients with chronic liver disease. While the
topic is quite interesting, there are several issues that require extensive revision. I have included
my comments and questions in the attached commented manuscript.
Review for 10.1186/s12876-025-03719-z (2025)

Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients
treated at hospitals in Bahir Dar city, North-west Ethiopia
Version: 4 Date: 21 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory.
Review for 10.1186/s12876-025-03691-8 (2025)

Title: The relationships between depression, inflammation and self-reported disease activity in
IBD and their impact on healthcare usage.
Version: 2 Date: 19 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Unfortunately endoscopical and histological pictures were unavailable Abstract Background
length could be reduced Covariates evaluated should be described Statistics Power of the study
should be calculated FCP has different special gravity for UC and CD Thus sub-analysis might
be worthwhile
Review for 10.1186/s12876-025-03691-8 (2025)

Title: The relationships between depression, inflammation and self-reported disease activity in
IBD and their impact on healthcare usage.
Version: 2 Date: 20 Nov 2024
Reviewer:  A. Barney Hawthorne
Reviewer's report:
This is a useful, well-written study, with adequate sample size and good methodology.
1) The main limitations are covered in the Discussion, but it would be helpful to spell out clearly,
what I consider to be the major limitation: which is that patients recruited to boost had to be
symptomatic individuals in clinical remission. This has selected a group more likely to have
functional symptoms.
2) the subset with calpro >200 (presumably about 120 pts could be assessed as a subgroup to
see if the associations/lack of associations remained
3)does the use of significant fatigue as an additional factor in the analysis make any difference?
Review for 10.1186/s12876-025-03691-8 (2025)

Title: The relationships between depression, inflammation and self-reported disease activity in
IBD and their impact on healthcare usage.
Version: 2 Date: 01 Dec 2024
Reviewer:  Yüksel Do#an
Reviewer's report:
What is the article about, what is new?
This article examines the association between depression, self-reported disease activity (SRDA)
and objective measures of inflammation (faecal calprotectin) in people with IBD. It assesses
whether these factors predict healthcare utilisation and economic indicators. The study
highlights the interaction between psychological factors and IBD management using data from
a randomised controlled trial.
As SRDA emerged as a stronger predictor of depression and functional outcomes than FCP, it
suggests that addressing patients' perceptions of disease control may be critical.
Being unemployed appears to play an important role in predicting increased depression. Specific
interventions to support work engagement or vocational rehabilitation may reduce this burden.
Collaborative care models, particularly for younger people and those with high SRDA scores,
combining psychological and medical management may improve outcomes.
1. Missing parts of the article
The introduction could further describe the implications of the gut-brain axis for therapeutic
strategies.
Mechanisms behind the lack of correlation between faecal calprotectin (FCP) and depression
are poorly discussed.
2.. Gaps in grammar
Inconsistent use of tenses (e.g. 'is' and 'was').
Strange phrasing in some sentences such as "Depression and inflammation may be causally
linked in IBD through the gut-brain axis..." could be made more precise.
Minor grammatical errors such as using unnecessary commas and misusing articles (e.g.
"Depression was also associated with..." instead of "Depression was also associated with...").
The data show complex associations between depression, disease activity and inflammation in
IBD. Highlights include the associations between depression and socio-demographic variables
and the predictors of disease activity and inflammation.
Review for 10.1186/s12876-025-03691-8 (2025)

Title: The relationships between depression, inflammation and self-reported disease activity in
IBD and their impact on healthcare usage.
Version: 3 Date: 30 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the introduction mentions that depression may be an "extraintestinal manifestation of
IBD," this point could be better explained. The authors refer to cytokines, microbiota dysbiosis,
and other factors as mechanisms, but the reader may benefit from more explicit clarification on
why depression is thought to be tied to inflammation in the context of IBD specifically (e.g.,
through cytokine release or HPA axis activation).
-A more concise explanation of how FCP specifically relates to both depression and disease
activity (beyond just being an inflammatory marker) could strengthen the argument for why it
is the focal biomarker in this study.
-The introduction mentions limited evidence on the contemporaneous relationships between
depression, disease activity, and SRDA, but the discussion could be expanded to explain some
of the contradictory findings in prior research. For example, how studies have shown both weak
and strong associations between depression and FCP, and why such discrepancies might exist
(e.g., variations in study populations, methodologies, or measurement tools). This could add
nuance to the presentation of prior literature.
-The discussion contrasts the findings with the conceptual framework of the gut-brain axis,
which suggests that depression might lead to inflammation and vice versa. However, the
relationship between these two variables (depression and inflammation) is described as weak or
nonsignificant, which could be confusing. The authors could clarify whether they are rejecting
the gut-brain axis entirely or suggesting that its effects might be less pronounced in this specific
cohort of IBD patients.
-The authors mention that there were no significant findings when splitting the data by disease
subtype (Crohn’s Disease vs. Ulcerative Colitis). However, it would be helpful to elaborate on
why the relationship between depression and inflammation might differ (or not) between these
two subtypes, especially considering the known differences in disease pathophysiology. A brief
explanation of potential reasons for this lack of differential findings would provide more depth
to the discussion.
-The weak negative correlation between SRDA and FCP is discussed, but it could benefit from
more explanation. Why might SRDA, a subjective measure, only weakly correlate with an
objective marker like FCP? The authors could consider psychological factors, cognitive biases,
or even medication use that may influence patients' perceptions of disease activity independent
of inflammation. This point could be strengthened by referencing literature on the cognitive and
psychological factors influencing symptom reporting in chronic diseases.
Review for 10.1186/s12876-025-03742-0 (2025)

Title: Development and validation of computer-aided detection for colorectal neoplasms using
deep learning incorporated with computed tomography colonography
Version: 2 Date: 09 Dec 2024
Reviewer's report:
Commments 1:  I believe it is essential to verify whether there is any overlap of patients across
the test, validation, and training datasets.
Commments 2: Sensitivity, as a true positive measure, does not account for instances where a
lesion is completely missed. Since ensuring no lesion is overlooked is critical for developing a
model fit for the intended purpose, model performance evaluation should also include metrics
such as NPV (Negative Predictive Value) to present the model's effective detection probability.
Commments 3: It would be helpful to provide justification for setting the IoU threshold at 0.125.
Commments 4: Comparing the classification performance with other state-of-the-art (SOTA)
models would strengthen the study. Alternatively, presenting metrics that align with and validate
the reported performance indicators would be valuable.  The sensitivity values provided—0.815,
0.738, and 0.883 for lesions # 6 mm, 6 to 10 mm, and # 10 mm, respectively—are difficult to
interpret in isolation. Further context or explanation regarding these metrics is needed.
Review for 10.1186/s12876-025-03742-0 (2025)

Title: Development and validation of computer-aided detection for colorectal neoplasms using
deep learning incorporated with computed tomography colonography
Version: 2 Date: 21 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the abstract and methods mention that lesions # 6 mm were the target for this study,
it would be useful to clarify how lesion annotations were made in more detail. For instance,
how was the agreement between the radiologists who annotated the lesions ensured? Was
there a consensus process or inter-rater reliability testing for annotation? Greater clarity on the
annotation process would help assess the reliability and accuracy of the training data.
-The study defines lesions in three categories: # 6 mm, 6 to 10 mm, and # 10 mm. However,
the rationale for this specific categorization could be further justified. For example, why were
lesions > 10 mm not grouped with those # 6 mm, and how were lesions between 6-10 mm
considered clinically relevant? Some brief justification for these categories would be helpful in
understanding the impact on detection accuracy and sensitivity.
-The study explores the use of CT colonography in two positions (supine and prone) to improve
lesion detection. While the authors mention that merging two positions improved sensitivity,
more information on the statistical analysis and the impact of different positions on lesion
detection would strengthen the interpretation of these results. For instance, what was the average
improvement in sensitivity when using both positions compared to a single position? Were
certain types or sizes of lesions more effectively detected in one position versus the other?
-A major limitation of this study is the absence of an image interpretation experiment in which
a physician independently validates the lesions identified by the AI algorithm. While the AI
algorithm shows promise, comparing the AI’s performance with expert radiologists' assessments
would provide further validation and demonstrate the clinical utility of the AI system in real-
world decision-making.
-The study could also explore the cost-effectiveness and logistical feasibility of implementing
dual-position imaging and AI in a real-world clinical setting, particularly in low-resource
environments where there may be a shortage of radiologists. Economic analyses would be useful
for assessing the value of such technologies in colorectal cancer screening programs.
Review for 10.1186/s12876-025-03742-0 (2025)

Title: Development and validation of computer-aided detection for colorectal neoplasms using
deep learning incorporated with computed tomography colonography
Version: 2 Date: 22 Dec 2024
Reviewer's report:
Thank you for your invitation to review the article titled: “Development and validation
of computer-aided detection using deep learning incorporated with computed tomography
colonography.” Here are my suggestions to improve the article.
While the authors aimed to develop deep learning algorithms using CT colonography, the goal
isn't clearly stated in the title and the beginning of the manuscript. They mention “neoplastic
lesions in CT colonography images,” but it's not clear if this includes all types of metastatic
lesions as well. Given that the data for training comes from colorectal cancer patients, it would
be helpful if the title and manuscript clearly indicated this focus.
Additionally, the manuscript lacks clear inclusion and exclusion criteria, along with information
about the tumor stages, CT properties, and the study duration. The details about the annotation
process, training, and how the data was divided into training and validation sets are also too
vague and general.
Overall, the manuscript suffers from some redundancy and vague language, making it difficult
to extract the necessary details. I recommend rewriting the methodology section to be clearer
and more concise.
At this stage, I believe the manuscript isn’t quite ready for publication and would benefit from
significant revisions before moving forward.
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 3 Date: 10 Nov 2024
Reviewer:  Luis del Carpio-Orantes
Reviewer's report:
After reviewing the modified version of the document, which complies with the reviewers'
observations, I consider it ready to be published.
I consider it to be an interesting exploratory study, supported by tables and appropriate statistics,
so I have no problem with its publication.
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 3 Date: 10 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Was response to treatment taken into consideration to evaluate the method ? What
authors mean by inflammatory diarrhea? By which method has it  been diagnosed? Why
treatment was given empirically while there was a result from stool?Those questions are valid
for methods section as well Methods Definitions of acute, persistent and chronic diarrhea
should be provided Demographic and clinical parameters recorded should be descibed  Were
there any additional exclusion criteria apart from age like clinical condition, inability to
provide medical history, metal illnesses? Statistics Would multivariated analysis be useful ?
Results SD should be provided apart from mean Was population homogenious comparing their
dwelling? In patients with C.Difficile , had authors proceeded to treatment without checking
for toxins in stool? Was there any diffrence between in-patients and out-patients? Was there
any difference between inflammatory and non-inflammatory diarrhea? Was there any diffrence
between immucompetent and immunosuppressed patients in identifing more than one organism?
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 4 Date: 27 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Instead of the statistical methods used it might be better to describe parameters included
in the model Results A subanalysis if possible might be useful between immunosuppressed and
immunocompetent patients concerning defining risk factors for a positive GIP
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 4 Date: 14 Dec 2024
Reviewer's report:
Regarding the study, my observations are:
There is no appropriate definition of the cases for study or analysis.  The authors only says that
were patients with diarrhea.  It does not clarify whether any of these patients were already being
treated or were undergoing a diagnostic approach for chronic diarrhea or if they were carriers
of diseases that produce chronic diarrhea such as inflammatory bowel disease or celiac disease.
It does not adequately define whether there were exclusion criteria.
It does not properly spell the scientific names of microorganisms.  A virus name should never
be italicized (norovirus is the correct form), only the virus species is always written in italics.
The words enteroaggregative or enteropathogenic or enterotoxigenic that precedes Escherichia
coli should never be written in italics.  This reveals a lack of knowledge of basic microbiological
aspects.  Use updated name of bacteria; although the panel still maintains the name Clostridium
difficile, the author must use the current name in his paper of Clostridioides difficile.
There is summation in the tables that do not coincide.  There were 350 patients but when
analyzed by place or site the sample was taken, they do so based on 348, that means they lose
that information from two patients.  Could it have been better if they excluded those 2 patients
from the beginning?
The tables are confusing.  For example, it says: Number of bacteria identified: 350.  This aspect
of confusion is repeated in several tables.
The wording of some English expressions needs to be improved.  Avoid for example the use of
decimal description in prose "Thirty-nine point one".
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 5 Date: 05 Jan 2025
Reviewer:  Luis del Carpio-Orantes
Reviewer's report:
After reviewing the revised document and following the reviewers' recommendations, I consider
that these were carried out, so the document is ready to be considered for publication
Just reviewing the entire document, in some segments words in Spanish appear
At the end of the point by point
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 5 Date: 10 Jan 2025
Reviewer's report:
Dear authors. I appreciate the corrections you have made.  There are still aspects to correct in
search of the best quality of the article so that it can be published in BMC Gastroenterology.
1.  I consider that the tables can still be visually enhanced to make them easy to see, analyze
and understand.
2. There are words that are misspelled such as the word Genre which should be Gender.
3.  There are also words written in Spanish such as “Positivo” and “Negativo” (Table 2) when
it should be Positive and Negative.
4. There are words that were included but do not have the meaning that is intended.  You are
using the word chronicle instead of chronic.
5. The terms EPEC, EAEC, ETEC and ESTEC should not be written in italics.
6. There are words that are written in italics on the tables and that should not be written that way.
Example (Table 3): Acute, Subacute, Trasplant, Hematologic neoplasia, HIV, Solid neoplasm,
etc.
7. The cells or lines of the tables must be adjusted.  The first letter of some sentences should be
capitalized, such as I for Inflammatory bowel disease in Table 3.
8.  The correct name and as described in the gastrointestinal panel method is Shiga-like toxin-
producing E. coli (STEC) stx1/stx2 and should be spelled as such.
General tip: details make a difference and are an indicator of quality!
Review for 10.1186/s12876-025-03693-6 (2025)

Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the
Gastrointestinal Panel in a High-Complexity Center
Version: 6 Date: 29 Jan 2025
Reviewer's report:
The great effort you have made to correct the points indicated is recognized.  It would still be
good if in the preview check that "Typeof" is written separately (Table 3)
Otherwise I think this product would be ready to be released.