JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-023-03063-0 (2024)

Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 8 Date: 07 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have substantial improvements to the manuscript, by
addressing most of the questions raised by me.
Some minor issues remain. If these are also addressed, the paper could be considered for
publication.
ADDITIONAL REQUESTS/SUGGESTIONS:
Several sections of the manuscript could benefit from revisions.
1.3 - Manometry process- This could be shortened, with the full description added as
supplementary material, or a standard textbook could be cited.
2.2.6 - Even after the revision, I find this section difficult to understand.
Review for 10.1186/s12876-023-03063-0 (2024)

Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 9 Date: 04 Nov 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
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 revised the manuscript based on the comments of
the reviewrs. The manometry procedure has been effectively summarised.
There is one section I flagged in my previous comments, which the authors have revised. I still
find this difficult to read, but will allow the editors to make the decision on that section.
The rest of the article is ready for publication.
REQUESTED REVISIONS:
Listed above
Review for 10.1186/s12876-023-03105-7 (2024)

Title: Evaluation of autoimmune liver disease natural history in patients referred to Middle East
Liver Diseases (MELD) center
Version: 0 Date: 14 Sep 2023
Reviewer's report:
I was really glad to read this study on the prevalence and clinical manifestations on autoimmune
liver disease in Iran. The stud y provides important information on the field, however it can
benefit from changes.
1)Title is accurate and reflects the content
2)Abstract is satisfactory
3)Introduction should focus on the fact that very few studies on this field have been published
from this region.
4) Patients and Methods should be better organized and definitions should be better explained.
How acute hepatitis is defined (levels of AST/ALT and Bil), what about the IgG on AIH patients,
how was cirrhosis defined?). Moreover, with which score was the outcome of PBC evaluated,
what do the authors mean with response in PSC? Autoantibodies and methods to determine them
should be clearly mentioned. How many patients had liver biopsy?
Results should also be better analyzed and presented. There are more patients with AIH than
PBC which is rare, how could we explain this? Separate paragraphs should be made for baseline
characteristics in each group, histological characteristics, treatment and outcome. The Figures
are necessary but should be designed better (two versions of the same graph are not needed and
in bars exceed the limits of the graph, maybe SE and not SD should be used).
How was reversal of cirrhosis defined? Was liver elastography available?
Discussion should include conclusions about how and if the results come in agreement with what
is observed in Europe and USA, where differences could be attributed and how results could be
affected from other reasons (economical, ethical, religious etc) in this geographical region.
To summarize, I think that it is very interesting to present what happens up to know with
autoimmune liver disease in this part of the world, but data should be better presented in order
to cover this field sufficiently.
Review for 10.1186/s12876-023-03105-7 (2024)

Title: Evaluation of autoimmune liver disease natural history in patients referred to Middle East
Liver Diseases (MELD) center
Version: 1 Date: 28 Oct 2023
Reviewer's report:
I appreciate that the authors have made some changes in the manuscript. However, the whole
concept still lacks precision. I was expecting to see that the authors would focus on what they
observed in the Iranian population and afterwards comment on the similarities and differences
with what is already published.
I am sorry to say that the final version of the manuscript is not what I was expecting.
Review for 10.1186/s12876-023-03105-7 (2024)

Title: Evaluation of autoimmune liver disease natural history in patients referred to Middle East
Liver Diseases (MELD) center
Version: 5 Date: 15 Dec 2023
Reviewer's report:
I really appreciate the great effort of the authors to address all changes and comments so as to
make the manuscript suitable for publication.
I think that the manuscript has benefited of changes, and since it is a unique study from this
geographic region I think it  is suitable for publication.
Review for 10.1186/s12876-023-03110-w (2024)

Title: VALIDATION OF DIAGNOSES OF LIVER DISORDERS IN USERS OF SYSTEMIC
ANTIFUNGAL MEDICATION IN SWEDEN
Version: 1 Date: 06 Oct 2023
Reviewer's report:
This is a well written and well conducted validation study. Patients treated with systemic anti
fugal drugs were identified through the Swedish Prescribed Drug Register and subsequent
diagnosis of toxic liver disease in the National Patient Register. The diagnoses were thoroughly
validated using predefined criteria based on information in the medical journals (including
biochemical data, pathology and imaging).
I only have a few minor comments
1) Line 72: Instead of "secondary databases" - I would suggest "Routinely collected clinical data
such as discharge diagnoses"
2) Lines 77-82 beginning with "Mislassification can occur......using positive predictive values."
This sound a bit like text book material. I would delete this or shorten and move to the discussion.
3) Did the authors have any information on azoles administered during hospital admissions?
4) I was considering whether you could apply algorithms to obtain higher PPVs for subgroups
of patients. a) Could there be a dose-dependent effect with higher PPV for those who received
higher doses and longer treatment? b) Could there be a difference according to cancer? You
could explore this and calculate PPVS for patients with active cancer and those with prior cancer/
no cancer.
5) Are you in Sweden allowed to present table cells with less than 5 cases (GDPR etc.)?
6) In table 2 I would suggest to combine n (%) in one column, so you will have only 3 columns
with liver diseases to improve readability.
7) Figure 1. The flow chart is not entirely self explanatory in the current version.  In order to
really understand the flow you need the text in the manuscript. I think it would benefit from a
revision to improve readability.
Review for 10.1186/s12876-023-03110-w (2024)

Title: VALIDATION OF DIAGNOSES OF LIVER DISORDERS IN USERS OF SYSTEMIC
ANTIFUNGAL MEDICATION IN SWEDEN
Version: 1 Date: 17 Oct 2023
Reviewer's report:
I read with interest the report from Giunta DH et al.
With this study, authors tried to characterize the possible link between azoles and liver
dysfunction within 6 months of onset. Following medical records review, PPV of 3 different
liver dysfunction diagnoses were diverse: low for toxic liver disease or hepatic failure; high for
jaundice.
Although interesting, results give rise to some questions:
- How did you select 150 from 335 patients?
- Definitions used of liver dysfunction were agreed based on which consensus?
- Why look only for azoles and not other antifungals?
- Were liver diagnoses defined to better reflect potential toxicity patterns of azoles?
- How can you account for liver disease arising after azole initiation but not related to that?
- What sort of malignancy do you report - liver related, other?
- There seems to be a potential association between discordance in liver diagnoses between
reviewers at the start and PPV at the end of the study - is this bias?
Overall, it would be nice to have more granular data to support a potential link between azoles
use and liver toxicity.
Review for 10.1186/s12876-023-03110-w (2024)

Title: VALIDATION OF DIAGNOSES OF LIVER DISORDERS IN USERS OF SYSTEMIC
ANTIFUNGAL MEDICATION IN SWEDEN
Version: 1 Date: 18 Oct 2023
Reviewer's report:
This study looked at validation of registry data using ICD codes for the diagnosis of drug
induced liver injury due to systemic anti-fungal agents in Sweden. The study appeared to be
carefully done and well designed. It appears to have been part of a larger study looking at post-
marketing events for voriconazole. As such it did not include patients treated with amphotericin
or caspofungin.  The authors conclude that the positive predictive value for the diagnosis of
jaundice was high but the PPVs for toxic liver injury and hepatic failure were lower (approx
50% to 60%).
Comments.
It is an interesting study and well done. It appears to produce results similar to previous studies,
although the authors note these studies were not homogeneous in either populations or methods.
I think it would be helpful if the authors could indicate where they feel this kind of data from
registries could be useful. Is this kind of registry data useful for detecting a toxicity signal
which must then be interrogated by looking at the source data or is there some other use for
this approach?
Given that amphotericin and caspofungin were not included in the study perhaps the title could be
amended as a significant fraction of users of systemic antifungal medications were not included.
The definition of hepatic failure (line 142-4) used says "persistent disease 26 weeks from the
diagnosis of liver disease".  Is this a typo? - The definition of acute hepatic failure used in the
AASLD practice guidelines states: evidence of coagulation abnormality (INR > 1.5) and any
degree of mental alteration (encephalopathy) in a patient without pre-existing cirrhosis and with
an illness of < 26 weeks duration. This is the classical Trey and Davidson definition from 1970.
EASL guidelines also quote the Trey and Davidson definition and note that disease duration
of greater than 28 weeks before onset of encephalopathy is defined as chronic liver disease.
Subacute hepatic failure is disease to encephalopathy time of between 5 and 24 weeks.
I agree with the authors that jaundice can be due to causes other than liver failure. While the PPV
for jaundice was high it would be useful to know what proportion of the patients with definite
jaundice had evidence of severe liver injury or hepatic failure.
Review for 10.1186/s12876-024-03122-0 (2024)

Title: Endoscopic gastrointestinal bypass anastomosis using deformable self-assembled
magnetic anastomosis rings (DSAMARs) in a pig model
Version: 1 Date: 12 Nov 2023
Reviewer:  Pieter Hindryckx
Reviewer's report:
This is a very interesting preclinical proof-of-concept study demonstrating feasibility of
gastroenterostomy creation using 2 series of endoscopically/fluoroscopically placed magnets.
I have a few questions that I would like to have addressed by the authors
1) The procedural time seems to be quite long to me (longer than EUS-guided gastroenterostomy
with LAMS). Can the authors elaborate on this in the discussion: what are the most difficult and
time-consuming steps?
2) Based on the endoscopic picture and what I would expect, the created anastomosis looks
inflammatory and hence, you can expect an early stenosis after the magnets migrate. Do the
authors have any longer term data on the patency of the gastroenterostomy over time?
3) In some patients with malignant gastric outlet obstruction the stenosis can be very tight and
pinpoint. Do the authors expect any difficulty in passing the magnets through a tight and hard
stenosis only supported by a guidewire?
4) The mass of magnets that falls of after anastomosis creation is probably considerable (2x10
magnets all fixed to each other). I'm a bit afraid of the risk for downstream obstruction caused
by the magnets. Can the authors comment on this?
Review for 10.1186/s12876-024-03122-0 (2024)

Title: Endoscopic gastrointestinal bypass anastomosis using deformable self-assembled
magnetic anastomosis rings (DSAMARs) in a pig model
Version: 1 Date: 26 Nov 2023
Reviewer's report:
Very good study and novel use of MCA for gastrointestinal bypass anastomosis in case of gastric
outlet obstruction. I want to comment on this novel device and experimental study.
Regarding this device and procedure:
1) One needs to know The height and width of individual magnets, as severe luminal narrowing
sometimes may not allow passage of a 12mm broad trapezoid (Assumed based on inner minus
outer diameter, 25-13=12).
2) Which guidewire and push catheter was used for the procedure? What was the diameter and
length of the guidewire and catheter? Are they specially designed for this procedure? It would
be great if a photo of the entire assembly were given.
3) In real gastric outlet obstruction, can this entire assembly be withdrawn if stricture does not
allow the passage of magnets across it?
4) Once magnets are in a ring shape, is there always attraction between two rings, or can there
be repulsion if they are placed randomly? Is there any specific need to put one surface up and
the other down so there is no repulsion?
5) Regarding the procedure, I suggest providing one video for a better understanding of the
procedure.
6) Was a proton pump inhibitor given post-procedure to decrease the risk of anastomotic site
ulcer and bleeding?
Regarding result and outcome
7) Was the animal model watched for symptoms of bowel obstruction? Two magnet rings of 25
mm diameter can possibly cause bowel obstruction, especially at the ileocecal valve or terminal
ileum.
8) Endoscopy was done after passage of the magnet through the anus, was the diameter of
anastomosis noted? What is anastomosis diameter after necropsy at four weeks? Is there any
discrepancy in sizes to suggest the possibility of restenosis?
9) The mean duration of magnet expulsion was 13 days; immediate feeding was started
in the pig model because they have normal passage through the pylorus. In gastric outlet
obstruction, feeding will be delayed for these days compared to an antral stent for EUS-guided
gastrojejunostomy. This is a limitation of MCA and should included in the limitations of the
study.
Review for 10.1186/s12876-024-03122-0 (2024)

Title: Endoscopic gastrointestinal bypass anastomosis using deformable self-assembled
magnetic anastomosis rings (DSAMARs) in a pig model
Version: 2 Date: 18 Dec 2023
Reviewer:  Pieter Hindryckx
Reviewer's report:
Many thanks for the comprehensive reply to my comments.
Review for 10.1186/s12876-024-03122-0 (2024)

Title: Endoscopic gastrointestinal bypass anastomosis using deformable self-assembled
magnetic anastomosis rings (DSAMARs) in a pig model
Version: 2 Date: 25 Dec 2023
Reviewer's report:
All points were well addressed, except point 3, where my concern is that if we cannot push the
magnets assembly over a guidewire completely across the stricture, If we get stuck in mid-way
with half magnets inside the stricture and half are in the stomach - can we withdraw the whole
magnet assembly along with the guidewire?
Review for 10.1186/s12876-023-03111-9 (2024)

Title: Evaluation of the causal effects of blood metabolites on irritable bowel syndrome:
Mendelian randomization
Version: 0 Date: 01 Nov 2023
Reviewer's report:
This paper is a solid contribution with novel results. However, there are some details that require
attention.
A general concern is that multiple testing is not addressed. 486  metabolites are tested but I don't
see any correction for that.
73 The phrasing “MR studies utilize genetic variations resulting from long-term exposure as …”
suggests that the genetic variation might be somatic mutations, and so it should be rephrased.
114 The narrative distinction between the two samples should be made more distinct (even just
a paragraph break would do). There is also a relative paucity of information on the IBS sample
relative to the description of the metabolites sample. Finally, the degree to which the sample
populations are comparable should be addressed.
121 “we eased the selection parameters and established a significance threshold …” is (I think)
just “we relaxed the significance threshold to …”. That is, no other criteria were changed.
125 There should be some explanation of why the criteria listed here are different than in the
preceding sentences.
127 The cited paper (16) specifically recommends against simply using a threshold of F of 10
to avoid weak instruments.
149 Post-hoc power analysis is almost always ill-advised, and I don’t believe ref (23) is intended
for post-hoc power as used here.
162 I don’t understand why the FinnGen data is used as part of meta analysis instead of
replication. Could the authors address this? The Finnish population is somewhat distinct from
other parts of Europe---the authors might address whether that matters in the present context.
168 “Genetic correlation is a common method of genetic correlation analysis …” has to be
rewritten.
171 I don’t think (25) is the intended reference.
I’m afraid I don’t understand the use of the term genetic correlation for association of a snp and
phenotype. Isn’t genetic correlation used in the context of two or more distinct phenotypes? Do
the authors mean snp-specific heritability? For example, table 2 is labeled as showing heritability
while genetic correlation is named.
214 A reference is missing.
248 Four subtypes are mentioned by only three are specified. Since these subtypes are not used
in the analysis, they could be omitted or the connection to the present study  made more explicit.
266 Given that four metabolites have been found to be associated, why write that two of them
“appear to be the risk factors for IBS”? Writing “the” is also rather assertive, rather than writing
“appear to be risk factors for IBS.”
Fig 1 has several typos.
Review for 10.1186/s12876-023-03111-9 (2024)

Title: Evaluation of the causal effects of blood metabolites on irritable bowel syndrome:
Mendelian randomization
Version: 0 Date: 14 Nov 2023
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
Manuscript highlights new possible biomarkers in IBS. These findings are essential in clinical
practice and are worthy of publication in scientific journals. Some minor revision suggested:
1. Expand the clinical use of omics technologies in the introduction. The paper doi: 10.3389/
fcimb.2022.1010979 should be cited.
2. Clarify in the methods how the diagnosis of IBS was made.
3. What are the future perspectives?
Review for 10.1186/s12876-023-03092-9 (2024)

Title: Prediction of injury localization in preoperative patients with gastrointestinal perforation:
A multiomics model analysis
Version: 1 Date: 04 Nov 2023
Reviewer:  Dongliang Yang
Reviewer's report:
The authors should   supplement the P-value of the Hosme-Lemeshow test for calibration of
the model
Review for 10.1186/s12876-023-03092-9 (2024)

Title: Prediction of injury localization in preoperative patients with gastrointestinal perforation:
A multiomics model analysis
Version: 1 Date: 19 Nov 2023
Reviewer:  Kenji Nakamura
Reviewer's report:
The authors created a prediction model for the perforation site, severity and cost, validated it,
and reported its usefulness.
This manuscript is interesting; however, it seems to be required some revisions.
Major
1) An inappropriate abbreviation appears for the first time in the abstract.
2) Introduction is too long.
3) Please indicate the criteria for ICU admission.
4) It is unclear what Figures 3 and 4 are comparing. What does "Ts patient" mean?
5) The explanation of the legend in Figure 9 is insufficient.
6) I think a and b are reversed in Figure 10.
7) Please further consider the limitations.
8) Regarding the conclusion, can this study mention the prediction of patient prognosis?
Minor
1) There are many spacing errors.
2) The red arrows in Figure 2 are the same arrows used for different parts, so please change them.
3) Please write the abbreviations in Table1.
Review for 10.1186/s12876-023-03092-9 (2024)

Title: Prediction of injury localization in preoperative patients with gastrointestinal perforation:
A multiomics model analysis
Version: 4 Date: 04 Dec 2023
Reviewer:  Kenji Nakamura
Reviewer's report:
Thank you for the chance to check the revised manuscript.
I feel that this manuscript has been appropriately revised.
I have no additional comments in particular.
Review for 10.1186/s12876-023-03092-9 (2024)

Title: Prediction of injury localization in preoperative patients with gastrointestinal perforation:
A multiomics model analysis
Version: 4 Date: 11 Dec 2023
Reviewer:  Dongliang Yang
Reviewer's report:
This is a very significant study, the use of statistical methods is appropriate, the conclusion is
credible
Review for 10.1186/s12876-023-03107-5 (2024)

Title: Incidental detection of upper gastrointestinal epithelial neoplasia by screening endoscopy
prior to endoscopic ultrasonography in patients with pancreaticobiliary disease
Version: 1 Date: 19 Oct 2023
Reviewer's report:
Comments to the Author
Comment:
In the present study, the authors investigated the utility of screening
esophagogastroduodenoscopy performed sequentially with endoscopic ultrasonography for
patients with pancreaticobiliary disease. The authors described in this article that the detection
rate of gastric epithelial neoplasms in the protocol was higher than that in the medical checkup
center. The authors also suggested that magnification endoscopy may facilitate detection in the
protocol. It is clinically valuable to examine the usefulness of this protocol, however, as many
institutions are probably already conducting this protocol. However, the manuscript has several
flaws that need to be assessed.
Comments
##      In Japan, Helicobacter pylori (H. pylori) is the main causative factor of gastric cancer.
  Regarding the Characteristics in Table 1, do you have any data on H. pylori infection?
## Comments on the comparison of gastric epithelial neoplasia detection rates between the EUS
and MCC groups: 31.1% of the EUS group used a magnification endoscope while the MCC
group did not use a magnification endoscope. Is there an analysis of both groups only with
subjects not using the magnification endoscope?
Review for 10.1186/s12876-023-03107-5 (2024)

Title: Incidental detection of upper gastrointestinal epithelial neoplasia by screening endoscopy
prior to endoscopic ultrasonography in patients with pancreaticobiliary disease
Version: 1 Date: 05 Nov 2023
Reviewer:  Jun-Hyung Cho
Reviewer's report:
The major concerns about this manuscript are as below;
First, the academic background for screening esophagogastroduodenoscopy (EGD) in patients
with pancreaticobiliary disease is not sufficient. Gastric cancer development is strongly
associated with chronic H. pylori infection, leading to atrophic gastritis and intestinal
metaplasia. To date, however, there is no association between premalignant gastric condition
and pancreaticobiliary disease. I think that the protocol of this study is just opportunistic
screening when these patients are scheduled for pancreaticobiliary EUS. In patients with severe
pancreaticobiliary disease, prior EGD before EUS may be harmful due to longer sedation time
and sequential examination.
Second, I hope that manuscript title is changed to ‘Incidental finding of esophageal and gastric
neoplasia in screening endoscopy performed prior to EUS in patients with pancreaticobiliary
disease’. Two patients were diagnosed as esophageal dysplasia or cancer.
Third, patient inclusion should be described as flow chart figure in EUS and MCC groups.
Fourth, expert or non-expert in Table 1 should be defined as doctor`s experience year and number
of endoscopy examination. Gastric mucosal atrophy in Table 1 should be classified into non-
severe/severe or closed/open type according to endoscopic or pathologic findings. The patients
with severe and open type are at higher risk of gastric cancer than non-severe and closed type.
Fifth, I don`t think magnifying endoscopy (model: H260Z, H290Z) in EUS group is randomly
selected according to doctor`s preference. In magnifying endoscopy, NBI may be used more
frequently for detecting early esophageal or gastric neoplasia. Please describe the proportion of
numbers of experts and procedure time when H260Z and H290Z endoscopies were used.
Sixth, the type of endoscopy machines is different between EUS (Olympus) and MCC (Fuji)
groups. The detection rate of gastric neoplasia may be affected by endoscopy image quality and
color contrast. This  is the big issue in present study.
Seventh, alcohol drinking and smoking history should be involved in comparison between
EUS and MCC groups (Table 2). Personal habits are important for cancer development. The
detection rates are not significant (p=0.18) between two groups after propensity score matching.
Nevertheless, the authors describe the only statistical significance of p < 0.01 before propensity
score matching in the abstract.
Lastly, the proportion of patients according to eight variables should be described in Table 3.
For example, ME and non-ME are x/xxx and x/xxx in detection of gastric neoplasia.
Review for 10.1186/s12876-023-03107-5 (2024)

Title: Incidental detection of upper gastrointestinal epithelial neoplasia by screening endoscopy
prior to endoscopic ultrasonography in patients with pancreaticobiliary disease
Version: 4 Date: 23 Dec 2023
Reviewer's report:
Peer review
Main comment
The title of this paper has been appropriately changed to ``Incidental detection of upper
gastrointestinal epithelial neoplasia by screening endoscopy prior to endoscopic ultrasonography
in patients with pancreaticobiliary disease,'' and the content has been improved to include logical
development that does not contradict the title and easy-to-understand text. .
Detailed comments
#Comparison between EUS group and MCC group. Propensity score matching was used to
properly compare the two groups, and the differences were examined.
#The Helicobacter pylori infection rate and eradication rate have only been investigated to the
extent that current data is available, but mucosal atrophy was used as a proxy for appropriate
consideration.
#During the observation period, whether the patients had undergone EGD for the first time or
multiple times was investigated and the ratio was examined, and the results showed that there
were a large number of patients in the first-time EGD group.
#The difference in scope used between the EUS group and the MCC group was also mentioned,
and its low impact on the results was demonstrated.
As mentioned above, the problem has been appropriately resolved in this article, even in the
details.
Review for 10.1186/s12876-023-03104-8 (2024)

Title: Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation:
A systematic literature review with meta-analysis and number needed to treat/harm
Version: 1 Date: 23 Jul 2023
Reviewer:  Kok-Ann Gwee
Reviewer's report:
General comments
This study is of clinical relevance and interest given the prevalence of constipation, plethora of
treatments and high patient dissatisfaction. The 3 selected agents have in common a relatively
new approach that involves inducing intestinal secretion. In essence this is a comparative review
that serves to provide clinical guidance in the selection of 3 treatments with overlapping modes
of action. The key findings are: all have similar efficacy, but differing side effect profile.
Overall the paper is very lengthy. In the Introduction, the paragraph detailing the various
treatment approaches: “Several treatment approaches have been defined for constipation” can
be removed as this is not a review paper on the general management of constipation. In its place,
a bit more details can be provided on the mechanisms of actions for the 3 agents under review.
This will allow for the details about mechanisms to be removed from the Discussion, so that
there is more space to discuss the findings of the study. As the title of the paper is after all
“Comparative profiles …” the authors should provide more critical evaluation of the similarities
and the differences among the 3 agents, based on their study findings.
Methods
The methodology is clearly defined, appropriate and relevant. Except, why was a large sample
size study (linaclotide) excluded? Is this appropriate?
Results
This is a very lengthy paper. There are enough data for 3 standalone papers; ie, one for each drug.
Essentially the authors are iterating a parallel list of findings for each drug.
I believe the paper will be more reader friendly if the bulk of the data are presented in table
format with brief explanatory notes. For example, the repetitive declaration that this study was
based in the US and this study was in Japan, become tedious reading.
All the key and relevant information is provided in the supplementary tables S2 to S6, while the
meta-analyses are contained in the supplementary figures S1-S5. These tables and figures are
useful and could be placed in the main paper.
Discussion
To report that “SBM frequency was a common primary outcome measure” is a self-fulfilling
prophecy as this is the outcome dictated by the Rome committee during the period when these
clinical trials were conducted, and as the authors ‘selected’ this as the primary outcome because
this was an endpoint used by studies for the 3 agents.
The following statement is speculative and not relevant to the objective of this paper.
“Linaclotide … at different doses … It is probably due to lifestyle and racial differences such
as diet, gut microbiota, genetic polymorphism.”
Another self-fulfilling assertion is to suggest as limitations of the study that “the evaluation for
traditional laxatives, topical agents, and other new agents is not conducted”.
Review for 10.1186/s12876-023-03104-8 (2024)

Title: Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation:
A systematic literature review with meta-analysis and number needed to treat/harm
Version: 1 Date: 07 Oct 2023
Reviewer's report:
This was a well conducted and well-written systematic review with network meta-analysis. The
authors should be commended for their work. However, the main limitation of this works, which
dramatically reduces the information drawn from this work is that only few studies, mostly non-
randomized, were available for meta-analysis. It must be noted, however, that the authors have
performed additional analyses to reduce bias. In addition, the authors have acknowledged the
limitations of their work In the discussion. I only have two major comments
MAJOR COMMENTS
1. Most of the analysis only included two studies. In addition, there is a funnel plot on only one
study (Figure 3b, linaclotide145mcg), which obviously accounts for 100% of the weight of the
evidence. This should be removed from the analysis.
2. In the meta-analysis results section I would add information on the duration of the treatment.
The reason is that this outcome was generally assessed in the very-short term (1-2 weeks). And
this should be stressed both in the results section and in the discussion section.
Review for 10.1186/s12876-023-03104-8 (2024)

Title: Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation:
A systematic literature review with meta-analysis and number needed to treat/harm
Version: 3 Date: 17 Dec 2023
Reviewer:  Kok-Ann Gwee
Reviewer's report:
The authors have adequately addressed my points.
Review for 10.1186/s12876-023-03102-w (2024)

Title: The effect of an acute aspirin challenge on intestinal permeability in healthy adults
with and without prophylactic probiotic consumption: a double-blind, placebo- controlled,
randomized trial
Version: 1 Date: 19 Oct 2023
Reviewer's report:
This MS interesting and clinically important. The research questions are relevant. The methods
are valid,  carefully described  and suitable to fulfill the aim of the study.
Even if the results do not follow the hypothesis they are clinically important. The possible
failures/limitations  (e.g. choice of probiotics, length of intervention, dose of aspirin, dose of
probiotics) are adequately  described.  As sufficient length  of the baseline period and  especially
the wash-out period  are important in probiotic studies  it had been good to discuss  also their
role, especially on what basis they were chosen and if the authors regard them sufficient.
In table 2 it is difficult to understand the footnotes especially footnote 2) the calculation of the
PPS points vs numbers in the table  and in footnote 3) the wording  "all such values". Please
clarify the text.
The MS is carefully written and well structured and earns to be published without any
reservations.
Review for 10.1186/s12876-023-03103-9 (2024)

Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 3 Date: 03 Aug 2023
Reviewer:  Claudia Mandato
Reviewer's report:
Dear Authors,
the manuscript deals with an interestic topic, however I have some methodological concerns.
In table 1, BMI results are not referred to percentiles (z.-score), this is not acceptable in a study
which refers to the pediatric age.
There is a significant difference of BMI between groups probably attributed to the difference
in age. The younger age (see standard deviation) can justify per se the difference in degree of
steatosis found in the group of NAFLD+CBI.
The results should be referred to age of the patients and to BMI zscore. It is possibe that the
reduced severity of steatosis in the CBI group is related to younger age /and or to a lower  BMI
zscore.
Best regards
Review for 10.1186/s12876-023-03103-9 (2024)

Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 3 Date: 11 Oct 2023
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study aims to investigate the effect of chronic hepatitis B infection (CBI) on hepatic
steatosis and assess the association between co-existing CBI and hepatic injury in the NAFLD
pediatric population with biopsy-proven data, which is a significant strength. While the data
is intriguing, there are substantial statistical issues, notably a time-lead bias. In fact, there are
significant differences in BMI and ALT between the two groups. These differences need to
be taken into account in the analysis. In this regard, using step-wise selection in multivariable
regression analysis is not appropriate. Age, gender, BMI (given the pediatric population, BMI
z-score should be used), ALT, platelet count, and either GGT or ALP should be adjusted for as
variables of clinical interest.
As it stands, I cannot evaluate this paper. However, if similar results can be demonstrated after
addressing these analyses, I believe there would be significant merit in conducting another peer-
review.
In addition, some minor modifications would be needed as follows.
1) Lines 78-79: Please cite the reference for the statement,
"Epidemiological evidence suggests an inverse association between CBI and hepatic steatosis."
2) Lines 108-111: Ensure that abbreviations are defined upon their first usage.
The diagnosis of NAFLD was based on the NAFLD Practice Guidance from the AASLD[1].
Chronic HBV infection (CBI) was determined by a positive serum hepatitis B surface antigen
(HBsAg) persisting for 6 months or longer, as defined by the American Association for the Study
of Liver Diseases (AASLD) 2018 Hepatitis B Guidance[14].
Review for 10.1186/s12876-023-03103-9 (2024)

Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 3 Date: 15 Oct 2023
Reviewer:  Haruki Komatsu
Reviewer's report:
The article is interesting. However, the characteristics of two groups are significantly  different
in BMI, TG, LDH and TC. GT. Therefore, it is impossible to draw the conclusions.
Review for 10.1186/s12876-023-03103-9 (2024)

Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 5 Date: 04 Dec 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics 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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Authors have addressed main concerns raised by previous reviewers.
The reported reverse association between liver steatosis and chronic Hep B in children with
NAFLD is important (despite major limitations stated by authors)  as it has been previously
reported in other populations. However, there are still pending concerns that authors should
consider.
REQUESTED REVISIONS:
Authors stated that “our previous study also found that a reciprocally inverse association
between NAFLD and CBI existed in pediatric population.”. Please provide an existing reference
supporting this statement.
In the abstract section authors tend to mix explanations that should be part of the method section
“In addition, we explored the relationship between CBI and liver injury in NAFLD children.
Hepatic necroinflammation and fibrosis, respectively, were divided into two groups according
to severity.”
Tables 2,3,4 reporting results of their models are poorly presented omitting the presentation
of crude OR as well as corresponding figures (numerator/denominator) for each considered
variables.
OR as well as their respective 95%CI should be reported with only 2 decimals.
Overall, I strongly suggest that the manuscript should be reviewed by an English native to
enhance clarity as there are many grammatical errors throughout de report."
Review for 10.1186/s12876-023-03067-w (2024)

Title: A newly developed deep learning-based system for automatic detection and classification
of small bowel lesions during double-balloon enteroscopy examination
Version: 2 Date: 12 Jun 2023
Reviewer's report:
• There are a lot of scopes for authors to improve this work by doing model selection, model
tuning, dataset revision (doing split of train-test-validation data), training improvement (using
cross validation).
• Section 1.2: The authors did not mention clearly how many normal and abnormal images were
used for Model1 and Model2. It is better to provide a table for this.
• Section 1.2: The training images for the models seem imbalanced as the number of
abnormal samples (4201) are four times more than that of normal samples (1000). Class-wise
augmentation can be used to address imbalance.
• Section 1.2: The description of dataset is confusing. The author mentioned 915 abnormal
images and 1318 normal images are obtained from 187 patients. In the next sentence the author
mentioned 915 abnormal images were obtained from 98 patients. It is not clear those 915 samples
belong to same group of patients.
• Section 1.2: Both Model1 and Model2 are using same set of samples (915) for testing?
• Section 1.2: “Each video clip was cropped into consecutive images by 25 frames per second”
this line seems misleading. Cropping refers to resizing the video into different resolution/
duration. The authors can rewrite as: “Each video clip was used to extract consecutive images
at 25 frames per second rate”.
• Section 2: The authors should provide some references for YOLO and Resnet-50. This section
needs a lot more details.
• Section 3.1: The title for this section should be “Image Preprocessing”?
• Section 3.1: The images are annotated using a hybrid approach that includes both annotator
and human experts. It is not clear how the annotator results are validated.
• Section 4.1: The Assessment of YOLO can be explained in more detailed way.
• Section 4.2: Model2 uses a threshold to classify samples. It is better to share the threshold
values/ranges for better understanding.
• The English of this paper needs a significant improvement.
Review for 10.1186/s12876-023-03067-w (2024)

Title: A newly developed deep learning-based system for automatic detection and classification
of small bowel lesions during double-balloon enteroscopy examination
Version: 2 Date: 26 Jun 2023
Reviewer's report:
Dear authors,
I believe the topic to be very interesting and relevant. The concept of developing a computer-
aided diagnostic that is able to identify different categories of pathology, as well as the methods
of developing a gold standard by 3 DBE-experts; and investigating the interobserver variation
are well developed.
My foremost comment is that the article is not well-written, with occasionally the wrong word,
as well as repeat information in the different sections. I would recommend a language review
by a native English speaker.
Secondly, I find it unclear who developed the algorithm, as most medical doctors do not have
the knowledge and experience needed, and nothing in the author contributions described who
developed and adjusted the algorithm.
The third major comment is that I find the discussion to be superficial and mainly focusing on
your nice results, I would love a more thorough assessment and rebuttal of the limitations of the
study. I would suggest to describe how your results compare to similar studies, an assessment
of limitations and an assessment of strengths of your study, followed by future perspectives.
Specific comments on the article:
The abstract does not describe the gold standard you developed, which is very relevant for the
whole article and should be mentioned in my opinion.
In the method section: is it really a retrospective study? I suppose I would call it an interobserver
study, comparing assessments of the CAD and human readers.
Were the images and videos collected retrospectively, or prospectively?
Why did you only select abnormal images in model2? I gather that some DBE-investigations
are without pathology, or multiple different lesions? Wouldn't it be important to detect all these
kind of real-life results? (Could be one of the limitations you comment on in your discussion.)
Why present percentages with 2 decimals, I do not believe it makes a difference in the results,
and it does make it harder to read the text with the extra decimals.
I would propose presenting supplementary table 5 and 6 in your results, since it is one of the
main results of your study.
Results: I do not appreciate the &-sign in your written text, would prefer a `,` or `and`.
Why not discuss in your discussion the lower accuracy of detection of erosions and ulcers by
the ENDOANGEL-DBE? (It appears to be significantly lower than the other pathologies)
Supplementery table 1: I doubt whether it is relevant what the age and sex of the different patients
are, can possibly be removed.
Supplementary figure 2: specify who misdiagnosed what as what, unclear from the current text.
Possibly figure 3 as a supplemental figure, is not as relevant as the videos in my opinion.
Figure 4 holds the same images as figure 1, why not remove it or add to supplemental figures?
Review for 10.1186/s12876-023-03067-w (2024)

Title: A newly developed deep learning-based system for automatic detection and classification
of small bowel lesions during double-balloon enteroscopy examination
Version: 5 Date: 09 Oct 2023
Reviewer's report:
Dear authors,
Thank you for your clear point-to-point reply.
I do believe this version to be much approved, and only have some minor mainly language issues.
With regards to table 2-4, I still feel the presentation of accuracy makes the data difficult to
comprehend, as compared to sensitivity and specificity, especially because there are only 2
videos with diverticula and 8 with angioectasia. In my opinion it is statistically incorrect to
analyze the accuracy in this manner.
My suggestions:
Use classes instead of classifications throughout the manuscript.
Be clear on what system you are writing about. You write 'this system' or 'the system' multiple
times, why not use 'The CAD system' or 'ENDOANGEL-DBE'? In my opinion that would be
more concise and improve the clarity in the language.
Use a simular conclusion in your abstract as in your article, I would put emphasis on that it is
especially useful for novices.
Page 4 line 19: potential to reduce diagnostic error
Page 7 line 22: enclosed
Page 11 line 7: delete Who were unaware of the standard answer process
Page 13 line 3: the accuracies of the CAD system and the human observers for the different
classes of lesions is shown in ...
Page 14 line 6-9: delete, is a repetition of your introduction
Page 15 line 2: delete, is a repetition
Page 16 line 1: recent instead of current
Line 2: delete DAE, if you are not going to use the word again, the abbreviation is irrelevant
Line 17: participated instead of were Use
Line 22: were humans
Page 17 line 11: consider writing a bit more about the relevance and possiblities of such a new
AI system