JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-024-03344-2 (2024)

Title: Validity of rapid urease test using swab of gastric mucus to mucosal forceps and 13C-
urease breath test: a multicenter prospective observational study
Version: 1 Date: 30 May 2024
Reviewer's report:
1. Line 96-98 Please explain the accuracy of diagnosing H. pylori according to the Kyoto
classification. Can it replace histology?
2. Please explain why not all subjects should undergo swab-RUT, forcep-RUT, and UBT. Since
UBT is used as the reference value, there should be no need to divide them into two groups.
3. For the group of susp. H. pylori infection, how to confirm H. pylori infection? The previous
study used histology, UBT, stool Ag test and RUT to diagnose H. pylori infection (at least 2
methods) (JRMS-16-1097)
Review for 10.1186/s12876-024-03344-2 (2024)

Title: Validity of rapid urease test using swab of gastric mucus to mucosal forceps and 13C-
urease breath test: a multicenter prospective observational study
Version: 2 Date: 27 Jun 2024
Reviewer's report:
1. Correlation with UBT and biopsy-RUT: The paper suggests that Swab-RUT shows good
correlation with both UBT and biopsy-RUT. This indicates that Swab-RUT could be a reliable
alternative to these tests when biopsy samples are not available or not preferred.
2. Limitation due to biopsy-RUT: Since a significant portion of subjects (>50%) did not undergo
biopsy-RUT, the study lacks direct biopsy confirmation for these individuals. Biopsy-RUT or
histology is typically considered the gold standard for detecting H. pylori infection because it
directly tests the gastric tissue where the bacteria reside.
3. Impact on accuracy assessment: Without biopsy-RUT results for a large portion of the
subjects, it's challenging to accurately determine the sensitivity, specificity, and overall
diagnostic accuracy of Swab-RUT for detecting H. pylori infection. The accuracy could
potentially be overestimated if biopsy-RUT-negative cases were missed among those who did
not undergo biopsy.
Conclusion: The findings suggest that while Swab-RUT correlates well with other tests like
UBT and biopsy-RUT, its true accuracy in diagnosing H. pylori infection remains uncertain
without biopsy confirmation. This uncertainty could affect treatment decisions, as biopsy results
are crucial for guiding appropriate therapy.
Review for 10.1186/s12876-024-03350-4 (2024)

Title: Clinical significance of transjugular liver biopsy in acute liver failure – a real-world
analysis
Version: 4 Date: 30 May 2024
Reviewer's report:
Thank you for your submission.
You provide data on the role of TJLB in patients with ALF but importantly its role it affecting
therapeutic management .
Overall, I think this is a well written paper. It provides critical evaluation of the role of TJLB.
It provides evidence that the procedure is safe but does not change clinical management and is
potentially high risk given the biochemical and physiological changes present in patients with
ALF.
Minor
1. Results  Impact of histo results:
- You list 5 patients that were initially catergorised as cryptogenic, of which a definitive
diagnosis was found.  Can you list what the 3 cases were? I appreciate its listed in Table 2 but
its worth highlighting it in the text.
2. It may be worth mentioning that in patients with sickle cell disease, assessment of sickle
fraction and exchange transfusions to reduce the fraction irrespective of a liver biopsy.
Review for 10.1186/s12876-024-03350-4 (2024)

Title: Clinical significance of transjugular liver biopsy in acute liver failure – a real-world
analysis
Version: 4 Date: 17 Jun 2024
Reviewer's report:
In this paper, Nalbant and co-workers aimed to evaluate the safety and clinical importance of
transjugular liver biopsies (TJLB) in the management of patients with acute liver failure. Based
on the data of this retrospective, mono-center study, including 43 patients, the authors found that
histologic results obtained by TJLB did not add any clinically important information regarding
diagnosis and/or therapeutic options in the majority of patients. Therefore, the authors question
the routine use of TJLB in patients with acute liver failure.
As mentioned by the authors, this study has several limitations, such as the retrospective design
and small number of patients.
The authors should comment on the main reasons why patients with ALF were not listed for LT.
In total, 15 patients were listed for HU-LT, but only 14 received a new graft. What happened
to the one patient, who was not transplanted?
Why did the authors give information only regarding the antibody status of the patients? At least,
information concerning viral serology should be added in table 1.
In table 2, information regarding the outcome of the patients (e.g. recovered, dead, transplanted)
should be added.
The conclusion of the abstract is confusing. A rewording is necessary.
The discussion is extremely lengthy and contains information of the “Background section”. The
authors should focus on the main findings of their study compared to the literature.
Review for 10.1186/s12876-024-03350-4 (2024)

Title: Clinical significance of transjugular liver biopsy in acute liver failure – a real-world
analysis
Version: 4 Date: 19 Jun 2024
Reviewer's report:
The authors report a single center experience with TJLB in patients presenting with acute liver
failure.  Consistent with previous  reports the authors conclude that TJLB does not routinely
add significantly to the management of acute liver failure.  Unfortunately this report does not
present novel findings.
Minor Questions or Concerns:
1.  Given this is retrospective study, can the authors comment on why liver biopsies were
performed in cases where the diagnosis was overall certain?
2.  The authors report that in three cases of suspected and biopsy confirmed autoimmune hepatitis
the biopsy influenced management.  This deserves more explanation, the standard of care
for autoimmune hepatitis is immunosuppressive therapy, not clear how the biopsy influenced
management in these cases.
3.  The authors include two patients in Table 2 which the presumed ALF etiology was
"alcoholic" .  Alcohol does not cause acute liver failure.  It may result in severe liver dysfunction
in the context of severe alcohol associated hepatitis but this is a form of acute on chronic liver
failure and not ALF.  These patients should be removed from the analysis.
4.  The authors report 2 cases of indeterminate ALF that were confirmed as drug induced.  It
would be beneficial to the reader to understand what feature on biopsy confirmed drug induced
liver injury.  It is not common that pathology can so clearly identify DILI, it is more often a
diagnosis of clinical history and biopsy findings can support but rarely confirm this.
Review for 10.1186/s12876-024-03350-4 (2024)

Title: Clinical significance of transjugular liver biopsy in acute liver failure – a real-world
analysis
Version: 4 Date: 24 Jun 2024
Reviewer's report:
The authors provide important findings evidence regarding the place of TJLB in patients with
ALF.
The manuscript is very well written and very informative, two questions.
1. Is there any way to pre identify patient for which liver biopsy will have increased impact ?
2. how the authors compile their results with those of Lin et al, Clin Gastroenterol Hepatol 2022
(PMID: 34389485).
3. please provide a detail of the Bile score in supplementary materials.
Review for 10.1186/s12876-024-03347-z (2024)

Title: Evaluation of the Rock1 and microRNA-148a expression in biopsies collected from
patients with Helicobacter pylori induced gastritis
Version: 1 Date: 18 Oct 2023
Reviewer:  Daniela Dobru
Reviewer's report:
The review of the manuscript leads to the following remarks :
- the article address an important pathological issue of the chronic H.Pylori infection - the genetic
expression of associated genes in positive H.Pylori patients as MicroRNA-148a is involved in
the regulation of various genes, including ROCK1, which is altered in gastric cancer. Decreased
expression of mir-148a leads to tumor metastasis and increased ROCK1 gene expression in
gastric cancer. However, according to some recent data , miRNA-148a is downregulated in
gastric cancers .
- the study design  and methodology is  accurate but small sample size of the present study is
an important limitation for the final results .
- in order to obtain more accurate results I would recommend to expand the study with more
patients and it would be interesting to study the gene expression in patients with premalignant
conditions for gastric cancer as atrophic gastritis.
Review for 10.1186/s12876-024-03347-z (2024)

Title: Evaluation of the Rock1 and microRNA-148a expression in biopsies collected from
patients with Helicobacter pylori induced gastritis
Version: 1 Date: 19 Jan 2024
Reviewer's report:
The authors need to show the results for the H pylori positive or negative confirmation, show
the giemsa stainnig.
Which was the criteria to consider h pylori positive (both test positives?)
How many samples at all were  collected?
Need to compare   samples with the same level of gastritis hpylori positive vs H pylori negative.
Between  H. pylori positive samples the authors have several levels of gastritis.
The authors should consider the possibility of testing others mirs which could inhibit Rock1
expression, also other mechanisms, not only mirs
Need english revision
Review for 10.1186/s12876-024-03347-z (2024)

Title: Evaluation of the Rock1 and microRNA-148a expression in biopsies collected from
patients with Helicobacter pylori induced gastritis
Version: 3 Date: 25 Jul 2024
Reviewer:  Daniela Dobru
Reviewer's report:
The authors have revised their manuscript in response to the points highlighted on our first
review report.
The answers and additional comments fulfill our requests therefor I recommend the manuscript
to be accepted for publication
Review for 10.1186/s12876-024-03315-7 (2024)

Title: The Effect of Solid Food Diet Therapies on the Induction and Maintenance of Remission
in Crohn’s Disease: A Systematic Review
Version: 1 Date: 06 May 2024
Reviewer's report:
This systematic review examines the effectiveness of solid food diets (without EEN or PEN) for
inducing and maintaining remission in Crohn’s disease. The analysis, based on 14 randomized
or head to head including both adult and pediatric patients.
Here are my comments to be addressed:
1. In the abstract, please distinguish more clearly between inactive and active disease.
2. The conclusion in the abstract states promising outcome for MD and CDED in inducing
remission in CD. It needs to be balance according to the quality of studies - there is one study
that didn’t separate between UC and CD in the reduction of inflammatory markers and another
study (the DINE study) failed to show improvement in inflammatory markers, and the CDED
is an unpowered pilot study.
3. Please elaborate further on the distinctions between inactive and active disease in the
background. Also, explain the role of diet, particularly PEN, in maintaining remission.
4. The focus, along with the reference, revolves around the palatability and adherence of EEN.
Please expand upon the utilization of PEN as a treatment for maintaining remission and elucidate
the rationale in including also inactive disease.
5. Correction of Typo: Line 249 contains a repetition of the word "no."
6.  In reference to the study by El Amrousy et al., correct the number of participants to 54, as
stated in the table.
7. Consider being more critical in the conclusion, particularly regarding the quality of evidence.
Also, moderate statements particularly in the absence of high quality evidence.
8. DINE study – It might be important to emphasize in the discussion that in the subset of patients
with raised CRP and FCAL at baseline, both MD and SCD failed to show improvement, which
highlights the lack of benefit of these diets in managing active CD.
Review for 10.1186/s12876-024-03315-7 (2024)

Title: The Effect of Solid Food Diet Therapies on the Induction and Maintenance of Remission
in Crohn’s Disease: A Systematic Review
Version: 1 Date: 13 May 2024
Reviewer:  Sarah M Ajabnoor
Reviewer's report:
This systematic review of different RCTs aimed to assess the effect of different solid diet
therapies on the induction and maintenance of remission in patients with Crohn’s disease. A total
of 14 trials were included in the systematic review. The authors concluded that some available
diet therapies may have positive outcomes, but the evidence is still limited due to the lack of
robust high-quality trials.
The focus of this systematic review provides interesting findings, which will help in directing
future research concerned with dietary management in IBD. However, the manuscript and the
review summary tables need some adjustments. Please see the comments below.
To author:
- Title: The word (maintenance) is missing from the title. The title should be like (The Effect of
Solid Food Diet Therapies on the Induction and Maintenance of Remission in Crohn’s Disease:
…………..…..etc.)
- Methods: Search strategy: the author needs to specify the selected time frame (years) for
included studies. Did the author exclude any study before a specific time frame? Need to be
stated.
- Methods: Critical appraisal: The author needs to provide the citation for the quality assessment
tool.
- Results: The Summary tables are crowded and not clear. It needs some modification for better
illustartation of studies’ findings. The author needs to tabulate the extracted data from the studies
in a better way (i.e., more informative and summarized). E.g., the following information can
be presented in a separate column: study sample size, participant age, duration of intervention,
Results of disease activity index/remission rate, results of inflammatory markers, results of gut
symptoms, and quality of life.
- Results: Line 249: there is a spelling mistake. Need to remove one (no) for the sentence.
- Discussion: Line 453 – 455: The textual results concerning the quality of included studies
need to be mentioned in the Results section of the systematic review and not in the discussion.
I suggest adding a paragraph in the results to better explain the results for Figure 2.
- Overall, the manuscript is good But needs to be proofread.
Review for 10.1186/s12876-024-03315-7 (2024)

Title: The Effect of Solid Food Diet Therapies on the Induction and Maintenance of Remission
in Crohn’s Disease: A Systematic Review
Version: 2 Date: 19 Jun 2024
Reviewer's report:
The authors have done a good job at addressing all my comments and I have no further
comments.
Review for 10.1186/s12876-024-03316-6 (2024)

Title: Preoperative Prediction of Rectal Cancer Staging Combining MRI Deep Transfer
Learning, Radiomics Features, and Clinical Factors: Accurate Differentiation from Stage T2 to
T3
Version: 1 Date: 12 Apr 2024
Reviewer's report:
The study first uses ResNet34 and PyRadiomics for features extraction, then uses LR, RF, DT
and SVM for the classification of Stage T2 and T3 for rectal cancer.
The study extracts 2048 features from the Average Pooling layer, but the layer with 2048 features
has not been found in Fig.3. Is it between (conv, 512) and (fc, 1000)? How was 2048 calculated?
24 features were preserved by LASSO. Are all these 24 features included in LR, RF, DT and
SVM models? Please show the structure of the decision trees for RF and DT methods. Please
add more details of the SVM model. For example, Gamma and C parameters. Does SVM model
also include 24 features?
Review for 10.1186/s12876-024-03316-6 (2024)

Title: Preoperative Prediction of Rectal Cancer Staging Combining MRI Deep Transfer
Learning, Radiomics Features, and Clinical Factors: Accurate Differentiation from Stage T2 to
T3
Version: 1 Date: 28 Apr 2024
Reviewer's report:
This study cleverly integrates MRI-based deep transfer learning techniques with radiomic
features, employing four different machine learning algorithms (LR, RF, DT, and SVM) to
develop predictive models. Clinical risk factors are integrated into the predictive framework,
creating a comprehensive model capable of accurately predicting the T2 and T3 staging of
colorectal cancer in a non-invasive manner preoperatively. The study is intriguing and holds
significant practical value, yet there are several noteworthy aspects to consider.
1. The primary innovation lies in employing the ResNet-34 model augmented with residual
connections for feature extraction through deep transfer learning. However, both the Results
and Discussion sections lack comparisons with conventional methods, necessitating such
comparisons to validate the study's design for effectively enhancing predictive performance over
conventional methods.
2. Why the setting of high-resolution T2 layer thickness and spacing of 3mm and 1mm needs
clarification.
3. ROI delineation.  Detailed explanations of "two seasoned radiologists" are required.  A
detailed description of 3D delineation is warranted. Figure 2 is suggested to feature typical cases
of rectal cancer.
4. More technical details should be provided regarding data processing and feature selection
methods.
5. The setting of cut-off values for CEA and CA199 needs elucidation.
6. There is a lack of in-depth discussion surrounding the study results. Specifically: 1. Why
deep transfer learning features exhibit significantly greater significance compared to radiomic
features. 2. LD and CEA are independent predictors, but why isn't CA199? 3. Why SVM
outperforms other models? 4. Whether the comprehensive model shows improvement over other
studies and the underlying reasons for such analysis.
7. Some figures lack annotations.
8. Abbreviations within the text lack precision.
Review for 10.1186/s12876-024-03316-6 (2024)

Title: Preoperative Prediction of Rectal Cancer Staging Combining MRI Deep Transfer
Learning, Radiomics Features, and Clinical Factors: Accurate Differentiation from Stage T2 to
T3
Version: 2 Date: 02 Jun 2024
Reviewer's report:
Thanks for replying to my concerns about feature number and the structures of RF and DT.
Could you introduce the software you used to produce Fig A and Fig B in the response letter
about RF and DT models? What is meaning of ‘0’ and ‘1’ in the figure? Could you also introduce
the software and packages for the classification by LR, RF, DT and SVM?
The study selects SVM as the best classifier and includes 24 features. Is it possible to use an
equation or a diagram to quantitively show the SVM model, just like the equation in LR, or
diagrams in RF or DT?
Because non-linear kernel was used, too many features may lead to over-fitting. Therefore, an
independent external validation is preferred.
Fig 5B, does the dotted line correspond to 24 features? There seems to be only 5 or 6 non-zero
features in the figure.
Review for 10.1186/s12876-024-03316-6 (2024)

Title: Preoperative Prediction of Rectal Cancer Staging Combining MRI Deep Transfer
Learning, Radiomics Features, and Clinical Factors: Accurate Differentiation from Stage T2 to
T3
Version: 2 Date: 12 Jun 2024
Reviewer's report:
The author has perfectly addressed the majority of concerns. Nonetheless, there are still several
minor aspects should be solved.
1. The addition of Model Comparison appears somewhat weird in its current placement. It is
more advisable to place into the Construction of Machine Learning Models section.
2. In the results section, it is recommended to present only the findings, with descriptions
involving methods and processes placed in the Materials and Methods section.
3. The author has offered an exhaustive clarification concerning the high-resolution T2 sequence.
Yet, the parameter settings currently do not convincingly demonstrate the high-resolution nature
of the sequence.
Review for 10.1186/s12876-024-03316-6 (2024)

Title: Preoperative Prediction of Rectal Cancer Staging Combining MRI Deep Transfer
Learning, Radiomics Features, and Clinical Factors: Accurate Differentiation from Stage T2 to
T3
Version: 3 Date: 01 Jul 2024
Reviewer's report:
Thank you for providing the revised version of the manuscript. The authors have addressed all
the points raised in the initial review. Therefore, I recommend the manuscript for acceptance.
Review for 10.1186/s12876-024-03286-9 (2024)

Title: Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are
effective in the treatment of colorectal cancer
Version: 1 Date: 21 Sep 2023
Reviewer's report:
I find this article very well written, details explained properly, a current topic and of great
importance with a coherent experimental approach; controls and results are acceptable, related to
conclusions and actually quite promising considering CAR-T cells growing benefits on cancer;
minimum grammatical or spelling errors (abstract - objective has an error). With the given
results i have no inconvenient on accepting this article. Please include standard deviation mark
on Figure 5C.
Review for 10.1186/s12876-024-03286-9 (2024)

Title: Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are
effective in the treatment of colorectal cancer
Version: 1 Date: 28 Sep 2023
Reviewer's report:
Authors propose in this manuscript the application of CAR-T cells targeting EpCAM as
treatment for colorectal cancer. CAR-T cell therapy have demonstrated to be effective in treating
hematological malignancies and its investigations have leaded to its application in solid tumors.
EpCAM has already been investigated as a potential target for treating solid tumors with
encouraging results. In this manuscript they also conclude that EpCAM-CAR-T cells can inhibit
tumor growth. The manuscript would be improved by consideration of the following points:
- Section 2.1 there is no information about where tumor cells come from and how they achieved
EpCAM expression in tumor cells. I also found missing the dose and route of CAR-T cells
treatment that have been infused into mice.
- In CAR-T cells production, I found missing T cell activation and expansion.
- Why did the authors use 4 cell lines (HEK293T, HT-29, HCT116 and Hela)? In results section
3.3 why authors just use HT-29 and Hela?.
- Section 3.4. Figures referenced does not match with the images.
- In discussion, justify why the tumoricidal effect is due to the increase in TNF and INF and
not to direct tumor destruction by CAR-T cells, and that the increase in TNF is merely an effect
of lymphocyte activation.
- Please discuss why tumor section showed no significant lymphocyte infiltration and how can
CAR-T cells can have an antitumor effect if no cells are detected in the tumor.
- In figure 5 description, it indicates that tumors were formed by subcutaneous implantation,
however, in methods appears as intraperitoneal injection. Please clarify this.
Review for 10.1186/s12876-024-03286-9 (2024)

Title: Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are
effective in the treatment of colorectal cancer
Version: 1 Date: 08 Jan 2024
Reviewer's report:
This  manuscript demonstrates new CAR T cells against EpCAM inhibiting the tumor growth
of colorectal tumor cells in vitro and in vivo. The experiments are well done and the manuscript
should be published.  Nevertheless some points have to be answered and discussed :
Results after abstract: please add peripheral blood mononuclear cells were extracted from
whome ? patients or mice ?
Conclusion: Last sentence: und can also better inhibit the growth and metastasis of colerectal
cancer in vitro and in vivo, better as what ?
In the introduction  you have to mention and to write about TCR engineered T cells, CAR T-
cells, TCR CARs and TCR like CARs which are all promising.  And please mention pro and
cons of these T cells. This is important for people that are not so familiar with the strategies
of T cell therapy. TCR engineered T cells, TCR CARs and TCR like CARs are able to target
intracellular neoantigens, which are specifically expressed only on tumor cells and not on normal
cells. Exist there an advantage of T cell therapy over therapies with antibodies, for example
bipecific antibodies targeting CD3 and  tumor associated antigens like EpCAM compared with
the strategy demonstrated in the manuscript.
Results:from where is the anti-scFv derived ? please add citation.
Can you please explain the amount of CD8, CD4 and CD3 positive cells found by FACs. What
is the amount of double positive CD4 and CD3 and double positive CD8 and CD3 cells? Could
you please  quantify the Ki67 experiments, Fig. 5F.
Discussion: Solid tumors are different from hematologic tumors, please explaine the differences
in more detail. Why do the T cell group injection of commun T cells have also an effect on tumor
growth and surveillance of mice ?
Conclusion: How can off/target effects by CAR T cells be prevented?  for example, Dual CARs
or Tandem CARs or synNotch CARs.
Please describe briefly the fourth generation CARs (Michael Hiltensperger and Angela M.
Krackhardt, Frontiers in Immunology 2023.
Review for 10.1186/s12876-024-03286-9 (2024)

Title: Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are
effective in the treatment of colorectal cancer
Version: 4 Date: 03 Apr 2024
Reviewer's report:
Dear authors,
Your answers to my comments are very excellent. Only comment 3 is not really answered from
my point of view: Exist there an advantage of T cell therapy over therapies with antibodies [11].
Please summarize some advantages of  T cell therapy over antibody therapy for example adverse
effects and efficiency of the two different strategies.
Thank you
Review for 10.1186/s12876-024-03286-9 (2024)

Title: Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are
effective in the treatment of colorectal cancer
Version: 4 Date: 07 Apr 2024
Reviewer's report:
Thanks for considering the comments. I am satisfied with the revision; however, minor
corrections should be considered before acceptation for publication.
1. In abstract, methods: Change interference for interferon.
2. Please specify if the tumor cells lines purchased expressed Epcam or this antigen was added.
3. Treatment groups doesn’t match in section 2.7, 3.3, 3.5 and also in the discussion.
4. In section 3.4  in HeLa cells group. All HeLa cells were EpCAM negative? If there were also
HeLa EpCAM positive cells, did they respond to treatment?
If these questions are addressed, I would happily accept this manuscript for publication.
Review for 10.1186/s12876-024-03343-3 (2024)

Title: Only repeatedly elevated IgG4 levels in primary sclerosing cholangitis may distinguish
a particular patient phenotype
Version: 1 Date: 15 Apr 2024
Reviewer's report:
Only repeatedly elevated IgG4 levels in primary sclerosing cholangitis
may distinguish a particular patient phenotype
Retrospective study of  PSC patients with and without constant elevated IgG4
Minor- fibroscan is a trademark, perhaps you should write elastografi with fibroscan (R)
- No comments about the amount males contra females
- how do you explain that none hade small-duct psc
- small groups, can you make conklusions out of these?
Major- how was IgG4 related disease excludes in those with elevated IgG 4 ( were all subjected
to liverbiopsy?)
Out of your data, are your conclusions relevant?
Review for 10.1186/s12876-024-03343-3 (2024)

Title: Only repeatedly elevated IgG4 levels in primary sclerosing cholangitis may distinguish
a particular patient phenotype
Version: 1 Date: 24 Apr 2024
Reviewer's report:
Well-written manuscript that clearly defines a relevant clinical question and aims of work herein.
Minor points:
Authors should specify mean observation period from first IgG4 measurement to final IgG4
measurement of patients that normalized and those who remained consistently high. Is there
a significant sampling difference that could explain the normalization of IgG4 values in some
patients and constant high levels in others?
Is immunosuppressive dosage for IBD  sufficient to ameliorate features of IAC in general? Could
PSC-IgG4const group benefit from stronger immune treatment if they were in fact IAC?
Are the IgG4-constant patients possibly IgG4-IAC patients that are slightly sub-threshold for
HISORt criteria or truly a unique subgroup of PSC? Related, were the IgG4 antibodies tested for
reactivity against known IgG4-IAC antigens (e.g. annexin A11). Did the IgG-constant patients
exhibit  more clinical features associated  with IAC than IgG4-normalize group?
Review for 10.1186/s12876-024-03343-3 (2024)

Title: Only repeatedly elevated IgG4 levels in primary sclerosing cholangitis may distinguish
a particular patient phenotype
Version: 1 Date: 27 Apr 2024
Reviewer's report:
Kalthoff S et al analyzed the role of constantly elevated (#2 measurements during mean 3.5
years f/u) in a retrospective study consisting of 6 persons with constantly elevated IgG4 > 1/
UNL and 8 cases where the initially elevated IgG4 normalized during the f/u. In addition, they
had 96 PSC patients with constantly normal S-IgG4.
The authors found that age at PSC diagnosis, presence of IBD, high-grade biliary strictures,
fibrosis detected by TE, and cirrhosis as well as the Amsterdam Oxford, Mayo risk and MELD
scores did not differ between the PSC-N and PSC-IgG4.
The only difference they found was that P-ALP and GT were higher in 6 cases with constantly
elevated IgG4 compared to those 8 patients who normalized the value.
Major comments:
Patients and Methods:
1. The study population and the f/u time is very limited to draw any firm conclusions of the
impact of elevation of IgG4 on PSC disease outcome.
2. Slight elevation of IgG4 is common among PSC patients (15%). How was IAC excluded:
elevation of S-IgG4 >4x UNL, sIgG4/sIgG- ratio>0.24, papilla Vateri biopsy with IgG4
immunohistochemistry, findings?
3. Did the patients with elevation of IgG4 have any extrahepatic manifestations/symptoms
suggesting of IAC?
4. Did you analyze correlation between the elevation of IgG4 and ALP/gGT?
5. Was any of those 14 cases with elevated IgG4 treated with steroids/AZA for long term?
Review for 10.1186/s12876-024-03343-3 (2024)

Title: Only repeatedly elevated IgG4 levels in primary sclerosing cholangitis may distinguish
a particular patient phenotype
Version: 2 Date: 23 Jun 2024
Reviewer's report:
The authors have adequately addressed most of my comments, but the main problem regarding
the very limited study population and the results showing no differences in death, cirrhosis or
liver transplantation between grpuops  do not support the authors' conclusions, that sequential
determinations of S- IgG4 levels may be of clinical benefit to more precisely identify those
individuals who are at increased risk of disease progression and thus increased morbidity and
mortality.
This conclusion cannot be drawn from the results and it should be rephrased.
Review for 10.1186/s12876-024-03334-4 (2024)

Title: Patient-reported symptoms and burden of eosinophilic esophagitis: evidence from real-
world clinical practice
Version: 0 Date: 04 Nov 2023
Reviewer's report:
Dear authors,
I kindly reviewed your paper finding interesting insights as well as downsides to be addressed.
The overall concept of the study, despite its thorough strong design, with far acceptable
reproducibility, lacks of innovative burst. The results of the survey based analysis basically
provide a picture of higher disease and quality of life burden of EoE patients especially of the
symptomatic (despite therapy) versus the asymptomatic ones. No insight is given towards the
characteristics of symptomatic despite treatment patients: why they still experience symptoms?
what kind of symptoms and what correlation is there to explain the substantial non-difference
in histologic activity between the two groups? EoE patients in histologic remission still
experiencing symptoms should be evaluated for functional assessment
and treated accordingly. My advice is to strengthen and apply more focus on this topic, going
beyond descriptive results.
Aside I advice to use acronym for the principle sub-group definition (dysphagia despite
treatment) in order to ease the reader experience.
Moreover extensive english revisions are needed
Review for 10.1186/s12876-024-03334-4 (2024)

Title: Patient-reported symptoms and burden of eosinophilic esophagitis: evidence from real-
world clinical practice
Version: 0 Date: 27 Nov 2023
Reviewer:  Jamal O. Hayat
Reviewer's report:
Well written and reads nicely. Large patients numbers from multiple sites.
Is there a breakdown of patients per sites/per country?
1. The dysphagia despite treatment number is high compared to published data on current
therapeutic options eg orodispersible budesonide. This may be due to inadequate access to
licensed medications/cost of prescribing /inappropriate treatment eg PPI's when not effective,
using other formulations of topical  steroids. This should be commented on.
2. Persistent symptoms may be due to concomitant disease eg gastro-oesophageal reflux disease
3. There is a comment in the discussion that patients would prefer dietary modification rather
than medication. I think this needs to be clarified further. I suspect this is for simple dietary
restrictions f they are effective - but unfortunately this will only apply to less than half of patients.
Most dietary exclusion studies have a high drop out rate the longer the study progresses and the
more foods are restricted (eg step up or six food elimination diets)
4. This discussion comment includes standard of care treatment but the wording implies that
elemental diet  is the primary treatment. This is not the case - and should be worded in a more
objective fashion eg therapeutic options include dietary elimination medications including PPIs
ad steroids etc. Treatment options should be determining using efficacy and patient choice....
5. Study reports a difference between patient reported outcomes and physician. Is  there a
statistical difference? Most common reported symptoms ie dysphagia is the same.  suggest may
need to revise this comment
6.  dysphagia despite treatment - is this more common in particular treatment groups eg PPI
vs steroids?
7. In discussion - first paragraph - there is a comment on  need for urgent novel treatment - but
one of the issues  that has been demonstrated  is that the delay  in diagnosis may lead to more
advanced disease, so this statement should be revised - to include this , plus optimising currently
available treatment +/- use of novel treatments.
8. The statement on lack of awareness of physicians on patients fears - i disagree with the use of
this statemnt. It is not clearly demonstrated from the results of that patients and  i would suggest
revise eg 'important to physicians to be aware of patinet fears'...
9. Figure 1 - check spelling of dysphagia on the diagram
Review for 10.1186/s12876-024-03334-4 (2024)

Title: Patient-reported symptoms and burden of eosinophilic esophagitis: evidence from real-
world clinical practice
Version: 2 Date: 25 May 2024
Reviewer:  Alberto Barchi
Reviewer's report:
Dear authors
It's been a pleasure to review your interesting paper
See my comments in the attached word file
Review for 10.1186/s12876-024-03345-1 (2024)

Title: Autophagy-mediated ferroptosis is involved in development of severe acute pancreatitis
Version: 4 Date: 08 May 2024
Reviewer's report:
The authors studied the pathogenesis of ferroptosis in SAP. This article suggested that ferroptosis
was a novel pathogenesis of SAP and is dependent on autophagy. However, autophagy
mediated ferroptosis has been reported (doi: 10.1080/15548627.2022.2152209). Ferroptosis
inhibitor has already known to protect SAP (doi: 10.1038/s41419-023-06216-x, 10.1016/
j.intimp.2024.111495). Therefore, the aim of this study is not clear. Moreover, many of the
images were not qualified for publication including IF pictures and WB blots.
Review for 10.1186/s12876-024-03277-w (2024)

Title: Metabolites mediate the causal associations between gut microbiota and NAFLD#a
Mendelian randomization study
Version: 2 Date: 12 Apr 2024
Reviewer's report:
ARTICLE
Metabolites mediate the causal associations between gut microbiota and NAFLD: a Mendelian
randomization study
COMMENTS :
Positive points :
1. This randomization satisfies the STROBE MR checklist
2. High-level statistical analysis was done at each step of the study to remove confounding
factors, even reverse Mendelian randomization to rule out revere causality.
Negative points :
1. The study used GWAS summary data primarily consisting of individuals with European
ancestry may introduce biased estimates and limit the generalizability to diverse ethnic
populations.
2. What is the practical implication of this study in clinical practice
3. Data used  was  pooled from the previous retrospective data
4. Methodology and statistical analysis could have been presented in a simplified way, very
complicated statistical analysis, very difficult to understand without the help of a highly skilled
statistician.
5. Was there any interaction between the organisms which can be a confounding factor?
6. One study suggested a possible bidirectional association between the genus Ruminococcus
and NAFLD; however, the reverse causality can be confounding,
7. Was Mendelian randomization needed?
8. Excellent work but a prospective longitudinal study is required.
Review for 10.1186/s12876-024-03277-w (2024)

Title: Metabolites mediate the causal associations between gut microbiota and NAFLD#a
Mendelian randomization study
Version: 2 Date: 23 Apr 2024
Reviewer's report:
Reviewed for the journal BMC Gastroenterology
The manuscript  Metabolites mediate the causal associations between gut microbiota and
NAFLD#a Mendelian randomization study, From the team in Tianjin, China
Obtained due ethical approval for the development of the research.
Mendelian randomization was used to search for causal connections between exposures and
outcomes. The assessment was based on the 20-item Strobe-MR (Strengthening the Reporting
of Observational Studies in Epidemiology using Mendelian Randomization)
They sought a causal association between the gut microbiota and NAFLD and then between
NAFLD and 1,400 metabolites.
It used microbiota data from 18,000 individuals, and NAFLD/control data from almost 400,000
people, the vast majority of whom were Europeans, which is an important limiting factor in
extrapolating conclusions to other populations.
He selected 1,400 plasma metabolites, also mostly of European origin.
It presents an adequate methodological description, allowing replication of the study in other
populations.
An inversely proportional correlation was identified between Ruminococcus2( an anaerobic,
Gram-positive Clostridia class bacterium), and NAFLD, so that the presence of this bacterium
in the microbiota reduces the risk of developing NAFLD.
After evaluating the 1,400 metabolites, 7 were identified with a potential relationship with
NAFLD, but after evaluating the Linkage disequilibrium score regression, a relationship
was defined only between 3-indoleglyoxylic acid and .cysteine-glutathione disulfide with
Ruminococcus2.
Despite being methodologically different, previous studies present a conflicting relationship
with the findings between Ruminococcus and NAFLD (doi: 10.1002/hep.28356), which can be
evaluated in the discussion.
Therefore, I believe that the research can add valuable information on the subject, and should
be accepted for publication.
Review for 10.1186/s12876-024-03277-w (2024)

Title: Metabolites mediate the causal associations between gut microbiota and NAFLD#a
Mendelian randomization study
Version: 3 Date: 14 May 2024
Reviewer:  Felipe David Mendonça Chaim
Reviewer's report:
After review by the authors of the points raised, the doubts were duly resolved and the points
discussed in the manuscript. Therefore, I consider the article suitable for publication
Review for 10.1186/s12876-024-03333-5 (2024)

Title: Assessment of Alvarado criteria, ultrasound, CRP, and their combination in patients with
suspected acute appendicitis: a single centre study
Version: 2 Date: 17 May 2024
Reviewer's report:
Dear authors;
First of all, I would like to congratulate the authors for the study. I think it is a good study.
However, I have a few questions for the authors.
• In my opinion, the age range of the study is very wide. Why were all age groups included in
the study?
• What percentage of the patients were children?
• What percentage of the patients were in the geriatric age group?
• Can physical examination findings be evaluated objectively in pediatric and geriatric patients?
Review for 10.1186/s12876-024-03333-5 (2024)

Title: Assessment of Alvarado criteria, ultrasound, CRP, and their combination in patients with
suspected acute appendicitis: a single centre study
Version: 2 Date: 14 Jun 2024
Reviewer's report:
The combined use of the Alvarado score, CRP, and ultrasound is an effective strategy to enhance
diagnostic accuracy. The Alvarado score provides a quick and convenient starting point for
clinical evaluation. CRP levels offer additional information as an inflammatory marker, and
ultrasonography provides visual confirmation, thereby increasing diagnostic certainty. Using
these three methods together minimizes false negative and positive results, thus avoiding
unnecessary surgical interventions and preventing delayed diagnoses.However, it is important
to note that these diagnostic methods have been known and used for years in suspected acute
appendicitis cases. Therefore, the contribution of this publication to the literature may be very
limited.
Review for 10.1186/s12876-024-03333-5 (2024)

Title: Assessment of Alvarado criteria, ultrasound, CRP, and their combination in patients with
suspected acute appendicitis: a single centre study
Version: 4 Date: 08 Jul 2024
Reviewer's report:
Dear authors;
I think it would be appropriate to publish the study in its revised version.
Best regards
Review for 10.1186/s12876-024-03333-5 (2024)

Title: Assessment of Alvarado criteria, ultrasound, CRP, and their combination in patients with
suspected acute appendicitis: a single centre study
Version: 4 Date: 21 Jul 2024
Reviewer's report:
I read the revised final version of the study. The study is acceptable for publication in its current
form.
Review for 10.1186/s12876-024-03335-3 (2024)

Title: Diagnosis and management of type II endoscopic retrograde cholangiopancreatography-
related perforations: a multicenter retrospective study
Version: 1 Date: 26 Apr 2024
Reviewer's report:
Thanks to the authors effort. Well written manuscript discussing important complication during
ERCP practice with appropriate design, clear figures and  discussion.
Review for 10.1186/s12876-024-03335-3 (2024)

Title: Diagnosis and management of type II endoscopic retrograde cholangiopancreatography-
related perforations: a multicenter retrospective study
Version: 1 Date: 27 Apr 2024
Reviewer's report:
The various types of perforations need to be clearly described in the manuscript.
At least Type II perforations need to be defined in the introduction and perhaps the other types
described in the discussion.
The Table reports some patients having pancreatitis.  The incidence and severity of post-ERCP
pancreatitis needs to be clearly described in the results.  Also, the rationale and results of treating
patients with post-ERCP pancreatitis plus perforation with fully covered metal stents needs
to be clarified.  There would be an increased risk for initiating and/or worsening post-ERCP
pancreatitis after placement of a fully covered metal stent.
Review for 10.1186/s12876-024-03335-3 (2024)

Title: Diagnosis and management of type II endoscopic retrograde cholangiopancreatography-
related perforations: a multicenter retrospective study
Version: 2 Date: 18 Jun 2024
Reviewer's report:
A prospective randomized controlled trial comparing cases with and without covered metal
stents is needed to evaluate whether covered metal stent placement is useful for type II
perforation. Careful consideration is required because metal stent placement carries a risk
of post-ERCP pancreatitis. The diameter and length of the metal stent used also need to be
considered.
Review for 10.1186/s12876-024-03335-3 (2024)

Title: Diagnosis and management of type II endoscopic retrograde cholangiopancreatography-
related perforations: a multicenter retrospective study
Version: 2 Date: 19 Jun 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract introduction is not coherent to the results and conclusion Methods should mention
from where the data come from Results are better to include numerical values  Last sentence of
conclusions should refer to hospital stay, so that it would be coherent to the results
Main text in the introduction authors should mention that although in older publications
mortality tended to be high it has been reduced  in the time been and stress in what way mortality
has changed and the risk factors for increased mortality and hospitalisation Methods should
mention if indications for ERCP were recorded as well what tests were evaluated after 6 and
12 hours What is the hospital practice is not clear Do they test every patient or only those
with suspicious symptomatology ?  What were the indications for CT apart from  abdominal
pain or back pain? Were there any cases without abdominal pain diagnosed by CT performed
due to unexplained biochemistry or elevation of inflammatory markers? Time and indications
for absess drainage under CT guidance should be mentioned That were the indications for
refeeding ? What were criteria for antibiotics selection? Was there a definite protocol? Results
should include indications for ERCP if available Sings and symptoms should be devided if
there is an incoherence to entry findings and signs and symptoms during patient hospitalisation
Time to diagnosis for the two groups that are statistically significantly different should be given
(numerical values ) Difficulty of ERCPs might be given only in the relevant Table but numerical
values for type II perforations should be given in the text Only statistical significant differences
should be mentioned Authors should not compare three values unless they use ANOVA or Chi-
square test 2X3 which they donot mention in the statistics  Numerical values should be given
for hospital stay in the three study groups.  Comparisons for mortality are not suitable If there
are adequate persons in each patient group patients with early and late stent placement should
be compared.  Discussion should be modofied adequately
Review for 10.1186/s12876-024-03298-5 (2024)

Title: Pathological complete response after conversion therapy in unresectable hepatocellular
carcinoma: A retrospective study
Version: 0 Date: 28 Dec 2023
Reviewer's report:
the paper by Jia et al is a paper on an intersting focus.
Radiological and confirmed pathologycal response rate after the conversion therapy for HCC
could be intersting for future real word approch and studies are laking.
the main focus is on result and statistical analysis:
However, starting from the data the first thing that seems to be strage is the classification of
patients with BCLC: 51.7 % in stage 0-A, 8.3%in B and 40% in C; but PVTT was present in
75%. This seems to be quite strange because in the correct definition of BCLC stage portal
invasion authomatically defined a BCLC of stage C. how is it possibile?
Data on liver function are totally absent, these data are necessary
COx regression analysis and factors that can influence the outcome are lacking
data on death causes are absent.
this information are necessary to better understend the data presented
Review for 10.1186/s12876-024-03298-5 (2024)

Title: Pathological complete response after conversion therapy in unresectable hepatocellular
carcinoma: A retrospective study
Version: 4 Date: 15 Jun 2024
Reviewer's report:
I thank the authors for addressing all the points I raised during the evaluation of the previous
draft.
The revised version of the introduction and discussion have been improved as requested.
The aim of study has been better explained.
The method section has been changed and it is more readable.
The results are now easy to understand.
The manuscript is suitable for publication.