JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02265-2 (2022)

Title: Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes
ontology clusters with tissue expression patterns
Version: 4 Date: 30 Oct 2021
Reviewer's report:
1. Recheck for grammar and typo errors (throughout the manuscript).
2. I could not find the response to Question 1.1. in the manuscript (Background section). Recheck
this.
Review for 10.1186/s12876-022-02265-2 (2022)

Title: Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes
ontology clusters with tissue expression patterns
Version: 4 Date: 15 Nov 2021
Reviewer's report:
The authors did not address any questions from this reviewer properly. It appears that the authors
have no idea about the difference  between ubiquitin ligases and deubiquitination enzymes. It it
improper for any journals to publish a paper with conceptual mistakes. Therefore, this reviewer
wish they revised their manuscript accordingly.
Review for 10.1186/s12876-022-02265-2 (2022)

Title: Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes
ontology clusters with tissue expression patterns
Version: 6 Date: 24 Dec 2021
Reviewer's report:
The authors have incorporated most of the changes that I have asked for into the manuscript. I
think this manuscript is now suitable for publication.
Review for 10.1186/s12876-022-02265-2 (2022)

Title: Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes
ontology clusters with tissue expression patterns
Version: 6 Date: 26 Dec 2021
Reviewer's report:
Studying one subunit of a complex would not give you  a real picture of a complex as a whole,
especially, if you only study a DUB subunit on an E3 complex.  One subunit would not give a
real picture for the entire complex, at leat two would do it.
Review for 10.1186/s12876-022-02265-2 (2022)

Title: Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes
ontology clusters with tissue expression patterns
Version: 7 Date: 20 Feb 2022
Reviewer's report:
This reviewer could not find the name of Bard1 in either Additional table 2 or Fig S2, although
BRCC3 is  indeed in Fig S2. The reviewer also has to point out that neither Diablo nor IRAK1
is considered as a ubiquitin ligase, however, the authors listed them in the data of Fig S2. The
reviewer searched the whole manuscript, and could not find any explanation why these two
genes are there.  Well, the reviewer understand this is about a method, however, you can’t prove
a method based on wrong information. The reviewer is just curious why the authors could not
find any better example to prove their method?
Review for 10.1186/s12876-022-02265-2 (2022)

Title: Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes
ontology clusters with tissue expression patterns
Version: 8 Date: 19 Mar 2022
Reviewer's report:
Veronika et al. demonstrated that the expression profiling of GIT-specific UB-ligases shows the
unique expression profiling by the semantic clustering protocol. Their work may help to develop
the functional classification of Ub-ligases. However, some issues should be addressed before
publication. Specific comments are described below.
1. Fig. 2 shows the GO analysis. Authors collected the whole intestinal tissues for analysis. The
intestinal tissue includes different cell-types, epithelial cells, immune cells, and muscular cells
etc. I am just wondering if these analyses nicely work with different cell-types.
2. Authors analyzed the stomach and small intestines as well as colon in DSS-colitic mice.
Evidences that DSS induced the tissue damage and regeneration in stomach and small intestines
will reinforce their findings.
Review for 10.1186/s12876-022-02256-3 (2022)

Title: The necessarity of treatment for small gastric subepithelial tumors#1cm-2cm# originating
from muscularis propria: An analysis of 972 tumors
Version: 0 Date: 19 Sep 2021
Reviewer:  Szu-chia Liao
Reviewer's report:
1. Please mention about the inclusion and exclusion criteria of your enrolled patients more
detailedly. In your study, if the tumors involved more layers including muscularis propria, did
you enroll them into your study?
2. For your study groups, how about the EUS characteristics of the lesions and the correlation
between pathological diagnosis and EUS characteristics? If there were no high-risk features
under EUS image of the lesions, would endoscopic treatment be performed in your study? And
Why?
3. In Table 1, the age of your inclusion patients ranged from 16-78. Were the patients below 18
years old approved by The Institutional Review Board?
4. In table 1, how about the subgroup analysis for SETs with size < 1cm or > 1cm for the risk
of GIST and non-GIST? Could you discuss about the result?
5. In table 2, how about subgroup analysis in GIST group for size <1 cm or > 1cm about the risk
in the pathological diagnosis? Could you discuss about the result?
6. In your conclusion, you only focus on safe and effective treatment. However, it is not correlate
with your topic ” The necessarity of treatment”. Would you adjust your topic or talk more about
the necessarity of the treatment according to your study result?
Review for 10.1186/s12876-022-02256-3 (2022)

Title: The necessarity of treatment for small gastric subepithelial tumors#1cm-2cm# originating
from muscularis propria: An analysis of 972 tumors
Version: 2 Date: 07 Nov 2021
Reviewer's report:
The reviewer requests that the authors should clearly describe how many patients had 1> or 1<
2> tumor, and how many patients or what percentage of each patients had GIST in each group.
Although the authors indicates 8.4 times risk of 1< 2> tumor, the data pointed out above will
help readers to understand the significance of resecting 1< 2> tumors which the authors stated.
Review for 10.1186/s12876-022-02256-3 (2022)

Title: The necessarity of treatment for small gastric subepithelial tumors#1cm-2cm# originating
from muscularis propria: An analysis of 972 tumors
Version: 2 Date: 26 Nov 2021
Reviewer:  Szu-chia Liao
Reviewer's report:
According to the result, I still could not understand why small gastric subepithelial tumors should
be removed.
Review for 10.1186/s12876-022-02256-3 (2022)

Title: The necessarity of treatment for small gastric subepithelial tumors#1cm-2cm# originating
from muscularis propria: An analysis of 972 tumors
Version: 3 Date: 23 Mar 2022
Reviewer's report:
Thank you for your responding to my comment.
Of course, I understand the higher incidence of intermediate or high-risk GIST in 1-2 cm gSET
than 1>. However, should gSETs of 1-2 cm be resected because of the results? The incidence
of intermediate or high-risk GIST in 1-2 cm gSETs was only 2.5% (8/318). Conversely, over
97% of patients did not need to undergo removal. The most important point of this discussion is
whether endoscopic resection of small gSETs is technically and oncologically safe. This study
reveals that 2 of 972 patients experienced perforation and no patients had positive resection
margin. Thus, the procedure is safe. Honestly speaking, I still recognize that such small lesions
does not need resection, but considering the safety of endoscopic resection and the incidence of
high-risk GIST, I finally agree with the authors’ conclusions.
Review for 10.1186/s12876-022-02247-4 (2022)

Title: Hemostatic Efficacy and Safety of the Hemostatic Powder UI-EWD in Patients with
Lower Gastrointestinal Bleeding
Version: 3 Date: 11 Jan 2022
Reviewer's report:
Cha et al. reported a retrospective cohort of 167 patients with LGIB  with hemoastasis performed
and divide them into convention group vs UI-EWD group to evaluate the efficacy and safety
of UI-EWD group.
Although this should be best evaluated by a randomized prospective study, the current cohort
demonstrated the effectiveness and safety of UI-EWD and form a foundation for further
evaluation.
The authors were able to address some of the interesting findings and provide a reasonable
paucity. For example, more UI-WED were applied for lesions in hepatic flexure and the authors
attributed it to the difficult position for endoscopic hemostasis and the lower perforation rate
due to lower pressure used in UI-WED. The authors also detailly examined the cases with re-
bleeding and provide relevant clinical information to the readers.
Minor comments:
- please be consistent in numbers (one hundred sixty seven patients vs 38 patients)
- include the unit for platelet count in the manuscript
Review for 10.1186/s12876-022-02247-4 (2022)

Title: Hemostatic Efficacy and Safety of the Hemostatic Powder UI-EWD in Patients with
Lower Gastrointestinal Bleeding
Version: 3 Date: 28 Feb 2022
Reviewer's report:
Hemostatic Efficacy and Safety of the Hemostatic Powder UI-EWD in Patients with Lower
Gastrointestinal Bleeding
by Boram Cha and others
General comments
This interesting retrospective study presents the efficacy of the hemostatic powder UI-EWD
in the aspect of rebleeding rate within 28 days as 5.5%, which is better than other hemostatic
powders. UI-EWD was mainly used for the cases of post procedure ulcer and was applied for
the hepatic flexure. UI-EWD was also safety and there were no adverse events.
The efficacy of UI-EWD for upper gastrointestinal bleeding was already reported, especially for
tumor bleeding. Hemostatic powder with high success rate for lower gastrointestinal bleeding is
needed, especially for diverticular and tumor bleeding, which is difficult to success hemostatic
procedure.
I would recommend if for acceptance after the minor points listed below and annotated on the
manuscript are addressed.
Specific comments
# Please describe how the patients with antithrombotic therapy were treated in METHOD
section. It may affect the rebleeding rate, and so the authors should describe whether the patients
stopped antithrombotic therapy or not, and if yes, when they restarted it.
# I would recommend to mention that there were no mortality cases in both groups, if none.
Were there any death cases?
# I would recommend to demonstrate the comorbidity of eligible patients; ex. Charlson
Comorbidity index. Patient’s background may affect rebleeding.
# I would like to know how was the efficacy of UI-EWD for diverticular bleeding? If effective,
it would be extremely helpful for all endoscopists and gastroenterologists in the world. I would
recommend to mention about the efficacy for diverticular bleeding.
# Typo in the title of Table 4. “UI-EWD” is correct instead of “U-EWD”.
Review for 10.1186/s12876-022-02247-4 (2022)

Title: Hemostatic Efficacy and Safety of the Hemostatic Powder UI-EWD in Patients with
Lower Gastrointestinal Bleeding
Version: 5 Date: 25 Mar 2022
Reviewer's report:
Thank you for your response and submission with revised manuscript. This paper provides an
important contribution to the lower gastrointestinal bleeding.
Review for 10.1186/s12876-022-02234-9 (2022)

Title: Examination of the characteristics of long-term survivors among patients with gallbladder
cancer with liver metastasis who underwent surgical treatment: A retrospective multicenter study
(ACRoS1406)
Version: 3 Date: 04 Mar 2022
Reviewer:  Anup Kumar
Reviewer's report:
Very interesting paper  on role of surgery and its outcome  in advanced gallbladder cancer ( stage
III/ IV), a multicentered , though a retrospective analysis. Following are some of the comments
1. There are too many tables . Table 4 may be deleted and  put in the text at appropriate place.
2. Authors have found significance  in the  surgical out come in the period 2007–2013  as
compared to year 2000–2006 . What are the possible explanation?  ie difference surgery or better
technical support etc. The reasons should be discussed under discussion.
3. As this was a multicentered retrospective data analysis, there must be difference  in surgical
approach which varies from center to center. Was there  any  significant  difference  on survival
or recurrence  when the centers were analyzed as a factors?  Provide a separate tables  including
data from all  five centers.
4. In conclusions  authors have described "-----minimally invasive minor hepatectomy with
R0 resection -----" . What the meaning of minimally invasive? Is it laparoscopic or minor
hepatectomy?
Review for 10.1186/s12876-022-02234-9 (2022)

Title: Examination of the characteristics of long-term survivors among patients with gallbladder
cancer with liver metastasis who underwent surgical treatment: A retrospective multicenter study
(ACRoS1406)
Version: 3 Date: 05 Mar 2022
Reviewer:  Marta Krawczyk
Reviewer's report:
The paper entitled “Examination of the characteristics of long-term survivors among patients
with gallbladder cancer with liver metastasis who underwent surgical treatment: A retrospective
multicenter study” is a retrospective analysis of the treatment of 503 patients with gallbladder
cancer with liver oligometastasis collected from several surgical departments in Japan.
The problem analyzed by the authors is important because in the Far East countries, gallbladder
cancer is quite a common disease, and the results of treatment are still unsatisfactory, especially
in the group of patients with metastases to the liver and other organs.
While analyzing the manuscript, I noticed two problems which, in my opinion, require
clarification or correction.
The first one concerns the inclusion of patients with gallbladder cancer of various
histopathological types. In my opinion, this part needs to be improved. The results of treatment
of patients with gallbladder adenocarcinoma and carcinosarcoma tumors, neuroendocrine
carcinomas or undifferentiated carcinomas should not be analyzed jointly. The biology and
malignancy of each of these histopathological types are different. Therefore, in my opinion, the
analysis should include only adenocarcinoma type gallbladder cancer, and other cases should
be excluded from the study.
The second point that is unclear to me is the scope of the operation. The authors write that they
analyzed patients with oligometastasis, while some patients had to undergo hemihepatectomy
or even duodenopancreatectomy. How it is possible to assume in advance that the patient with
oligometastasis requires such huge surgical procedure. This, in my opinion, needs an explanation
or a separate analysis.
Review for 10.1186/s12876-022-02242-9 (2022)

Title: Steroid-mediated liver steatosis is CD1d-dependent while steroid-induced liver necrosis,
inflammation, and metabolic changes are CD1d-independent
Version: 2 Date: 05 Feb 2022
Reviewer's report:
1,  the label of the graphs should be consistent if  they are the  mesurements for the same
motabolic parameters;
2, Page 5,  in significance statement, the spelling of the 2nd "Steroid" missed a "t".
3, in the text , it saids group A,B, C and group D,E,F are the same, but in the table  shows  8
weeks and 12 weeks  respectively;
4, Figure 3B , the Y-axies label  0-600, maybe better 0-500, same as Figure 2B and Figure 1B,
these three graphs should be plotted more consistent.
5,  Figure 2G, there is huge error bar ,  is this really reliable to say GC function from this? maybe
show the hepatic TG content bar data of group A,B,C also?
6, Also Figure 3F  show the GC 's function  on reducing the steroid -mediated steatosis, but the
orally administered steroids  not increased the hepatic TG content in  both wild type and the
CD-/- mice.  not sure if this is enough to get the conclusion.
Review for 10.1186/s12876-022-02242-9 (2022)

Title: Steroid-mediated liver steatosis is CD1d-dependent while steroid-induced liver necrosis,
inflammation, and metabolic changes are CD1d-independent
Version: 2 Date: 28 Feb 2022
Reviewer:  Nazmul Huda
Reviewer's report:
Adar et al. have tried to develop a steroid-mediated mouse model  of NAFLD.  Using this model,
they claimed that steroid-mediated  steatosis was CD1d-dependent and the liver inflammation
and necrosis was  CD1d-independent .  This work has some merits for this particular field  of
research. However, the manuscript is not carefully produced. It  has many spelling/grammatical
mistakes. The statistical analysis was not correctly done ( instead of using ANOVA test, they
had used student's t-test for multiple comparison). The figures are not presented professionally.
Some figures do not have error bars. The data look very raw. They have to reproduce all of
the figures.
Review for 10.1186/s12876-022-02242-9 (2022)

Title: Steroid-mediated liver steatosis is CD1d-dependent while steroid-induced liver necrosis,
inflammation, and metabolic changes are CD1d-independent
Version: 2 Date: 11 Mar 2022
Reviewer's report:
Increasing data have shown the involvement of steroid hormones in hepatic steatosis. In the
current study, the authors tried to further elucidate the role of CD1d in steroid-mediated NAFLD
by recruiting CD1d-knockout mouse line. By measuring the fasting glucose and insulin level,
serum or hepatic TG level, and so on, they concluded that steroid-induced liver steatosis was
CD1d-dependent while steroid-induced liver inflammation and metabolic disorders were CD1d-
independent. To some extent, this MS is kind of informative, however, the overall experimental
design and analyses are incomplete, and the conclusion is too hasty.
1) Experimental design is one of the major concerns. To understand the role of CD1d in the
steroid-mediated NAFLD, the authors should’ve analyzed the phenotypes of wild type and
CD1d-knockout mice side by side, by recruiting both wild type and knockout littermates,
instead of performing all the analyses separately. Otherwise it would be very hard to draw any
convincing conclusion. For instance, the only data that leads to the main conclusion that the
steroid-induced liver steatosis is CD1d-dependent is fig. 3F showing the TG concentration in
steroid-treated CD1d-knockout liver is not increased compared to that in CD1d-knockout non-
treatment group, however, no any wild-type littermate group was included in this experiment
as a control. In this scenario, there might be many possibilities leading to the outcome. For
example, the steroid treatment per se might not be working at all? or the method to measure the
TG concentration might be unreliable?
2) The current data are very ambiguous and incomplete. As mentioned above, according to the
fig.3F,  the authors claim that the steroid-mediated liver steatosis is CD1d dependent, however,
in Fig. 3E, the H&E staining with liver tissue sections indeed shows some difference between
non-treatment and steroid-treatment groups (Groups H and I), even though the quality of the
staining is really not good. It is hard to draw any conclusion from the current data, unless more
rigid experiments are employed, such as liver morphology analysis, Oil red O staining to indicate
the lipid deposition, QPCR analysis, immunostaining,  western blotting (to indicate the NAFLD-
related gene and/or protein expression profiling), and so on. Besides, the H&E staining needs
to be repeated and improved because of its bad quality.
3) The title is kind of too long and too wordy. Besides, there are some grammatical errors and
typos that need to be carefully corrected.
Review for 10.1186/s12876-022-02254-5 (2022)

Title: Epidemiology and outcomes of gastrointestinal mucosal melanomas: A national database
analysis
Version: 3 Date: 20 Feb 2022
Reviewer:  Fabio Melandro
Reviewer's report:
I read with great interest the paper of Shah et al. The authors  highlighted the treatment
strategies on very rare disease namely gastrointestinal mucosal melanomas analyzing  US
national database.
The study is interesting and innovative.
The Introduction is well written and has sufficient background information in particular in
epidemiology aspects.
Nevertheless, there is a lack of information In surgical procedure, extension of resection,
limphoadenectomy, surgical complications.
The same limited informations are evident in chemotherapy and radiotherapy schedules.
Please move the limitations of the study at the end of discussion paragraph.
The take home message in therapeutic approach in this field should be added in the conclusions.
Review for 10.1186/s12876-022-02254-5 (2022)

Title: Epidemiology and outcomes of gastrointestinal mucosal melanomas: A national database
analysis
Version: 3 Date: 05 Mar 2022
Reviewer:  Ali S. Taha
Reviewer's report:
As a whole, this is well written and fairly informative report. The authors highlighted both the
strengths and the limitations of their work.
In my opinion, the main limitation is the lack of information about the chemotherapy regimes
used. This is because the outcomes of melanoma treatments have been significantly boosted
in recent years by the use of immune therapy: such therapy did not exist in 1970s-1990s. This
should be added the limitations
Review for 10.1186/s12876-022-02254-5 (2022)

Title: Epidemiology and outcomes of gastrointestinal mucosal melanomas: A national database
analysis
Version: 3 Date: 16 Mar 2022
Reviewer's report:
Saha et al reported the epidemiology and outcomes of gastrointestinal mucosal melanomas by
reviewing a large national database.
The number of patient enrolled is very respectable across a very long period of time. There is
certain limitations but are all well addressed by the authors.
Overall, it provide a good insight on this rare disease entity.
Review for 10.1186/s12876-022-02255-4 (2022)

Title: Fecal biomarkers of environmental enteric dysfunction and associated factors among
children aged 24-59 months in east Dembiya district, northwest Ethiopia
Version: 0 Date: 18 Dec 2021
Reviewer's report:
Comments to author
In the Abstract section, the authors need to avoid abbreviation
Background
It is better to mention the global epidemiology of EED so as to show the gap of the study.
Methods
EED may be caused by parasites, bacteria, virus or fungi. However, the authors have mainly
focused on parasites.  I do not understand why the author did not isolate other microorganism
from the children’s stool rather than from food or water.
Line 100 : The author selected 238 out of 372 children, is 372 children the total population?
make it clear.
Line 108: Stool samples were collected without fixative for ELISA test. What about samples
used for intestinal parasite detection, with fixative or without fixative? If with with fixative,
what chemical was used?
Besides ELISA test procedures, A laboratory procedures for intestinal parasites and E. coli
detection should be mentioned in detail.
Result
line 160:  which parasites were predominantly identified ? B/se mentioning which parasites are
associated with fecal biomarker is something attractive to readers
Table 4 What is the purpose of analyzing EED b/se EED is measured by the three (AAT, MPO,
and NEO) . It is also better to say Adjusted odds ratio instead of adjusted beta
Review for 10.1186/s12876-022-02255-4 (2022)

Title: Fecal biomarkers of environmental enteric dysfunction and associated factors among
children aged 24-59 months in east Dembiya district, northwest Ethiopia
Version: 1 Date: 10 Feb 2022
Reviewer's report:
The authors unable to sufficiently address most of my previous comments. I strongly suggest to
address my previous comments that can significantly improve the readability of the manuscript
instead of  displaying other manuscript which I have not invited to review. The responses
given  to most of the comments are not in the proper way and convincing. Therefore, I further
recommend authors to  carefully see the comments and revise the manuscript as the work
addresses an interesting topic and is original
Review for 10.1186/s12876-022-02255-4 (2022)

Title: Fecal biomarkers of environmental enteric dysfunction and associated factors among
children aged 24-59 months in east Dembiya district, northwest Ethiopia
Version: 3 Date: 21 Mar 2022
Reviewer's report:
Authors  addressed the previous comments and the manuscript significantly improved than
before and is suitable for publication in BMC Gastroenterology if the following minor
comments   are addressed.
1. In the sample collection section, who were field workers?  Who actually collected the soil,
food and stool samples. Please specify the actual data collectors with regard to their profession.
The term ''field workers'  is not proper and professional.
2.  line 165-166, revise the phrase samples preserved on ice?  and stored in the laboratory on ice?
You mean samples stored in ice box for transportation and preserved at 4 O C in the laboratory
until microscopic examination?  Look how  similar papers written on sample transportation and
preservation in the laboratory.
3. The manuscript requires edition for language usage and smooth transitions between
paragraphs particularly to the methodology and result sections.
Thank you.
Review for 10.1186/s12876-022-02255-4 (2022)

Title: Fecal biomarkers of environmental enteric dysfunction and associated factors among
children aged 24-59 months in east Dembiya district, northwest Ethiopia
Version: 4 Date: 30 Mar 2022
Reviewer's report:
Authors sufficiently addressed all the given comments. I strongly recommend this manuscript
to be published in BMC Gastroenterology
Review for 10.1186/s12876-022-02258-1 (2022)

Title: Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control
study
Version: 1 Date: 13 Dec 2021
Reviewer's report:
Dear authors,
I really enjoy this article, the information is complete and the structure is appropiate. Despite
being a retrospective article, the topic is very interesting and important coz signet ring cells are
agressive and worst prognosis in any part of the gastrointestinal tube, colon is not the exception ,
lucky the incidence is very low but very important suspect in young patients.
Congratulations for a great job ¡¡¡¡
Review for 10.1186/s12876-022-02258-1 (2022)

Title: Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control
study
Version: 1 Date: 05 Jan 2022
Reviewer's report:
In the current study, the authors utilized clinical data of 11,515 colorectal cancers (CRCs) and
analyzed 18 primary signet ring cell carcinoma of the colon and rectum (PSRCCR) found in the
cohort. Their data provide important information regarding this rare entity, but methods for data
analyses may not be optimal.
Major comments:
1. The authors identified 18 PSRCCR among 11,515 CRCs registered in their pathological
databank, but the criteria for pathological diagnosis of PSRCCR are not clearly mentioned,
perhaps due to the retrospective nature of the current study. To ensure the legitimacy of the
original pathological diagnosis, pathological review should be performed at least for the tumors
with available H&E slides.
2. They utilized 72 non-PSRCCR CRC as controls. Because the comparisons between PSRCCR
and non-PSRCCR CRCs are essential part of the current study, how they selected these 72
tumors out of all the non-PSRCCR CRCs must be clearly mentioned. To justify their analyses,
bioinformatical rationale for the selection of control cases should be explained.
3. The authors aimed to find clues for diagnosis of PSRCCR. Because CRCs are usually
diagnosed by colonoscopy, I would recommend analyzing endoscopic findings at least for
available cases.
4. The authors mentioned that in PSRCCR cases, infiltrative/ulcerative configuration as well as
long segmental wall thickening detected by CT scan could lead to possible misdiagnosis as non-
malignant disease such as Crohn’s disease. Importantly, they showed that endoscopic biopsy
failed to identify malignant cells in more than one third of PSRCCRs. Because these findings
provide relevant information for gastroenterologists, detailed analyses of colonoscopic, CT,
and histological findings are recommended. In addition, please clarify the definition of tumor
configuration (exophytic, ulcerative, or infiltrative) as well as “long segment colonic stenosis”.
Minor comments:
1. Please do not use non-standard abbreviation such as “CFS”. I suppose it stands for
colonoscopy but not sure.
2. Because PSRCCR patients were younger than non-PSRCC CRC patients, I wonder if they
contain any patients with hereditary cancer syndromes such as Lynch syndrome and hereditary
diffuse gastric cancer. Information on personal and familial cancer occurrence and microsatellite
instability testing may be useful if available.
3. I think it is difficult to evaluate the efficacy of bevacizumab and cetuximab against PSRCCR
in such a small number of cases, especially without information on major confounding factors
such as RAS/BRAF mutations and chemotherapeutic regimen.
4. Features associated with PSRCCR such as poor outcome, high CEA, and low albumin may
be all attributed to advanced stage at diagnosis rather than biological nature of PSRCCR itself.
I prefer to see those data stratified by tumor stages (especially stage III vs stage IV).
Review for 10.1186/s12876-022-02258-1 (2022)

Title: Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control
study
Version: 3 Date: 09 Mar 2022
Reviewer's report:
I appreciated the authors effort to improve this manuscript.
Comments:
1. I think the most relevant findings of the current study are the unique features of RSRCCR
such as infiltrative configuration by colonoscopy and long segmental wall thickening by CT.
Therefore, I would advise to include endoscopic and CT images of typical case(s).
2. Table 4 and Table 5 may be revised into one table.
Review for 10.1186/s12876-022-02215-y (2022)

Title: Real-world characteristics, treatment experiences and corticosteroid utilisation of patients
treated with tofacitinib for moderate to severe ulcerative colitis
Version: 4 Date: 27 Dec 2021
Reviewer's report:
Chiorean et al present a retrospective study using a US claims database to describe the clinical
characteristics, treatment utilisation, and steroid use of tofacitinib-treated patients over a 14-
month period. Patients were reported and outcomes were categorised according to prior biologic.
The pool of real-world studies for tofacitinib are increasing but remain small and studies that
add to this limited cohort, particularly those with longer-term follow up, are welcomed.
It is not entirely clear why the authors chose to include patients treated with vedolizumab and
TNF inhibitors from the claims database when the focus of the manuscript and further analyses
regards tofacitinib. It appears that this is simply to highlight that these groups had a different
percentage of prior biologic exposures, but this is axiomatic given tofacitinib was approved later.
I am not sure this adds anything if there is no further analysis.
The authors report that patients receiving immunomodulators decreased from 30% to 9%
following tofacitinib initiation. However, concomitant immunomodulator use with tofacitinib is
not standard UC practice and so I suspect these are rheumatology patients. The authors briefly
mention this in the discussion and thus the cohort presented as UC are very much likely to be
a mix of both UC and RA/PsA patients.
Unfortunately, this study is significantly limited by its scope and provides little to what
is already known i.e. that tofacitinib patients are more likely to be bio-exposed (note that
tofacitinib was approved after anti-TNF and vedolizumab) and that corticosteroid use declines in
tofacitinib-treated patients (the drug was evaluated for this in the registration studies and in most
effectiveness studies since then).  The inherent limitations of studies from a claims database also
adversely impacts the validity of their findings.
Review for 10.1186/s12876-022-02215-y (2022)

Title: Real-world characteristics, treatment experiences and corticosteroid utilisation of patients
treated with tofacitinib for moderate to severe ulcerative colitis
Version: 4 Date: 08 Jan 2022
Reviewer's report:
In this paper, the authors use big data to investigate the efficacy and continuation of tofacitinib
treatment for refractory UC, mainly in the early stages of treatment.  This Real world analysis
highlights the clinical characteristics of patients with UC treated by tofacitinib, and also reveals
that it reduces the need for oral steroid therapy, even in patients who are refractory to multiple
optional therapy.  These results are considered to be clinically important facts,even in actual
UC medical care. For these reasons, this paper is judged to be suitable for publication in
BMC Gastroenterology.  However, we believe that the following points need to be added or
commented.
(1) It would be better to show the study design using this Big Data in a figure.
(2) Is it possible that the FDA alert or the timing of health approval of tofacitinib affected the
reason for the very low number of biologic-naïve in patients treated with tofacitinib?
(3) It is necessary to add the history of treatment with oral corticosteroids in the baseline period
to the demographic table of patients treated by tofacitinib and Biologics.
(4) In this study, the authors reported a decrease in the proportion of patients with UC treated
with TOF who received concomitant oral corticosteroids, comparing the index date with the 6-
month follow-up period. It would be desirable to show, if possible, whether the dose of oral
corticosteroids was also reduced for overall patients treated with tofacitinib.
(5) In this paper, the authors show that for UC patients treated with tofacitinib, the comorbidity
of extra-intestinal manifestations at 12 month baseline was 44.4%. The comorbidity of extra-
intestinal manifestations in patients treated with biologics should also be explained in the
discussion. This is because it is clinically important as one of the background factors for UC
patients treated with each drug, and may influence drug selection.
Review for 10.1186/s12876-022-02233-w (2022)

Title: IMMUNOHISTOCHEMICAL DETECTION OF CHLAMYDIA TRACHOMATIS IN
SEXUALLY TRANSMITTED INFECTIOUS PROCTITIS
Version: 2 Date: 12 Feb 2022
Reviewer:  Sergey Minaev
Reviewer's report:
I congratulate the authors on their ability to manage a challenging proctologic problem in
homosexual man with sexually transmitted infections. Because sexually transmitted infections
related proctitis is overlooked and misdiagnosed. However, the manuscript has several critical
flaws regarding publication.
1. Specify Leica manufacturers (Methods)
2. Specify the manufacturer of specific mouse IgG2a monoclonal antibody to chlamydia
trachomatis (Methods)
3. Statistics are not indicated in the Methods
4. Everywhere, tenths of a percent should be indicated in calculations.
5. No decoding HAART, VDRL, STD
6. The title indicates "... TRANSMITTED INFECTIOUS PROCTITIS", and in the table. 1
"Proctitis only 28%". Not quite clear.
7. There is no link to Figure 1 in the article
8. Describe all Figures. What can readers and should see in each of the photos?
9. References have a different type of design. It is necessary to follow the rules of the journal
Review for 10.1186/s12876-022-02233-w (2022)

Title: IMMUNOHISTOCHEMICAL DETECTION OF CHLAMYDIA TRACHOMATIS IN
SEXUALLY TRANSMITTED INFECTIOUS PROCTITIS
Version: 2 Date: 14 Feb 2022
Reviewer's report:
Comments:
1. Abstract. Methods section. What was considered as risky sexual activity should be specified.
2. 33.3% should be corrected to 33%. The total number of cases with IHC and the positive case
number should be provided.
3. Abstract. “We retrospectively applied immunohistochemistry with paraffin blocks and a
mouse monoclonal antibody (Santa Crutz Biotechnology) for the identification of Chlamydia
trachomatis”.
4. What was HH should be specified.
5. It’s “Chlamydia trachomatis” and “Treponema pallidum” not “clamydia trachomatis” and
“treponema pallidum”.
6. Reference no. 6. “Am J Surg Pathol. 2013 Enero 2013;37(1):38-46.” This should be corrected.
7. The Introduction should be restructured into two or three paragraphs, not as many as the
current form.
8. Methods section. The study design and inclusion and exclusion criteria should be written as
text, not as bullet points.
9. Sections of 1.5 to 2 microns for immunohistochemistry. This is extremely thin. Any reason
for this?
10. Any need for antigen retrieval?
11.  Professional English editing is needed to correct numerous grammatical and typographic
errors in the text and tables.
12. How many among the 54 patients were tested positive for HIV should be specified as the
authors mentioned that 13 patients had not been tested.
13. The format of the references is inconsistent. The reviewer could not find Reference no. 21
in PubMed using the information provided in the text.
Review for 10.1186/s12876-022-02239-4 (2022)

Title: Long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver
failure: a retrospective study
Version: 2 Date: 10 Nov 2021
Reviewer's report:
Dear Authors, the manuscript has been written well, some editing has to be done.
The manuscript in the present form does not add any new information, findings to the  already
published studies.
The study has to clarify that why anti viral treatment was not given to HBV cirrhosis patients.
Review for 10.1186/s12876-022-02239-4 (2022)

Title: Long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver
failure: a retrospective study
Version: 2 Date: 16 Dec 2021
Reviewer:  Premashish Kar
Reviewer's report:
The paper needs revision with refence to the clarification which are communicated to the editor.
Review for 10.1186/s12876-022-02239-4 (2022)

Title: Long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver
failure: a retrospective study
Version: 3 Date: 19 Jan 2022
Reviewer:  Premashish Kar
Reviewer's report:
1. It is not mentioned in t  text of the paper whether it is a prospective or retrospective study,
this should be mentioned in the methodology.
2. The various risk factors assessing the long term prognosis of the in both study groups should
be mentioned clearly in the methodology .
3. It was not mentioned what were the non cirrhotic cases in these groups
4. What was the distribution of the cases of cirrhosis with refer to child Pugh score
5. Why was liver biopsy done to document the diagnosis cirrhosis when it could have been made
on the basis of clinically features imaging and radiological features. how this was overlooked
by the ethical community of the institution.
These days liver biopsy is never done for confirmation of cirrhosis
Limitations of such retrospective  interpretation of data for clinical interpretation requires
validation and this should be mentioned in the discussion
Review for 10.1186/s12876-022-02239-4 (2022)

Title: Long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver
failure: a retrospective study
Version: 3 Date: 09 Feb 2022
Reviewer's report:
Dear Authors
I have following comments and suggestions for your manuscript:
1. Since their was increased 90 day mortality noted in the study, it is better to incorporate ACLF
survival models : AARC score (APASL ACLF score) and or CLIF-SOFA score in the results
and final analysis. Please add these scores if possible and make a comparison based on the scores
and final outcomes.
2. Please add a detailed analysis on the time line of the patient recruitment. It is clear that the
recruitment finished in 2020 but it is not clear when was the last patient inducted (onset of ACLF)
Review for 10.1186/s12876-022-02244-7 (2022)

Title: Gene variants of the SLC2A5 gene encoding GLUT5, the major fructose transporter, do
not contribute to clinical presentation of acquired fructose malabsorption.
Version: 2 Date: 30 Jan 2022
Reviewer:  Zoia Rossokha
Reviewer's report:
Dear Authors!
You provided the article with the original design. A serious clinical study was conducted to select
patients. Molecular genetic analysis is well organized. The article is well written and accessible.
The authors proved the absence of the influence of non-pathogenic gene variants on the acquired
disease. It was the expected result. The authors obtained the same frequencies of gene variants
as in the genomic databases, but they did not confirm this by statistical analysis. The next step of
this study is to compare the frequencies of investigated gene variants in patients with the results
of healthy individuals (may be from the genomic database). The article can be published after
statistical analysis - comparison of the obtained results of the distribution of the studied gene
variants with the results in healthy individuals.
Review for 10.1186/s12876-022-02244-7 (2022)

Title: Gene variants of the SLC2A5 gene encoding GLUT5, the major fructose transporter, do
not contribute to clinical presentation of acquired fructose malabsorption.
Version: 3 Date: 14 Feb 2022
Reviewer's report:
The paper is well written and ready for publication now. The authors have addressed all raised
issues appropriately.
I would only suggest to report patient age as median (range) or mean (standard deviation) in
table 2 accordingly to  skewed or normal distribution of this data.
Review for 10.1186/s12876-022-02244-7 (2022)

Title: Gene variants of the SLC2A5 gene encoding GLUT5, the major fructose transporter, do
not contribute to clinical presentation of acquired fructose malabsorption.
Version: 3 Date: 24 Mar 2022
Reviewer:  B. Yan
Reviewer's report:
This is an interesting genetic study with a small group of samples. Basically, authors tried to
investigated the genetics of acquired fructose malabsorption. SLC2A5 gene encoding GLUT5
was analyzed in 35 patients. Ten genetic variants were identified, frequencies of which in this
group of patients were similar to that in general population in  public database. Therefore, author
concluded that genetic variants of SLC2A5 gene, including coding exons, adjacent intronic
regions and proximal promoter region,  are unlikely to contribute to genetic predisposition of
acquired fructose malabsorption. Though negative results were presented here, the data would
provide a piece fo new information. In addition,  the column "Different conditions  from standard
protocol" In Table 2 might be left out, which did not added much information.
Review for 10.1186/s12876-022-02245-6 (2022)

Title: PEPTIC ULCER DISEASE AMONG DYSPEPTIC PATIENTS AT ENDOSCOPY
UNIT, UNIVERSITY OF GONDAR HOSPITAL, NORTH WEST ETHIOPIA
Version: 1 Date: 29 Oct 2021
Reviewer's report:
Title
# Cancel the word “prevalence” from the title
Abstract
# Background lacks to show the gaps
# Methods& result --somewhat wide, you have make it short and informative
#  What do mean “consecutive sampling method”?
# Result—you have report the prevalence of PUD with 95% CI
# Conclusion—your result and conclusion is not in line with your objective
Background
# You  background is very shallow and should rewrite again  by including  basic component
of  background
# You have to show gap  between  the existing literatures  and what add your paper for  the
existing literatures
Methods
# Study design and setting—please information like date of service that have been give and
overall patient follow endoscopy department
# Your study population and inclusion criteria is the same. If it is you have to merge.
# In your exclusion criteria… what are contraindication you use. You have mentioned in details
# Dependent variable: Proportion of peptic ulcer disease…please cancel the word proportion
#  Socioeconomic status—how could you assesses it?
# How could you assess behavioral factors like smoking and alcohol intake? There are standard
tool for this variable. With single question  you can assesses it
# Taking a 15% estimated proportion of peptic ulcer disease among dyspeptic patients---where
did you get it….if there no pervious study you have use 50%. With these sample size you can
get desired effect.
# A consecutive sampling method---as per my knowledge there is no such type of sampling
method
# Further operation definition is required when  we say the patient have PUD
# I do have doubt with you ethical consideration. All endoscopic procedures you follow
somewhat invasive and need further consent.
# Over all methods is not write in good manner and even not follow appropriate sequence.
Result
# You have to report the prevalence PUD with 95% CI
# In method section you said “variables with a P-value < 0.25 in the bi-variable analysis were
exported to multi-variable analysis”. But in your table 2, there variables whose P-value > 0.25
in the bi-variable analysis but included multi-variable analysis.
# Over all result section is not attractive and need rewrite
Discussion
# You discussion is very shallow and should rewrite again.
# You said “The major strength of this study was its prospective study design” what does
mean???
# Total I disagree with Strength and limitation of the study.
Conclusion and recommendations
# Your conclusion in line with your objective and should rewrite again.
# Your recommendations is also based on your finding.
Ethics approval and consent to participate
# I have seen this part in method section. Please cancel one them
Consent for publication
# Your consent for publication not correct and please check it
Reference
# The reference was not write as per standard and even inserted manually
Review for 10.1186/s12876-022-02245-6 (2022)

Title: PEPTIC ULCER DISEASE AMONG DYSPEPTIC PATIENTS AT ENDOSCOPY
UNIT, UNIVERSITY OF GONDAR HOSPITAL, NORTH WEST ETHIOPIA
Version: 1 Date: 10 Jan 2022
Reviewer's report:
General comments
The paper is technically and statistical analysis of the data sounds good and the claims are fully
supported by the experimental data. The claims are fully supported by the experimental data and
the availability of data adheres to the expected standards of our research community. Also the
claims appropriately discussed in the context of previous literature. However, the author needs
to address the following comments to make the manuscript potentially suitable for publication.
1. The headings and sub headings font sizes are similar with body/ paragraphs, the author should
format the manuscript properly
2. The name of bacterial species is not written in proper way, the author must italicize the name
of bacteria throughout the document.
3. In the method section, how did you assured the quality of your data including laboratory data?
Review for 10.1186/s12876-022-02245-6 (2022)

Title: PEPTIC ULCER DISEASE AMONG DYSPEPTIC PATIENTS AT ENDOSCOPY
UNIT, UNIVERSITY OF GONDAR HOSPITAL, NORTH WEST ETHIOPIA
Version: 4 Date: 12 Feb 2022
Reviewer's report:
1. The name of bacteria should be written according to the standard way of writing bacteria
name. For example Helicobacter pylori or  H.pylori , both way of writing should be written in
italics. please correct it accordingly.
2. Please clearly state how you assured the quality of your laboratory data? or what was your
quality control you used during laboratory procedure to assure the quality of your findings?
Review for 10.1186/s12876-022-02245-6 (2022)

Title: PEPTIC ULCER DISEASE AMONG DYSPEPTIC PATIENTS AT ENDOSCOPY
UNIT, UNIVERSITY OF GONDAR HOSPITAL, NORTH WEST ETHIOPIA
Version: 4 Date: 10 Mar 2022
Reviewer's report:
First of I would like to thanks the authors for effort to revised the manuscript. Having saying
this I do to have  two major concern.
1) First concern regarding your sampling method. you used non-probability sampling method
which don't allow a conclusion to your general population. if so you have justify it clearly or
mention it as you limitation your study.
2) Second regarding your finding. You reported two associated factors PUD. but this factors are
well known. So what did you add to scientific community from your study .