JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-023-02917-x (2023)

Title: Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic
quality
Version: 0 Date: 18 Jun 2023
Reviewer's report:
This manuscript intended to compare the complication and specimen quality between
percutaneous liver biopsy (PLB) and transjugular liver biopsy (TJLB) patients to assess the
safety and efficacy of TJLB. However, several comments are given to this paper.
1. The abstract requires modifications, such as the clinical value and clinical implications of
the study.
1# by controlling confounding factors through propensity score matching (PSM).
2# Coagulation index and ascites were not considered as matching factors.
3# with excellent diagnostic quality.
2. The Complication rates of TJLB and PLB were the most important issue in the clinical
practice. This should be more detail and clear (Complication rates  of TJLB and PLB were 3.3%
(1/30) and 5.6% (152/2711), with no statistical difference.).
3. English writing should be improved.
1) In technical details, the success rate of TJLB was 100%.
2) the pathological diagnosis can be largely met.
3) which was equivalent to the rate reported in the previous literature
4. Please add the references for these sentence.
1) But a tissue length of #15 mm and 6 CPTs are sufficient for pathological diagnosis.
Review for 10.1186/s12876-023-02917-x (2023)

Title: Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic
quality
Version: 3 Date: 28 Jul 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Yes, the authors have addressed all concerns and I have no addition
critiques.
ADDITIONAL REQUESTS/SUGGESTIONS:
None
Review for 10.1186/s12876-023-02918-w (2023)

Title: Selective COX-2 inhibitors do not increase gastrointestinal reactions after colorectal
cancer surgery#A systematic review and meta-analysis
Version: 2 Date: 17 Jul 2023
Reviewer:  Shoban Babu Varthya
Reviewer's report:
I congratulate the authors for conducting Selective COX-2 inhibitors do not increase
gastrointestinal reactions after colorectal cancer surgery: A systematic review and meta-analysis
My suggestions are:
1. In the Abstract: Results: rephrase the sentence as celecoxib and rofecoxib was not significantly
improved disease response rate ( mention the OR)
2. Mention the protocol registration, if any in the methods section
3. In search strategy: rewrite random controlled studies as “Randomized controlled studies”
4. Table 1: in mean age add (years); write the expansion of CRT and 5-FU in the bottom of
the table; label RCTs in included studies as authors mentioned 3 RCTs in the characteristics of
included studies.
5. Remove . before Outcome of the interest
6. What 29 stands for in outcome of interest in line no. 3 and 5
7. Add a reference to Jadad scale and Review managers meta-analysis in data extraction and
quality assessment in line. No.7 and data synthesis and assessment in line no. 1 respectively.
8. Mention the detailed reasons for the exclusion of full text (n=49) in Figure 1
9. In figure 2: RR is mentioned. However, in figure OR is calculated. Kindly verify and label
appropriately.
10. Add strengths, limitations and proper conclusion after discussion.
11. What is the reason for using Jadad quality assessment tool instead of ROB-2?
12. Results of quality assessment not mentioned in the results and their interpretation in the
results section.
Review for 10.1186/s12876-023-02918-w (2023)

Title: Selective COX-2 inhibitors do not increase gastrointestinal reactions after colorectal
cancer surgery#A systematic review and meta-analysis
Version: 3 Date: 07 Aug 2023
Reviewer:  Shoban Babu Varthya
Reviewer's report:
Dear Editor,
I have gone through the manuscript and the author's response to the earlier comments. comments
are well addressed and all the recommended modifications are performed.
kindly proceed with an editorial response. nothing from my side.
Review for 10.1186/s12876-023-02924-y (2023)

Title: CLDN18.2 Expression and Its Impact on Prognosis and the Immune Microenvironment
in Gastric Cancer
Version: 1 Date: 13 Jul 2023
Reviewer's report:
Thank you for gave me the opportunity to revise this interesting paper about CLDN18.2
Expression and its Impact on Prognosis and Immune Microenvironment in Gastric Cancer.
I found the topic of interest and the paper well written.
However, I suggest making some changes in order to improve the quality of the manuscript.
In particular, I suggest:
Major:
- to clarify what do you mean for paracancerous tissue. In particular, in the discussion the authors
state that "In our cohort of 342 gastric tumor tissues and their corresponding adjacent tissues...".
However, when they cited paracancerous tissue in the material and method section, it is not clear
what is a paracancerous tissue (normal tissue?) and if those tissues were from the same patient
in pairs (tumour/normal tissue). Please add some comments on that and revise those sections
accordingly;
- to clarify the cut off used to define PDL1 positive and PDL1 negative. In fact, even though
the authors have described the type of analysis (“The expression of PD-L1 was evaluated using
the combined positive score (CPS), etc”), they concluded that “based on the median number of
stained cells, patients were categorized into high and low expression groups.”. However, the cut
off is not clear and this might affect the results. Please, clarify this issue, add the cut-off and
modify all accordingly.
- to add clearly all the limitations of the analysis. Among them, I suggest to add a comment
regarding the value of PDL1 ant tumour microenvironment cells evaluated on samples collected
from March 2008 to August 2017 (ancient archival blocks).
Minor:
- in the introduction, please specify the phase of the trials you have cited, eg  FAST and MONO
trials are phase 2 trials;
- in the introduction, please add the recently presented preliminary results of SPOTLIGHT trial;
- to carefully revise the paper to avoid typos (e.g Lauran- in the text, in the figures, etc)
- to revise the abbreviation in order to use them at the first appearance (eg. IHC, GC and so on);
- to revise the references regarding GLOBOCAN in order to be sure to use the same newest
version (see references 1 and 28);
- The authors found that “CLDN18.2 expression levels are associated with the degree of
tumor differentiation, Borrmann type, and PD-L1 expression levels.”.  However, in the first
sentence they state “the expression level of CLDN18.2 in gastric cancer showed little significant
correlation with various clinicopathological characteristics, except for the level of PD-L1
expression (p = 0.004).” It is a bit confounding. Please clarify the issue about PDL1.
- Please show data about the multivariate Cox analysis in a table.
Review for 10.1186/s12876-023-02924-y (2023)

Title: CLDN18.2 Expression and Its Impact on Prognosis and the Immune Microenvironment
in Gastric Cancer
Version: 1 Date: 14 Jul 2023
Reviewer's report:
Using immunohistochemistry on TMA analysis authors evaluated expression of Claudin 18.2 in
series of 451 therapy-naive gastric cancers (GC) and performed analysis of clinicopathological
features and survival data.  The methods seem appropriate and the results are described in detail.
However, I have some important points that the authors should consider:
1) In the introduction section, a hypothesis could be added. What was the hypothesis at the
beginning of the study?
2) In the “Immunohistochemical evalutation” section it is shortly mentioned that representative
samples of GC tissue, normal tissue and lymph nodes are selected for preparation of TMAs. How
many TMAs were used per case? In particular, how many tissue cores per case were taken from
the cancer area? I think this information is very important, as previous studies have described
the heterogenous expression of Claudin 18.2 in the cancer tissue.
3) How did you assess the percentage of stained cells? Did you counted only the cancer cells /
the epithelial cells in the normal adjacent tissue? Or was the stromal compartment also included
in the assessment? From what I see in the representative images (Figure 2A), this could be the
case. If yes, this should be noted in Materials & Methods.
4) Why did you use the cutoff H-Score = 6? Does it differ from previous studies and the cut-
offs being used for eligibility in Zolbetuximab studies?
5) Were there any cases that showed different expression levels in cancer area and in matched
lymph node metastase? Do cases with high CLDN18.2 expression in the metastasis were
associated with poor prognosis when compared to CLDN18.2-negative cases?
6) The paragraph “Relationship between expression of the CLDN18.2 protein and
clinicopathological features” can lead to confusion, as the p values in the text/Figure 2 does not
fit to the data in the Table 2. If 2 different statistical methods were used, this could be shortly
indicated in the text. That would make the results more clear.
7) Different from previous studies, a positive correlation between CLDN18.2 and PD-L1 is
demonstrated in this study. How would you explain this association and the discrepancies with
previous data?
8) The strengths and limitations of the study should be added at the end of the discussion section.
What are the strengths and limitations of this study?
9) In my opinion, the Figure 1 (plots from databases) could be transfered to the supplement.
You could add larger representative histological images here, because Figure 2A is too small to
appreciate the CLDN18.2 expression.
10) If possible, professional language editing should be carried out. For example, there is no
such “Lauran” type, it is Lauren or Laurén. Perhaps better use the term “adjacent tissue” or
“peritumoral tissue” instead of paraneoplastic tissue.
Review for 10.1186/s12876-023-02867-4 (2023)

Title: Bioinformatics Analysis Of Hedgehog Interacting Protein In Colorectal Cancer#A Study
Based On GEO Data And TCGA Data
Version: 0 Date: 02 Jun 2023
Reviewer's report:
Authors did pan-cancer expression analysis of Hedgehog Interacting Protein (HHIP) genes.
And they detected downregulated HHIP genes in patients with colorectal (CRC) compared to
the normal and as a potential diagnosis biomarker for CRC. HHIP also showed a significant
correlation to immnue infiltration in CRC. HHIP genes. They further did non-coding RNA
analysis that relates to HHIP, and LINC02381 that has been reported as a carcinogenic in CRC
highly correlated to the expression of HHIP gene. The paper shows a poor language organization,
the abstract, subtitle, last sentence in some parts should be nice reorganized.
01. In the last sentence in abstract, there is no any support for which HHIP associated with poor
prognosis, the relate result should be exhibited.
02. LINC02381/miR-577 axis is a pathway? The concept here should be explain more clear
here, it just likes a complex that consists of miRNA and lncRNA rather than a pathway.
03. We can define a gene is an differential genes (at line 103) through the differential expression
level, differential structural and even different function, etc.. Which aspect do authors want to
show here.
04. Unclear intention of 2.2 part. Predicted miRNAs were considered as candidate miRNAs of
HHIP, candidate miRNAs for further analysis? The candidate here should be well-defined.
05. It's better use "a" rather "the" in line 152. And "lowly expressed" at line 161 should be
substituted by a "downregulated", and the comparison group should be listed.
06. The subtitle of 3.1 is not sufficient to comprehensively summarize the content of this section,
in this part, there also includes the association between HHIP expression and OS.
07. Misspelling word at line 168.
08. Line 185-186, poor language organization, and the conclusion (the most influential
regulatory ..) not suitable here.
09. Biomarkers of immune cells should be referred before line 229. Replenish the introduction
or at the begin in 3.5 part.
10. The px of the picture catch to standard level or not? The letters and symbols should have
a visual adjustment.
11. Figure 2 and 3 should be integrated together.
Review for 10.1186/s12876-023-02867-4 (2023)

Title: Bioinformatics Analysis Of Hedgehog Interacting Protein In Colorectal Cancer#A Study
Based On GEO Data And TCGA Data
Version: 0 Date: 06 Jun 2023
Reviewer's report:
In this study, the author analyzed the molecular characteristics of HHIP in colorectal cancer
patients and found that HHIP is low expressed in tumor tissue, and recognizes HHIP related
miRNAs and lncRNAs, which are closely related to immune cells and checkpoints, and may
have a potential role in the immunotherapy of colorectal cancer. This study has clear logic and
reasonable methods, but the results still require extensive editing.
1. In the abstract section, the author describes that "There is growing evidence that Hedgehog
Interaction Protein (HHIP) plays critical roles in the development of severe types of CRC.
However, the specific role and mechanism of HHIP in CRC remains not fully understood. If
HHIP has been found to play a crucial role in various colorectal cancers, there is no need to
explore it.
2. In the method section, what is the threshold for differential expression analysis used by
GEO2R, which should be described by the author.
3. In order to enrich the research results, it is recommended that the author search for
immunohistochemical results of HHIP between colorectal cancer and normal tissues in the HPA
database to confirm its differential expression at the protein level.
4. In order to explore the biological processes involved in the HHIP gene, the author can use
GSEA to conduct gene enrichment analysis of a single gene to confirm the impact of HHIP on
the occurrence and development of colorectal cancer.
5. The HHIP gene has been found to be associated with the prognosis of colorectal cancer
patients. It is recommended that the author add a correlation analysis between clinical features
and the expression level of this gene, including molecular typing and tumor staging of colorectal
cancer.
6. For the characterization of HHIP gene, the author can also use the DNA methylation data in
the TCGA database to analyze the change of DNA methylation level in the promoter region of
HHIP gene and whether it affects the gene expression level.
7. For the correlation analysis between HHIP and immunity, it is suggested that the author
can add correlation analysis between HHIP and immune pathway activity, use ssGSEA method
to calculate immune pathway activity, and analyze the correlation between immune pathway
activity and HHIP.
8. Figure 3 only has one lncRNA expression differential analysis and cannot be displayed as a
main graph. It is recommended that the author combine this graph with Figure 2.
9. Both Table 2 and Table 3 suggest that the author use a three line table for presentation.
Review for 10.1186/s12876-023-02914-0 (2023)

Title: Magnetic-Controlled Capsule Endoscopy Performance in Aging Patients
Version: 1 Date: 02 Dec 2022
Reviewer:  Konosuke Nakaji
Reviewer's report:
This is a retrospective study of magnetic controlled capsule endoscopy for the gastric lesion
(MCE) in China. Although several studies have already reported on the usefulness and safety
profile of MCE, this study focused on elderly patients, especially those over 80 years old.
Compared to the middle-aged group, the top results showed that although the transit times are
prolonged in the oldest, the overall visualizing scale is not statistically different, and findings
are more common in the most senior group. There are no severe adverse events in this study.
From this viewpoint, this study provided new helpful evidence in this field of study; therefore, it
is an exciting study for the coming “Old aged society” in Asia. However, there are some minor
concerns about this article. 1. The authors could provide an image of the system of MCE and each
part of gastric lesions for better understanding for general readers. 2. The authors could provide
more specific inclusion and exclusion criteria (e.g., pacemaker implantation) in the methods. It
is better to present the flow chart. 3. Could the authors be concerned about the HP infection and
state of atrophic gastritis? 4. The authors could present the detail of gastric tumors. Are these
included in early gastric cancer? Did they follow up by EGD, and what outcomes? The authors
could present their case examples.
Review for 10.1186/s12876-023-02914-0 (2023)

Title: Magnetic-Controlled Capsule Endoscopy Performance in Aging Patients
Version: 1 Date: 21 May 2023
Reviewer's report:
Thank you for your submitted manuscript. I enjoyed the topic and your results are interesting. I
understand this to be a single centre retrospective review of findings and procedural outcomes
using MCE in older adults, however the aim of the abstract does not match the abstract
conclusion or the aim/conclusion of the main study.
There are areas which I found surprising, such as the overall male:female ratio across the whole
cohort (as >80% were male). Comparison of GTT is also hard to assess when the capsule is
being pulled through the pylorus in some, but not others.
There were instances of poor English grammar and sentence construction which confused the
meaning of sentences. Square brackets are positioned throughout without clear rationale and
abbreviations also require checking for continuity.
Sections of the Discussion seem to depart from the themes of the manuscript (lines 224-230)
without contributing to the readers understanding.
I found it hard to interpret the safety data as the population denominator changes between
293 (the total group), and 197 (only those with complete SB studies) - which could mask SB
complications. This is further confounded by less than 20% receiving SB preparation. From the
study protocol this would suggest that SB examination was not required, or being sought in the
vast majority of those being reported on.  As a minor point my understanding from reading the
manuscript is that there were no small bowel retentions, but if this is the case it should be clearly
stated, as this is an important safety consideration. A comparison between the visualisation of
those who had PEG, versus those who had simethicone/pronase could help to clarify some of
the differences.
Overall I found this an interesting read. It confirms, as we would expect, that transit time
increases with age and response to preparation changes. This does have value, but there do
remain a few issues, as listed above.
Review for 10.1186/s12876-023-02914-0 (2023)

Title: Magnetic-Controlled Capsule Endoscopy Performance in Aging Patients
Version: 3 Date: 25 Jul 2023
Reviewer's report:
We thank the authors for taking the time to review and address our comments, we feel this has
improved the manuscript. However, there are a couple of points remaining.
1. The wrong paragraph has been removed in response to comment 5. The following was in the
original manuscript (lines 218-223) and is relevant:
In this retrospective study, MCE procedures of the interested oldest-old patients have
been reviewed. This is the first study assessed transit time and gastric visualization and
cleanliness scores in oldest-old patients compared with middle-old patients. Meantime, this
study demonstrated that the MCE could be a feasible and safe method of non-invasive
gastrointestinal examination for oldest-old patients. Another strength of this study was the
extended age field to 100 years old.
The text in the original manuscript that does not make sense in the context of the discussion
remains in the updated manuscript  (Lines 274-278)  and we feel this should be removed (see
below):
Age-related neurodegenerative functional changes in the enteric nervous system were reported
in rodents[16, 17]. Neuronal populations decreased mainly within the colon but also in the
esophagus, stomach, and small bowel[16, 18]. Moreover, the releasable pools of acetylcholine
and nNOS in the myenteric plexus [19] were reduced.
2.  The conclusion requires amending for clarity. The use of the term "older patients" twice is
confusing as earlier in the manuscript "older" has been used to define those aged 60-80years,
when the results show the conclusion to be indicated in those who are "oldest" >80 years. (see
below)
This retrospective study compared transit times and gastric preparation between patients over
80 years and patients 60–80 years old. We confirmed the benefits and safety of MCE for
older patients. For older patients with gastrointestinal diseases and poor motility, the gastric
examination may take longer and strategies for better gastric visibility should be considered.
Review for 10.1186/s12876-023-02908-y (2023)

Title: Differential expression of PLAC1 and Netrin-1 in liver metastasis of colorectal cancer
and its predictive value
Version: 1 Date: 14 Jun 2023
Reviewer's report:
1. Please provide more information of how important of PLAC1 and Netrin-1 involved in cancer
metastasis in the introduction section.
2.Despite the statement in limitation, What is the potential mechanism of PLAC1 and Netrin-1
on liver metastasis in CRC patients?
3.The novelty and significance of the current study should be further emphasized.
4.1.1Inclusion criteria(1) All patients were definitely diagnosed as CRC by pathology. What is
pathology? Indicate the experiment or methodology. Also, (2) All patients diagnosed as liver
metastasis met the clinical diagnostic criteria. Specify what are the the clinical diagnostic criteria.
5.More detailed explanations should be reported in the results section.
Review for 10.1186/s12876-023-02908-y (2023)

Title: Differential expression of PLAC1 and Netrin-1 in liver metastasis of colorectal cancer
and its predictive value
Version: 1 Date: 25 Jun 2023
Reviewer's report:
1.Introduction section is too simple in describing the role of PLAC1 and Netrin-1 in diseases.
The author need to add relevant content of PLAC1 and Netrin-1 as predictive indicators in liver
metastasis in colorectal cancer, or other diseases.
2.Revise the descriptions: “ The content of PLAC1 in the tissues of CRC with liver metastasis
had a close relationship with differentiation degree and lymph node metastasis (P<0.05). The
expression of Netrin-1 in the tissues of CRC with liver metastasis was associated with Dukes
stage, differentiation degree and lymph node metastasis (P<0.05, Table 2)”. The expression is
inaccurate. Table 2 only compared different levels without conducting correlation analysis.
3. According to Table 4, the regression coefficients and constant terms are used to construct the
model, and the prediction model equation is Logit (P). Does this equation include PLAC1 and
Netrin-1 indicators, and does it deviate from the theme and content of the article?
4. "Logistic regression analysis showed that Dukes stage, differentiation degree, lymph node
metastasis, CEA, Alb and D-dimer were the independent risk factors for liver metastasis of CRC
(P<0.05, Table 4)." The statement is incorrect. All indicators should be assigned values before
multiple factor analysis. It is suggested to carry out two classifications. The risk factors should
reach a certain level
5. The discussion and analysis are lacking details. It is recommended to conduct a detailed
analysis based on the order of the tables, with a focus on analyzing the results with statistical
difference.
6.The two groups are divided according to whether liver metastasis occurs. The authors need to
state how to separate the groups first, followed by other data detection methods.
7. Add the sources, and origins for instruments, drugs, and reagents mentioned in the paper.
8. Add discussions about why PLAC1 and Netrin-1 can serve as factors affecting liver metastasis
in colorectal cancer and why they have high diagnostic value.
Review for 10.1186/s12876-023-02895-0 (2023)

Title: Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R -/- mice
Version: 1 Date: 14 Feb 2023
Reviewer:  Sahar H. Orabi
Reviewer's report:
-The manuscript should be carefully revised for typos and grammatical errors
- The author should mention the kind on antithetic that he used for anesthesia
-Describe also on which base you select the dose
-In commercial kits, please add the company, and catalog number.
-Assessment of serum biochemical parameters needs to be explained in more detail in the
methods.
-please insert approval number
-please mention weight  of mice used
Review for 10.1186/s12876-023-02895-0 (2023)

Title: Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R -/- mice
Version: 1 Date: 23 Feb 2023
Reviewer's report:
Dear editor of BMC Gastroenterology below is my opinion of the manuscript.
I suggest that add at least one type of method to the keywords.
Materials and Methods
In general, this research applied many related methods that are very good, but the writing in
this part is very brief.
- Why you didn't use the normal mice that make results more logical and beneficial?
-  Did you prepare the high-cholesterol diet dally or was it ready-made? or what?
-  Is there a reference for the period of animal treatment?
-  Please, add a reference for the euthanized method that you used
-  Why you did not measure the HDL?
-  Please, give a reference for the standard protocol of H&E tissue preparation or write it in
more detail.
-  Please, put the explanation of NLRP3 below table 1 as well as write the complete words of
F and R or explain them below the table.
- Were you applying the same secondary antibody of all parameters in the western blot
technique?
Results (also, the writing in this part is very brief)
- What is the significance level in the hepatic biochemical parameters and metabolic
characteristics among groups? All were smaller than 0.05 or what?
- In the H&E histology pictures, the changes are not clear. You should point to changes with
arrows or letters or else.
- (The HD + TQ group exhibited a markedly reduced accumulation of CD68-positive cells in
the LT compared with the ND group. There was no variation with respect to the aforementioned
parameters in the ND group.) This part needs more revision.
Discussion
Why did body weight decrease in the HD group?
- This part is very good as a comparison, but you do not give any explanation of the results that
may be related to Thymoquinone components. You may find that in some previous research. So,
I encourage you to continue working on this point in corporation with biochemistry scientists.
Review for 10.1186/s12876-023-02895-0 (2023)

Title: Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R -/- mice
Version: 1 Date: 04 Mar 2023
Reviewer's report:
The topic is novel and using thymoquinone as nutraceutical is promising in a number of diseases
while some points needs to be addressed to improve the work:
-This paragraph needs revision ''Blood samples were obtained from the inferior vena cava,
collected in serum tubes, and stored at –80 °C until use. Longitudinal sections of the livers
were fixed in 10% formalin and embedded in paraffin for histological evaluation. The remaining
liver was snap-frozen in liquid nitrogen for mRNA isolation and immunoblotting analyses.
All animal experiments were performed in accordance with the Guide for the Care and Use
of Laboratory Animals. This study was approved by the Ethical Committee of the Affiliated
Zhongshan Hospital of the Dalian University of China.'' Did you store the blood samples or
serum? Is the remaining liver snap frozen? did you freeze the remaining liver as it is? The ethical
approval should be at the start not the end of the paragraph.
-The blood samples were collected, and serum was prepared by centrifugation at 3000 rpm for
15 min.  this should be in the experimental model
- What do the authors mean by this ''There was no variation with respect to the aforementioned
parameters in the ND group.'' between ND group and which group?
- Regarding figure 4, the scale bar should be in all fields, arrows and explanations should be
added, It is highly recommended if you can add the percentage of CD68 positive cells in each
field.
-Figure 8 needs to be more representative, PI3K, CD68 upregulated or downregulated? the
metabolic characteristics and the biochemical parameters are very wide expressions that need
to be more specified.
- Full gel picture with no editing need to be added as supplementary
- Discussion needs to be improved by linking all the parameters together.
-Please revise the primer sequence of IL-18. Is this the sequence you used?
Review for 10.1186/s12876-023-02895-0 (2023)

Title: Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R -/- mice
Version: 6 Date: 11 Jul 2023
Reviewer's report:
Firstly, thanks for your response.
1- My suggestion is to add words about methodology in key words section that is attractive to
readers.
2- I suggest continuing the idea of this research on normal animals.
3- In the materials and methods section, you added a part about Hematoxylin and eosin staining,
please revise this part because the anesthetic substance name is different as well as remove the
heart word.
4- In the result section: why did you show the histological figures in a small size, for that the
changes are unclear, especially in HD group.  Also, you added arrows but did not demonstrate
the type of changes. You can put arrows with different colors or put small letters on the changes
then write about that below the figures.
5- What is the method or program that you applied to obtain the percentage of CD68+.
Review for 10.1186/s12876-023-02902-4 (2023)

Title: A nomogram based on CT texture features to predict the response of patients with
advanced pancreatic cancer treated with chemotherapy
Version: 1 Date: 24 Mar 2023
Reviewer's report:
Very interesting study. I have some methodlogical comments:
1) Validation cohort is too small. I would suggest to apply an internal validation approach
through bootstrapping. If not feasible, the authors should comment at least among the limitations
and they should cite some relevant papers on this approach (cite PMID: 27005802 and  PMID:
35451041)
2) The authors should specify in the title that a nomogram was used.
3) Why they used RECIST criteria and not mRECIST or other similar criteria?
4) The authors should briefly comment that also other methods for diagnosis of pancreatic
cancers are effective such as EUS (cite the recent meta-analysis PMID: 29026598 )
Review for 10.1186/s12876-023-02902-4 (2023)

Title: A nomogram based on CT texture features to predict the response of patients with
advanced pancreatic cancer treated with chemotherapy
Version: 1 Date: 21 May 2023
Reviewer's report:
The authors found a CT-based radiomics model  to predict the reponse of chemotherapy for APC
patients. The research method is reasonable. Although the sample size is small, it still give us
some infomation to increase the therapetic efficency. I think this manuscipt could be published
in BMC Gastroenterology.
Review for 10.1186/s12876-023-02902-4 (2023)

Title: A nomogram based on CT texture features to predict the response of patients with
advanced pancreatic cancer treated with chemotherapy
Version: 1 Date: 04 Jun 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: - The topic of this study is very interesting. It is well known that the
understanding of a response to chemotherapy is of primary importance. And this is very true in
pancreatic cancer, which can be associated to poor rensponse to drugs
- The authors designed a very detailed study to understant if CT scan can be used to predict and
monitor the chemo response
- Reading "methods" and "results" it is not easy to understand what can be the real clinical
application. It is appreciable that all the process is described in technical details. However
eventually it should be better explained how clinicians can use CT scan for their patients. This
should happen also in the "discussion" section
- It is not clear why they created two groups (training and validation), and how they decided the
number of patients for each group
REQUESTED REVISIONS:
- They should explain how they divided the patients in the two groups and how they identified
the numbers
- The authors should discuss more about the clinical application of such techniques, simplifying
the complex results
ADDITIONAL REQUESTS/SUGGESTIONS:
As stated above
Review for 10.1186/s12876-023-02902-4 (2023)

Title: A nomogram based on CT texture features to predict the response of patients with
advanced pancreatic cancer treated with chemotherapy
Version: 3 Date: 21 Jul 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: - The authors have responded well and adequately to the reviewers,
explaining better their study and their decisions about strategy and methods
- According to the reviewers' suggestions, where applicable, the authors have changed the
manuscript, improving the final result
- I think the manuscript is acceptable for publication after the revisions
ADDITIONAL REQUESTS/SUGGESTIONS:
I think the paper is ok now
Review for 10.1186/s12876-023-02919-9 (2023)

Title: Validation of a new simple scoring system to predict spontaneous bacterial peritonitis in
patients with cirrhosis and ascites
Version: 1 Date: 25 Apr 2023
Reviewer's report:
It is difficult to diagnose spontaneous bacterial peritonitis (SBP). This study was to externally
validate a diagnostic model for SBP in patients with cirrhosis and ascites, which had certain
clinical significance.
Comments:
1.In multivariate analysis, we found that NLR, MPV, and CRP were independent variables
related to the presence of SBP (Table 2). The performances of the variables are compared and
summarized in Fig. 1.
It was univariate analysis. The four variables, including age, NLR, MPV, and CRP from the
original study, should be brought into a logistic regression model at the same time in this
external validation data to figure out whether they still were all independent risk factors. The
OR (95%CI ) of the four variable alone and the Mansoura simple scoring system in this external
data should be disclosed.
2. Mansoura simple scoring system (Eur J Gastroenterol Hepatol. 2019 Aug;31(8):1017-1024.):
A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas
CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the
diagnosis of SBP of 88.1% (score#4). At a threshold of 1 point, the negative predictive value
is 97.5% with a sensitivity of 92.9%.
As an external validation study, calibration (Calibration curve and Brier score) based on the two
cutoffs (1 for negative prediction, 4 for positive prediction) should be disclosed in addition to
providing discrimination (AUROC). 95% CI should be shown too.
3. The discussion is not in-depth. It does not bring much apart from repeating facts already stated
in the introduction and the original study proposed the Mansoura simple scoring system.
4. Several models predicting SBP could be retrieved in Pubmed. It would be more meaningful
to validate the Mansoura simple scoring system and the others.
Review for 10.1186/s12876-023-02919-9 (2023)

Title: Validation of a new simple scoring system to predict spontaneous bacterial peritonitis in
patients with cirrhosis and ascites
Version: 1 Date: 13 May 2023
Reviewer:  Ahmed Abdel-Razik
Reviewer's report:
Nice work, but the authors may have some drawbacks to be clarified.
1-Recurrence of SBP in this university hospital should be mentioned in the introduction section
(Eur J Gastroenterol Hepatol. 2020 Jun;32(6):718-726. doi:10.1097/MEG.0000000000001578.)
2-Diagnosis of SBP and its variants may need more explanations.
3-The exclusion criteria should be written as follows: (a) patients who had received antibiotic
and/or prophylaxis for SBP before admission; (b) participants who had other causes of
ascites, for example, pancreatitis, peritoneal carcinomatosis, tuberculosis, congestive heart
failure, renal diseases, or hemorrhage into ascites; (c) patients with malignancy; (d) patients
with hemato logical diseases; (e) patients with surgical abdominal interference within 3
months of study entry; (f) participants who had received antiplatelet medications before their
admission; (g) participants who had received bone marrow transplantation or chemotherapy or
radiotherapy 1 month before admission; (h) pregnancy; (i) patients with secondary peritonitis;
(j) immunocompromised patients; (k) patients receiving NSAIDs or contraceptive pills before
hospital admission; (l) bacterial infection other than SBP; (m) patients with conditions associated
with increased MPV, for example, dyslipidemia, thyroid disorders, peripheral vascular disease,
hypertension, and diabetes mellitus; (n) patients with recent hemorrhage; and (o) patients who
had been infused with platelet or blood before their admission.
4-Please for high-resolution figures.
5-Discussion needs more revision.
Review for 10.1186/s12876-023-02919-9 (2023)

Title: Validation of a new simple scoring system to predict spontaneous bacterial peritonitis in
patients with cirrhosis and ascites
Version: 1 Date: 21 May 2023
Reviewer's report:
1. Authors need to further strengthen the rationale of the study by highlighting the importance
of non-invasive scoring for the prediction of SBP. The issues related to diagnostic paracentesis
should be elaborated further.
2. Was ascetic fluid analysis including detection of RBC count apart from WBC count to rule
out spontaneous and iatrogenic hemorrhagic ascites (post paracentesis)? As in the case of the
hemorrhagic component it will affect the CRP levels a main component of the Mansoura scoring
system.
3. Were patients having underlying evidence of HCC excluded too? as HCC will again affect
the CRP level?
4. Were all sub-sets of SBP like Culture-negative Neutrocytic ascites excluded?
5. Were patients of cirrhosis having rifaximin as part of their routine treatment to prevent HE
excluded? As current evidence suggests the reduction in SBP with rifaximin.
6. For validation of the diagnostic performance of the Mansoura scoring system larger and multi-
centric samples are required.
7. Discussion section needs to be more relevant to the current evidence.
Review for 10.1186/s12876-023-02919-9 (2023)

Title: Validation of a new simple scoring system to predict spontaneous bacterial peritonitis in
patients with cirrhosis and ascites
Version: 2 Date: 09 Jul 2023
Reviewer's report:
Query no 3
Was ascetic fluid analysis including detection of RBC count apart from WBC count to rule out
spontaneous and iatrogenic hemorrhagic ascites (post paracentesis)? As in the case of the
hemorrhagic component it will affect the CRP levels a main component of the Mansoura scoring
system?
Response by the authors:
In cases of iatrogenic hemorrhagic ascites (post-paracentesis), the neutrophil counts were
corrected. One neutrophil was subtracted from the absolute neutrophil count for every 250 red
blood cells to yield the "corrected neutrophil count".
Please mention this in the methodology section of the revised manuscript.
Review for 10.1186/s12876-023-02919-9 (2023)

Title: Validation of a new simple scoring system to predict spontaneous bacterial peritonitis in
patients with cirrhosis and ascites
Version: 3 Date: 24 Jul 2023
Reviewer's report:
In the Study population part, the authors said “The exclusion criteria were as follows: (a)… (b)...
(c)… and (d)… (e)… (f)… (g)… (h)… (i)…”, where the “and” should be deleted and the “(i)”
should be revised as “and (i)”.
In the Results part, the title “Patients characteristics” should be revised as “Patient
characteristics”.
The sentence “At a cut-off of 1 scoring point, the PPV was 28.6% and 100%, respectively” is
confusing. Did the authors mean to say that the PPV was 28.6% and the NPV was100%?
Review for 10.1186/s12876-023-02907-z (2023)

Title: Differences in clinical characteristics and liver injury between patients diagnosed with the
Omicron subvariant BA.5.2 and the prototype of SARS-CoV-2: A single center retrospective
study
Version: 1 Date: 26 Jun 2023
Reviewer's report:
The authors compared Omicron and SARS-Cov2 and reported in detail on clinical presentation,
respiratory complications, and blood tests for liver function. A comparison between the 2 groups
of blood tests showed that Omicron was significantly milder, and multivariate analysis was
performed regarding the factors presenting with abnormal liver function, and elevated CRP was
extracted.
The biggest problem is that it is not clear whether this analysis can evaluate the true liver
dysfunction. As authors reported in this article, SARDs-CoV2 causes systemic inflammation,
but in this report it is not possible to evaluate whether there is true liver damage. Coronaviruses
cause inflammation in blood vessels throughout the body and can affect levels of FDP, Dimeri
and PT. It is also well known that systemic tissue damage is reflected in an increase in
transaminases and a decrease levels of Alb. And these changes of parameter do not automatically
indicate liver damage. As far as the analysis results of this time are concerned, it is highly likely
that the status of liver damage has not been fully evaluated. If there is hepatosplenomegaly on
physical examination, the presence of hepatomegaly on image evaluation, and if hepatitis is
present, for example, the presence of periportal edema, and if actual pathological evaluation
such as liver biopsy can be added, the presence of liver damage can be further evaluated.
In this report, liver function test is checked in many patients but is not shown why these
omicron showed mild liver dysfunction compared with prototype. As previous studies have
reported, SARD-CoV-2 has systemic inflammatory disease, accompanied by hematological
abnormalities' including PT-INR, Ddier, and low-Alb.  How hoes authors show Is it really liver-
specific damage? If authors have evaluated liver biopsies, these parameters would strengthen
evidence, but at this point, we cannot understand why these omicron is milder phenotype, or
even liver-specific damage by omicron, or SARS-Cov-2.
Review for 10.1186/s12876-023-02907-z (2023)

Title: Differences in clinical characteristics and liver injury between patients diagnosed with the
Omicron subvariant BA.5.2 and the prototype of SARS-CoV-2: A single center retrospective
study
Version: 2 Date: 19 Jul 2023
Reviewer's report:
The authors replied my comments with courtesy in the R version paper.
Review for 10.1186/s12876-023-02824-1 (2023)

Title: Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by
Multi-Omic data analysis
Version: 1 Date: 02 Jan 2023
Reviewer's report:
A novel study which may lead to more research as this is an emerging field.
There is a requirement of prospective multi centre large trials
Minor spell check and format errors require rectification
Review for 10.1186/s12876-023-02824-1 (2023)

Title: Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by
Multi-Omic data analysis
Version: 1 Date: 03 Jan 2023
Reviewer's report:
A novel study which may lead to more research as this is an emerging field.
There is a requirement of prospective multi centre large trials
Minor spell check and format errors require rectification
Review for 10.1186/s12876-023-02824-1 (2023)

Title: Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by
Multi-Omic data analysis
Version: 1 Date: 10 Jan 2023
Reviewer's report:
The authors analyzed and validated the OSBPL3 in a cohort study and found a correlation
with clinical prognostic values. The results of this study contributed to the advancement of
treatment of CRC and were very valuable. I think the paper is well organized, with no excesses
or deficiencies in the construction of the research design, the statistical treatment of the results,
and the conclusions drawn from the results. I read it with great interest.
I have the following comments.
Minor points
1. No explanation of abbreviations in Fig. 1 (e.g. BLCA, BRCA, CESC...)
2. In Fig. 1, OSBPL3 was conversely decreased in KIRC and PRAD. No discussion derived
from these comparisons.
3. In Fig. 7, the data was presented without any explanation of the relationship between the
function of OSBPL3 and the regulatory mechanism of drug resistance, which seemed abrupt.
Although the data is clinically significant, the significance of presenting the data is not clear.
In addition, the results were at odds with the correlation with prognosis shown in previous
experiments.
4. In “discussion” line 329, “However, these results indicated the expression of OSBPL3 had
changed in CRC”. I think this is an important point: if OSBPL3 expression levels may change
depending on the clinical stage of CRC, then it should be properly analyzed for use as a
biomarker.