PONE-D-24-23322Analysis of the efficacy of splenic artery superselective embolization in cirrhosis with hepatocellular carcinomaPLOS ONE

Dear Dr. Zhao,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Aug 21 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

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Additional Editor Comments:

The manuscript contains several grammatical and language errors. Please revise it before we can proceed further.

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

PONE-D-24-23322R1Analysis of the efficacy of splenic artery superselective embolization in cirrhosis with hepatocellular carcinomaPLOS ONE

Dear Dr. Zhao,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Nov 30 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have conducted a retrospective cohort study to assess the difference in clinical outcomes between super selective partial splenic embolization (PSE) in comparison to non-selective/conventional PSE. The authors report that while both PSE are associated with similar clinical efficacy, there is no statistically significant difference in efficacy in each intervention. However, the authors also report that super selective PSE is associated with lower incidence of post-operative fever and vomiting, and lower degree of pain than conventional PSE.

I have the following comments:

1. The study is based on a small sample size possibly due to rarity of the cohort. The authors should add study’s power calculation, in methods, to justify whether it is statistically sufficient for the conclusions.

2. While the authors highlighted that existing literature gap on PSE’s application for HCC, they did not strengthen the need for assessing PSE in this subgroup. This is especially important since there is evidence available for PSE’s application in cirrhotic patients, HCC’s most common precursor lesion, and the major complication, portal hypertension, leading to hypersplenism, is same for either cohort of patients. The authors should highlight how selection of HCC cohort of patients effects clinical decision-making.

3. The effect of liver function on the PSE should be elaborated in more detail in the discussion along with the efforts made in this study to minimize or standardize these effects.

4. Even though the authors have found both methods equally clinically efficacious, the authors have found a difference in post-operative adverse effects of each intervention. The authors should provide more insight into how these findings can influence clinical practice, particularly regarding patient selection for either technique.

5. There are multiple grammatical and punctuation mistakes throughout the manuscript, especially in the introduction. These should be addressed.

Reviewer #2: The authors conducted a retrospective cohort study from August 2020 to December 2022 to assess the safety and efficacy of partial splenic artery embolization in patients with hypersplenism combined hepatocellular carcinoma. The authors compared the efficacy of superselective and non-superselective embolization. The author reported that both superselective embolization had comparable outcomes and demonstrated partial splenic artery embolization to be a safe and effective treatment option. I congratulate the authors on a well-conducted study. I have a few comments.

Introduction:

Several statements in introduction need a reference.

Methods:

1. No mention of data source. Was it institutional data? Was it administrative national database?

2. Ethics consideration section on page 10 needs reformatting and better phrasing.

3. Figures are not referenced in the proper manner. Figure 4 is cited before Figure 3 and 2.

4. For clarity Figures 1 in the methods and its sub-figures can be mentioned as Figure 1 a,b,c,d, and e.

5. In statistical methods on page 12, the first line states interquartile range but has no mention of median.

6. Method of pain score should be stated. Which standardized method of pain score was used?

7. Diagnosis basis of liver cirrhosis needs a reference.

8. Other statements in methods such as calculation of infarcted spleen volume need a reference.

Results:

1. No mention of percentages in results first paragraph.

2. Need to define cohort properly before comparing the two groups. No mention of overall rate of complications in the overall cohort. First paragraph needs formatting.

3. Number and percentages missing in paragraph 2 in results on page 13. Please add numbers.

4. On page 14, the wording “the analysis results showed that most patients n group a score 0-3, is not phrased properly. There should be clear mention of this pain score.

5. On page 14, the line “mitigated after treatment” is unclear.

6. On page 15, the figure is not in ideal quality. I was not able to understand whats included in the figure. Please attach figure separately if its embedded in the word document.

Tables

1. Table 1 caption should be improved to show: Demographics and clinical characteristics of patients undergoing treatment.

2. Table 1: The agemean is not a variable name. It should be written as Age. At the end of table, it can be mentioned that age has been reported as mean and standard deviation. Please report standard deviation instead of min-max for variables reported as mean.

3. For hypertension, no need to report "no" values. Only incidence of hypertension can be reported in one row. Same for other conditions.

4. For Etiology, the second category is unclear. Please clarify this.

5. The authors have not mentioned changes in lab values such as WBC, RBC etc for the overall cohort.

6. Footnote of table 1 should give full forms of all abbreviations.

7. Table 2 title needs improvement. Clearly state the data represented in this table.

8. For splenic abscess, results are not repported properly.

9. Table 4 needs full forms of abbreviations in footnote.

Discussion:

1. The first para of discussion should briefly discuss the results section instead of giving statements of the results section. It should be a summary.

2. Several lines in paragraph 2 and 3 of discussion lack a citation. Please cite references for all lines stating any findings in the literature or any known facts.

3. Paragraph 3 of discussion is just stating results instead of actual useful inferences of conclusion of this study. It should be stating whats was reported (briefly), how it compares to the given literature, and what its future implications can be.

4. The study lacks a clear paragraph for future directions. How are these results useful or significant? How can these findings shape the clinical practice?

Minor Comments:

1. Typographical error on page 9, last line of introduction: “Emobilzationfor”

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

PONE-D-24-23322R2Analysis of the efficacy of splenic artery superselective embolization in cirrhosis with hepatocellular carcinomaPLOS ONE

Dear Dr. Zhao,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Apr 07 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Thank you for submitting your paper titled "Analysis of the efficacy of splenic artery superselective embolization in cirrhosis with hepatocellular carcinoma" The study has clinical significance in the treatment of hypersplenism, and the research design is reasonable with clear experimental results. However, there are several problems could be improved, and I recommend minor revisions.

1. In the specific procedure of splenic artery embolization, although the steps are described, additional details on the embolic agent dosage and the use of microcatheters could be added. For example, it would be useful to discuss why 710-1000um gelatin sponge particles were chosen, how the size of these particles affects the embolization outcome, and the advantages of using these particles compared to other embolic materials such as polyvinyl alcohol (PVA) particles or metallic coils.

2. Pain and Complication Management: In addition to pain and nausea/vomiting, pain management strategies could be added, such as whether analgesics were used postoperatively and the effectiveness of pain relief.

3. The discussion section summarizes the main findings of the study well, but some comparisons could be explored more deeply. For example, although the discussion mentions that pain and fever are common postoperative complications of PSE, further exploration could be done on the relationship between the duration of fever and splenic infarction. Related literature could be cited to explain how the duration of fever relates to embolization dose, embolization site, and individual patient differences.

4. There are a few minor grammatical and expression issues, such as some sentences being wordy. It is recommended to streamline the language for better readability. Specifically, language optimization in the methods and discussion sections would help ensure clarity and conciseness.

Overall, this paper has high academic value and provides new insights into the treatment of hypersplenism. After the suggested

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

PONE-D-24-23322R3Analysis of the efficacy of splenic artery superselective embolization in cirrhosis with hepatocellular carcinomaPLOS ONE

Dear Dr. Zhao,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please refer to the editorial comments below.

Please submit your revised manuscript by Apr 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Additional Editor Comments:

This manuscript has a lot of grammatical errors which need correction. I have only listed and suggested paraphrasing for a few errors in Abstract, Introduction, and Methods. There are further grammatical errors in Methods, Results, and Discussion that I have not highlighted.

Please note that PLOS one’s publication criteria mandates each accepted article to be “presented in an intelligible fashion and written in standard English.” The authors’ work is clinically relevant and within the scope of this journal. We would invite the peer reviewer again to evaluate the revised version but only after the authors have corrected all grammatical errors in their next revision.

Some grammatical errors are highlighted below; please note that there are further errors as I mentioned previously.

Abstract:

• “To explore the safety and effectiveness of partial splenic embolization (PSE) in patients of hypersplenism combined with hepatocellular carcinoma”. Please revise to:

“…in patients with hypersplenism and hepatocellular carcinoma”.

• “compare the efficacy of splenic artery branch superselective and non superselective embolization.” Should be “non-superselective embolization”. Please insert the hyphen.

• “The safety and effectiveness of the two methods was evaluated, and the changes in peripheral blood cell [mainly white blood cells (WBC) and red blood cells (RBC)] and platelet (PLT) counts at different time points after PSE. As well as postoperative adverse events (AEs), were compared between the two groups.”

This sentence is grammatically incorrect. Please revise to:

“The safety and effectiveness of the two methods was evaluated along with changes in peripheral blood cells [mainly white blood cells (WBC) and red blood cells (RBC)] and platelet (PLT) counts at different time points after PSE. Postoperative adverse events (AEs) were also compared between the two groups.”

• “PLT and WBC also remained at a certain level, which were statistically different from those before PSE (P<0.05). But RBC count had no difference (P>0.05).”

Revise to:

“PLT and WBC counts consistently remained statistically different from those before PSE (P<0.05), but RBC counts had no differences (P>0.05).

• “In term of security, the incidence of fever and pain in group B was significantly higher than that in group A (P<0.05).”

Revise to: “The incidence of fever and pain in group B was significantly higher than that in group A (P<0.05).”

• “But superselective embolization exhibited a lower incidence of post-procedure complications compared to non-superselective embolization.”

Revise to: “However, superselective embolization exhibited a lower incidence of post-procedure complications compared to non-superselective embolization.”

Introduction:

• What do the authors mean by this in the last Introduction paragraph: “pleural/ascites”?

• “Therefore, we hypothesized that the use of splenic artery superselective embolization could reduce the extent of necrotic tissue to peripheral stimulation, in the expectation of fewer complications to be observed clinically.”

This sentence is unclear; please paraphrase.

Methods:

• “Patients with vascular invasion and distant specialties were excluded.” This sentence is vague, what do the authors mean here?

• Several grammatical errors in the following sentence; please improve.

“Liver cirrhosis is diagnosed based on "Chinese consensus on the management of liver cirrhosis". Diagnosis basis of liver cirrhosis and hypersplenism by computerized tomography (CT): (1) The hepatic fissure was obviously widened, the hepatic margin showed wavy features, and the gallbladder was displaced, the gallbladder fossa was enlarged to a large extent, accompanied by imaging features such as uneven density of liver parenchyma, portal vein was thickened, collateral circulation was formed, splenomegaly and portal hypertension were observed. (2) Splenomegaly was diagnosed when the maximum splenic diameter (maximum anteroposterior size of the splenic hilum) exceeded 12 cm on CT transverse plane.”

• “Patients were divided into Group A and Group B according to the different methods of splenic artery embolization. Group A superselective splenic artery branch embolization,while Group B using conventional PSE.”

Paraphrase to: “Patients were divided into Group A and Group B according to the different methods of splenic artery embolization. Group A included patients who underwent superselective splenic artery branch embolization, while Group B included those who were managed with conventional PSE”.

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Analysis of the efficacy of splenic artery superselective embolization in cirrhosis with hepatocellular carcinoma

PONE-D-24-23322R4

Dear Dr. Zhao,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: This revised manuscript demonstrates substantial improvements compared to the previous version, with comprehensive modifications that effectively address the reviewers' comments. Notably, the author has implemented significant grammatical enhancements throughout the paper, resulting in a polished presentation that fully complies with the journal's publication standards. Considering these substantial refinements in both content and linguistic quality, I strongly recommend acceptance for publication.

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #3: No

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