Overall success rate of permanent teeth pulpotomy using ProRoot MTA: A systematic review and meta-analysis of randomized clinical trials

Emmanuel J. N. L. Silva; Karem P. Pinto; Mahmoud Torabinejad; Estefano B. Sarmento; Jorge N. R. Martins; Marco A. Versiani; Gustavo De-Deus

doi:10.1371/journal.pone.0320838

Peer Review History

Original SubmissionSeptember 11, 2024
11 Sep 2024 Author Response Attachments Attachment Submitted filename: Rebuttal letter.docx https://doi.org/10.1371/journal.pone.0320838.r001
3 Jan 2025 Decision Letter - Mohmed Isaqali Karobari, Editor PONE-D-24-38286Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trialsPLOS ONE Dear Dr. Silva, 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. ============================== Dear Authors, Kindly read all the comments given by the reviewers carefully and address them; make the changes in the revised manuscript accordingly. Best regards and keep well ============================== Please submit your revised manuscript by Feb 17 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, Mohmed Isaqali Karobari, BDS, MScD.Endo, Ph.D. Endo, FDS, FPFA, MFDS Academic Editor PLOS ONE Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Peer review at PLOS ONE is not double-blinded (https://journals.plos.org/plosone/s/editorial-and-peer-review-process). For this reason, authors should include in the revised manuscript all the information removed for blind review. 3. As required by our policy on Data Availability, please ensure your manuscript or supplementary information includes the following: A numbered table of all studies identified in the literature search, including those that were excluded from the analyses. For every excluded study, the table should list the reason(s) for exclusion. If any of the included studies are unpublished, include a link (URL) to the primary source or detailed information about how the content can be accessed. A table of all data extracted from the primary research sources for the systematic review and/or meta-analysis. The table must include the following information for each study: Name of data extractors and date of data extraction Confirmation that the study was eligible to be included in the review. All data extracted from each study for the reported systematic review and/or meta-analysis that would be needed to replicate your analyses. If data or supporting information were obtained from another source (e.g. correspondence with the author of the original research article), please provide the source of data and dates on which the data/information were obtained by your research group. If applicable for your analysis, a table showing the completed risk of bias and quality/certainty assessments for each study or outcome. Please ensure this is provided for each domain or parameter assessed. For example, if you used the Cochrane risk-of-bias tool for randomized trials, provide answers to each of the signalling questions for each study. If you used GRADE to assess certainty of evidence, provide judgements about each of the quality of evidence factor. This should be provided for each outcome. An explanation of how missing data were handled. This information can be included in the main text, supplementary information, or relevant data repository. Please note that providing these underlying data is a requirement for publication in this journal, and if these data are not provided your manuscript might be rejected. Additional Editor Comments: Dear Authors, Kindly read all the comments given by the reviewers carefully and address them; make the changes in the revised manuscript accordingly. Best regards and keep well [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. 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: Yes Reviewer #3: Yes Reviewer #4: No ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ****** 3. 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: Yes Reviewer #3: Yes Reviewer #4: Yes ****** 4. 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: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ****** 5. 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: I thank the Editorial Board of PLoS One for the opportunity to review the manuscript titled "Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trials." I commend the authors for their efforts on the manuscript so far. However, the article has significant limitations that cannot be addressed through revision, which prevents me from recommending its publication. Despite the efforts to meta-analyze the data, the data handling was not appropriate. First, a fixed-effect analysis assumes that all studies evaluated a common true effect and that the differences among the results are due only to chance or sampling error. However, upon reviewing the included studies, there are potential sources of discrepancies, whether due to diagnostic criteria, sample characteristics, the pulpotomy protocol applied, or even the potential biases identified by the RoB assessment. The subgroup analysis does not align with the stated objective; a meta-regression would be more appropriate. Furthermore, treatment-related protocols were not even considered by the authors, except for the biomaterial used. While I understand this is the primary focus of the study, the pulpotomy technique is far more comprehensive, and its outcome is not solely dependent on the capping biomaterial used. In addition, There is a clear lack of novelty in the review, and the data duplicates findings from other recently published reviews with a more focused research question. Other reviews have investigated the outcomes of pulpotomy in various aspects: partial vs. total, immature vs. mature teeth, irreversible vs. reversible pulpitis, or even according to the etiology of the indication. Moreover, the findings of this review have already been confirmed in the literature, where the success rate of pulpotomy using ProRoot MTA is significantly higher than when using calcium hydroxide. Please refer to (1) Silva EJNL, Pinto KP, Belladonna FG, Ferreira CMA, Versiani MA, De-Deus G. Success rate of permanent teeth pulpotomy using bioactive materials: A systematic review and meta-analysis of randomized clinical trials. Int Endod J. 2023 Sep;56(9):1024-1041. doi: 10.1111/iej.13939. (2) Li W, Yang B, Shi J. Efficacy of pulpotomy for permanent teeth with carious pulp exposure: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024 Jul 5;19(7). doi: 10.1371/journal.pone.0305218. Reviewer #2: The submitted paper, titled "Overall Success Rate of Permanent Teeth Pulpotomy Using ProRoot MTA: A Systematic Review and Meta-Analysis of Randomized Clinical Trials," aimed to evaluate the success rate of pulpotomy in permanent teeth using ProRoot MTA through a systematic review and meta-analysis. This review is highly relevant to the field of Endodontics and adheres to established guidelines. Overall, the paper is well-written. This reviewer has only minor suggestions to enhance its readability. Minor comments: - Page 2. Abstract: Replace "RevMan 5.3 and R software" with "RevMan 5.3 and R softwares." - Page 5. Line 4: Correct "MTA been established" to "MTA has been established." - Page 5. Line 8: Include the city, state, and country of Dentsply Tulsa Dental. - Page 6. Line 4 (Search strategy): The phrase "The search was performed without any filters, language restrictions, or August 2024" is incomplete and requires clarification. - Page 12. Line 2: Replace "evolved" with "involved." - Page 12. Line 8: Use the abbreviation AFR (Annual Failure Rate), as it was already defined earlier. - Page 16: Revise "the remaining nine studies were categorized as having a low risk of bias" to reflect the correct number of studies, which is likely 12. - Page 16. Line 3 (Meta-analysis): Use the abbreviation AFR instead of the full term Annual Failure Rate. - Page 17. Line 1: Change "The assessment of 23 studies" to "The assessment of 26 studies," as the correct number is 26. - Page 17. Line 1: Use AFR for consistency instead of spelling out Annual Failure Rate. - Page 17. Line 9: The phrase "Random-effect models were employed as heterogeneity could not be established" appears incomplete and needs clarification or additional context. - Page 19. Line 5: Replace "randomized clinical trials was to assess" with "RCTs was to assess." - Page 19. Line 7: Use AFR instead of spelling out Annual Failure Rate. - Page 19. Line 8: Correct the Annual Failure Rate to 8%, as the reported value is incorrect. - Page 19: Revise "In this review, it was observed that permanent teeth of younger patients with an open apex displayed notably higher success rates in comparison to mature teeth, respectively." The word "respectively" seems misplaced and should be removed or rephrased for clarity. Reviewer #3: Thank you for the opportunity to review the manuscript titled “Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trials.” I am pleased to inform you that I found the manuscript to be exceptionally well-written, with a clear and concise presentation of the research. The authors have done an excellent job in articulating their findings and supporting them with robust evidence. I have no recommendations for revisions or improvements, as the manuscript meets the high standards expected for publication in PLOS One. Reviewer #4: The article present relevant information for Endodontic practice and it was well designed. This article will show that MTA is still relevant and that bioceramic cements are not as essential as they are trying to make them out to be. ****** 6. 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 #1: No Reviewer #2: No Reviewer #3: No Reviewer #4: 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. https://doi.org/10.1371/journal.pone.0320838.r002
Revision 1
23 Jan 2025 Author Response Dear Dr. Mohmed Isaqali Karobari Academic Editor of PLOS ONE On behalf of co-authors, I am submitting the revised version of the manuscript PONE-D-24-38286 entitled Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trials to the PLoS One Journal. We would like to express our gratitude to you and the reviewers for their meticulous and insightful review of our work. Considering their valuable suggestions and comments, we have made some revisions to the manuscript. To clearly highlight these changes, we have marked them in blue throughout the document. We appreciate the opportunity to contribute to the PLoS One Journal and look forward to your favorable decision. Reviewer #1 I thank the Editorial Board of PLoS One for the opportunity to review the manuscript titled "Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trials." I commend the authors for their efforts on the manuscript so far. However, the article has significant limitations that cannot be addressed through revision, which prevents me from recommending its publication. Response: We thank Reviewer #1 for their thorough review and constructive comments on our manuscript. Below, we address each concern point by point, providing clarifications and justifications for our methodology and approach. 1. Despite the efforts to meta-analyze the data, the data handling was not appropriate. First, a fixed-effect analysis assumes that all studies evaluated a common true effect and that the differences among the results are due only to chance or sampling error. However, upon reviewing the included studies, there are potential sources of discrepancies, whether due to diagnostic criteria, sample characteristics, the pulpotomy protocol applied, or even the potential biases identified by the RoB assessment. Response: We thank the reviewer concern. We also acknowledge the reviewer’s observation regarding the fixed-effect model. We chose this model because the statistical heterogeneity observed in our analyses was minimal, with I² values ranging from 0% to 20%. This indicator supports the appropriateness of a fixed-effect model in this context. Moreover, random-effects models were used in subgroup analyses where heterogeneity was higher. Importantly, this approach was conducted following the advice of our Biostatistical Advisor, who recommended using fixed-effect models for overall analyses with low heterogeneity and random-effects models for subgroup analyses to ensure methodological accuracy. Our approach aligns with established meta-analytic practices and ensures that the data handling reflects the characteristics of the included studies. 2. The subgroup analysis does not align with the stated objective; a meta-regression would be more appropriate. Response: We also thank the reviewer for this concern. Although we understand the reviewer comment, we opted for subgroup analyses rather than meta-regression due to the limited number of included studies and the lack of sufficient covariates to perform a reliable meta-regression. Subgroup analyses allowed us to explore variations in success rates across key factors while maintaining statistical robustness. Conducting meta-regression with sparse data could risk overfitting and lead to unreliable conclusions, which we aimed to avoid. This approach was also recommended by our Biostatistical Advisor, who emphasized that subgroup analyses were the most suitable method given the data characteristics and the study design. 3. Furthermore, treatment-related protocols were not even considered by the authors, except for the biomaterial used. While I understand this is the primary focus of the study, the pulpotomy technique is far more comprehensive, and its outcome is not solely dependent on the capping biomaterial used. Response: We thank the reviewer for this comment which is interesting indeed. While we agree that pulpotomy outcomes are influenced by multiple factors, our study's primary focus was on evaluating the success rate of ProRoot MTA as a capping material. However, we did consider and discuss other treatment-related factors, such as the type of pulpotomy (partial or full), root maturity, and pulpal diagnosis, in our subgroup analyses. A more comprehensive evaluation of additional treatment protocols (such as hemostatic agents, operator expertise) could be an avenue for future research, as detailed in the end of our discussion section. 4. In addition, there is a clear lack of novelty in the review, and the data duplicates findings from other recently published reviews with a more focused research question. Other reviews have investigated the outcomes of pulpotomy in various aspects: partial vs. total, immature vs. mature teeth, irreversible vs. reversible pulpitis, or even according to the etiology of the indication. Response: We thank the reviewer for this comment. In our point of view, the present systematic review provides a unique contribution by exclusively focusing on ProRoot MTA, the most extensively studied MTA brand, and consolidating evidence from randomized clinical trials. While other reviews have explored broader or more specific aspects of pulpotomy, none have comprehensively synthesized RCT data on ProRoot MTA’s overall success rate in permanent teeth across various contexts. This focused approach ensures clinically relevant insights for practitioners using this specific biomaterial. Furthermore, we explicitly acknowledge in the Introduction section the existence of prior systematic reviews and discuss their limitations, such as selective inclusion criteria and narrower scopes. Our work builds upon these prior efforts to address these gaps and provide a comprehensive and clinically valuable synthesis of the available evidence. However, in order to avoid disappointing the reviewer, we have added it now to a new limitations sentence in the Discussion. 5. Moreover, the findings of this review have already been confirmed in the literature, where the success rate of pulpotomy using ProRoot MTA is significantly higher than when using calcium hydroxide. Response: We have appreciated the reviewer concern. In our perspective, while the higher success rate of ProRoot MTA compared to calcium hydroxide is documented, our study extends this knowledge by presenting an updated and rigorous meta-analysis of 26 RCTs. Additionally, we evaluated success rates at multiple follow-up periods (6, 12, and 24 months), assessed the annual failure rate, and conducted subgroup analyses, offering a more granular understanding of ProRoot MTA’s performance in different clinical scenarios. 6. Please refer to (1) Silva EJNL, Pinto KP, Belladonna FG, Ferreira CMA, Versiani MA, De-Deus G. Success rate of permanent teeth pulpotomy using bioactive materials: A systematic review and meta-analysis of randomized clinical trials. Int Endod J. 2023 Sep;56(9):1024-1041. doi: 10.1111/iej.13939. (2) Li W, Yang B, Shi J. Efficacy of pulpotomy for permanent teeth with carious pulp exposure: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024 Jul 5;19(7). doi: 10.1371/journal.pone.0305218. Response: We appreciate this recommendation. The study (1) was already part of the bibliographic reference list, while the study (2) has now been added. Reviewer #2 The submitted paper, titled "Overall Success Rate of Permanent Teeth Pulpotomy Using ProRoot MTA: A Systematic Review and Meta-Analysis of Randomized Clinical Trials," aimed to evaluate the success rate of pulpotomy in permanent teeth using ProRoot MTA through a systematic review and meta-analysis. This review is highly relevant to the field of Endodontics and adheres to established guidelines. Overall, the paper is well-written. This reviewer has only minor suggestions to enhance its readability. Response: We thank Reviewer #2 for their thorough review and constructive comments on our manuscript. All requested changes were performed as suggested by the reviewer. Minor comments: - Page 2. Abstract: Replace "RevMan 5.3 and R software" with "RevMan 5.3 and R softwares." Response: Considering that “software” is an uncountable noun, the plural should be software. Therefore, in this specific point we do not made any modification. - Page 5. Line 4: Correct "MTA been established" to "MTA has been established." Response: Thank you! We have changed. - Page 5. Line 8: Include the city, state, and country of Dentsply Tulsa Dental. Response: It was added as suggested by the reviewer. - Page 6. Line 4 (Search strategy): The phrase "The search was performed without any filters, language restrictions, or August 2024" is incomplete and requires clarification. Response: Thank you! We have changed! - Page 12. Line 2: Replace "evolved" with "involved." Response: Thank you! We have changed! - Page 12. Line 8: Use the abbreviation AFR (Annual Failure Rate), as it was already defined earlier. Response: Thank you! We have changed! - Page 16: Revise "the remaining nine studies were categorized as having a low risk of bias" to reflect the correct number of studies, which is likely 12. Response: Thank you! It was changed. - Page 16. Line 3 (Meta-analysis): Use the abbreviation AFR instead of the full term Annual Failure Rate. Response: Thank you! We have changed! - Page 17. Line 1: Change "The assessment of 23 studies" to "The assessment of 26 studies," as the correct number is 26. Response: In fact for this specific assessment 23 studies were evaluated. Please check figure 4. - Page 17. Line 1: Use AFR for consistency instead of spelling out Annual Failure Rate. Response: Thank you! We have changed! - Page 17. Line 9: The phrase "Random-effect models were employed as heterogeneity could not be established" appears incomplete and needs clarification or additional context. Response: Thank you! We have changed! - Page 19. Line 5: Replace "randomized clinical trials was to assess" with "RCTs was to assess." Response: Thank you! We have eliminated RCT and used randomized clinical trial in the entire manuscript. - Page 19. Line 7: Use AFR instead of spelling out Annual Failure Rate. Response: Thank you! We have changed - Page 19. Line 8: Correct the Annual Failure Rate to 8%, as the reported value is incorrect. Response: Thank you! We have changed - Page 19: Revise "In this review, it was observed that permanent teeth of younger patients with an open apex displayed notably higher success rates in comparison to mature teeth, respectively." The word "respectively" seems misplaced and should be removed or rephrased for clarity. Response: Thank you! It was removed. Reviewer #3 Thank you for the opportunity to review the manuscript titled “Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trials.” I am pleased to inform you that I found the manuscript to be exceptionally well-written, with a clear and concise presentation of the research. The authors have done an excellent job in articulating their findings and supporting them with robust evidence. I have no recommendations for revisions or improvements, as the manuscript meets the high standards expected for publication in PLOS One. Response: We thank Reviewer #3 for their thorough review and constructive comments on our manuscript Reviewer #4 The article present relevant information for Endodontic practice and it was well designed. This article will show that MTA is still relevant and that bioceramic cements are not as essential as they are trying to make them out to be. Response: We thank Reviewer #4 for their thorough review and constructive comments on our manuscript Attachments Attachment Submitted filename: Response to the reviewers.docx https://doi.org/10.1371/journal.pone.0320838.r003
26 Feb 2025 Decision Letter - Mohmed Isaqali Karobari, Editor Overall success rate of permanent teeth pulpotomy using ProRoot MTA: a systematic review and meta-analysis of randomized clinical trials PONE-D-24-38286R1 Dear Dr. Silva, 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, Mohmed Isaqali Karobari, BDS, MScD.Endo, Ph.D. Endo, FDS, FPFA, MFDS Academic Editor PLOS ONE Additional Editor Comments (optional): Dear Authors, The authors have addressed all the comments and suggestions reviewers gave, and the manuscript has dramatically improved. The manuscript can be accepted for publication in its current form. I would like to congratulate the authors and wish them all the very best in their future endeavours. Best regards and keep well 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 #2: All comments have been addressed ******** 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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: 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 #2: 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 #2: 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 #2: This reviewer would like to thank the authors for the modifications made. I accept the paper in its current form. ****** 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 #2: No ******** https://doi.org/10.1371/journal.pone.0320838.r004
Formally Accepted
Acceptance Letter - Mohmed Isaqali Karobari, Editor PONE-D-24-38286R1 PLOS ONE Dear Dr. Silva, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Prof Dr. Mohmed Isaqali Karobari Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0320838.r005

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .