Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: A systematic review and meta-analysis

Xiaohong Chen; Lifang Feng; Hui Yao; Luhong Yang; Yuan Qin

doi:10.1371/journal.pone.0246463

Peer Review History

Original SubmissionJune 6, 2020
2 Nov 2020 Decision Letter - Cho Naing, Editor PONE-D-20-17226 Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis PLOS ONE Dear Dr. Chen, 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 Dec 17 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Cho Naing, MBBS, PhD, FRCP 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. Please confirm that you have included all items recommended in the PRISMA checklist including the full electronic search strategy used to identify studies with all search terms and limits for at least one database. 3.In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ Additional Editor Comments (if provided): This is an interesting research area. The authors can improve the quality of their manuscript. Introduction The authors need to state the objective in the last paragraph, although it has been described in the Abstract Methods The authors need to improve this section. Study selection It will be informative to provide more details of search strategy used for Embase in appendix. Study selections The authors have indicated clinical studies as an inclusion criteria. However, it has indicated in the abstract that cohort studies are included. The quality assessment use was the NOS checklist. Hence, the included studies were observational type, rather than clinical studies. Please, provide what type of observational studies....... Only cohort or/ and case-control designs. In Table 1, please add 1 more column for study design. Data extraction Please, indicate the initials of two authors who had done study selection/data extraction Statistical analysis It is essential to describe the outcome measurement ( e.g OR or RR and its 95%CI). To be more informative, please define the response rate (e.g what is numerator/ denominator, etc) Reference In addition to #21 (Lu et al).......... It will be better to refer Higgins et al 2019 ( available from the Cochrane Library website) . Thank you [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: Overall, the manuscript was well written, and presented adequate study methodology, results and discussion. Some minor clarifications are required on the following. Discussion Para 2, Line 2: “Its use has increased… having more babies than ever before.” – This statement is unclear. Para 2, Line 9: “However, the exception is that children with ABCC8 mutation respond to diazoxide, indicating cellular adaptation and red blood cells”- The statement regarding red blood is unclear ****** 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 [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.0246463.r001
Revision 1
9 Dec 2020 Author Response Dear editor, On behalf of all co-authors, we would like to express our great appreciation to you and the reviewers for your positive, constructive and insightful comments on our manuscript entitled “Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis”. These comments and suggestions are really helpful in improving the quality of our manuscript. Accordingly, we have revised the manuscript. In addition, point-by-point responses to the editor’s and reviewers’ comments are listed below. We, again, thank you and the reviewers for your constructive comments and hope that the revision is acceptable for publication in your journal. We are looking forward to hearing from you soon. Sincerely, Point-by-point responses to the editor’s comments: Important Comments: Comment 1: Introduction The authors need to state the objective in the last paragraph, although it has been described in the Abstract. Response: We thank you for this kind reminding. Accordingly, we have added it to Introduction in the newly revised version. Comment 2: Study selection It will be informative to provide more details of search strategy used for Embase in appendix. Response: As suggested, we have added it in the newly revised version (Table S1). Comment 3: The authors have indicated clinical studies as an inclusion criteria. However, it has indicated in the abstract that cohort studies are included. The quality assessment use was the NOS checklist. Hence, the included studies were observational type, rather than clinical studies. Please, provide what type of observational studies....... Only cohort or/ and case-control designs. In Table 1, please add 1 more column for study design. Response: Thanks for this kind suggestion, we have added it to Table 1 in the newly revised version. Comment 4: Data extraction Please, indicate the initials of two authors who had done study selection/data extraction. Response: Thanks for this kind suggestion, we have added them in the newly revised version. Comment 5: Statistical analysis It is essential to describe the outcome measurement ( e.g OR or RR and its 95%CI). To be more informative, please define the response rate (e.g what is numerator/ denominator, etc). Response: Thanks for this kind suggestion, we have added them to Statistical analysis in the newly revised version. Comment 6: Reference. In addition to #21 (Lu et al).......... It will be better to refer Higgins et al 2019 (available from the Cochrane Library website). Response: Thanks for this kind suggestion, we have added it to Reference in the newly revised version. Point-by-point responses to the reviewer’s comments: Reviewer #1: Important Comments: Comment 1: Overall, the manuscript was well written, and presented adequate study methodology, results and discussion. Some minor clarifications are required on the following. Response: It is pleasing to have acknowledged our diligence in completed this manuscript. We appreciate the reviewer’s kindly comments. Comment 2: Discussion Para 2, Line 2: “Its use has increased… having more babies than ever before.” – This statement is unclear. Response: Thanks for this kind suggestion, we have rewritten them in the newly revised version. Comment 3: Para 2, Line 9: “However, the exception is that children with ABCC8 mutation respond to diazoxide, indicating cellular adaptation and red blood cells”- The statement regarding red blood is unclear. Response: Thanks for this kind suggestion, we have rewritten them in the newly revised version. Attachments Attachment Submitted filename: Response Letter.doc https://doi.org/10.1371/journal.pone.0246463.r002
14 Dec 2020 Decision Letter - Cho Naing, Editor PONE-D-20-17226R1 Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis PLOS ONE Dear Dr. Chen, 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 Jan 28 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Cho Naing, MBBS, PhD, FRCP Academic Editor PLOS ONE Additional Editor Comments (if provided): The current analysis was based on six cohort studies. In the Background, six clinical studies. Please make a correction. The inclusion criteria were as follows: (1) clinical studies focusing on ..................... This was incorrect. The authors have selected only cohort studies. No clinical studies. Plese update this. selection criteria. I have already highlighted this point in initial comments. The authors still need substantial improvements in grammar/language throughout the text Examples, In abstrct The meta-analysis of the efficacy and safety of diazoxidein treating HH was performed by searching the PubMed, Embase, .............. Two missing words "relevant studies" between searching the and PubMed, A total of 6studies, ................... It should be presented 'a total of six cohort studies'., Among the cohort studies, the pooled estimate of patients who were diazoxide responsive was 71% (95% CI 50%–93%.................. Please rephrase this sentence by adding pool estimates of what outcome. In Text A meta-analysis of cohorts based on the random-effects............................ It should describe 'cohort studies, instead of cohorts. . [Note: HTML markup is below. Please do not edit.] [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.0246463.r003
Revision 2
30 Dec 2020 Author Response Dear editor, On behalf of all co-authors, we would like to express our great appreciation to you for your positive and constructive comments on our manuscript entitled “Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis”. These comments and suggestions are really helpful in improving the quality of our manuscript. Accordingly, we have revised the manuscript. In addition, point-by-point responses to the editor’s comments are listed below. We hope that the revision is acceptable for publication in your journal. We are looking forward to hearing from you soon. Sincerely, Point-by-point responses to the editor’s comments: Important Comments: Comment 1: The current analysis was based on six cohort studies. In the Background, six clinical studies. Please make a correction. Response: Accordingly, we have corrected it in the newly revised version. Comment 2: The inclusion criteria were as follows: (1) clinical studies focusing on ..................... This was incorrect. The authors have selected only cohort studies. No clinical studies. Plese update this. selection criteria. I have already highlighted this point in initial comments. Response: Accordingly, we have corrected it in the newly revised version. Comment 3: The authors still need substantial improvements in grammar/language throughout the text. Examples, In abstract The meta-analysis of the efficacy and safety of diazoxidein treating HH was performed by searching the PubMed, Embase, .............. Two missing words "relevant studies" between searching the and PubMed, A total of 6studies, ................... It should be presented 'a total of six cohort studies'., Among the cohort studies, the pooled estimate of patients who were diazoxide responsive was 71% (95% CI 50%–93%.................. Please rephrase this sentence by adding pool estimates of what outcome. In Text A meta-analysis of cohorts based on the random-effects............................ It should describe 'cohort studies, instead of cohorts. . Response: Accordingly, we have carefully proofread the manuscript and corrected the spelling and grammatical errors in the revised manuscript. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0246463.r004
6 Jan 2021 Decision Letter - Cho Naing, Editor PONE-D-20-17226R2 Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis PLOS ONE Dear Dr. Chen, 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 Feb 20 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Cho Naing, MBBS, PhD, FRCP Academic Editor PLOS ONE Additional Editor Comments (if provided): The authors have addressed almost all comments provided. 1) It is necessary to include your revised text in your reply to the comments. 2) The authors have to update literature search whether there may be additional published studies after your initial search in 2019. This is crucially important in this field as the evidence must be based on comprehensive review of all eligible studies. Thank you [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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.0246463.r005
Revision 3
18 Jan 2021 Author Response Dear editor, On behalf of all co-authors, we would like to express our great appreciation to you for your positive and constructive comments on our manuscript titled “Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis.” These comments and suggestions are really helpful in improving the quality of our manuscript. Accordingly, we have revised the manuscript. In addition, point-by-point responses to the editor’s comments are listed below. We hope that the revision is acceptable for publication in your journal. We look forward to hearing from you soon. Sincerely, Point-by-point responses to the editor’s comments: Important Comments: Comment 1: The current analysis was based on six cohort studies. In the Background, six clinical studies. Please make a correction. Response: Thank you for the comments. We have corrected it in the revised version. Revised text: “This meta-analysis based on six cohort studies was conducted and aimed to investigate the efficacy and safety of diazoxide for treating CHI.” Comment 2: The inclusion criteria were as follows: (1) clinical studies focusing on ..................... This was incorrect. The authors have selected only cohort studies. No clinical studies. Please update this. selection criteria. I have already highlighted this point in initial comments. Response: Thank you for the comments. We have corrected it in the revised version. Revised text: “Cohort studies focusing on the efficacy and safety of diazoxide in treating HH.” Comment 3: The authors still need substantial improvements in grammar/language throughout the text. Examples, In abstract The meta-analysis of the efficacy and safety of diazoxidein treating HH was performed by searching the PubMed, Embase, .............. Two missing words "relevant studies" between searching the and PubMed, A total of 6studies, ................... It should be presented 'a total of six cohort studies'., Among the cohort studies, the pooled estimate of patients who were diazoxide responsive was 71% (95% CI 50%–93%.................. Please rephrase this sentence by adding pool estimates of what outcome. In Text A meta-analysis of cohorts based on the random-effects............................ It should describe 'cohort studies, instead of cohorts. . Response: Thank you for the suggestion. We have carefully proofread the manuscript and corrected the spelling and grammatical errors in the revised manuscript. Revised text: “The meta-analysis of the efficacy and safety of diazoxide in treating HH was performed by searching relevant studies in the PubMed, Embase, and Cochrane databases.” “A total of 6 cohort studies, involving 1142 participants, met the inclusion criteria.” “Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71%.” “A meta-analysis of cohort studies based on the random-effects model was conducted to evaluate the clinical response rate.” Comment 4: The authors have to update literature search whether there may be additional published studies after your initial search in 2019. This is crucially important in this field as the evidence must be based on comprehensive review of all eligible studies. Response: Thank you for the suggestion. The literature search has been updated up to January 2021. Revised text: “The PubMed, Embase, and Cochrane databases were searched for studies published up to January 2021.” “The electronic search identified 348 studies. Three additional studies were found by hand searching from the reference lists of other review studies. According to the inclusion criteria, 227 studies remained after removing the duplicates. Subsequently, 193 irrelevant studies were excluded. Of the remaining 34 studies, 15 were letters, reviews, and meta-analyses, and hence excluded. The remaining studies were systematically reviewed, and 19 were qualified for full-text reading. After full-text reading, five studies not focusing on children, three lacking usable data, and five case reports were excluded.” (Figure 1) Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0246463.r006
20 Jan 2021 Decision Letter - Cho Naing, Editor Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis PONE-D-20-17226R3 Dear Dr. Chen, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Cho Naing, MBBS, PhD, FRCP Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have addressed the comments. Thank you Reviewers' comments: https://doi.org/10.1371/journal.pone.0246463.r007
Formally Accepted
2 Feb 2021 Acceptance Letter - Cho Naing, Editor PONE-D-20-17226R3 Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis Dear Dr. Chen: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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 Professor Cho Naing Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0246463.r008

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 .