Reasons for encounter in primary care among French patients: Gender differences in presentation rates more pronounced among the patients of male practitioners

Eugenia Alcalde; Laurent Rigal; Henri Panjo; Laurent Letrilliart; Colinne Patrice

doi:10.1371/journal.pone.0345781

Peer Review History

Original SubmissionAugust 26, 2025
8 Oct 2025 Decision Letter - Li-Da Wu, Editor Dear Dr. Patrice, 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 22 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.. 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. 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 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 . 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, 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 and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. 3. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. 4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 5. Thank you for stating the following financial disclosure: “The author(s) received no specific funding for this work.” At this time, please address the following queries: a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b) State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c) If any authors received a salary from any of your funders, please state which authors and which funders. d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 6. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 7. 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. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Partly Reviewer #2: Partly Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #1: The study topic is good, but it is not completely clear and needs to be clarified, especially with regard to the study summary. The study needs to detail the methodology, the summary, and even the results, and why gender affects medical issues. Reviewer #2: The article provides a relevant analysis of gender differences in reasons for encounter in primary care, based on a large and representative dataset from France. The findings are valuable and the manuscript is well structured. However, it is important for the authors to clarify that the results are not directly generalizable to the present context, since gender ideologies and the distribution of male and female physicians have changed in the last decade. In addition, the manuscript would benefit from a deeper consideration of the interaction between gender and age, for example discussing whether younger men and older men differ in consultation patterns, or explaining why this aspect was not explored. Overall, the study is suitable for publication and represents a relevant contribution, but it would be strengthened by these additions to the discussion. Reviewer #3: Abstract: 1. Line 27- You should show the (abbreviation) for general practitioner (GP). Line 31—You use GP, but it is not defined earlier. 2. Line 34 – Capitalize “To.” Introduction 1. Recommend that authors provide background on the French healthcare system. For example, do patients have the flexibility to visit different GPs? What are insurance restrictions, if any, on seeking providers? You provide some insight into the health system now in the strengths and limitations section, but I recommend providing some details earlier in the paper. Methods 1. Clarify if the GP was present while the intern collected data on RfE and/or symptoms and complaints. 2. Were these first visits to the particular GP? Did the survey include a question specific to the number of times the patient has seen this particular GP, and if these were follow-up visits related to the chief health complaint? If so, adding these variables to your analysis could further explain gender preferences. 3. Please explain/state whether or not incentives were given to the GPs, interns, or patients for participating in the data collection? Discussion 1. Recommend that authors address whether the gender of the intern made a difference in patient communicated complaint or RfE, in addition to the gender of the supervising GP. Conclusion 2. Suggest that the authors state that future studies, collecting data over several time points, could explore whether patients remained with their gender-preferred GP once the health complaint resolved. ****** what does this mean? ). If published, this will include your full peer review and any attached files.). 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 For information about this choice, including consent withdrawal, please see our Privacy Policy .--> Reviewer #1: No Reviewer #2: No 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 . 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.. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0345781.r001
Revision 1
12 Jan 2026 Author Response Dear Editor and Reviewers, Thank you for taking the time to review our article, and for your important remarks. You will find our point by point answers to the comments made in the Decision Letter below, in the body text. I have also joined a document in the "Attach files section" with these anwers highlighted in color for more clarity. 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 provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. Thank you for these important remarks. We have added information about patients' consent to participate in the study: [Line 113 from the Methods section/Study design] : Patients were given oral and visual information about the study, including the presence of the intern. Verbal consent was obtained from patients or the parents of minor participants. Patients could refuse the intern's presence while still participating in the study, or refuse both. Visits for which patients refused participation were excluded. [Line 122 from the Methods section/Study design] A declaration was filed with the former Advisory Committee on the Processing of Information in Health Research (CCTIRS, active at the time ECOGEN was designed) and then with the National Commission for Information Technology and Civil Liberties (CNIL) – both advisory boards approved the research methodology. Further, the ECOGEN survey was approved by Ethics Committee Sud-Est IV (No.L11-149), which explicitly approved the oral form of consent obtained from patients 3. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. Thank you for this remark. The data is available by request at the Université Claude Bernard Lyon 1 (UCBL), where they are stored on the UCBL servers. 4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Thank you for this remark. We have modified our statements and added the information to the article. [Ligne 359 from Disclosure statement] “The ECOGEN study was supported by the French National College of teachers in general practice via a grant from Pfizer laboratories (grant number not applicable), received by Laurent Letrillart. Eugenia Alcalde was funded by the Gender and Health Inequalities (GENDHI) project (grant agreement No. [ERC-2019-SyG n° 856478]). This funding had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” 5. Thank you for stating the following financial disclosure: “The author(s) received no specific funding for this work.” At this time, please address the following queries: a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b) State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c) If any authors received a salary from any of your funders, please state which authors and which funders. d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Thank you for this remark. a) The ECOGEN study was supported by the French National College of teachers in general practice via a grant from Pfizer laboratories (grant number not applicable), received by Laurent Letrillart. Eugenia Alcalde was funded by the Gender and Health Inequalities (GENDHI) project (grant agreement No. [ERC-2019-SyG n° 856478]). This funding had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The rest of the authors had no relevant or material financial interests that relate to the research described in this paper b) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. c) None of the authors received a salary from the funders. We have included the amended statement to our revised cover letter. 6. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 7. 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. 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: Partly Reviewer #2: Partly Reviewer #3: Yes ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 ________________________________________ 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 ________________________________________ 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: The study topic is good, but it is not completely clear and needs to be clarified, especially with regard to the study summary. The study needs to detail the methodology, the summary, and even the results, and why gender affects medical issues. We’d like to thank the reviewer for this global comment. We agree that our summary lacks clarity. We have modified all sections as follows: Background: Evidence has shown that the gender of general practitioners (GPs) and of patients plays a role in primary care, both in communication and practice style. However, less is known about how both genders interact in the reasons for encounter (RfE). Studying RfEs by both patient and GP gender may help elucidate what symptoms or complaints lead women and men to consult a GP and specifically, if patients have preferences regarding the gender of their GP for specific problems. Given that men tend to consult less frequently and are often diagnosed at later stages of disease, it is essential to disentangle whether GP gender may act as a barrier for men in disclosing certain health concerns. Then, in the methods section: Methods: This is an ancillary study from the French ECOGEN survey, an observational cross-sectional multicentre study conducted between November 2011 and April 2012. 54 GP interns working alongside 128 GP supervisors collected RfEs during consultations. Using mixed models, we first assessed the association between patient gender and each RfE chapter (i.e., 13 independent variables) among all patients. We then stratified models according to GP gender. Finally, we compared the four physician–patient gender dyads (male physician–male patient, male physician–female patient, female physician–male patient, and female physician–female patient) in pairwise analyses. The results section: Results: Overall, 20 613 patients were included, of whom 58% were women. Of the 128 participating GPs, 85 were men. Women patients had higher presentation rates across all chapters. The most common RfE were those related to the respiratory system. Modest differences in presentation rates were observed between men and women when visiting male GPs, with men being less likely to present RfEs from the General and Unspecified, Digestive, Eyes, Ears, Neurological, and Respiratory chapters. And finally the conclusion statement: Conclusions: Our study adds evidence on how gender plays a role in presenting or disclosing health concerns in primary care. Specifically, our findings suggest that male patients may be reluctant to present certain RfEs to male GPs. Acknowledging these gender effects in primary care may help strengthen the partnership between GPs and patients. We have also revised certain paragraphs in the introduction to clarify the topic and the relationship between gender and medical issues. [Line 76, Introduction]: ‘One interesting way to analyse this gender gap is to investigate reasons for encounter (RfE), particularly symptoms and complaints, as they reflect what prompts men and women to seek care and what they decide to disclose to their GPs. In other words, RfEs provide insight into how individuals evaluate and prioritize health concerns in their decision-making process to seek help’. [Line 102, Introduction]: ‘Previous studies investigating the effect of patients’ and GPs’ gender on RfE usually present results based on one or the other, but rarely together. As both seem to influence the care process, the challenge lies in distinguishing how they operate within a wide range of RfEs presented in primary care. Given that men consult less frequently and are often diagnosed at later stages of disease, it is important to disentangle whether GP gender may act as a barrier for men in disclosing certain health problems’. Reviewer #2: The article provides a relevant analysis of gender differences in reasons for encounter in primary care, based on a large and representative dataset from France. The findings are valuable and the manuscript is well structured. However, it is important for the authors to clarify that the results are not directly generalizable to the present context, since gender ideologies and the distribution of male and female physicians have changed in the last decade. In addition, the manuscript would benefit from a deeper consideration of the interaction between gender and age, for example discussing whether younger men and older men differ in consultation patterns, or explaining why this aspect was not explored. Overall, the study is suitable for publication and represents a relevant contribution, but it would be strengthened by these additions to the discussion. We’d like to thank the reviewer for this valuable comment. We agree with the fact that our study is likely not generalizable to the present context and that we lacked a more engaged discussion about age and gender interaction. We added these elements in the limitation section: “Regarding our analyses, for simplicity reasons, our models were adjusted for patients’ age, but this did not allow us to assess the interaction between patients’ age and gender when presenting a given RfE. Indeed, it is possible that younger men or women have different attitudes towards GPs when presenting their health problems compared to older counterparts. We believe further studies should address this gap, especially considering how cohort effects regarding gender attitudes have changed in recent years.” About the generalizability to our current context: “Finally, the analysed data were collected over 10 years prior to our study. Since then, many changes in society and medical demographics have occurred, including a potential increase in gender awareness among patients and GPs, as well as the continued feminization of the GP population (31), which makes our results less generalizable to the current context. At the same time, the number of GPs in France declined in recent years until 2021 (32). Although more recent data suggest a slight increase since then (31), the reduced density of GPs per capita (33) may lead people to consult a GP based on availability. For these reasons, the gender of GPs may have less impact on RfEs than before, as people have fewer options. Still, using data from the Attachments Attachment Submitted filename: Response to Reviewers.pdf https://doi.org/10.1371/journal.pone.0345781.r002
10 Mar 2026 Decision Letter - Li-Da Wu, Editor Reasons for encounter in primary care among French patients: gender differences in presentation rates more pronounced among the patients of male practitioners PONE-D-25-38524R1 Dear Dr. Patrice, 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. For questions related to billing, please contact and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .. 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, PLOS One Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> 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??> Reviewer #3: Yes ****** Reviewer #3: I have no additional comments. I am pleased that the authors carefully considered my previous comments and appropriately addressed them. ****** what does this mean? ). If published, this will include your full peer review and any attached files.). 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 For information about this choice, including consent withdrawal, please see our Privacy Policy .--> Reviewer #3: No ******** https://doi.org/10.1371/journal.pone.0345781.r003
Formally Accepted
Acceptance Letter - Li-Da Wu, Editor PONE-D-25-38524R1 PLOS One Dear Dr. Patrice, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. 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 Dr. Li-Da Wu Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0345781.r004

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 .