Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma

Malagobadan Johnathan; Siti Aminah Muhamad; Siew Hua Gan; Johnson Stanslas; Wan Ezumi Mohd Fuad; Faezahtul Arbaeyah Hussain; Wan Amir Nizam Wan Ahmad; Asma Abdullah Nurul

doi:10.1371/journal.pone.0249091

Peer Review History

Original SubmissionNovember 9, 2020
8 Jan 2021 Decision Letter - Yu Ru Kou, Editor PONE-D-20-35276 Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyper-responsiveness in a murine model of asthma PLOS ONE Dear Dr. Nurul, 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. While the reviewer #1 was less critical, the comments from the reviewer #2 were very important. The authors need to effectively respond to their comments in their revision. Please submit your revised manuscript by Feb 19 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, Yu Ru Kou, PhD 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. As part of your revision, please complete and submit a copy of the Full ARRIVE 2.0 Guidelines checklist, a document that aims to improve experimental reporting and reproducibility of animal studies for purposes of post-publication data analysis and reproducibility: https://arriveguidelines.org/sites/arrive/files/Author%20Checklist%20-%20Full.pdf (PDF). Please include your completed checklist as a Supporting Information file. Note that if your paper is accepted for publication, this checklist will be published as part of your article. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 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 ****** 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 ****** 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 objective of the study is to assess the effect of Lignosus rhinocerotis Cooke Ryvarden on airway inflammation, mucus hypersecretion and airway hyper-responsiveness in a murine model of asthma. The manuscript is generally well written and the results are presented in good manner. The data supports the statements in results and discussion. However authors need to address the following. 1) The authors need to discuss the selection of the doses of LRE extract used in the present study. 2) Also need to provide the proper rationale for OVA induced asthma, preferably in the introduction. 3) More recent citations about inflammatory responses and airway hyper responsiveness to be added in the introduction. Reviewer #2: This manuscript examined the effect of lignosus rhinocerotis(LR), a traditional medication, on an allergic asthmatic response in murine. The pretreatment of LR extract suppresses the airway inflammation and airway hyper responsiveness nicely as steroid. The results make significant contributions to applied asthmatic research. 1. This study is descriptive without any intervention design. The authors are encouraged to include more discussion points along possible mechanism. 2. The dose effect of LRE is required in the study. 3. What is the difference between those two allergic model? The rationale for the LRE applied to those similar model is not clear. 4. In ANOVA, the dependent variable must be a continuous. The statistic employed in the mucus score not appropriate. 5. What is the index for stability of the pharmaceutical product? ****** 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 [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. Attachments Attachment Submitted filename: Comments.pdf https://doi.org/10.1371/journal.pone.0249091.r001
Revision 1
19 Feb 2021 Author Response 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 - Amended as required. 2. As part of your revision, please complete and submit a copy of the Full ARRIVE 2.0 Guidelines checklist, a document that aims to improve experimental reporting and reproducibility of animal studies for purposes of post-publication data analysis and reproducibility: https://arriveguidelines.org/sites/arrive/files/Author%20Checklist%20-%20Full.pdf (PDF). Please include your completed checklist as a Supporting Information file. Note that if your paper is accepted for publication, this checklist will be published as part of your article. - Included on the submission as requested. Reviewers' comments: Reviewer #1: 1) The authors need to discuss the selection of the doses of LRE extract used in the present study. During allergen stimulation, dendritic cells induce the differentiation of T cells into Th2 cells. Th2 cells secrete cytokines i.e. IL-4, IL-5 and IL-13 which facilitate recruitment and activation of eosinophils in the airway. Meanwhile Th2 cells will induce the production of IgE by the B cells via IL-4 and IL-13 stimulation. Inflammatory mediators such as histamine and leukotrienes released by the eosinophils, T cells, macrophages, and neutrophils in the airway environment will result in damage to the airway, bronchoconstriction, and finally remodelling of the lung. In this study, oral administration of LRE at different doses (125, 250 and 500 mg/kg) showed varying responses. Among the doses tested in this study, LRE at 500 mg/kg significantly attenuated the level of IgE in serum, Th2 cytokines IL-4, IL-5 and IL-13 in BALF as well as leukocyte infiltrations in the lung tissues, in contrast to the other two lower doses, 125 and 20 mg/kg which were not consistently attenuated the responses. Based on the dose-response study, LRE 500 mg/kg was chosen for the subsequent studies. 2) Also need to provide the proper rationale for OVA induced asthma, preferably in the introduction. Sensitisation methods utilising ovalbumin (OVA) and house dust mite (HDM) are known to enhance manifestations of asthmatic features. OVA- and HDM-induced model are considered the appropriate methods for experimental allergic asthma. These models have similar clinical symptoms to human asthma, which are characterized by airway mucosal oedema, bronchial wall thicknesses, mucus hypersecretion and increased infiltration of inflammatory cells into the lung. However, there has been limited success with OVA-induced model and only moderate pulmonary inflammation and mild AHR have been observed. HDM has become more commonly used in mouse models to induce AHR because it has immunogenic properties, so the use of an adjuvant is not required. In addition, inhaled delivery of HDM has been more successful in inducing AHR, possibly because of the intrinsic enzymatic activity of this allergen. 3) More recent citations about inflammatory responses and airway hyper responsiveness to be added in the introduction. During allergen stimulation, dendritic cells induce the differentiation of T cells into Th2 cells. Th2 cells secrete cytokines i.e. interleukin (IL)-4, IL-5, IL-9 and IL-13 which facilitate recruitment and activation of eosinophils in the airway. IL-5 and IL-9 are critical for promoting tissue eosinophilia and mast cell hyperplasia, whereas IL-13 stimulates mucus production by goblet cells and airway hyperresponsiveness (AHR). Meanwhile, Th2 cells will induce the production of IgE by the B cells via IL-4 stimulation. In the presence of airway inflammation, the cellular components especially the eosinophils and mast cells will be prompted to release a number of different mediators with the capacity to cause AHR. The inflammatory mediators such as IL-13, histamine, major basic proteins (MBP) and leukotrienes are known to cause AHR which lead to bronchoconstriction, and finally remodelling of the lung. Reviewer #2: 1. This study is descriptive without any intervention design. The authors are encouraged to include more discussion points along possible mechanism. Added as suggested. Please see in discussion section. 2. The dose effect of LRE is required in the study. Some preliminary works to determine dose-response effect are included. Effects of LRE on IgE production in serum As shown in Fig. 1, the OVA-induced asthmatic rats (OVA group) presented significantly increased IgE levels compared to normal group. Significant decreased in the mean serum of IgE level was observed after treatments with LRE at 250 and 500 mg/kg (p < 0.05) when compared with OVA group. However, no significant decrease could be observed from the rats treated with LRE 125 mg/kg (Fig. 1). Effects of LRE on Th2 cytokines in BALF As shown in Fig. 2, the levels of IL-4, IL-5 and IL-13 were significantly increased in BALF of OVA group. Treatment with LRE 500 mg/kg resulted in significantly decreased of IL-4, IL-5 and IL-13 levels when compared to OVA group. In contrast, treatment with LRE 250 mg/kg significantly decreased only IL-5 level, while LRE 125 mg/kg significantly decreased IL-4 and IL-5 levels. Effects of LRE on histopathological change in lung tissue Histopathological analysis by H&E staining demonstrated that lung tissue exposed with OVA had a marked increase in the leukocyte infiltration into the lung tissues. Treatment with LRE 250 or LRE 500 mg/kg significantly decreased infiltration of leukocytes in the peribronchial region and perivascular connective tissue of the airway compared with that observed in the OVA group (Fig. 3). No significant attenuation was observed by the LRE 125 mg/kg treatment group. Based on the dose-response study, LRE at the 500 mg/kg concentration was selected for the downstream experiments. 3. What is the difference between those two allergic models? The rationale for the LRE applied to those similar model is not clear. Some points on OVA and HDM models are included in the introduction. This study was started using ovalbumin-induced model. Using this model, we were able to induce a significant level of inflammation characterised by elevated IgE level, Th2 cytokines level, leukocytes infiltration and mucous in the lung tissue. However, when we tested AHR using OVA-induced model, we were not able to induce significant AHR level in the mouse model. Therefore, for AHR study, we used house dust mite (HDM) to induce the mice. The result as presented in this manuscript. 4. In ANOVA, the dependent variable must be a continuous. The statistic employed in the mucus score not appropriate. Data were expressed as mean ± standard deviation (SD). Statistical differences were assessed by one-way analysis of variance (ANOVA) test followed by Scheffe’s post hoc correction and Student’s t test using Statistical Programme for Social Science (SPSS) version 20.0 (New York, USA). p < 0.05 was considered statistically significant. 5. What is the index for stability of the pharmaceutical product? The product shelf life is 5 years. Attachments Attachment Submitted filename: Response to reviewer.docx https://doi.org/10.1371/journal.pone.0249091.r002
5 Mar 2021 Decision Letter - Yu Ru Kou, Editor PONE-D-20-35276R1 Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyper-responsiveness in a murine model of asthma PLOS ONE Dear Dr. Nurul, 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. One reviewer still raised an issue regarding statistical method. Please submit your revised manuscript by Apr 19 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, Yu Ru Kou, PhD Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: (No Response) Reviewer #2: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: 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 #1: Yes 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 #1: (No Response) Reviewer #2: The author’s responses to common # 5 do not reach my expectations. Please choose the right statistical test for mucus score which is discontinuous data. ****** 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 #1: No Reviewer #2: 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.0249091.r003
Revision 2
10 Mar 2021 Author Response Editor Comment: We have uploaded all the figures in PACE and modified according to Plos ONE requirement. Reviewer Comment: Thank you for the comment. For mucus score results, as the ordinal data are not normally distributed, Kruskal Wallis test is used as the appropriate test to compare the median among groups. The correct statistical test is mentioned and rephrased. Statistical analysis Data were expressed as mean ± standard deviation (SD). Statistical significance (p<0.05) was determined by a one-way ANOVA test followed by Scheffe’s post hoc correction using Statistical Programme for Social Science (SPSS) version 20.0 (New York, USA). For inflammation and mucus scoring, statistical analyses were performed using Kruskal Wallis tests with confidence interval adjustment by Bonferroni correction. The data from PCR array studies were analysed by the web-based software (SABiosciences) using a 2−∆∆CT method. The expression level for genes of interest was normalized by the expression of housekeeping genes. Attachments Attachment Submitted filename: Rebuttal letter 100321.docx https://doi.org/10.1371/journal.pone.0249091.r004
11 Mar 2021 Decision Letter - Yu Ru Kou, Editor Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyper-responsiveness in a murine model of asthma PONE-D-20-35276R2 Dear Dr. Nurul, 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, Yu Ru Kou, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #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: (No Response) ****** 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.0249091.r005
Formally Accepted
19 Mar 2021 Acceptance Letter - Yu Ru Kou, Editor PONE-D-20-35276R2 Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma Dear Dr. Nurul: 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 Dr. Yu Ru Kou Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0249091.r006

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 .