Clinical validation of enhanced CT imaging for distal radius fractures through conditional Generative Adversarial Networks (cGAN)

Hyojune Kim; Seung Min Ryu; Ji-Soo Keum; Sang-Il Oh; Kyung-Nam Kim; Young Ho Shin; In-Ho Jeon; Kyoung Hwan Koh

doi:10.1371/journal.pone.0308346

Peer Review History

Original SubmissionMarch 21, 2024
10 Jun 2024 Decision Letter - Ngie Min Ung, Editor PONE-D-24-07461Clinical validation of enhanced CT imaging for distal radius fractures through deep learning based interpolation and thickness reductionPLOS ONE Dear Dr. Koh, 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 Jul 25 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Ngie Min Ung Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. The American Journal Experts (AJE) (https://www.aje.com/) is one such service that has extensive experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. Please note that having the manuscript copyedited by AJE or any other editing services does not guarantee selection for peer review or acceptance for publication. Upon resubmission, please provide the following: The name of the colleague or the details of the professional service that edited your manuscript A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a supporting information file) A clean copy of the edited manuscript (uploaded as the new manuscript file)”. 3. We note that your Data Availability Statement is currently as follows: [All relevant data are within the manuscript and its Supporting Information files.] Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition). For example, authors should submit the following data: - The values behind the means, standard deviations and other measures reported; - The values used to build graphs; - The points extracted from images for analysis. Authors do not need to submit their entire data set if only a portion of the data was used in the reported study. If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. 4. We note that Figure(s) 4 and 7 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a. You may seek permission from the original copyright holder of Figure(s) 4 and 7 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an ""Other"" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b. If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. 5. 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: Yes Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 ****** 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: Tha manuscript focuses on new methodologies to present high resolution (z-axis) images from low resolution images using neural networks. The methods are sound and logical, presented in an intelligible fashion. It is a very interesting read indeed. However, there are minor issues that require some additional information that it is not possible for me to recommend for an acceptance, at least on its current state. Please consider the following comments: Please use "xxx mm" not "xxxmm" as this is more grammatically acceptable in writing physical measurement units. In the introduction, there was mention of risk regarding patient dose, but this is not discussed at all throughout the manuscript. It is obvious that the dose (at least the dose length product, DLP) of 3 mm images will be lower than 1 mm. So generating 1 mm image from 3 mm acquisition will be beneficial at this point that deserves to be mentioned/discussed to support the idea of this paper. A first thought was that the 1 mm image is generated from 3 mm images through two-times exposure (1 mm and 3 mm) of the subject as pairs with the accuracy of generated 1 mm being checked against the real 1 mm along the process of evaluation, but the case in the manuscript seems to be the other way around. Is it possible to disclose the reason? I suspect this is ethically-motivated (?) Since the 3 mm images are generated (pg 7, lines 122-124), is there any mechanism discussed to verify between generated 3 mm images and real (CT-acquired) 3 mm images? Reviewer #2: The paper presents an evaluation on the potential of conditional GANs in achieving superior CT image resolution without compromising patient safety in orthopedic imaging. The paper is well-written (with few grammatical errors) and can be accepted with few revisions. Here are the suggestions to be considered by the authors: 1. The title should be revised. The term 'conditional Generative Adversarial Networks (cGAN)' should be included in the title to clarify the advanced method being discussed. 2. Please revise the range '3 mm-1 mm', it should be written from small to large, 1 mm - 3 mm. Add space between the value and unit (eg. 1 mm). Please correct the range throughout the text. 3. In methodology, the metrics part - please explain in details the calculation of mean squared error (MSE), and structural similarity index (SSIM). Any related equation? 4. In methodology, the qualitative evaluation part - two orthopedic surgeons were included, but no radiologist was included as observers, justify? The criteria for the evaluation should be discussed in details, any specific anatomical or bony structure that been observed for spatial resolution evaluation? Please explain in details the criteria for each grade 1 to 4. 4. Please recheck the arrangement of figures and figures legends. It seems not matching to each other. Figures in last page should be label or indicated with arrow(s) to show the differences between each images. If possible, the authors can provide the zoom version on the structures (that shows improvement). 5. In results, the figure (A-B) that shows the histogram of the evaluation of the clinicians, it is suggested to add label or notes that described the grade 1 to 4 for better understanding. Justify the significance of the figure B, for the choice for higher resolution image (why need this graph?), because from the grading, it seems like acquired images by 1 mm thickness appear to be superior among all. 6. In conclusion, please revise the sentence 'consistently yielded superior image resolution compared to traditional approaches'. What does it means by 'traditional methods'?. From the grading, it seems like images acquisition by 1 mm thickness appear to be superior among all. ******* 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. https://doi.org/10.1371/journal.pone.0308346.r001
Revision 1
26 Jun 2024 Author Response Response to Reviewers Reviewer Comments: Reviewer #1: 1. Please use "xxx mm" not "xxxmm" as this is more grammatically acceptable in writing physical measurement units. � Response: Thank you for highlighting these key concerns. I revised it all through manuscript. 2. In the introduction, there was mention of risk regarding patient dose, but this is not discussed at all throughout the manuscript. It is obvious that the dose (at least the dose length product, DLP) of 3 mm images will be lower than 1 mm. So generating 1 mm image from 3 mm acquisition will be beneficial at this point that deserves to be mentioned/discussed to support the idea of this paper. � Response: Thank you for your comments. We mentioned that the need for high quality of images by 1 mm slice CT get higher. Therefore, additional CT examination could be required for the patients who had 3 mm CT. It could induce the radiation exposure risk. It was mentioned in discussion (Line 417-420). However, we did not measure directly the exposed radiation dose from 3 mm CT and 1 mm CT. Therefore, we did not discuss the radiation dose. 3. A first thought was that the 1 mm image is generated from 3 mm images through two-times exposure (1 mm and 3 mm) of the subject as pairs with the accuracy of generated 1 mm being checked against the real 1 mm along the process of evaluation, but the case in the manuscript seems to be the other way around. Is it possible to disclose the reason? I suspect this is ethically-motivated (?) � Response: Thank you for your insightful comment. We understand the potential confusion regarding the generation of 1 mm images from 3 mm images. In our study, we used paired 3 mm-1 mm CT data from patients who had undergone a single CT examination at 1 mm slice thickness. The 3 mm images were virtually derived from these 1 mm scans. This approach was chosen to minimize patient exposure to radiation, adhering to ethical standards that prioritize patient safety by reducing the need for multiple exposures. We will clarify this in the manuscript to emphasize the ethical considerations and the method used to generate the 3 mm images from the initial 1 mm scans. This method ensures that patients are not subjected to unnecessary additional radiation, aligning with best practices in medical imaging. � Revisions to Manuscript: � Line 120-123: In this study, we utilized paired 3 mm-1 mm CT data from patients who underwent a single CT examination at 1 mm slice thickness. The 3 mm images were virtually generated from these 1 mm scans to minimize radiation exposure, adhering to ethical standards and prioritizing patient safety. 4. Since the 3 mm images are generated (pg 7, lines 122-124), is there any mechanism discussed to verify between generated 3 mm images and real (CT-acquired) 3 mm images? � Response: Thank you for pointing out this important aspect. In our study, the 3 mm images were virtually generated from the 1 mm CT images. We did not perform a direct comparison between these virtually generated 3 mm images and real (CT-acquired) 3 mm images. This approach was primarily focused on demonstrating the feasibility of using conditional GANs to enhance the resolution of CT images. We acknowledge that verifying the similarity between virtually generated 3 mm images and real 3 mm images could further validate our approach. We will discuss this limitation in our manuscript and propose it as a direction for future research. � Revisions to Manuscript: � Line 446-450: Lastly, we had the lack of direct comparison between virtually generated 3 mm images and real CT-acquired 3 mm images. While our primary focus was on the enhancement of CT image resolution using conditional GANs, future research could benefit from including such comparisons to further validate the accuracy and effectiveness of the virtual generation process. Reviewer #2: 1. The title should be revised. The term 'conditional Generative Adversarial Networks (cGAN)' should be included in the title to clarify the advanced method being discussed. � Response: Thank you for comments. We revised it, as ‘Clinical validation of enhanced CT imaging for distal radius fractures through conditional Generative Adversarial Networks (cGAN)’. 2. Please revise the range '3 mm-1 mm', it should be written from small to large, 1 mm - 3 mm. Add space between the value and unit (eg. 1 mm). Please correct the range throughout the text. � Response: We revised. 3. In methodology, the metrics part - please explain in details the calculation of mean squared error (MSE), and structural similarity index (SSIM). Any related equation? � Response: Thank you for comments. The referred metrics (MSE, SSIM) were generally used for evaluating the image generating experiments. Therefore, we just used them by reference article, which was ‘Sun Y, Pan B, Li Q, Wang J, Wang X, Chen H, et al. Clinical ultra-high resolution CT scans enabled by using a generative adversarial network. Med Phys. 2023;50(6):3612-22.‘. 4. In methodology, the qualitative evaluation part - two orthopedic surgeons were included, but no radiologist was included as observers, justify? The criteria for the evaluation should be discussed in details, any specific anatomical or bony structure that been observed for spatial resolution evaluation? Please explain in details the criteria for each grade 1 to 4. � Response: Thank you for your valuable feedback. We appreciate the opportunity to clarify and improve our methodology section. We have revised the methodology section to include detailed criteria for the evaluation. The surgeons focused on specific anatomical and bony structures (carpal bones and distal radius, joint space), such as cortical bone margins, fracture lines, and trabecular bone patterns. � Revisions to Manuscript: Line 274-285 The grading criteria have been explicitly defined as follows: - Grade 1: Excellent resolution with clear visualization of fine anatomical details for carpal bone and distal radius, including sharp cortical bone margins, fracture lines and distinct trabecular patterns. - Grade 2: Good resolution with minor blurring but still adequate for clinical assessment of anatomical details for carpal bone and distal radius, but not exact for the fracture lines or trabecular patterns. - Grade 3: Fair resolution with noticeable blurring, affecting the visibility of finer details, such as carpal bone and fracture patterns, but still allowing for basic clinical evaluation. - Grade 4: Poor resolution with significant blurring, making it difficult to distinguish anatomical structures and unsuitable for clinical use for evaluating the fractures or anatomical structures. 5. Please recheck the arrangement of figures and figures legends. It seems not matching to each other. Figures in last page should be label or indicated with arrow(s) to show the differences between each image. If possible, the authors can provide the zoom version on the structures (that shows improvement). � Response: Thank you for comments. We revised the figs 7 and 8. 6. In results, the figure (A-B) that shows the histogram of the evaluation of the clinicians, it is suggested to add label or notes that described the grade 1 to 4 for better understanding. Justify the significance of the figure B, for the choice for higher resolution image (why need this graph?), because from the grading, it seems like acquired images by 1 mm thickness appear to be superior among all. � Response: Thank you for comments. Even though our method could nearly enhance the 3 mm images into the quality, the extent of 1 mm original version, the grading showed clearly difference between 1 mm image and generating images from Method 1 and 2. And the grading between Method 1 and 2 was not significantly different. As we want to figure out the superiority between Method 1 and 2, we try to choose from two generated images, which was more similar to 1 mm image by clinicians. 7. In conclusion, please revise the sentence 'consistently yielded superior image resolution compared to traditional approaches'. What does it means by 'traditional methods'?. From the grading, it seems like images acquisition by 1 mm thickness appear to be superior among all. � Response: Thank you for comments. We revised the sentence. ‘Our quantitative findings indicated that our proposed method, which emphasizes learning the difference value between the 3 mm input and the 1 mm corresponding image, consistently yielded superior image resolution.’ Attachments Attachment Submitted filename: Response to Reviewers.docx* https://doi.org/10.1371/journal.pone.0308346.r002
23 Jul 2024 Decision Letter - Ngie Min Ung, Editor Clinical validation of enhanced CT imaging for distal radius fractures through conditional Generative Adversarial Networks (cGAN) PONE-D-24-07461R1 Dear Dr. Kyoung Hwan Koh, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Ngie Min Ung 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 #1: All comments have been addressed 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 #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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 #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: The authors have addressed all the comments. It is now appropriate for me to recommend for an acceptance. Reviewer #2: The authors have addressed all the comments and suggestions provided. The responses and the subsequent revisions have adequately addressed reviewers' concerns, and the manuscript is significantly improved. I am pleased to recommend the acceptance of the revised manuscript for publication. ****** 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 ******** https://doi.org/10.1371/journal.pone.0308346.r003
Formally Accepted
8 Aug 2024 Acceptance Letter - Ngie Min Ung, Editor PONE-D-24-07461R1 PLOS ONE Dear Dr. Koh, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Ngie Min Ung Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0308346.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 .