Height development and multiple bone health indicators in children aged 2–12 years with Duchenne muscular dystrophy (DMD)

Bingying Wang; Linyuhan Zhou; Shuangru Li; Huayan Xu; Yingkun Guo; Qin Hu; Min Huang; Dan Zhou; Xiaotang Cai; Qiu Wang; Xiaomei Sun

doi:10.1371/journal.pone.0316938

Peer Review History

Original SubmissionJuly 18, 2024
25 Sep 2024 Decision Letter - Claudia Brogna, Editor PONE-D-24-27979Height development and multiple bone health indicators in children aged 2-12 years with Duchenne muscular dystrophy (DMD)PLOS ONE Dear Dr. Cai, 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 09 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. 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Thank you for stating in your Funding Statement: This work was supported by grants from the Sichuan Science and Technology Support Program :2023YFG0284 & 2023ZYD0121 (receiver:Xiaotang Cai), Natural Science Foundation of Sichuan Province :24NSFC1085 (receiver:Huayan Xu), and the Chengdu Municipal Health Commission Project: 21PJ048 (receiver: Xiaotang Cai). URL: Sichuan Science and Technology Support & Natural Science Foundation of Sichuan Province: https://kjt.sc.gov.cn/ Program Chengdu Municipal Health Commission Project：https://cdwjw.chengdu.gov.cn/ There is not any sponsors or funders play any role in this study. Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. 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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: Yes ******** 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: Bone health impairment and short stature are significant issues faced by children with Duchenne Muscular Dystrophy (DMD), regardless of whether they are undergoing glucocorticoid treatment. This manuscript is valuable for its aim to shed light on these problems. However, there are several critical points that require clarification: 1. The authors mention that height and weight were measured using standard equipment. It would be beneficial to clarify what is meant by "standard equipment." Additionally, in ambulatory patients, accurate height measurement can be challenging in DMD children due to factors such as scoliosis, increased lumbar lordosis, and contractures. Therefore, it is important to specify the percentage of patients with scoliosis, contractures, and increased lumbar lordosis. For non-ambulatory patients, it is evident that height measurement cannot be performed using standard equipment, so a detailed explanation is necessary. 2. The abbreviation "MDT" in line 114 should be explained. 3. Bone Mineral Density (BMD) is typically expressed in units of g/cm². The authors should clarify their use of the mg/cc unit. 4. The authors report a vertebral fracture (VF) rate of 0% in their patients. However, asymptomatic vertebral fractures can occur in 30-50% of DMD children, especially those on glucocorticoid therapy. Therefore, annual (or more frequent if symptoms are present) monitoring with lateral spinal radiographs is recommended. The manuscript does not clearly state the frequency of routine follow-ups, nor whether asymptomatic vertebral fractures were actively investigated through lateral spinal radiographs. Without this monitoring, claiming a 0% VF rate may not be accurate. 5. Are there any patients with long bone fractures, diagnosed osteoporosis, or those receiving bisphosphonate treatment? 6. In Figure 1-d, the authors should explain why height growth velocity is so low at age 3 in the DMD population. Reviewer #2: The authors present an impressive large cohort of early- to late- ambulatory DMD patients and their associated growth parameters and assessments of bone health. Introduction Givinostat now also shown to be effective so glucocorticoids are no longer the only pharmacologic option. Line 82: What is "Molly"? Methods For how many subjects was parents' stature known re. the exclusion criterion? This may be documented in Endocrine assessments but isn't typical in neurology clinic. Was DXA and bone age measured at the same age in all participants? How many had multiple available? Results Table 1 and 2 require a legend explaining the abbreviations Figure one: why is the data point for 9 years in D so low? Line 153 - "stature" to replace "statue" Line 170 - "affecting" to replace "affect" Discussion Recommend combining the bone marker discussion into one rather than repeating it - the first discussion of its use in clinical care is overly strong given lack of normative pediatric data and variability; the discussion is more fairly balanced when repeated later on. Comment on the limitation of not assessing contractures or scoliosis in the data which both impact height and BMI measurement. Line 273: Unclear sentence: Earlier study rather than age? After the age of 8 years? Line 302: suggest "adult" as "elderly" is not typical of the DMD population. This data is remarkable for the size of the cohort and will be useful to clinicians in understanding the trajectory of bone health in early stages of DMD. ****** 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: Yes: Dr. Meral Bilgilisoy Filiz 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: pone DMD review.docx https://doi.org/10.1371/journal.pone.0316938.r001
Revision 1
4 Nov 2024 Author Response Dear editors and reviewers, Thank you for the detailed review and the precious opportunity to revise our manuscript titled “Height development and multiple bone health indicators in children aged 2-12 years with Duchenne muscular dystrophy (DMD)” (ID: PONE-D-24-27979). We are very grateful for your constructive comments and suggestions, which are very valuable and helpful for improving our manuscript. In the following, the responses to all the comments are provided one by one. We have tried our best to make all the revisions clear, and we hope that the revised manuscript can satisfy the requirements for publication. The main revisions in the new manuscript are: 1.Line 42 - Edited funding resource. 2.Line 77 - Added the abbreviation of MDT. 3.Line 108 - “Lamb et al” to replace “Molly” 4.Line 134&136 - Details of the ethics approval have been reported. 5.Line 147 - Frequency of regular monitoring has been supplemented 6.Line 152 - Added the full name of “MDT”, which stands for “Multidisciplinary Team”. 7.Line 162~167 - Added detailed methods for height and weight measurement. 8.Line 206 - Added the explanations for the abbreviations of table 1. 9.Line 211 - “stature” to replace “statue” 10.Line 235 - “affecting” to replace “affect” 11.Line 252 - Added the meaning of symbol “” 12.Line 253 - Added the explanations for the abbreviations of table 2. 13.Line 348 - The description of bone turnover markers has been revised . 14.Line 380 - the unclear sentence had been revised. 15.Line 429 - “adult” to replace “elderly”. 16.Line 432 - The limitation of measuring method was added. Responses to reviewer 1# 1.The authors mention that height and weight were measured using standard equipment. It would be beneficial to clarify what is meant by "standard equipment." Additionally, in ambulatory patients, accurate height measurement can be challenging in DMD children due to factors such as scoliosis, increased lumbar lordosis, and contractures. Therefore, it is important to specify the percentage of patients with scoliosis, contractures, and increased lumbar lordosis. For non-ambulatory patients, it is evident that height measurement cannot be performed using standard equipment, so a detailed explanation is necessary. Response: Thank you for this constructive suggestion. There is some inevitable bias, but we can confirm that its impact on the accuracy of the measurements is minimal by the quality control. In this study, a calibrated device was used to measure height and weight. Each individual was measured three times, and the average value was recorded for accuracy. Also, the children were examined for spinal health (including scoliosis and spina bifida/fracture) every six months. Because the participants in this study were all under 12 years old, most of them have healthy spine and only few of them have very mild curve that is lower than 10° (which did not meet the diagnostic criteria of scoliosis that cobb > 10°) and have little impact on measurement accuracy. Moreover, for participants with scoliosis (cobb >10°), severe contractures, or inability to stand independently, the ulnar calculation and are span have been performed for height. The exact formula and reference are as follows: Calculation formula: height (cm) = (4.605 ulna length)+(1.308age in years)+28.003 Reference: 1) Gauld LM, et al. Height prediction from ulna length. Dev Med Child Neurol. 2004 Jul;46(7):475-80. 2) Forman MR, et al. Arm span and ulnar length are reliable and accurate estimates of recumbent length and height in a multiethnic population of infants and children under 6 years of age. J Nutr. 2014 Sep;144(9):1480-7. According to the reviewer’s insight advice, we have added description of our measuring methods in the manuscript, and limitation of height measurement for children with minor curvature of the spine (which is not clinically significant) had been added, we will try more comprehensive methods to reduce measurement errors. 2.The abbreviation "MDT" in line 114 should be explained. Response： Thank you for your kind suggestion. explanation for “MDT” has been added, which stands for “Multidisciplinary Team”. 3.Bone Mineral Density (BMD) is typically expressed in units of g/cm². The authors should clarify their use of the mg/cc unit. Response: Thank you for the suggestion. g/cm² is the unit for the DAX measurement, which measures flat data for standard screening, while mg/cc is the unit for the QCT measurement which provides 3D imaging data for detailed bone architecture analysis. Our BMD data were provided by QCT. 4.The authors report a vertebral fracture (VF) rate of 0% in their patients. However, asymptomatic vertebral fractures can occur in 30-50% of DMD children, especially those on glucocorticoid therapy. Therefore, annual (or more frequent if symptoms are present) monitoring with lateral spinal radiographs is recommended. The manuscript does not clearly state the frequency of routine follow-ups, nor whether asymptomatic vertebral fractures were actively investigated through lateral spinal radiographs. Without this monitoring, claiming a 0% VF rate may not be accurate. Response: Thank you for the suggestion. The frequency of routine monitoring had been added in our manuscript. According to other research, the prevalent of VF in DMD patients aged 7-12 with daily oral prednisone is about 2% from UK NorthStar database. For our study, the participants were aged 2-12, which is also too young to have high VF rate, while the regular monitoring (spinal radiographs every 6 to 12 months), standarized care of our multidisciplinary team (pediatric neurology, endocrinology, radiology, cardiovascular, rehabilitation, nutrition), early intervention, and tailored therapies (including spinal management) helped children with DMD maintain muscle strength and bone health. In our center, the VF prevalent was about 2%, consistent with the prevalence in other researches. 5.Are there any patients with long bone fractures, diagnosed osteoporosis, or those receiving bisphosphonate treatment? Response: Thank you for the suggestion. 8 participants had a previous fracture, including ankle, elbow, femur, upper arm, tibia and nose, most of these fractures happened in their early age before GC use. 91 participants with BMD z-score < -2 were diagnosed osteoporosis. 6 participants with oral Alendronate sodium and 7 participants with zoledronic acid injection in this study. 6. In Figure 1-d, the authors should explain why height growth velocity is so low at age 3 in the DMD population. Response: Thank you for this question. As diagnosis of DMD is usually after 3 years old, the sample size of age 3 was relatively small which may lead to bias in results. With improvement of people’s awareness and diagnostic methods, the age of diagnosis is gradually advanced, more data before age 3 will be included in our cohort. Responses to reviewer 2# Line 82: What is "Molly"? Response: We apologize that we confused the first and last name of this researcher, thank you for finding out. We had corrected this in the manuscript. For how many subjects was parents' stature known re. the exclusion criterion? This may be documented in Endocrine assessments but isn't typical in neurology clinic. Response: Just as you mentioned, there are Endocrinologists in the multidisciplinary team to conduct the growth and stature monitoring. At the time of writing, no patient at our center meets this exclusion criterion in question. Nevertheless, this was retained in the manuscript because, in endocrinology, very short stature in adult parents may be regarded as a form of short stature that deviates from the familial genetic background. Was DXA and bone age measured at the same age in all participants? How many had multiple available? Response: Thank you for the questions. Patients were followed-up in our center every 6 month to one year. BMD (QCT) was not measured each visit, in accordance with guideline, we started to measure BMD around the onset of GC use, BMD was measured at least once a year. Endocrinologists will conduct bone age testing according to children's growth and development needs. In this study, all participants were measured at the same age, 291 multiple data (BMD and bone age) were available. Results Table 1 and 2 require a legend explaining the abbreviations Repones: Thank you for your suggestion, explanation for abbreviations had been added. Figure one: why is the data point for 9 years in D so low? Response: Figure1-D shows the growth velocity, it indicates that children's height is still increasing but at a slower rate by the age 9. The total sample size is large, but the sample size in group age 9 might insufficient, it can lead abnormal distribution, instability and bias in the statistical results. As the number of patients in our cohort increases and more repeated-measures data are collected, a longitudinal study with a larger simple supplement and verify the results in our future study. Line 153 - "stature" to replace "statue" Line 170 - "affecting" to replace "affect" Line 302: suggest "adult" as "elderly" is not typical of the DMD population. Reponse: Thank you for all the detailed corrections. we replace these words for more accurate statements Discussion Recommend combining the bone marker discussion into one rather than repeating it - the first discussion of its use in clinical care is overly strong given lack of normative pediatric data and variability; the discussion is more fairly balanced when repeated later on. Response: Thank you for the suggestion. This part has been condensed in the manuscript. Comment on the limitation of not assessing contractures or scoliosis in the data which both impact height and BMI measurement. Repones: Thank you for your helpful advice. We have added a discussion on the impact of scoliosis on height measurement in limitation section. The children who were followed up by our team were examined for spinal health (including scoliosis and spina bifida/fracture) every six months to one year. The participants in this cohort were under age 12, most of them did not meet the diagnostic criteria of scoliosis (cobb > 10°). A mild curvature of spine can also affect the accuracy of height measurement, although height measurement for scoliosis is difficult, we will apply more comprehensive approach to improve the accuracy of height measurement, including the use of X-ray assisted measurement. Line 273: Unclear sentence: Earlier study rather than age? After the age of 8 years? Response: We apologize for the unclear expression. We had revised the statements to make the sentences clearer. The revised paragraph is as follows: It has long been shown that in healthy individuals, peak bone mass is almost completely reached by late adolescence or early adulthood[30]. However, our result revealed that BMD kept accumulating during the first two years of prolonged GC exposure (aged around 5.5 to 7.5), yet after which it greatly slumped, probably influenced by both progressive myopathy and cumulative osteo-toxicity of steroids[31]. This was in agreement with the previous findings of our team, where we have reported that children with DMD no longer maintain their BMD leave at least age 8 years[32]. 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. Response: Yes, we agree to publish the peer review history of this article. Thanks to the professional comments again that point out the above problems. The manuscript has revised carefully and thoroughly according to each point. We hope these explanations would answer the doubts. Sincerely, Dr. Xiaotang Cai Attachments Attachment Submitted filename: Response to Reviewers.docx* https://doi.org/10.1371/journal.pone.0316938.r002
1 Dec 2024 Decision Letter - Claudia Brogna, Editor PONE-D-24-27979R1Height development and multiple bone health indicators in children aged 2-12 years with Duchenne muscular dystrophy (DMD)PLOS ONE Dear Dr. Cai, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== Please submit your revised manuscript by Jan 15 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. 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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, Claudia Brogna 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. 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: (No Response) Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) 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: (No Response) 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: (No Response) Reviewer #2: No ****** 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: Recommend an additional revision of the language for grammatical fluency. Two small edits: "Tanner' is misspelled in second use line 356. The sentence starting in 376 is repeated further down the page, with a difference reference - one should be deleted. ****** 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: Yes: Meral Bilgilisoy Filiz 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.0316938.r003
Revision 2
3 Dec 2024 Author Response Response Letter Dear editors and reviewers, Thank you for the detailed review and the precious opportunity to revise our manuscript titled “Height development and multiple bone health indicators in children aged 2-12 years with Duchenne muscular dystrophy (DMD)” (ID: PONE-D-24-27979). We are very grateful for your constructive comments and suggestions, which are very valuable and helpful for improving our manuscript. In the following, the responses to all the comments are provided one by one. We have tried our best to make all the revisions clear, and we hope that the revised manuscript can satisfy the requirements for publication. The main revisions in the new manuscript are: 1.Line 358 - “Tanner” to replace “Tunner” 2.Line 381 - Repeated sentence and reference had been deleted. Responses to reviewer 2# "Tanner' is misspelled in second use line 356. Response: We appreciate your careful reading of our manuscript. The misspelled word have been corrected, thank you for finding out. The sentence starting in 376 is repeated further down the page, with a difference reference - one should be deleted. Response: We sincerely apologize for the oversight of repeating a sentence in the manuscript. We have removed the duplicate sentence in the revised version. Thank you for your attention to detail, which has been invaluable in improving the clarity and quality of our work. Thank you once again to the professional comments that point out the above problems. The manuscript has revised carefully and thoroughly according to each point. We hope these explanations would answer the doubts. Sincerely, Dr. Xiaotang Cai Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0316938.r004
18 Dec 2024 Decision Letter - Claudia Brogna, Editor Height development and multiple bone health indicators in children aged 2-12 years with Duchenne muscular dystrophy (DMD) PONE-D-24-27979R2 Dear Dr. Xiaotang Cai, 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, Claudia Brogna Academic Editor PLOS ONE Reviewers' comments: https://doi.org/10.1371/journal.pone.0316938.r005
Formally Accepted
2 Jan 2025 Acceptance Letter - Claudia Brogna, Editor PONE-D-24-27979R2 PLOS ONE Dear Dr. Cai, 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. Claudia Brogna Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0316938.r006

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