Handgrip strength cutoff value predicting successful extubation in mechanically ventilated patients

Narongkorn Saiphoklang; Nattawadee Mokkongphai

doi:10.1371/journal.pone.0258971

Peer Review History

Original SubmissionApril 13, 2021
27 May 2021 Decision Letter - Robert Ehrman, Editor PONE-D-21-10826 Handgrip Strength Cutoff Value Predicting Successful Extubation in Mechanically Ventilated Patients PLOS ONE Dear Dr. Saiphoklang, 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. This is certainly an interesting study and one that potentially makes a meaningful contribution to the literature in this area. However, I agree with the reviewers that there are several critical points that need to be addressed prior to consideration for publication. In addition to reviewer comments, please address the following concerns in your revision: -the statistical analysis description is not sufficiently detailed for readers to understand what was done and why -my biggest concern is that it is not clear how repeated weaning attempts were handled from an analysis standpoint. the flow chart shows ~93% success overall, but not all of these were on the first attempt--how were the patients/values for those that failed a first (or 2nd) attempt but ultimately extubated handled? was each weaning trial considered an independent event? there is likely within-patient correlation on grip strength so i am not certain that this is the best approach. ultimately, there are so few failures to extubate that it is difficult to draw firm conclusions from these results, and excessive sub-group analysis probably only clouds the picture, but i do think that an analysis of the first weaning trial only would be worthwhile. however, clearly stating what was done is of critical importance -please clarify when and how these patients were consented as this potentially speaks to concerns over selection bias Please submit your revised manuscript by Jul 10 2021 11:59PM. 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Kind regards, Robert Ehrman, MD, MS 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. Thank you for stating the following in the Acknowledgments Section of your manuscript: "The work was supported by Faculty of Medicine, Thammasat University, Thailand." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: This study aims to investigate the usefulness of handgrip strength (HGS) in the predicting successful extubation. They found HGS could be a useful predictive toll to guide extubation. Overall, the study is well-designed and the manuscript is well-written. I just have several suggestions. 1. I just wonder why more than 80% of patients were in general medical wards. 2. Please briefly describe study sites, including both general ward and ICU. 3. Please add something more in the table 2, including patients’ characteristics, use of sedation, neuromuscular blockage and steroid. 4. We need more discussion about HSG, not only the description of each study’s finding about HSG. Reviewer #2: This is a very interesting article with a simple method to evaluate the patient’s readiness to be weaned/extubated. Although, some important points need to be elucidate and some additional analysis should be performed. - SBT failure and extubation failure should be considered different outcomes. - The variation in the SBT duration (30 to 120 minutes) can interfere in the outcome, and even in the HGS result. For some patients, 120 min is a big challenge. The standardization of the SBT duration is very important (all patients with 30 min or all with 120 min). Another possibility is to analyze separated those with 30 min form those with 120 min. - The type of SBT performed can affect the results. This method should be standardized or analyze separated patients test in PSV and those tested in t-piece. - How many measures of the HGS was performed? Do you consider the first try? There was a training time or explanation? - How did you define the patient’s capacity to perform the HGS? Glasgow coma scale? RASS? The capacity to follow 2 o 3 commands? - How can you explain/discuss the low ROC value of RSBI in this cohort? This is very different from others studies that used RSBI. ****** 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: Yes:** Antuani Rafael Baptistella [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.0258971.r001
Revision 1
25 Jun 2021 Author Response Dear Reviewers of PLOS ONE: I submitted an original contribution to PLOS ONE entitled “Handgrip Strength Cutoff Value Predicting Successful Extubation in Mechanically Ventilated Patients” (Manuscript Number PONE-D-21-10826). You have kindly expressed some interesting points with your comments. Therefore, my response to the comment is below. RESPONSE TO REVIEWER 1: REVIEWER COMMENT 1: I just wonder why more than 80% of patients were in general medical wards. RESPONSE: I have added more texts to explain the reasons in Paragraph 1 of Discussion section. REVIEWER COMMENT 2: Please briefly describe study sites, including both general ward and ICU. RESPONSE: I have added more descriptions in Paragraph 1 of Methods section (Study design and participants). REVIEWER COMMENT 3: Please add something more in the table 2, including patients’ characteristics, use of sedation, neuromuscular blockage and steroid. RESPONSE: I have added more data including patient characteristics in Table 2. REVIEWER COMMENT 4: We need more discussion about HSG, not only the description of each study’s finding about HSG. RESPONSE: I have added more discussions in Paragraph 1 to 4 of Discussion section. RESPONSE TO REVIEWER 2: REVIEWER COMMENT 1: SBT failure and extubation failure should be considered different outcomes. RESPONSE: I have added data of extubation failure as weaning outcome in Table 1. REVIEWER COMMENT 2: The variation in the SBT duration (30 to 120 minutes) can interfere in the outcome, and even in the HGS result. For some patients, 120 min is a big challenge. The standardization of the SBT duration is very important (all patients with 30 min or all with 120 min). Another possibility is to analyze separated those with 30 min form those with 120 min. RESPONSE: I have added more data on SBT duration in Table 1 and Table 2. REVIEWER COMMENT 3: The type of SBT performed can affect the results. This method should be standardized or analyze separated patients test in PSV and those tested in t-piece. RESPONSE: I have added PSV data in Table 2. REVIEWER COMMENT 4: How many measures of the HGS was performed? Do you consider the first try? There was a training time or explanation? RESPONSE: I have added more details in Methods section (Measurements). REVIEWER COMMENT 5: How did you define the patient’s capacity to perform the HGS? Glasgow coma scale? RASS? The capacity to follow 2 o 3 commands? RESPONSE: I have added more details in Paragraph 1 of Methods section (Study design and participants). REVIEWER COMMENT 6: How can you explain/discuss the low ROC value of RSBI in this cohort? This is very different from others studies that used RSBI. RESPONSE: I have added more discussions in Paragraph 2 of Discussion section. I appreciate your consideration of my manuscript for publication in PLOS ONE. Sincerely, Narongkorn Saiphoklang, M.D. Attachments Attachment Submitted filename: Response to Reviewers_v1.docx https://doi.org/10.1371/journal.pone.0258971.r002
21 Jul 2021 Decision Letter - Robert Ehrman, Editor PONE-D-21-10826R1 Handgrip strength cutoff value predicting successful extubation in mechanically ventilated patients PLOS ONE Dear Dr. Saiphoklang, 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. Thank you for the time and effort out forth in revising your manuscript. While it is substantially improved, a few issues remain that require clarification prior to proceeding with publication. Please submit your revised manuscript by Sep 04 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. 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, Robert Ehrman, MD, MS 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: All comments have been addressed 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: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: (No Response) ****** 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: (No Response) ****** 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: (No Response) ****** 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 response well, so I have no more comment. Therefore, I recommend the present manuscript can be accepted. Reviewer #2: Authors answered most of my comments, although, some important points are not completely clear. 1- The outcome used in table 2 is weaning success and failure, but the outcome described in methods and even mentioned in the title is extubation success or failure. Weaning success and extubation success are two different outcomes. Weaning success is defined as to pass for the SBT without any sign of intolerance, while extubation success is to breathe spontaneously for 48 hours without NIV dependence or reintubation. Authors must standardize the outcome used. 2- Regarding my previous comment “The type of SBT performed can affect the results. This method should be standardized or analyze separated patients test in PSV and those tested in t-piece.” There was difference in the outcome in patients who performed the SBT in PSV or T piece. If you analyze the HGS in this 2 groups separately, the result would be the same? 3- Results section – first paragraph – “weaning success was 6.5%” – I suppose you mean “weaning failure”. ****** 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: Yes:** Antuani Rafael Baptistella [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.0258971.r003
Revision 2
3 Sep 2021 Author Response Dear Reviewers of PLOS ONE: I submitted an original contribution to PLOS ONE entitled “Handgrip Strength Cutoff Value Predicting Successful Extubation in Mechanically Ventilated Patients” (Manuscript Number PONE-D-21-10826). You have kindly expressed some interesting points with your comments. Therefore, my response to the comment is below. RESPONSE TO REVIEWER 1: REVIEWER COMMENT: The authors response well, so I have no more comment. Therefore, I recommend the present manuscript can be accepted. RESPONSE: I would like to gratefully thank the reviewer for kindly reviews. RESPONSE TO REVIEWER 2: REVIEWER COMMENT 1: The outcome used in table 2 is weaning success and failure, but the outcome described in methods and even mentioned in the title is extubation success or failure. Weaning success and extubation success are two different outcomes. Weaning success is defined as to pass for the SBT without any sign of intolerance, while extubation success is to breathe spontaneously for 48 hours without NIV dependence or reintubation. Authors must standardize the outcome used. RESPONSE: I have added the definition of extubation failure for this study in Method section, paragraph 5. Also, I have changed the weaning outcome to new words; extubation success and extubation failure, in Table 1, the heading title of Table 2, and Figure 1. REVIEWER COMMENT 2: Regarding my previous comment “The type of SBT performed can affect the results. This method should be standardized or analyze separated patients test in PSV and those tested in t-piece.” There was difference in the outcome in patients who performed the SBT in PSV or T piece. If you analyze the HGS in this 2 groups separately, the result would be the same? RESPONSE: I have added T-piece data as the weaning mode in Table 2 which is separated from PSV data. REVIEWER COMMENT 3: Results section – first paragraph – “weaning success was 6.5%” – I suppose you mean “weaning failure”. RESPONSE: I have corrected this word to “extubation failure” in Results section. Also, I have corrected to new words in Abstract section, Results section, the heading title of Table 2 and 3, and Figure 1. I appreciate your consideration of my manuscript for publication in PLOS ONE. Sincerely, Narongkorn Saiphoklang, M.D. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0258971.r004
6 Oct 2021 Decision Letter - Robert Ehrman, Editor PONE-D-21-10826R2Handgrip strength cutoff value predicting successful extubation in mechanically ventilated patientsPLOS ONE Dear Dr. Saiphoklang, 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. ==============================Overall, the manuscript is improved in its current version. I would recommend adding a brief acknowledgement in the limitations section about the relatively small sample size--while the point estimates indicate good accuracy, the CIs are wide and thus the results should be cautiously interpreted. ============================== Please submit your revised manuscript by Nov 20 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: 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, Robert Ehrman, MD, MS 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: [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.0258971.r005
Revision 3
7 Oct 2021 Author Response RESPONSE TO EDITOR EDITOR COMMENT: Overall, the manuscript is improved in its current version. I would recommend adding a brief acknowledgement in the limitations section about the relatively small sample size--while the point estimates indicate good accuracy, the CIs are wide and thus the results should be cautiously interpreted. RESPONSE: Thank you for your kindly comments. I have added this sentence in the limitations section. I appreciate your consideration of my manuscript for publication in PLOS ONE. Sincerely, Narongkorn Saiphoklang, M.D. Attachments Attachment Submitted filename: Response to Reviwers.docx https://doi.org/10.1371/journal.pone.0258971.r006
11 Oct 2021 Decision Letter - Robert Ehrman, Editor Handgrip strength cutoff value predicting successful extubation in mechanically ventilated patients PONE-D-21-10826R3 Dear Dr. Saiphoklang, 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, Robert Ehrman, MD, MS Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0258971.r007
Formally Accepted
13 Oct 2021 Acceptance Letter - Robert Ehrman, Editor PONE-D-21-10826R3 Handgrip strength cutoff value predicting successful extubation in mechanically ventilated patients Dear Dr. Saiphoklang: 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. Robert Ehrman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0258971.r008

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