Transcranial direct current simulation as an adjunctive treatment for treatment-resistant depression in hospitalized patients: A feasibility study protocol

John W. Li; Caili Ren; Vanessa K. Pazdernik; Simon Kung; Michael R. Basso; Paul E. Croarkin; Bina Aaron; Amanda M. Anderson; Courtney A. Caves; Misty N. Hemm; Ashley L. Holland; Charlie R. Hoth; Emily A. Jazdzewski; Eduardo Kabristante; Mahathi Kandimalla; Carly B. Mickle; Hoon-Ki Min; Can Ozger; Justine M. Parsons; Roberta L. Sheldon; Michelle K. Skime; Erik K. St. Louis; Yogatheesan Varatharajah; Neeraj Wagh; Kirk M. Welker; Sarah M. Williams; Gregory A. Worrell; Maria I. Lapid

doi:10.1371/journal.pone.0324808

Peer Review History

Original SubmissionJune 19, 2024
19 Jun 2024 Author Response https://doi.org/10.1371/journal.pone.0324808.r001
22 Jul 2024 Decision Letter - Abdolvahed Narmashiri, Editor Dear Dr. Lapid, 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 Sep 05 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. 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'. 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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, Abdolvahed Narmashiri 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 noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://www.ajgponline.org/article/S1064-7481(24)00192-1/abstract In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. 3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 4. When completing the data availability statement of the submission form, you indicated that you will make your data available on acceptance. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If you are unable to adhere to our open data policy, please kindly revise your statement to explain your reasoning and we will seek the editor's input on an exemption. Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process. 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Additional Editor Comments: This protocol study provides evidence for the use of tDCS as an adjunct to standard care in the treatment of TRD in hospitalized patients. However, I have significant concerns regarding the methodological and scientific standards of this paper. A complete rewrite and reorganization are necessary to align it with accepted scientific standards. 1. Introduction: Remove the section titles and rewrite the introduction to present a coherent narrative. 2. Results: Add a dedicated results section to report pre- and post-tDCS outcomes, including measures of depression and cognition. 3. Methods: Rewrite the methods section to adhere to scientific standards. 4. Results Reporting: Ensure your results include: o Depression measures (Montgomery-Asberg Depression Rating Scale (MADRS)) o Cognitive measures (Stroop Test, Revised Hopkins Verbal Learning Test (HVLT-R), Digital Symbol Coding Test (DSCT)) o EEG changes in peak alpha frequency (PAF) o Cerebral hemodynamic changes (functional near-infrared spectroscopy (fNIRS)) o Attention to statistical analysis and accurate reporting in the results section. 5. Discussion: Remove the section titles and discuss the results in the context of the study protocol. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? Reviewer #1: Yes Reviewer #2: Partly ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??> Reviewer #1: Partly Reviewer #2: Partly ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??> Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. Reviewer #1: 1. This paper outlines a protocol to investigate the feasibility of implementing a 5-day tDCS treatment in hospitalized patients with TRD. The research also aims to explore the potential positive effects on depression and cognition and the neurophysiological mechanisms underlying tDCS. The authors did not indicate the specific descriptive statistics that will be used to summarize the data for continuous and categorical variables. They only mentioned descriptive statistics, which are too broad. 2. Since you are measuring the outcome measures before and after treatment for the same patients, the paired t-test or the non-parametric alternative will be more appropriate due to the correlation in the outcome measures. 3. Kindly state the statistical software that will be used for the analysis and at what level of significance the null hypothesis of no treatment effect will be rejected. 4. There was no justification for selecting 10 patients. There was no power analysis or sample size estimation to justify the choice of 10 and no reference to previous studies or expert documentation to justify the selection of 10 patients for the study. 5. Authors must provide references for the definition of feasibility outcomes. Some were set at >70% and others >80%. There must be references or justification to support the cut-off points or the 70% and 80% thresholds. Why not 90%, 50%, etc.? Kindly provide detailed justification or references to support the cut-off points. 6. Again, the authors indicated that treatment response will be defined as 50% or more improvement in MADRS score post-treatment from pre-treatment, but no justification was provided as to why they are setting the cut-off at 50% and not any other threshold. My concern is that setting the threshold at different cutoffs can generate entirely different results and conclusions, and that is more reason why justification must be provided 7. The authors anticipate the possibility of missing data but did not indicate which statistical technique will be used to handle missing values if it does occur. This is important as only 10 patients will be studied. 8. Complete case analysis, as suggested by the authors, in the presence of missing data reduces the sample size and the power of the study. This is particularly important when the authors have decided to study only 10 patients without details on how they arrived at the number 10 and the implications for missing observations. 9. Authors may re-consider running logistic regression on just 10 observations, with the possibility of a reduced sample size to an even smaller figure below 10. Reviewer #2: Title: - Please do not use acronyms in the title. Keywords: - Please do not use the same words/expressions used in the title as keywords. Ethics Statement: - Please add information about the registration of the randomized clinical trial that will be carried out from the study protocol. Add the name and registration number to the Abstract session as well. Introduction - Line 76: What does “FDA” mean? Please write it in full before using the acronym. - In general, I found the writing of the introduction to be exaggeratedly long. Information about TMS and fNIRS is not necessary here. I suggest placing more emphasis on the main focus of the study (effects of tDCS in TRD populations). Methods - Please add information about the sample calculation. - Please add information about study blinding and randomization between active and sham. - Please indicate when the participant recruitment period will begin and the expected date for the completion of interventions/evaluations. - Explain the reason for applying tDCS twice a day. - Please include references that support your interpretations for the “feasibility”, “acceptability” and “tolerability” measures. - Please provide more details on the equipment used to measure cortical activity (EEG and fNIRS). - Do you not intend to evaluate changes in deoxyhemoglobin? Please contextualize Discussion - This section needs to be better written, it is necessary to present information about protocols of other similar studies. Furthermore, I recommend making the innovative aspect of the study more evident. ****** 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: Gabriel Antonio Gazziero Moraca ******** [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.0324808.r002
Revision 1
11 Dec 2024 Author Response Reviewer #1: 1. This paper outlines a protocol to investigate the feasibility of implementing a 5-day tDCS treatment in hospitalized patients with TRD. The research also aims to explore the potential positive effects on depression and cognition and the neurophysiological mechanisms underlying tDCS. The authors did not indicate the specific descriptive statistics that will be used to summarize the data for continuous and categorical variables. They only mentioned descriptive statistics, which are too broad. Response: Thank you. We have revised the sentence to be more specific as follows: “Baseline values for demographic, clinical, and outcome variables (primary and secondary) will be reported as means and standard deviations for continuous data, or medians and interquartile ranges for skewed data, and frequencies and percentages for categorical data.” 2. Since you are measuring the outcome measures before and after treatment for the same patients, the paired t-test or the non-parametric alternative will be more appropriate due to the correlation in the outcome measures. Response: Thank you. We have clarified that the t-test used will indeed be paired. The Wilcoxon signed-rank test is the appropriate non-parametric alternative. 3. Kindly state the statistical software that will be used for the analysis and at what level of significance the null hypothesis of no treatment effect will be rejected. Response: Thank you. We have added the following statement: “The analysis will use SAS Studio 3.82 and R 4.3.2, with a significance level of 0.05 to reject the null hypothesis. However, the primary focus will be on descriptive statistics and effect size estimation, with a p-value interpretation considered secondary.” 4. There was no justification for selecting 10 patients. There was no power analysis or sample size estimation to justify the choice of 10 and no reference to previous studies or expert documentation to justify the selection of 10 patients for the study. Response: Thank you. We acknowledge the absence of a formal power analysis or sample size estimation. As this is a feasibility study, the selection of 10 patients was based on practical considerations such as resource availability. Future studies will include power calculations based on this study and references to prior research to support sample size decisions. We have added a Sample size section to the manuscript to clarify this. 5. Authors must provide references for the definition of feasibility outcomes. Some were set at >70% and others >80%. There must be references or justification to support the cut-off points or the 70% and 80% thresholds. Why not 90%, 50%, etc.? Kindly provide detailed justification or references to support the cut-off points. Response: The cut-off points of >70% and >80% were selected based on common practices observed in similar feasibility studies and guidelines for early-phase research, where these thresholds often represent realistic and challenging benchmarks for assessing feasibility. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646008/ reports a target of <20% citing tDCS as reason for refusal to enroll and not quite similar is the target >10% enrolled out of those eligible. 6. Again, the authors indicated that treatment response will be defined as 50% or more improvement in MADRS score post-treatment from pre-treatment, but no justification was provided as to why they are setting the cut-off at 50% and not any other threshold. My concern is that setting the threshold at different cutoffs can generate entirely different results and conclusions, and that is more reason why justification must be provided Response: Thank you. We have added two references (Leucht, Fennema et al. 2017, Turkoz, Alphs et al. 2021) supporting that MADRS total score of ≥50% corresponds to a clinically significant improvement such as correlation with the Clinical Global Impression Severity (CGI-S) score of 2 (i.e. much improved). 7. The authors anticipate the possibility of missing data but did not indicate which statistical technique will be used to handle missing values if it does occur. This is important as only 10 patients will be studied. Response: Thank you. We have added that maximum likelihood estimation will be used in models with incomplete data to handle missing data. If missing data occurs, addressing this issue will become a primary focus regarding the feasibility study. More specifically we’ll be adhering to these guidelines depending on the scenario and data missing mechanism: https://statisticalhorizons.com/wp-content/uploads/MissingDataByML.pdf 8. Complete case analysis, as suggested by the authors, in the presence of missing data reduces the sample size and the power of the study. This is particularly important when the authors have decided to study only 10 patients without details on how they arrived at the number 10 and the implications for missing observations. Response: We acknowledge this analysis may not be sufficiently powered to detect the true effects of this intervention on our measured outcomes. However, feasibility studies are not expected to have the large sample sizes that are needed to adequately power statistical null hypothesis testing. Indeed, pilot studies that are published often do not show statistically significant findings and rarely lead to larger trials to adequately power the hypothesis testing (Arain, Campbell et al. 2010, Shanyinde, Pickering et al. 2011). We have clarified this aspect of the study as documented in our response to comment #4. 9. Authors may re-consider running logistic regression on just 10 observations, with the possibility of a reduced sample size to an even smaller figure below 10. Response: We acknowledge the concern regarding the small sample size for logistic regression. Given the limited number of observations, we recognize that the results may be unstable and lack power. We have changed to “…will be assessed using descriptive statistics and paired t-tests or Wilcoxon signed-rank tests.” Reviewer #2: Title: - Please do not use acronyms in the title. Response: Thank you. We have removed the acronyms. Keywords: - Please do not use the same words/expressions used in the title as keywords. Response: Thank you. We have removed the duplicate words used in title. Ethics Statement: - Please add information about the registration of the randomized clinical trial that will be carried out from the study protocol. Add the name and registration number to the Abstract session as well. Response: Thank you. We have added the name and registration number of the trial in the Abstract. Introduction - Line 76: What does “FDA” mean? Please write it in full before using the acronym. Response: Thanks for pointing out the undefined acronym. FDA is now written in full “Food and Drug Administration.” - In general, I found the writing of the introduction to be exaggeratedly long. Information about TMS and fNIRS is not necessary here. I suggest placing more emphasis on the main focus of the study (effects of tDCS in TRD populations). Response: Thank you for the suggestions. We modified the introduction to be more concise and focused on the main objective of the study. Methods - Please add information about the sample calculation. Response: Thank you. We acknowledge the absence of a formal power analysis or sample size estimation. As this is a feasibility study, the selection of 10 patients was based on practical considerations such as resource availability. Future studies will include power calculations based on this study and references to prior research to support sample size decisions. We have added a Sample size section to the manuscript to clarify this. - Please add information about study blinding and randomization between active and sham. Response: This is an open label study. Clarification is added in Study design section - Please indicate when the participant recruitment period will begin and the expected date for the completion of interventions/evaluations. Response: We expect patient recruitment to start in December 2024 and all interventions and evaluations will be completed about one year from the start of the recruitment. - Explain the reason for applying tDCS twice a day. Response: The reason for applying tDCS twice per day over 5 consecutive days is to maximize the number of treatments over a typical course of inpatient stay, which is on average 5 to 7 days long in our facility. Previous studies have shown that it is safe to administer 10 sessions of 30 minutes tDCS over 5 days in depressed patients and that two daily tDCS sessions were potentially two daily tDCS sessions were potentially more effective in reducing depressive symptoms when compared to a single session per day (Bennabi, Nicolier et al. 2015, Zanardi, Poletti et al. 2020). - Please include references that support your interpretations for the “feasibility”, “acceptability” and “tolerability” measures. Response: The cut-off points of >70% and >80% were selected based on common practices observed in similar feasibility studies and guidelines for early-phase research, where these thresholds often represent realistic and challenging benchmarks for assessing feasibility. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646008/ reports a target of <20% citing tDCS as reason for refusal to enroll and not quite similar is the target >10% enrolled out of those eligible. - Please provide more details on the equipment used to measure cortical activity (EEG and fNIRS). Response: Thank you. We have modified the method section to include more details about the equipment and procedures for the EEG and fNIRS acquisition. - Do you not intend to evaluate changes in deoxyhemoglobin? Please contextualize Response: We are not planning on examine the changes in deoxyhemoglobin in the current study. It would one of our goals for a larger trial once the feasibility of acquiring fNIRS data during tDCS treatment of TRD in the inpatient environment. Discussion - This section needs to be better written, it is necessary to present information about protocols of other similar studies. Furthermore, I recommend making the innovative aspect of the study more evident. Response: Thank you. We have modified the discussion section as suggested. Editor comments 1. Introduction: Remove the section titles and rewrite the introduction to present a coherent narrative. Response: We have removed the section titles and modified the introduction. 2. Results: Add a dedicated results section to report pre- and post-tDCS outcomes, including measures of depression and cognition. Response: We do not have results to report with this manuscript as this is a proposal for a clinical trial. 3. Methods: Rewrite the methods section to adhere to scientific standards. Response: We have modified the methods section. 4. Results Reporting: Ensure your results include: - Depression measures (Montgomery-Asberg Depression Rating Scale (MADRS)) - Cognitive measures (Stroop Test, Revised Hopkins Verbal Learning Test (HVLT-R), Digital Symbol Coding Test (DSCT)) - EEG changes in peak alpha frequency (PAF) - Cerebral hemodynamic changes (functional near-infrared spectroscopy (fNIRS)) - Attention to statistical analysis and accurate reporting in the results section. Response: We do not have results to report with this manuscript as this is a proposal for a clinical trial. Currently, we are expecting patient recruitment to start soon, and all interventions and measurements above will be acquired then. 5. Discussion: Remove the section titles and discuss the results in the context of the study protocol. Response: We have removed the section titles and modified the discussion section. We are not able to discuss any results at this time as we are currently in the process of starting the recruitment. 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… Response: We have modified the manuscript to meet the PLOS ONE’s style requirements baed on the guidelines. 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://www.ajgponline.org/article/S1064-7481(24)00192-1/abstract In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Response: Thank you for pointing out the overlapping with our previous publication. We have updated the citation in the manuscript and made modifications to the text. 3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Response: Thank you. We have addressed this issue in the manuscript. 4. When completing the data availability statement of the submission form, you indicated that you will make your data available on acceptance. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If you are unable to adhere to our open data policy, please kindly revise your statement to explain your reasoning and we will seek the editor's input on an exemption. Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process. Response: Thank you for the explanation regarding open data policy. 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Response: Thank you. We have modfied the manuscript to include the ethics statement only in the Methods section. References Arain, M., et al. (2010). "What is a pilot or feasibility study? A review of current practice and editorial policy." BMC Medical Research Methodology 10(1): 67. Bennabi, D., et al. (2015). "Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram." Clin Neurophysiol 126(6): 1185-1189. Leucht, S., et al. (2017). "What does the MADRS mean? Equipercentile linking with the CGI using a company database of mirtazapine studies." J Affect Disord 210: 287-293. Shanyinde, M., et al. (2011). "Questions asked and answered in pilot and feasibility randomized controlled trials." BMC Medical Research Methodology 11(1): 117. Turkoz, I., et al. (2021). "Clinically meaningful changes on depressive symptom measures and patient-reported outcomes in patients with treatment-resistant depression." Acta Psychiatr Scand 143(3): 253-263. Zanardi, R., et al. (2020). "Transcranial direct current stimulation: A novel approach in the treatment of vascular depression." Brain Stimul 13(6): 1559-1565. https://doi.org/10.1371/journal.pone.0324808.r003
2 May 2025 Decision Letter - Abdolvahed Narmashiri, Editor Transcranial direct current simulation as an adjunctive treatment for treatment-resistant depression in hospitalized patients: A feasibility study protocol PONE-D-24-24817R1 Dear Dr. Lapid, 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, Abdolvahed Narmashiri Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? Reviewer #1: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??> Reviewer #1: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??> Reviewer #1: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete??> The PLOS Data policy Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes ****** Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. Reviewer #1: The authors have addressed all my concerns from the previous review. The manuscript has significantly improved ****** 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 ******** https://doi.org/10.1371/journal.pone.0324808.r004
Formally Accepted
Acceptance Letter - Abdolvahed Narmashiri, Editor PONE-D-24-24817R1 PLOS ONE Dear Dr. Lapid, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. 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. Abdolvahed Narmashiri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0324808.r005

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