Hyperbaric oxygen therapy improves symptoms, brain’s microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: A prospective, randomized, controlled trial

Keren Doenyas-Barak; Merav Catalogna; Ilan Kutz; Gabriela Levi; Amir Hadanny; Sigal Tal; Shir Daphna-Tekoha; Efrat Sasson; Yarden Shechter; Shai Efrati

doi:10.1371/journal.pone.0264161

Peer Review History

Original SubmissionNovember 4, 2020
5 Nov 2021 Decision Letter - Miquel Vall-llosera Camps, Editor PONE-D-20-34405Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: a prospective, randomized, controlled trial.PLOS ONE Dear Dr. Doenyas, 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. I would like to sincerely apologize for the delay you have incurred with your submission. It has been exceptionally difficult to secure reviewers to evaluate your study. We have now received three completed reviews; their comments are available below. Reviewers#2 and #3 have raised significant scientific concerns about the study that need to be addressed in a revision. Please revise the manuscript to address all the reviewer's comments in a point-by-point response in order to ensure it is meeting the journal's publication criteria. Please note that the revised manuscript will need to undergo further review, we thus cannot at this point anticipate the outcome of the evaluation process. Please submit your revised manuscript by Dec 19 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: 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, Miquel Vall-llosera Camps Senior 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 study was funded by the Research Fund of Shamir Medical Center, Israel. We are grateful to Prof. Rachel Lev-Wiesel, (The Emili Sagol University of Haifa, Israel CAT Research Center). Yair Bechor PhD, Yonathan Zemel, Katia Adler, Dr. Erez, Lang, Dr. Shachar Fynci, Dr. Nir Poliak, Dr. Gregory Fishlev, Dr. Mony Fridman, Moran Adler, Or Nagauker, Rahav Boussi-Gross, Ido May-Raz and Gil Suzin (Sagol Center for hyperbaric medicine), Merav Ben Yosef, Galina Sakliarvski (Department of radiology) and Revital Ozeri (Beit Halochem) for their participation in treatment monitoring, data acquisition and medical support. We thank Hadas Okon-Zinger (Department of Psychology, University of Haifa, Haifa, Israel) for her consultation regarding fMRI tasks. We would also like to thank all the patients for their motivation, cooperation, and confidence." 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 study was funded by the Research Fund of Shamir Medical Center, Israel." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. [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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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 Reviewer #3: 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 is an excellent paper on a important topic. It is well written and the conclusions are sound. The groups are clearly define, as well as the diagnosis and treatment methods. It is also easy to understand. It provides a new way to address PTSD by optimizing brain function. Reviewer #2: I thank the authors for the opportunity to review the reporting of their important research study. While I found the manuscript generally well written and concise, clarification of a couple of things could improve the quality and scientific impact of the paper in the field. 1) On page 11, it’s not clear why prescribed cannabis (mean grams/month) is reported differently than the other prescribed medication (number of patients (% of group)). The reader is left wondering what number and percentage in each group were using prescribed cannabis during the study. 2) On page 16, line 28, the authors write: "One of the interesting findings in the current study, was the surfacing of unaccusable memories in half of the patients from the HBOT group." If the adjective "unaccusable" (not charged with wrongdoing) used here was intended to convey psychological meaning regarding the nature of previously "inaccessible" memories, then "unaccusable memories" should be operationally defined here. Moreover, since this phenomenon occurred in half those receiving treatment (n=7?) and this has only been reported once previously in the literature, this could be an important psychological predicter of therapeutic response that deserves further quantitative and qualitative analysis and discussion, especially in regards to maximizing psychological interventions for PTSD. For example, quantitatively, did those who experienced these repressed memories differ on clinical outcome measures from those who didn’t experience them within the HBOT treatment group? Were any time course patterns observed in regards to when these repressed memories began to emerge following the start of treatment? For example, in the previous fibromyalgia HBOT study cited by the authors, time course information was only provided for two of the nine patients, with reemergence of repressed memories occurring between HBOT days 17 and 34 in one and HBOT days 37 and 44 in the second patient. It would also be of interest to provide more information regarding the qualitative nature of these repressed memories and how they resolved psychotherapeutically. For example, the authors should consider providing a brief and concise clinical vignette on one or more of these 7 PTSD patients as illustrative examples as was provided in the previous fibromyalgia HBOT study. Reviewer #3: 1. Sample size determination is not acceptable. Need to add more details, e.g. effect size. 2. Data analysis section needs more work. Be consistent with the statistical terms. Just use “Repeated ANOVA” instead of “within-subject RM ANOVA ” or “mixed design RM ANOVA”. Two names were used for p value correction also: “sequence Hochberg” and “FDR (Figure 4)”, use one. What method was used if the data does not follow normal distribution? What is the “net effect size”? Page 9 line 6 the sentence “univariate analyses were performed … significant variables” can be omitted. It does not seem that you performed univariable or multivariable analyses. 3. Results: For RM ANOVA, it is not meaningful to show a significant interaction. For each outcome, better show at least three p values and mean differences (with 95% confidence intervals) for the following tests: 1) pre-post test within the treatment group, 2) pre-post test within the control group, 3) a comparison of pre-post change between the treatment and control group. The p value and mean difference (95%) for pre-post change between the two groups should be shown in Table 2 and 3. Need to test normality for RM ANOVA. Bonferroni not mentioned in method but not in the results. Page 17 line 6 “affect” instead of “effect” ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Reviewer #3: 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.0264161.r001
Revision 1
17 Nov 2021 Author Response Reply to Review Comments to the Author Reviewer #1: This is an excellent paper on a important topic. It is well written and the conclusions are sound. The groups are clearly define, as well as the diagnosis and treatment methods. It is also easy to understand. It provides a new way to address PTSD by optimizing brain function. Reply: we thank the reviewer for his support. Reviewer #2: I thank the authors for the opportunity to review the reporting of their important research study. While I found the manuscript generally well written and concise, clarification of a couple of things could improve the quality and scientific impact of the paper in the field. Comment 1: “On page 11, it’s not clear why prescribed cannabis (mean grams/month) is reported differently than the other prescribed medication (number of patients (% of group)). The reader is left wondering what number and percentage in each group were using prescribed cannabis during the study”. Reply: The number and percentage of patients using cannabis in each group were added to table 1. Comment 2: “On page 16, line 28, the authors write: "One of the interesting findings in the current study, was the surfacing of unaccusable memories in half of the patients from the HBOT group." If the adjective "unaccusable" (not charged with wrongdoing) used here was intended to convey psychological meaning regarding the nature of previously "inaccessible" memories, then "unaccusable memories" should be operationally defined here.” Reply: Thank you for the comment. The term “unaccusable memories” was replaced by the more appropriate term “inaccessible memories”. Comment 3: “since this phenomenon occurred in half those receiving treatment (n=7?) and this has only been reported once previously in the literature, this could be an important psychological predicter of therapeutic response that deserves further quantitative and qualitative analysis and discussion, especially in regards to maximizing psychological interventions for PTSD. For example, quantitatively, did those who experienced these repressed memories differ on clinical outcome measures from those who didn’t experience them within the HBOT treatment group? Were any time course patterns observed in regards to when these repressed memories began to emerge following the start of treatment? For example, in the previous fibromyalgia HBOT study cited by the authors, time course information was only provided for two of the nine patients, with reemergence of repressed memories occurring between HBOT days 17 and 34 in one and HBOT days 37 and 44 in the second patient. It would also be of interest to provide more information regarding the qualitative nature of these repressed memories and how they resolved psychotherapeutically. For example, the authors should consider providing a brief and concise clinical vignette on one or more of these 7 PTSD patients as illustrative examples as was provided in the previous fibromyalgia HBOT study.” Reply: Additional data regarding the time and pattern of the reported memories was added to the results section of the revised manuscript. The surfacing of the repressed memories was not anticipated prior to the study so no intentional questioning and monitoring of this phenomenon was done as part of the study protocol. Since it might be possible that other participants had recovery of memories and did not report it, we cannot use the current data for additional conclusions on the psychological meaning of this effect. we agree that the surfacing memories has the potential to serve as a psychological predictor of therapeutic response and it indeed deserves further quantitative and qualitative analysis. Accordingly, our next study will include in depth evaluation and actively monitored of all participants with multiple aspects related to their memory. Reviewer #3: Comment 1: “Sample size determination is not acceptable. Need to add more details, e.g. effect size. Replay: Data related to sample size calculation based on effect size was added to the Statistical analysis - Sample size section. Comment 2: “Data analysis section needs more work. Be consistent with the statistical terms. Just use “Repeated ANOVA” instead of “within-subject RM ANOVA ” or “mixed design RM ANOVA”. Two names were used for p value correction also: “sequence Hochberg” and “FDR (Figure 4)”, use one. Replay: Thank you for this comment. The ANOVA and the multiple comparisons methods were not described clearly enough. A mixed-model repeated-measure ANOVA was performed to compare post-treatment and pre-treatment data. The model included time, group and the group-by-time interaction (detailed results are presented in Supporting Tables SI-1, SI-2). Brain imaging parametric maps were corrected using the Benjamini–Hochberg False Discovery Rate (FDR) method (ref. 22 in the revised manuscript). Group-by-time interaction imaging analysis was corrected using the sequential Hochberg correction (ref. 23 in the revised manuscript). The data analysis section was revised accordingly. Comment 3: “What method was used if the data does not follow normal distribution?” Replay: In this study, all continuous data were tested by the Kolmogorov-Smirnov test and found to be normally distributed. Comment 4: “What is the “net effect size”?” Replay: Net effect size is the relative Cohen’s d effect size, defined as the improvement from baseline after HBOT minus control three months improvement divided by the pooled standard deviation (SD) of the composite score. Positive effect sizes indicate improvement. An explanation was added to the statistical analysis section. Comment 5: “Page 9 line 6 the sentence “univariate analyses were performed … significant variables” can be omitted. It does not seem that you performed univariable or multivariable analyses.” Replay: This was referred to the categorical data, and corrected in the revised manuscript. Comment 6: “Results - For RM ANOVA, it is not meaningful to show a significant interaction. For each outcome, better show at least three p values and mean differences (with 95% confidence intervals) for the following tests: 1) pre-post test within the treatment group, 2) pre-post test within the control group, 3) a comparison of pre-post change between the treatment and control group. The p value and mean difference (95%) for pre-post change between the two groups should be shown in Table 2 and 3.” Replay: The group-by-time interaction ANOVA method is a common method for demonstrating outcomes between groups controlling for time. However, we also added p-values and mean differences with 95% confidence intervals, as suggested (Tables 2 and 3). Comment 7: “Need to test normality for RM ANOVA. Bonferroni not mentioned in method but not in the results.” Replay: Indeed, RM ANOVA model is valid for normally distributed data. All continuous data in this study were normally distributed. Non-imaging data was corrected for multiple comparisons using the Bonferroni correction. Marked and added to Tables 2 and 3. Comment 8: “Page 17 line 6 “affect” instead of “effect”” Replay: Done. Attachments Attachment Submitted filename: PONE-D-20-34405 rebuttal letter.docx https://doi.org/10.1371/journal.pone.0264161.r002
19 Jan 2022 Decision Letter - Burak Yulug, Editor PONE-D-20-34405R1 Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: a prospective, randomized, controlled trial. PLOS ONE Dear Dr. Doenyas, 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 Mar 05 2022 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, Burak Yulug 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. Additional Editor Comments (if provided): This is an interesting paper indicating the therapeutic role of HBOT on PTSD associated with relevant changes in the brain network and microstructure. Although the authors responded well to the reviewers' recommendation, I think that more detail regarding the cognitive baseline data of the patients should be included in the main text. For instance, were all patients cognitively homogeneously distributed in this respect, which could be critical in affecting both the clinical and imaging data. More relevant data regarding the questions should be provided in the main text since cognitive status could be game-changer in such clinical neuroimaging studies: What is the dementia/cognitive impairment threshold of MindStream. Why the authors did not use MMSE which is widely used for dementia exclusion. [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 #3: 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 #3: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: (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 #3: (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 #3: (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 #3: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #3: 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.0264161.r003
Revision 2
27 Jan 2022 Author Response Dear Prof. Burak Yulug We thank you for your review of our manuscript. The Neurotrax tool box was chosen for baseline cognitive evaluation, as it is fully computerized test that was validated also among cognitively healthy subjects (1-2). The cognitive scores are presented as normalized scores according to age and education groups, on an IQ-style scale, where 100 represents the mean normalized score and one standard deviation equals to 15 points. The baseline global cognitive score was on the normal range expected for the patients’ age and gender, 99.4±6.2 and 98.5±8.7 in the HBOT and control group respectively, p=0.75. We have added the requested data regarding baseline cognitive score to the revised manuscript. Best regards, Keren Doenyas-Barak Attachments Attachment Submitted filename: rebuttal letter.docx https://doi.org/10.1371/journal.pone.0264161.r004
7 Feb 2022 Decision Letter - Burak Yulug, Editor Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: a prospective, randomized, controlled trial. PONE-D-20-34405R2 Dear Dr. Doenyas 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, Burak Yulug Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0264161.r005
Formally Accepted
10 Feb 2022 Acceptance Letter - Burak Yulug, Editor PONE-D-20-34405R2 Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: a prospective, randomized, controlled trial. Dear Dr. Doenyas-Barak: 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. Burak Yulug Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0264161.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .