A protocol to simultaneously examine cardiorespiratory, cerebrovascular and neurophysiological responses inside a hypobaric chamber

Evan A. Hutcheon; Sherri Ferguson; Victoria E. Claydon; Urs Ribary; Sam M. Doesburg

doi:10.1371/journal.pone.0312622

Peer Review History

Original SubmissionNovember 28, 2023
10 Apr 2024 Decision Letter - Vincenzo Lionetti, Editor PONE-D-23-38539A protocol to simultaneously examine cardiorespiratory, cerebrovascular and neurophysiological responses inside a hypobaric chamberPLOS ONE Dear Dr. Hutcheon, 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. ============================== ACADEMIC EDITOR: All issues raised by expert reviewers are required. Please provide a point-by-point revision. ============================== Please submit your revised manuscript by May 23 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Vincenzo Lionetti, M.D., PhD 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. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement. 3. We note that Figure(s) 1 and 2 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a. You may seek permission from the original copyright holder of Figure(s) 1 and 2 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an ""Other"" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b. If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. 4. 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. Does the manuscript report a protocol which is of utility to the research community and adds value to the published literature? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the protocol been described in sufficient detail? To answer this question, please click the link to protocols.io in the Materials and Methods section of the manuscript (if a link has been provided) or consult the step-by-step protocol in the Supporting Information files. The step-by-step protocol should contain sufficient detail for another researcher to be able to reproduce all experiments and analyses. Reviewer #1: Partly Reviewer #2: Yes ****** 3. Does the protocol describe a validated method? The manuscript must demonstrate that the protocol achieves its intended purpose: either by containing appropriate validation data, or referencing at least one original research article in which the protocol was used to generate data. Reviewer #1: Yes Reviewer #2: No ****** 4. If the manuscript contains new data, have the authors made this data 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: N/A Reviewer #2: N/A ****** 5. Is the article 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 highlight any specific errors that need correcting in the box below. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Method. If a mask leak occurs, the measured end-tidal gases will not be accurate. How is it planned to measure the inspiratory fraction of gases (oxygen, carbon dioxide) in the mask? I mean, in addition to the fact that the internal hypobaric safety assistant will make sure that the reserve bag of respiratory gases never collapses on itself or becomes too full. Expertise needed to implement protocol “The need for and qualifications of supervising medical personnel depends on the level of the hypoxic stimulus, at a more severe hypoxic dose we recommend having a physician present”. Comment: As this is a research protocol where there may be unexpected events, it is strongly recommended that the physician with expertise in emergency medicine be present at all times. References. 26 out of 44 manuscripts (59%) are older than ten years ago. Where possible, it is recommended that the references be updated. Reviewer #2: Comments on manuscript “A protocol to simultaneously examine cardiorespiratory, cerebrovascular and neurophysiological responses inside a hypobaric chamber” by Evan A Hutcheon. The study, authored by Dr Hutcheon, is a proposal for a protocol to investigate neuro-physiological, cerebro-vascular and cardio-respiratory responses in a hypobaric chamber. Based on their previous experimental experience, the authors describe a setup designed to address several complex physio-pathological questions related to high altitude physiology by integrating data derived from EEG, transcranial Doppler ultrasound, blood pressure, oxygen saturation, end-tidal gases and respiratory rate. Major comment The main problem with this study is that it does not produce any real results, although the subject of the study is worthy of attention in view of all the considerations made by the authors. However, real and reproducible data are needed to confirm feasibility and to evaluate physiological responses to hypoxia in different conditions. In addition, the description of the protocol setup has already been published in a dedicated journal, as claimed by the authors. (https://protocols.io/view/aprotocol-to-simultaneouslyexamine-cardiorespirac46cyzaw). Minor comments What about hypobaric normoxia (e.g. mountaineers breathing oxygen blends at high altitude)? What about simulation of acclimatisation responses? In your protocol, depressurisation is quite fast (a few minutes)? ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Pasquale Longobardi Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0312622.r001
Revision 1
15 Aug 2024 Author Response 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. We have made the changes to our headings and author list. We also added supplementary document captions at the end of the manuscript, but before the references. 2. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement. We have updated the statement. Due to legal and ethical restriction, data cannot be made publicly available. Data will be made available upon request. Additional published or public analyses would only be permitted with ethics approval for secondary data access. Requests for access to datasets should be made to the corresponding author. 3. We note that Figure(s) 1 and 2 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a. You may seek permission from the original copyright holder of Figure(s) 1 and 2 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an ""Other"" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b. If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. We bought a license for BioRender and remade Figure 2 with it. Figure 1 was commissioned by a co-author (Sherri Ferguson). I have used modified versions of this figure in the past without issue, and this is the first time I am using the original version. I simply stated that it is revised from another paper, which it is. 4. 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. We have added captions to our supporting information at the end of the manuscript. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript report a protocol which is of utility to the research community and adds value to the published literature? Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 2. Has the protocol been described in sufficient detail? To answer this question, please click the link to protocols.io in the Materials and Methods section of the manuscript (if a link has been provided) or consult the step-by-step protocol in the Supporting Information files. The step-by-step protocol should contain sufficient detail for another researcher to be able to reproduce all experiments and analyses. Reviewer #1: Partly Reviewer #2: Yes ________________________________________ 3. Does the protocol describe a validated method? The manuscript must demonstrate that the protocol achieves its intended purpose: either by containing appropriate validation data, or referencing at least one original research article in which the protocol was used to generate data. Reviewer #1: Yes Reviewer #2: No I did reference two previous research articles where we used the protocol to generate data. When we applied for ethics for those studies we did not state that the data would be available for secondary uses. ________________________________________ 4. If the manuscript contains new data, have the authors made this data 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: N/A Reviewer #2: N/A ________________________________________ 5. Is the article 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 highlight any specific errors that need correcting in the box below. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Method. If a mask leak occurs, the measured end-tidal gases will not be accurate. How is it planned to measure the inspiratory fraction of gases (oxygen, carbon dioxide) in the mask? I mean, in addition to the fact that the internal hypobaric safety assistant will make sure that the reserve bag of respiratory gases never collapses on itself or becomes too full. Expertise needed to implement protocol “The need for and qualifications of supervising medical personnel depends on the level of the hypoxic stimulus, at a more severe hypoxic dose we recommend having a physician present”. Comment: As this is a research protocol where there may be unexpected events, it is strongly recommended that the physician with expertise in emergency medicine be present at all times. Thank you for this consideration. We have included this in the revised manuscript References. 26 out of 44 manuscripts (59%) are older than ten years ago. Where possible, it is recommended that the references be updated. We have added some updated references. Reviewer #2: Comments on manuscript “A protocol to simultaneously examine cardiorespiratory, cerebrovascular and neurophysiological responses inside a hypobaric chamber” by Evan A Hutcheon. The study, authored by Dr Hutcheon, is a proposal for a protocol to investigate neuro-physiological, cerebro-vascular and cardio-respiratory responses in a hypobaric chamber. Based on their previous experimental experience, the authors describe a setup designed to address several complex physio-pathological questions related to high altitude physiology by integrating data derived from EEG, transcranial Doppler ultrasound, blood pressure, oxygen saturation, end-tidal gases and respiratory rate. Major comment The main problem with this study is that it does not produce any real results, although the subject of the study is worthy of attention in view of all the considerations made by the authors. However, real and reproducible data are needed to confirm feasibility and to evaluate physiological responses to hypoxia in different conditions. I have cited my results from two previous studies where we published with this data. In addition, the description of the protocol setup has already been published in a dedicated journal, as claimed by the authors. (https://protocols.io/view/aprotocol-to-simultaneouslyexamine-cardiorespirac46cyzaw). The description I published to protocols.io is a requirement for writing a PloS ONE lab protocol. Minor comments What about hypobaric normoxia (e.g. mountaineers breathing oxygen blends at high altitude)? We did not include this condition as we wanted to explicitly compare normbaric and hypobaric hypoxia, as the literature is sparse as to whether both are equivalent. If they are similar, which has to be validated by more studies, then normobaric hypoxia can be utilized as a surrogate in place of a hypobaric chamber for those studies. We did include a short section stating that diverse paradigms, such as hypobaric normoxia are possible with our paradigm. What about simulation of acclimatisation responses? In your protocol, depressurisation is quite fast (a few minutes)? In theory, acclimatisation protocols are possible; however, these protocols are more complicated and beyond this papers scope. Individuals could stay in the chamber for several days with a commode toilet and food deliveries through the hatch. I have included a short section on how to potentially adapt the paradigm to reflect this. ________________________________________ 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Pasquale Longobardi Reviewer #2: No Attachments Attachment Submitted filename: reviewer_comments_plos.docx https://doi.org/10.1371/journal.pone.0312622.r002
11 Sep 2024 Decision Letter - Vincenzo Lionetti, Editor PONE-D-23-38539R1A protocol to simultaneously examine cardiorespiratory, cerebrovascular and neurophysiological responses inside a hypobaric chamberPLOS ONE Dear Dr. Hutcheon, 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. ============================== ACADEMIC EDITOR: Some issues should be addressed in order to further strenght background. ============================== Please submit your revised manuscript by Oct 24 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Vincenzo Lionetti, M.D., PhD 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. Does the manuscript report a protocol which is of utility to the research community and adds value to the published literature? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the protocol been described in sufficient detail? To answer this question, please click the link to protocols.io in the Materials and Methods section of the manuscript (if a link has been provided) or consult the step-by-step protocol in the Supporting Information files. The step-by-step protocol should contain sufficient detail for another researcher to be able to reproduce all experiments and analyses. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Does the protocol describe a validated method? The manuscript must demonstrate that the protocol achieves its intended purpose: either by containing appropriate validation data, or referencing at least one original research article in which the protocol was used to generate data. Reviewer #1: Yes Reviewer #2: Yes ****** 4. If the manuscript contains new data, have the authors made this data 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: N/A Reviewer #2: N/A ****** 5. Is the article 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 highlight any specific errors that need correcting in the box below. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The manuscript has been diligently revised. A search for similar manuscripts reports for some not cited in your references (see below, ie. Theunissen dated 2022). It remains doubtful that the proposed search protocol is not up to date with the current state of knowledge. I recommend a thorough meta-analysis of the literature. 1) Theunissen S, Balestra C, Bolognési S, Borgers G, Vissenaeken D, Obeid G, Germonpré P, Honoré PM, De Bels D. Effects of Acute Hypobaric Hypoxia Exposure on Cardiovascular Function in Unacclimatized Healthy Subjects: A "Rapid Ascent" Hypobaric Chamber Study. Int J Environ Res Public Health. 2022 Apr 28;19(9):5394. doi: 10.3390/ijerph19095394. PMID: 35564787; PMCID: PMC9102089. 2) Neuhaus C, Hinkelbein J. Cognitive responses to hypobaric hypoxia: implications for aviation training. Psychol Res Behav Manag. 2014 Nov 10;7:297-302. doi: 10.2147/PRBM.S51844. PMID: 25419162; PMCID: PMC4234165 Reviewer #2: The authors of the present paper have responded thoroughly to the reviewers' questions, thereby improving their work. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Pasquale Longobardi MD Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0312622.r003
Revision 2
18 Sep 2024 Author Response 6. Response to reviewer comments Thank you for recommending those two references. They have been added to the manuscript. We have also included the following papers: Rosales AM, Shute RJ, Hailes WS, Collins CW, Ruby BC, Slivka DR. Independent effects of acute normobaric hypoxia and hypobaric hypoxia on human physiology. Sci Rep. 2022 Nov 15;12(1):19570. doi: 10.1038/s41598-022-23698-5. PMID: 36379983; PMCID: PMC9666440. Chroboczek M, Kujach S, Łuszczyk M, Grzywacz T, Soya H, Laskowski R. Acute Normobaric Hypoxia Lowers Executive Functions among Young Men despite Increase of BDNF Concentration. Int J Environ Res Public Health. 2022 Aug 30;19(17):10802. doi: 10.3390/ijerph191710802. PMID: 36078520; PMCID: PMC9518314 Hohenauer E, Freitag L, Costello JT, Williams TB, Küng T, Taube W, Herten M, Clijsen R. The effects of normobaric and hypobaric hypoxia on cognitive performance and physiological responses: A crossover study. PLoS One. 2022 Nov 10;17(11):e0277364. doi: 10.1371/journal.pone.0277364. PMID: 36355846; PMCID: PMC9648783. Hohenauer E, Taube W, Freitag L, Clijsen R. Sex differences during a cold-stress test in normobaric and hypobaric hypoxia: A randomized controlled crossover study. Front Physiol. 2022 Sep 23;13:998665. doi: 10.3389/fphys.2022.998665. PMID: 36225301; PMCID: PMC9549379. Attachments Attachment Submitted filename: response_to_reviewer.docx https://doi.org/10.1371/journal.pone.0312622.r004
10 Oct 2024 Decision Letter - Vincenzo Lionetti, Editor A protocol to simultaneously examine cardiorespiratory, cerebrovascular and neurophysiological responses inside a hypobaric chamber PONE-D-23-38539R2 Dear Dr. Hutcheon, 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, Vincenzo Lionetti, M.D., PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript report a protocol which is of utility to the research community and adds value to the published literature? Reviewer #1: Yes ******** 2. Has the protocol been described in sufficient detail? To answer this question, please click the link to protocols.io in the Materials and Methods section of the manuscript (if a link has been provided) or consult the step-by-step protocol in the Supporting Information files. The step-by-step protocol should contain sufficient detail for another researcher to be able to reproduce all experiments and analyses. Reviewer #1: Yes ****** 3. Does the protocol describe a validated method? The manuscript must demonstrate that the protocol achieves its intended purpose: either by containing appropriate validation data, or referencing at least one original research article in which the protocol was used to generate data. Reviewer #1: Yes ****** 4. If the manuscript contains new data, have the authors made this data 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: N/A ****** 5. Is the article 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 highlight any specific errors that need correcting in the box below. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The text has been updated with the latest literature. I suggest following the other authors' advice in the protocol, at least as far as deemed appropriate. I recommend publishing the manuscript. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Pasquale Longobardi ******** https://doi.org/10.1371/journal.pone.0312622.r005
Formally Accepted
14 Oct 2024 Acceptance Letter - Vincenzo Lionetti, Editor PONE-D-23-38539R2 PLOS ONE Dear Dr. Hutcheon, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Prof. Vincenzo Lionetti Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0312622.r006

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