PONE-D-22-16707Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.PLOS ONE

Dear Dr. Ramos da Silva,

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.

The manuscript is interesting, but both reviewers pointed out important aspects to be adjusted. Note the considerations pointed out in the methods and statistical treatment and in the results and conclusions. I also recommend proofreading in English throughout the text.

Please submit your revised manuscript by Oct 06 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:

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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,

Alvaro Reischak-Oliveira, Ph.D.

Academic Editor

PLOS ONE

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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

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“Bruna Ramos da Silva was founded by São Paulo Research Foundation (FAPESP). Grant number: 2017/07963-0 and FAPESP fellowship Grant number: 2019/09877-9”

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If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

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We will update your Data Availability statement to reflect the information you provide in your cover letter.

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: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: No

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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

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors aimed to examine the association between PhA and inflammatory and oxidative stress biomarkers in women with breast cancer before and after one month of chemotherapy. The authors should be congratulated by the relevance of the research. However, several methodological issues should be addressed:

1. Please clarify if inclusion criteria involves active smoking status, metabolic syndrome, hypertension. 

2. More details about the recruitment and screening process of the control group are required (ex, where were they recruited from? Other medical appoitments? How was the physical level of CG females? Did this women also present the metabolic syndrome and its features and were active smokers?

3. Before describing the methods used to assess the participants, clarify if a fasted condition was assured.

4. In the BIA description more details are required about the protocol (position, electrodes, etc). 

5. Also, provide information about the raw BIA parameters that were assessed (resistance, reactance, PhA) and which frequency was used.

6. Please include the precision (coefficient of variation-CV, for instances) for body composition variables and specifically for the PhA. The authors mentioned the precision for the biochemical variables but did not state which measurement was used (was it the CV?) and was it the same across all variables?

7. Please include a reference that supports the expected effect size of 0.35.

8. If the authors are interested in exploring how PhA could be a simple marker of health-related parameters (in this case oxidative stress and inflammation), the multiple regression analysis should consider PhA as the independent variable and not the dependent variable. The authors want to test the potential usefulness of PhA in tracking health-related parameters after adjusting for confounding factors (age, weight and height), because it is a simple marker, and not the other way around. Please make the required changes in the results and discussion.

Minor comment: please correct the word "statically" throughout the manuscript.

Reviewer #2: The manuscript is generally well written although in places the English is not entirely clear. Some examples are noted below. A thorough reading and sub-editing would be beneficial. Points to be considered.

Intro, para 1, line 5 "pathogenesis"

Intro, para 2, line 2 "that triggers inflammatory"

Intro, [ara 3, line 3 "the bad outcomes related to the aftertreatment, especially regarding metabolic alterations ". This is not clearly worded - what is actually meant by "after-treatment"? An example of a metabolic alteration would be useful.

Methods, population, para 3, last line Please provide some details about the control group recruitment. Were the age, sex-matched etc.?

Data collection, para 1. Please provide some information in relation to time of diagnosis, surgical treatment etc., presence of lymphedema (known to effect impedance measurements)....

Anthropometric measurements. To what resolution were these measurements made, in replicate...? More detail required.

BIA. BIA is an indirect assessment method that is known to be population specific and requires careful standardization of the measurement procedures (see doi: 10.1080/03091902.2017.1333165. this is in children but the same principles apply in all age groups). Please provide details. The device used is a BIS device, hence a PhA is available at all measurement frequencies. Make it clear that this study is using PhA at 50 kHz (I assume!).

Statistical analysis, last para. "t-test" not "T-test". It is not entirely clear but it seems that the test group were assessed twice (To and T1) but the control group once only. In this case, the test group differences should be assessed using a paired-tests and the CG versus test group using a group analysis. A weakness of this study design is that the CG group were not followed for a similar time period as the test group. Thud change in the test group may simply be a reflection of normal fluctuation but unknown in the absence of comparable control data. This needs to be addressed and discussed as study limitation.

Multiple regression analysis was used but what type, was it simple OLS or a derivative e.g. ridge regression or even a Bayesian approach. More details are required. For example which of the many potential variables were included and why? How was multi-collinearity assessed?

Statistical analysis, penultimate sentence. "To assess the ability of regressions models making predictions, it was used the verification by the least square methods". What exactly does this mean? Assessment of predictive power requires some form of cross-validation, e.g., split-grroup, LOOCV, K-means etc. This appears not to have been undertaken. Table 3 indicates that a particular set of variables may have some value in terms of explaining variability but this is not the same of developing a predictive model or algorithm. Please be more explicit in what you are wishing to achieve.

Results, Table 1. Please present all data to a consistent number of significant places, i.e., one. Also the the column headings, e.g., "T0xT1" requires more explanation. Are the values "t " values?, "P" values? Be consistent with units, e.g., both kg and KG are used. Use SI units. Abbreviations are not consistent, e.g., ECW and EX.

The BIA data do not seem to be consistent. For example, mean FFM at T0 = 34 kg for CG = 35.6 kg, The corresponding TBW values are 31. 9 and 33.4 L. BIA is a 2C model and is typically calibrated against deuterium dilution to provide TBW and then FFM calculate using the hydration fraction of FFM (0.732). THus the calculated FFM from TBW are 43.6 and 45.6 for CG. These are not the FFM values provided? Why the discrepancy? THis casts a cloud over the quality of the data. This must be explained.

Discussion. The authors discuss the relationship between PhA and various variables in their study and those of others. They are, however, not duly critical that these are simply empirically-observed relationships that may have tenuous biological or physiological links. Although, not specifically stated I assume that the data are whole body (wrist to ankle) impedance data. Thus the PhA value represents some form of average value arising from all cells and structures along the conductive path. This will be all variety of tissue types including, muscles, organs etc. Consequently, it is difficult to see a real (causal?) connection between PhA and, for example, circulating albumin. This point needs to be made. Study limitations are not discussed, particularly, the absence of repeat measurements in the control group to allow for time-related changes in parameters in the test group irrespective of treatment or disease status.

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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.

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Reviewer #1: No

Reviewer #2: No

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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.

PONE-D-22-16707R1Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.PLOS ONE

Dear Dr. Ramos da Silva,

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: Reviewer 2 raised some intersting points that must be considered. Please submit your revised manuscript by 16th December. 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,

Alvaro Reischak-Oliveira, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: 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 authors addressed the raised comments. The paper was improved and is now able to provide additional insights to the related research field

Reviewer #2: The authors have addressed most of the issues raised but I remain concerned about the BIA data in Table 1, i.e., the discrepancy between the stated TBW and FFM values. The authors have provided a brief but comprehensive review of the BIA methods and made reference to differences in hydration fraction in different populations. But this does not address the key issue. Going back to my example from the Table, for a TBW of 31.9 L and an FFM of 34 kg suggests an HF of 31.9/34 or 93.8%, physiologically unrealistic. Hydration values such as this are simply not seen.

Something is wrong here. I may be misinterpreting the data but I do not think so. To state that the papers focus is not on FM and FFM is missing the point. If these are not correct then how can the reader be assured that the phase data are correct since FFM and FM have been calculated from the measured BIA data. This MUST be explained for, at least, this reader to have confidence in data validity.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: 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.

PONE-D-22-16707R2Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.PLOS ONE

Dear Dr. Silva,

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.

Although one of the reviewers has already accepted the manuscript, the second reviewer still highlights an aspect that deserves attention.

He remains concerned about the BIA data in Table 1, i.e., the discrepancy between the stated TBW and FFM values. His concern makes sense, and so I'd like you to respond carefully to him.

Please submit your revised manuscript by Feb 04 2023 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,

Alvaro Reischak-Oliveira, Ph.D.

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.]

[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.

PONE-D-22-16707R3Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.PLOS ONE

Dear Dr. Silva,

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 fully understand that the delay in accepting the manuscript can cause some frustration. However, reviewer 2 makes a point that needs to be clarified. The issue of the incorrect BIS TBW and FFM remains, so it is essential that you provide a proper explanation for this aspect.

Please submit your revised manuscript by Apr 03 2023 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,

Alvaro Reischak-Oliveira, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #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 #2: Thank you for now calculating FFM according to the Kotler equation.

I do not wish to delay the paper further but the issue of the incorrect BIS TBW and FFM remains. The authors are correct about BIA being a 2C model etc., thus it is disturbing that BIS_FM + BIS_FFM do not equal weight (Table 1: 34 + 28.8 = 62.8 yet weight is 71.7 kg). I wonder if this is a nomenclature issue and that BIS-FFM is actually BIS_Lean, i.e. FFM - BMC. This could be the explanation. I suggest that the authors consult the device manual to check this.

This discrepancy needs to be explained and/or discussed. I am sorry about this but the paper must be scientifically correct.

**********

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 #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.

Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.

PONE-D-22-16707R4

Dear Dr. Silva,

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.

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Kind regards,

Alvaro Reischak-Oliveira, Ph.D.

Academic Editor

PLOS ONE

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 #2: All comments have been addressed

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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 #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

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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 #2: Yes

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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 #2: Yes

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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 #2: Thanks for checking and making the correction regarding Lean versus FFM. You are not the first who have been caught by this nomenclature error!

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Reviewer #2: No

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