https://orcid.org/0000-0002-2856-4233
Peer Review History
| Original SubmissionJune 2, 2022 |
|---|
|
PONE-D-22-15953Plasma sphingolipid abnormalities in neurodegenerative diseasesPLOS ONE Dear Dr. Takeda, 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. Comments of reviewer #1 Please address these two issues:1. Information on the separation of GalCer from GlcCer is necessary to understand to which compound are referred the results. 2. Quantitative data are necessary to understand the yield of extraction and the correct determination and comparison within samples. Comments of reviewer #2 Comments 1: Do you have information on fluid biomarkers such as plasma Ab42/Ab40 ratio and ptau? Comment 2: Can you address the question as to how changes in plasma sphingolipids relate to brain and CSF changes? Comment 3: you must address the issue relating to the different ages (are changes age-related or AD-related?) Comment 4: you must address this concern. Comment 5: please answer these two questions comment 6: address the issue regarding adding statements in the limitations section Note: Given that age is a significant risk factor in Alzheimer’s disease, the age differences should be factored into the statistical analyses. Please submit your revised manuscript by Aug 11 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:
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, Stephan N. Witt, Ph.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 2. Please amend the manuscript submission data (via Edit Submission) to include authors Yoko Sugimura, Iori Kawasaki, Saki Ohshiro, Toru Baba, Teiko Kimpara, and Hiroaki Sakuma. Additional Editor Comments: Major issue: lines 190-213 (Results section on S1P): The authors repeat in words what is depicted in the figures. This is far too repetitive. What is the purpose of the figures, if all of the findings are given in words? Example: " Plasma S1P d16.1 levels were significantly lower in the IPD group of cohort A (plasma S1P d16.1 levels: 30 IPD vs. 28 CNs; 0.0091 (0.0103-0.00713) vs. 0.0115 (0.013-0.0103); t = 4.34, p 0.0001) (Fig 1A), Suggested way to rephrase the above sentence: Plasma S1P d16.1 levels were significantly (p,0.0001) lower in the IPD group of cohort A (N= 30) versus the control group (N=28) (Fig 1A)..." Bottom line: the entire RESULTS section of the manuscript should be simplified by eliminating this redundancy of saying in words what is given in the figures. [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: Partly Reviewer #2: Yes ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: No ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This manuscript is interesting, but very preliminary. Only a few sphingolipids on the total species present in plasma were analyzed. Of course the analysis of plasma lipids from GBA1 associated neurodegenerative disease patients would be necessary, but I believe that more important would be the knowledge on the others, not considered sphingolipids. Information on the separation of GalCer from GlcCer is necessary to understand to which compound are referred the results. Quantitative data are necessary to understand the yield of extraction and the correct determination and comparison within samples. Reviewer #2: General Comment to authors The authors examine plasma sphingolipid in several neurodegenerative diseases and show striking changes in sphingosine-1-phosphate and GluCer and LacCer species. However, the small sample sizes and the significant age differences in cohort B are concerns, given that age is a significant risk factor in Alzheimer’s disease. Specific Comments to Authors 1) Interestingly, sphingolipids change in all neurodegenerative diseases examined. How do the changes in S1P, GluCer, and LacCer relate to known changes in fluid biomarkers such as plasma A�42 and A�40 ratio, and plasma ptau levels?. It would be necessary also to measure these fluid biomarkers and not merely rely on MMSE, given the small sample sizes. 2) How do the plasma changes in sphingolipids relate to brain and CSF changes? 3) The age of the CN population (cohort B) is significantly lower than that of the DLB and AD populations. Since age is a significant risk factor for AD, it is unclear whether the changes are AD-related or age-related. Additional analyses with age as a variable may help tease out whether these data are age-related or pathological. 4) What is the recovery of sphingolipids extracted with the SPE column (page 11)? What internal standards were used, and how quantitative were these standards? 5) Is there a correlation/link between the decrease in S1P and the increase in GlcCer and LacCer in plasma? What enzyme pathways may cause the decrease in S1P and the increase in GluCer and LacCer? 6) The limitations (page 22) should include that this is a small discovery/cross sectional study that can not account for multiple comparisons for several analytes detected in plasma. ********** 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 ********** [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. |
| Revision 1 |
|
PONE-D-22-15953R1Plasma sphingolipid abnormalities in neurodegenerative diseasesPLOS ONE Dear Dr. Takeda, 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. 1) Is the manuscript technically sound, and do the data support the conclusions?In response to this question, reviewer #3 says "partly" while reviewer #1 had no response. 2) Have the authors made all data underlying the findings in their manuscript fully available?Reviewer #3 says "no." 3) Reviewer #1 says that his comments pertaining to the original manuscript were not addressed: (i) I believe that more important would be the knowledge on the others, not considered sphingolipids. Editor: Point 3(i) has not been addressed, and this was also brought up by reviewer #3. Information on the separation of GalCer from GlcCer is necessary to understand to which compound are referred the results. Editor: I accept your explanation on the difficulties in separating GalCer from GlcCer. (iii) Quantitative data are necessary to understand the yield of extraction and the correct determination and comparison within samples. Editor: The reviewer was not satisfied as to your response to 3(iii). 4) Reviewer#3 comments:(i)The authors do not provide an explanation of which enzyme pathways can be affected in the observed alterations. It would provide important insights if the authors can perform additional experiments in testing the protein levels of the enzymes involved in the pathways. Editor: Please respond to 4(i). Testing protein levels of the enzymes could be helpful. Can this be done? (ii) What is the outcome of other lipids that were analyzed in this lipidomics analyses? For completeness, they should also include those, even if no differences were observed. If no other lipids were analyzed, the authors should include a reasoning why they only tested these lipids. Editor: You should include the results for other lipids tested. (iii) The collection of probands remains on very low, which lowers the impact of the manuscript. Editor: Please respond to this comment. (iv) The authors should be careful in claiming that the SL are similar in plasma compared to CSF or brain as was questioned by a reviewer; the papers the authors refer to are indirect and one even identified different findings in serum versus CSF. Perhaps it is better to include this in the limitations that these findings need to be confirmed in CSF or brain for further validation.Editor: please address this comment. (v) In addition, a few other questions are still open. Did the authors check for different lipid species as different chain length is important to define their function and hence a more in-depth analyses provides a better understanding of the findings.Editor: please address this question. (vi) Can the authors test if the IPD samples contain mutations in LRRK2 and SNCA as these are regularly identified in IPD and may provide a link to genetic forms of PDEditor: Can you test for these mutations; doing so would definitely increase the impact of your paper. 5) Editor: lines 427-431, revised: "Seventh, Quantitative data were not used as metabolites values in this study. In present lipidomic analysis, the coefficient of variation (CV) ranged from 4.4 to 9.7%, with a mean of 6.7%. Because of the variability of metabolites values, present method should be compared with healthy subjects for each cohort. Therefore, the relative areas were used as metabolites values in this study." Editor: The above explanation is very hard to understand. Please submit your revised manuscript by Dec 01 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:
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-emailutm_source=authorlettersutm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Stephan N. Witt, Ph.D. Academic Editor PLOS ONE [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: (No Response) Reviewer #3: (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: (No Response) Reviewer #3: Partly ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) Reviewer #3: 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 #1: (No Response) Reviewer #3: No ********** 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: (No Response) Reviewer #3: 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: I requested additional results, but the Authors did not add any technical new result. According to this I maintain my previous comments. Reviewer #3: Oizumi et al., performed a lipidomics analyses on plasma of patients suffering from different neurodegenerative disorders, including idiopathic Parkinson’s disease and dementia with Lewy bodies. The lipidomics focused on sphingolipidomics and revealed S1P, MonCer, and LacCer to be altered in the plasma from patients suffering from neurodegenerative diseases compared to control groups. In this revised manuscript the authors do not fully address the questions raised by the reviewers for instance: The authors do not provide an explanation of which enzyme pathways can be affected in the observed alterations. It would provide important insights if the authors can perform additional experiments in testing the protein levels of the enzymes involved in the pathways What is the outcome of other lipids that were analyzed in this lipidomics analyses? For completeness, they should also include those, even if no differences were observed. If no other lipids were analyzed, the authors should include a reasoning why they only tested these lipids. The collection of probands remains on very low, which lowers the impact of the manuscript. The authors should be careful in claiming that the SL are similar in plasma compared to CSF or brain as was questioned by a reviewer; the papers the authors refer to are indirect and one even identified different findings in serum versus CSF. Perhaps it is better to include this in the limitations that these findings need to be confirmed in CSF or brain for further validation. In addition, a few other questions are still open. Did the authors check for different lipid species as different chain length is important to define their function and hence a more in-depth analyses provides a better understanding of the findings. Can the authors test if the IPD samples contain mutations in LRRK2 and SNCA as these are regularly identified in IPD and may provide a link to genetic forms of PD ********** 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 #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. |
| Revision 2 |
|
PONE-D-22-15953R2Plasma sphingolipid abnormalities in neurodegenerative diseasesPLOS ONE Dear Dr. Takeda, Thank you for submitting your manuscript to PLOS ONE. Please make the minor corrections to table S1, and resubmit with no other changes. See my comments below. Please submit your revised manuscript by Jan 13 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:
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-emailutm_source=authorlettersutm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Stephan N. Witt, 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. Additional Editor Comments : I will accept your manuscript after you make corrections to S1 Table. In S1 Table, you repeatedly misspell the word "sphingolipids." Throughout the table sphingolipids is spelled "sphinogolipids." Please fix. [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: (No Response) 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 #1: Partly Reviewer #3: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #3: 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 #1: Yes Reviewer #3: 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 #3: 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 human plasma sphingolipid pattern has been described using different methodological approaches. It would be important to understand which are the changes of sphingolipid pattern in neurodegenerative diseases. At least a simple TLC procedure could give the preliminary information. GlcCer and GalCer sphingolipids are the result of completely different metabolic pathways. In my opinion it is necessary to know the behavior of these two compounds. There are several procedures that allow their separation. Reviewer #3: The authors have sufficiently addressed my comments and added profound explanation to unresolved questions that they also included in 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: 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. |
| Revision 3 |
|
Plasma sphingolipid abnormalities in neurodegenerative diseases PONE-D-22-15953R3 Dear Dr. Takeda, 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, Stephan N. Witt, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: |
| Formally Accepted |
|
PONE-D-22-15953R3 Plasma sphingolipid abnormalities in neurodegenerative diseases Dear Dr. Takeda: 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. Stephan N. Witt Academic Editor PLOS ONE |
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 .