A case-control regression analysis of liver enzymes in obesity-induced metabolic disorders in South Asian females

Tamseela Mumtaz; Kainat Tariq; Khadija Kanwal; Zainab Tariq

doi:10.1371/journal.pone.0303835

Peer Review History

Original SubmissionSeptember 8, 2023
7 Nov 2023 Decision Letter - Samiullah Khan, Editor PONE-D-23-28668A case control regression analysis of altered liver enzymes in obesity-induced metabolic disordersPLOS ONE Dear Dr. Mumtaz, 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. Dear author, Revise the whole manuscript as suggested by reviewers and submit for evaluation. Thanks Please submit your revised manuscript by Dec 22 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. 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Especially rephrase the title of study as advised by reviewer-2. Submit the revised version of manuscript for evaluation. Thanks [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 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: No Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No 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: 1- To control diabetes or blood pressure, patients may have been treated with drugs. How did you separate their effects on liver enzymes from the effects of obesity on liver enzymes? 2- Not consuming alcohol should be an exclusion criteria. 3- Triglyceride, bilirubin and PT-INR - could provide more comprehensive information. Are these data available? 4- In daily practice, ultrasound of the upper abdomen and fibroscan of the liver provide valuable information about liver disease. It is even possible that the liver enzymes are normal and the fibroscan shows moderate degrees of fibrosis. Not using liver imaging is one of the limitations of the study and should be mentioned Reviewer #2: The authors describe the relationship between obesity and alterations in liver enzymes potentially increasing the risk of liver diseases. The manuscript is well structured with a specific focus on South Asian females. The research sheds light on the unique health dynamics within this demographic. With that said, I have some suggestions for further improvement: Title: The manuscript title is a critical element that sets the tone for the study. To enhance clarity, it may be beneficial to rephrase the title to specify that the study exclusively focuses on data obtained from female individuals. Additionally, consider including the demographic area of the population, for instance, "South Asian Female Population," to provide a more precise context. Abstract: I would like to kindly point out that the abstract in the manuscript appears to be incomplete. Results: 1. Descriptive Titles: I recommend providing more descriptive titles for the ‘Results’ section that directly convey the key observations. This will help readers navigate the content more effectively. 2. Combining WHR and BMI Results: Given the brevity of the WHR and BMI sections and their shared focus on size-related factors, it could be advantageous to combine these into a single section to streamline the presentation. 3. Improving Table Legends: Enhance the clarity of table legends in terms of variable comparisons, particularly in Table 1, and ensure that the context of p-values is clearly defined. If applicable, consider conducting pairwise comparisons to improve data interpretation. 4. Visualization Enhancements: For Figure 1, I suggest utilizing a box plot format with overlaying individual scatter dots, which can provide a clearer representation of the data compared to dynamite plots. 5. Incorporate Regression Dot Plots: In addition to tables, it would be beneficial to present regression dot plots, displaying all data points alongside the main results. Additionally, consider including correlation plots with confidence intervals, and if authors find it suitable, these analyses can be integrated into a single plot. 6. Clear and Accessible Conclusions: Concluding each results section with a clear and less technical statement summarizing the main findings would greatly benefit the manuscript. This will facilitate a more accessible understanding of the research outcomes. 7. Supplementary Equations: To streamline the manuscript, it would be better to move the equations in line number 177/185/194/202/209 (e.g., yˆ=x+y+z) from the main text to a supplementary section, citing them where necessary for clarity. 8. Cholesterol Data and Correlations: To provide a comprehensive context, consider including correlation between cholesterol and obesity. Additionally, clarify whether the authors exclusively measured total cholesterol or if data is available for HDL, LDL, and triglycerides. Correlating this data with obesity would enhance the manuscript's depth. ****** 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: Yes: Hafez Fakheri Reviewer #2: Yes: Shrestha Mohapatra ******** [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.0303835.r001
Revision 1
7 Jan 2024 Author Response All the authors are very grateful for evaluating the manuscript through critical peer review. The reviewers indeed swotted the article with an eagle eye that depicts their competency. They raised such valuable points that greatly altered the study design and its outcome as well. We are much indebted for the reviewers' valuable comments and suggestions that improve the article's quality. The manuscript has been revised in light of reviewer’s recommendation. A detailed, point-to-point response to the reviewers’ comments is as follows Reviewer Comments Response Reviewer 1 1 To control diabetes or blood pressure, patients may have been treated with drugs. How did you separate their effects on liver enzymes from the effects of obesity on liver enzymes? It was made sure that patients either did not have any treatment for obesity-related co-morbidities or if treated, they must have shallow potency treatment that could not affect the efficacy of live function. See page 5 lines 107-109 2 Not consuming alcohol should be an exclusion criterion The study population is assumed to not be addicted to alcohol however to resolve the concern it has been mentioned in the manuscript. See page 5 line 106. 3 Triglyceride, bilirubin and PT-INR - could provide more comprehensive information. Are these data available Yes, these data are available but are part of another manuscript that is under process, hence cannot be provided. 4 In daily practice, ultrasound of the upper abdomen and fibro scan of the liver provide valuable information about liver disease. It is even possible that the liver enzymes are normal and the fibro scan shows moderate degrees of fibrosis. Not using liver imaging is one of the limitations of the study and should be mentioned The study was focused on serology and variations in liver enzyme production due to obesity, therefore, a fibro scan or ultrasound of the upper abdomen was not performed. A fibro scan with mild fibrosis may not fulfil the study objectives. This point could be valid if the study focused on liver echotexture rather than its function. However, the authors appreciated the logic, and they conceived the idea that obesity may cause fibrosis which may be asymptomatic with normal liver enzymes Reviewer 2 Response 1 Title: The manuscript title is a critical element that sets the tone for the study. To enhance clarity, it may be beneficial to rephrase the title to specify that the study exclusively focuses on data obtained from female individuals. Additionally, consider including the demographic area of the population, for instance, "South Asian Female Population," to provide a more precise context. Thanks for bringing this point to our attention. Indeed, it is a very good suggestion. The title has been rephrased as suggested. See title page 1 lines 1-3 2 Abstract: I would like to kindly point out that the abstract in the manuscript appears to be incomplete Acknowledged. The word cirrhosis was omitted from the abstract typographically. Issue resolved. see page 2 line 35 3 Results: Descriptive Titles: I recommend providing more descriptive titles for the ‘Results’ section that directly convey the key observations. This will help readers navigate the content more effectively. Titles of results sections have been changed that indicate the key observations of results being discussed. 4 Combining WHR and BMI Results: Given the brevity of the WHR and BMI sections and their shared focus on size-related factors, it could be advantageous to combine these into a single section to streamline the presentation. The sections have been combined. See title page 6 lines 129-130 5 Improving Table Legends: Enhance the clarity of table legends in terms of variable comparisons, particularly in Table 1, and ensure that the context of p-values is clearly defined. If applicable, consider conducting pairwise comparisons to improve data interpretation. Table 1 legends are described more clearly indicating P=0.05 and pairwise comparisons are indicated in the form of percentage increase or decrease. Table 2 Page # 8 Visualization Enhancements: For Figure 1, I suggest utilizing a box plot format with overlaying individual scatter dots, which can provide a clearer representation of the data compared to dynamite plots. Thank you for your valuable suggestion scatter plot provides a better illustration of data. Figure 1 is updated with individual scatter dots. See Fig 1 Incorporate Regression Dot Plots: In addition to tables, it would be beneficial to present regression dot plots, displaying all data points alongside the main results. Additionally, consider including correlation plots with confidence intervals, and if authors find it suitable, these analyses can be integrated into a single plot. Regression dot plots incorporated as suggested. See Fig. 7. The correlation plots with confidence intervals cannot be integrated into a single plot, thus presented in a table format. See page no.15 Table 8 Clear and Accessible Conclusions: Concluding each results section with a clear and less technical statement summarizing the main findings would greatly benefit the manuscript. This will facilitate a more accessible understanding of the research outcomes. Done as suggested. Supplementary Equations: To streamline the manuscript, it would be better to move the equations in line number 177/185/194/202/209 (e.g., yˆ=x+y+z) from the main text to a supplementary section, citing them where necessary for clarity. The equations have been moved from the main file to the supplementary file (S8 File). Cholesterol Data and Correlations: To provide a comprehensive context, consider including the correlation between cholesterol and obesity. Additionally, clarify whether the authors exclusively measured total cholesterol or if data is available for HDL, LDL, and triglycerides. Correlating this data with obesity would enhance the manuscript's depth. We appreciate your suggestion; indeed, it has given a new dimension to our manuscript as we have to go through the results once again thoroughly. Correlation between cholesterol and BMI is done as suggested in each respective comorbid group. See Fig. 2-6. Further data about HDL, LDL, and triglycerides cannot be provided now because it is used in another manuscript that is under process. Hope the answer will satisfy the reviewers and make the understanding of the research better. We believe that manuscript is now suitable for publication in PLOS ONE Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0303835.r002
8 Feb 2024 Decision Letter - Samiullah Khan, Editor PONE-D-23-28668R1A case-control regression analysis of liver enzymes in obesity-induced metabolic disorders in South Asian femalesPLOS ONE Dear Dr. Mumtaz, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Mar 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, Samiullah Khan, 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. 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Reviewer #1: (No Response) 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 #1: (No Response) Reviewer #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know 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: (No Response) Reviewer #2: Dear Authors, 1. Please mention the post-hoc tests performed after ANNOVA in the methods and the figure legends. 2. Please mention the number of samples i.e., n=? at appropriate places including figure legends. 3. Please write the key observation as the title of each result instead of writing the method and the statistical test used. For example, result 1 shows the relationship of obesity, diabetes, and hypertension on key health indicators in women. 4. In Figure 2,3,4,5 & 6: 1. Please include Correlation coefficient (R2) and the P-value on the regression plots. 2. Please mention axis titles. 3. It would be visually appealing to put all these plots in a single page. 4. All the plots should have consistent Y axis limits for enhanced clarity and interpretability. Thank you. ****** 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: Yes: Shrestha Mohapatra ******** [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.0303835.r003
Revision 2
23 Apr 2024 Author Response The authors are very much obliged for the suggestion of the reviewer 2 for valuable comments. The suggestion to express the results as a title rather than methods or statistical analysis changed the whole impact of the article. We have tried to address all the points raised by the reviewers except one that the Y-axis should have consistent limits. We are unable to make the Y-axis values consistent because every variable has a different unit value and can’t be set at uniformity. All regression dot plots are also incorporated on a single page to explain the results more obviously. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0303835.r004
2 May 2024 Decision Letter - Samiullah Khan, Editor A case-control regression analysis of liver enzymes in obesity-induced metabolic disorders in South Asian females PONE-D-23-28668R2 Dear Dr. Tamseela, 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, Samiullah Khan, Ph. D Academic Editor PLOS ONE Additional Editor Comments (optional): Dear author, the manuscript is now suitble for publication in PLoS ONE because all the corections have been done and addressed all the queries raised by the reviewers. Reviewers' comments: https://doi.org/10.1371/journal.pone.0303835.r005
Formally Accepted
14 May 2024 Acceptance Letter - Samiullah Khan, Editor PONE-D-23-28668R2 PLOS ONE Dear Dr. Mumtaz, 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 Dr. Samiullah Khan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0303835.r006

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