Behavioral assessment of children and adolescents with Graves’ disease: A prospective study

Sherifa Ahmed Hamed; Fadia Ahmed Attiah; Samir Kamal Abdulhamid; Mohamed Fawzy

doi:10.1371/journal.pone.0248937

Peer Review History

Original SubmissionDecember 9, 2020
6 Jan 2021 Decision Letter - Melissa A Brotman, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-20-38682 Behavioral assessment of children and adolescents with Graves' disease: A prospective study PLOS ONE Dear Dr. Hamed, 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 Feb 14 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Melissa A Brotman, PhD Academic Editor PLOS ONE Additional Editor Comments: Thank you very much for your manuscript to PLOS ONE. We have secured a review who saw great merits with the manuscript, but also raised some concerns, which are noted below. We encourage you to address the comments and submit a revised version. Thank you again for submitting to PLOS ONE. Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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: 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 ****** 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. This report describes behavior in children with Graves disease prior to treatment with antithyroid drugs and following such treatment. Behavior is assessed using the Child Behavior Checklist. 2. The authors refer to the period during which the children with Graves disease are treated with anti-thyroid drugs as the 'remission state.' This description is misleading since 'remission' is commonly used to describe the phase of Graves disease in which treatment is not required as a result of decreased production of thyroid stimulating immunoglobulins or as a result of concurrent thyroiditis rendering the thyroid gland unable to respond to these stimulating immunoglobulins. A preferable term to describe normalization of thyroid hormone levels resulting from antithyroid drug therapy is 'normalized thyroid hormone levels.' 3. There are three occurrences in the manuscript in which the authors erroneously describe hyperthyroidism as 'hyperparathyroidism' :first and fifth sentences of the Introduction and third paragraph of the Discussion. Parathyroid hormone is produced by parathyroid glands (which are close to the thyroid gland. Parathyroid hormone regulates circulating levels of calcium and phosphorus.) This distinction is particularly important since parathyroid hormone excess can be associated with abnormal brain function. 4. Under 'Methods,' the second sentence should read: 'Their age ranged...' 5. Under 'Methods' in the first paragraph, third sentence: best to use the spelling 'thyroxine' rather than 'thyroxin' 6. Under 'Methods' in the first paragraph, fourth sentence: instead of 'thyroid hormone state' use 'thyroid hormone status.' 7. In the next sentence under 'Methods,' '(2) those in remission (ie, maintained in euthyroid state' best to spell euthyroid as above instead of 'euothyroid.' In addition best to refer to this state as normalized thyroid state' rather than as 'euthyroid.' The next sentence also has 'euthyroid' misspelled as 'euothyroid.' 8. Under 'Exclusion Criteria': the authors should consider including children with Graves ophthalmopathy since this condition should not confound findings in the WISC-III or in the CBCL/8-18. 9. Under 'Laboratory Testing': TSH should not be included under the term 'thyroid hormones.' Best to refer to all of these tests as 'thyroid function tests.' 10. Under 'Statistical analyses' eighth line--do not refer to status during treatment with antithyroid drugs as 'remission state.' Better to use 'drug-corrected state.' 11. In first paragraph under 'Results' and in first 2 paragraphs under 'Discussion': do not refer to drug-corrected state as 'remission.' 12. In second paragraph of the discussion, the authors should substitute 'normalized thyroid thyroid hormone levels' for 'euthyroid state.' 13. In the first line on page 10 (part of the Discussion), the last word should be 'following' rather than 'followings.' 14. In second line on page 10: ' There are a large number...' 15. The authors refer to thyroid hormones as accepted treatment for depression. Recent studies and reviews question this. The authors should provide a recent reference supporting this practice. ****** 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:** Donald Zimmerman, MD [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.0248937.r001
Revision 1
15 Jan 2021 Author Response We are grateful to the reviewers for the valuable and helpful editor's and reviewers' comments on our manuscript ID # [PONE-S-20-48013] with the title "Behavioral assessment of children and adolescents with Graves' disease: A prospective study" submitted as an original article wishing to be published in Plos One. We have addressed all comments (point-by-point), as indicated in the attached pages and considered their corrections within the main text. We hope that the explanations and revisions of our work are satisfactory. We have highlighted the changes in the revised manuscript (yellow color). Response to reviewer's # 1 comments Reviewer: 1- This report describes behavior in children with Graves disease prior to treatment with antithyroid drugs and following such treatment. Behavior is assessed using the Child Behavior Checklist. 2- The authors refer to the period during which the children with Graves disease are treated with anti-thyroid drugs as the 'remission state.' This description is misleading since 'remission' is commonly used to describe the phase of Graves disease in which treatment is not required as a result of decreased production of thyroid stimulating immunoglobulins or as a result of concurrent thyroiditis rendering the thyroid gland unable to respond to these stimulating immunoglobulins. A preferable term to describe normalization of thyroid hormone levels resulting from antithyroid drug therapy is 'normalized thyroid hormone levels.' Author: We used the preferable term "normalized thyroid hormone levels state" instead of "in remission" whenever cited throughout the text. Reviewer: 3. There are three occurrences in the manuscript in which the authors erroneously describe hyperthyroidism as 'hyperparathyroidism': first and fifth sentences of the Introduction and third paragraph of the Discussion. Parathyroid hormone is produced by parathyroid glands (which are close to the thyroid gland. Parathyroid hormone regulates circulating levels of calcium and phosphorus.) This distinction is particularly important since parathyroid hormone excess can be associated with abnormal brain function. Author: They have been edited correctly Reviewer: 4. Under 'Methods,' the second sentence should read: 'Their age ranged...' Author: It has been edited correctly Reviewer: 5. Under 'Methods' in the first paragraph, third sentence: best to use the spelling 'thyroxine' rather than 'thyroxin' Author: We have replaced the term "thyroxin" with "thyroxine" throughout the manuscript text. Reviewer: 6. Under 'Methods' in the first paragraph, fourth sentence: instead of 'thyroid hormone state' use 'thyroid hormone status.' Author: It has been edited. Reviewer: 7. In the next sentence under 'Methods,' '(2) those in remission (ie, maintained in euthyroid state' best to spell euthyroid as above instead of 'euothyroid.' In addition best to refer to this state as normalized thyroid state' rather than as 'euthyroid.' The next sentence also has 'euthyroid' misspelled as 'euothyroid.' Author: We replaced euothyroid by "normalized thyroid state". Reviewer: 8. Under 'Exclusion Criteria': the authors should consider including children with Graves ophthalmopathy since this condition should not confound findings in the WISC-III or in the CBCL/8-18. Author: - None of the recruited children had Ophthalmopathy - We revised the text of "previous relapse or presence of Graves Ophthalmopathy," into "previous relapse," Reviewer: 9. Under 'Laboratory Testing': TSH should not be included under the term 'thyroid hormones.' Best to refer to all of these tests as 'thyroid function tests.' Author: We have revised it as thyroid function tests Reviewer: 10. Under 'Statistical analyses' eighth line--do not refer to status during treatment with antithyroid drugs as 'remission state.' Better to use 'drug-corrected state.' Author: We have revised it as 'drug-corrected Reviewer: 11. In first paragraph under 'Results' and in first 2 paragraphs under 'Discussion': do not refer to drug-corrected state as 'remission.' Author: We have done and wherever found, we replace in remission by drug-corrected. Reviewer: 12. In second paragraph of the discussion, the authors should substitute 'normalized thyroid thyroid hormone levels' for 'euthyroid state.' Author: We have substituted it by "normalized thyroid hormone levels" Reviewer: 13. In the first line on page 10 (part of the Discussion), the last word should be 'following' rather than 'followings.' Author: It has been edited Reviewer: 14. In second line on page 10: ' There are a large number...' Author: We have edited it. Reviewer: 15. The authors refer to thyroid hormones as accepted treatment for depression. Recent studies and reviews question this. The authors should provide a recent reference supporting this practice. Author: Page 10 and 11: This has been revised as follow and we provided a recent reference supporting this practice as follow: "(6) Thyroxine and TRH are used successfully for treatment of major depression [29,30]. However, some recent studies and reviews showed controversial evidence [31]." Trifu S, Popescu A, Dragoi AM, Trifu AI. Thyroid hormones as a third line of augmentation medication in treatment-resistant depression. Acta Endocrinol (Buchar). 2020;16(2):256-261. http://doi.org./10.4183/aeb.2020.256. PMID: 33029246 Reviewer: Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Author: The text of manuscript has been revised by a colleague who naive language is English. With this manuscript, there are 4 tables which we wish to be published. I certify that the materials of this work “Behavioral assessment of children and adolescents with Graves' disease: A prospective study” have not been submitted simultaneously elsewhere and that there is no part of the text or any of the tables has been copyrighted, published, or reproduced elsewhere. I certify that all individuals included as authors of papers have contributed substantially to the scientific process leading up to the writing of the paper and its revised version. Thank you for accepting reviewing our manuscript. https://doi.org/10.1371/journal.pone.0248937.r002
10 Feb 2021 Decision Letter - Melissa A Brotman, Editor PONE-D-20-38682R1 Behavioral assessment of children and adolescents with Graves' disease: A prospective study PLOS ONE Dear Dr. Hamed, 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 27 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Melissa A Brotman, PhD 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) ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: 1. Abstract-1st sentence: Previous studies have...instead of 2. Abstract-second sentence: These studies are scarce [not scare] 3. Abstract -3rd sentence: This study aimed to STUDY [rather than 'determine.'] 4. Abstract- The authors appear to associate worse outcomes with low TSH levels and then with higher TSH levels (both in abstract and in first paragraph of Results. Please explain these apparently contradictory findings. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Donald Zimmerman, MD [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.0248937.r003
Revision 2
12 Feb 2021 Author Response We are grateful to the reviewers for the valuable and helpful editor's and reviewers' comments on our manuscript ID # [PONE-D-20-38682R1] with the title "Behavioral assessment of children and adolescents with Graves' disease: A prospective study" submitted as an original article wishing to be published in Plos One. We have addressed all comments (point-by-point), as indicated in the attached pages and considered their corrections within the main text. We hope that the explanations and revisions of our work are satisfactory. We have highlighted the changes in the revised manuscript (yellow color). Response to reviewer's # 1 comments Reviewer: 1. Abstract-1st sentence: Previous studies have...instead of Author: It has been revised to "Previous studies have identified frequent…." Reviewer: 2. Abstract-second sentence: These studies are scarce [not scare] Author: It has been corrected. Reviewer: 3. Abstract -3rd sentence: This study aimed to STUDY [rather than 'determine.'] Author: It has been revised as follow: "This work aimed to study…." Reviewer: 4. Abstract- The authors appear to associate worse outcomes with low TSH levels and then with higher TSH levels (both in abstract and in first paragraph of Results. Please explain these apparently contradictory findings. Author: This has been clarified as in the abstract as the results of the study as follow: Abstract: "Multiple linear regression analysis showed that lower concentrations of TSH (P=0.001; P=0.03) and higher fT4 (P=0.001, P=0.01), fT3 (P=0.01; P=0.06) and TRAbs (P=0.001; P=0.001) (at presentation)" Results: "Multiple linear regression analysis showed that "at presentation" lower concentrations of TSH (P=0.001; P=0.03) and higher fT4 (P=0.001, P=0.01), fT3 (P=0.01; P=0.06) and TRAbs (P=0.001; P=0.001) were predictors of behavioral problems in children with active GD and normalized thyroid hormone levels' states (table 4)." Reviewer: Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Author: The text of manuscript has been revised by a colleague who naive language is English. With this manuscript, there are 4 tables which we wish to be published. I certify that the materials of this work “Behavioral assessment of children and adolescents with Graves' disease: A prospective study” have not been submitted simultaneously elsewhere and that there is no part of the text or any of the tables has been copyrighted, published, or reproduced elsewhere. I certify that all individuals included as authors of papers have contributed substantially to the scientific process leading up to the writing of the paper and its revised version. Thank you for accepting reviewing our manuscript. https://doi.org/10.1371/journal.pone.0248937.r004
3 Mar 2021 Decision Letter - Melissa A Brotman, Editor PONE-D-20-38682R2 Behavioral assessment of children and adolescents with Graves' disease: A prospective study PLOS ONE Dear Dr. Hamed, 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 Apr 17 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Melissa A Brotman, PhD 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: 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: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: 1. The manuscript is improved. Most of the problems which remain are related to language rather than to scientific issues. 2. Abstract Line 7: Instead of 'active and normalized thyroid hormone levels' states'---'during periods of thyroid hormone elevation and of normalized thyroid hormones.' Use these terms also in line 16. Similar verbiage should be used in line 4 and in the final paragraph of the introduction. 3.In 'Methods' section--line 3: omit comma between 'out-patient clinic' and and 'of Assiut University Hospital.' 4. 'Methods' section line 8: (2) those with normal thyroid hormone levels 5. 'Methods' section line 10: '...which was subsequently titrated to maintain normal thyroid hormone levels based on...' ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Donald Zimmerman, MD [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.0248937.r005
Revision 3
4 Mar 2021 Author Response We are grateful to the valuable and helpful reviewers' and editor's comments on our manuscript ID # [PONE-D-20-38682R2] with the title "Behavioral assessment of children and adolescents with Graves' disease: A prospective study" submitted as an original article wishing to be published in Plos One. We have addressed all comments (point-by-point), as indicated in the attached pages and considered their corrections within the main text. We hope that the explanations and revisions of our work are satisfactory. We have highlighted the changes in the revised manuscript (yellow color). Response to Editor's comments - The text of manuscript has been edited by a colleague who naive language is English. - We have included this statement in your website related to Data Availability "Data cannot be shared publicly because they contain potentially sensitive information. Data are available from the ethics committee of Faculty of Medicine, Assiut, University (medicinegraduate@aun.edu.eg)". Response to reviewer's # 1 comments Reviewer: 1. The manuscript is improved. Most of the problems which remain are related to language rather than to scientific issues. Author: Reviewer: 2. Abstract Line 7: Instead of 'active and normalized thyroid hormone levels' states'---'during periods of thyroid hormone elevation and of normalized thyroid hormones.' Use these terms also in line 16. Similar verbiage should be used in line 4 and in the final paragraph of the introduction. Author: We have done the required corrections Reviewer: 3. In 'Methods' section--line 3: omit comma between 'out-patient clinic' and and 'of Assiut University Hospital.' Author: It has been corrected. Reviewer: 4. 'Methods' section line 8: (2) those with normal thyroid hormone levels Author: It has been corrected. Reviewer: 5. 'Methods' section line 10: '...which was subsequently titrated to maintain normal thyroid hormone levels based on...' Author: It has been corrected. With this manuscript, there are 4 tables which we wish to be published. I certify that the materials of this work “Behavioral assessment of children and adolescents with Graves' disease: A prospective study” have not been submitted simultaneously elsewhere and that there is no part of the text or any of the tables has been copyrighted, published, or reproduced elsewhere. I certify that all individuals included as authors of papers have contributed substantially to the scientific process leading up to the writing of the paper and its revised version. Thank you for accepting reviewing our manuscript. Attachments Attachment Submitted filename: Response to reviewers comments R3.docx https://doi.org/10.1371/journal.pone.0248937.r006
9 Mar 2021 Decision Letter - Melissa A Brotman, Editor Behavioral assessment of children and adolescents with Graves' disease: A prospective study PONE-D-20-38682R3 Dear Dr. Hamed, 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, Melissa A Brotman, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0248937.r007
Formally Accepted
11 Mar 2021 Acceptance Letter - Melissa A Brotman, Editor PONE-D-20-38682R3 Behavioral assessment of children and adolescents with Graves' disease: A prospective study Dear Dr. Hamed: 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. Melissa A Brotman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0248937.r008

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