Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonization

Hayfa Sharif; Caroline L. Hoad; Nichola Abrehart; Penny A. Gowland; Robin C. Spiller; Sian Kirkham; Sabarinathan Loganathan; Michalis Papadopoulos; Marc A. Benninga; David Devadason; Luca Marciani

doi:10.1371/journal.pone.0296311

Peer Review History

Original SubmissionAugust 29, 2023
16 Oct 2023 Decision Letter - Tsutomu Kumamoto, Editor PONE-D-23-27259Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonizationPLOS ONE Dear Dr. Marciani, 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 Nov 30 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Tsutomu Kumamoto Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: Colonic Volume Changes in Paediatric Constipation Compared to Normal Values Measured Using MRI - https://doi.org/10.3390/diagnostics11060974 3. In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. 4. 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: The authors presented colon length in pediatric health and constipation using MRI. This study is a very interesting, but I have a few questions. Specific comments 1. The authors indicated the colon length for all participants correlated significantly with their age, height and weight. Specifically, to what age do the results of this study apply to children? Would it be a good idea to include data on age and gender etc.. as a supplemental table? 2. I comprehended the largest differences between groups were the ascending colon and the recto-sigmoid colon. What do these results mean? 3. MRI was used in this study. Is there any difference or advantage between MRI and other tests such as intravenous or CT? [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: Yes 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: Yes 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: 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 is an interesting paper that introduces a novel and simple approach to measure colonic length using non-radioactive measurements (MRI). They measure some simple colon length measures using a skeletonization algorithm. In my opinion, the manuscript only needs minor editing before it is suitable for publication. In general, check the punctuations, there are some places where there is a space too much between e.g., the p-value and the “=” sign. For example, in line 177, 189, 203, 205. These needs to be consistent and in line with the journal specifications. Line 128, figure caption. There is a “is” to much. Line 162, “are” instead of “and” Line 234, “thank” instead of “than” Line 256, “with sex and ..” missing a word Abstract: - You only mention the age of the constipated children. Can you add that the control group is age-matched or provide their range of age also? Methods: - To my knowledge of skeleton algorithms (I have not tried the plugin you have used), it can be difficult to avoid that the colon midline does not take “shortcuts” between the colon segments in the cases, where the segmented volumes are very close to each other, for example in the flexures or in the sigmoid area. This will potentially underestimate the true length measure. If you took any precautions to avoid this, then please describe it so others can easier replicate the work. o You have described some of the precautions in the discussion. It would be simpler to get the relevant information in the methods section. o When doing the skeleton algorithm on the different segments one at a time, then the midline will end at the top/bottom of the segment and not at the middle of the segment/junction to the next segment. Do the used algorithm take this into account, i.e., using a predefined start/end point. Or else each segment might be a little overestimated. Can you elaborate a little bit more on the analysis steps, so there is no doubt on how this works. I would like to see figure 1c from a sagittal view also. Results - You state that the hypothesis is about colon length differences between the groups. That result should be mentioned before the BSA corrected values. One might argue that the BSA corrected values are most representative, however you should be truer to your initial hypothesis. Discussion: - Can you include your opinion on measures of colon ptosis in relation to your total colon or transverse colon estimation? A very recent study has shown the correlation between slow transit constipation and transverse colon ptosis as measured on abdominal x-rays: Sun et al; Degree of transverse colon ptosis: an alternative surrogate for evaluation of slow transit constipation. Quantitative Imaging in Medicine and Surgery; Vol 13, No 9 (September 01, 2023) - In line 232 you mention that colon length was correlated with age in the FC group only. Could that be due to the fact that the control group was older than the FC group, meaning that many of the controls might have reached the full-grown length of the colon, why a correlation only exists when you are still growing? Reviewer #2: Comments on this study: 1. The authors should provide information concerning the reliability of MRI images using 3D image analysis skeletonization technique in measurement of colon length. 2. It is well accepted that MRI study has a limitation in young children who are not cooperative with this time consuming technique. It is noted that the children enrolled in this study aged over 10 years, therefore, the data of this study would be applicable to only older children , not children in general. 3. Data in this study shows that the colon length of constipated children is longer than healthy children. However, the results do not clearly indicate that colonic length contributes to the pathogenesis of functional constipation. To investigate whether the longer colon is a cause of functional constipation or secondary to prolonged fecal retention , a study should be designed to compare colonic length measured by MRI studies in the same patient at pre treatment and at recovery post treatment of functional constipation. ****** 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: Esben Bolvig Mark Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0296311.r001
Revision 1
25 Nov 2023 Author Response PONE-D-23-27259 Revision R1 Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonization Response to Reviewers We are very grateful for the comments received from the Academic Editor and from the two Reviewers. We have addressed all the points raised as detailed below in this point-by-point response. All changes made to the manuscript are highlighted in yellow in the tracked changes version enclosed. We believe that the changes made in response to the reviews have indeed improved the manuscript and we hope that it would meet now the journal’s criteria. Editorial Comments: 1. When submitting your revision, we need you to address these additional requirements. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Answer: We checked the formatting examples and we used the template provided 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: Colonic Volume Changes in Paediatric Constipation Compared to Normal Values Measured Using MRI - https://doi.org/10.3390/diagnostics11060974 3. In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Answer: Apologies for the similarities with the previous paper, we have revised in the Introduction and Methods Lines 58-62, Lines 76-77, Lines 92-94, Lines 95-100, Lines 112-118 and Lines 154-156 to avoid overlap. The source of the original data for this work is clearly referenced. 4. 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. Answer: we checked the references list and only added the one suggested by a Reviewer below. Additional Editor Comments: The authors presented colon length in pediatric health and constipation using MRI. This study is a very interesting, but I have a few questions. Specific comments 1. The authors indicated the colon length for all participants correlated significantly with their age, height and weight. Specifically, to what age do the results of this study apply to children? Would it be a good idea to include data on age and gender etc.. as a supplemental table? Answer: In response to this and also Reviewer 2 comments we have specified more clearly what is the age range and that there was a 7 years (and older) cut-off in the inclusion criteria and why at the end of Discussion Lines 294-297. As suggested, we have also added a supplemental table S1 with the demographic details. 2. I comprehended the largest differences between groups were the ascending colon and the recto-sigmoid colon. What do these results mean? Answer: Thank you for this comment, in response to this and also to a point made by Reviewer 2 we have added to the discussion at Lines 274-281, to say that these regions have functional and pathological relevance and that from these data only one cannot derive whether the length differences are an effect of being constipated or a cause of constipation. 3. MRI was used in this study. Is there any difference or advantage between MRI and other tests such as intravenous or CT? Answer: Thank you for this comment, we have added a comment in Discussion Lines 291-294 to make the point that MRI uses radio waves and is safe to use in children, providing they do not have incompatible metal implants in their body. Other medical imaging techniques such as computed tomography deliver a considerable dose of ionizing radiation, making them unsuitable for this purpose. General comments to the Author We are very grateful for the positive appraisals of technical soundness, conclusions supported by data, appropriate and rigorous statistics, data availability and manuscript presentation. Thank you. Review Comments to the Author: Reviewer #1 This is an interesting paper that introduces a novel and simple approach to measure colonic length using non-radioactive measurements (MRI). They measure some simple colon length measures using a skeletonization algorithm. In my opinion, the manuscript only needs minor editing before it is suitable for publication. Answer: Thank you for the very positive appraisal of our manuscript. In general, check the punctuations, there are some places where there is a space too much between e.g., the p-value and the “=” sign. For example, in line 177, 189, 203, 205. These needs to be consistent and in line with the journal specifications. Line 128, figure caption. There is a “is” to much. Line 162, “are” instead of “and” Line 234, “thank” instead of “than” Line 256, “with sex and ..” missing a word Answer: thank you so much, apologies for the imperfections, we have looked out for those and run a new full spelling and grammar check. Abstract: You only mention the age of the constipated children. Can you add that the control group is age-matched or provide their range of age also? Answer: agreed, we provide now the specific age range of the control group (10-18 years old) in the Abstract Line 40. Methods: - To my knowledge of skeleton algorithms (I have not tried the plugin you have used), it can be difficult to avoid that the colon midline does not take “shortcuts” between the colon segments in the cases, where the segmented volumes are very close to each other, for example in the flexures or in the sigmoid area. This will potentially underestimate the true length measure. If you took any precautions to avoid this, then please describe it so others can easier replicate the work. Answer: thank you for this comment, we agree that our description in Discussion was not making this clear. In answer to this, and to a similar point raised by Reviewer #2, we have added in Discussion a section to this effect at Lines 259-267. In that section we mention the possibility that the algorithm would ‘jump’ between loops and that visual inspection is necessary. We also reinforce what was already said at the beginning of Results, that in 3 cases careful re-segmentation of the sigmoid-rectum region was necessary to prevent the ‘jumps’. We point out now that ‘jumping’ would underestimate the segment length measured. o You have described some of the precautions in the discussion. It would be simpler to get the relevant information in the methods section. Answer: agreed we have added a description of the precaution in the Methods at lines 142-145 and also left some discussion of this in the Discussion section. o When doing the skeleton algorithm on the different segments one at a time, then the midline will end at the top/bottom of the segment and not at the middle of the segment/junction to the next segment. Do the used algorithm take this into account, i.e., using a predefined start/end point. Or else each segment might be a little overestimated. Can you elaborate a little bit more on the analysis steps, so there is no doubt on how this works. Answer: agreed, the algorithm did not allow to predefine start and stop points in the binary masks so you are correct, when the separate segments were summed up, this will have overestimated the total length by a small amount. We have now inserted a comment to this effect to make the point clear in Discussion lines 267-270. I would like to see figure 1c from a sagittal view also. Answer: we tried to do this at least for one example figure to answer your request positively, but the manual segmentation of the colon is done on multi-slice coronal images with larger slice resolution than in-plane, and when trying to reconstruct in a different orientation the quality of the resulting images and projections is not very good. Apologies for not satisfying this one request. Results - You state that the hypothesis is about colon length differences between the groups. That result should be mentioned before the BSA corrected values. One might argue that the BSA corrected values are most representative, however you should be truer to your initial hypothesis. Answer: Agreed, we have now added this first in Results at lines 170-171. Discussion: - Can you include your opinion on measures of colon ptosis in relation to your total colon or transverse colon estimation? A very recent study has shown the correlation between slow transit constipation and transverse colon ptosis as measured on abdominal x-rays: Sun et al; Degree of transverse colon ptosis: an alternative surrogate for evaluation of slow transit constipation. Quantitative Imaging in Medicine and Surgery; Vol 13, No 9 (September 01, 2023) Answer: thank you for this comment, we have added this interesting reference and a comment to this effect in Discussion at Lines 287-290. In these participants we did not encounter substantial colon ptosis and further, larger studies will need to be carried out to investigate this. - In line 232 you mention that colon length was correlated with age in the FC group only. Could that be due to the fact that the control group was older than the FC group, meaning that many of the controls might have reached the full-grown length of the colon, why a correlation only exists when you are still growing? Answer: Thank you for the comment, we have added a sentence to this effect in Discussion at lines 237-239. Review Comments to the Author: Reviewer #2 1. The authors should provide information concerning the reliability of MRI images using 3D image analysis skeletonization technique in measurement of colon length. Answer: Although the paper mentioned this at the beginning of the Results, we entirely agree that this point was not made clearly in Discussion. As such, and also in answer to a similar point raised by Reviewer #1, we have added in Discussion a section to this effect at Lines 259-270. 2. It is well accepted that MRI study has a limitation in young children who are not cooperative with this time consuming technique. It is noted that the children enrolled in this study aged over 10 years, therefore, the data of this study would be applicable to only older children , not children in general. Answer: agreed. We have inserted a comment detailing this point and the reasons for the 7 years old cut-off in the inclusion criteria at the end of Discussion Lines 294-297. 3. Data in this study shows that the colon length of constipated children is longer than healthy children. However, the results do not clearly indicate that colonic length contributes to the pathogenesis of functional constipation. To investigate whether the longer colon is a cause of functional constipation or secondary to prolonged fecal retention , a study should be designed to compare colonic length measured by MRI studies in the same patient at pre treatment and at recovery post treatment of functional constipation. Answer: thank you for this, it is an important point and we have inserted the comment towards the end of Dicsussion Lines 278-281. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0296311.r002
1 Dec 2023 Decision Letter - Tsutomu Kumamoto, Editor PONE-D-23-27259R1Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonizationPLOS ONE Dear Dr. Marciani, 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 Jan 15 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, Tsutomu Kumamoto 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 believe that the authors have addressed the reviewers’ comments. However, as can be seen from this revision, this study has several limitations. Considering these, it may be necessary to rephrase lines 302 to 305 in the conclusion. Also, please consider whether it would be better to modify the content of the limitations and change where they are mentioned. [Note: HTML markup is below. Please do not edit.] [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0296311.r003
Revision 2
8 Dec 2023 Author Response PONE-D-23-27259 Revision R2 Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonization Response to the Editor Thank you for your comments. We have addressed all the points raised as detailed below in this point-by-point response. All changes made to the manuscript are tracked in the tracked changes Word version enclosed. We hope that the manuscript would now meet the journal’s criteria. Journal Requirements Comments: 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. Answer: We checked each reference individually as recommended and spotted an incorrect title and some typos in References 4, 10, 21 and 22 which are now corrected. Apologies for not seeing these before. Additional Editor Comments: I believe that the authors have addressed the reviewers’ comments. Answer: Thank you. However, as can be seen from this revision, this study has several limitations. Considering these, it may be necessary to rephrase lines 302 to 305 in the conclusion. Answer: Agreed. We have rewritten that conclusion to stress that whilst providing new data that will help improve our understanding of colon pathophysiology and drug release modelling in children, the study also highlighted some fundamental limitations of the skeletonization technique that will need addressing to make the method more applicable in the future. Also, please consider whether it would be better to modify the content of the limitations and change where they are mentioned. Answer: We reconsidered the location of the limitations paragraph in the Discussion which appeared half-way through the more physio-pathological discussion. As such, we have now moved that section towards the end of the Discussion where such consideration are more traditionally placed. The content of the limitations was already quite comprehensive especially following the comments of the previous technical Reviewer. Accordingly we left the content unchanged. Figure Upload Comments: 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. Answer: We run again the three figure files through PACE, which found no image problems. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0296311.r004
10 Dec 2023 Decision Letter - Tsutomu Kumamoto, Editor Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonization PONE-D-23-27259R2 Dear Dr. Marciani, 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, Tsutomu Kumamoto Academic Editor PLOS ONE Additional Editor Comments (optional): I believe that this study should be accepted by PLOS ONE as the authors have sufficiently addressed the reviewers’ queries. I hope that this research will contribute to further advancements in this field. Reviewers' comments: https://doi.org/10.1371/journal.pone.0296311.r005
Formally Accepted
19 Dec 2023 Acceptance Letter - Tsutomu Kumamoto, Editor PONE-D-23-27259R2 PLOS ONE Dear Dr. Marciani, 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 M.D., Ph.D. Tsutomu Kumamoto Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0296311.r006

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