Unlocking the power of reticulocyte analysis: Advancing care for patients with abnormal haemoglobin variants at Eastern Regional Hospital, Koforidua

Richard Vikpebah Duneeh; Israel Bedzina; Melody Yaaba Korkor Johnson; Francis Agyei Amponsah; Wina Ivy Ofori Boadu; Kenneth Ablordey

doi:10.1371/journal.pone.0323056

Peer Review History

Original SubmissionJuly 22, 2024
22 Jul 2024 Author Response https://doi.org/10.1371/journal.pone.0323056.r001
19 Nov 2024 Decision Letter - Ochuwa Adiketu Babah, Editor PONE-D-24-30332Unlocking the Power of Reticulocyte Analysis: Advancing care for patients with abnormal haemoglobin variants at Eastern Regional Hospital, KoforiduaPLOS ONE Dear Dr. Duneeh, 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 03 2025 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, Ochuwa Adiketu Babah, M.Sc.PH (Epidemiology), FWACS, FMCOG 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. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Additional Editor Comments: Dear Authors, Please address all comments made by the reviewers and submit for re-assessment. Best regards, Dr Ochuwa A. Babah [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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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 Reviewer #3: 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: Study site--> Page 10; Line 85: Suggestion: The description of the study site is too long. May be cut short. Sample and Data Collection--> Page 12; Line 116: Written consent was obtained from adults’ participants whiles assent was obtained from guardians and parents Suggestion: Spell check. Assent is the a child's affirmative agreement to participate in research, and is taken from children between 7-17 years; when it is the agreement from the parent/guardian it is called as consent from the parent/guardian. Definition of production defects and maturation defects--> Page- 12 Suggestion: What is the reference for these definitions? Is there any cut off for the fluorescence baed on which reticulocytes are categorised into high, medium and low? Results --> page 13; Lines 149-150 The median age of the study participants was 7.00 years,.... Half were men (50.2%) and half were women 151 (49.8%). Suggestion: Better to mention the range along with median age. Mention as males and females rather than men and women as >70% were children. Table 1-->page 13 Haemoglobin phenotype -'S". Suggestion: What is Hb 'S' phenotype? Is it homozygous sickle? Then it is better to mention 'SS' phenotype Alignment of the variables in the table to be corrected Reticulocyte characteristics of patients with abnormal haemoglobin variants-->Page 14; Lines 159- The median reticulocyte count and the absolute reticulocyte count were 0.71 x10^6/μL and 5.40%, respectively. Suggestions: How can the absolute count be in percentage? Always mention range along with median. Lines 161-162 The median low, medium and high fluorescence levels were 63.70%, 17.80%, and 17.50%, respectively. Suggestion: Is it the median low, medium and high fluorescence reticulocyte %? Lines 163-164: Most 163 of the participants had elevated reticulocyte counts (60.8%), reticulocytes (76.5%), and 164 immature reticulocyte fractions (94.5%). Suggestion: Sentence is not clear. How are Reticulocyte count and reticulocytes different here? Lines 164-166:Furthermore, most had elevated medium (89.4%) and high (94.5%) fluorescence reticulocytes. However, most had decreased low fluorescence (92.6%) and reticulocyte haemoglobin levels (67.1%). Suggestion: Rephrase the sentence. The message conveyed is not clear. Table --> Pages 14, 15 When you are mentioning absolute Reticulocyte count, Is there any significance for the reticulocyte %? Better index would be the reticulocyte index or reticulocyte production index. The last portion in the table 2, can be incorporated in the upper part of the table only. Eg; Table 2: Reticulocyte characteristics of study participants (N=217) Variable Median (range)/N(%) Reticulocyte Count (106/uL) 0.17 (0.10-0.25) Normal 16 (7.4) Sociodemographic factors associated with the severity of anaemia--> page 15 Lines- 177- Additionally, most patients with mild (53.5%) and moderate (60.2%) anaemia had 'S' haemoglobin phenotypes, followed by 'SC' haemoglobin phenotypes (39.5% and 36.7%, respectively). Similarly, most subjects with severe (65.4%) and severe life-threatening (66.7%) anaemia had 'SS' haemoglobin phenotypes followed by 'SC' phenotypes (28.8% and 29.2%, respectively). Suggestion: Is Haemoglobin 'S' and 'SS' the same? Better to use the same short forms Discussion-->Page 21 Contrary to this study, (8) reported that SS and AS were significantly associated with severe anaemia. (14) in Sri Lankan adolescents also reported that haemoglobin variants are significantly associated with haemoglobin levels. Suggestion: Please mention the study/author details; not just reference number. Lines 297- Interestingly, most patients with abnormal haemoglobin variants have been found to experience haemolytic episodes Patel et al., (2021) and infections Alkot et al., (2018). This leads to increased anaemia and haematopoiesis to supplement the metabolic rates of the body. Suggestion: Sentences need rephrasing. Do not convey the message. Use same pattern of reference through out the manuscript. The result and discussion parts are too long and confusing the reader. When all the findings are mentioned in the tables, mention only the relevant findings in the text part of the result. The sentences in most places are incomplete and do not convey the clear message. The patient selection, characteristics, inclusion and exclusion criteria are not clearly mentioned. How many were transfusion dependent/symptomatic? If transfusion dependent, what was the interval between transfusion and blood analysis for study in these patients? Was the iron study done? Was any patient on iron chelation? Was there splenomegaly? Overall this is an interesting study. The result and discussion part have to be done with more clarity. Reviewer #2: The manuscript has been well written but however, please go through my comments and make the necessary corrections suggested. I am commending you again for a good work done. I hope this continues and i get to review more papers from you. Reviewer #3: Abstract contains repeated statements which will need to be corrected. Conclusion in abstract and the conclusion section of the manuscript should be re-written to clearly state findings and implications without necessarily repeating the results segment. Statement on written consent and assent was repeated under sample collection and ethical approval. Several other repeated statements in the manuscript should be avoided. "The median age of the study participants was 7.00 years, with the majority within 1-5 years (40.1%), followed by 6-10 years (29.0%). Half were men (50.2%) and half were women (49.8%)." - It is better to use males and females especially as the mean age of participants was just 7 years. The levels of HB used to define and categorize anaemia should be stated either be in text or in the table especially since the age range of the study participants cut across both paediatric and adult age groups. Figures presented do not adequately explain the findings described in text for example, the association between reticulocyte production indices and haemoglobin level and the association between reticulocyte maturation-dependent indices and haemoglobin levels among patients with abnormal haemoglobin variants would have been better presented in tables. Referencing in the discussion section does not follow acceptable methods. Some referenced authors were not named in text while some that were named did not have the reference number indicated. (Line 289, 290 and 298 are examples) The authors did not explain why the increase in low-fluorescence reticulocytes is associated with an increase in haemoglobin levels while increase in medium and high-fluorescence reticulocytes had an opposite effect. Why were Haemoglobin A individuals not included in the study as controls? The findings in these individuals versus those with abnormal haemoglobin variants may have helped explain some of the findings not well addressed in the discussion section. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: Yes: Juliana Aggrey Reviewer #3: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Comments for 30332.docx https://doi.org/10.1371/journal.pone.0323056.r002
Revision 1
12 Dec 2024 Author Response Reviewer #1: Comment: Study site--> Page 10; Line 85: Suggestion: The description of the study site is too long. May be cut short. Response: Authors have summarised study site. See line 87-92. Comment: Sample and Data Collection--> Page 12; Line 116: Written consent was obtained from adults’ participants whiles assent was obtained from guardians and parents Suggestion: Spell check. Assent is the a child's affirmative agreement to participate in research, and is taken from children between 7-17 years; when it is the agreement from the parent/guardian it is called as consent from the parent/guardian. Response: Authors have revised the written consent accordingly. See line 145-146. Comment: Definition of production defects and maturation defects--> Page- 12 Suggestion: What is the reference for these definitions? Is there any cut off for the fluorescence baed on which reticulocytes are categorised into high, medium and low? Response: Authors have defined and added reference for these definitions. See line 116-120. Results --> page 13; Lines 149-150 Comment: The median age of the study participants was 7.00 years,.... Half were men (50.2%) and half were women 151 (49.8%). Suggestion: Better to mention the range along with median age. Mention as males and females rather than men and women as >70% were children. Response: We appreciate your input on the range, however our IQR was the best considering the dataset we had. Second option has been revised accordingly. See line 150-155. Comment: Table 1-->page 13 Haemoglobin phenotype -'S". Suggestion: What is Hb 'S' phenotype? Is it homozygous sickle? Then it is better to mention 'SS' phenotype. Alignment of the variables in the table to be corrected. Response: The term "Hb S phenotype" is used intentionally to describe the electrophoretic band observed during testing. Due to the possibility of comigrating haemoglobin’s, such as Hb S and Hb D, both of which can appear on the same band, the testing technique necessitates reporting the observed band rather than presuming the specific genotype or assuming homozygosity. This approach ensures accuracy and avoids potential misrepresentation of results. Regarding the alignment of variables in the table, we have reviewed and corrected any inconsistencies to enhance readability and ensure proper formatting. Comment: Reticulocyte characteristics of patients with abnormal haemoglobin variants-->Page 14; Lines 159- The median reticulocyte count and the absolute reticulocyte count were 0.71 x10^6/μL and 5.40%, respectively. Suggestions: How can the absolute count be in percentage? Always mention range along with median. Response: Authors have revised this section. See line 159-160. Comment: Lines 161-162 The median low, medium and high fluorescence levels were 63.70%, 17.80%, and 17.50%, respectively. Suggestion: Is it the median low, medium and high fluorescence reticulocyte %? Response: Yes. See line 163-164. Comment: Lines 163-164: Most 163 of the participants had elevated reticulocyte counts (60.8%), reticulocytes (76.5%), and 164 immature reticulocyte fractions (94.5%). Suggestion: Sentence is not clear. How are Reticulocyte count and reticulocytes different here? Response: Corrections has been revised accordingly. See line 165-167. Comment: Lines 164-166: Furthermore, most had elevated medium (89.4%) and high (94.5%) fluorescence reticulocytes. However, most had decreased low fluorescence (92.6%) and reticulocyte haemoglobin levels (67.1%). Suggestion: Rephrase the sentence. The message conveyed is not clear. Response: Authors have rephrased the sentence as suggested. See line 165-167. Comment: Table --> Pages 14, 15 When you are mentioning absolute Reticulocyte count, Is there any significance for the reticulocyte %? Better index would be the reticulocyte index or reticulocyte production index. The last portion in the table 2, can be incorporated in the upper part of the table only. Eg; Table 2: Reticulocyte characteristics of study participants (N=217) Variable Median (range)/N(%) Reticulocyte Count (106/uL) 0.17 (0.10-0.25) Normal 16 (7.4) Response: Comments have been accepted and revised according. See line 160-161 and table 2. The last portion of table 2 had different unit incorporating it at the upper part of the table might make reading difficult for our audience. Comment: Sociodemographic factors associated with the severity of anaemia--> page 15 Lines- 177- Additionally, most patients with mild (53.5%) and moderate (60.2%) anaemia had 'S' haemoglobin phenotypes, followed by 'SC' haemoglobin phenotypes (39.5% and 36.7%, respectively). Similarly, most subjects with severe (65.4%) and severe life-threatening (66.7%) anaemia had 'SS' haemoglobin phenotypes followed by 'SC' phenotypes (28.8% and 29.2%, respectively). Suggestion: Is Haemoglobin 'S' and 'SS' the same? Better to use the same short forms Response: Authors have revised this section. See line 150, 180-182. Comment: Discussion-->Page 21 Contrary to this study, (8) reported that SS and AS were significantly associated with severe anaemia. (14) in Sri Lankan adolescents also reported that haemoglobin variants are significantly associated with haemoglobin levels. Suggestion: Please mention the study/author details; not just reference number. Response: Authors have revised this section accordingly. See line 281-283. Comment: Lines 297- Interestingly, most patients with abnormal haemoglobin variants have been found to experience haemolytic episodes Patel et al., (2021) and infections Alkot et al., (2018). This leads to increased anaemia and haematopoiesis to supplement the metabolic rates of the body. Suggestion: Sentences need rephrasing. Do not convey the message. Use same pattern of reference through out the manuscript. Response: Authors have revised this section as suggested. See line 289-290. Comment: The result and discussion parts are too long and confusing the reader. When all the findings are mentioned in the tables, mention only the relevant findings in the text part of the result. The sentences in most places are incomplete and do not convey the clear message. The patient selection, characteristics, inclusion and exclusion criteria are not clearly mentioned. Response: Though the authors do not clearly understand what the reviewer required here, we have read and address most of the issues raised with clarity. Comment: How many were transfusion dependent/symptomatic? Response: This was beyond the scope of our study. Thank you. Comment: If transfusion dependent, what was the interval between transfusion and blood analysis for study in these patients? Response: This was beyond the scope of our study. Thank you. Comment: Was the iron study done? Response: No please. Thank you. Comment: Was any patient on iron chelation? Response: No please. Thank you. Comment: Was there splenomegaly? Response: No please. Thank you. Reviewer #2: The manuscript has been well written but however, please go through my comments and make the necessary corrections suggested. I am commending you again for a good work done. I hope this continues and i get to review more papers from you. Abstract Comment: The abstract could be enhanced by briefly mentioning the clinical implications of the findings, particularly how reticulocyte analysis could influence patient care. Response: Authors have revised this section. See line 48-55. Comment: A more detailed summary of limitations would be beneficial, as this would provide a realistic perspective on the study’s generalizability. Response: Limitation have been duly acknowledged at the limitation section. See line 359-361. Introduction The introduction clearly articulates the importance of the study, linking reticulocyte analysis to the management of abnormal hemoglobin variants, which is a valuable diagnostic gap. However, I recommend the following for improvements: Comment: Key terms, such as “production defects” and “maturation defects,” are introduced but not adequately defined. Providing clear definitions upfront would enhance readability, especially for a broader audience. Response: Authors have defined and added reference for these definitions. See line 116-120. Comment: The introduction could be strengthened by mentioning prior studies, if any, that relate reticulocyte parameters to hemoglobinopathies. This would provide a clearer context for the study's novelty. Response: Although there are no recent studies in regard to our study, authors have revised this section accordingly. See line 63-64 Methods Comment: The use of convenience sampling and the limited three-month recruitment period introduce potential biases. The methodology should address the possible impact of this sampling approach on the findings. Response: The convenience sampling, we believe, had minimal or no impact on the findings of this study because the individuals with these abnormal haemoglobin variants attended a structured clinic where they could be accessed easily hence their targeting. Also, the three months period was sufficient to obtain the appropriate sample size to give us a statistical power of analysis due to the sampling technique Comment: The Methods section does not mention controlling for confounding factors (e.g., nutritional status, infection history) that could affect both reticulocyte indices and hemoglobin levels. Including these factors would strengthen the study’s rigor. Response: We agree to this suggestion and has captured it as a limitation. See line 361-363. Comment: The lack of a control group limits the ability to compare findings against a baseline. Including or discussing a control group (healthy individuals or those without abnormal hemoglobin variants) would make results more meaningful. Response: Authors have capture it as a limitation to be considered in future studies. See line 361-363. Results Comment: While informative, the visuals could benefit from more descriptive labels and clearer footnotes. For example, Figure 1’s asterisks lack a corresponding explanation about their statistical significance levels. Response: Asterisks have been defined. Comment: The high prevalence of maturation defects (91.7%) is reported, but the clinical significance of this finding is not thoroughly discussed here. Readers would benefit from a brief comment on why this statistic is relevant for clinical settings. Response: Clinical significance of our study findings was discussed in the discussion section, from line 299-304. Discussion Comment: Links to prior studies and theories (e.g., chronic hemolytic episodes and organ damage) are well integrated, supporting the study's interpretation. The following are some areas for Improvement: Comment: The discussion should acknowledge the potential influence of unmeasured factors like nutritional status or recent blood transfusions, which could impact reticulocyte counts. Response: Authors have revised accordingly. See line 299-304. Comment: The manuscript would benefit from a clearer emphasis on the clinical applications of fluorescence reticulocyte measurements in patient management and treatment planning. Response: Authors have revised accordingly. See line 323-331. Comment: Without a control group, it is challenging to contextualize the results within a standard population. The discussion should reflect on this limitation and suggest how future studies might address this gap. Response: Authors have revised this accordingly. See line 342-349. Conclusion Comment: The conclusion could benefit from more specific recommendations for clinical practice. While the potential for reticulocyte analysis is highlighted, providing explicit guidance on how these findings could alter current protocols would make the conclusion more impactful. Response: Suggestions have been accepted and revised accordingly. See line 351-358. Comment: A broader reflection on the study’s limitations and suggestions for future research, especially the need for multicenter studies, would also improve the depth of this section. Response: Suggestions accepted and revised accordingly. See line 361-363. Limitations and Recommendations Comment: Additional discussion on sampling limitations (e.g., convenience sampling) and their impact on data generalizability would provide readers with a fuller perspective on the study's constraints. Response: Suggestions accepted and revised accordingly. See line 361-364. Comment: The recommendations are valid but could be enhanced by proposing specific avenues for future research, such as exploring the role of reticulocyte indices in therapeutic monitoring for hemoglobinopathies. Response: Suggestions accepted and revised accordingly. See line 368-372. Language and Technical Presentation Comment: A few spelling errors (e.g., “recticulocytes” instead of “reticulocytes”) and minor grammatical mistakes were found, which could detract from the professionalism of the manuscript. Careful proofreading would resolve these. Response: Authors have proofread manuscript again and corrected minor spelling errors. Comment: Consistently defining and using terms throughout would improve readability, especially for an international audience not familiar with specific local practices. Response: Authors have accepted suggested corrections and revised accordingly. Reviewer #3: Comment: Abstract contains repeated statements which will need to be corrected. Response: Could the reviewer be specific?? Comment: Conclusion in abstract and the conclusion section of the manuscript should be re-written to clearly state findings and implications without necessarily repeating the results segment. Response: Authors have revised accordingly at conclusion in abstract and the conclusion section of manuscript. See line 48-55 in abstract and line 349-356. Comment: Statement on written consent and assent was repeated under sample collection and ethical approval. Several other repeated statements in the manuscript should be avoided. Response: Authors have revised the written consent accordingly. See line 144-146. Comment: "The median age of the study participants was 7.00 years, with the majority within 1-5 years (40.1%), followed by 6-10 years (29.0%). Half were men (50.2%) and half were women (49.8%)." - It is better to use males and females especially as the mean age of participants was just 7 years Response: Comment has been revised accordingly. See line 149-150. Comment: The levels of HB used to define and categorize anaemia should be stated either be in text or in the table especially since the age range of the study participants cut across both paediatric and adult age groups. Response: Comments has been revised accordingly. See page 122-125. Comment: Figures presented do not adequately explain the findings described in text for example, the association between reticulocyte production indices and haemoglobin level and the association between reticulocyte maturation-dependent indices and haemoglobin levels among patients with abnormal haemoglobin variants would have been better presented in tables. Response: We acknowledge the comment to present the associations between reticulocyte production indices and haemoglobin levels, as well as reticulocyte maturation-dependent indices and haemoglobin levels, in tables. However, we believe that the figures included in the manuscript are the most effective way to convey these associations. The figures provide a clear visual representation of the relationships, enabling readers to grasp trends and patterns at a glance. These visualizations effectively highlight the strength and nature of the associations, which may be less apparent in a tabular format. Therefore, we respectfully believe that the figures best serve the purpose of illustrating these findings and align with the manuscript's goals of clarity and impact. Authors have explained findings in text at the result section. Comment: Referencing in the discussion section does not follow acceptable methods. Some referenced authors were not named in text while some that were named did not have the reference number indicated. (Line 289, 290 and 298 are examples) Response: Authors have revised the suggested comments accordingly. Comment: The authors did not explain why t Attachments Attachment Submitted filename: Reponse to Reviewers.pdf https://doi.org/10.1371/journal.pone.0323056.r003
28 Feb 2025 Decision Letter - Mehmet Baysal, Editor PONE-D-24-30332R1Unlocking the Power of Reticulocyte Analysis: Advancing care for patients with abnormal haemoglobin variants at Eastern Regional Hospital, KoforiduaPLOS ONE Dear Dr. Duneeh, 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. Overall the manuscript has merit and meets the standards for the publication but the abstract part is too long (391 words) it is hard to follow. Please shorten it. And the language with the abstract part is somehow challenging. And some parts of the abstract is written and generated by AI. Please remove the parts that was generated by AI and re-write the abstract. It didn't make sense to write "this study" when reporting your own manuscirpt. Please change or correct it. Please submit your revised manuscript by Apr 14 2025 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, Mehmet Baysal Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This is an interesting study with potential impact on clinical practice. Reviewer #2: All comments reserved as authors have addressed all comments. Authors have adequately addressed my comments raised in a previous round of review. Reviewer #3: Issues highlighted in the first review have been addressed by the authors. I am satisfied with the corrections implemented and the current state of the manuscript. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: Yes: Juliana Aggrey Reviewer #3: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Recommendation for the Revised Submission for 30332.docx https://doi.org/10.1371/journal.pone.0323056.r004
Revision 2
27 Mar 2025 Author Response Journal Requirements Comment: 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. Response: References were checked for completeness. No changes have been made. Thank you Comment: “Overall the manuscript has merit and meets the standards for the publication but the abstract part is too long (391 words) it is hard to follow. Please shorten it. And the language with the abstract part is somehow challenging. And some parts of the abstract is written and generated by AI. Please remove the parts that was generated by AI and re-write the abstract. It didn't make sense to write "this study" when reporting your own manuscirpt. Please change or correct it.” Response: The manuscript abstract has been revised manually to reflect editors suggestions and comments. See line 21-44. Reviewer #1: This is an interesting study with potential impact on clinical practice. Response: Thank you for dedicating your time to reviewing our manuscript. We, the authors, greatly appreciate your expertise and insights in enhancing the quality of our work.. Reviewer #2: All comments reserved as authors have addressed all comments. Authors have adequately addressed my comments raised in a previous round of review. Response: Thank you for dedicating your time to reviewing our manuscript. We, the authors, greatly appreciate your expertise and insights in enhancing the quality of our work. Reviewer #3: Issues highlighted in the first review have been addressed by the authors. I am satisfied with the corrections implemented and the current state of the manuscript. Response: Thank you for dedicating your time to reviewing our manuscript. We, the authors, greatly appreciate your expertise and insights in enhancing the quality of our work. Attachments Attachment Submitted filename: Reponse to Reviewers.docx https://doi.org/10.1371/journal.pone.0323056.r005
1 Apr 2025 Decision Letter - Mehmet Baysal, Editor Unlocking the Power of Reticulocyte Analysis: Advancing care for patients with abnormal haemoglobin variants at Eastern Regional Hospital, Koforidua PONE-D-24-30332R2 Dear Dr. Duneeh, 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, Mehmet Baysal Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0323056.r006
Formally Accepted
Acceptance Letter - Mehmet Baysal, Editor PONE-D-24-30332R2 PLOS ONE Dear Dr. Duneeh, 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. Mehmet Baysal Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0323056.r007

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .