Dear Dr. Chen,

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.

==============================

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We look forward to receiving your revised manuscript.

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Erfan Babaee Tirkolaee, PhD

Academic Editor

PLOS ONE

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The first author would like to express gratitude for the support from Yibin University

(No.412-2022QH23) and Sichuan Provincial Key Laboratory of Automobile Measurement and

Control and Safety (No.QCCK2019-006) and Yibin Federation of Social Science Associations (No.

2024YBSKL81).

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Thank you for your submission of the manuscript. Your study tackles an important and timely issue regarding the management of medical waste, especially during the COVID-19 pandemic. The aim of developing a multi-objective optimization model to minimize costs and risks is commendable and has the potential to contribute significantly to the field. However, there are several areas that require clarification and improvement to enhance the overall quality and comprehensibility of your manuscript.

1. Can you elaborate on why a two-echelon model was chosen over other potential models? What specific advantages does it offer in the context of medical waste transportation?

2. The paper mentions a three-dimensional risk measurement sub-model. Could you provide more details on how this model was constructed and the specific parameters it includes?

3. The manuscript states that the weight ratio of optimization objectives lacks a basis. Can you clarify how you determined the weights for transportation costs and risks in your model?

4. You mention a lack of stability and sensitivity analysis. Could you provide a plan for how you intend to conduct this analysis in future work?

5. In the NSGA-II algorithm, how is the initial population generated? What criteria are used to ensure diversity in the initial solutions?

6. Ensure that all references are up-to-date and formatted according to the journal's guidelines. Some citations appear to be missing or incomplete. In general, the authors are recommended to refer to more recent papers in the manuscript, such as: doi.org/10.1016/j.eswa.2023.121035, doi.org/10.1109/TITS.2023.3285430.

7. The case study in Yibin City is mentioned, but details on the data used (e.g., waste generation rates, vehicle capacities) are sparse.

8. What assumptions did you make in your model regarding vehicle capacities, waste generation rates, and transit point locations? How might these assumptions impact the results?

9. Some figures and tables lack clear explanations in the text. Can you ensure that all visual aids are adequately referenced and explained?

10. What are the limitations of your study, and how might they affect the applicability of your model in different contexts or regions?

11. What are the next steps for this research? Are there plans to extend the model to include other types of medical waste or different geographical areas?

I look forward to seeing the revised manuscript that addresses these concerns.

Reviewer #2: This paper use NGGA-II to find the optimum transportation routes for infectious medical waste. The problem of this work is interesting because this optimization problem due with many parameters. However, this paper msut be improve in some point to increase the quality of this work. My comments are below:

1) I reccommend the author to change the description of objective f_3 from section 4.4 to 4.2.3. It very hard and find where is the description of objective 3. Because the 4.1.1 and 4.2. is describe about f_1 and f_2.

2) This paper use NGSA-II to find the 3 objectives optimization problem. However, I cannot see you Pareto solutions of your problem. I reccomend the author to added the figure of Pareto solutions in your manuscript.

3) The author must be implied why where is the selected optimum solution from the Pareto solutions and explained why this point is good for selected.

4) In general, the history search of multi/many-objective optimization can measured by multi-objective optimiztion metrics. I reccomend the author to used some metrics to shown your optimum solution has been converge.

5) This paper try to compared the results of improve NSGA-II and traditional NSGA-II. However, the comparison isn't fair because now you due with the multi-objective optimization. I reccommend the author compared the Pareto solution from each method and compared the convergence rate of each algorithm using some metric such as hypervolume.

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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[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.

Dear Dr. Chen,

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 Jun 28 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.

• 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,

Erfan Babaee Tirkolaee, 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

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

Reviewer #3: I Don't Know

Reviewer #4: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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Reviewer #2: I agree with the author's response, and all of comments have been addressed. Now the paper is ready for publication.

Reviewer #3: Manuscript ID: PONE-D-3149R1, entitled "Research Optimization of Transportation Routes for Infectious Medical Waste".

The manuscript presents a timely and pertinent contribution to the field by proposing a multi-objective optimization model for the routing of infectious medical waste. While the topic is significant and the methodological approach is well-motivated, there are several aspects of the manuscript that require further refinement to meet the standards of academic publication.

1. Abstract

The abstract would benefit from a clearer emphasis on the main numerical findings of the study. Explicitly stating quantitative results will strengthen the perceived value of the work.

2. Introduction

The introduction should avoid vague qualifiers such as "important issue" and instead provide quantified evidence, preferably supported by current references or statistics. Additionally, the articulation of research gaps needs to be more prominent. The authors are encouraged to use visual or structural enhancements—such as bullet points or bolded text—to emphasize the novelty and motivation of their work.

3. Literature Review

The literature review section identifies several relevant studies, but does so without critical analysis. It is recommended that the authors include a summary table comparing key features of the most closely related works with their own proposed approach. This will help clarify the distinct contributions of the current study.

4. Solution Methodology

In the methodology section, it is important to justify the choice of the improved NSGA-II over other leading multi-objective evolutionary algorithms (MOEAs). A comparative rationale, perhaps supported by relevant citations or empirical evidence, would enhance the credibility of the algorithmic selection.

5. Numerical Experiments

Figures should be more clearly referenced and interpreted within the main text. Furthermore, the use of units and performance metrics should be standardized and clearly defined throughout the experimental analysis.

6. Conclusion

The limitations section is appreciated and a good starting point. However, it would benefit from further elaboration to include:

• Real-time traffic uncertainty;

• Dynamic generation rates of medical waste;

• Regulatory constraints and compliance issues related to infectious waste logistics.

Reviewer #4: In the introduction, you need to connect the state of the art to your paper goals. Please follow the literature review by a clear and concise state of the art analysis. This should clearly show the knowledge gaps identified and link them to your paper goals. Please reason both the novelty and the relevance of your paper goals. Clearly discuss what the previous studies that you are referring to. What are the Research Gaps/Contributions? Please note that the paper may not be considered further without a clear research gap and novelty of the study and compare your paper with municipal cooperative waste supply chain papers and sustainable medical waste supply chain network

Constraints such as “uniqueness,” “logicality,” and “load capacity” are vaguely defined. Can you explicitly formulate these constraints mathematically within the model and explain their operational relevance?

The paper states it adopts a "segmented strategy" for modeling without adequately explaining what this segmentation entails or how it improves over a holistic model. Could you elaborate on what stages are modeled and how segmentation affects the computational efficiency or route design?

While the improved NSGA-II is claimed to outperform a traditional genetic algorithm, no formal statistical validation or benchmark comparison is shown. Could the authors compare with at least one other modern multi-objective algorithm (e.g., MOEA/D, SPEA2) and report metrics such as hypervolume or spread?

The problem instances and solution parameters (e.g., 58 production points, locations, transfer point limits) are not fully detailed. Can the authors provide a table summarizing the data and parameters used in simulations to ensure replicability?

The transport risk is quantified as “t·person/km³,” which is unclear and lacks explanation. What is the theoretical or empirical basis for this risk metric, and how does it influence decision-making in route optimization?

The methodology and results sections contain excessive narrative text and insufficient formalism (e.g., pseudocode, mathematical notation). Would the authors consider rewriting key parts using clear pseudocode for the algorithm and structured tables for solution outcomes?

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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 #2: No

Reviewer #3: No

Reviewer #4: 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.

Research on Optimization of Transportation Routes for Infectious Medical Waste

PONE-D-24-35149R2

Dear Dr. Chen,

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.

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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,

Erfan Babaee Tirkolaee, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

Reviewer #4: Yes

**********

Reviewer #3: (No Response)

Reviewer #4: No comments

No comments

No comments

No comments

No comments

No comments

No comments

No comments

No comments

**********

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 #3: No

Reviewer #4: No

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