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Does the introduction explain the objective of the research presented in the preprint?

Yes

The introduction clearly explain the study objectives by first outlining the stages of treatment in chronological order.

Are the methods well-suited for this research?

Somewhat inappropriate

The methodology remains conceptual rather than operational. While the paper proposes an interesting multi-layer therapeutic architecture, it fails to provide measurable definitions, modelling procedures, or empirical strategies which would be necessary to evaluate or implement the conceptualized cascade medicine. Key components such as gate criteria, therapeutic load Budget and multi -layered interactions are described narratively without quantitative thresholds, biomarkers, or even statistical decision methods. It also lacks simulation, case studies or retrospective analyses. This limits the ability to access the cascade's claim benefits. The authors ought to adopt measurable state variables (eg the disease burden, organ load, support levels), integrate pharmacodynamics or systems-biology modelling to justify sequencing effects, provide disease-specific examples, and demonstrate feasibility through real-world data.

Are the conclusions supported by the data?

Highly unsupported

The paper does not present any empirical data, simulations, case studies or quantitative analyses from which conclusions could be drawn.

Are the data presentations, including visualizations, well-suited to represent the data?

Highly inappropriate or unclear

The paper does not include any data presentations or visualization because it does not present empirical data, figures, tables or even graphical models. Nothing to evaluate whether visualizations are well-suited with the data.

How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research?

Somewhat unclearly

While the conceptual discussion is coherent, it lacks data to support the claims, and as such, the interpretation is theoretical rather than analytical.

Is the preprint likely to advance academic knowledge?

Somewhat likely

The article will contribute significantly with modifications of the suggestions made above. It presents an interesting and original conceptual frame-work which would contribute to academic discussions on therapeutic sequencing, system medicine, and biomarker-guided treatments.

Would it benefit from language editing?

Yes

While the core ideas are communicated, it contains sections which are wordy, abstract, overly conceptual which may make it difficult for clinicians and regulators to understand the practical implications. Some sentences are unclear eg "engineering of conditions", "safety links","architecture of therapy" etc.

Would you recommend this preprint to others?

Yes, but it needs to be improved

The suggestions are already outlined above

Is it ready for attention from an editor, publisher or broader audience?

No, it needs a major revision

Competing interests

The authors declare that they have no competing interests.

Use of Artificial Intelligence (AI)

The authors declare that they did not use generative AI to come up with new ideas for their review.