The 3-level biological model of DISH: Post-publication reflections

Disclaimer This document represents a conceptual synthesis of observations arising from a series of investigations conducted within the Camargo Cohort and focused on the biological heterogeneity of this condition. After three recently published papers by our group (references 1-3) aimed at describing a biological model of DISH, we found that with each study, the landscape appeared to become increasingly complex: New constructs, new trajectories and new biological layers were introduced, raising the concern that the overall picture might be becoming more difficult to interpret. However, when the final landscape was viewed as a whole, a different impression emerged. The apparent complexity was not generating confusion; rather, it was revealing a relatively simple underlying organisation. In this sense, complexity became the pathway to simplicity. This integrative analysis may be useful to other researchers. should not be interpreted as an additional research manuscript, or an extension of the studies from which it originated. Rather, it No new data are presented, and no attempt is made to establish definitive mechanistic explanations. Instead, the objective is to explore whether findings related to susceptibility, biological activation and structural trajectories may be interpreted within a common organisational framework. The concepts discussed throughout this document, including the proposed three-level model, the FOSSI constructs, the DAI-5 activation index and the trajectory framework, should be regarded as working hypotheses requiring independent validation and further refinement. The reflections presented here are offered as a possible interpretation of existing observations and as a contribution to ongoing discussion regarding the biological organisation and heterogeneity of DISH.

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