GENESIS Framework R20.3: A Dynamical Systems Framework for Modeling Chronicity, Hysteresis, and Functional Irreversibility in Complex Disease States

GENESIS Framework R20. 3: A Dynamical Systems Framework for Modeling Chronicity, Hysteresis, and Functional Irreversibility in Complex Disease States Abstract Background: Chronic diseases often exhibit nonlinear progression, partial reversibility, and clinically observed hysteresis effects that are not easily captured by linear or purely descriptive models. This work introduces GENESIS R20. 3, a conceptual dynamical systems framework designed to explore chronicity as an emergent property of state-dependent feedback and cumulative drift. Methods: GENESIS R20. 3 is formulated as a low-dimensional nonlinear system consisting of a state variable (S), a regulatory response component (R), and a cumulative drift variable (D). The model introduces cubic feedback dynamics enabling bistability and separatrix formation. Drift modulates regenerative capacity and sensitivity parameters, producing gradual shrinkage of the healthy basin of attraction. Structural validation included bifurcation analysis, basin topology mapping, hysteresis testing, numerical solver comparison, and Monte Carlo robustness analysis (±20% parameter perturbation). Results: The system exhibits robust bistability for low-to-moderate drift levels and demonstrates intrinsic hysteresis independent of external forcing. Increasing drift produces a functional critical threshold (Dfunc ≈ 0. 42) characterized by progressive basin contraction rather than abrupt topological collapse. Mild initial conditions remain reversible, whereas moderate and severe states transition into stable chronic attractors. Numerical stability, solver independence, and structural robustness were confirmed across simulations. Interpretation: GENESIS R20. 3 does not claim disease-specific validity but provides a mechanistic hypothesis framework for understanding chronicity as a dynamical systems phenomenon. The model formalizes concepts such as threshold behavior, partial irreversibility, and phase-space migration using minimal nonlinear structure. It is intended as a computational research scaffold rather than a clinically validated predictive tool. Conclusion: Chronicity may be interpretable as a drift-modulated bistable system with hysteresis and gradual basin extinction. GENESIS R20. 3 demonstrates how low-dimensional nonlinear dynamics can generate clinically plausible progression patterns while remaining structurally transparent and testable.