Topological Latent Manifold Model v6.9: ABF Mechanistic Integration Framework — Partial ABF Cascade Coupling and Vascular Latent Extension toward TLMM v7.0

Topological Latent Manifold Model (TLMM) v6.9 extends the mechanistic enrichment framework established in TLMM v6.8 by introducing a vascular-aware latent representation and partial integration of the Amyloid–Blood Flow (ABF) cascade. The framework introduces six methodological advances: Partial ABF Cascade Coupling through a learnable soft bidirectional interaction between Amyloid (Aβ) and Cerebral Blood Flow (CBF) Vascular Latent Extension expanding the latent space from five to six dimensions (z₆) Learnable Mechanistic Priors jointly optimized from biological knowledge and multi-modal observations Cohort-Adaptive Calibration using hierarchical Bayesian adaptation and distribution-aware calibration Mechanism-Aware Missing Data Recovery under MCAR, MAR, and MNAR settings Mechanism-Aware Feedback Loop for iterative model refinement and intervention optimization TLMM v6.9 also introduces an eighth falsifiability criterion: C8 — Vascular Coupling Consistency which extends the canonical falsifiability battery inherited from TLMM v6.8 (C1–C7) while preserving complete backward compatibility across the TLMM series. The paper further presents an exploratory mechanistic falsifiability taxonomy intended as a conceptual foundation for the planned TLMM v7.0 framework. This release contains: Complete TLMM v6.9 manuscript (34 figures) Zenodo README Fully reproducible Python demonstration script Synthetic illustrative datasets and figure generation workflow All figures, numerical results, and datasets are illustrative synthetic demonstrations for methodological development only. They do not represent clinical performance estimates, patient data, medical advice, or clinical recommendations.

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Publication Details

Journal
Zenodo (CERN European Organization for Nuclear Research)
Published
2026-06-26
DOI
https://doi.org/10.5281/zenodo.20921438
Primary Topic
Machine Learning in Healthcare
Type
preprint
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preprint

Topological Latent Manifold Model v6.9: ABF Mechanistic Integration Framework — Partial ABF Cascade Coupling and Vascular Latent Extension toward TLMM v7.0

Koji Okino
Zenodo (CERN European Organization for Nuclear Research)
Machine Learning in Healthcare
preprint

Topological Latent Manifold Model v6.9: ABF Mechanistic Integration Framework — Partial ABF Cascade Coupling and Vascular Latent Extension toward TLMM v7.0

Koji Okino
preprint en

Abstract

Topological Latent Manifold Model (TLMM) v6.9 extends the mechanistic enrichment framework established in TLMM v6.8 by introducing a vascular-aware latent representation and partial integration of the Amyloid–Blood Flow (ABF) cascade. The framework introduces six methodological advances: Partial ABF Cascade Coupling through a learnable soft bidirectional interaction between Amyloid (Aβ) and Cerebral Blood Flow (CBF) Vascular Latent Extension expanding the latent space from five to six dimensions (z₆) Learnable Mechanistic Priors jointly optimized from biological knowledge and multi-modal observations Cohort-Adaptive Calibration using hierarchical Bayesian adaptation and distribution-aware calibration Mechanism-Aware Missing Data Recovery under MCAR, MAR, and MNAR settings Mechanism-Aware Feedback Loop for iterative model refinement and intervention optimization TLMM v6.9 also introduces an eighth falsifiability criterion: C8 — Vascular Coupling Consistency which extends the canonical falsifiability battery inherited from TLMM v6.8 (C1–C7) while preserving complete backward compatibility across the TLMM series. The paper further presents an exploratory mechanistic falsifiability taxonomy intended as a conceptual foundation for the planned TLMM v7.0 framework. This release contains: Complete TLMM v6.9 manuscript (34 figures) Zenodo README Fully reproducible Python demonstration script Synthetic illustrative datasets and figure generation workflow All figures, numerical results, and datasets are illustrative synthetic demonstrations for methodological development only. They do not represent clinical performance estimates, patient data, medical advice, or clinical recommendations.

Zenodo (CERN European Organization for Nuclear Research)
United States Department of Labor (US)
Machine Learning in Healthcare
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Topological Latent Manifold Model v6.9: ABF Mechanistic Integration Framework — Partial ABF Cascade Coupling and Vascular Latent Extension toward TLMM v7.0 — Koji Okino · Zenodo (CERN European Organization for Nuclear Research) (2026) | TGRS Research Map | TGRS