The Human Variable 

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is profoundly sensitive to environmental stressors. Pollutants such as polycyclic aromatic hydrocarbons (PAHs), particulate matter (PM₂.₅, PM₁₀), nitrogen dioxide (NO₂), ground-level ozone (O₃), sulfur dioxide (SO₂), and volatile organic compounds (VOCs), combined with weather triggers like heat, cold, barometric pressure swings, mold, humidity, and pollen, drive flares that push patients into cycles of severe disabi

CYNAERA has the first clinical intelligence system designed to simulate and stratify patient response across the full complexity of infection-associated chronic conditions (IACCs) such as ME/CFS, Long COVID, POTS, MCAS, EDS, Lyme, CRPS, and related syndromes. Unlike traditional models that flatten patients into crude categories, CYNAERA builds individualized profiles across 11 stratification axes and integrates them with six mechanistic phenotyping domains.

The Cultural Gendered Patriarchy Index (CGPI), developed by CYNAERA (2025), is the first cross-national system designed to quantify the effect of patriarchy on male diagnostic rates. By integrating data from 180 countries—including global gender indices, masculinity scales, health-seeking behavior datasets, and IACC prevalence studies—we reveal that millions of men are statistically invisible.

CYNAERA’s AI simulations analyze 120+ therapeutic candidates across 6 mechanisms, weighting them by patient endotype, Pathos™ severity score, and predicted remission probability. This map provides the first public-facing mechanism reference, while full dosing logic, contraindication overlays, and trial-ready protocols remain licensed.

The CDF-Peds-ME/CFS™, developed by CYNAERA, is the first child-adapted Composite Diagnostic Fingerprint designed for school, home, and clinical settings. Built on CYNAERA’s validated CDF-ME framework, it integrates multi-system biomarkers, digital phenotyping, and school-based records into a practical, developmentally appropriate diagnostic solution.

CYNAERA’s PHAROS™ + REWIRE™ framework introduces a longitudinal, multi-pathway diagnostic system. By tracking cytokine rhythms over days, mapping vagal-histaminergic amplification, and integrating viral reactivation profiles, PHAROS™ + REWIRE™ replaces linear models with terrain-aware detection. This paper expands on the biological foundations of this model, critiques failed legacy approaches, and outlines a replicable path to mechanism-specific, real-world diagnostics.

ME/CFS is a relapsing, multisystem condition characterized by immune disruption, neuroinflammation, autonomic dysfunction, and energy metabolism abnormalities. Trials should anchor in stabilization before pursuing cure.

Clinician Guide For MECFS Therapeutics: Built from CYNAERA Diagnostic Fingerprints™ + IACCI Terrain Logic + XR/CR Pharmacology Doctrine

For decades, ME/CFS has been treated as a monolith in research, despite overwhelming evidence of heterogeneity across patients. This failure to stratify has been a primary driver of trial collapse, clinical mismanagement, and neglect. The CYNAERA 25+ ME/CFS Phenotyping List integrates biological, environmental, and social terrain factors into a structured classification system.

Clinical trials for ME/CFS have consistently failed not because therapies were inherently ineffective, but because the system was never built for conditions like ME/CFS and related IACCs. FDA gold-standard trial design assumes predictable progression, uniform subtypes, and tolerance for interventions — none of which apply to ME/CFS The CYNAERA Thesis asserts that repurposed drugs can work for ME/CFS if trials account for post-exertional malaise (PEM),(MCAS), and POTS

The Va-IRI™ (Vaccination Immune Readiness Index) provides a structured 0–100 readiness score derived from common labs, symptom baselines, and patient function. Built on the STAIR Stable Method™ (Stabilization, Tolerance, And Immune Readiness), Va-IRI™ adapts low-and-slow principles pioneered by patients and refined through collaboration with leading researchers.

Using CYNAERA’s recalibrated US-CCUC™ prevalence models, which place the U.S. burden between 8.7 million (conservative) and 21.5 million (realistic), the annual economic impact rises to $243–817 billion.