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Results of proteomic analysis displayed the involvement of multiple cellular functions affecting inflammatory, immune and antioxidant responses, autophagy, Ca2+ -homeostasis, and cell adhesion. The combined multi-omic approach revealed new biosignatures in PD, providing novel insights in disease pathophysiology with potential future clinical application.In this article, we discuss four vexing problems in risk-based decision making that John Evans has addressed over the last nearly 40 years and has perennially challenged the two of us and