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Several conditions and lifestyle factors can lower ApoA-I: Genetic Factors ApoA-I deficiency (rare) ApoA-I mutations such as ApoA-I Milano (unique variant with protective function despite low levels) Metabolic Syndrome & Diabetes Insulin resistance lowers HDL function and ApoA-I expression

doi: 10.1016/j.molp.2023.09.010 8 DemecsovL.ZelinovV.Liptkov.TamsL

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In general, for both the optimization and robust validation of metabolite-derived machine learning models, independent analyses with larger sample sizes of de novo patients across multiple distinct cohorts are needed