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They were discovering them themselves, comparing protocols online, discussing personal experiences, and arriving in physicians' offices asking questions about therapies that many clinicians were only beginning to investigate

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Elevated HMGB1 levels have been detected in the blood of patients, where it interacts with receptors such as RAGE and TLR4, forming complexes with IL-1β or LPS to activate proinflammatory signaling pathways (Shimizu et al., 2017)