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Predictive computational tools are emerging to de-risk these platforms, but thorough in vivo assessment is indispensable ( 4 Challenges, future directions, and the promise of precision medicine 4.1 Key challenges in targeting oxidative stress for MIRI treatment Despite compelling preclinical evidence highlighting the central role of oxidative stress in MIRI pathophysiology, translating these findings into effective clinical therapies has proven remarkably challenging, largely contributing to the unmet promise observed thus far