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The combined p value for the trend of increased ferroptosis sensitivity with dedifferentiation across both the CTRP results and the validation results is based on correlation (p=10 −12 ) with similar results with Jonckheere-Terpstra trend test assessing ordered significance across the 4 differentiation stages (p=10 −13 )

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This extraordinary result shows that ground state destabilization through hyperconjugation in the external aldimine intermediate is a major factor in determining reaction specificity and catalytic power in AAT by moving the substrate very substantially from its structure in solution toward the transition state