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We classify the functional characteristics of currently known paralogs into two distinct groups (Figure 25A): (1) paralogs that have lost metal coordinating residues and may or may not dispense of the need for metal altogether (Category 1), and (2) paralogs that are metal-promiscuous and require a metal for catalysis but may or may not retain function with Zn II (Category 2)

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Frequent interruptions may lead to a "yo-yo" pattern that undermines long-term success

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The PIONEER programme included a large number of patients, and data from more than 2800 were included in these analyses