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In 2000, the prevalence was reported as 1 in 150 children, which progressively decreased to 1 in 125 in 2004, 1 in 110 in 2006, 1 in 88 in 2008, 1 in 68 in 2010 and 2012, 1 in 59 in 2014an 2018, and 1 in 36 in 2023 in the U.S

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This selective signaling behavior allows researchers to examine how peptide fragments can retain specific biological functions while avoiding broader receptor activation