mRNA display is an effective tool to identify high-affinity macrocyclic binders for challenging protein targets. The success of an mRNA display selection is dependent on generating highly diverse libraries with trillions of peptides. While translation elongation can canonically accommodate the 61 proteinogenic triplet codons, translation initiation is restricted to the native start codon AUG.
View Article and Find Full Text PDFThe epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood.
View Article and Find Full Text PDFPhysical activity is recommended for older adults; however, the benefits of previous active engagement in physical activity that can be sustained after one becomes inactive remain to be determined. This study investigated the longitudinal associations between physical activity engagement patterns and older adults' well-being. This population-based cohort study used data from the China Health and Retirement Longitudinal Study between 2015 and 2020.
View Article and Find Full Text PDFBackground: Immune effector cell-associated neurotoxicity syndrome (ICANS) can be a severe, life-threatening toxicity following CAR T-cell therapy. While currently evaluated by the immune effector cell-associated encephalopathy (ICE) score, not all patients have changes in their ICE score and not all signs and symptoms of neurotoxicity are captured.
Methods: We conducted a prospective, single center cohort pilot study to evaluate a novel, rapid neurocognitive assessment tool (CART-NS) in detecting early, subtle neurotoxicity prior to the onset of ICANS and any deterioration in the ICE score.
Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.
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