Engineering of CRISPR-Cas PAM recognition using deep learning of vast evolutionary data.

CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, significantly limiting the range of targetable sequences in a genome. Machine learning-based protein engineering provides a powerful solution to efficiently generate Cas protein variants tailored to recognize specific PAMs. Here, we present Protein2PAM, an evolution-informed deep learning model trained on a dataset of over 45,000 CRISPR-Cas PAMs.

Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial.

Purpose: Transurethral resection of bladder tumor (TURBT) is the initial staging procedure for new bladder cancers (BCs). For muscle-invasive bladder cancers (MIBCs), TURBT may delay definitive treatment. We investigated whether definitive treatment can be expedited for MIBC using flexible cystoscopic biopsy and multiparametric magnetic resonance imaging (mpMRI) for initial staging.

Discovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa.

Pathogenic mutations that cause rhodopsin misfolding lead to a spectrum of currently untreatable blinding diseases collectively termed retinitis pigmentosa. Small molecules to correct rhodopsin misfolding are therefore urgently needed. In this study, we utilized virtual screening to search for drug-like molecules that bind to the orthosteric site of rod opsin and improve its folding and trafficking.

Long-Term Impact of Childhood Dental Attendance on Perceived Adult Oral Health: The British Cohort Study.

Objective: To evaluate the effect of childhood dental attendance pattern on self-rated oral health in middle adulthood among the British population.

Methods: Data from the 1970 British Cohort Study involving participants born in England, Scotland, and Wales were used. Self-rated oral health was assessed at age 46.

Bidirectional longitudinal associations between subjective oral health and subjective well-being.

Objective: This study investigated the bidirectional longitudinal association between subjective oral health (SOH) and subjective well-being (SWB) over time.

Methods: This cohort study was based on a four-wave surveys conducted by the English Longitudinal Study of Aging. SOH was measured by oral impacts on daily performance (OIDP), self-rated oral health (SROH), and SWB was measured by the Center for Epidemiologic Studies-Depression (CES-D) scale, Control, Autonomy, Self-Realization, and Pleasure (CASP-19), and satisfaction with life scale (SWLS).