Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Dementia Care Research and Psychosocial Factors.

Background: For care of persons with dementia (PWDs), the healthcare system relies on informal care partners (CPs), who are disproportionately at risk of detrimental health outcomes. Psychosocial interventions, including via telehealth, have been shown to buffer against negative outcomes and improve CPs' ability to provide care. We aimed to develop and pilot an evidence-informed CP intervention using in-person and telehealth modalities.

Dementia Care Research and Psychosocial Factors.

Background: Prior research on factors associated with sleep problems among care partners (CPs) of persons with cognitive decline (PwCD) are often limited by imprecise (i.e., single yes/no questions) measures of insomnia, burden, and CP mental health.

Dementia Care Practice.

Background: The increasing population of older adults and growing number of disease-modifying therapies for Alzheimer's disease (AD) highlight the need for timely differential diagnosis of neurodegenerative disorders despite high referral volumes. This study aimed to develop and pilot a brief neuropsychological battery to evaluate cognitive functioning in adults with suspected AD and improve service delivery by reducing the time between referral and diagnosis.

Methods: Patients were referred to the "early AD pathway" by their neurologist or geriatrician after an initial evaluation in an outpatient multidisciplinary dementia clinic.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.