Biomarkers.

Background: Neurodegenerative diseases are a heterogeneous group of illnesses. Differences across patients exist in the underlying biological drivers of disease. Furthermore, cross-diagnostic disease mechanisms exist, and different pathologies often co-occur in the brain.

Biomarkers.

Background: Precision neuroscience is emerging as a transformative approach that aims to identify the right treatment for the right patient at the right time. To enable this, it is important to move beyond the categorization of patients based on clinical symptoms towards a biological definition of disease. For Alzheimer's disease, significant progress has been made in this direction, with the development of the "A/T/N" biomarker framework that classifies patients based on underlying pathophysiology.

Goliath clades and tracking of clonal dynamics show three phases of UV-induced skin carcinogenesis.

While the genetic paradigm of cancer etiology has proven powerful, it remains incomplete as evidenced by the widening spectrum of non-cancer cell-autonomous "hallmarks" of cancer. Studies have demonstrated the commonplace presence of high oncogenic mutational burdens in homeostatically-stable epithelia. Hence, the presence of driver mutations alone does not result in cancer.

Rare germline structural variants increase risk for pediatric solid tumors.

Pediatric solid tumors are a leading cause of childhood disease mortality. In this work, we examined germline structural variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequencing of 1765 affected children, their 943 unaffected parents, and 6665 adult controls. We discovered a sex-biased association between very large (>1 megabase) germline chromosomal abnormalities and increased risk of solid tumors in male children.

Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy.

Importance: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.

Objective: To assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.