A double dissociation between semantic and spatial cognition in visual to default network pathways.

Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories.

Chronic Health Conditions in the Workplace: Work Stressors and Supportive Supervision, Work Design, and Programs.

A large and growing number of workers are managing chronic physical and mental health conditions while working, necessitating attention from both researchers and leaders and practitioners in organizations. Much of the current discourse around research and practice in this area is focused on prevention of chronic disease and rehabilitation of disability to help workers return to work. Less commonly attended to are workplace factors that can support the quality of working life and the longevity of working life for workers with chronic health conditions.

Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a non-cancer-related developmental disorder, has not been systematically assessed.

Exome Sequencing in the Diagnostic Pathway for Suspected Rare Genetic Diseases: Does the Order of Testing Affect its Cost-Effectiveness?

Background: Patients with suspected rare diseases often experience lengthy and uncertain diagnostic pathways. This study aimed to estimate the cost-effectiveness of exome sequencing (ES) in different positions in the diagnostic pathway for patients suspected of having a rare genetic disease.

Methods: Data collected retrospectively from 305 patients suspected of having a rare genetic disease (RGD), who received clinical-grade ES and participated in the Canadian multicentre Care4Rare-SOLVE study, informed a discrete event simulation of the diagnostic pathway.

Embryotoxicity of statins and other prescribed drugs with reported off-target effects on cholesterol biosynthesis.

Cholesterol plays pivotal cellular functions ranging from maintaining membrane fluidity to regulating cell-cell signaling. High cholesterol causes cardiovascular diseases, low cholesterol is linked to neuropsychiatric disorders, and inborn errors of cholesterol synthesis cause multisystem malformation syndromes. Statins lower cholesterol levels by inhibiting the first, rate-limiting reaction of the cholesterol biosynthesis pathway catalyzed by hydroxymethyl-glutaryl-Coenzyme A reductase (HMGCR).