Plant-based dietary patterns are associated with improved cardiometabolic health, but causal dietary components are unclear. Protein has been proposed to play a role, but the importance of protein quantity versus quality remains unknown. We investigated the contributions of total protein amount, amino acid (AA) composition, and plant versus animal source. Analysis of total protein and AA composition of food items and dietary patterns revealed differences between individual food items, but few differences between AA profiles of vegan versus omnivorous dietary patterns. Effects of protein quantity, but not quality, on cardiometabolic health markers were observed in mice using semi-purified diets with crystalline AAs in plant versus animal-based ratios and naturally sourced diets with whole-food ingredients. Our data show relatively little difference in protein quality between plant-based and omnivorous dietary patterns and that reduced total protein intake in plant-based dietary patterns may be a contributor to the benefits of plant-based diets.Cancer heterogeneity impacts therapeutic response, driving efforts to discover over-arching rules that supersede variability. Here, we define pan-cancer binary classes based on distinct expression of YAP and YAP-responsive adhesion regulators. Combining informatics with in vivo and in vitro gain- and loss-of-function studies across multiple murine and human tumor types, we show that opposite pro- or anti-cancer YAP activity functionally defines binary YAPon or YAPoff cancer classes that express or silence YAP, respectively. YAPoff solid cancers are neural/neuroendocrine and frequently RB1-/-, such as retinoblastoma, small cell lung cancer, and neuroendocrine prostate cancer. YAP silencing is intrinsic to the cell of origin, or acquired with lineage switching and drug resistance. The binary cancer groups exhibit distinct YAP-dependent adhesive behavior and pharmaceutical vulnerabilities, underscoring clinical relevance. Mechanistically, distinct YAP/TEAD enhancers in YAPoff or YAPon cancers deploy anti-cancer integrin or pro-cancer proliferative programs, respectively. YAP is thus pivotal across cancer, but in opposite ways, with therapeutic implications. Alcohol use is causally linked to multiple cancers. We present global, regional, and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally. In this population-based study, population attributable fractions (PAFs) calculated using a theoretical minimum-risk exposure of lifetime abstention and 2010 alcohol consumption estimates from the Global Information System on Alcohol and Health (assuming a 10-year latency period between alcohol consumption and cancer diagnosis), combined with corresponding relative risk estimates from systematic literature reviews as part of the WCRF Continuous Update Project, were applied to cancer incidence data from GLOBOCAN 2020 to estimate new cancer cases attributable to alcohol. We also calculated the contribution of moderate (<20 g per day), risky (20-60 g per day), and heavy (>60 g per day) drinking to the total alcohol-attributable cancer burden, as well as the contribution by 10 and drinking up to 10 g per day contributed 41 300 (35 400-145 800) cases. Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to prevent the burden of alcohol-attributable cancers. None.None.Pulmonary hypertension is associated with increased morbidity and mortality, and growing evidence suggests that even mild elevations in pulmonary artery pressure estimated with echocardiography are linked to increased mortality. In healthy individuals who undergo right heart catheterisation, the average pulmonary artery systolic pressure ranges from 17 mm Hg to 25 mm Hg; on echocardiography, estimated pulmonary artery systolic pressure of more than 30 mm Hg is outside the normal range for most healthy individuals. Increased pulmonary artery systolic pressure (>30 mm Hg) is reported on more than 40% of clinically indicated echocardiograms, often in the presence of metabolic and cardiopulmonary comorbidities, and is associated with a 5-year mortality of 25-40%. However, current guidelines do not sufficiently highlight risk and risk-reduction approaches for the sizable patient population with elevated pulmonary artery pressure who do not have underlying severe pulmonary vascular disease such as pulmonary arterial hypertension. Increased awareness of this frequently reported high-risk echocardiographic finding, and multidisciplinary risk-reduction approaches for patients with metabolic and cardiopulmonary comorbidities and elevated pulmonary artery pressure, are urgently needed.Integral membrane proteins (MPs) are important drug targets across most fields of medicine, but historically have posed a major challenge for drug discovery due to difficulties in producing them in functional forms. We review the state of the art in drug discovery strategies using recombinant multipass MPs, and outline methods to successfully express, stabilize, and formulate them for small-molecule and monoclonal antibody therapeutics development. Advances in structure-based drug design and high-throughput screening are allowing access to previously intractable targets such as ion channels and transporters, propelling the field towards the development of highly specific therapies targeting desired conformations.The human brain undergoes a prolonged period of cortical development that spans multiple decades. During childhood and adolescence, cortical development progresses from lower-order, primary and unimodal cortices with sensory and motor functions to higher-order, transmodal association cortices subserving executive, socioemotional, and mentalizing functions. The spatiotemporal patterning of cortical maturation thus proceeds in a hierarchical manner, conforming to an evolutionarily rooted, sensorimotor-to-association axis of cortical organization. This developmental program has been characterized by data derived from multimodal human neuroimaging and is linked to the hierarchical unfolding of plasticity-related neurobiological events. Critically, this developmental program serves to enhance feature variation between lower-order and higher-order regions, thus endowing the brain's association cortices with unique functional properties. this website However, accumulating evidence suggests that protracted plasticity within late-maturing association cortices, which represents a defining feature of the human developmental program, also confers risk for diverse developmental psychopathologies.