Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modification.

Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.

Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries.

The consumption of sugar-sweetened beverages (SSBs) is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). However, an updated and comprehensive assessment of the global burden attributable to SSBs remains scarce. Here we estimated SSB-attributable T2D and CVD burdens across 184 countries in 1990 and 2020 globally, regionally and nationally, incorporating data from the Global Dietary Database, jointly stratified by age, sex, educational attainment and urbanicity.

Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial.

Over 46% of African pregnant women are anemic. Oral iron is recommended but often suboptimal, particularly late in pregnancy. Intravenous ferric carboxymaltose (FCM) could treat anemia in women in the third trimester in sub-Saharan Africa.

Target product profile for cell-based and gene-based therapies to achieve a cure for HIV.

This target product profile (TPP) highlights the minimal and optimal characteristics for ex-vivo and in-vivo cell and gene therapy-based products aimed at achieving an HIV cure (ie, durable antiretroviral-free viral control). The need for an effective, safe, scalable, affordable, accessible, and acceptable cure for HIV infection remains a major global priority. The possibilities for cell and gene therapy-based products for an HIV cure are rapidly expanding.

The helmeted hornbill casque is reinforced by a bundle of exceptionally thick, rod-like trabeculae.

Among hornbill birds, the critically endangered helmeted hornbill (Rhinoplax vigil) is notable for its casque (a bulbous beak protrusion) being filled with trabeculae and fronted by a very thick keratin layer. Casque function is debated but appears central to aerial jousting, where birds (typically males) collide casques at high speeds in a mid-flight display that is audible for more than 100 m. We characterized the structural relationship between the skull and casque anatomy using X-ray microtomography and quantitative trabecular network analysis to examine how the casque sustains extreme impact.

Modelling the health labour market outlook in Kenya: Supply, needs and investment requirements for health workers, 2021-2035.

Kenya is committed to achieving Universal Health Coverage (UHC) within its devolved health system in which significant investments have been made in health infrastructure, workforce development, and service delivery. Despite these efforts, the country faces considerable health workforce challenges. To address these, the Ministry of Health undertook a comprehensive Health Labour Market Analysis (HLMA) in 2022 to generate evidence supporting the development of responsive health workforce policies.

Parenting Self-Efficacy Moderates the Association Between Unmet Parenting Expectations and NICU-Related PTSD Symptoms Reported by Mothers 1-5 Years Post-Infant NICU Hospitalization.

Infant neonatal intensive care unit (NICU) hospitalization increases maternal risk for post-traumatic stress disorder (PTSD) symptoms, which may negatively impact mother-child attachment and infant growth and development. Prior studies have documented positive associations between unmet parenting expectations and adverse maternal psychological outcomes, including post-NICU discharge. However, no studies have yet explored how unmet parenting expectations may be associated with maternal NICU-related PTSD symptoms.

Patient activation improves with a multi-component personalized mHealth intervention in older patients at risk of cardiovascular disease: a pilot randomized controlled trial.

Aims: This study aimed to determine the effect of a multi-component mHealth intervention on patient activation and examine its predictors among older adults at risk of cardiovascular disease (CVD).

Methods And Results: This pilot randomized controlled trial compared two groups: Get FIT (control), who received healthy lifestyle counselling from a licensed health coach, a mHealth app (MyFitnessPal) with push alerts, and an activity tracker, and Get FIT + (intervention), who received the same interventions and had personalized text messages with 3- and 6-month follow-up periods. Patient activation was measured using the 13-item Patient Activation Measure; higher scores indicated better activation.

Measuring the uptake of clinic-based HIV treatment and prevention services following HIV testing and referral at private pharmacies in Kenya.

Background: Despite their ubiquity across sub-Saharan Africa, private pharmacies are underutilized for HIV service delivery beyond the sale of HIV self-test kits. To understand what uptake of HIV prevention and treatment services might look like if private pharmacies offered clients free HIV self-testing and referral to clinic-based HIV services, we conducted a pilot study in Kenya.

Methods: At 20 private pharmacies in Kisumu County, Kenya, pharmacy clients (≥ 18 years) purchasing sexual health-related products (e.

The Costs of a Multisectoral Nutrition Program Implemented Through a Poultry Value Chain Platform in Burkina Faso.

Undernutrition in women and young children in Burkina Faso is a critical problem. Egg consumption is low despite many households raising poultry. The Soutenir l'Exploitation Familiale pour Lancer l'Élevage des Volailles et Valoriser l'Économie Rurale (SELEVER) project, an integrated agriculture-nutrition intervention, promoted egg consumption and sales to investigate the impact of poultry production on child nutrition.

Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings.

Amino alcohols are vital in natural products, pharmaceuticals and agrochemicals, and as key building blocks for various applications. Traditional synthesis methods often rely on polar bond retrosynthetic analysis, requiring extensive protecting group manipulations that complicate direct access. Here we show a streamlined approach using a serine-derived chiral carboxylic acid in stereoselective electrocatalytic decarboxylative transformations, enabling efficient access to enantiopure amino alcohols.

Development of the membrane ceiling method for in vitro spermatogenesis.

Spermatogenesis is one of the most complex processes of cell differentiation and its failure is a major cause of male infertility. Therefore, a proper model that recapitulates spermatogenesis in vitro has been long sought out for basic and clinical research. Testis organ culture using the gas-liquid interphase method has been shown to support spermatogenesis in mice and rats.

Governance Considerations for Point-of-Care Ultrasound: a HIMSS-SIIM Enterprise Imaging Community Whitepaper in Collaboration with AIUM.

Point-of-care ultrasound (POCUS) has emerged as a standard of care across a variety of healthcare settings due to its ability to provide critical clinical information and as well as procedural guidance to clinicians directly at the bedside. Implementation of enterprise imaging (EI) strategies is needed such that POCUS images can be appropriately captured, indexed, managed, stored, distributed, viewed, and analyzed. Because of its unique workflow and educational requirements, reliance on traditional order-based workflow solutions may be insufficient.

Artificial Intelligence and Cancer Health Equity: Bridging the Divide or Widening the Gap.

Purpose Of Review: This review aims to evaluate the impact of artificial intelligence (AI) on cancer health equity, specifically investigating whether AI is addressing or widening disparities in cancer outcomes.

Recent Findings: Recent studies demonstrate significant advancements in AI, such as deep learning for cancer diagnosis and predictive analytics for personalized treatment, showing potential for improved precision in care. However, concerns persist about the performance of AI tools across diverse populations due to biased training data.

Degrowth as a plausible pathway for food systems transformation.

Food systems require urgent transformation towards social and ecological sustainability. Degrowth posits a radical pathway of transformation to reduce ecological impacts while increasing well-being and reducing inequality. Here we highlight that degrowth and food systems-albeit both linked to transformation-are not well integrated.

Application of a targeted amplicon sequencing panel to screen for insecticide resistance mutations in Anopheles darlingi populations from Brazil.

Large-scale surveillance and informed vector control approaches are urgently needed to ensure that national malaria programs remain effective in reducing transmission and, ultimately, achieving malaria elimination targets. In South America, Anopheles darlingi is the primary malaria vector and is responsible for the majority of Plasmodium species transmission. However, little is known about the molecular markers associated with insecticide resistance in this species.

HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies.

HLA-E is a nonclassical, nonpolymorphic, class Ib HLA molecule. Its primary function is to present a conserved nonamer peptide, termed VL9, derived from the signal sequence of classical MHC molecules to the NKG2x-CD94 receptors on NK cells and a subset of T lymphocytes. These receptors regulate the function of NK cells, and the importance of this role, which is conserved across mammalian species, probably accounts for the lack of genetic polymorphism.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Meeting summary: Global vaccine and immunization research forum, 2023.

At the 2023 Global Vaccine and Immunization Research Forum (GVIRF), researchers from around the world gathered in the Republic of Korea to discuss advances and opportunities in vaccines and immunization. Many stakeholders are applying the lessons of Covid-19 to future emergencies, by advancing early-stage development of prototype vaccines to accelerate response to the next emerging infectious disease, and by building regional vaccine research, development, and manufacturing capacity to speed equitable access to vaccines in the next emergency. Recent vaccine licensures include: respiratory syncytial virus vaccines, both for the elderly and to protect infants through maternal immunization; a new dengue virus vaccine; and licensure of Covid-19 vaccines previously marketed under emergency use authorizations.

Can a plant biologist fix a thermostat?

The shift to reductionist biology at the dawn of the genome era yielded a 'parts list' of plant genes and a nascent understanding of complex biological processes. Today, with the genomics era in full swing, advances in high-definition genomics enabled precise temporal and spatial analyses of biological systems down to the single-cell level. These insights, coupled with artificial intelligence-driven in silico design, are propelling the development of the first synthetic plants.

A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae.

Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE).