AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.

Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice.

Celastrol boosts fluconazole efficacy against vaginal candidiasis: in vitro and in vivo evidence.

Candida albicans is a commensal fungus that naturally inhabits the vagina. However, overgrowth of C. albicans can result in vulvovaginal candidiasis (VVC), one of the most prevalent fungal infections affecting women.

Implementation Determinants of PrEP and Behavioral Health Treatment Referral among HIV Test Counselors.

Pre-exposure prophylaxis (PrEP), an effective biomedical prevention intervention, is not sufficiently reaching populations experiencing high HIV incidence. Behavioral health (BH) treatment addressing mental health and substance use similarly requires increased reach to HIV-affected populations. HIV testing is an opportunity to refer individuals to PrEP and BH treatment.

Androgen deprivation therapy does not increase rates for reintervention, complication, or infection in primary penile implant or artificial urinary sphincter surgery: a retrospective cohort study from the TriNetX network.

Prostate cancer treatment-related erectile dysfunction and stress urinary incontinence are commonly treated with inflatable penile prosthesis (IPP) or artificial urinary sphincter (AUS). Given the association with androgens and penile/urethral health, we aim to evaluate whether patients on androgen deprivation therapy (ADT) undergoing IPP or AUS surgery are at increased risk for reintervention, complication, or infection. We queried the TriNetX database for adult males receiving IPP or AUS.

Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs).

Purpose: A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

Ongoing Symptoms and Concerns Experienced by Low-Risk Breast Cancer Survivors Following Active Treatment.

Introduction: Little is known about the symptom burden of breast cancer survivors with early-stage disease. Many studies have focused on symptoms of patients who are undergoing or recently completed systemic therapy. However, with the increased use of Oncotype DX, the proportion of early-stage hormone receptor-positive patients who undergo chemotherapy has declined, making existing studies of the symptom experience less useful for these patients.

Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers.

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients.

Enhanced energy storage in antiferroelectrics via antipolar frustration.

Dielectric-based energy storage capacitors characterized with fast charging and discharging speed and reliability play a vital role in cutting-edge electrical and electronic equipment. In pursuit of capacitor miniaturization and integration, dielectrics must offer high energy density and efficiency. Antiferroelectrics with antiparallel dipole configurations have been of significant interest for high-performance energy storage due to their negligible remanent polarization and high maximum polarization in the field-induced ferroelectric state.

An evaporite sequence from ancient brine recorded in Bennu samples.

Evaporation or freezing of water-rich fluids with dilute concentrations of dissolved salts can produce brines, as observed in closed basins on Earth and detected by remote sensing on icy bodies in the outer Solar System. The mineralogical evolution of these brines is well understood in regard to terrestrial environments, but poorly constrained for extraterrestrial systems owing to a lack of direct sampling. Here we report the occurrence of salt minerals in samples of the asteroid (101955) Bennu returned by the OSIRIS-REx mission.

Generative AI as a tool to accelerate the field of ecology.

The emergence of generative artificial intelligence (AI) models specializing in the generation of new data with the statistical patterns and properties of the data upon which the models were trained has profoundly influenced a range of academic disciplines, industry and public discourse. Combined with the vast amounts of diverse data now available to ecologists, from genetic sequences to remotely sensed animal tracks, generative AI presents enormous potential applications within ecology. Here we draw upon a range of fields to discuss unique potential applications in which generative AI could accelerate the field of ecology, including augmenting data-scarce datasets, extending observations of ecological patterns and increasing the accessibility of ecological data.

Perioperative outcomes of robotic vs laparoscopic pancreatoduodenectomy: a meta-analysis and trial sequential analysis.

Background: Minimally invasive pancreatoduodenectomy has gained widespread acceptance among hepatopancreatobiliary surgeons due to its demonstrated advantages in perioperative outcomes compared to the conventional open approach. This meta-analysis, along with trial sequential analysis, aimed to compare the outcomes of robotic pancreatoduodenectomy and laparoscopic pancreatoduodenectomy based on the current available evidence.

Methods: A systematic search of PubMed, Cochrane, Scopus, and Web of Science was conducted from inception to July 2024.

Expanding the human gut microbiome atlas of Africa.

Population studies provide insights into the interplay between the gut microbiome and geographical, lifestyle, genetic and environmental factors. However, low- and middle-income countries, in which approximately 84% of the world's population lives, are not equitably represented in large-scale gut microbiome research. Here we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,801 women from Burkina Faso, Ghana, Kenya and South Africa.

CARD domains mediate anti-phage defence in bacterial gasdermin systems.

Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Following pathogen recognition by nucleotide binding-domain, leucine-rich, repeat-containing (NLR) proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore-forming proteins to induce pyroptotic cell death. Here we show that CARD domains are present in defence systems that protect bacteria against phage.

Contrasting drought sensitivity of Eurasian and North American grasslands.

Extreme droughts generally decrease productivity in grassland ecosystems with negative consequences for nature's contribution to people. The extent to which this negative effect varies among grassland types and over time in response to multi-year extreme drought remains unclear. Here, using a coordinated distributed experiment that simulated four years of growing-season drought (around 66% rainfall reduction), we compared drought sensitivity within and among six representative grasslands spanning broad precipitation gradients in each of Eurasia and North America-two of the Northern Hemisphere's largest grass-dominated regions.

Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase.

γ-Glutamyl carboxylase (GGCX) is the sole identified enzyme that uses vitamin K (VK) as a cofactor in humans. This protein catalyses the oxidation of VK hydroquinone to convert specific glutamate residues to γ-carboxyglutamate residues in VK-dependent proteins (VDPs), which are involved in various essential biological processes and diseases. However, the working mechanism of GGCX remains unclear.

Engineered heart muscle allografts for heart repair in primates and humans.

Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques.

Global meta-analysis shows action is needed to halt genetic diversity loss.

Mitigating loss of genetic diversity is a major global biodiversity challenge. To meet recent international commitments to maintain genetic diversity within species, we need to understand relationships between threats, conservation management and genetic diversity change. Here we conduct a global analysis of genetic diversity change via meta-analysis of all available temporal measures of genetic diversity from more than three decades of research.

The Ronne Ice Shelf survived the last interglacial.

The fate of the West Antarctic Ice Sheet (WAIS) is the largest cause of uncertainty in long-term sea-level projections. In the last interglacial (LIG) around 125,000 years ago, data suggest that sea level was several metres higher than today, and required a significant contribution from Antarctic ice loss, with WAIS usually implicated. Antarctica and the Southern Ocean were warmer than today, by amounts comparable to those expected by 2100 under moderate to high future warming scenarios.

Degradable thermosets via orthogonal polymerizations of a single monomer.

Crosslinked thermosets are highly durable materials, but overcoming their petrochemical origins and inability to be recycled poses a grand challenge. Many strategies to access crosslinked polymers that are bioderived or degradable-by-design have been proposed, but they require several resource-intensive synthesis and purification steps and are not yet feasible alternatives to conventional consumer materials. Here we present a modular, one-pot synthesis of degradable thermosets from the commercially available, biosourced monomer 2,3-dihydrofuran (DHF).

Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Carbon-hydrogen (C-H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp)-H bond. In recent years, metalloenzymes have been found to perform C(sp)-H bond functionalization.