Mitochondrial unfolded protein response-dependent β-catenin signaling promotes neuroendocrine prostate cancer.

The mitochondrial unfolded protein response (UPR) maintains mitochondrial quality control and proteostasis under stress conditions. However, the role of UPR in aggressive and resistant prostate cancer is not clearly defined. We show that castration-resistant neuroendocrine prostate cancer (CRPC-NE) harbored highly dysfunctional oxidative phosphorylation (OXPHOS) Complexes.

X-ray linear dichroic tomography of crystallographic and topological defects.

The functionality of materials is determined by their composition and microstructure, that is, the distribution and orientation of crystalline grains, grain boundaries and the defects within them. Until now, characterization techniques that map the distribution of grains, their orientation and the presence of defects have been limited to surface investigations, to spatial resolutions of a few hundred nanometres or to systems of thickness around 100 nm, thus requiring destructive sample preparation for measurements and preventing the study of system-representative volumes or the investigation of materials under operational conditions. Here we present X-ray linear dichroic orientation tomography (XL-DOT), a quantitative, non-invasive technique that allows for an intragranular and intergranular characterization of extended polycrystalline and non-crystalline materials in three dimensions.

Climate-based modelling and forecasting of dengue in three endemic departments of Peru.

Amid profound climate change, incidence of dengue continues to rise and expand in distribution across the world. Here, we analysed dengue in three coastal departments of Peru which have recently experienced public health emergencies during the worst dengue crises in Latin American history. We developed a climate-based spatiotemporal modelling framework to model monthly incidence of new dengue cases in Piura, Tumbes, and Lambayeque over 140 months from 2010 to 2021.

Being and Doing Together in a Naturally Occurring Retirement Community: Pandemic Experiences of Older Adults.

Developing effective, sustainable strategies that promote social inclusion, reduce isolation, and support older adults' wellbeing continues to be important to aging communities in Canada. One strategy that targets community-living older adults involves identifying naturally occurring retirement communities (NORCs) and supporting them through supportive service programs (NORC-SSPs). This qualitative descriptive study utilized semi-structured interviews to explore how older adults living in a NORC supported by an SSP, sought to build, and maintain, a sense of community during the COVID-19 pandemic.

Deficits in Pre- and Post-transplant Functional, Motor, and Cognitive Deficits Associated With Graft Failure and Mortality in Pediatric Heart Transplant Recipients.

Background: Pretransplant functional, motor, cognitive, and academic deficits are common in pediatric patients requiring heart transplantation (HT); some persist post-HT. We assessed the association between these quality of life (QoL) deficits and post-HT outcomes.

Methods: Using SRTR data 2008-2023, we evaluated the functional, motor, cognitive, and academic status of pediatric HT recipients from listing to 15 years post-HT.

2025 Roadmap on 3D Nano-magnetism.

The transition from planar (2D) to three-dimensional (3D) magnetic nanostructures represents a significant advancement in both fundamental research and practical applications, offering vast potential for next-generation technologies like ultrahigh-density storage, memory, logic, and neuromorphic computing. Despite being a relatively new field, the emergence of 3D nanomagnetism presents numerous opportunities for innovation, prompting the creation of a comprehensive roadmap by leading international researchers. This roadmap aims to facilitate collaboration and interdisciplinary dialogue to address challenges in materials science, physics, engineering, and computing.

Health care utilization and costs among coordinated care patients in Southeastern Ontario: A difference-in-differences study of a double propensity score-matched cohort.

Objectives: Coordinated care plans (CCPs) for high-cost health care system users aim to improve system-level performance. We evaluated health care resource use and costs among CCP patients (enrollees) versus a control group that did not receive coordinated care (comparators) in Southeastern Ontario.

Methods: A difference-in-differences analysis of a quasi-experimental, double propensity score-matched and adjusted cohort was conducted.

Characteristics of Madariaga and Venezuelan Equine Encephalitis Virus Infections, Panama.

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, clinical and epidemiologic reports are limited, and outbreaks are occurring at an increasing frequency. We addressed the data gap by analyzing all available clinical and epidemiologic data of MADV and VEEV infections recorded since 1961 in Panama.

Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.

Hsp70 prevents protein aggregation and is cytoprotective, but sustained Hsp70 overexpression is problematic. Therefore, we characterized small molecule agonists that augment Hsp70 activity. Because cumbersome assays were required to assay agonists, we developed cell-based and in vivo assays in which disease-associated consequences of Hsp70 activation can be quantified.

The utility of wastewater surveillance for monitoring SARS-CoV-2 prevalence.

Public health authorities have increasingly used wastewater-based epidemiology (WBE) to monitor community transmission of SARS-CoV-2 and other agents. In this study, we evaluate the utility of WBE during the COVID-19 pandemic in England for estimating SARS-CoV-2 prevalence. We use wastewater data from the Environmental Monitoring for Health Protection program and prevalence data from the REal-time Assessment of Community Transmission-1 study.

COVID-19 testing and reporting behaviours in England across different sociodemographic groups: a population-based study using testing data and data from community prevalence surveillance surveys.

Background: Understanding underlying mechanisms of heterogeneity in test-seeking and reporting behaviour during an infectious disease outbreak can help to protect vulnerable populations and guide equity-driven interventions. The COVID-19 pandemic probably exerted different stresses on individuals in different sociodemographic groups and ensuring fair access to and usage of COVID-19 tests was a crucial element of England's testing programme. We aimed to investigate the relationship between sociodemographic factors and COVID-19 testing behaviours in England during the COVID-19 pandemic.

Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways.

Adenoviral pVII proteins are multifunctional, highly basic, histone-like proteins that can bind to and transport the viral genome into the host cell nucleus. Despite the identification of several nuclear localization signals (NLSs) in the pVII protein of human adenovirus (HAdV)2, the mechanistic details of nuclear transport are largely unknown. Here we provide a full characterization of the nuclear import of precursor (Pre-) pVII protein from an ancient siadenovirus, frog siadenovirus 1 (FrAdV1), using a combination of structural, functional, and biochemical approaches.

Block Copolymer-Directed Single-Diamond Hybrid Structures Derived from X-ray Nanotomography.

Block copolymers are recognized as a valuable platform for creating nanostructured materials. Morphologies formed by block copolymer self-assembly can be transferred into a wide range of inorganic materials, enabling applications including energy storage and metamaterials. However, imaging of the underlying, often complex, nanostructures in large volumes has remained a challenge, limiting progress in materials development.

Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.

Background: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated.

Clinical and biobehavioral phenotypic assessments and data harmonization for the RE-JOIN research consortium: Recommendations for common data element selection.

Background: The Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium is part of the Helping to End Addiction Long-term® (HEAL) Initiative. HEAL is an ambitious, NIH-wide initiative to speed scientific solutions to stem the national opioid public health crisis. The RE-JOIN consortium's over-arching goal is to define how chronic joint pain-mediating neurons innervate different articular and -articular tissues, with a focus on the knee and temporomandibular joints (TMJ) across species employing the latest neuroscience approaches.

Live-cell visualization of tau aggregation in human neurons.

Alzheimer's disease (AD) and more than twenty other dementias, termed tauopathies, are pathologically defined by insoluble aggregates of the microtubule-associated protein tau (MAPT). Although tau aggregation correlates with AD symptomology, the specific tau species, i.e.

Craniofacial malformations in a stillborn mixed-breed dog as a cause for dystocia.

This case report describes the findings of craniofacial anomalies associated with dystocia in a mixed-breed bitch. A bitch in labour was presented for evaluation of dystocia, and an emergency caesarean section was performed. Two pups with craniofacial abnormalities were delivered by hysterotomy.

The Feasibility of the Diabetes Self-Management Coaching Program in Primary Care: A Mixed-Methods Randomized Controlled Feasibility Trial.

Background: Diabetes mellitus, a chronic metabolic disorder associated with elevated blood sugar levels, is a significant cause of morbidity, mortality, and disability globally. The rampant rise in the prevalence of diabetes presents a public health burden and a challenge to the primary care setting. Diabetes self-management coaching is an emergent, client-centered, solution-focused approach to enhance self-efficacy and self-care behavior, control glycemia, and prevent acute and chronic complications.

Strengthening collaboration for interprofessional primary care teams: Insights and key learnings from six disciplinary perspectives.

We provide a case example of the collaborative process required to plan and implement initiatives to enhance team-based primary care, drawing on experiences of six disciplines working together to create new curricula as part of Team Primary Care. Recommendations to strengthen collaboration from our team include building capacity requires an understanding of unique disciplinary roles and understanding of unique elements of primary care; competencies have to be specifically articulated and demonstrated within a primary care context; interprofessional education within and across disciplines is needed; establishing primary care competencies would provide a common set of skills, knowledge, values, and attitudes to form a foundation in which to build the capacity of the interprofessional primary care workforce; and interprofessional collaboration is needed in implementing team-based primary care in practice and in preparing an interprofessional workforce prepared to leverage the expertise of the entire team.

An extensive re-evaluation of evidence and analyses of the Randomised Badger Culling Trial II: In neighbouring areas.

In the second investigation in a pair of analyses which re-evaluates the Randomised Badger Culling Trial (RBCT), we estimate the effects of proactive badger culling on the incidence of tuberculosis (TB) in cattle populations in unculled neighbouring areas. Throughout peer-reviewed analyses of the RBCT, proactive culling was estimated to have detrimental effects on the incidence of herd breakdowns (i.e.

An extensive re-evaluation of evidence and analyses of the Randomised Badger Culling Trial (RBCT) I: Within proactive culling areas.

Here, in the first of two investigations, we evaluate and extend the analyses of the Randomised Badger Culling Trial (RBCT) to estimate the effectiveness of proactive badger culling for reducing incidence of tuberculosis (TB) in cattle within culling areas. Using previously reviewed, publicly available data, alongside frequentist and Bayesian approaches, we re-estimate culling effects for confirmed incidence of herd breakdowns (TB incidents in cattle) within proactive culling areas. We appraise the varying assumptions and statistical structures of individual models to determine model appropriateness.

Modelling hepatitis C infection acquired from blood transfusions in the UK between 1970 and 1991 for the Infected Blood Inquiry.

The Statistics Expert Group was convened at the request of the Infected Blood Inquiry to provide estimates of the number of infections and deaths from blood-borne infections including hepatitis B virus, human immunodeficiency virus, hepatitis C virus (HCV) and variant Creutzfeldt Jakob disease, as a direct result of contaminated blood and blood products administered in the United Kingdom of Great Britain and Northern Ireland (UK). In the absence of databases of HCV infections and related deaths for all nations of the UK, a statistical model was required to estimate the number of infections and subsequent deaths from HCV acquired from blood transfusions from January 1970 to August 1991. We present this statistical model in detail alongside the results of its application to each of the four nations in the UK.