Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

Regional patterns and climatic predictors of viruses in honey bee (Apis mellifera) colonies over time.

Honey bee viruses are serious pathogens that can cause poor colony health and productivity. We analyzed a multi-year longitudinal dataset of abundances of nine honey bee viruses (deformed wing virus A, deformed wing virus B, black queen cell virus, sacbrood virus, Lake Sinai virus, Kashmir bee virus, acute bee paralysis virus, chronic bee paralysis virus, and Israeli acute paralysis virus) in colonies located across Canada to describe broad trends in virus intensity and occurrence among regions and years. We also tested climatic variables (temperature, wind speed, and precipitation) as predictors in an effort to understand possible drivers underlying seasonal patterns in viral prevalence.

Dopaminergic signaling to ventral striatum neurons initiates sniffing behavior.

Sniffing is a motivated behavior displayed by nearly all terrestrial vertebrates. While sniffing is associated with acquiring and processing odors, sniffing is also intertwined with affective and motivated states. The systems which influence the display of sniffing are unclear.

CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells.

High mortality and low response rates in lung cancer patients call for novel therapeutic targets. Data mining of whole-genome genetic dependency screens suggest Cell Division Cycle 40 (CDC40) to be an essential protein for lung cancer cell survival. We characterized CDC40 knockdown effects in multiple lung cancer cell lines, revealing induced cell cycle defects that resulted in strong growth inhibition and activation of apoptosis.

Self-Learning Videos in Focused Transthoracic Echocardiography Training.

Background: Focused transthoracic echocardiography (FOTE) is crucial for patients' bedside management. However, limited opportunities exist for practical FOTE training, prompting the use of simulation and self-learning videos to overcome this constraint. This study aimed to evaluate the impact of incorporating self-learning videos into a simulation FOTE training course.

Influence of non-pharmaceutical COVID-19 interventions on speed-related and alcohol-related traffic injuries in five cities of the province of Québec, Canada.

Introduction: Understanding the impact of non-pharmaceutical COVID-19 interventions (NPIs) on road safety has become increasingly important to uncover the unintended consequences of the pandemic. This study explores how NPIs influenced alcohol-related and speed-related traffic collisions, including fatalities and serious injuries, in five cities of the province of Québec, Canada: Montréal, Québec, Laval, Longueuil and Sherbrooke.

Methods: We performed Poisson interrupted time-series analyses using daily traffic fatality and injury data from 2015 to 2022, to assess the change in rate expressed per 10 000 population.

Random forest algorithm reveals novel sites in HA protein that shift receptor binding preference of the H9N2 avian influenza virus.

A switch from avian-type α-2,3 to human-type α-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus. Some H9N2 viruses exhibit a preference for binding to human-type α-2,6 receptors. This identifies their potential threat to public health.

Comparison of Renal Adverse Events Between Intravitreal Anti-Vascular Endothelial Growth Factor Agents: A Meta-Analysis.

Purpose: To assess the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.

Design: Meta-analysis.

Methods: A systematic literature search was conducted on Ovid Medline, Embase and the Cochrane Library for randomized controlled trials (RCTs) published from January 2005 to February 2024 involving adult patients receiving anti-VEGF intravitreal injections for agerelated macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion.

The Relationship Between Meeting Workplace Accommodation Needs and Job Disruptions Among Canadians Working With Disabilities: A Cross-Sectional Analysis.

Objective: This research explores whether having accommodation needs met reduces job disruptions.

Methods: A cross-sectional survey (n = 955) of Canadians working with physical and/or mental/cognitive disabilities was used to assess the association between having workplace accommodations (ie, flexibility, modifications) needs met and four types of job disruptions. Analyses used marginal effects models to adjust for demographic and work context variables.

Health needs of older people and age-inclusive health care in humanitarian emergencies in low-income and middle-income countries: a systematic review.

Health needs of older people in humanitarian settings are poorly documented, negatively affecting the appropriateness of health services they receive. This Review identified the major health needs of older people across humanitarian contexts, including non-communicable diseases and mental health conditions (eg, psychological distress and depression). Barriers to health care of older people included inaccessibility of health-care services; shortage of appropriate health care; insufficient availability of medications and medical equipment; poor geriatric expertise of health-care staff, health policy makers, and health authorities; and age discrimination by health-care personnel.

Mechanical properties of the bicipital aponeurosis.

As a biarticular muscle, the biceps brachii both supinates the forearm and flexes the elbow and shoulder, thus allowing the upper limb to perform a variety of activities of daily living (ADL). The biceps brachii originates on the coracoid apex as well as the supraglenoid tubercle and inserts on the radial tuberosity. At the distal end, the bicipital aponeurosis (BA) provides a transition of the biceps tendon into the antebrachial fascia.

Longitudinal associations between intersectional stigmas, antiretroviral therapy adherence, and viral load among women living with HIV using multidimensional latent transition item response analysis.

Background: In the US, Women, especially Black and Latina women living in disadvantaged environments, are disproportionally affected by HIV. Women living with HIV (WLHIV) have higher rates of suboptimal antiretroviral therapy (ART) adherence, and detectable viral load (VL). Experiences of intersectional poverty, HIV, gender, and racial stigmas may increase the rates of detectable VL through suboptimal ART adherence.

Tirzepatide Associated With Reduced Albuminuria in Participants With Type 2 Diabetes: Pooled Post Hoc Analysis From the Randomized Active- and Placebo-Controlled SURPASS-1-5 Clinical Trials.

Objective: Tirzepatide, a long-acting, glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, reduced urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline in people with type 2 diabetes and high cardiovascular risk in the SURPASS-4 trial. To examine the generalizability of these findings, we assessed change from baseline in UACR for tirzepatide (5, 10, and 15 mg) compared with active and placebo treatment in a broad population from the SURPASS-1-5 trials.

Research Design And Methods: This post hoc analysis examined data from the overall pooled SURPASS-1-5 population and subgroups defined by baseline UACR ≥30 mg/g.

TNF/TNFR Superfamily Members in Costimulation of T Cell Responses-Revisited.

Prosurvival tumor necrosis factor receptor (TNFR) superfamily (TNFRSF) members on T cells, including 4-1BB, CD27, GITR, and OX40, support T cell accumulation during clonal expansion, contributing to T cell memory. During viral infection, tumor necrosis factor superfamily (TNFSF) members on inflammatory monocyte-derived antigen-presenting cells (APCs) provide a postpriming signal (signal 4) for T cell accumulation, particularly in the tissues. Patients with loss-of-function mutations in TNFR/TNFSF members reveal a critical role for 4-1BB and CD27 in CD8 T cell control of Epstein-Barr virus and other childhood infections and of OX40 in CD4 T cell responses.

How Should Epidemiologists Respond to Data Genocide?

Data quality for and about American Indian/Alaska Native (AI/AN) people is undermined by deeply entrenched, colonial practices that have become standard in US federal data systems. This article draws on cases of maternal mortality and COVID-19 to demonstrate the ethical and clinical need for inclusive, diverse, and accurate data when researching AI/AN health trends. This article further argues that epidemiologists specifically must challenge implicit bias, question methods and practices, and recognize colonial, racist reporting practices about AI/AN people that have long undermined data collection, analytical, and dissemination practices that are fundamental to epidemiological research.

Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial.

Importance: Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).

Objective: To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.

Cost-Effectiveness of Breast Cancer Screening Using Digital Mammography in Canada.

Importance: Evolving breast cancer treatments have led to improved outcomes but carry a substantial financial burden. The association of treatment costs with the cost-effectiveness of screening mammography is unknown.

Objective: To determine the cost-effectiveness of population-based breast cancer screening in the context of current treatment standards.

The radiologic spectrum of neuroendocrine tumors in emergent care.

Neuroendocrine tumors (NETs) are a diverse group of neoplasms whose prevalence is increasing globally, primarily due to advancements in diagnostic techniques. NETs arise from cells of the diffuse endocrine system and can occur in various locations, with the gastrointestinal tract being the most common. Their diverse clinical presentations, which range from asymptomatic to severe hormone-induced syndromes, pose significant diagnostic challenges.

Intra- and interobserver agreement in evaluation of image-defined risk factors on computed tomography in pediatric neuroblastoma.

Background: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.

Objective: To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.

Materials And Methods: Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent.