Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Assessment of radioactivity in soil samples from Wolaita Sodo town, Ethiopia: implications for environmental and public health.

This study assesses the activity concentrations of the radionuclides 238U, 232Th, and 40K in soil samples collected from Wolaita Sodo town, located in the Southern Nations, Nationalities, and Peoples' (SNNP) Region, Ethiopia. A gamma-ray spectrometer equipped with a NaI(Tl) detector was used for the measurements. The concentrations of 238U, 232Th, and 40K varied from 3.

Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non-MSI-H/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results.

Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non-MSI-H/non-dMMR advanced EC (cohort D).

Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.

Associations and potential epigenetic changes between air pollution and osteoarthritis risk and survival: Insights from a prospective cohort study.

Background: The influence of air pollution on osteoarthritis (OA) remains underexplored.

Methods: We conducted a prospective cohort study in the UK Biobank, estimating exposure levels of particulate matter (PM, PM, PM) nitrogen oxides (NO, NO), and air pollutants exposure score (APES). Cox models assessed associations between air pollution exposure and OA incidence, joint replacement, and survival.

Precision Oncology: A Global Perspective on Implementation and Policy Development.

Despite the acknowledged merits of precision oncology (PO) and its increasing global implementation, its full potential for advancing care and prevention remains unrealized. The benefits are currently accessible to only limited patient segments because of multifaceted barriers. Successful implementation hinges on various factors-scientific complexities not limited to technical, clinical, regulatory, economic, administrative, and health care policy-related challenges.

Survival Outcomes for Adolescent and Young Adults With Cancer in Low- and Middle-Income Countries: A Systematic Review.

Purpose: Patients with adolescent and young adult (AYA) cancer are recognized as a vulnerable subpopulation in high-income countries (HICs). Although survival gaps between HIC and low- and middle-income country (LMIC) children with cancer are well described, LMIC AYAs have been neglected. We conducted a systematic review to describe cancer outcomes among LMIC AYAs.

Support for and likely impacts of endgame measures in the Smokefree Aotearoa Action Plan: findings from the 2020-2021 International Tobacco Control New Zealand (EASE) surveys.

Aim: In February 2024, the Aotearoa New Zealand Government repealed legislation to mandate very low nicotine cigarettes (VLNCs), greatly reduce the number of tobacco retailers and disallow sale of tobacco products to people born after 2008 (smokefree generation). We investigated acceptability and likely impacts of these measures among people who smoke or who recently (≤2 years) quit smoking.

Method: We analysed data from 1,230 participants from Wave 3 (conducted in late 2020 and early 2021) and 615 participants from Wave 3.

18F-DCFPyL PET/MRI Radiomics for Intraprostatic Prostate Cancer Detection and Metastases Prediction Using Whole-Gland Segmentation.

Objectives: To evaluate 18F-DCFPyL-PET/MRI whole-gland-derived radiomics for detecting clinically significant (cs) prostate cancer (PCa) and predicting metastasis.

Methods: Therapy-naïve PCa patients who underwent 18F-DCFPyL PET/MRI were included. Whole-prostate-segmentation was performed.

Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52.

G Protein-Coupled Receptor Heteromers in Brain: Functional and Therapeutic Importance in Neuropsychiatric Disorders.

G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers.

Patient Experiences and Perspectives When MyChart is Introduced in a Large Community Hospital: Mixed Methods Study.

Background: Patient portals, or secure websites linked to electronic medical records, have emerged as tools to provide patients with timely access to their health information. To support the potential benefits of patient portals such as improved engagement in health care, it is essential to understand how patients and caregivers experience these portals.

Objective: This study aimed to explore patient and caregiver experiences, facilitators, and barriers to accessing and using a patient portal called MyChart during the initial stages of its implementation.

Governing in the face of a global crisis: When do voters punish and reward incumbent governments?

The recent COVID-19 pandemic offers a rare opportunity to understand how citizens attribute responsibility for governments' responses to unanticipated negative-and in this case, systemic-exogenous shocks. Classical accounts of responsibility are complicated when crises are pervasive, involve multiple valence dimensions, and where individuals can make relative assessments of performance. We fielded a conjoint experiment in 16 countries with 22,147 respondents.

A Canadian real-world, multi-center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2-negative advanced breast cancer.

Purpose: Understanding real-world treatment patterns and their effectiveness in HR + HER2- advanced breast cancer (aBC) in Canadian patients.

Patient And Methods: This was a multi-center, observational, prospective cohort study including men and pre-/peri-/postmenopausal women with HR + HER2- aBC receiving endocrine therapy (ET) or ET + targeted therapy (ET + TT). The primary objective was duration of treatment (DOT) with ET and ET + TT.

Delay discounting predicts COVID-19 vaccine booster willingness.

Developing ways to predict and encourage vaccine booster uptake are necessary for durable immunity responses. In a multi-nation sample, recruited in June-August 2021, we assessed delay discounting (one's tendency to choose smaller immediate rewards over larger future rewards), COVID-19 vaccination status, demographics, and distress level. Participants who reported being vaccinated were invited back one year later (n = 2547) to report their willingness to receive a booster dose, along with reasons for their decision.

Organometallic-Polypeptide Block Copolymers: Synthesis and Crystallization-Driven Self-Assembly in Aqueous Solutions to Rod-like and Plate-like Micelles with Polypeptide Coronas.

The synthesis of polyferrocenyldimethylsilane-b-poly(L-glutamic acid) block copolymers was systematically explored. Rod-like and plate-like micelles were prepared from self-assembly of the block copolymers in aqueous solution with two different approaches. In a dissolution-dialysis approach, micelles were prepared by dissolving a block copolymer sample in excess aqueous base followed by the dialysis of the solution against water.

Tranexamic Acid and Heterotopic Ossification Formation Following Elbow Surgery: A Prospective Randomized Controlled Trial.

Objectives: This study investigates whether the intra-operative administration of intravenous tranexamic acid (TXA), known for its hemostatic and potential anti-inflammatory properties, affects the incidence of heterotopic ossification (HO) following surgery for elbow fracture-dislocations.

Methods: Design: Prospective, randomized clinical trial.

Setting: Hand and Upper Extremity Surgery Unit.

Safety and Efficacy of a 48-Month Efinaconazole 10% Solution Treatment/Maintenance Regimen: 24-Month Daily Use Followed by 24-Month Intermittent Use.

Background/objectives: In an 18- to 24-month Treatment Phase with once-daily efinaconazole 10% solution, subjects with onychomycosis showed an increased rate of cure at Month 24 versus the phase III trials. In order to further improve efficacy, we initiated an extended intermittent efinaconazole Maintenance Phase with use 2-3 times weekly for an additional 24 months from Month 24 to Month 48. These are the first data presented for a 48-month efinaconazole use period.

Ultrahigh Specific Strength by Bayesian Optimization of Carbon Nanolattices.

Nanoarchitected materials are at the frontier of metamaterial design and have set the benchmark for mechanical performance in several contemporary applications. However, traditional nanoarchitected designs with conventional topologies exhibit poor stress distributions and induce premature nodal failure. Here, using multi-objective Bayesian optimization and two-photon polymerization, optimized carbon nanolattices with an exceptional specific strength of 2.

Newborn screening for common genetic variants associated with permanent hearing loss: Implementation in Ontario and a review of the first 3 years.

Purpose: Universal newborn hearing screening (UNHS) programs using audiometric techniques alone are limited in ability to detect non-congenital childhood permanent hearing loss (PHL). In 2019, Ontario launched universal newborn screening (NBS) for PHL risk factors: congenital cytomegalovirus (cCMV) and 22 common variants in GJB2 and SLC26A4. Here we describe our experience with genetic risk factor screening.

Vertical Graphene Growth on LDH Nanosheets and Carbon Cloth Nanofibers with NiCo Nanoparticles as a Freestanding Host for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries have been recognized as one of the excellent candidates for next-generation energy storage batteries because of their high energy density and low cost and low pollution. However, lithium-sulfur batteries have been challenged by low conductivity, low sulfur utilization, poor cycle life, and the shuttle effect of polysulfides. To address these problems, we report here an independent mixed sulfur host.

Placental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia.

Background: Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance and placental hypoxia are independent contributors to the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, the mechanisms by which their interaction impinge on maternal and placental health remain elusive.

Methods: We used placentae from normotensive and preeclampsia pregnancy cohorts, human H9 embryonic stem cells differentiated into cytotrophoblast-like cells, and placenta-specific preeclamptic mice.

Trends and Themes in the Study of Value in Orthopedic Surgery: A Systematic Review.

Background: The study of value in orthopedic surgery aims to maximize health outcomes gained per unit cost through various health economic tools but is fragmented across various subspecialties and geographies. Therefore, it is difficult to ascertain whether this research methodology is being used to its full potential across all orthopedic subspecialties and geographies.

Purpose: We sought to assess the distribution of prior health economics literature in orthopedic surgery across subspecialties and geographies.