Far Cortical Locking Versus Standard Constructs for Locked Plate Fixation in the Treatment of Acute, Displaced Fractures of the Distal Femur: A Multicenter Randomized Trial.

Background: Fixation of distal femoral fractures remains a challenge, and nonunions are common with standard constructs. Far cortical locking (FCL) constructs have been purported to lead to improved fracture-healing as compared with that achieved with traditional locking bridge plates. We sought to test this hypothesis in a comparative effectiveness clinical trial.

Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.

The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study.

Purpose: The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers.

Methods: Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient).

Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).

Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).

Bat Viral Shedding: A Review of Seasonal Patterns and Risk Factors.

Bats act as reservoirs for a variety of zoonotic viruses, sometimes leading to spillover into humans and potential risks of global transmission. Viral shedding from bats is an essential prerequisite to bat-to-human viral transmission and understanding the timing and intensity of viral shedding from bats is critical to mitigate spillover risks. However, there are limited investigations on bats' seasonal viral shedding patterns and their related risk factors.

Enhanced multiscale human brain imaging by semi-supervised digital staining and serial sectioning optical coherence tomography.

A major challenge in neuroscience is visualizing the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features but suffers from staining variability, tissue damage, and distortion, which impedes accurate 3D reconstructions. The emerging label-free serial sectioning optical coherence tomography (S-OCT) technique offers uniform 3D imaging capability across samples but has poor histological interpretability despite its sensitivity to cortical features.

Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage.

Broadly neutralizing antibodies (bNAbs) targeting the apex of the HIV-1-envelope (Env) trimer comprise the most potent category of HIV-1 bNAbs and have emerged as promising therapeutics. Here, we investigate the development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage and report cryo-EM structures at 3.4 Å resolution of PGDM1400 and of an improved PGT145 variant (PGT145-R100aS), each bound to the BG505 Env trimer.

A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom.

Background: Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload.

Case Presentation: In the early 2000s the United Kingdom created a new occupational role, that of physician assistant.

Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders.

Purpose: We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study.

Methods: Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion ( = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision.

Navigating "regulatory fog": Challenges to rigorous abortion research after the Dobbs v. Jackson decision.

In 2022, the United States' Supreme Court ruling in Dobbs v. Jackson Women's Health Organization overturned Roe v. Wade and federal protections for abortion.

The Future Hospital in Global Health Systems: The Future Hospital Within the Healthcare System.

Future hospitals must be able to adapt in many ways to the changing demands on their roles and functions within evolving healthcare delivery infrastructures. These include changing population structures and needs, new models of healthcare provision, technological advances, and innovations in design, all while enhancing their environmental sustainability. This article sets out the issues that those determining healthcare policy and designing future hospitals must consider if they are to become and remain fit for purpose within the wider health and social care system.

Discovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa.

Pathogenic mutations that cause rhodopsin misfolding lead to a spectrum of currently untreatable blinding diseases collectively termed retinitis pigmentosa. Small molecules to correct rhodopsin misfolding are therefore urgently needed. In this study, we utilized virtual screening to search for drug-like molecules that bind to the orthosteric site of rod opsin and improve its folding and trafficking.

Considerations for adapting digital competencies and training approaches to the public health workforce: an interpretive description of practitioners' perspectives in Canada.

Background: Widespread digital transformation necessitates developing digital competencies for public health practice. Given work in 2024 to update Canada's public health core competencies, there are opportunities to consider digital competencies. In our previous research, we identified digital competency and training recommendations within the literature.

Common pitfalls in oncology drug applications aiming for conditional marketing authorization.

Early approval mechanisms, such as conditional approval in the EU, have been used extensively to provide timely access to therapeutic innovations to cancer patients with unmet medical needs. While based on promising early evidence, such approvals are challenging from many perspectives due to the lack of comprehensive data. The limitation typically relates to data that demonstrates clinical benefit via early endpoints and is only acceptable when the early evidence is particularly convincing to assume that the benefits of early access are greater than the potential harms.

Mediators of a randomized controlled trial of a preventive intervention for youth of parents with depressive disorders.

Objective: The present study assessed two theory-driven mediators of the effects of a family group cognitive-behavioral (FGCB) preventive intervention for youth of parents with a history of major depressive disorder (MDD) or dysthymia on long-term youth psychopathology symptoms and diagnoses.

Method: Sample included 180 parents ( = 41.9, 89% female, 82% White, non-Hispanic) and one of their children/adolescents ages 9-15 years ( = 11.

Design and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease.

Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.

Navigating new threats: Prey naïveté in native mammals.

Invasive predators pose a substantial threat to global biodiversity. Native prey species frequently exhibit naïveté to the cues of invasive predators, and this phenomenon may contribute to the disproportionate impact of invasive predators on prey populations. However, not all species exhibit naïveté, which has led to the generation of many hypotheses to explain patterns in prey responses.

The Future Hospital in Global Health Systems: The Future Hospital as an Entity.

Health care is changing rapidly. Hospitals are, and will remain, an essential setting to deliver it. We discuss how to maximise the benefits of hospitals in the future in different geographic and health system settings, highlighting a series of cross-cutting issues.

Predicting sinonasal inverted papilloma attachment using machine learning: Current lessons and future directions.

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed.

US mortality trends from alcohol-associated hepatitis by sex, age, race, and ethnicity, 1999-2020.

Background: Alcohol-associated hepatitis (AH) is a subtype of alcohol-associated liver disease (ALD) resulting in severe acute liver inflammation. This study aims to examine longitudinal trends in mortality from AH in the United States (US) from 1999 to 2020, stratifying the data by sex, age, and racial/ethnic groups.

Methods: We performed a cross-sectional study using data from the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) to determine annual AH-related mortality rates (MR) in adults ≥21 years between 1999 and 2020.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Factors Associated with Pediatric Drowning-Associated Lung Injury.

Objective: To identify risk factors for clinically-important drowning-associated lung injury (ciDALI) in children.

Study Design: This was a cross-sectional study of children (0 through 18 years) who presented to 32 pediatric emergency departments (EDs) from 2010 through 2017. We reviewed demographics, comorbidities, prehospital data, chest radiographs reports, and ED course from emergency medical services, medical, and fatality records.

Pathways to Hypertension Control: Unfinished Journeys of Low-Income Individuals in Malaysia and the Philippines.

Background: Reducing inequities in hypertension control among those affected in low- and middle-income countries requires person-centred health system responses based on a contextualised understanding of the choices and care pathways taken by those who rely on the services provided, particularly those from poor and marginalised communities. We examine patterns of care seeking and pathways followed by individuals with hypertension from low-income households in the Philippines and Malaysia. This study aims to fill a significant gap in the literature by analysing the stages at which individuals make decisions that may affect the successful control of their blood pressure.

Improving colonoscopy quality in the national VA healthcare system.

Background: Colorectal cancer (CRC) prevention is a Veterans Affairs (VA) priority. Colonoscopy quality, especially adenoma detection rate (ADR), is critical for effective screening. Our research indicates considerable variation in ADR among VA providers.