Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy.

Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Two serious adverse event cases of immune-mediated myositis (IMM) were reported in the phase Ib ENDEAVOR trial (NCT04626674).

Deleterious Impacts of Western diet on Jejunum Function and Health are Reversible.

The goal of this study was to determine whether the influence of high-fat high-sugar diet (Western diet) on intestinal function and health was reversible. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from male C57Bl/6J mice randomly assigned to one of the following groups for the study duration: high-fat high-sugar diet for 24-weeks (HFHS), HFHS diet for 12-weeks then switched to standard chow and water for a further 12 weeks (Std), and lean controls (standard chow and water for 24-weeks). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence.

Repurposed Medicines: A Scan of the Non-commercial Clinical Research Landscape.

Medicine repurposing is a strategy to identify new uses for the existing medicines for the purpose of addressing areas of unmet medical need. This paper aims to provide horizon scanning intelligence on repurposed medicines that are evaluated by non-commercial organizations such as academia and highlights opportunities for further research to improve patient health outcomes. A scan of the clinical landscape of non-commercially sponsored repurposed medicines is routinely conducted by the NIHR Innovation Observatory (IO).

Genetic Manipulation of Caveolin-1 in a Transgenic Mouse Model of Aortic Root Aneurysm: Sex-Dependent Effects on Endothelial and Smooth Muscle Function.

Marfan syndrome (MFS) is a systemic connective tissue disorder stemming from mutations in the gene encoding Fibrillin-1 (Fbn1), a key extracellular matrix glycoprotein. This condition manifests with various clinical features, the most critical of which is the formation of aortic root aneurysms. Reduced nitric oxide (NO) production due to diminished endothelial nitric oxide synthase (eNOS) activity has been linked to MFS aortic aneurysm pathology.

Long-Term Survival and Myocardial Function Following Systemic Delivery of Delandistrogene Moxeparvovec in DMD Rats.

Delandistrogene moxeparvovec is a gene transfer therapy for Duchenne muscular dystrophy (DMD) that uses an adeno-associated viral vector to deliver a micro-dystrophin transgene to skeletal and cardiac muscle. This study evaluated the long-term survival and cardiac efficacy of delandistrogene moxeparvovec in a DMD-mutated (DMD) rat model of DMD-related cardiomyopathy. DMD male rats, aged 21-42 days, were injected with 1.

Emerging Technologies for Improving Musculoskeletal Health: A Systematic Evidence Gap Map.

Introduction: Musculoskeletal (MSK) conditions are the largest contributor to disability worldwide. The aim of this project was to undertake a horizon scan and generate an evidence gap map (EGM) to highlight technological innovations in development for preventing and managing MSK conditions at early stages of the clinical treatment pathway, and to identify areas of unmet need.

Methods: In February 2024, bibliographic databases, a clinical trial registry, research funding portals, and company websites were searched for relevant records.

Phase transitions in random circuit sampling.

Undesired coupling to the surrounding environment destroys long-range correlations in quantum processors and hinders coherent evolution in the nominally available computational space. This noise is an outstanding challenge when leveraging the computation power of near-term quantum processors. It has been shown that benchmarking random circuit sampling with cross-entropy benchmarking can provide an estimate of the effective size of the Hilbert space coherently available.

Visualizing Inequities: A Step Toward Equitable Student Outcomes.

The underrepresentation and underperformance of low-income, first-generation, gender minoritized, Black, Latine, and Indigenous students in Science, Technology, Engineering, and Mathematics (STEM) occurs for a variety of reasons, including, that students in these groups experience opportunity gaps in STEM classes. A critical approach to disrupting persistent inequities is implementing policies and practices that no longer systematically disadvantage students from minoritized groups. To do this, instructors must use data-informed reflection to interrogate their course outcomes.

Conformational ensembles in FimH impact uropathogenesis.

is an important pathogen causing difficult-to-treat urinary tract infections (UTIs). Over 1.5 million women per year suffer from recurrent UTI, reducing quality of life and causing substantial morbidity and mortality, especially in the hospital setting.

Association Between the Regular Use of Vaginal Dilators and/or Sexual Activity and Vaginal Morbidity in Locally Advanced Cervical Cancer Survivors: An EMBRACE-I Study Report.

Purpose: The purpose of this study was to provide risk estimations for vaginal morbidity with regard to vaginal dilation (summarizing the use of dilators and/or sexual activity) in patients with locally advanced cervical cancer treated with definitive radiochemotherapy and image guided adaptive brachytherapy within the prospective, multi-institutional EMBRACE-I study.

Methods And Materials: Physician-assessed vaginal morbidity (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0), use of vaginal dilators, and patient-reported sexual activity (EORTC-CX24) were prospectively assessed at baseline and during regular follow-ups.

Joint ICOH-WOPS & APA-PFAW global roundtable perspectives: exploring national policy approaches for psychological health at work through the 'National Policy Index' lens.

Worker psychological health is a significant global imperative that requires national policy action and stakeholder engagement. While national policy is a critical lever for improving worker psychological health, some countries are more progressive than others in relation to policy development and/or implementation. At the Joint Congress of the International Commission on Occupational Health, Scientific Committee on Work Organization and Psychosocial Factors and the Asia Pacific Academy for Psychosocial Factors at Work in Tokyo (September 2023), a Global Roundtable was held that to initiate international dialogue and knowledge exchange about national policy approaches for work-related psychological health.

The progression of neurovascular features and chemokine signatures of the intervertebral disc with degeneration.

Inflammatory cytokine production and de novo neurovascularization have been identified in painful, degenerated intervertebral discs (IVDs). However, the temporal trajectories of these key pathoanatomical features, including the cascade of inflammatory chemokines and neo- vessel and neurite infiltration, and their associations with IVD degeneration, remain relatively unknown. Investigating this process in the caudal mouse IVD enables the opportunity to study the tissue-specific response without confounding inflammatory signaling from neighboring structures.

Biomarker Expression and Clinical Outcomes in International Study of Chemoradiation and Magnetic Resonance Imaging-Based Image-Guided Brachytherapy for Locally Advanced Cervical Cancer: BIOEMBRACE.

Purpose: BIOEMBRACE was designed to study the impact of biomarkers in addition to clinicopathological factors on disease outcomes in patients treated with chemoradiation and magnetic resonance imaging (MRI)-guided brachytherapy (BT) for locally advanced cervical cancer in the EMBRACE study.

Methods And Materials: Between 2018 and 2021, 8 EMBRACE-I sites contributed tumor tissue for the immunohistochemistry of p16, PD-L1, and L1CAM. These biomarkers and clinicopathological factors (International Federation of Gynecology and Obstetrics 2009 stage, nodal status, histology, and necrosis on MRI) were analyzed to predict poor response at BT (high-risk clinical target volume [HR-CTV] ≥ 40 cc) at BT) and 5-year local control, pelvic control, and disease-free survival.

Are we making progress in curing advanced cervical cancer-again?

Major improvements in radiotherapy over the past two decades in the definitive treatment of locally advanced cervical cancer have significantly improved loco-regional control and survival, whereas little progress has been made with chemotherapy since the implementation of concomitant cisplatin 25 years ago. However, the randomized study INTERLACE (A phase III multicenter trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer) of neoadjuvant chemotherapy presented recently, has shown significant improvement in survival with the use of six cycles of weekly carboplatin and paclitaxel. Although INTERLACE is yet to be published, neoadjuvant chemotherapy is already being advocated as the new standard, and studies are being designed with neoadjuvant chemotherapy followed by chemoradiation and brachytherapy as the standard arm.

Migration from Epi Info to District Health Information Software 2 for Vaccine-Preventable Disease Surveillance - World Health Organization African Region, 2019-2023.

High-quality vaccine-preventable disease (VPD) surveillance data are critical for timely outbreak detection and response. In 2019, the World Health Organization (WHO) African Regional Office (AFRO) began transitioning from Epi Info, a free, CDC-developed statistical software package with limited capability to integrate with other information systems, affecting reporting timeliness and data use, to District Health Information Software 2 (DHIS2). DHIS2 is a free and open-source software platform for electronic aggregate Integrated Disease Surveillance and Response (IDSR) and case-based surveillance reporting.

Exposing kinetic disparities between inflammasome readouts using time-resolved analysis.

The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others.

Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text].

Comparative assessment of Riesling wine fault development by the electronic tongue and a sensory panel.

Wine faults threaten brand recognition and consumer brand loyalty. The objective of this study was to compare the acuteness of e-tongue and human sensory evaluation of wine fault development in Riesling wine over 42 days of storage. Riesling wines uninoculated (control) or inoculated with 10 CFU/mL cultures of Wickerhamomyces anomalus, Acetobacter aceti, Lactobacillus brevis, or Pediococcus parvulus were assessed every 7 days with the e-tongue and a rate-all-that-apply (RATA) sensory panel.

Stable quantum-correlated many-body states through engineered dissipation.

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.

Dual membrane-spanning anti-sigma factors regulate vesiculation in .

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part by uter embrane esicles (OMVs). Here, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in ().

Aging impairs the osteocytic regulation of collagen integrity and bone quality.

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties.