Can Sex-based Variations in the Immune Responses to AAV Gene Therapy Affect Safety and Efficacy? A Review of Current Understanding.

As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.

Slowing down the clock on ovarian aging-does the ovary hold the secret to the fountain of youth?

In the past century, the human Lifespan has doubled. However, this is not equivalent to Healthspan which refers to the number of years spent healthy and free from disease. Women have an additional level of complexity on the path to optimal healthspan where health resilience dramatically decreases following menopause and this is due to their ovaries aging by midlife.

Coronary periarteritis in IgG4-RD: A case series.

Objectives: IgG4-related disease (IgG4-RD) can affect multiple organ systems, with coronary artery involvement being rare. Coronary periarteritis may lead to complications such as myocardial infarction and ischemic cardiomyopathy. This case series characterizes the clinical and radiological features, complications, and treatment strategies in patients with IgG4-RD-associated coronary periarteritis.

Detection of Wolbachia in Natural Populations of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) Infesting Argan Fruits in Morocco.

The argan tree (Argania spinosa L. Skeels), native to the sub-Saharan region of Morocco, is an endangered agroforestry species renowned for producing one of the world's most expensive and sought-after oils. However, this valuable resource is threatened by the Mediterranean fruit fly (Ceratitis capitata (Wied.

Effectiveness of the SHARE Approach for Improving Clinician Shared Decision Making Skills: A Trial in 12 Practices Located in Colorado, USA.

Background: The SHARE Approach Model and training curriculum was developed by the Agency for Healthcare Research and Quality (AHRQ) to teach clinicians practicing in diverse settings how to engage in more effective Shared Decision Making (SDM).

Objective: To determine the effectiveness of the SHARE Approach at improving SDM in practices located across Colorado, USA.

Design: A longitudinal study with pre- and post-intervention observations.

Factors Associated with Loneliness Among Older Adults Who Experienced Homelessness: Results from the HOPE HOME Study.

Background: Older homeless-experienced adults are at higher risk of loneliness than general older adults. Loneliness is associated with multiple adverse health and mental health outcomes. Less is known about factors contributing to loneliness among older adults who experience homelessness.

The Use of Pictorial or Graphic Representation in Reading Comprehension Interventions for Students with Autism Spectrum Disorders: A Meta-Analysis.

This meta-analysis examines the effectiveness of pictorial and graphic representations (PGR) in enhancing reading comprehension among K-12 students with autism spectrum disorder (ASD). Through synthesizing findings from five single-case experimental design studies, the analysis explores how different modalities, age groups, instructional contexts, and task types influence comprehension outcomes. Results indicate that interventions utilizing PGR show moderate-to-strong positive effects overall (Tau-U = 0.

Host Egg Preference and Density-Dependent Parasitism of Telenomus remus in Spodoptera litura and Spodoptera frugiperda Eggs.

Successful biological control requires accurate knowledge of the host preference of the released parasitoid. Telenomus remus Nixon (1973) is an effective parasitoid of Spodoptera frugiperda (J.E.

The Practical Value of Bayesian Inference in Describing the Epidemiology of Sports Injuries.

Sports injury surveillance programs have been vital in advancing the understanding of injury epidemiology across various athlete populations. Surveillance-based epidemiological measures of injury occurrence are ubiquitous in the sports medicine literature, and the injury rate is one such commonly used measure. Traditional approaches to calculating injury rates have predominantly relied on frequentist methods, which, while informative, have limitations in addressing certain practical questions.

Drug Delivery and Binding in a Tissue with Irregularly Shaped Binding Regions.

Objective: A fundamental understanding of drug diffusion and binding processes is critical for the design and optimization of a wide variety of drug delivery devices. Most of the past literature assume binding to occur uniformly throughout the tissue, or, at best, in specific layers of a multilayer tissue. However, in many realistic scenarios, such as in cancer-targeting drugs, drug binding occurs in discrete irregularly shaped regions.

In vivo itaconate tracing reveals degradation pathway and turnover kinetics.

Itaconate is an immunomodulatory metabolite that alters mitochondrial metabolism and immune cell function. This organic acid is endogenously synthesized by tricarboxylic acid (TCA) metabolism downstream of TLR signalling. Itaconate-based treatment strategies are under investigation to mitigate numerous inflammatory conditions.

Patient Characteristics Associated with 30-Day Readmission to a Pediatric Cardiac Center.

Patients with acquired and congenital heart disease (CHD) are at higher risk of hospitalization. Despite quality improvement (QI) initiatives, many patients experience readmission soon after discharge. We aimed to identify risk factors for 30-day readmission and hypothesized that direct discharge from the cardiac intensive care unit (CICU) is associated with an increased readmission rate.

Crape myrtle bark scale Acanthococcus lagerstroemiae (Coccidae: Eriococcidae) infestation seasonally alters the insect biodiversity on crape myrtle trees.

Understanding changes to local communities brought about by biological invasions is important for conserving biodiversity and maintaining environmental stability. Scale insects (Hemiptera: Coccoidea) are a diverse group of insects well known for their invasion potential and ability to modify local abundance of multiple insect groups. Here, we tested how the presence of crape myrtle bark scale (Acanthococcus lagerstroemiae, CMBS), an invasive felt scale species, seasonally impacted local insect abundance, biodiversity, and community structure on crape myrtle trees.

Harmonizing mouse anatomy terminology: a common language?

The mouse remains the principal animal model for investigating human diseases due, among other reasons, to its anatomical similarities to humans. Despite its widespread use, the assumption that mouse anatomy is a fully established field with standardized and universally accepted terminology is misleading. Many phenotypic anatomical annotations do not refer to the authority or origin of the terminology used, while others inappropriately adopt outdated or human-centric nomenclature.

Epigenomic landscape of single vascular cells reflects developmental origin and disease risk loci.

Vascular sites have distinct susceptibility to atherosclerosis and aneurysm, yet the epigenomic and transcriptomic underpinning of vascular site-specific disease risk is largely unknown. Here, we performed single-cell chromatin accessibility (scATACseq) and gene expression profiling (scRNAseq) of mouse vascular tissue from three vascular sites. Through interrogation of epigenomic enhancers and gene regulatory networks, we discovered key regulatory enhancers to not only be cell type, but vascular site-specific.

Antibacterial Potential of Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae) Maggot Excretions/Secretions in Presence of Human Tear Fluid.

Lucilia sericata (Meigen, 1826) maggot excretions/secretions (ES) have demonstrated anti-inflammatory and wound healing potential on corneal epithelial cells. This study aimed to evaluate the in vitro antibacterial potential of the ES against clinically relevant Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus epidermidis in the presence of human tear fluid. The ES was collected from sterile first- and second-instar L.

Hippocampal Cofilin and CFL1 gene variants are linked to Alcohol Use Disorder phenotypes.

Alcohol use disorder (AUD) is characterized by pathological motivation to consume alcohol and cognitive inflexibility, leading to excessive alcohol seeking and use. In this study, we investigated the molecular correlates of impaired extinction of alcohol seeking during forced abstinence using a mouse model of AUD in the automated IntelliCage social system. This model distinguished AUD-prone and AUD-resistant animals based on the presence of ≥2 or <2 criteria of AUD, respectively.

Genetic and epigenetic analysis of plasma glial fibrillary acidic protein (GFAP) levels in PTSD.

Glial fibrillary acidic protein (GFAP) is an astrocytic marker that can be assessed in blood using single molecule array technology. Recent studies suggest that individuals with posttraumatic stress disorder (PTSD) have suppressed circulating levels of this CNS biomarker. This study examined the hypothesis that PTSD and plasma GFAP levels share common genetic and epigenetic pathways.

Genetically modeled GLP1R and GIPR agonism reduce binge drinking and alcohol-associated phenotypes: a multi-ancestry drug-target Mendelian randomization study.

Pharmacological modulation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) through dual GIP/GLP-1 receptor agonists, commonly used for diabetes and obesity, shows promise in reducing alcohol consumption. We applied drug-target Mendelian randomization (MR) using genetic variation at these loci to assess their long-term effects on problematic alcohol use (PAU), binge drinking, alcohol misuse classifications, liver health, and other substance use behaviors. Genetic proxies for lowered BMI, modeling the appetite-suppressing and weight-reducing effects of variants in both the GIPR and GLP1R loci ("GIPR/GLP1R"), were linked with reduced binge drinking in the primary (β = -0.

Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.

Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.

Probing the Kitaev honeycomb model on a neutral-atom quantum computer.

Quantum simulations of many-body systems are among the most promising applications of quantum computers. In particular, models based on strongly correlated fermions are central to our understanding of quantum chemistry and materials problems, and can lead to exotic, topological phases of matter. However, owing to the non-local nature of fermions, such models are challenging to simulate with qubit devices.

Probing non-equilibrium topological order on a quantum processor.

Out-of-equilibrium phases in many-body systems constitute a new paradigm in quantum matter-they exhibit dynamical properties that may otherwise be forbidden by equilibrium thermodynamics. Among these non-equilibrium phases are periodically driven (Floquet) systems, which are generically difficult to simulate classically because of their high entanglement. Here we realize a Floquet topologically ordered state theoretically proposed in ref.

The emergence of globular clusters and globular-cluster-like dwarfs.

Globular clusters (GCs) are among the oldest and densest stellar systems in the Universe, yet how they form remains a mystery. Here we present a suite of cosmological simulations in which both dark-matter-free GCs and dark-matter-rich dwarf galaxies naturally emerge in the Standard Cosmology. We show that these objects inhabit distinct locations in the size-luminosity plane and that they have similar ages, age spread, metallicity and metallicity spread to globulars and dwarfs in the nearby Universe.