Outer hair cells stir cochlear fluids.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery.

Rural Roads to cognitive Resilience (RRR): A prospective cohort study protocol.

Background: Ambient air pollution, detrimental built and social environments, social isolation (SI), low socioeconomic status (SES), and rural (versus urban) residence have been associated with cognitive decline and risk of Alzheimer's disease and related dementias (ADRD). Research is needed to investigate the influence of ambient air pollution and built and social environments on SI and cognitive decline among rural, disadvantaged, ethnic minority communities. To address this gap, this cohort study will recruit an ethnoracially diverse, rural Florida sample in geographic proximity to seasonal agricultural burning.

is required to maintain supporting cell identity and vestibular function during maturation of the mammalian balance organs.

The inner ear houses both hearing and balance sensory modalities. The hearing and balance organs consist of similar cell types, including sensory hair cells and associated supporting cells. Previously we showed that is required for maintaining supporting cell survival during cochlear maturation.

Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line.

StarPhase: Comprehensive Phase-Aware Pharmacogenomic Diplotyper for Long-Read Sequencing Data.

Pharmacogenomics is central to precision medicine, informing medication safety and efficacy. Pharmacogenomic diplotyping of complex genes requires full-length DNA sequences and detection of structural rearrangements. We introduce StarPhase, a tool that leverages PacBio HiFi sequence data to diplotype 21 CPIC Level A pharmacogenes and provides detailed haplotypes and supporting visualizations for , , and .

Human-Centered Design in Graduate Nursing Education: Outcomes From a Cohort Study.

Background: Many nursing curricula lack human-centered design (HCD) learning opportunities, and minimal evidence exists about HCD educational outcomes.

Purpose: The study explored the effects of HCD experiential learning activities on graduate nursing students.

Methods: The quasi-experimental mixed-method design employed an explanatory approach.

The impact of art, storytelling, and STEAM-based approaches on creativity development in autistic youth and young adults: A mixed methods study protocol.

There are contradicting perspectives regarding autistics' ability to be creative. Some researchers cite autistics' underlying social communication and interaction differences, fixated interests, and inflexible patterns as fundamentally inhibiting creativity. However, many autistics refute this mindset and produce creative works as painters, sculptors, photographers, and graphic artists.

Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies.

Purpose: Intravitreal delivery of therapeutic transgenes to the retina via engineered viral vectors can provide sustained local concentrations of therapeutic proteins and thus potentially reduce the treatment burden and improve long-term vision outcomes for patients with neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy.

Methods: We performed directed evolution in nonhuman primates (NHP) to invent an adeno-associated viral (AAV) variant (R100) with the capacity to cross vitreoretinal barriers and transduce all regions and layers of the retina following intravitreal injection. We then engineered 4D-150, an R100-based genetic medicine carrying 2 therapeutic transgenes: a codon-optimized sequence encoding aflibercept, a recombinant protein that inhibits VEGF-A, VEGF-B, and PlGF, and a microRNA sequence that inhibits expression of VEGF-C.

RGS10 Attenuates Systemic Immune Dysregulation Induced by Chronic Inflammatory Stress.

Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator of immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson's Disease (PD). Interestingly, subjects with idiopathic PD display reduced levels of RGS10 in subsets of peripheral immune cells. Additionally, individuals with PD have been shown to have increased activated peripheral immune cells in cerebral spinal fluid (CSF) compared to age-matched healthy controls.

Protocol for a randomised, double-blinded, controlled trial of youth with childhood-onset obesity treated with semaglutide 2.4 mg/week: the RESETTLE trial.

Introduction: Childhood-onset obesity poses significant health risks, including early-onset type 2 diabetes, cardiovascular disease, and reduced quality of life. Hospital-based non-pharmacological obesity care can reduce childhood obesity, but 25% of children do not respond. Therefore, this study investigates the effect of the glucagon-like peptide-1 receptor agonist, semaglutide, as an add-on to hospital-based obesity care in youth who still have obesity following hospital-based obesity care as children.

Weight Loss Induces Changes in Vitamin D Status in Women with Obesity but not in Men: a Randomized Clinical Trial.

Context: Obesity is associated with low vitamin D and recent studies have suggested a difference in vitamin D metabolism between females and males.

Objective: The aim of this study was to investigate the effects of weight loss on vitamin D status in individuals with obesity, and secondarily, whether vitamin D metabolism differs between women and men.

Methods: Secondary analysis from a randomized placebo-controlled trial, designed to investigate the efficacy of 52 weeks of treatment with either liraglutide, exercise or combined, compared with placebo on weight loss maintenance after an 8-week low-calorie diet-induced weight loss in 195 individuals with obesity (BMI 32-43 kg/m2).

Rural Roads to Cognitive Resilience (RRR): A prospective cohort study protocol.

Background: Ambient air pollution, detrimental built and social environments, social isolation (SI), low socioeconomic status (SES), and rural (versus urban) residence have been associated with cognitive decline and risk of Alzheimer's disease and related dementias (ADRD). Research is needed to investigate the influence of ambient air pollution and built and social environments on SI and cognitive decline among rural, disadvantaged, ethnic minority communities. To address this gap, this cohort study will recruit an ethnoracially diverse, rural Florida sample in geographic proximity to seasonal agricultural burning.

Modelling pollutants transport scenarios based on the X-Press Pearl disaster.

The MV X-Press Pearl accident near Sri Lanka in May 2021 released several pollutants into the ocean, including 1843.3 t of urea, raising concerns about the impact on the region. This study uses a coupled ocean (NEMO)-biogeochemistry (ERSEM) model to simulate urea dispersion under various scenarios.

Jointly benchmarking small and structural variant calls with vcfdist.

In this work, we extend vcfdist to be the first variant call benchmarking tool to jointly evaluate phased single-nucleotide polymorphisms (SNPs), small insertions/deletions (INDELs), and structural variants (SVs) for the whole genome. First, we find that a joint evaluation of small and structural variants uniformly reduces measured errors for SNPs (- 28.9%), INDELs (- 19.

A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity.

Cancers develop resistance to inhibitors of oncogenes mainly due to target-centric mechanisms such as mutations and splicing. While inhibitors or antagonists force targets to unnatural conformation contributing to protein instability and resistance, activating tumor suppressors may maintain the protein in an agonistic conformation to elicit sustainable growth inhibition. Due to the lack of tumor suppressor agonists, this hypothesis and the mechanisms underlying resistance are not understood.

Three-dimensional assessment of subchondral arc and hip joint coverage angles in the asymptomatic young adult hip.

The primary objective of this study was to develop a custom algorithm to assess three-dimensional (3D) acetabular coverage of the femoral head based on surface models generated from computed tomography (CT) imaging. The secondary objective was to apply this algorithm to asymptomatic young adult hip joints to assess the regional 3D acetabular coverage variability and understand how these novel 3D metrics relate to traditional two-dimensional (2D) radiographic measurements of coverage. The algorithm developed automatically identifies the lateral- and medial-most edges of the acetabular lunate at one-degree intervals around the acetabular rim based on local radius of curvature.

Dispersal of a dominant competitor can drive multispecies coexistence in biofilms.

Despite competition for both space and nutrients, bacterial species often coexist within structured, surface-attached communities termed biofilms. While these communities play important, widespread roles in ecosystems and are agents of human infection, understanding how multiple bacterial species assemble to form these communities and what physical processes underpin the composition of multispecies biofilms remains an active area of research. Using a model three-species community composed of Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, we show with cellular-scale resolution that biased dispersal of the dominant community member, P.

Outer hair cells stir cochlear fluids.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery.

An image-based screen for secreted proteins involved in breast cancer G0 cell cycle arrest.

Secreted proteins regulate the balance between cellular proliferation and G0 arrest and therefore play important roles in tumour dormancy. Tumour dormancy presents a significant clinical challenge for breast cancer patients, where non-proliferating, G0-arrested cancer cells remain at metastatic sites, below the level of clinical detection, some of which can re-enter proliferation and drive tumour relapse. Knowing which secreted proteins can regulate entry into and exit from G0 allows us to manipulate their signalling to prevent tumour relapse.

Continuous Monitoring of Heart Rate Variability in Free-Living Conditions Using Wearable Sensors: Exploratory Observational Study.

Background: Wearable physiological monitoring devices are promising tools for remote monitoring and early detection of potential health changes of interest. The widespread adoption of such an approach across communities and over long periods of time will require an automated data platform for collecting, processing, and analyzing relevant health information.

Objective: In this study, we explore prospective monitoring of individual health through an automated data collection, metrics extraction, and health anomaly analysis pipeline in free-living conditions over a continuous monitoring period of several months with a focus on viral respiratory infections, such as influenza or COVID-19.

Insect-microbe interactions and their influence on organisms and ecosystems.

Microorganisms are important associates of insect and arthropod species. Insect-associated microbes, including bacteria, fungi, and viruses, can drastically impact host physiology, ecology, and fitness, while many microbes still have no known role. Over the past decade, we have increased our knowledge of the taxonomic composition and functional roles of insect-associated microbiomes and viromes.