Neuroligin-3 R451C induces gain-of-function gene expression in astroglia in an astroglia-enriched brain organoid model.

Astroglia are integral to brain development and the emergence of neurodevelopmental disorders. However, studying the pathophysiology of human astroglia using brain organoid models has been hindered by inefficient astrogliogenesis. In this study, we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development.

Epigenetic Modifications as Novel Therapeutic Strategies of Cancer Chemoprevention by Phytochemicals.

Purpose: Epigenetic modifications, such as aberrant DNA methylation, histone alterations, non-coding RNA remodeling, and modulation of transcription factors, are pivotal in the pathogenesis of diverse malignancies. Reactive oxygen species (ROS) have the capacity to impact these epigenetic mechanisms, including DNA methylation, throughout the different stages of cancer development. Therefore, the aim of this review is to address the impact of.

US Real-World Effectiveness, Tolerability, and Healthcare Resource Utilization After Addition of Fremanezumab for Preventive Treatment in Patients Using Gepants for Acute Treatment of Migraine: Results From a Retrospective Chart Review.

Introduction: Fremanezumab, a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway, and gepants, small molecule CGRP receptor antagonists, are both approved for the treatment of migraine or its symptoms. This study assessed effectiveness, tolerability, and migraine-related healthcare resource utilization (HCRU) after the addition of fremanezumab for preventive migraine treatment in patients using gepants for acute treatment.

Methods: Data were extracted during a retrospective chart review from electronic medical records from the Dent Neurologic Institute.

Schemas, reinforcement learning and the medial prefrontal cortex.

Schemas are rich and complex knowledge structures about the typical unfolding of events in a context; for example, a schema of a dinner at a restaurant. In this Perspective, we suggest that reinforcement learning (RL), a computational theory of learning the structure of the world and relevant goal-oriented behaviour, underlies schema learning. We synthesize literature about schemas and RL to offer that three RL principles might govern the learning of schemas: learning via prediction errors, constructing hierarchical knowledge using hierarchical RL, and dimensionality reduction through learning a simplified and abstract representation of the world.

Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease.

PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). The primary endpoint was change in 6-min walk distance (6MWD) from baseline to week 52. During PROPEL, COVID-19 interrupted some planned study visits and assessment windows, leading to delayed visits, make-up assessments for patients who missed ≥ 3 successive infusions before planned assessments at weeks 38 and 52, and some advanced visits (end-of-study/early-termination visits).

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

Comparative analysis of EGFR mutations in circulating tumor DNA and primary tumor tissues from lung cancer patients using BEAMing PCR.

In this study, we measured human epidermal growth factor receptor (EGFR) mutations in both tissue and circulating tumor DNA (ctDNA) by using beads, emulsions, amplifications and magnetic polymerase chain reaction (BEAMing PCR). Noninvasive mutation detection by assessing circulating tumor DNA (ctDNA) offers many advantages over tumor biopsy. One hundred non-small cell lung cancer (NSCLC) patients were enrolled, and both preoperative plasma samples and formalin-fixed and paraffin-embedded (FFPE) samples were collected for the study.

Prevalence of urinary tract infections in women with vulvovaginal atrophy and the impact of vaginal prasterone on the rate of urinary tract infections.

Objective: The aims of this study were to assess the prevalence of urinary tract infections (UTI) in women newly diagnosed with vulvovaginal atrophy (VVA) versus women without VVA and to evaluate the potential of vaginal prasterone to be used in postmenopausal VVA women with UTI as prophylaxis to reduce the future UTI risk. As a first subgroup analysis, women using aromatase inhibitors, medications that stop the production of estrogen were analyzed. As a second subgroup analysis, we looked at women with diabetes to investigate whether the same prophylaxis approach should be considered.

Efficacy of cleaning, disinfection and sterilization modalities for addressing infectious drug-resistant fungi: A review.

This is a timely and important review that focuses on the appropriateness of established cleaning, disinfection and sterilization methods to safely and effectively address infectious fungal drug-resistant pathogens that can potentially contaminate reusable medical devices used in healthcare environment in order to mitigate the risk of patient infection. The release of the World Health Organisation (WHO) fungal priority pathogen list (FPPL) in 2022 highlighted the public health crisis of antimicrobial resistance (AMR) in clinically relevant fungal species. Contamination of medical devices with drug-resistant fungal pathogens (including those on the FPPL) in healthcare are rare events that are more likely to occur due to cross-transmission arising from lapses in hand-hygiene practices.

Exciton-polariton ring Josephson junction.

Macroscopic coherence in quantum fluids allows the observation of interference effects in their wavefunctions, and enables applications such as superconducting quantum interference devices based on Josephson tunneling. The Josephson effect manifests in both fermionic and bosonic systems, and has been well studied in superfluid helium and atomic Bose-Einstein condensates. In exciton-polariton condensates-that offer a path to integrated semiconductor platforms-creating weak links in ring geometries has so far remained challenging.

Mechanical Failure of the Stryker T2 Alpha Retrograde Femoral Nail.

Objective: To evaluate mechanical failure rates of retrograde femoral nails in the treatment of distal femur fractures.

Methods: Design: Retrospective chart review.

Setting: Urban Academic Level 1 Trauma Center.

In Vitro and In Vivo Visualization of Perfluorohexyloctane, an Eye Drop for Dry Eye Disease, Using Infrared Emissivity.

Purpose: To visualize the behavior of perfluorohexyloctane (PFHO), an eye drop to treat dry eye disease (DED), on the surface of saline in vitro and on the human ocular surface using infrared emissivity.

Methods: Emissivity videos were used to measure the spreading and disappearance rates of PFHO on saline (with and without mucin for spreading rate) and layered over a 125 nm film of meibum on the surface of saline using a TearView camera. Ocular surface emissivity was videoed in a volunteer without DED before and after instillation of 1 drop of PFHO.

Effects of different educational interventions on cervical cancer knowledge and human papillomavirus vaccination uptake among young women in Japan: Preliminary results of a cluster randomized controlled trial.

The incidence and mortality rates of cervical cancer are increasing among young Japanese women. In November 2021, the Japanese Ministry of Health, Labour, and Welfare reinstated the active recommendation of the human papillomavirus (HPV) vaccine, after it had been suspended in June 2013 due to reports of adverse reactions. However, vaccine hesitancy is prevalent in the younger generation in Japan.

Formalin-free tissue embedding is less hazardous and results in better DNA quality.

Disease diagnosis, prognosis, and therapy choice progressively rely on good-quality Deoxyribonucleic acid (DNA) for molecular analysis. As tissue processing is routinely performed worldwide with ancient techniques using toxic and DNA-damaging formaldehyde, the quality of DNA isolated from embedded tissues used for diagnostics is poor. We used a novel formalin-free tissue embedding method to process tissues and show that, after 5 years, DNA quality is superior to formalin fixation.

Anti-nucleocapsid SARS-CoV-2 antibody seroprevalence in previously infected persons with immunocompromising conditions-United States, 2020-2022.

People with immunocompromising conditions (IC) are at increased risk of severe COVID-19 and death. These individuals show weaker immunogenicity following vaccination than individuals without IC, yet immunogenicity after SARS-CoV-2 infection is poorly understood. To address this gap, the presence of infection-induced antibodies in sera following a positive COVID-19 test result was compared between patients with and without IC.

The WAVE complex in developmental and adulthood brain disorders.

Actin polymerization and depolymerization are fundamental cellular processes required not only for the embryonic and postnatal development of the brain but also for the maintenance of neuronal plasticity and survival in the adult and aging brain. The orchestrated organization of actin filaments is controlled by various actin regulatory proteins. Wiskott‒Aldrich syndrome protein-family verprolin-homologous protein (WAVE) members are key activators of ARP2/3 complex-mediated actin polymerization.

Impact of Prior Biologic Exposure on Ozanimod Efficacy and Safety in the Phase 3 True North Clinical Trial.

Introduction: Patients with ulcerative colitis (UC) and prior biologic failure may have reduced or delayed efficacy with subsequent advanced therapies. This analysis evaluated the efficacy and safety of ozanimod during the True North (TN) study and its open-label extension (OLE) in biologic-exposed patients with UC.

Methods: TN was a randomized, placebo-controlled 52-week trial (10-week induction, 42-week maintenance period).

"That Came Back to Haunt Me": Violence Against Women Survivors' Concerns About Police Use of Body-Worn Cameras.

Despite the substantial contact police have with survivors of violence against women, empirical accounts of survivors' perceptions of police use of body-worn cameras (BWCs) are limited. This study examines survivors' concerns with BWCs. We present qualitative data from semi-structured interviews with 33 survivors of intimate partner abuse and sexual assault.

Predictors of Third-Party Tested Nutritional Supplementation Use Among DI and DIII Student-Athletes at A Northeast University.

Nutritional supplements (NS) are linked to adverse events and unintentional doping among college-athletes. The use of third-party tested (TPT) NS can increase safety and reduce the risk of inadvertent consumption of banned substances. The purpose of this study was to examine self-reported use of TPT supplements between the National Collegiate Athletic Association (NCAA) Division I (DI) and Division III (DIII) college-athletes and explore the potential predictors of TPT use.

Closing the gaps in the access to quality-assured medicines for global health: The case for oxytocin for postpartum haemorrhage.

Introduction: Access to quality-assured medicines remains unequal between high-income and low-income countries. To bridge this gap, product development and supply in low- and middle-income countries (LMICs) should follow World Health Organization (WHO)'s policies and recommendations whilst aligning with international standards.

Areas Covered: We reviewed two cases on oxytocin access for postpartum hemorrhage (PPH), a condition that disproportionately affects mothers in low-income countries.

The magnitude of legal wildlife trade and implications for species survival.

The unsustainable use of wildlife is a primary driver of global biodiversity loss. No comprehensive global dataset exists on what species are in trade, their geographic origins, and trade's ultimate impacts, which limits our ability to sustainably manage trade. The United States is one of the world's largest importers of wildlife, with trade data compiled in the US Law Enforcement Management Information System (LEMIS).

Infection-induced lysine lactylation enables herpesvirus immune evasion.

Aerobic glycolysis is a hallmark of many viral infections, leading to substantial accumulation of lactate. However, the regulatory roles of lactate during viral infections remain poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages lactate to induce widespread protein lactylation and promote viral spread.