Velopharyngeal Timing and Speech Sound Disorders of Unknown Etiology.

The purpose of the study was to investigate velopharyngeal timing in children with and without speech sound disorders (SSDs) of unknown etiology. Six preschool-aged children participated in the investigation. Three of the children had typically developing speech and language and three had SSDs of unknown etiology.

The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data.

Genome-wide association studies have been highly successful at identifying common variants associated with cancer; however, they do not explain all the inherited risks of cancer. Family-based studies, targeted sequencing, and, more recently, exome-wide association studies have identified rare coding variants in some genes associated with cancer risk, but the overall contribution of these variants to the heritability of cancer is less clear. Here, we describe a method to estimate the genome-wide contribution of rare coding variants to heritability that fits models to the burden effect sizes using an empirical Bayesian approach.

Validation of the Sudbury Vertigo Risk Score to risk stratify for a serious cause of vertigo.

Introduction: In 2022, nearly 0.5 million Canadians visited an emergency department (ED) for dizziness, accounting for over 3.5% of all ED visits.

Assessing the rates of overtriaging with prehospital trauma team activation protocols.

Introduction: Prehospital trauma team activation protocols are increasingly used to expedite clinical care and potentially improve patient outcomes. However, there is little evidence describing the rates of overtriaging following prehospital activation.

Methods: In June 2018, prehospital trauma team activation protocols were implemented at the Ottawa Hospital.

Canine genome-wide association study identifies as an obesity gene in dogs and humans.

Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score, a measure of obesity, in 241 Labrador retrievers.

Multidimensional feature analysis shows stratification in robotic-motor-training gains based on the level of pre-training motor impairment in stroke.

Stroke involves heterogeneity in injury and ongoing endogenous recovery, which are seldom stratified before testing post-stroke robot assisted motor training (RAMT). Pretraining variations, especially sensory-motor differences may also affect the gains achieved from the RAMT. Moreover, one assessment test may not effectively characterize the baseline sensory-motor status or the RAMT gains.

Effects of rare coding variants in severe early-onset obesity genes in the population-based UK Biobank study.

Objectives: Clinical case-based studies have identified rare pathogenic variants in several genes as causes of severe early-onset obesity, but their penetrance and interaction with polygenic susceptibility in the general population remain unclear. We analysed the UK Biobank (UKBB) whole exome sequence data to assess the effects of heterozygous variants in nine previously reported genes on adult BMI and recalled childhood adiposity.

Methods: Among 419,581 UKBB participants, we identified heterozygous carriers of coding variants that were i) experimentally-characterised as loss-of-function (LoF), or ii) bioinformatically-predicted as rare (minor allele frequency <0.

Erratum: Noninductively Driven Tokamak Plasmas at Near-Unity Toroidal Beta [Phys. Rev. Lett. 119, 035001 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.119.

Metabolic engineering to facilitate anti-tumor immunity.

Fructose consumption is elevated in western diets, but its impact on anti-tumor immunity is unclear. Fructose is metabolized in the liver and small intestine, where fructose transporters are highly expressed. Most tumors are unable to drive glycolytic flux using fructose, enriching fructose in the tumor microenvironment (TME).

Remdesivir and Obeldesivir Retain Potent Antiviral Activity Against SARS-CoV-2 Omicron Variants.

As new SARS-CoV-2 variants continue to emerge, it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. Here we show these two compounds retain antiviral activity against the Omicron variants BA.

Transfection via RNA-Based Nanoparticles: Comparing Encapsulation vs Adsorption Approaches of RNA Incorporation.

Historically, RNA delivery via nanoparticles has primarily relied on encapsulation, as demonstrated by lipid nanoparticles in SARS-CoV-2 vaccines. Concerns about RNA degradation on nanoparticle surfaces initially limited the exploration of adsorption-based approaches. However, recent advancements have renewed interest in adsorption as a viable alternative.

Impact of Conventional Stroke Risk Factors on Early- and Late-Onset Ischemic Stroke: A Mendelian Randomization Study.

Background: Stroke incidence is decreasing in older ages but increasing in young adults. These divergent trends are at least partially attributable not only to diverging trends in stroke risk factors but may also be due to differences in the impact of stroke risk factors at different ages. To address this latter possibility, we used Mendelian randomization to assess differences in the association of stroke risk factors between early-onset ischemic stroke ([EOS]; onset 18-59 years) and late-onset ischemic stroke ([LOS]; onset ≥60 years).

A multiparametric anti-aging CRISPR screen uncovers a role for BAF in protein synthesis regulation.

Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Here, we report a whole genome, multiparametric CRISPR screen, identifying 43 genes that can rescue multiple cellular phenotypes associated with progeria. We implement the screen in fibroblasts from Néstor-Guillermo Progeria Syndrome male patients, carrying a homozygous A12T mutation in BAF.

Prospective reciprocal relations between psychosocial impairment and eating disorder symptoms in a high-risk sample.

Impairment in psychosocial functioning increases risk for future onset of eating disorders and a treatment that produced larger reductions in eating disorder symptoms also produced larger improvements in psychosocial functioning. However, no studies have tested whether there is a prospective reciprocal relationship between psychosocial impairment and eating disorder symptoms. Accordingly, the current study tested the hypotheses that baseline psychosocial functioning would predict future increases in eating disorder symptoms and that baseline eating disorder symptoms would predict future increases in psychosocial impairment.

Immunological responses and clinical outcomes in pet dogs with osteosarcoma receiving standard of care therapy and a recombinant Listeria vaccine expressing HER2/neu.

A clinical trial in dogs with spontaneous osteosarcoma was performed to assess a recombinant Listeria expressing a chimeric human HER2/neu (ADXS31-164) as an adjunctive vaccine strategy to prevent metastatic disease and determine immunological correlates of clinical outcome. 118 dogs with appendicular osteosarcoma were recruited into a 1-arm, multicenter, prospective trial of standard of care (SOC) therapy followed by ADXS31-164. ADXS31-164 was well tolerated with mostly transient, low-grade side effects.

Development and evaluation of a training program for implementation of velopharyngeal MRI in the clinical setting.

Background: Many craniofacial teams are interested in using velopharyngeal magnetic resonance imaging (MRI) clinically for surgical planning for management of velopharyngeal insufficiency (VPI). However, many teams report training and resources are barriers that prevent them from implementing MRI.

Objective: (1) To describe a training program for implementation of velopharyngeal magnetic resonance imaging (MRI) in the clinical setting, (2) to assess the effectiveness of the training program, and (3) to identify factors associated with successful implementation of velopharyngeal MRI.

Implementation of a Pharmacist-led Outpatient Penicillin Allergy Testing Clinic.

Background: Penicillin allergies affect approximately 10% of the population, leading to increased healthcare costs, treatment failures, and multidrug resistant organisms.

Objective: To determine the feasibility of implementing a pharmacist-led outpatient penicillin allergy testing program.

Methods: This single-site, retrospective cohort study was conducted from July 2022 through December 2023.

Unresolved ethical issues of genetic counseling and testing in clinical psychiatry.

Objective: This position article discusses current major ethical and social issues related to genetic counseling and testing in clinical psychiatry (PsyGCT).

Methods: To address these complex issues in the context of clinical psychiatry relevant to PsyGCT, the interdisciplinary and pan-European expert Network EnGagE (Enhancing Psychiatric Genetic Counseling, Testing, and Training in Europe; CA17130) was established in 2018. We conducted an interdisciplinary, international workshop at which we identified gaps across European healthcare services and research in PsyGCT; the workshop output was summarized and systematized for this position article.

Chromogenic hydroxyanthraquinone-based enzyme substrates for the detection of microbial β-d-galactosidase, β-d-glucuronidase and β-d-ribosidase.

Di-β-d-galactopyranoside derivatives of quinizarin (1,4-dihydroxyanthraquinone) and anthrarufin (1,5-dihydroxyanthraquinone) were evaluated as microbial enzyme substrates in Columbia agar medium for the detection of clinically important microorganisms. Furthermore, these substrates were evaluated both in the presence and absence of iron salts which could chelate to the aglycone after microbial hydrolysis of the substrate. The quinizarin-based substrate resulted in the formation of black microbial colonies in the presence of iron salts and orange colonies in their absence.

A comprehensive spatio-cellular map of the human hypothalamus.

The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions. However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies. Here we combine single-nucleus sequencing of 433,369 human hypothalamic cells with spatial transcriptomics, generating a comprehensive spatio-cellular transcriptional map of the hypothalamus, the 'HYPOMAP'.