Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g.

High-grade liver injury: outcomes with a trauma surgery-liver surgery collaborative approach.

Background: Operative mortality for high-grade liver injury (HGLI) remains 42% to 66%, with near-universal mortality after retrohepatic caval injury. The objective of this study was to evaluate mortality and complications of operative and nonoperative management (OM and NOM) of HGLI at our institution, characterized by a trauma surgery-liver surgery collaborative approach to trauma care.

Methods: This was an observational cohort study of adult patients (age ≥16) with HGLI (The American Association for Surgery of Trauma (AAST) grades IV and V) admitted to an urban level I trauma center from January 2010 to November 2021.

Narrow linewidth distributed feedback lasers utilizing distributed phase shift.

This study proposes and experimentally demonstrates a distributed feedback (DFB) laser with a distributed phase shift (DPS) region at the center of the DFB cavity. By modeling the field intensity distribution in the cavity and the output spectrum, the DPS region length and phase shift values have been optimized. Experimental comparisons with lasers using traditional π-phase shifts confirm that DFB lasers with optimized DPS lengths and larger phase shifts (up to 15π) achieve stable single longitudinal mode operation over a broader current range, with lower threshold current, higher power slope efficiency, and a higher side mode suppression ratio (SMSR).

Do the biological characteristics of trout (Salmo trutta) smolts influence their spring migration timing and maiden marine sojourn duration?

Anadromous salmonids migrate seaward to exploit feeding and growth opportunities in marine habitats, yet how smolt biological characteristics influence their marine migratory behavior remains poorly understood. This study used 9 years of trout (Salmo trutta) population monitoring data from 15,595 tagged age-0+ parr, 1033 smolts detected migrating downstream in spring, and 99 adults detected returning from their first marine migration to the River Frome (Dorset, UK) to investigate the influence of smolt biological characteristics on their migration timing and maiden marine sojourn duration. Age-specific differences in the influence of smolt length on migration timing were found, with longer 1-year-old smolts emigrating later than their shorter counterparts within the same age class, but the opposite association existed for 2-year-old smolts.

Multi-methods process evaluation of the SToP (See, Treat, Prevent) trial: a cluster randomised, stepped wedge trial to support healthy skin.

Background: Healthy skin is important for maintaining overall physical and cultural health and wellbeing. However, remote-living Australian Aboriginal children contend with disproportionally high rates of (Strep A) infected impetigo. The SToP Trial was a large stepped-wedge cluster randomised trial of See, Treat, and Prevent (SToP) skin health activities implemented between 2019 and 2022 in the Kimberley region of Western Australia, during which a decrease in impetigo was observed.

When softer sounds are more distracting: Task-irrelevant whispered speech causes disruption of serial recall.

Two competing accounts propose that the disruption of short-term memory by irrelevant speech arises either due to interference-by-process (e.g., changing-state effect) or attentional capture, but it is unclear how whispering affects the irrelevant speech effect.

The hockey fans in training intervention for men with overweight or obesity: a pragmatic cluster randomised trial.

Background: Obesity disproportionately impacts men's health yet fewer men engage in preventive healthcare. We examined the effectiveness of Hockey Fans in Training (Hockey FIT), a gender-sensitised lifestyle intervention that engages men with overweight/obesity through their passion as fans of a local sports team, on weight change and other health indicators.

Methods: Pragmatic, cluster randomised trial (aged 35-65 years, body mass index ≥ 27 kg/m) within 42 community-based sites in Canada and the United States, randomly assigned (1:1) to intervention (Hockey FIT) or control (wait-list) and stratified by region.

The Platform Trial In COVID-19 priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of licensed COVID-19 vaccinations administered as a second booster in BNT162b2 primed individuals aged 18-<50 and 50-<70 years old.

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we present data for second boosters among individuals aged 18-<50 and 50-<70 years old primed with BNT162b2 until Day (D) 84.

Methods: Immunocompetent adults who had received two doses of BNT162b2 and any licensed COVID-19 booster at least three months prior were eligible.

Development of a deep learning algorithm for Paneth cell density quantification for inflammatory bowel disease.

Background: Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation.

Scalp condition improvement with botanical extracts possessing chemical and physical antioxidant activity.

Objective: Oxidative stress is implicated in scalp and hair health manifesting in several ways, including skin barrier, hair retention, healthy hair appearance and scalp sensation. We previously linked markers of oxidative damage to dandruff and skin barrier impairment and have linked key anti-dandruff technologies to the resolution of these issues. Here we expand the therapeutic space demonstrating many botanical extracts offer protective benefits against ROS stress via both chemical and biological antioxidant mechanisms.

Local haplotyping reveals insights into the genetic control of flowering time variation in wild and domesticated soybean.

The timing of flowering in soybean [Glycine max (L.) Merr.], a key legume crop, is influenced by many factors, including daylight length or photoperiodic sensitivity, that affect crop yield, productivity, and geographical adaptation.

Curating genomic disease-gene relationships with Gene2Phenotype (G2P).

Genetically determined disorders are highly heterogenous in clinical presentation and underlying molecular mechanism. The evidence underpinning these conditions in the peer-reviewed literature requires robust critical evaluation for diagnostic use. Here, we present a structured curation process for Gene2Phenotype (G2P).

Ventral subiculum control of avoidance behavior and hypothalamic-pituitary-adrenal axis reactivity via the bed nucleus of the stria terminalis in male and female mice - ISPNE 2024 Dirk Helhammer Award.

Avoidance or anxiety-like behavior is accompanied by corresponding changes in hypothalamic-pituitary-adrenal (HPA) axis activation. The underlying neural circuitry for this coordinated behavioral and neuroendocrine control is not well established. Prior studies pointed to a neural projection from the ventral subiculum (vSub) to the bed nucleus of the stria terminalis (BNST) that can inhibit the HPA axis response to stress.

Understanding the heterogeneous performance of variant effect predictors across human protein-coding genes.

Variant effect predictors (VEPs) are computational tools developed to assess the impacts of genetic mutations, often in terms of likely pathogenicity, employing diverse algorithms and training data. Here, we investigate the performance of 35 VEPs in the discrimination between pathogenic and putatively benign missense variants across 963 human protein-coding genes. We observe considerable gene-level heterogeneity as measured by the widely used area under the receiver operating characteristic curve (AUROC) metric.

Unveiling Gaps in High School Strength and Conditioning: CSCS Certification, Coaching Leadership, and Facilities.

Judge, LW, Marsh, JP, Petersen, JC, Pearson, D, and Bellar, D. Unveiling gaps in high school strength and conditioning: CSCS certification, coaching leadership and facilities. J Strength Cond Res 38(12): 2088-2098, 2024-The aim of this study was to examine the prevalence of Certified Strength and Conditioning Specialist (CSCS) and/or dedicated strength coaches overseeing strength and conditioning facilities (SCFs) at the high school level in a Southwestern state.

Protein structural context of cancer mutations reveals molecular mechanisms and candidate driver genes.

Advances in protein structure determination and modeling allow us to study the structural context of human genetic variants on an unprecedented scale. Here, we analyze millions of cancer-associated missense mutations based on their structural locations and predicted perturbative effects. By considering the collective properties of mutations at the level of individual proteins, we identify distinct patterns associated with tumor suppressors and oncogenes.

Asthma control in severe asthma and occupational exposures to inhalable asthmagens.

Introduction: Work-related asthma accounts for ≥25% of asthma in working-age populations, though the relationship between work exposures and symptoms is frequently missed, leading to poor health and employment outcomes. We hypothesised that inhalable exposures at work are associated with poor asthma control in severe asthma (SA).

Methods: We searched the Birmingham (UK) Regional NHS SA Service clinical database (n=1453 records; 1 March 2004 to 1 March 2021) and undertook a cross-sectional study using baseline data collected at diagnosis.

The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old.

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84.

Methods: Immunocompetent adults who received any first booster ≥three months prior were eligible.

Short-Term Active Safety Surveillance of the Spikevax and Nuvaxovid Priming Doses in Australia.

Australia commenced administration of the Spikevax (Moderna mRNA-1273) COVID-19 vaccine in August 2021 and Nuvaxovid (Novavax NVX-CoV2373) in January 2022. This study describes the short-term safety profile of priming doses of the Spikevax and Nuvaxovid vaccines given between September 2021 and September 2023. Online surveys were sent via AusVaxSafety, Australia's active vaccine safety surveillance system, three and eight days after vaccination.