Standardized Measurement of Type 1 Diabetes Polygenic Risk Across Multi-Ancestry Population Cohorts.

Type 1 diabetes (T1D) polygenic risk scores (PRS) are effective tools for discriminating T1D from other diabetes types and predicting T1D risk, with applications in screening and intervention trials. A previously published T1D Genetic Risk Score 2 (GRS2) is widely adopted, but challenges in standardization and accessibility have hindered broader clinical and research utility. To address this, we introduce GRS2x, a standardized and cross- compatible method for accurate T1D PRS calculation, demonstrating genotyping and reference panel independent performance across diverse datasets.

The pulmonary contusion score: Development of a simple scoring system for blunt lung injury.

Background: Pulmonary contusions (PC) are common after blunt chest trauma and can be identified with computed tomography (CT). Complex scoring systems for grading PC exist, however recent scoring systems rely on computer-generated algorithms that are not readily available at all hospitals. We developed a scoring system for grading PC to predict the need for prolonged mechanical ventilation and initial hospital admission location.

Investigating misclassification of type 1 diabetes in a population-based cohort of British Pakistanis and Bangladeshis using polygenic risk scores.

Correct classification of type 1 (T1D) and type 2 diabetes (T2D) is challenging due to overlapping clinical features and the increasingly early onset of T2D, particularly in South Asians. Polygenic risk scores (PRSs) for T1D and T2D have been shown to work relatively well in South Asians, despite being derived from largely European-ancestry samples. Here we used PRSs to investigate the rate of potential misclassification of diabetes amongst British Bangladeshis and Pakistanis.

Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis.

Background: In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case-control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables.

Methods: We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes.

Trace: A research media player measuring real-time audience engagement.

Measuring attention and engagement is essential for understanding a wide range of psychological phenomena. Advances in technology have made it possible to measure real-time attention to naturalistic stimuli, providing ecologically valid insight into temporal dynamics. We developed a research protocol called Trace, which records anonymous facial landmarks, expressions, and patterns of movement associated with engagement in screen-based media.

Putative biomarkers of hepatic dysfunction in critically ill sepsis patients.

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach.

Type 1 diabetes genetic risk score variation across ancestries using whole genome sequencing and array-based approaches.

A Type 1 Diabetes Genetic Risk Score (T1DGRS) aids diagnosis and prediction of Type 1 Diabetes (T1D). While traditionally derived from imputed array genotypes, Whole Genome Sequencing (WGS) provides a more direct approach and is now increasingly used in clinical and research studies. We investigated the concordance between WGS-based and array-based T1DGRS across genetic ancestries in 149,265 UK Biobank participants using WGS, TOPMed-imputed, and 1000 Genomes-imputed array genotypes.

Widespread admixture blurs population structure and confounds Lake Trout (Salvelinus namaycush) conservation even in the genomic era.

Intraspecific variation is important for species' long-term persistence in changing environments. Conservation strategies targeting intraspecific variation often rely on the identification of management or policy units below the species level based on biological differences among populations. To identify management units, this paper examines intraspecific divergence of Lake Trout (Salvelinus namaycush) in Great Slave Lake (GSL), Canada, using low-coverage whole-genome sequencing data.

Metabolomic signature of pediatric diabetic ketoacidosis: key metabolites, pathways, and panels linked to clinical variables.

Background: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes (T1D), arising from relative insulin deficiency and leading to hyperglycemia, ketonemia, and metabolic acidosis. Early detection and treatment are essential to prevent severe outcomes. This pediatric case-control study utilized plasma metabolomics to explore metabolic alterations associated with DKA and to identify predictive metabolite patterns.

Eliminating the 'Impossible': Recent Progress on Local Measurement Theory for Quantum Field Theory.

Arguments by Sorkin (Impossible measurements on quantum fields. In: Directions in general relativity: proceedings of the 1993 International Symposium, Maryland, vol 2, pp 293-305, 1993) and Borsten et al. (Phys Rev D 104(2), 2021.

A systematic review of botulinum toxin as a treatment for Raynaud's disease secondary to scleroderma.

Raynaud's phenomenon (RP) is a vasospastic disorder that affects the small blood vessels in the extremities such as the hands, feet, fingers or toes. It is a debilitating condition that can severely impact the patient's quality of life. Botulinum toxin (BTX) has been examined as a treatment option for RP, but its effect has been inconclusive.

Temporal Variability in Effective Size ( ) Identifies Potential Sources of Discrepancies Between Mark Recapture and Close Kin Mark Recapture Estimates of Population Abundance.

Although efforts to estimate effective population size, census size and their ratio in wild populations are expanding, few empirical studies investigate interannual changes in these parameters. Hence, we do not know how repeatable or representative many estimates may be. Answering this question requires studies of long-term population dynamics.

Short communication: Can Vitamin D be supplied from the large intestine?

The discovery that vitamin D is being generated by anaerobic microbial metabolism in the alimentary tract, raises the question whether such a source of vitamin D could contribute to vitamin D supply for the animal hosting this microbial production system. In ruminants, this microbial generation in the forestomach allows vitamin D to be readily absorbed when it reaches the small intestine, contributing to vitamin D and 25-hydroxyvitamin D [25(OH)D] found in their tissues. In monogastric animals like humans, the microbial generation of vitamin D is occurring in the large intestine.

Development of SNP Panels from Low-Coverage Whole Genome Sequencing (lcWGS) to Support Indigenous Fisheries for Three Salmonid Species in Northern Canada.

Single nucleotide polymorphism (SNP) panels are powerful tools for assessing the genetic population structure and dispersal of fishes and can enhance management practices for commercial, recreational and subsistence mixed-stock fisheries. Arctic Char (Salvelinus alpinus), Brook Trout (Salvelinus fontinalis) and Lake Whitefish (Coregonus clupeaformis) are among the most harvested and consumed fish species in Northern Indigenous communities in Canada, contributing significantly to food security, culture, tradition and economy. However, genetic resources supporting Indigenous fisheries have not been widely accessible to northern communities (e.

Prescribing pre-exposure prophylaxis for HIV prevention: a cross-sectional survey of general practitioners in Australia.

Background Pre-exposure prophylaxis (PrEP) is a safe and effective medication for preventing HIV acquisition. We examined Australian general practitioners' (GP) knowledge of PrEP efficacy, characteristics associated with ever prescribing PrEP and barriers to prescribing. Methods We conducted an online cross-sectional survey of GPs working in Australia between April and October 2022.

Tobacco Quitline Retreatment Interventions Among Adults With Socioeconomic Disadvantage: A Factorial Randomized Clinical Trial.

Importance: A single round of standard tobacco quitline treatment may not be sufficient to sustain abstinence, particularly among people experiencing socioeconomic disadvantage. Adaptive retreatment may help more individuals with socioeconomic disadvantage achieve abstinence and reduce disparities in smoking cessation outcomes.

Objective: To evaluate 4 evidence-based strategies for adults with limited education, no insurance, or Medicaid eligibility who continued smoking after quitline treatment.

Circulating IL-17F, but not IL-17A, is elevated in severe COVID-19 and leads to an ERK1/2 and p38 MAPK-dependent increase in ICAM-1 cell surface expression and neutrophil adhesion on endothelial cells.

Background: Severe COVID-19 is associated with neutrophilic inflammation and immunothrombosis. Several members of the IL-17 cytokine family have been associated with neutrophilic inflammation and activation of the endothelium. Therefore, we investigated whether these cytokines were associated with COVID-19.

UK Foot and Ankle Thromboembolism (UK-FATE).

Aims: Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture.

Investigating the Risk Factors Associated With Acute Neurologic Dysfunction in Pediatric Hyperglycemic Emergencies on Transport.

Objective: This study aims to identify key characteristics of hyperglycemic emergencies in pediatric patients and those at risk for acute neurologic dysfunction during transport.

Methods: We conducted a retrospective chart review of pediatric patients during interfacility transport by Ornge, Ontario's critical care transport service, from January 1, 2009, to December 31, 2019. Data were extracted from electronic patient care records and included demographic, clinical, and transport-specific variables.

Quality Improvement Initiative: Identifying Barriers to Reducing Time to First Feed With Human Milk in Low Birth Weight Infants.

Early exposure to human milk and time to first trophic feed in low birth weight (LBW) infants (<2 kg) is associated with a decreased risk of mortality, sepsis, and length of hospital stay. This project, focused on infants born at less than 2 kg, aimed to identify the mean time to first feed after birth, identify barriers to initiation of the first feed, and meet the target of having 90% of infants receive their first feed within the first 6 hours of life. This quality improvement (QI) project occurred in a thirty-bed level III NICU over 29 months using two Plan-Do-Study-Act (PDSA) cycles.

Extensive longevity and DNA virus-driven adaptation in nearctic bats.

The genus is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated near-complete genome assemblies and cell lines for 8 closely related species of . Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cell lines, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats.

Sex-specific proximal tubular cell differentiation pathways identified by single-nucleus RNA sequencing.

Postnatal kidney growth is substantial and involves expansion in kidney tubules without growth of new nephrons, which are the functional units of the kidney. Proliferation and differentiation pathways underpinning nephron elongation are not well defined. To address this, we performed sequential characterization of mouse kidney transcriptomics at the single cell level.

Development and validation of automated methods for COVID-19 PCR Master Mix preparation.

Polymerase chain reaction (PCR)-based assays were widely deployed during the SARS-CoV-2 pandemic for population-scale testing. High-throughput molecular diagnostic laboratories required a high degree of process automation to cope with huge testing demands, fast turnaround times, and quality requirements. However, process developers and optimizers often neglected the critical step of preparing a PCR Master Mix.