The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup.

Diagnosis and Management of Legg-Calvé-Perthes Disease in the Obese Pediatric Population.

Legg-Calvé-Perthes Disease (LCPD) is a condition marked by temporary blood flow disruption to the proximal femur, commonly afflicting children aged 15 and younger. The etiology of the disease is often idiopathic and involves the development of avascular necrosis of the femoral head, subsequently leading to bone weakening and deformity. Obesity exacerbates LCPD, correlating with delayed diagnosis, increased disease severity, and bilateral involvement.

Multilevel Mediators on the Associations of Neighborhood Social Environmental Factors and Severity of Metabolic Syndrome: The Jackson Heart Study.

Background: Neighborhood characteristics serve as risk factors for metabolic syndrome (MetS). However, the intermediary factors linking this relationship remain understudied. Thus, we investigated the sex-specific mediating role of C-reactive protein, physical activity (PA), and perceived stress in the associations of perceived neighborhood social environment (PNSE) with MetS severity among Black adults.

Evaluation of Multidentate Ligands Derived from Ethyl 1,2,4-triazine-3-carboxylate Building Blocks as Potential An(III)-Selective Extractants for Nuclear Reprocessing.

Bis-1,2,4-triazine ligands are amongst the most promising soft N-donor ligands for the partitioning of trivalent actinides from trivalent lanthanides; a key separation proposed in the future reprocessing of spent nuclear fuels. In an effort to improve the extraction properties of these benchmark ligands, we propose herein a general ligand design approach that is inspired by the field of drug discovery, and we apply it to a new class of ligands in which the bidentate 3-(2-pyridyl)-1,2,4-triazine unit of the benchmark ligands is replaced by a bidentate 1,2,4-triazine-3-carboxamide unit. A series of nine novel ligands were synthesized by reactions of readily available ethyl 1,2,4-triazine-3-carboxylate building blocks with different polyamine cores and evaluated for their ability to extract and separate Am(III) and Cm(III) from Eu(III).

A Modular Approach to Tuning Emissive -Quinolyl Through-Space Charge Transfer States Using sp-Scaffolds.

We have shown that palladium-catalyzed cascade processes provide modular access to rigid quinoline-containing tetracyclic amines. This modular approach enables fine-tuning of the through-space charge transfer (TSCT) state formation between the lone pair localized on the nitrogen atom in the cage moiety and the quinoline moiety by variation of both the intramolecular -aryl distance and quinoline substitution. Decreasing this -aryl distance enhances the formation of the TSCT species, giving control over the emission color and photoluminescence quantum yield.

The common VTE-protective G haplotype of F5 increases factor V-short, TFPI function, and risk of bleeding.

The G haplotype is a group of co-inherited single nucleotide variants in the F5 gene that reduce venous thromboembolism (VTE) risk. Although 7% of the population is homozygous for the G haplotype (F5-G/G), the underlying mechanism of VTE protection is poorly understood. Using RNA sequencing data from 4651 blood donors in the INTERVAL study, we detected a rare excision event at the factor V (FV)-short splice sites in 5% of F5-G/Gs carriers as compared with 2.

SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins.

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology.

Annealing 1,2,4-triazine to iridium(III) complexes induces luminogenic behaviour in bioorthogonal reactions with strained alkynes.

A phenanthroline-type ligand containing an annealed 1,2,4-triazine ring was used to prepare novel Ir(III) complexes 3 and 4. The complexes are non-luminescent but show luminogenic behaviour following the inverse electron demand Diels-Alder (IEDDA) reaction with bicyclononyne (BCN) derivatives. It was observed that the complexes react with BCN-C10 faster than the corresponding free ligands.

Narrowband noise induces frequency-specific underwater temporary threshold shifts in freshwater turtles.

Freshwater turtles exhibit temporary threshold shifts (TTS) when exposed to broadband sound, but whether frequency-restricted narrowband noise induces TTS was unknown. Underwater TTS was investigated in two freshwater turtle species (Emydidae) following exposures to 16-octave narrowband noise (155-172 dB re 1 μPa2 s). While shifts occurred in all turtles at the noise center frequency (400 Hz), there were more instances of TTS and greater shift magnitudes at 12 octave above the center frequency, despite considerably lower received levels.

Deep Diving Into the Cardiovascular Health Paradox: A Journey Towards Personalized Prevention.

Objectives: The Life's Simple 7 score (LS7) promotes cardiovascular health (CVH). Despite this, some with optimal LS7 develop cardiovascular disease (CVD), while others with poor CVH do not, termed the "CVH paradox." This paper explores pathways explaining this paradox.

A data harmonization project of three large prospective cardiovascular health-focused cohorts.

Few prospective studies examine multilevel resilience resources and psychosocial factors in relation to cardiovascular health and disease. Recent research indicates that resilience resources are associated with a reduction in the incidence of cardiovascular disease-related events, but few studies have examined this relationship across different racial/ethnic populations or in large cohorts. Harmonization may address these limitations because it allows data from several cohorts to be analyzed together, potentially increasing sample size and in turn power overall and in minority populations.

DNA methylation near MAD1L1, KDM2B, and SOCS3 mediates the effect of socioeconomic status on elevated body mass index in African American adults.

Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

Introduction: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

Objective, Design, And Patients: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

Critical Consciousness and Sex Positivity: Opinions on Race Play within Alternate Sexuality Communities.

Race play, the act of making explicit overtures to race, racial differences, or political racial dynamics within the context of a kink or BDSM (bondage dominance/submission, sadism/masochism) can be a contentious topic among scholars and members of alternative sexuality communities. In the current study, we explored how individuals' ideologies about race and sex are associated with their opinions of race play. Two-hundred thirty-four participants recruited through sex-positive and BDSM community spaces between January and June of 2021 completed measures of color-blind racial ideology and sexual comfort as assessments of critical consciousness and sex-positive values.

Clinical and Financial Outcomes of a Pilot Pharmacist-Led Continuous Glucose Monitoring Clinic.

What are the clinical and financial outcomes of patients using a continuous glucose monitor (CGM) as part of a pilot pharmacist-led service in a Federally Qualified Health Center (FQHC)? This single-center, prospective cohort conducted in a FQHC from October 2022 to September 2023 was submitted to IRB for review [EXMT-P-22-F-17]. Patients were seen by a pharmacist in collaboration with an attending physician during diabetes specific visits. A total of 15 patients were seen in the pharmacist-led clinic (5 males and 10 females).

Identification and characterisation of functional K6.1-containing ATP-sensitive potassium channels in the cardiac ventricular sarcolemmal membrane.

Background And Purpose: The canonical K6.2/SUR2A ventricular K channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity.

Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma.

Unlabelled: Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance.

Cardiovascular Risk Associated With Social Determinants of Health at Individual and Area Levels.

Importance: The benefit of adding social determinants of health (SDOH) when estimating atherosclerotic cardiovascular disease (ASCVD) risk is unclear.

Objective: To examine the association of SDOH at both individual and area levels with ASCVD risks, and to assess if adding individual- and area-level SDOH to the pooled cohort equations (PCEs) or the Predicting Risk of CVD Events (PREVENT) equations improves the accuracy of risk estimates.

Design, Setting, And Participants: This cohort study included participants data from 4 large US cohort studies.