Potential mechanisms of non-coding RNA regulation in Alzheimer's disease.

Alzheimer's disease, a progressively degenerative neurological disorder, is the most common cause of dementia in the elderly. While its precise etiology remains unclear, researchers have identified diverse pathological characteristics and molecular pathways associated with its progression. Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed the effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N = 491,111) and African (N = 21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.

Dynamic Importance of Genomic and Clinical Risk for Coronary Artery Disease Over the Life Course.

Background: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction.

Sex-Specific Clinical and Genetic Factors Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy.

Background: Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry.

Considerations and expectations for the administration of dispersible arpraziquantel to young children: a landscape analysis.

Schistosomiasis is a serious public health problem in many African countries and beyond. Preventive chemotherapy with praziquantel is a successful public health intervention that is recommended for all communities at risk, commonly reached through large-scale mass drug administration campaigns. However, preschool-age children are currently not routinely targeted for treatment due to operational challenges related to dosing and administration with the standard drug formulation.

Recognition of by the pattern recognition molecules langerin, mannan-binding lectin, and surfactant protein D: the influence of capsular polysaccharides and wall teichoic acid.

The innate immune system plays a critical role in the rapid recognition and elimination of pathogens through pattern recognition receptors (PRRs). Among these PRRs are the C-type lectins (CTLs) langerin, mannan-binding lectin (MBL), and surfactant protein D (SP-D), which recognize carbohydrate patterns on pathogens. Each represents proteins from different compartments of the body and employs separate effector mechanisms.

A comparative study of hospitalization costs of TKA inpatients before and after National Volume-based Procurement in Guangdong, China: an interrupted time-series analysis.

Background: This study aims to explore the impact of the National Volume-based Procurement Policy in Guangdong Province on hospitalization costs for total knee arthroplasty inpatients.

Methods: Interrupted time-series analysis were used to examine the expenses associated with total knee arthroplasty for inpatients at a hospital in Guangzhou between May 10, 2021, and December 26, 2023. The period was divided into two phases based on the implementation of the policy, the pre-policy phase (May 10, 2021, to April 30, 2022) and the post-policy phase (May 1, 2022, to December 26, 2023).

Effects of vitamin D supplementation on cardiac biomarkers: Results from the STURDY trial.

Objectives: In observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD.

Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10-29 ng/mL).

Synthetic data in generalizable, learning-based neuroimaging.

Synthetic data have emerged as an attractive option for developing machine-learning methods in human neuroimaging, particularly in magnetic resonance imaging (MRI)-a modality where image contrast depends enormously on acquisition hardware and parameters. This retrospective paper reviews a family of recently proposed methods, based on synthetic data, for generalizable machine learning in brain MRI analysis. Central to this framework is the concept of domain randomization, which involves training neural networks on a vastly diverse array of synthetically generated images with random contrast properties.

Machine learning for antimicrobial peptide identification and design.

Artificial intelligence (AI) and machine learning (ML) models are being deployed in many domains of society and have recently reached the field of drug discovery. Given the increasing prevalence of antimicrobial resistance, as well as the challenges intrinsic to antibiotic development, there is an urgent need to accelerate the design of new antimicrobial therapies. Antimicrobial peptides (AMPs) are therapeutic agents for treating bacterial infections, but their translation into the clinic has been slow owing to toxicity, poor stability, limited cellular penetration and high cost, among other issues.

Piloting a battery to evaluate parasympathetic reactivity and externalizing behaviours during early childhood in autism spectrum disorder.

Background: Respiratory Sinus Arrhythmia Reactivity (RSA-R) correlates both positively and negatively with externalizing behavior in autistic individuals. These inconsistencies may result from task-based differences. This pilot study measured RSA-R in 4-to 6-year-olds, across two time-points, using four validated tasks with matched baseline and challenge periods.

Impaired Visuospatial Processing in Cerebral Visual Impairment Revealed by Performance on a Conjunction Visual Search Task.

Cerebral visual impairment (CVI) is a brain-based visual disorder associated with injury and/or maldevelopment of central visual pathways. Visuospatial processing impairments are a cardinal feature of the complex clinical profile of individuals with CVI. Here, we assessed visuospatial processing abilities using a classic conjunction search task.

A Longitudinal Investigation of Trans and Nonbinary Youth Identity: Individual Processes and Family Agreement in the Trans Teen and Family Narratives Project.

Few studies have focused on transgender and nonbinary youths' (TNBY) gender development and even less well understood is how family members understand TNBY identity. The current study investigated: a) how TNBY describe their gender identity over time, and b) how family members understand TNBY gender identity over time. The baseline sample included 96 members of 33 families (33 TNBY, 48 cisgender caregivers, 15 siblings) from the United States; 30 families continued after Wave 1.

Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.

Multi-ancestry genome-wide association analyses: a comparison of meta- and mega-analyses in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Background: There is increasing need for effective incorporation of high-dimensional genetics data from individuals with varied ancestry in genome-wide association (GWAS) analyses. Classically, multi-ancestry GWAS analyses are performed using statistical meta-analysis to combine results conducted within homogeneous ancestry groups. The emergence of cosmopolitan reference panels makes collective preprocessing of GWAS data possible, but impact on downstream GWAS results in a mega-analysis framework merits investigation.

Rapid human oogonia-like cell specification via transcription factor-directed differentiation.

The generation of germline cells from human induced pluripotent stem cells (hiPSCs) represents a milestone toward in vitro gametogenesis. Methods to recapitulate germline development beyond primordial germ cells in vitro have relied on long-term cell culture, such as 3-dimensional organoid co-culture for ~four months. Using a pipeline with highly parallelized screening, this study identifies combinations of TFs that directly and rapidly convert hiPSCs to induced oogonia-like cells (iOLCs).

Prenatal Diagnosis of Congenital Heart Disease in Liveborn Infants in the New England Region.

Prenatal diagnosis of congenital heart disease requiring early cardiac catheterization or surgical intervention enables optimal delivery planning for appropriate postnatal cardiovascular intervention and care. This allows for improved morbidity and mortality. Prior national data reported prenatal diagnosis rates of 32% for congenital heart disease requiring intervention in infants in the first 6 months of life in the New England region.

Advanced Automated Model for Robust Bone Marrow Segmentation in Whole-body MRI.

Rationale And Objectives: To establish an advanced automated bone marrow (BM) segmentation model on whole-body (WB-)MRI in monoclonal plasma cell disorders (MPCD), and to demonstrate its robust performance on multicenter datasets with severe myeloma-related pathologies.

Materials And Methods: The study cohort comprised multi-vendor, multi-protocol imaging data acquired with varying field strength across 8 different centers. In total, 210 WB-MRIs of 207 MPCD patients were included.

Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis.

Background And Objective: Selection of patients harboring mutations in homologous recombination repair (HRR) genes for treatment with a PARP inhibitor (PARPi) is challenging in metastatic castration-resistant prostate cancer (mCRPC). To gain further insight, we quantitatively assessed the differential efficacy of PARPi therapy among patients with mCRPC and different HRR gene mutations.

Methods: This living meta-analysis (LMA) was conducted using the Living Interactive Evidence synthesis framework.

Azygos Vein Stenosis in Frontotemporal Dementia Sagging Brain Syndrome.

Background And Purpose: Symptoms indistinguishable from behavioral-variant frontotemporal dementia (bvFTD) can develop in patients with spontaneous intracranial hypotension associated with severe brain sagging. An underlying spinal CSF leak can be identified in only a minority of these patients and the success rate of nondirected treatments, such as epidural blood patching and dural reduction surgery, is low. The disability associated with bvFTD sagging brain syndrome is high and, because of the importance of the venous system in the pathophysiology of CSF leaks in general, we have investigated the systemic venous circulation in those patients with recalcitrant symptoms.

B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells.

Background: Chordoma is a slow-growing, primary malignant bone tumor that arises from notochordal tissue in the midline of the axial skeleton. Surgical excision with negative margins is the mainstay of treatment, but high local recurrence rates are reported even with negative margins. High-dose radiation therapy (RT), such as with proton or carbon ions, has been used as an alternative to surgery, but late local failure remains a problem.