Interpretable GWAS by linking clinical phenotypes to quantifiable immune repertoire components.

Bridging the gap between genotype and phenotype in GWAS studies is challenging. A multitude of genetic variants have been associated with immune-related diseases, including cancer, yet the interpretability of most variants remains low. Here, we investigate the quantitative components in the T cell receptor (TCR) repertoire, the frequency of clusters of TCR sequences predicted to have common antigen specificity, to interpret the genetic associations of diverse human diseases.

Trends in severe maternal morbidity following an institutional team goal strategy for disparity reduction.

Background: Racial disparities in maternal pregnancy outcomes, specifically in morbidity and mortality, are persistent in the U.S., and a multifaceted approach to mitigating these disparate outcomes is critical.

Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD.

First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies.

Purpose: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

Patients And Methods: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules.

Barriers to and facilitators of physical activity in pediatric pulmonary hypertension.

Therapeutic exercise has not been widely adopted in pediatric pulmonary hypertension (PH), despite adult data supporting its safety and efficacy. While physical limitations may prevent children with PH from participating in physical activity, other barriers to and facilitators of physical activity are unknown. Youth ages 8-18 years with World Symposium of PH diagnostic Groups 1-4, functional class I or II, and ambulatory status were prospectively enrolled in a cross-sectional study including separate 30-min participant and caregiver interviews regarding attitudes toward physical activity and a proposed exercise intervention in pediatric PH.

Morphometric measurements of intraoral anatomy in children with Beckwith-Wiedemann syndrome: a novel approach.

Background: An easy-to-use tool to objectively measure intraoral anatomy with meaningful clinical correlations may improve care for patients with Beckwith-Wiedemann syndrome (BWS), who commonly have symptomatic macroglossia.

Methods: Children aged 2-17 years with BWS were enrolled between 12/2021 and 01/2024. Digital intraoral photographs with a laser ruler were taken, and morphometric measurements were made using ImageJ software.

Handheld Cellphone Use and Risky Driving in Adolescents.

Importance: Handheld cellphone use while driving is associated with increased motor vehicle crash risk among adolescents.

Objective: To examine the association of handheld cellphone use while driving with kinematic risky driving (KRD) events-hard braking and rapid acceleration-in adolescent drivers.

Design, Setting, Participants: Adolescents aged 16.

Current state of quality improvement research across cardiac ICUs: a Pediatric Cardiac Intensive Care Society (PCICS) survey.

Background: Outcomes for children with heart disease improved over the past decades. Quality improvement (QI) research in paediatric cardiac critical care is a key driver of improvement. The availability and variability of QI research across the field is unknown.

Artificial intelligence for diagnosing exudative age-related macular degeneration.

Background: Age-related macular degeneration (AMD) is a retinal disorder characterized by central retinal (macular) damage. Approximately 10% to 20% of non-exudative AMD cases progress to the exudative form, which may result in rapid deterioration of central vision. Individuals with exudative AMD (eAMD) need prompt consultation with retinal specialists to minimize the risk and extent of vision loss.

NIAGADS: A Comprehensive National Data Repository for Alzheimer's Disease and Related Dementia Genetics and Genomics Research.

NIAGADS is the National Institute on Aging (NIA) designated national data repository for human genetics research on Alzheimer's Disease and related dementia (ADRD). NIAGADS maintains a high-quality data collection for ADRD genetic/genomic research and supports genetics data production and analysis. NIAGADS hosts whole genome and exome sequence data from the Alzheimer's Disease Sequencing Project (ADSP) and other genotype/phenotype data, encompassing 209,000 samples.

Contrastive Functional Connectivity Defines Neurophysiology-informed Symptom Dimensions in Major Depression.

Background: Major depressive disorder (MDD) is a prevalent psychiatric disorder characterized by substantial clinical and neurobiological heterogeneity. Conventional studies that solely focus on clinical symptoms or neuroimaging metrics often fail to capture the intricate relationship between these modalities, limiting their ability to disentangle the complexity in MDD. Moreover, patient neuroimaging data typically contains normal sources of variance shared with healthy controls, which can obscure disorder-specific variance and complicate the delineation of disease heterogeneity.

CDK8/19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes.

Neonatal and adult megakaryocytes differ in proliferative capacity and ploidy levels, and neonatal and adult platelets differ in function, gene expression, and protein content. The mechanisms underlying these differences are incompletely understood. CDK8 and CDK19 are transcriptional kinases part of the CDK-mediator complex, which regulates gene transcription in a cell-specific manner.

Liver Lymphatic Anatomy and Its Role in Systemic Health and Disease.

Lymphatic anatomy of the abdomen is reviewed with focus on hepatic and mesenteric vessels in normal and pathologic conditions. Anatomy and pathophysiology is highlight using both specialized fluoroscopy and T2 Dynamic Contrast MR lymphangiography (DCMRL). Plastic bronchitis, chylothorax, protein losing enteropathy, and both cirrhosis and ascites due to hepatic lymphatics are highlighted.

Imaging and Interventional Management of Lymphatic Disorders.

Lymphatic flow disorders are reviewed, and a classification based on magnetic resonance lymphography findings outlined. Examples of successful interventional management based on this classification are provided. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease.

Lymphatic Imaging and Intervention in Central Lymphatic Disorders.

Advances in lymphatic imaging for both diagnosis and intervention are reviewed, and specific examples given for protein-losing enteropathy, multi compartment lymphatic failure, congestive heart failure. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease.

Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.

Background: Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead.

Objectives: We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase () 677C>T genotype.

Methods: We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study.

Multicenter validation of automated detection of paramagnetic rim lesions on brain MRI in multiple sclerosis.

Background And Purpose: Paramagnetic rim lesions (PRLs) are an MRI biomarker of chronic inflammation in people with multiple sclerosis (MS). PRLs may aid in the diagnosis and prognosis of MS. However, manual identification of PRLs is time-consuming and prone to poor interrater reliability.