Development of a model to predict electroencephalographic seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

Objective: Electroencephalographic seizures (ES) are common in neonates with hypoxic-ischemic encephalopathy (HIE), but identification with continuous electroencephalographic (EEG) monitoring (CEEG) is resource-intensive. We aimed to develop an ES prediction model.

Methods: Using a prospective observational study of 260 neonates with HIE undergoing CEEG, we identified clinical and EEG risk factors for ES, evaluated model performance with area under the receiver operating characteristic curve (AUROC), and calculated test characteristics emphasizing high sensitivity.

PD-L1 expression is mediated by microRNA processing, Wnt/β-catenin signaling, and chemotherapy in Wilms tumor.

Inhibition of immune checkpoint proteins is effective in adult cancers but has shown limited efficacy in pediatric cancers. While factors regulating expression of immune checkpoint proteins such as PD-L1 are well-documented in adult cancers, their regulation is poorly understood in pediatric cancers. Here, we show that PD-L1 is upregulated in distinct subsets of Wilms tumor, the most common pediatric kidney cancer.

Leukemia-mutated proteins PHF6 and PHIP form a chromatin complex that represses myeloid leukemia stemness.

Myeloid leukemias are heterogeneous cancers with a diverse mutational landscape. Though many mutated genes fall within common protein complexes, some lack known functional partners and have unclear roles. PHF6 is a poorly-understood chromatin-binding protein with recurrent mutations that confer an unfavorable prognosis in acute and chronic myeloid leukemias.

Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset.

The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's Disease and Related Dementias (AD/ADRD) by sequencing whole genomes of affected participants and age-matched cognitive controls from diverse populations. The Genome Center for Alzheimer's Disease (GCAD) processed whole-genome sequencing data from 36,361 ADSP participants, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 2.

Posterior hippocampal sparing in Lewy body disorders with Alzheimer's copathology: An in vivo MRI study.

Background: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration.

Spatial regulation of NSUN2-mediated tRNA m5C installation in cognitive function.

Enzyme-mediated modifications of tRNA, such as 5-methylcytosine (m5C) installed by nuclear-enriched NOP2/Sun RNA methyltransferase 2 (NSUN2), play a critical role in neuronal development and function. However, our understanding of these modifications' spatial installation and biological functions remains incomplete. In this study, we demonstrate that a nucleoplasm-localized G679R NSUN2 mutant, linked to intellectual disability, diminishes NSUN2-mediated tRNA m5C in human cell lines and Drosophila.

Echocardiographic Changes in Infants with Severe Congenital Diaphragmatic Hernia After Fetoscopic Endoluminal Tracheal Occlusion (FETO).

Fetoscopic endoluminal tracheal occlusion (FETO) induces lung growth and may improve survival in congenital diaphragmatic hernia (CDH) but the effect on post-natal right (RV) and left (LV) ventricular size and cardiac function is unknown. Quantitative measures of heart size and function including tricuspid annular plane systolic excursion Z-score (TAPSEZ), RV fractional area change (RVFAC), RV global longitudinal and free wall strain (RVGLS, RVFWS), RV/LV ratio, LV eccentricity index (LVEI), and LV M-mode diastolic and systolic Z-scores (LVIDDZ, LVIDSZ) were compared between FETO and control patients on first post-natal echocardiogram, prior to and post CDH repair, and on last available echocardiogram using non-parametric Wilcoxon rank-sum test in a single-center, retrospective cohort study. Linear regression models evaluated change over time, adjusting for clustering and interaction of echocardiogram parameters with time.

Prime Editor Gene Therapy and TREX1 Mosaicism in Retinal Vasculopathy with Cerebral Leukoencephalopathy.

TREX1 mutations underlie a variety of human diseases, including retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S), a catastrophic adult-onset vasculopathy that is often confused with multiple sclerosis, systemic vasculitis, or systemic lupus erythematosus. Patients with RVCL develop brain, retinal, liver, and kidney disease around age 35-55, leading to premature death in 100% of patients expressing an autosomal dominant C-terminally truncated form of TREX1. We previously demonstrated that RVCL is characterized by high levels of DNA damage, premature cellular senescence, and risk of early-onset breast cancer before age 45.

Risk of Hypoglycemia Associated with Concomitant Use of Insulin Secretagogues and ACE Inhibitors in Adults with Type 2 Diabetes: A Systematic Review.

Insulin secretagogues and angiotensin-converting enzyme inhibitors (ACEIs) are commonly co-prescribed for patients with type 2 diabetes (T2D). Case reports suggesting that co-administration of insulin secretagogues with ACEIs is associated with an increased risk of serious hypoglycemia have led to warnings regarding a drug-drug interaction in widely used drug compendia. However, subsequent studies have had inconsistent results.

Connecting intermediate phenotypes to disease using multi-omics in heart failure.

Heart failure (HF) is one of the most common, complex, heterogeneous diseases in the world, with over 1-3% of the global population living with the condition. Progression of HF can be tracked via MRI measures of structural and functional changes to the heart, namely left ventricle (LV), including ejection fraction, mass, end-diastolic volume, and LV end-systolic volume. Moreover, while genome-wide association studies (GWAS) have been a useful tool to identify candidate variants involved in HF risk, they lack crucial tissue-specific and mechanistic information which can be gained from incorporating additional data modalities.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017.

Prospective Intervention Study Using Immediate-Fit, Adjustable Prostheses for Persons With Lower Limb Loss in Botswana-A Feasibility and Patient Acceptance Trial.

Objective: The aim of the study is to test the feasibility of an immediate-fit, adjustable prosthesis (iFIT Prosthesis) for persons with limb loss in Botswana.

Design: As part of the University of Pennsylvania and University of Botswana's long-term partnership, 18 persons with limb loss were fit at four different locations in Botswana. Patients were followed for 4-9 mos after fitting with an interview and Prosthetic Comfort and Utility questionnaire.

Imaging Findings and Management Strategies for Liver Masses in Children with Predisposition Disorders: A Review by the Pediatric LI-RADS Group.

Liver masses in children with underlying systemic disease or a predisposing syndrome can be benign or malignant, ranging from focal fat to hepatocellular carcinoma (HCC). Knowledge of the underlying condition, the pathophysiologic effect on the liver, and the development of liver disease and specific liver lesions allows radiologists to guide imaging with regard to modality and frequency and give recommendations for biopsy when appropriate. In some predisposition disorders, such as Beckwith Wiedemann spectrum, familial adenomatous polyposis syndrome, and tuberous sclerosis complex, established guidelines for imaging screening exist.

Inter-center variations in inpatient outcomes for infants with gastroschisis from the Children's Hospitals Neonatal Consortium.

Objective: To estimate inter-center variation (ICV) in hospital length of stay (LOS) and oral feeding at discharge among infants with gastroschisis.

Study Design: The Children's Hospitals Neonatal Consortium's (CHNC) database was used to identify hospitalized survivors with gastroschisis. Two outcomes were evaluated: LOS and discharge without tube feedings.

Patient and provider experiences with opioid use disorder care delivered via telehealth: A systematic mixed-studies review.

Introduction: Since the onset of the COVID-19 pandemic and loosening of some opioid use disorder (OUD) treatment regulations in the U.S. and Canada, there has been a rapid rise in the use of telehealth for buprenorphine induction, maintenance, and counseling (tele-bupe).

Symptom perception in adults with chronic physical disease: A systematic review of insular impairments.

Background: To perform self-care, individuals with a chronic illness must be able to perceive bodily changes (ie., interoception) so they can respond to symptoms when they arise. Interoception is regulated by the insular cortex of the brain.

Skin immune-mesenchymal interplay within tertiarylymphoid structures promotes autoimmunepathogenesis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by keratinized epithelial tunnels that grow deeply into the dermis. Here, we examined the immune microenvironment within human HS lesions. Multi-omics profiling and multiplexed imaging identified tertiary lymphoid structures (TLSs) near HS tunnels.

HIV Clinical Providers' Awareness, Attitudes, and Willingness to Support Patient Outreach Efforts for HIV Cure-Directed Research in Philadelphia, United States.

Background: Ethical patient outreach is critical for engaging patients with HIV in HIV cure-directed research. We sought to examine HIV clinical providers' awareness of current HIV cure-directed research strategies investigated through the Martin Delaney Collaboratories (MDC) and providers' attitudes toward patient outreach for HIV cure-directed research and to identify opportunities for clinical provider education on MDC research strategies.

Methods: We conducted a 1-time, cross-sectional, web-based survey with 64 HIV clinical providers (physicians, physician assistants, and nurses) in Philadelphia.

Toward an artificial intelligence code of conduct for health and healthcare: implications for the biomedical informatics community.

Introduction: The rapid advancement of artificial intelligence (AI) has led to significant transformations in health and healthcare. As AI technologies continue to evolve, there is an urgent need to establish a unified framework that guides the design, implementation, and evaluation of AI-driven interventions across individual and population health contexts.

Approach: In response to this need, the National Academy of Medicine (NAM) has initiated the development of an AI code of conduct (AICC) through its Digital Health Action Collaborative.