USP7 Inhibitors Destabilize EBNA1 and Suppress Epstein-Barr Virus Tumorigenesis.

Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt's lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7).

Atrial Fibrillation Recurrence Risk After Catheter Ablation in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Background: The association between rheumatoid arthritis (RA) and the risk of developing atrial fibrillation (AF) is well-established. However, data on the impact of RA on AF recurrence postcatheter ablation (CA) remain unclear. This current study aimed to assess the impact of RA on AF recurrence after catheter-based pulmonary vein isolation.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

Clinical characteristics of bullous pemphigoid patients of different ages and the possible mechanism.

Bullous pemphigoid (BP) is an acquired autoimmune bullous disease that often occurs in elderly patients. Some BP patients with early age of disease onset were observed to have difficulty in receiving applicable disease control. It remains challenging for clinicians to choose the appropriate treatment for these patients.

Real World Data in Stage III Melanoma in Latino Low Middle Income Country: Prognostic Factors and Outcomes.

Introduction: Malignant melanoma is a heterogeneous disease, with varying outcomes depending on the patient's race and ethnicity. Advanced stages can be tackled by novel targeted therapies and immunotherapy. We aimed to investigate the real-world data in Latino-Hispanic patients diagnosed with Stage III melanoma residing in Peru, a region marked by limited resources and healthcare infrastructure.

Risk Profile and Prognostic Implications of Premature Advanced Coronary Atherosclerotic Disease Among Young to Early Middle-aged Adults: The Coronary Artery Calcium Consortium.

Introduction: Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized.

Methods: We used data from 44,047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium.

Differences in time to surgery and defect sizes after Mohs micrographic surgery for black versus white patients with cutaneous squamous cell carcinoma.

Few studies have examined outcomes for Mohs micrographic surgery (MMS) for cutaneous squamous cell carcinoma (cSCC) in Black versus White patients. We compared time to surgery and defect sizes after MMS between Black versus White patients with cSCC. Patients with biopsy-proven cSCC treated with MMS at the Hospital of the University of Pennsylvania were identified from a prospectively maintained database (2006-2023).

Geriatrics-Focused vs Traditional Primary Care in the Veterans Affairs Health Care System.

Importance: Older adults often require specialized health care expertise, but the effects of geriatrics-focused models of primary care have not been fully evaluated.

Objective: To compare the effects of geriatrics-focused primary care vs traditional primary care for older patients in the Veterans Affairs (VA) health care system.

Design, Setting, And Participants: In this cohort study, geriatrics-focused primary care and traditional primary care patient dyads matched on variables associated with geriatrics-focused primary care entry and outcomes were enrolled from VA medical centers with operational geriatrics-focused primary care clinics serving 500 or more patients annually in fiscal year 2016.

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

Background: The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine.

Methods: The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-89 ml/min/1.

Application of the Diagnosis Grouping System to Pediatric Emergency Department Encounters.

Objective: Diagnosis grouping systems are essential for health services and epidemiological and health outcomes research. The Diagnosis Grouping System (DGS) was developed to classify International Classification of Diseases, 10th Revision diagnosis codes for pediatric emergency department (ED) encounters. We applied and compared the DGS to large samples of US ED encounters for children using 3 large health system databases.

Female oviposition decisions are influenced by the microbial environment.

In ovipositing animals, egg placement decisions can be key determinants of offspring survival. One oviposition strategy reported across taxa is laying eggs in clusters. In some species, mothers provision eggs with diffusible defence compounds, such as antimicrobials, raising the possibility of public good benefits arising from egg clustering.

Loneliness and biomarkers of Alzheimer's disease, axonal damage, and astrogliosis: A coordinated analysis of two longitudinal cohorts.

Objectives: Loneliness is associated with an elevated risk of dementia. There is mixed evidence from imaging studies on whether loneliness is associated with neuropathology in dementia-free adults. This study tests whether loneliness is associated with plasma neurobiomarkers of amyloid (Aβ42/Aβ40), phosphorylated tau 181 (pTau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and imaging measures of amyloid and tau.

Health Care Utilization and Costs for Older Adults Aging Into Medicare After the Affordable Care Act.

Importance: The Affordable Care Act (ACA) expanded Medicaid and Marketplace insurance to nonelderly adults in 2014, but whether these policies improved outcomes later in life is unknown.

Objective: To examine whether exposure to ACA expansions during middle age (50-64 years) was associated with changes in health, utilization, and spending after these adults entered Medicare at 65 years of age.

Design, Setting, And Participants: This serial analysis of the Health and Retirement Study cohort linked to Medicare enrollment and claims data from January 1, 2010, to December 31, 2018.

Trial of Labor After Cesarean Delivery in Individuals With Twin Pregnancies and Two Prior Cesarean Deliveries.

Objective: To investigate short-term maternal and neonatal outcomes in individuals with twin pregnancies and two prior cesarean deliveries who underwent trial of labor after cesarean (TOLAC).

Methods: A cross-sectional study of live-birth data was conducted between 2014 and 2021 in the United States. Individuals with more than two prior cesarean deliveries and multiple gestations higher than twins were excluded.

The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis.

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.

Phase I study of adavosertib with radiation therapy and temozolomide in newly diagnosed glioblastoma and intratumoral drug levels in recurrent glioblastoma.

Purpose: Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM.

Patients And Methods: The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ.

pDCs, type 1 IFN, and the female predileXion of SSc.

Systemic sclerosis (SSc) is a debilitating autoimmune disease that preferentially afflicts women. The molecular origins of this female bias are unclear. A new study of plasmacytoid dendritic cells from SSc patients by Du et al.

Mode of Delivery and Subsequent Motor Function in Children With Myelomeningocele Without In Utero Repair.

Objective: To assess the association between mode of delivery and 2-year motor function in children with prenatal diagnosis of myelomeningocele.

Methods: A multisite retrospective cohort study of children with myelomeningocele across 14 NAFTNet (North American Fetal Therapy Network) centers born between 2007 and 2020 who had a physical examination available at 2 years of life. Exclusion criteria were in utero myelomeningocele repair, postnatal myelomeningocele diagnosis, missing data on fetal presentation at delivery, and contraindications to labor.

Biomarker Panels for Discriminating Risk of CKD Progression in Children.

Background: We have previously studied biomarkers of tubular health (EGF), injury (KIM-1), dysfunction (alpha-1 microglobulin), and inflammation (TNFR-1, TNFR-2, MCP-1, YKL-40, suPAR), and demonstrated that plasma KIM-1, TNFR-1, TNFR-2 and urine KIM-1, EGF, MCP-1, urine alpha-1 microglobulin are each independently associated with CKD progression in children. In this study, we used bootstrapped survival trees to identify a combination of biomarkers to predict CKD progression in children.

Methods: The CKiD Cohort Study prospectively enrolled children 6 months to 16 years old with an eGFR of 30-90 ml/min/1.

Universal parent-focused child sexual abuse prevention: A quasi-experimental protocol.

Background: Child sexual abuse (CSA) is a significant public health concern, and there is a lack of universal, evidence-based primary prevention interventions that extend beyond a focus solely on children. Parents remain a consistently underutilized target for primary prevention efforts aimed at mitigating CSA despite their unique relationship and close proximity to their children. CSA risk is not confined to any specific demographic, and its effects on affected children are well-documented, significantly impacting numerous dimensions of their wellbeing.

Structural characterization of the ACDC domain from ApiAP2 proteins, a potential molecular target against apicomplexan parasites.

The apicomplexan AP2 (ApiAP2) proteins are the best characterized family of DNA-binding proteins in Plasmodium spp. malaria parasites. Apart from the AP2 DNA-binding domain, there is little sequence similarity between ApiAP2 proteins.