Landscape of somatic mutations and clonal evolution in NUP98-rearranged adult acute myeloid leukaemia.

Acute myeloid leukaemia with NUP98 rearrangement (AML-NUP98) has been previously described in paediatric patients, and the clinical significance in adult AML patients remains largely unexplored. In this study, we identified specific partner fusion genes and examined somatic co-mutations and clonal evolution longitudinally in adult AML-NUP98 patients. Our comprehensive analysis provides an understanding of NUP98 rearrangement and co-mutations influencing clonal evolution and disease progression and offers valuable insights into potential therapeutic strategies.

A Randomized Phase II Study of Efmarodocokin Alfa, an interleukin-22 Agonist, Versus Vedolizumab in Patients With Ulcerative Colitis.

Background & Aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared with vedolizumab in patients with ulcerative colitis (UC).

Methods: This randomized phase II trial evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n = 43], 60 μg/kg [n = 44], and 90 μg/kg [n = 43]) compared with placebo (n = 22) and with vedolizumab (n = 43) in the treatment of moderate to severe UC.

Benefits and challenges of the integration of haptics-enhanced virtual reality training within dental curricula.

Background: Haptics-enhanced virtual reality (VR-haptic) simulation in dental education has evolved considerably during the past decade, representing a promising resource of simulation-based training opportunities to support conventional practice. We aim to summarize current literature on the applications of VR-haptics in learning, practicing, and teaching dental education.

Methods: A literature search was performed using PubMed, focusing on research articles published between January 2010 and January 2024.

Phenotypes Associated With Polycystic Ovary Syndrome Risk Variants.

Context: Polycystic ovary syndrome (PCOS) affects 10% of women of reproductive age. The genetic architecture of the disease is emerging, but there is little data exploring the effect of genetic risk on clinical presentation.

Objective: We hypothesized that genetic risk loci would influence measurable phenotypic traits.

Bladder exstrophy-epispadias-cloacal exstrophy complex: characteristics, aetiologies, and epidemiologic findings.

Bladder exstrophy-epispadias-cloacal exstrophy complex (BEEC) is a spectrum of congenital urologic anomalies that involve the bladder, urethra, genitalia, and pelvic musculoskeletal system, and can affect urinary continence, sexual health, and fertility. BEEC includes a wide spectrum of anatomical abnormalities with different levels of severity: epispadias represents the mildest phenotype, classic bladder exstrophy (CBE) is the most common defect, and cloacal exstrophy (CE) - often referred to as omphalocele, exstrophy, imperforate anus, and spinal defects (OEIS) complex - is the most severe form. BEEC disorders cause significant health problems and affect the health-related quality of life (QoL) of affected individuals.

Neuropsin, TRPV4 and intracellular calcium mediate intrinsic photosensitivity in corneal epithelial cells.

Purpose: To investigate intrinsic phototransduction in the corneal epithelium and its role in intracellular and inflammatory signaling.

Methods: Optical imaging in isolated corneal epithelial cells (CECs) and debrided epithelia was combined with molecular, biochemical, pharmacological assays and gene deletion studies to track UVB-induced calcium signaling and release of cytokines, chemokines and matrix remodeling enzymes. Results from wild type mouse CECs were compared to data obtained from Opn5 and Trpv4 cells.

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.

Mammography Among Women Residing in Urban Versus Rural Utah: Breast Cancer Survival.

Background: Annual or biennial breast cancer screenings are recommended for women 40 and older. Women residing in rural areas have worse breast cancer survival rates than urban women, but no study has focused on rural versus urban residence in Utah regarding breast cancer screening and mortality.

Methods: Cases (n = 14,516) were women aged > 39 diagnosed with a first primary invasive breast cancer between 1998 and 2017 in Utah.

Natural Language Processing to Identify Infants Aged 90 Days and Younger With Fevers Prior to Presentation.

Objective: Natural language processing (NLP) can enhance research studies for febrile infants by more comprehensive cohort identification. We aimed to refine and validate an NLP algorithm to identify and extract quantified temperature measurements from infants aged 90 days and younger with fevers at home or clinics prior to emergency department (ED) visits.

Patients And Methods: We conducted a cross-sectional study using electronic health record (EHR) data from 17 EDs in 10 health systems that are part of the Pediatric Emergency Care Applied Research Network Registry.

Newborn Screening for Critical Congenital Heart Disease: A New Algorithm and Other Updated Recommendations: Clinical Report.

Critical congenital heart disease (CCHD) screening was added to the US Recommended Uniform Screening Panel in 2011 and adopted by all US states and territories by 2018. In addition to reviewing key developments in CCHD screening since the initial American Academy of Pediatrics (AAP) endorsement in 2011, this clinical report provides 3 updated recommendations. First, a new AAP algorithm has been endorsed for use in CCHD screening.

Estimation of Air Travel-Related Greenhouse Gas Emissions for the In-Person Anesthesiology Oral Board Examination.

With an increased focus on climate change in graduate medical education (GME), the environmental implications of travel for board certification examinations remain poorly described. The return to the mandatory in-person applied examination (AE) for board eligible anesthesiologists presents potentially sizeable greenhouse gas (GHG) emissions when compared to the virtual format administered during the COVID-19 pandemic. To estimate the GHG emissions from air travel to the in-person AE and discuss its implications for various specialties as they return to in-person examinations.

Dnmt3a-mediated methylation balances memory Th1 and Tfh cell plasticity and functionality.

Following acute viral infection, naïve CD4+ T cells differentiate into T follicular helper (Tfh) and T helper 1 (Th1) cells that generate long-lived memory cells. However, it is unclear how memory Tfh and Th1 cells maintain their lineage commitment. Here we demonstrate that Tfh and Th1 lineages acquire distinct DNA methylation programs that are preserved into memory.

Evaluating a Child Presenting with Symptoms Concerning for Sjögren Disease: A Clinical Tool for Practice.

Background/purpose: Childhood Sjögren disease (cSjD) is a rare disease. There are no widely accepted diagnostic or classification criteria for cSjD. To fill this gap, members from CARRA Sjogren Workgroup and the International cSjD Workgroup created a clinical diagnostic algorithm.

Gender Minority Physician Assistant/Associate Applicants and Likelihood of Matriculation: A Retrospective Analysis.

Introduction: Gender minorities are undermeasured among physician assistant/associate programs and across the profession. This study describes the 2020 to 2021 Centralized Application Service for Physician Assistants self-identified gender minority applicant pool, examining whether gender minority status is associated with matriculation.

Methods: A retrospective cohort of 2020 to 2021 admission cycle participants (n = 30,123) was described and evaluated for associations between self-identified gender minority status and likelihood of program matriculation using logistic regression.

The Age-Friendly Learning Healthcare System: Replicating electronic health record based documentation metrics for 4Ms care.

Background: University of Utah Health (UUH) is an academic medical center that achieved "committed to care excellence" in age-friendly care in 2021 and has a long-standing culture of quality improvement central to a learning health system. University of California San Francisco (UCSF) developed electronic health record (EHR) documentation metrics for inpatient assessment of the 4Ms (What Matters, Medication, Mentation, and Mobility) based on the Institute for Healthcare Improvement's recommended care practice for an Age-Friendly Healthcare System. In partnership with UCSF, we replicated the assessment and action EHR metrics with local adaptations for each of the 4Ms at UUH.

Immunomodulatory Effects of Modified Colostrum, Whey, and Their Combination With Other Natural Products: Effects on Natural Killer Cells.

Objectives: Natural killer (NK) cells are important immune system effector cells providing innate defenses against intracellular infections, including viral infections, immune surveillance, and cancer immunoediting. The primary purpose of this study was to investigate whether modified ultra-filtrated colostrum (UC) and hydrolyzed whey (W) products or their combinations with other natural products with reported immunomodulatory properties will stimulate NK cell cytotoxic activity by activation of granzyme B and IFN-γ production.

Methods: The ability of study products to stimulate the cytotoxic activity of human-purified CD56 NK cells and the production of granzyme B and IFN-γ by activated NK cells was evaluated in the cytotoxic assay.

Firearm Injury Risk Prediction Among Children Transported by 9-1-1 Emergency Medical Services: A Machine Learning Analysis.

Objective: Among children transported by ambulance across the United States, we used machine learning models to develop a risk prediction tool for firearm injury using basic demographic information and home ZIP code matched to publicly available data sources.

Methods: We included children and adolescents 0-17 years transported by ambulance to acute care hospitals in 47 states from January 1, 2014 through December 31, 2022. We used 96 predictors, including basic demographic information and neighborhood measures matched to home ZIP code from 5 data sources: EMS records, American Community Survey, Child Opportunity Index, County Health Rankings, and Social Vulnerability Index.

Lessons from Maternal Mortality Reviews. How Addiction Care Providers can help improve Outcomes for Pregnant, Postpartum, and Parenting people.

Background: Drug-related deaths, including accidental and intentional overdose and other drug-related causes, are among the leading causes of maternal mortality in the United States.

Analysis: Addiction care providers can contribute to efforts to decrease maternal mortality related to substance use disorder. In this report, we review current research to inform the care of pregnant and parenting people with substance use disorder (SUD) to address rising drug-related deaths.