Development and Validation of a Brief Age-Normed Screening Tool for Subthreshold Psychosis Symptoms in Youth.

Background And Hypothesis: Improvements in screening tools for early subthreshold psychosis symptoms are needed to facilitate early identification and intervention efforts, especially given the challenges of rapidly differentiating age-appropriate experiences from potential early signs of emerging psychosis. Tools can be lengthy and time-consuming, impacting their utility and accessibility across clinical settings, and age-normed data are limited. To address this gap, we sought to develop and validate a brief, empirically derived, age-normed, subthreshold psychosis screening tool, for public use.

Moving Beyond Static, Individualistic Approaches to Agency: Theories of Agency for Medical Education Researchers: AMEE Guide No. 177.

Agency - the capacity to produce an effect - is a foundational aspect of medical education. Agency is usually conceptualized at the level of the , with each learner charged with taking responsibility to pull themselves up by their bootstraps. This conceptualization is problematic.

Intelligent biology and medicine: Accelerating innovative computational approaches.

In this editorial, we summarize the 2023 International Conference on Intelligent Biology and Medicine (ICIBM 2023) conference which was held on July 16-19, 2023 in Tampa, Florida, USA. We then briefly describe the nine research articles included in this special issue. ICIBM 2023 scientific program included four tutorials and workshops, four keynote lectures, four eminent scholars' presentations, 11 concurrent scientific sessions, and a poster session.

Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function.

Thromboembolic Risk in Juvenile Dermatomyositis Patients Treated With Intravenous Immunoglobulin.

This single-institution retrospective cohort study evaluates the risk of thromboembolic events (TE) in patients with juvenile dermatomyositis (JDM) treated with intravenous immunoglobulin (IVIg). We found no difference in the occurrence of TE in JDM patients treated with IVIg as compared to those without IVIg exposure; both cohorts had no TEs. Patients in both JDM cohorts had matched levels of other clotting risk factors, such as periods of limited mobility and hormonal contraceptive use.

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling.

In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all 'adult' cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes.

Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series.

Background: Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is encoded by the SUMF1 gene. Disease-causing homozygous or compound heterozygous variants in SUMF1 result in MSD.

Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).

UW supplementation with AP39 improves liver viability following static cold storage.

Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (HS) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. HS is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations.

Circle of Willis Variants and Their Association with Outcome after Successful Revascularization of Anterior Large Vessel Occlusion.

Background And Purpose: Leptomeningeal collaterals have been associated with better outcomes in large-vessel stroke, but little is known about how the Circle of Willis (CoW) collaterals affect stroke outcomes. We aimed to determine the relationship between three anatomically distinct CoW subtypes and 90-day outcomes in acute ischemic stroke patients after successful revascularization via endovascular thrombectomy (EVT).

Materials And Methods: We performed a retrospective analysis of patients treated with successful EVT for large-vessel occlusion at a comprehensive stroke center between May 2016 and November 2023.

Towards a Provider Builder Maturity Model to Empower Clinicians to Actively Participate in Electronic Health Record Design.

Background: Engagement of clinicians who understand clinical workflows and technology constraints can accelerate the development and implementation of better electronic health record (EHR) designs that improve quality and reduce burnout. Provider builder programs can accelerate clinical informatics education for a broader coalition of clinical specialties.

Objective: In this State of the Art / Best Practice paper, we aim to (1) propose a provider builder maturity model informed by the experience of three institutions using a single EHR vendor (Epic Systems©) and (2) describe the program elements and relationships necessary to advance along this model to yield organizational benefits.

Measurement of urine calcium, magnesium and phosphate: Preanalytical considerations in the elimination of the acidification step.

Background: Traditionally, urine analysis of calcium (Ca), magnesium (Mg) and phosphate (Phos) requires acidification of the sample. This study aims to assess the need for acidification and evaluate preanalytical factors that influence the accurate measurement of these analytes in urine.

Results: A total of 107 spot urine samples from patients with a median age of 9 years (95 % ≤ 21 years of age, range 5 days to 46 years) were analyzed for Ca (n = 94), Mg (n = 97), and Phos (n = 102) with and without acidification.

Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study.

Background: Infliximab and adalimumab are the only biologics thus far approved for paediatric patients with inflammatory bowel disease (IBD), so other biologics, such as vedolizumab, are prescribed off-label. Despite its frequent use, prospective data for vedolizumab treatment in children are available only for short-term induction outcomes. We aimed to evaluate the long-term efficacy and safety of maintenance therapy with vedolizumab in paediatric patients with IBD.

Motor function and compound muscle action potential amplitude in children with spinal muscular atrophy treated with nusinersen.

Background: Disease-modifying therapies can improve motor function in patients with spinal muscular atrophy (SMA), but efficacy varies between individuals. The aim was to evaluate the efficacy and safety of nusinersen treatment in children with SMA and to investigate prognostic factors.

Methods: Motor function, compound muscle action potential (CMAP), and other indicators were prospectively collected before and 14 months after nusinersen treatment.

Updating an HIV Knowledge Questionnaire With Pre-exposure Prophylaxis Through Expert Opinions in the United States Using Delphi Methodology: A Qualitative Study.

Our study was designed to update the HIV Knowledge Questionnaire by incorporating pre-exposure prophylaxis (PrEP) knowledge questions, as previous HIV knowledge tools lack this focus. Four rounds of Delphi surveys were conducted with 47 expert participants, each with extensive HIV-related expertise (mean experience: 18.94 years).

A Qualitative Assessment of Barriers, Facilitators, and Outcomes in a Simulation-Based Collaborative Quality Improvement Program: The ImPACTS Project.

Objectives: ImPACTS (Improving Acute Care Through Simulation) is a collaborative simulation-based program partnering pediatric specialty centers ("hubs") with general emergency departments (GEDs) to improve pediatric acute care. Objective measurements of ImPACTS, such as evaluating Pediatric Readiness Score (PRS) and simulation-based outcome improvements, have been reported previously. Barriers to and facilitators of program involvement and the downstream effects of the program have not been previously described.

CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.

Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive.

Children's executive functioning and health behaviors across pediatric life stages and ecological contexts.

Executive functioning (EF) has been linked to chronic disease risk in children. Health behaviors are thought to partially explain this association. The current cross-sectional study evaluated specific domains of EF and varied health behaviors in three pediatric life stages.

Survey of Urogynecology Fellows on the Care of Patients with Differences in Sex Development/Intersex Traits.

Introduction And Hypothesis: Patients with differences in sex development or intersex traits (DSD/I) struggle to find clinically competent care in adulthood. We sought to describe the surgical exposure of Urogynecology and Reconstructive Pelvic Surgery (URPS) fellows who had previously trained in ObGyn (URPS-Gyn) to patients with DSD/I and their interest in performing 18 relevant procedures. We hypothesized that most graduating fellows would not have had exposure to many of the surgeries.

Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.

Purpose: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma that develops sporadically or in Neurofibromatosis type 1 patients. Its development is marked by the inactivation of specific tumor suppressor genes (TSGs): NF1, CDKN2A and SUZ12EED (Polycomb Repressor Complex 2). Each TSG loss can be targeted by particular drug inhibitors and we aimed to systematically combine these inhibitors, guided by TSG inactivation status, to test their precision medicine potential for MPNSTs.

Biomarkers.

Background: Structural and functional heterogeneity in the brains of patients with Alzheimer's disease (AD) leads to diagnostic and prognostic uncertainty and confounds clinical treatment planning. Normative modelling, where individual-level deviations in brain measures from a reference sample are computed to infer personalized effects of disease, allows parsing of disease heterogeneity. In this study, GAN based normative modelling technique quantifies individual level neuroanatomical abnormality thereby facilitating measurement of personalized disease related effects in AD patients.

Biomarkers.

Background: Studying brain reserve - the brain's resilience to age-related changes or damage - is crucial for understanding protective mechanisms against cognitive decline. The cerebellum may be a key region in brain reserve, but it has been historically understudied. This investigation delves into this critical area within the largest aging multi-cohort to date.