Expanding molecular and clinical spectrum of CPT1C-associated hereditary spastic paraplegia (SPG73)-a case series.

Autosomal-dominant variants in the CPT1C gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity and is therefore considered a pure form of hereditary spastic paraplegia. However, we report two unrelated males with novel CPT1C variants (NM_001199753.2: patient 1: c.

Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

Purpose: The TAOK proteins are a group of serine/threonine-protein kinases involved in signalling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity.

Increasing Incidence of Serious Head and Neck Infections Among US Children, 2018-2023.

There has been a significant, post-pandemic increase in the incidence of serious head and neck infections (HNI) among children aged < 18 years since 2021, compared with the stable incidence of non-transmissible osteomyelitis and serious HNI in adults from 2018 to 2023. The etiology of this increase requires further study.

Diversity-Related, Student-Led National Medical Organizations: Leadership Opportunities for Learners.

Introduction: In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine.

Methods: We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises.

Women and the Heart: Webcast April 16 2024.

This 62-minute webcast features a conversation about "Women and the Heart: Gender-Related Differences in Cardiovascular Care"-the focus of Issue 20.2. Led by the issue's editor, the discussion engages the authors on emerging themes and lessons learned while researching and writing the articles.

Size-dependent Nanoparticle Accumulation In Venous Malformations.

Objective: The current treatment of venous malformations (VMs) consists of medications with systemic toxicity and procedural interventions with high technical difficulty and risk of hemorrhage. Using nanoparticles (NPs) to enhance drug delivery to VMs could enhance efficacy and decrease systemic toxicity. NPs can accumulate in tissues with abnormal vasculature, a concept known as the enhanced permeation and retention (EPR) effect.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Approaches and outcomes of adalimumab discontinuation in patients with well-controlled inflammatory arthritis: a systematic search and review.

Objective: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.

Methods: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease.

Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis.

Background/objectives: Genetic variants in PRSS1 encoding human cationic trypsinogen are associated with hereditary pancreatitis. The clinically frequent variants exert their pathogenic effect by increasing intrapancreatic trypsin activity, while a distinct subset of variants causes disease via mutation-induced trypsinogen misfolding and endoplasmic reticulum (ER) stress. Here, we report a novel misfolding PRSS1 variant.

From Bystander-to-Upstander: A Novel Intervention Framework to Address Microaggressions in a Pediatric Academic Medical Center.

Microaggressions undermine health professionals' performance in patient care, research, and education. This study aimed to develop and evaluate an intervention addressing microaggressions in healthcare settings by empowering bystanders to act as upstanders across an academic medical center (AMC). This was achieved through an educational intervention that included a novel framework, didactics, video demonstrations, and practice with realistic scenarios.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part IV. Patient Important Outcomes.

Chronic graft versus host disease (cGVHD), occurs in approximately one in five pediatric allogeneic HCT patients and is a leading cause of late morbidity and mortality. Late effects of HCT may lead to long-term chronic health conditions and shortened life expectancy. In addition to direct physiological challenges from cGVHD and other late-effects, numerous patient-important outcomes impact the quality of life (QOL) of patients and their families.

- a large-scale dataset of 3D medical shapes for computer vision.

Objectives: The shape is commonly used to describe the objects. State-of-the-art algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from the growing popularity of ShapeNet (51,300 models) and Princeton ModelNet (127,915 models).

Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death.

Heart transplantation remains the ultimate treatment strategy for neonates and children with medically refractory end-stage heart failure and utilization of donors after circulatory death (DCD) can expand th donor pool. We have previously shown that mitochondrial transplantation preserves myocardial function and viability in neonatal swine DCD hearts to levels similar to that observed in donation after brain death (DBD). Herein, we sought to investigate the transcriptomic and proteomic pathways implicated in these phenotypic changes using ex situ perfused swine hearts.

#Skin-Lightening: A content analysis of the most popular videos promoting skin-lightening products on TikTok.

Highly visual and appearance-focused social media often exhibit appearance ideals that center around fairness and whiteness, resulting in the promotion of dangerous over-the-counter skin-lightening products to consumers to achieve such ideals. Our study aims to better understand the skin-lightening claims and products that TikTok users are exposed to on the platform. We conducted a cross-sectional content analysis to examine the top 100 most-viewed videos across the most popular skin-lightening hashtag (#skinlightening) through the TikTok website interface (N = 79) and generated descriptive statistics.

Cross-species analyses of thymic mimetic cells reveal evolutionarily ancient origins and both conserved and species-specific elements.

Thymic mimetic cells are molecular hybrids between medullary-thymic-epithelial cells (mTECs) and diverse peripheral cell types. They are involved in eliminating autoreactive T cells and can perform supplementary functions reflective of their peripheral-cell counterparts. Current knowledge about mimetic cells derives largely from mouse models.

The T cell receptor sequence influences the likelihood of T cell memory formation.

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells.

Psychosocial correlates of alcohol and substance use in college youth with type 1 diabetes.

Objective: Adolescents and young adults with chronic diseases face unique challenges during the college years and may consume alcohol and other substances to cope with stressors. This study aimed to assess the patterns of substance use and to determine psychosocial correlates of these behaviors among college youth with type 1 diabetes (T1D).

Methods: College youth with T1D were recruited via social media and direct outreach into a web-based study.

Family Genetic Risk Communication and Reverse Cascade Testing in the BabySeq Project.

Purpose: Genomic sequencing of newborns (NBSeq) can initiate disease surveillance and therapy for children, and may identify at-risk relatives through reverse cascade testing. We explored genetic risk communication and reverse cascade testing among families of newborns who underwent exome sequencing and had a risk for autosomal dominant disease identified.

Methods: We conducted semi-structured interviews with parents of newborns enrolled in the BabySeq Project who had a pathogenic or likely-pathogenic (P/LP) variant associated with an autosomal dominant (AD) childhood- and/or adult-onset disease returned.

Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.

Objectives: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modelling the natural history, and uncovering genotype-phenotype associations.

Methods: A cross-sectional analysis of 90 published and one novel case was performed, employing a Human Phenotype Ontology-based approach.

Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.

Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.

Aperiodic spectral slope tracks the effects of brain state on saliency responses in the human auditory cortex.

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics of activity in the neocortex, shifting the balance between low- and high-frequency fluctuations.

Emergency department utilization patterns for pediatric urinary stone patients in the United States.

Background: The prevalence of pediatric urolithiasis has increased rapidly, leading to more emergency department (ED) visits across the United States.

Objective: The purpose of this study was to determine emergency care practices for children and adolescents with urinary stones and characteristics associated with management.

Methods: We performed a cross-sectional study of the 2021 Nationwide Emergency Department Sample to identify pediatric patients (≤21 years) presenting to an ED in the United States with a primary diagnosis of urinary stone disease.

Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement.

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations.

More Than Body Parts: A New Ethos of Anatomy Education.

A new ethos of anatomy education goes beyond the learning of body parts in the traditional curriculum. In the traditional curriculum, the focus of only providing information on the structure of the human body left certain learning opportunities overlooked, marginalized, or dismissed as irrelevant; thus, opportunities to foster and shape professional attributes in health care learners were lost. Furthermore, changes in curricula structures and reductions in anatomy teaching hours have necessitated a transformation in how anatomy education is perceived and delivered.