MEN1 mutations mediate clinical resistance to menin inhibition.

Chromatin-binding proteins are critical regulators of cell state in haematopoiesis. Acute leukaemias driven by rearrangement of the mixed lineage leukaemia 1 gene (KMT2Ar) or mutation of the nucleophosmin gene (NPM1) require the chromatin adapter protein menin, encoded by the MEN1 gene, to sustain aberrant leukaemogenic gene expression programs. In a phase 1 first-in-human clinical trial, the menin inhibitor revumenib, which is designed to disrupt the menin-MLL1 interaction, induced clinical responses in patients with leukaemia with KMT2Ar or mutated NPM1 (ref.

Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation.

Background: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare, fatal, premature aging disease caused by a toxic protein called progerin. Circulating progerin has not been previously detected, precluding research using readily available biological samples. This study aimed to develop a plasma progerin assay to evaluate progerin's quantity, response to progerin-targeted therapy, and relationship to patient survival.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.

Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age.

In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well-studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months.

Genetically Triggered Thoracic Aortic Disease: Who Should be Tested?

Up to 25% of patients with thoracic aortic disease have an underlying Mendelian pathogenic variant. This is a heterogeneous group of disorders known as heritable thoracic aortic diseases (HTAD). Diagnosing associated pathogenic gene variants and syndromes is critical, as the underlying genetics have an implication in medical management, surveillance, thresholds for surgical intervention, surgical risk, pregnancy risk, and risk of inheritance by the offspring.

Outcome after surgical treatment of venous malformations of the hand in childhood.

Objective: Surgical treatment of venous malformations (VMs) of the hand is challenging. The hand's small functional units, dense innervation, and terminal vasculature can be easily compromised during invasive interventions like surgery or sclerotherapy, leading to an increased risk of functional impairment, cosmetic consequences, and negative psychological effects.

Methods: We have conducted a retrospective review of all surgically treated patients diagnosed with VMs of the hand between 2000 and 2019 and evaluated their symptoms, diagnostic investigations, complications, and recurrences.

Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus.

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH.

Barriers to recovery for medical professionals: Assessing financial support through a survey of Physician Health Programs.

Background And Objectives: There is increasing focus on physician burnout, psychiatric problems, and substance use disorders. Costs of recovery for physicians enrolled in Physician Health Programs (PHPs) remain unexamined with little known regarding funding resources. We sought to elucidate perceived costs of recovery from impairing conditions and highlight resources for financial strain.

Risk Ractors for Strabismus Surgery after Pediatric Cataract Surgery in the United States.

Purpose: To determine the cumulative incidence of strabismus surgery after pediatric cataract surgery and identify the associated risk factors.

Design: US population-based insurance claims retrospective cohort study.

Participants: Patients ≤ 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics Data Mart (2003-2021) and IBM MarketScan (2007-2016).

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence.

Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleiotropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts.

Socioeconomic determinants of asthma health.

Purpose Of Review: The current review provides an assessment of the recent pediatric literature evaluating socioeconomic drivers of asthma incidence and morbidity. The review addresses the specific social determinants of health related to housing, indoor and outdoor environmental exposures, healthcare access and quality, and the impact of systematic racism.

Recent Findings: Many social risk factors are associated with adverse asthma outcomes.

Helicobacter pylori Seropositivity, ABO Blood Type, and Pancreatic Cancer Risk From 5 Prospective Cohorts.

Background: Helicobacter pylori infection may be a risk factor for pancreatic cancer, particularly infection by strains without the cytotoxin-associated gene A (CagA) virulence factor. Non-O blood type is a known risk factor for pancreatic cancer, and H. pylori gastric colonization occurs largely from bacterial adhesins binding to blood group antigens on gastric mucosa.

An effective rehydrating formula for reconditioning dried, irreplaceable heart specimens for teaching.

Formalin-fixed whole heart specimens are essential for studying the anatomy of congenital heart defects. Because of the improvement in diagnostic imaging and treatment, and cultural transition, heart specimens with congenital heart defects have become more and more rare and irreplaceable but are at risk of accidental deterioration through dehydration during long-term storage. In this article, we share our experience in reconditioning our inadvertently dehydrated heart specimens using a simple Formol-Glycerol solution that allowed for rehydration and recovery of such specimens.

Subcutaneous Granuloma Annulare vs. Subcutaneous Vascular Malformations in Children: A Diagnostic Challenge.

Objectives: There are various subcutaneous lesions in children and often there is difficulty in obtaining an accurate diagnosis by non-invasive diagnostic procedures. Subcutaneous granuloma annulare (SGA) is a rare granulomatous disease that, even after imaging, is often mistaken for a low-flow subcutaneous vascular malformation (SVM). This study aimed to accurately identify clinical and imaging clues to distinguish SGA from low-flow SVM.

From tensegrity to human organs-on-chips: implications for mechanobiology and mechanotherapeutics.

The field of mechanobiology, which focuses on the key role that physical forces play in control of biological systems, has grown enormously over the past few decades. Here, I provide a brief personal perspective on the development of the tensegrity theory that contributed to the emergence of the mechanobiology field, the key role that crossing disciplines has played in its development, and how it has matured over time. I also describe how pursuing questions relating to mechanochemical transduction and mechanoregulation can lead to the creation of novel technologies and open paths for development of new therapeutic strategies for a broad range of diseases and disorders.

Integration of structural MRI and epigenetic analyses hint at linked cellular defects of the subventricular zone and insular cortex in autism: Findings from a case study.

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, communication and repetitive, restrictive behaviors, features supported by cortical activity. Given the importance of the subventricular zone (SVZ) of the lateral ventrical to cortical development, we compared molecular, cellular, and structural differences in the SVZ and linked cortical regions in specimens of ASD cases and sex and age-matched unaffected brain.

Methods: We used magnetic resonance imaging (MRI) and diffusion tractography on postmortem brain samples, which we further analyzed by Whole Genome Bisulfite Sequencing (WGBS), Flow Cytometry, and RT qPCR.

Evaluating criminal justice reform during COVID-19: The need for a novel sentiment analysis package.

The health and safety of incarcerated persons and correctional personnel have been prominent in the U.S. news media discourse during the COVID-19 pandemic.

Liver transplantation for alpha 1 antitrypsin deficiency (A1ATD) using a heterozygous donor: Outcomes and review of the literature.

Introduction: Alpha 1 antitrypsin deficiency (A1ATD) accounts for 21% of all pediatric liver transplants due to metabolic disease in the western world. Donor heterozygosity has been evaluated in adults but not to a recipient with A1ATD.

Methods: The data of patient were retrospectively analyzed and a literature review performed.

Variants in DTNA cause a mild, dominantly inherited muscular dystrophy.

DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype, but variants in DTNA have not previously been associated with human skeletal muscle disease. We present 12 individuals from four unrelated families with two different monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin.

Sensitivity of Rapid Antigen Tests Against SARS-CoV-2 Omicron and Delta Variants.

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples.

Impaired protein hydroxylase activity causes replication stress and developmental abnormalities in humans.

Although protein hydroxylation is a relatively poorly characterized posttranslational modification, it has received significant recent attention following seminal work uncovering its role in oxygen sensing and hypoxia biology. Although the fundamental importance of protein hydroxylases in biology is becoming clear, the biochemical targets and cellular functions often remain enigmatic. JMJD5 is a "JmjC-only" protein hydroxylase that is essential for murine embryonic development and viability.