Inspiring Student Entrepreneurship and Innovation.

Background While student entrepreneurial interest is significantly correlated with the intention to pursue innovative healthcare ventures, many medical schools lack formal programs to nurture entrepreneurial skills. To investigate student interest in entrepreneurship and their experiences with medical innovation, the Biomedical Entrepreneurship Network at Rutgers Robert Wood Johnson Medical School engaged students nationally in a Healthcare Innovation Summit featuring a keynote address, pitch competition, and interactive workshops with accomplished innovators. Methods A Rutgers electronic Institutional Review Board (eIRB)-approved survey was disseminated to student attendees at the summit, with questions categorized into four themes: interest/motivation, barriers to ideation and execution, support for innovation, and confidence in entrepreneurial pursuits.

Providers' Experiences Discussing Care for Patients with Kidney Failure Who Forgo KRT: A National Qualitative Study.

Background: Many nephrology providers express difficulty in discussing care options for patients who forgo KRT, which hampers their ability to help patients make decisions about their current and future treatment of kidney disease.

Methods: We conducted a qualitative study using interviews with a national sample of nephrology providers (i.e.

How Super Is Supertrack? Expediting Care of Fast-track Patients through a Pediatric Emergency Department.

Background: Fast-track models decrease patient crowding in emergency departments (EDs) by redirecting low-acuity patients to an expedited care pathway. In 2016, this institution's pediatric ED created a fast-track pathway for patients evaluated in a rapid assessment triage area who needed further management in the primary ED. This "Supertrack" designation was intended for patients requiring up to 1 hour of additional care, though means of ensuring these patients were discharged within their anticipated timeframe were lacking.

Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development.

The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development.

A patient-enriched MEIS1 coding variant causes a restless legs syndrome-like phenotype in mice.

Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable or unpleasant sensations in the legs during rest periods. To relieve these sensations, patients move their legs, causing sleep disruption. While the pathogenesis of RLS has yet to be resolved, there is a strong genetic association with the MEIS1 gene.

Best Case/Worst Case: protocol for a multisite randomised clinical trial of a scenario planning intervention for patients with kidney failure.

Introduction: Given the burdens of treatment and poor prognosis, older adults with kidney failure would benefit from improved decision making and palliative care to clarify goals, address symptoms, and reduce unwanted procedures. Best Case/Worst Case (BC/WC) is a communication tool that uses scenario planning to support patients' decision making. This article describes the protocol for a multisite, cluster randomised trial to test the effect of training nephrologists to use the BC/WC communication tool on patient receipt of palliative care, and quality of life and communication.

Discovery of mobocertinib, a new irreversible tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer harboring EGFR exon 20 insertion mutations.

Epidermal growth factor receptor (EGFR) is essential for normal cellular functions. Mutations of EGFR's kinase domain can cause dysregulation leading to non-small cell lung cancer (NSCLC). Exon 20 insertion (ex20ins) mutations in EGFR are one of the leading contributors to oncogenesis and confer insensitivity to most available therapeutics.

Use of e-triggers to identify diagnostic errors in the paediatric ED.

Background: Diagnostic errors (DxEs) are an understudied source of patient harm in children rarely captured in current adverse event reporting systems. Applying electronic triggers (e-triggers) to electronic health records shows promise in identifying DxEs but has not been used in the emergency department (ED) setting.

Objectives: To assess the performance of an e-trigger and subsequent manual screening for identifying probable DxEs among children with unplanned admission following a prior ED visit and to compare performance to existing incident reporting systems.

Collagen VI Regulates Motor Circuit Plasticity and Motor Performance by Cannabinoid Modulation.

Collagen VI is a key component of muscle basement membranes, and genetic variants can cause monogenic muscular dystrophies. Conversely, human genetic studies recently implicated collagen VI in central nervous system function, with variants causing the movement disorder dystonia. To elucidate the neurophysiological role of collagen VI, we generated mice with a truncation of the dystonia-related collagen α3 VI (COL6A3) C-terminal domain (CTD).

Intronic elements associated with insomnia and restless legs syndrome exhibit cell-type-specific epigenetic features contributing to MEIS1 regulation.

A highly evolutionarily conserved myeloid ecotropic viral integration site 1 (MEIS1) intronic region is strongly associated with restless legs syndrome (RLS) and insomnia. To understand its regulatory function, we dissected the region by analyzing chromatin accessibility, enhancer-promoter contacts, DNA methylation and expression quantitative trait locus (eQTLs) in different human neural cell types and tissues. We observed specific activity with respect to cell type and developmental maturation, indicating a prominent role for distinct highly conserved intronic elements in forebrain inhibitory neuron differentiation.

Proteomic profiling dataset of chemical perturbations in multiple biological backgrounds.

While gene expression profiling has traditionally been the method of choice for large-scale perturbational profiling studies, proteomics has emerged as an effective tool in this context for directly monitoring cellular responses to perturbations. We previously reported a pilot library containing 3400 profiles of multiple perturbations across diverse cellular backgrounds in the reduced-representation phosphoproteome (P100) and chromatin space (Global Chromatin Profiling, GCP). Here, we expand our original dataset to include profiles from a new set of cardiotoxic compounds and from astrocytes, an additional neural cell model, totaling 5300 proteomic signatures.

Investigation of dopaminergic signalling in Meis homeobox 1 (Meis1) deficient mice as an animal model of restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological disorder in which sensorimotor symptoms lead to sleep disturbances with substantial impact on life quality. RLS is caused by a combination of genetic and environmental factors, and Meis homeobox 1 (MEIS1) was identified as the main genetic risk factor. The efficacy of dopaminergic agonists, including dopamine D receptor (DRD2) agonists, for treating RLS led to the hypothesis of dopaminergic impairment.

Decreased sensitivity to the anorectic effects of leptin in mice that lack a Pomc-specific neural enhancer.

Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been limited. Recently, we have identified two partially redundant enhancers, nPE1 and nPE2, that drive proopiomelanocortin gene expression in the hypothalamus.

Author Correction: Cas9 activates the p53 pathway and selects for p53-inactivating mutations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cas9 activates the p53 pathway and selects for p53-inactivating mutations.

Cas9 is commonly introduced into cell lines to enable CRISPR-Cas9-mediated genome editing. Here, we studied the genetic and transcriptional consequences of Cas9 expression itself. Gene expression profiling of 165 pairs of human cancer cell lines and their Cas9-expressing derivatives revealed upregulation of the p53 pathway upon introduction of Cas9, specifically in wild-type TP53 (TP53-WT) cell lines.

Creating a Palliative Care Inpatient Response Plan for COVID-19-The UW Medicine Experience.

Context: The coronavirus disease 2019 (COVID-19) pandemic is stressing health care systems throughout the world. Significant numbers of patients are being admitted to the hospital with severe illness, often in the setting of advanced age and underlying comorbidities. Therefore, palliative care is an important part of the response to this pandemic.

Update on KMT2B-Related Dystonia.

Purpose Of Review: To summarize the molecular and clinical findings of KMT2B-related dystonia (DYT-KMT2B), a newly identified genetic dystonia syndrome.

Recent Findings: Since first described in 2016, 66 different KMT2B-affecting variants, encompassing a set of frameshift, nonsense, splice-site, missense, and deletion mutations, have been reported in 76 patients. Most mutations are de novo and expected to mediate epigenetic dysregulation by inducing KMT2B haploinsufficiency.

Role of MEIS1 in restless legs syndrome: From GWAS to functional studies in mice.

MEIS1 is a transcription factor playing an important role in the development of several organs, including central and peripheral nervous systems. A genetic locus spanning the MEIS1 coding region has been associated with the risk of RLS in genome-wide association studies, with increasing evidence that MEIS1 is the causal RLS gene. The RLS-linked genetic signal has been mapped to an intronic regulatory element within MEIS1.

Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.

Purpose: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a CH domain-containing transcription factor.

Methods: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform.

A Conceptual Framework of Palliative Care across the Continuum of Advanced Kidney Disease.

Kidney palliative care is a growing discipline within nephrology. Kidney palliative care specifically addresses the stress and burden of advanced kidney disease through the provision of expert symptom management, caregiver support, and advance care planning with the goal of optimizing quality of life for patients and families. The integration of palliative care principles is necessary to address the multidimensional impact of advanced kidney disease on patients.

Muscle-induced loading as an important source of variation in craniofacial skeletal shape.

The shape of the craniofacial skeleton is constantly changing through ontogeny and reflects a balance between developmental patterning and mechanical-load-induced remodeling. Muscles are a major contributor to producing the mechanical environment that is crucial for "normal" skull development. Here, we use an F hybrid population of Lake Malawi cichlids to characterize the strength and types of associations between craniofacial bones and muscles.

A unique de novo gain-of-function variant in associated with intellectual disability and hyperkinetic movement disorder.

Calcium/calmodulin-dependent protein kinases (CaMKs) are key mediators of calcium signaling and underpin neuronal health. Although widely studied, the contribution of CaMKs to Mendelian disease is rather enigmatic. Here, we describe an unusual neurodevelopmental phenotype, characterized by milestone delay, intellectual disability, autism, ataxia, and mixed hyperkinetic movement disorder including severe generalized dystonia, in a proband who remained etiologically undiagnosed despite exhaustive testing.