Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study.

Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the -related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design: Prospective natural history study.

Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Flexible TiCT-Polyurethane Electrodes for Versatile Wearable Applications.

With the development of science and technology, wearable electronics are increasingly widely used in medical, environmental monitoring, and other fields. Thus, the demand for flexible electrodes is increasing. The two-dimensional material TiCT has attracted much attention in the manufacture of flexible electrodes due to its excellent mechanical and electrical properties.

Highly tough and ionic conductive starch/poly(vinyl alcohol) hydrogels based on a universal soaking strategy.

High-performance hydrogels with favorable mechanical strength, high modulus, sufficient ionic conductivity and freezing resistance have far-ranging applications in flexible electronic equipment. Nevertheless, it is challenging to combine admirable mechanical properties and high ionic conductivity into one hydrogel. Herein, a facile strategy was developed for the preparation of the hydrogel with excellent strength (1.

Cost-effectiveness of a Digital Health Intervention for Acute Myocardial Infarction Recovery.

Background: Acute myocardial infarction (AMI) is a common cause of hospital admissions, readmissions, and mortality worldwide. Digital health interventions (DHIs) that promote self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction may improve health outcomes in this population. The "Corrie" DHI consists of a smartphone application, smartwatch, and wireless blood pressure monitor to support medication tracking, education, vital signs monitoring, and care coordination.

Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

Background: Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice.

Methods: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion.

An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence.

Treatment-persistent residual tumors impede curative cancer therapy. To understand this cancer cell state we generated models of treatment persistence that simulate the residual tumors. We observe that treatment-persistent tumor cells in organoids, xenografts, and cancer patients adopt a distinct and reversible transcriptional program resembling that of embryonic diapause, a dormant stage of suspended development triggered by stress and associated with suppressed Myc activity and overall biosynthesis.

Tunable Electrical Properties of Embossed, Cellulose-Based Paper for Skin-like Sensing.

This article describes a process of fabricating highly porous paper from cellulosic fibers and carbon black (CB) with tunable conductivity. By embossing such paper, its porosity decreases while its conductivity increases. Tuning the porosity of composite paper alters the magnitude and trend of conductivity over a spectrum of concentrations of conductive particles.

Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.

Background: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes.

Methods: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF).

Cost-effectiveness analysis of multimodal prognostication in cardiac arrest with EEG monitoring.

Objective: To determine cost-effectiveness parameters for EEG monitoring in cardiac arrest prognostication.

Methods: We conducted a cost-effectiveness analysis to estimate the cost per quality-adjusted life-year (QALY) gained by adding continuous EEG monitoring to standard cardiac arrest prognostication using the American Academy of Neurology Practice Parameter (AANPP) decision algorithm: neurologic examination, somatosensory evoked potentials, and neuron-specific enolase. We explored lifetime cost-effectiveness in a closed system that incorporates revenue back into the medical system (return) from payers who survive a cardiac arrest with good outcome and contribute to the health system during the remaining years of life.

Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells.

Homeostatic and early-recruited CD101 eosinophils suppress endotoxin-induced acute lung injury.

Introduction: Acute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, although little is known about the functions of eosinophils in the pathogenesis of ALI. Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI.

Methods: Pulmonary eosinophils were identified by flow cytometry.

Mechanically strong and electrically conductive multilayer MXene nanocomposites.

Polymer nanocomposites offer the opportunity to bridge properties of nanomaterials to the macroscale. In this work, layer-by-layer (LbL) assembly is used to demonstrate nanocomposites of 2D titanium carbide nanosheets (MXene) and clay nanoplatelets (montmorillonite) to fabricate freestanding thin films with unique multifunctional properties. These thin films can be tuned by adjusting the thickness to exhibit a tensile strength of 138 MPa-225 MPa, EMI specific shielding effectiveness normalized to thickness and density up to 24 550 dB cm g, and sheet resistance from 855 Ω sq-3.

Corrie Health Digital Platform for Self-Management in Secondary Prevention After Acute Myocardial Infarction.

Background: Unplanned readmissions after hospitalization for acute myocardial infarction are among the leading causes of preventable morbidity, mortality, and healthcare costs. Digital health interventions could be an effective tool in promoting self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction. A digital health intervention developed at Johns Hopkins-the Corrie Health Digital Platform (Corrie)-includes the first cardiology Apple CareKit smartphone application, which is paired with an Apple Watch and iHealth Bluetooth-enabled blood pressure cuff.

Diagnostic Utility of Exome Sequencing for Kidney Disease.

Background: Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally.

Methods: We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings.

Simultaneously improving the mechanical and electrical properties of poly(vinyl alcohol) composites by high-quality graphitic nanoribbons.

Although carbon nanotubes (CNTs) have shown great potential for enhancing the performance of polymer matrices, their reinforcement role still needs to be further improved. Here we implement a structural modification of multi-walled CNTs (MWCNTs) to fully utilize their fascinating mechanical and electrical properties via longitudinal splitting of MWCNTs into graphitic nanoribbons (GNRs). This nanofiller design strategy is advantageous for surface functionalization, strong interface adhesion as well as boosting the interfacial contact area without losing the intrinsic graphitic structure.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

Background And Purpose: Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes.

Methods: We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression.