SLC16A8 is a causal contributor to age-related macular degeneration risk.

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter.

A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia.

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells.

Methods: We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP.

A Modular Communicative Leadless Pacing-Defibrillator System.

Background: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown.

Methods: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system.

A family of oxychloride amorphous solid electrolytes for long-cycling all-solid-state lithium batteries.

Solid electrolyte is vital to ensure all-solid-state batteries with improved safety, long cyclability, and feasibility at different temperatures. Herein, we report a new family of amorphous solid electrolytes, xLiO-MCl (M = Ta or Hf, 0.8 ≤ x ≤ 2, y = 5 or 4).

Phase 1b trial of anti-EGFR antibody JMT101 and Osimertinib in EGFR exon 20 insertion-positive non-small-cell lung cancer.

EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is an uncommon disease with limited therapeutic options and dismal prognosis. Here we report the activity, tolerability, potential mechanisms of response and resistance for dual targeting EGFR 20ins with JMT101 (anti-EGFR monoclonal antibody) plus osimertinib from preclinical models and an open label, multi-center phase 1b trial (NCT04448379). Primary endpoint of the trial is tolerability.

The mA reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia.

N-Methyladenosine (mA) modification and its modulators play critical roles and show promise as therapeutic targets in human cancers, including acute myeloid leukemia (AML). IGF2BP2 was recently reported as an mA binding protein that enhances mRNA stability and translation. However, its function in AML remains largely elusive.

Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy.

Background: Transcriptional reconfiguration is central to heart failure, the most common cause of which is dilated cardiomyopathy (DCM). The effect of 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive.

Methods: We generated a compendium of 3-dimensional epigenome and transcriptome maps from 101 biobanked human DCM and nonfailing heart tissues through highly integrative chromatin immunoprecipitation (H3K27ac [acetylation of lysine 27 on histone H3]), in situ high-throughput chromosome conformation capture, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin using sequencing, and RNA sequencing.

Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro.

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection.

Photo-Mediated Ultrasound Therapy for the Treatment of Corneal Neovascularization in Rabbit Eyes.

Purpose: Corneal neovascularization (CNV) is the invasion of new blood vessels into the avascular cornea, leading to reduced corneal transparency and visual acuity, impaired vision, and even blindness. Current treatment options for CNV are limited. We developed a novel treatment method, termed photo-mediated ultrasound therapy (PUT), that combines laser and ultrasound, and we tested its feasibility for treating CNV in a rabbit model.

Safety of Aspirin Use in Patients With Stroke and Small Unruptured Aneurysms.

Objective: We initiated a multicenter, prospective cohort study to test the hypothesis that aspirin is safe for patients with ischemic cerebrovascular disease (ICVD) harboring unruptured intracranial aneurysms (UIAs) <7 mm.

Methods: This prospective, multicenter cohort study consecutively enrolled 1,866 eligible patients with ICVD harboring UIAs <7 mm in diameter from 4 hospitals between January 2016 and August 2019. Baseline and follow-up patient information, including the use of aspirin, was recorded.

Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study.

Background And Purpose: The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm.

Methods: This prospective cohort study consecutively enrolled patients with UIAs <7 mm with ischemic cerebrovascular disease between January 2016 and December 2019.

The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance, by C.-Q. Liang, Y.

Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury.

The article "Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury, by Y.-M. Yang, Y.

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.

Rationale: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.

Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.

Methods And Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.

ecTMB: a robust method to estimate and classify tumor mutational burden.

Tumor Mutational Burden (TMB) is a measure of the abundance of somatic mutations in a tumor, which has been shown to be an emerging biomarker for both anti-PD-(L)1 treatment and prognosis; however, multiple challenges still hinder the adoption of TMB as a biomarker. The key challenges are the inconsistency of tumor mutational burden measurement among assays and the lack of a meaningful threshold for TMB classification. Here we describe a new method, ecTMB (Estimation and Classification of TMB), which uses an explicit background mutation model to predict TMB robustly and to classify samples into biologically meaningful subtypes defined by tumor mutational burden.

Hierarchically Porous Co/Co M (M = P, N) as an Efficient Mott-Schottky Electrocatalyst for Oxygen Evolution in Rechargeable Zn-Air Batteries.

Tailoring composition and morphology of electrocatalysts is of great importance in improving their catalytic performance. Herein, a salt-templated strategy is proposed to construct novel multicomponent Co/Co M (M = P, N) hybrids with outstanding electrocatalytic performance for the oxygen evolution reaction (OER). The obtained Co/Co M hybrids present porous sheet-like architecture consisting of many hierarchical secondary building-units.

Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine.

Objective: To identify a plasma metabolomic biomarker signature for migraine.

Methods: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g.

Optogenetic Inhibition of Striatal GABAergic Neuronal Activity Improves Outcomes After Ischemic Brain Injury.

Background And Purpose: Striatal GABAergic neuron is known as a key regulator in adult neurogenesis. However, the specific role of striatal GABAergic neuronal activity in the promotion of neurological recovery after ischemic stroke remains unknown. Here, we used optogenetic approach to investigate these effects and mechanism.

Outcomes of Transvenous Lead Extraction for Cardiovascular Implantable Electronic Device Infections in Patients With Prosthetic Heart Valves.

Background: Lead-related or valve-related endocarditis can complicate cardiovascular implantable electronic device (CIED) infection in patients with both CIED and prosthetic valves. The objective of this study was to determine the outcomes of transvenous lead extraction for CIED infection in patients with prosthetic valves.

Methods And Results: We retrospectively screened 794 transvenous lead extraction procedures, between September 1, 2001 and August 31, 2012, at Mayo Clinic to identify patients with prosthetic valves who underwent lead extraction for infection.

Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation.

Objective: Hyperlipidemia-induced endothelial cell (EC) activation is considered as an initial event responsible for monocyte recruitment in atherogenesis. However, it remains poorly defined what is the mechanism underlying hyperlipidemia-induced EC activation. Here, we tested a novel hypothesis that mitochondrial reactive oxygen species (mtROS) serve as signaling mediators for EC activation in early atherosclerosis.

The effects of starvation on fast-start escape and constant acceleration swimming performance in rose bitterling (Rhodeus ocellatus) at two acclimation temperatures.

To investigate the effects of starvation and acclimation temperature on the escape ability of juvenile rose bitterling (Rhodeus ocellatus), we measured the fast-start escape and constant acceleration swimming performance of fish fasted for 0 (control), 1 and 2 weeks and half-lethal periods (6 or 4 weeks) at two temperatures (15 and 25 °C). Fish acclimated at a high temperature exhibited shorter response latency (R), higher maximum linear velocity (V max) and longer escape distance during escape movement (D 120ms) than those at the low temperature. Starvation resulted in a significant decrease in V max and D 120ms at either low or high temperature and a significant increase in R at only the high temperature in the half-lethal period groups (P < 0.