Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.

Pannexin 1 (PANX1) forms cell-surface channels capable of releasing signaling metabolites for diverse patho-physiological processes. While inhibiting dysregulated PANX1 has been proposed as a therapeutic strategy for many pathological conditions, including inflammatory bowel disease (IBD), low efficacy, or poor specificity of classical PANX1 inhibitors introduces uncertainty for their applications in basic and translational research. Here, hit-to-lead optimization is performed and a naphthyridone, compound 12, is identified as a new PANX1 inhibitor with an IC of 0.

Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms.

CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity.

Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas (BCLs). CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell lymphoma (MCL), follicular lymphoma, and large BCL (LBCL) over the course of 5 years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients.

Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity.

Emerging and recurrent infectious diseases caused by human coronaviruses (HCoVs) continue to pose a significant threat to global public health security. In light of this ongoing threat, the development of a broad-spectrum drug to combat HCoVs is an urgently priority. Herein, we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment (SELEX).

Antithrombotic Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials.

Background:  We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan.

Material And Methods:  The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials.

Rivaroxaban for Prevention of Thrombotic Events, Hospitalization, and Death in Outpatients With COVID-19: A Randomized Clinical Trial.

Background: COVID-19 (coronavirus disease 2019) is associated with heightened risks of venous and arterial thrombosis and hospitalization due to respiratory failure. To assess whether prophylactic anticoagulation can safely reduce the frequency of venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor, we conducted the PREVENT-HD double-blind, placebo-controlled randomized trial (A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19] Infection).

Methods: PREVENT-HD was conducted between August 2020 and April 2022 at 14 US integrated health care delivery networks.

Evaluating brain white matter hyperintensity, IQ scores, and plasma neurofilament light chain concentration in early-treated patients with infantile-onset Pompe disease.

Purpose: The study aimed to describe central nervous system (CNS) progression in patients with infantile-onset Pompe disease (IOPD) and explore the potential clinical impact and predictors.

Methods: Patients with IOPD treated with enzyme replacement therapy were longitudinally followed with brain magnetic resonance imaging (MRI) and evaluation for IQ scores from 2004 to 2021. Investigation of CNS involvement focused on white matter (WM) abnormalities and was quantified using a scoring system for metachromatic leukodystrophy.

Difference between "Lung Age" and Real Age as a Novel Predictor of Postoperative Complications, Long-Term Survival for Patients with Esophageal Cancer after Minimally Invasive Esophagectomy.

Background: This study aimed to investigate whether the difference between "lung age" and real age (L-R) could be useful for the prediction of postoperative complications and long-term survival in patients with esophageal cancer followed by minimally invasive esophagectomy (MIE).

Methods: This retrospective cohort study included 625 consecutive patients who had undergone MIE. "Lung age" was determined by the calculation method proposed by the Japanese Respiratory Society.

Fibroblasts Drive Metabolic Reprogramming in Pacemaker Cardiomyocytes.

Background: The sino atrial node (SAN) is characterized by the microenvironment of pacemaker cardiomyocytes (PCs) encased with fibroblasts. An altered microenvironment leads to rhythm failure. Operable cell or tissue models are either generally lacking or difficult to handle.

CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial.

Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease.

Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.

CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma.

The prognosis of patients with large B-cell lymphoma (LBCL) that progresses after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first 3 consecutive patients with autologous CAR19-refractory LBCL who were treated with a single infusion of autologous 1 × 106 CAR+ T cells per kilogram targeting CD22 (CAR22) as part of a phase 1 dose-escalation study. CAR22 therapy was relatively well tolerated, without any observed nonhematologic adverse events higher than grade 2.

Black Dipole or White Dipole: Using Susceptibility Phase Imaging to Differentiate Cerebral Microbleeds from Intracranial Calcifications.

Background And Purpose: Phase imaging helps determine a lesion's susceptibility. However, various inhomogenous phase patterns could be observed in the serial phase images of a lesion and render image interpretation challenging. We evaluated the diagnostic accuracy of differentiating cerebral microbleeds and calcifications from phase patterns in axial locations.

Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation.

Reactive oxygen species (ROS) are believed to play a major role in the proinflammatory, M1-polarized form of neuroinflammation. However, it has been difficult to assess the role of ROS and their role in neuroinflammation in animal models of disease because of the absence of probes capable of measuring their presence with the functional imaging technique positron emission tomography (PET). This study describes the synthesis and in vivo evaluation of [F]ROStrace, a radiotracer for imaging superoxide in vivo with PET, in an LPS model of neuroinflammation.

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.

Longitudinal relationships among biomarkers for Alzheimer disease in the Adult Children Study.

Objective: To determine whether and how longitudinal rates of change in MRI volumetrics, CSF concentrations of Alzheimer-related proteins, molecular imaging of cerebral fibrillar amyloid with PET using the [(11)C] benzothiazole tracer, Pittsburgh compound B (PiB), and cognition were associated among asymptomatic middle-aged to older individuals.

Methods: Multivariate mixed models for repeated measures were used to assess the correlations on the rates of changes across markers.

Results: Among 209 asymptomatic middle-aged to older individuals longitudinally followed for up to 11 years (mean 6.

Simultaneous analysis of small organic acids and humic acids using high performance size exclusion chromatography.

An accurate and fast method for simultaneous determination of small organic acids and much larger humic acids was developed using high performance size exclusion chromatography. Two small organic acids, i.e.

Search for dark matter and large extra dimensions in pp collisions yielding a photon and missing transverse energy.

Results are presented from a search for new physics in the final state containing a photon (γ) and missing transverse energy (E[combininb /](T)). The data correspond to an integrated luminosity of 5.0 fb(-1) collected in pp collisions at √[s]=7 TeV by the CMS experiment.

Search for pair production of a heavy up-type quark decaying to a W boson and a b quark in the lepton + jets channel with the ATLAS detector.

A search is presented for production of a heavy up-type quark (t') together with its antiparticle, assuming subsequent decay to a W boson and a b quark, t't[over ¯]'→W(+)bW(-)b[over ¯]. The search is based on 1.04 fb(-1) of proton-proton collisions at √[s]=7 TeV collected by the ATLAS detector at the CERN Large Hadron Collider.

Search for gluinos in events with two same-sign leptons, jets, and missing transverse momentum with the ATLAS detector in pp collisions at sqrt[s]=7 TeV.

A search is presented for gluinos decaying via the supersymmetric partner of the top quark using events with two same-sign leptons, jets, and missing transverse momentum. The analysis is performed with 2.05  fb(-1) of integrated luminosity from pp collisions at sqrt[s]=7  TeV collected by the ATLAS detector at the LHC.

Search for tb resonances in proton-proton collisions at √s=7 TeV with the ATLAS detector.

This Letter presents a search for tb resonances in 1.04 fb(-1) of LHC proton-proton collision data collected by the ATLAS detector at a center-of-mass energy of 7 TeV. Events with a lepton, missing transverse momentum, and two jets are selected and the invariant mass of the corresponding final state is reconstructed.