Long-Term Safety and Immunogenicity of AZD1222 (ChAdOx1 nCoV-19): 2-Year Follow-Up from a Phase 3 Study.

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity.

Aficamten is a small-molecule cardiac myosin inhibitor designed to treat hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited disease of the sarcomere resulting in excessive cardiac contractility. The first-in-class cardiac myosin inhibitor, mavacamten, improves symptoms in obstructive HCM. Here we present aficamten, a selective small-molecule inhibitor of cardiac myosin that diminishes ATPase activity by strongly slowing phosphate release, stabilizing a weak actin-binding state.

Reevaluating the role of platinum-based chemotherapy in the evolving treatment landscape for patients with advanced urothelial carcinoma.

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial.

Update on Low-Renin Hypertension: Current Understanding and Future Direction.

Low-renin hypertension is common and affects 1 in 4 people with hypertension. Understanding the different causes and management of low-renin hypertension is becoming increasingly relevant as renin measurements are more widely ordered in clinical practice. Importantly, many people with low-renin hypertension do not fit traditional definitions of known causes, and the approach to management of these people is not unclear.

Phenylboronic Acid-Functionalized Ratiometric Surface-Enhanced Raman Scattering Nanoprobe for Selective Tracking of Hg and CHHg in Aqueous Media and Living Cells.

The development of appropriate molecular tools to monitor different mercury speciation, especially CHHg, in living organisms is attractive because its persistent accumulation and toxicity are very harmful to human health. Herein, we develop a novel activity-based ratiometric SERS nanoprobe to selectively monitor Hg and CHHg in aqueous media and in vivo. In this nanoprobe, a new bifunctional Raman probe bis-s-s'-[(s)-(4-(ethylcarbamoyl)phenyl)boronic acid] (b-(s)-EPBA) was synthesized and immobilized on the surface of gold nanoparticles via a Au-S bond, in which the phenylboronic acid group was employed as the recognition unit for Hg and CHHg based on the Hg-promoted transmetalation reaction.

Co-targeting SOS1 enhances the antitumor effects of KRAS inhibitors by addressing intrinsic and acquired resistance.

Combination approaches are needed to strengthen and extend the clinical response to KRAS inhibitors (KRASi). Here, we assessed the antitumor responses of KRAS mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRAS inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling.

Association Between Greater Social Vulnerability and Delayed Glaucoma Surgery.

Purpose: Timing of surgical intervention in glaucoma is crucial to preserving sight. While ocular characteristics that increase surgical risk are known, the impact of neighborhood-level social risk factors such as the Social Vulnerability Index (SVI) and Area Deprivation Index (ADI) on time to glaucoma surgery is unknown. The objective of this study was to evaluate the association between SVI or ADI scores and the timing of glaucoma surgical intervention.

Utility of Serial Microbial Cell-free DNA Sequencing for Inpatient and Outpatient Pathogen Surveillance Among Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Background: This study characterizes the clinical utility and validity of the Karius test (KT), a plasma microbial cell-free DNA sequencing platform, as an infection surveillance tool among hematopoietic stem cell transplant (HCT) recipients, including monitoring for cytomegalovirus (CMV) and detecting infections relative to standard microbiologic testing (SMT).

Methods: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT.

Costs and Timing of Surgery in the Management of Meniscal Tears.

Background: Treatment strategies for meniscal tears range from nonoperative management to surgical intervention. However, national trends in cost-related outcomes and patient factors related to the failure of nonoperative management remain poorly understood.

Purpose: To describe the costs associated with nonoperative versus operative management of meniscal tears in the 2 years after diagnosis and examine the relationship between patient characteristics and timing of surgery.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

Contrast Sensitivity and Low Contrast Visual Acuity in Children With Normal Visual Acuity.

Purpose: To measure and report the distribution of distance and near contrast sensitivity (CS) and low contrast visual acuity (LCVA) at 5% and 2.5% contrast in children aged 5-15 years with normal visual acuity (VA).

Design: Prospective, cross-sectional study.

Easy Access to Bright Oxygen Defects in Biocompatible Single-Walled Carbon Nanotubes via a Fenton-like Reaction.

The covalent functionalization of single-walled carbon nanotubes (SWNTs) with luminescent oxygen defects increases their brightness and enables their application as optical biosensors or fluorescent probes for in vivo imaging in the second-biological window (NIR-II). However, obtaining luminescent defects with high brightness is challenging with the current functionalization methods due to a restricted window of reaction conditions or the necessity for controlled irradiation with ultraviolet light. Here, we report a method for introducing luminescent oxygen defects via a Fenton-like reaction that uses benign and inexpensive chemicals without light irradiation.

Direct Comparison of Methods to Differentiate Wide Complex Tachycardias: Novel Automated Algorithms Versus Manual ECG Interpretation Approaches.

Background: Differentiating wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia via 12-lead ECG interpretation is a crucial but difficult task. Automated algorithms show promise as alternatives to manual ECG interpretation, but direct comparison of their diagnostic performance has not been undertaken.

Methods: Two electrophysiologists applied 3 manual WCT differentiation approaches (ie, Brugada, Vereckei aVR, and VT score).

Radioprotective effect of the anti-diabetic drug metformin.

Metformin is a biguanide currently used in the treatment of diabetes mellitus type 2. Besides its anti-glycemic effects, metformin has been reported to induce different cellular pleiotropic effects, depending on concentration and time of treatment. Here we report one administration of metformin (0.

Consensus Statement on the Management of Nonthrombotic Iliac Vein Lesions From the VIVA Foundation, the American Venous Forum, and the American Vein and Lymphatic Society.

A nonthrombotic iliac vein lesion is defined as the extrinsic compression of the iliac vein. Symptoms of lower extremity chronic venous insufficiency or pelvic venous disease can develop secondary to nonthrombotic iliac vein lesion. Anatomic compression has been observed in both symptomatic and asymptomatic patients.

Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

Introduction: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 298 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023.

Hepatitis B Virus in People who Inject Drugs and Men who Have Sex With Men With HIV in India: A Cross-sectional Study.

Background: People with HIV (PWH) who are coinfected with hepatitis B virus (HBV) have a higher risk of mortality compared with PWH alone. Populations such as people who inject drugs (PWID) and men who have sex with men (MSM) are particularly at high risk for HBV acquisition; yet, limited epidemiological data from these populations exist on HBV prevalence from low- and middle-income country settings (LMICs).

Methods: We characterized the prevalence and correlates of HBV serological markers in a sample of PWID and MSM with HIV recruited across 15 Indian cities using hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs).

Low Temperature NO and CO Conversion with a Mechanistic Approach on Ru-Composed Cerium Oxide.

Catalytic reduction of NO with CO at a lower temperature is an extremely challenging task, thus requiring conceivable surfaces to overcome such issues. Ru-substituted CeO catalysts prepared via the solution combustion method were employed in CO oxidation and NO-CO conversion studies. The characterization for material formation and surface structure was carried out through XRD, SEM, TEM, and BET surface area.

Semivortex solitons and their excited states in spin-orbit-coupled binary bosonic condensates.

It is known that two-dimensional two-component fundamental solitons of the semivortex (SV) type, with vorticities (s_{+},s_{-})=(0,1) in their components, are stable ground states (GSs) in the spin-orbit-coupled (SOC) binary Bose-Einstein condensate with the contact self-attraction acting in both components, in spite of the possibility of the critical collapse in the system. However, excited states (ESs) of the SV solitons, with the vorticity set (s_{+},s_{-})=(S_{+},S_{+}+1) and S_{+}=1,2,3,..

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies.

Monitoring of terrestrial gamma dose rate from the Kumaun Himalayan region of the Bageshwar district in Uttarakhand, India.

The present study is carried out in 42 sampling sites for the measurement of background gamma dose rate in six tehsils of the Bageshwar district that comes under the Kumaun Himalaya, Uttarakhand. The annual effective dose in the pre-monsoon and post-monsoon seasons was estimated from the measured values of the Gamma dose rate. It is found that the minimum and maximum values ranged between 0.

Time to Total Knee Arthroplasty (TKA) Post Intra-Articular Injection.

Disease-modifying treatments are not currently developed to target the underlying causes of knee osteoarthritis (KOA). Corticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP) intra-articular (IA) injections are commonly used for patients that do not respond to non-pharmacological treatments, oral nonsteroidal anti-inflammatory, or pain medications to address solely KOA symptoms. Utilizing TKA as an endpoint in the KOA disease progression provides a basis to determine efficacy of this treatment pathway.

Impact of Social Vulnerability Index on the Development of Severe Visual Impairment or Blindness From Glaucoma.

Purpose: To evaluate whether geocoded social risk factor data predict the development of severe visual impairment or blindness due to glaucoma during follow-up using a large electronic health record (EHR) database.

Design: Cohort study.

Methods: Patients diagnosed with open-angle glaucoma (OAG) at a tertiary care institution.

PI3K Inhibitors in Hematology: When One Door Closes….

The PI3K signaling pathway regulates key cellular processes and is one of the most aberrantly activated pathways in cancer. The class I PI3K catalytic subunits p110γ and p110δ are highly enriched in leukocytes, providing an additional rationale for targeting these PI3Ks in hematologic malignancies. In 2014, the PI3Kδ inhibitor idelalisib was the first of four PI3K inhibitors (PI3Ki) to receive regulatory approval for relapsed B-cell malignancies.