Impact of race and ethnicity on glaucoma progression detection by perimetry and optical coherence tomography.

This study assessed the impact of race and ethnicity on longitudinal test variability and time to detect glaucoma progression using standard automated perimetry (SAP) and optical coherence tomography (OCT). The sample consisted of 47,003 SAP tests from 5402 eyes and 25,480 OCT tests from 4125 eyes, with 20% of participants self-identifying as Black or African American and 80% as White; 29% as Hispanic or Latino and 71% as Not Hispanic or Latino. Variability was measured using standard deviations of residuals from linear regression models for SAP mean deviation (MD) and OCT retinal nerve fiber layer (RNFL) thickness over time.

Minimalist Natural ORPphilin Macarangin B Delineates OSBP Biological Function.

OSBP ligands from the ORPphilin family are chemically complex natural products with promising anticancer properties. Here, we describe macarangin B, a natural racemic flavonoid selective for OSBP, which stands out from other ORPphilins due to its structural simplicity and distinct biological activity. Using a bioinspired strategy, we synthesized both (,,) and (,,)-macarangin B enantiomers, enabling us to study their interaction with OSBP based on their unique optical properties.

Intranasal influenza-vectored vaccine expressing pneumococcal surface protein A protects against Influenza and Streptococcus pneumoniae infections.

Streptococcus pneumoniae and influenza A virus (IAV) are significant agents of pneumonia cases and severe respiratory infections globally. Secondary bacterial infections, particularly by Streptococcus pneumoniae, are common in IAV-infected individuals, leading to critical outcomes. Despite reducing mortality, pneumococcal vaccines have high production costs and are serotype specific.

Sensing Hachimoji DNA Bases with Janus MoSH Monolayer Nanodevice: Insights from Density Functional Theory (DFT) and Non-Equilibrium Green's Function Analysis.

Detection of nucleobases is of great significance in DNA sequencing, which is one of the main goals of the Human Genome Project. The synthesis of Hachimoji DNA, an artificial genetic system with eight nucleotide bases, has induced a transformative shift in genetic research and biosensing. Here, we present a systematic investigation of the adsorption behavior and electronic transport properties of natural and modified DNA bases on a Janus molybdenum sulfur hydride (MoSH) monolayer using density functional theory (DFT) and nonequilibrium Green's function (NEGF) methods.

Sulfur-functionalized sawdust biochar for enhanced cadmium adsorption and environmental remediation: A multidisciplinary approach and density functional theory insights.

Pristine biochar typically exhibits limited capacity for heavy metal adsorption due to its inadequate pore development and insufficient surface functionality. This study introduces an innovative chemical strategy to enhance the surface of sawdust biochar with sulfur-based functional groups (C=S, C-S, S-S, S, S-H, -SO, -SO) to significantly improve cadmium (Cd) adsorption. Sulfur-doping using HSO, NaS, and NaSO markedly increased the sulfur content from 0.

Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats.

Allogeneic modified bone marrow-derived human mesenchymal stromal/stem cells (hMSC-SB623 cells) are in clinical development for the treatment of chronic motor deficits after traumatic brain injury and cerebral ischemic stroke. However, their exact mechanisms of action remain unclear. Here, we investigated the effects of this cell therapy on cortical network excitability, brain tissue, and peripheral blood at a chronic stage after ischemic stroke in a rat model.

High-affinity T cell receptor ImmTAC® bispecific efficiently redirects T cells to kill tumor cells expressing the cancer-testis antigen PRAME.

Background: PRAME (eferentially expressed ntigen in lanoma) is a cancer-testis antigen expressed in several tumor indications, representing an attractive anticancer target. However, its intracellular location limits targeting by traditional methods. PRAME peptides are presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules, indicating that a T cell receptor (TCR)-based strategy that redirects T cells to kill PRAME tumors could be a novel immunotherapeutic option.

Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease.

Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease.

Double-Hit Diffuse Large B-Cell Lymphoma in AIDS.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of immunoblastic lymphoma associated with AIDS, with the stomach being the most frequent extranodal site of involvement. Despite the widespread use of combined antiretroviral therapy (cART), the incidence of systemic lymphomas remains relatively high. These lymphomas often present in the early stages of AIDS as high-grade malignancies.

High throughput application of the NanoBiT Biochemical Assay for the discovery of selective inhibitors of the interaction of PI3K-p110α with KRAS.

The NanoBiT Biochemical Assay (NBBA) was designed as a biochemical format of the NanoBiT cellular assay, aiming to screen weak protein-protein interactions (PPIs) in mammalian cell lysates. Here we present a High Throughput Screening (HTS) application of the NBBA to screen small molecule and fragment libraries to identify compounds that block the interaction of KRAS-G12D with phosphatidylinositol 3-kinase (PI3K) p110α. This interaction promotes PI3K activity, resulting in the promotion of cell growth, proliferation and survival, and is required for tumour initiation and growth in mouse lung cancer models, whilst having little effect on the health of normal adult mice, establishing the significance of the p110α/KRAS interaction as an oncology drug target.

Mortality in septic patients treated with short-acting betablockers: a comprehensive meta-analysis of randomized controlled trials.

Background: Treatment with short-acting betablockers in septic patients remains controversial. Two recent large multicenter trials have provided additional evidence on this therapeutic approach. We thus performed a meta-analysis, including the most recent data, to evaluate the potential impacts of treatment with short-acting betablockers on mortality in adult septic patients.

Analogous copper nanoclusters (Cu) with two electron superatomic and mixed valence copper(II)/copper(I) and copper(I)/copper(0) characters.

The reported copper nanoclusters (Cu NCs) of either Cu or Cu or mixed valence (MV) Cu/Cu or Cu/Cu characters are found to be stabilized with a discrete set of ligand donors; hence, analogous Cu NCs with a common architecture supported by the same or nearly the same donor set that exhibit different MV states of Cu, such as Cu/Cu and Cu/Cu, are unknown. Such a series of highest nuclearity copper clusters supported by aromatic thiol-S donor ligands, namely [(L4)CuI15Cu(μ-S)](PF) (1), [(L4)CuI15Cu(μ-S)]ClO·8CH (2) and [(L4)CuI15Cu(DMF)](PF)·CHOH·2CH (3), where L = 2-((3-X-thiophen)-(2-yl-methylene)amino)-4-(trifluoromethyl)benzenethiol (X = H/Me), have been synthesized and their electronic structural properties have been examined and reported herein. The Cu NCs, 1 and 2, feature a central sulfido-S (S) bridged tetracopper SCu core inside a sphere-shaped CuS truncated octahedron.

Phosphorylation of S-S-S Motif in Nuclear Export Protein (NEP) Plays a Critical Role in Viral Ribonucleoprotein (vRNP) Nuclear Export of Influenza A and B Viruses.

The phosphorylation of three highly conserved serine residues S23, S24, and S25 (S-S-S motif) has been previously identified in NEP of influenza virus. However, it remains obscure whether and how this motif regulates the vRNPs nuclear export. Here the influenza A H5N6 viruses harboring NEP S23C, S24L, or S25L is generated, allowing to impair the phosphorylation on these sites without mutating viral NS1 protein.

Potent neutralization by a RBD antibody with broad specificity for SARS-CoV-2 JN.1 and other variants.

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed.

Large- and Small-Animal Studies of Safety, Pharmacokinetics, and Biodistribution of Inflammasome-Targeting Nanoligomer in the Brain and Other Target Organs.

Immune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions and multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids can offer limited relief for systemic inflammation for some organs, many patients never achieve remission, and such drugs do not cross the blood-brain barrier, making them ineffective for tackling neuroinflammation. Especially in the brain, unintended activation of microglia and astrocytes is hypothesized to be directly or indirectly responsible for multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease.

Sodium-Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Glaucoma in Patients With Type 2 Diabetes: A Target Trial Emulation.

Purpose: Pleiotropic cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) due to vascular remodeling effects have been demonstrated in patients with type 2 diabetes mellitus. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study was to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes.

Electrochemically Switchable Sulfurized Polyacrylonitrile for Controllable Recovery of Copper in Wastewater Based on Reversible Adsorption/Desorption Regulation.

Within the context of circular economy and industrial ecology, adsorption offers an effective manner for recycling resources from wastewater, but controllable desorption remains a challenge. Inspired by metal-thiol binding and reversible thiol-disulfide redox transformation in biological systems, this study reports the development of a reversible adsorption/desorption (RAD) system for controllable recovery of copper based on electrochemically switchable sulfurized polyacrylonitrile (SPAN). Density functional theory calculations offered theoretical prediction for the formation of S-Cu bonds and reversible weak interaction between S-S bonds and Cu.

Head-Up Tilt Sleeping to Treat Orthostatic Intolerance in a Patient with Advanced Parkinson's Disease: A Case Report.

Introduction: Orthostatic hypotension is common in people with Parkinson's disease (PD) due to autonomic dysfunction and medication use and can have a significant negative impact on quality of life. Pharmacological treatment is often complicated due to complex blood pressure regulation problems. This case report presents a patient whose symptoms of orthostatic intolerance were successfully treated with the non-pharmacological method of head-up tilt sleeping (HUTS).

Deep learning improves physician accuracy in the comprehensive detection of abnormalities on chest X-rays.

Chest X-rays are the most commonly performed medical imaging exam, yet they are often misinterpreted by physicians. Here, we present an FDA-cleared, artificial intelligence (AI) system which uses a deep learning algorithm to assist physicians in the comprehensive detection and localization of abnormalities on chest X-rays. We trained and tested the AI system on a large dataset, assessed generalizability on publicly available data, and evaluated radiologist and non-radiologist physician accuracy when unaided and aided by the AI system.