Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2.

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2 cell subsets, which was distinct from that of ancestral cases.

Location-specific net water uptake and malignant cerebral edema in acute anterior circulation occlusion ischemic stroke.

Background And Purpose: Early identification of malignant cerebral edema (MCE) in patients with acute ischemic stroke is crucial for timely interventions. We aimed to identify regions critically associated with MCE using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) to evaluate the association between location-specific-net water uptake (NWU) and MCE.

Materials And Methods: This multicentre, retrospective cohort study included patients with acute ischemic stroke following large anterior circulation occlusion.

Reverse osmosis membrane fouling caused by typical surfactants in the integrated circuit industry: Fouling mechanism and control strategies.

In the integrated circuit manufacturing process, reverse osmosis (RO) membranes are widely used for wastewater reclamation. However, fouling by typical surfactants significantly reduces membrane efficiency and lifespan. This study investigates the fouling mechanisms of typical surfactants-cetyl trimethyl ammonium bromide (CTAB, cationic), sodium dodecyl sulfate (SDS, anionic), and polyoxyethylene octyl phenyl ether (TX, nonionic)-on RO membranes.

Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.

Prostate cancer remains a significant global health concern, with over 1.4 million new cases diagnosed and more than 330,000 deaths each year. The primary clinical challenge that contributes to poor patient outcomes involves the failure to accurately predict and treat at the onset of metastasis, which remains an incurable stage of the disease.

Inheritance of Imaging Parameters of Arrhythmic Risk in Mitral Valve Prolapse: A Pedigree Study.

Background: A subset of patients with mitral valve prolapse (MVP), a highly heritable condition, experience sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, the inheritance of phenotypic imaging features of arrhythmic MVP remains unknown.

Methods: We recruited 23 MVP probands, including 9 with SCA/SCD and 14 with frequent/complex ventricular ectopy.

The type 2 cytokine Fc-IL-4 revitalizes exhausted CD8 T cells against cancer.

Current cancer immunotherapy predominately focuses on eliciting type 1 immune responses fighting cancer; however, long-term complete remission remains uncommon. A pivotal question arises as to whether type 2 immunity can be orchestrated alongside type 1-centric immunotherapy to achieve enduring response against cancer. Here we show that an interleukin-4 fusion protein (Fc-IL-4), a typical type 2 cytokine, directly acts on CD8 T cells and enriches functional terminally exhausted CD8 T (CD8 T) cells in the tumour.

Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission.

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL), approximately 50% of patients relapse within the first year, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.

Cardiorespiratory Fitness Benefits of High-Intensity Interval Training After Stroke: A Randomized Controlled Trial.

Background: Limited evidence supports the effects of short-interval high-intensity interval training (HIIT) for improving cardiorespiratory fitness (V̇Opeak) after stroke. We aimed to compare the effects of 12 weeks of short-interval HIIT versus moderate-intensity continuous training (MICT) on V̇Opeak, cardiovascular risk factors, and mobility outcomes among individuals ≥6 months poststroke.

Methods: This study was a multi-site, 12-week randomized controlled trial (NCT03614585) with an 8-week follow-up.

A chimeric vaccine derived from Australian genotype IV Japanese encephalitis virus protects mice from lethal challenge.

In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus (JEV) caused an unprecedented and widespread outbreak of disease in pigs and humans in Australia. As no veterinary vaccines against JEV are approved in Australia and all current approved human and veterinary vaccines are derived from genotype (G) III JEV strains, we used the recently described insect-specific Binjari virus (BinJV) chimeric flavivirus vaccine technology to produce a JEV GIV vaccine candidate. Herein we describe the production of a chimeric virus displaying the structural prM and E proteins of a JEV GIV isolate obtained from a stillborn piglet (JEV) in the genomic backbone of BinJV (BinJ/JEVprME).

Rapid, Multiplexed, and Enzyme-Free Nucleic Acid Detection Using Programmable Aptamer-Based RNA Switches.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. We describe a class of aptamer-based RNA switches or aptaswitches that recognize target nucleic acid molecules and initiate folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide an intense fluorescent readout without intervening enzymes, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment.

Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial.

Background And Purpose: Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

Near Infrared Autofluorescence Lifetime Imaging of Human Retinal Pigment Epithelium Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities.

Methods: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart.

Fluorescence Lifetime Imaging of Human Retinal Pigment Epithelium in Pentosan Polysulfate Toxicity Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease.

[Endoscopic ultrasonography features of benign esophageal stenosis in children].

Objectives: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children.

Methods: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC.

Methods: The study group included 49 patients with stage I-III LUSC.

DockOpt: A Tool for Automatic Optimization of Docking Models.

Molecular docking is a widely used technique for leveraging protein structure for ligand discovery, but it remains difficult to utilize due to limitations that have not been adequately addressed. Despite some progress toward automation, docking still requires expert guidance, hindering its adoption by a broader range of investigators. To make docking more accessible, we developed a new utility called DockOpt, which automates the creation, evaluation, and optimization of docking models prior to their deployment in large-scale prospective screens.

Calculating Relative Lung Perfusion Using Fluoroscopic Sequences and Image Analysis: The Fluoroscopic Flow Calculator.

Background: Maldistribution of pulmonary blood flow in patients with congenital heart disease impacts exertional performance and pulmonary artery growth. Currently, measurement of relative pulmonary perfusion can only be performed outside the catheterization laboratory. We sought to develop a tool for measuring relative lung perfusion using readily available fluoroscopy sequences.

Associations between attitudes towards and reported intakes of sugars, low/no-calorie sweeteners, and sweet-tasting foods in a UK sample.

Public health initiatives are currently aiming to lower free sugar intakes for health benefits, but attitudes towards sugars, their alternatives such as low/no-calorie sweeteners (LNCS), and towards sweet-tasting foods may be hampering efforts. This work investigated associations between attitudes towards and the reported intakes of sugars, LNCS and sweet-tasting foods, and identified latent attitude profiles in subpopulations of adults in the United Kingdom. A total of 581 adults completed a questionnaire assessing their usual intake of sugars, LNCS and sweet-tasting foods, attitudes towards these foods and various demographic characteristics.

Clinical Outcomes of Deferred Lesions by IVUS Versus FFR-Guided Treatment Decision.

Background: There are limited data regarding the safety of deferral of percutaneous coronary intervention based on intravascular ultrasound (IVUS) findings. The current study sought to compare the prognosis between deferred lesions based on IVUS and fractional flow reserve (FFR)-guided treatment decision.

Methods: This study is a post hoc analysis of the FLAVOUR randomized trial (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) that compared 2-year clinical outcomes between IVUS- and FFR-guided treatment decision on intermediate coronary artery lesions using predefined criteria.

Feasibility of Coronary Access Following Redo-TAVR for Evolut Failure: A Computed Tomography Simulation Study.

Background: Coronary accessibility following redo-transcatheter aortic valve replacement (redo-TAVR) is increasingly important, particularly in younger low-risk patients. This study aimed to predict coronary accessibility after simulated Sapien-3 balloon-expandable valve implantation within an Evolut supra-annular, self-expanding valve using pre-TAVR computed tomography (CT) imaging.

Methods: A total of 219 pre-TAVR CT scans from the Evolut Low-Risk CT substudy were analyzed.

Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.

MLL/KMT2A amplifications and translocations are prevalent in infant, adult, and therapy-induced leukemia. However, the molecular contributor(s) to these alterations are unclear. Here, we demonstrate that histone H3 lysine 9 mono- and di-methylation (H3K9me1/2) balance at the MLL/KMT2A locus regulates these amplifications and rearrangements.