Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

Introduction: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.

Methods: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.

Results: PVS was significantly associated with sEF (c = -0.

Multisite Validation of a Functional Assay to Adjudicate Brugada Syndrome-Associated Variants.

Background: Brugada syndrome is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in . Interpreting the pathogenicity of missense variants is challenging, and ≈79% of missense variants in ClinVar are currently classified as variants of uncertain significance. Automated patch clamp technology enables high-throughput functional studies of ion channel variants and can provide evidence for variant reclassification.

Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage: Location, Distribution Patterns, Infarct Load, and Effect on Outcome.

Background And Objectives: Delayed cerebral ischemia (DCI) is one of the main contributing factors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Unsuccessful treatment can cause irreversible brain injury in the form of DCI-related infarction. We aimed to assess the association between the location, distribution, and size of DCI-related infarction in relation to clinical outcome.

An aptamer-mediated base editing platform for simultaneous knockin and multiple gene knockout for allogeneic CAR-T cells generation.

Gene editing technologies hold promise for enabling the next generation of adoptive cellular therapies. In conventional gene editing platforms that rely on nuclease activity, such as clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9), allow efficient introduction of genetic modifications; however, these modifications occur via the generation of DNA double-strand breaks (DSBs) and can lead to unwanted genomic alterations and genotoxicity. Here, we apply a novel modular RNA aptamer-mediated Pin-point base editing platform to simultaneously introduce multiple gene knockouts and site-specific integration of a transgene in human primary T cells.

Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A.

Background: Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII. Immunosuppressive therapy (IST) is standard of care to eradicate autoantibody production and protect from further bleeding but carries a risk of severe infection and mortality in frail patients with AHA. Recently, emicizumab has been studied for its potential to reduce the need for early and aggressive IST.

ChatGPT-4 Performs Clinical Information Retrieval Tasks Using Consistently More Trustworthy Resources Than Does Google Search for Queries Concerning the Latarjet Procedure.

Purpose: To assess the ability of ChatGPT-4, an automated Chatbot powered by artificial intelligence, to answer common patient questions concerning the Latarjet procedure for patients with anterior shoulder instability and compare this performance with Google Search Engine.

Methods: Using previously validated methods, a Google search was first performed using the query "Latarjet." Subsequently, the top 10 frequently asked questions (FAQs) and associated sources were extracted.

Glycolytic PFKFB3 and Glycogenic UGP2 Axis Regulates Perfusion Recovery in Experimental Hind Limb Ischemia.

Background: Despite being in an oxygen-rich environment, endothelial cells (ECs) use anaerobic glycolysis (Warburg effect) as the primary metabolic pathway for cellular energy needs. PFKFB (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase)-3 regulates a critical enzymatic checkpoint in glycolysis and has been shown to induce angiogenesis. This study builds on our efforts to determine the metabolic regulation of ischemic angiogenesis and perfusion recovery in the ischemic muscle.

A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.

Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells.

Metabolomic and Physiological Effects of a Cardiorenal Protective Diet Intervention in African American Adults with Chronic Kidney Disease.

Chronic kidney disease (CKD) impacts 14% of adults in the United States, and African American (AA) individuals are disproportionately affected, with more than 3 times higher risk of kidney failure as compared to White individuals. This study evaluated the effects of base-producing fruit and vegetables (FVs) on cardiorenal outcomes in AA persons with CKD and hypertension (HTN) in a low socioeconomic area. The "Cardiorenal Protective Diet" prospective randomized trial evaluated the effects of a 6-week, community-based FV intervention compared to a waitlist control (WL) in 91 AA adults (age = 58.

Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

Objectives: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor.

Methods: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay.

Re-Imagining Hospital Patient Room Design for People After stroke: A Randomized Controlled Study Using Virtual Reality.

Background: The hospital's physical environment can impact health and well-being. Patients spend most of their time in their hospital rooms. However, little experimental evidence supports specific physical design variables in these rooms, particularly for people poststroke.

Preparation and Judd-Ofelt Analysis of Warm Red Luminescent Eu Complexes for Semiconductor Lasing Devices.

Six novel red photoluminescent Eu complexes with 3-formyl chromone as the primary sensitizer (L) were synthesized using the solution precipitation method. These complexes are [Eu(L).X] where X is 2HO (C1), phen (C2), neo (C3), bipy (C4), dmph (C5), and biquno (C6).

The role of socio-economic disparities in the relative success and persistence of SARS-CoV-2 variants in New York City in early 2021.

Socio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation of SARS-CoV-2 variants during the second wave in NYC. We tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.

Robotic-enhanced hybrid ablation for persistent and long-standing atrial fibrillation: Early assessment of feasibility, safety, and efficacy.

Objectives: To assess feasibility, safety, and early efficacy of robotic-enhanced epicardial ablation (RE-EA) as first stage of a hybrid approach to patients with persistent (PsAF) and long-standing atrial fibrillation (LSAF).

Methods: Single-center, retrospective analysis of patients with documented PsAF and LSAF who underwent RE-EA followed by catheter-guided endocardial ablation. Postoperatively, patients were monitored for major adverse events and underwent rhythm follow-up at 3 and 12 months.

FLT3-TKD Measurable Residual Disease Detection Using Droplet Digital PCR and Clinical Applications in Acute Myeloid Leukemia.

The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common -TKD mutations (D835Y, D835H, D835V, D835E).

Decoding the hallmarks of allograft dysfunction with a comprehensive pan-organ transcriptomic atlas.

The pathogenesis of allograft (dys)function has been increasingly studied using 'omics'-based technologies, but the focus on individual organs has created knowledge gaps that neither unify nor distinguish pathological mechanisms across allografts. Here we present a comprehensive study of human pan-organ allograft dysfunction, analyzing 150 datasets with more than 12,000 samples across four commonly transplanted solid organs (heart, lung, liver and kidney, n = 1,160, 1,241, 1,216 and 8,853 samples, respectively) that we leveraged to explore transcriptomic differences among allograft dysfunction (delayed graft function, acute rejection and fibrosis), tolerance and stable graft function. We identified genes that correlated robustly with allograft dysfunction across heart, lung, liver and kidney transplantation.

Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

Introduction: The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology.

Methods: We imaged post mortem human tissue at 100 μm with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case).

Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.

Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study.

An economic framework for assessing the impact of domestic mining policies on affordable energy transition.

The global transition towards sustainable energy sources necessitates a delicate balance between incentivizing domestic mineral inputs and ensuring affordable energy transition. This paper investigates a diverse set of policies aimed at promoting domestic mining and their implications for achieving an affordable energy transition. Through a comprehensive economic framework, we analyze the effects of demand and supply-side policies on import reliance, production costs, and the overall progress of the energy transition.