Cas12e orthologs evolve variable structural elements to facilitate dsDNA cleavage.

Exceptionally diverse type V CRISPR-Cas systems provide numerous RNA-guided nucleases as powerful tools for DNA manipulation. Two known Cas12e nucleases, DpbCas12e and PlmCas12e, are both effective in genome editing. However, many differences exist in their in vitro dsDNA cleavage activities, reflecting the diversity in Cas12e's enzymatic properties.

Glucose Testing Methods: A Systematic Review and Meta-Analysis of Diagnostic Accuracy of Point-of-Care Devices for Neonatal Hypoglycemia.

Objective: To evaluate the accuracy of various point-of-care device methodologies for measuring blood glucose concentrations in babies at risk of neonatal hypoglycemia.

Study Design: This systematic review and meta-analysis included studies from Ovid MEDLINE, Ovid Embase, and Web of Science up to May 20, 2024. Studies comparing point-of-care testing methods for neonatal blood glucose to a standard laboratory method were included, excluding those on continuous glucose monitoring or conducted before 1990.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Development and Evaluation of a Novel Resuscitation Teamwork Model for Out-of-Hospital Cardiac Arrest in the Emergency Department.

Study Objective: Cardiopulmonary resuscitation (CPR) is critical for out-of-hospital cardiac arrest patients but is prone to rapid changes and errors. Effective teamwork and leadership are essential for high-quality CPR. We aimed to introduce the Airway-Circulation-Leadership-Support (A-C-L-S) teamwork model in the emergency department (ED) to address these challenges.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance.

Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the tumor microenvironment (TME).

Long noncoding RNA VENTHEART is required for ventricular cardiomyocyte specification and function.

Rationale: Cardiac-expressed long noncoding RNAs (lncRNAs) are important for cardiomyocyte (CM) differentiation and function. Several lncRNAs have been identified and characterized for early CM lineage commitment, however those in later CM lineage specification and maturation remain less well studied. Moreover, unique atrial / ventricular lncRNA expression has never been studied in detail.

The Physiological Response of for Water Pollution by 2,4-Dinitrophenol.

In this study, the effects of different concentrations of 2,4-dinitrophenol (2,4-DNP) stress on physiological parameters, as well as the uptake and removal of 2,4-DNP in , were investigated using hydroponic simulation experiments to explore the potential of the use of in the phytoremediation of wastewater polluted by 2,4-DNP. The results showed that (net photosynthetic rate), (transpiration rate), (stomatal conductance), (stomatal limitation value), / (maximal quantum yield of PSII photochemistry), and (photochemical quenching coefficient) of seedlings showed an overall decreasing trend, while (intercellular CO concentration) showed an increasing trend with the increase in 2,4-DNP concentration. The net photosynthetic rate and intercellular carbon dioxide concentration showed an opposite trend in the leaves with the increase in 2,4-DNP stress concentration, and the inhibition of net photosynthesis by 2,4-DNP on seedlings was mainly based on non-stomatal factors.

A deep learning algorithm for the detection of aortic dissection on non-contrast-enhanced computed tomography via the identification and segmentation of the true and false lumens of the aorta.

Background: Aortic dissection is a life-threatening clinical emergency, but it is often missed and misdiagnosed due to the limitations of diagnostic technology. In this study, we developed a deep learning-based algorithm for identifying the true and false lumens in the aorta on non-contrast-enhanced computed tomography (NCE-CT) scans and to ascertain the presence of aortic dissection. Additionally, we compared the diagnostic performance of this algorithm with that of radiologists in detecting aortic dissection.

Arthroscopy Patients in Medicare Population Became Sicker While Reimbursement Decreased From 2013 to 2020.

Purpose: To assess surgeon reimbursement for common arthroscopic procedures, including arthroscopic meniscal debridement and arthroscopic rotator cuff repair, in patients with differing risk profiles within the Medicare population.

Methods: A publicly available Medicare database was used to identify all cases of arthroscopic meniscal debridement and arthroscopic rotator cuff repair procedures billed to Medicare from 2013 to 2020. The surgeon reimbursement from Medicare was collected and adjusted for inflation.

A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy.

Pan-tumor validation of a NGS fraction-based MSI analysis as a predictor of response to Pembrolizumab.

Microsatellite instability high (MSI-H) and mismatch repair deficient (dMMR) tumor status have been demonstrated to predict patient response to immunotherapies. We developed and validated a next-generation sequencing (NGS)-based companion diagnostic (CDx) to detect MSI-H solid tumors via a comprehensive genomic profiling (CGP) assay, FoundationOne®CDx (F1CDx). To determine MSI status, F1CDx calculates the fraction of unstable microsatellite loci across >2000 loci using a fraction-based (FB) analysis.

Post-COVID-19 recovery and geriatric rehabilitation care: a European inter-country comparative study.

Purpose: There is variation in organization of geriatric rehabilitation across Europe. The purpose of this study was to describe the selection criteria for referral to geriatric rehabilitation, care provided, and recovery trajectories of post-COVID-19 patients referred to geriatric rehabilitation in Europe.

Methods: This observational cohort study included 723 patients in 59 care facilities for geriatric rehabilitation across 10 countries.

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL.

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed).

Trends and comparative outcomes between operative approaches for segmentectomy in lung cancer.

Background: Segmentectomy is increasingly performed for non-small cell lung cancer. However, comparative outcomes data among open, robotic-assisted, and video-assisted thoracoscopic approaches are limited.

Methods: A retrospective cohort study of non-small cell lung cancer segmentectomy cases (2013-2021) from the Society of Thoracic Surgeons General Thoracic Surgery Database was performed.

Washed Microbiota Transplantation Is Associated With Improved Lipid Profiles: Long-Term Efficacy and Safety in an Observational Cohort From South China.

Introduction: Dyslipidemia is one of the main risk factors of chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study was to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia.

Protocol for performing deep learning-based fundus fluorescein angiography image analysis with classification and segmentation tasks.

Fundus fluorescein angiography (FFA) examinations are widely used in the evaluation of fundus disease conditions to facilitate further treatment suggestions. Here, we present a protocol for performing deep learning-based FFA image analytics with classification and segmentation tasks. We describe steps for data preparation, model implementation, statistical analysis, and heatmap visualization.

Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor.

Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist, has, in clinical trials, demonstrated greater reductions in glucose, body weight, and triglyceride levels compared with selective GLP-1R agonists in people with type 2 diabetes (T2D). However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte and mouse models, we investigated how long-acting GIPR agonists regulate fasted and fed adipocyte functions.

Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.

Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca release and mitogen-activated protein kinase (MAPK) pathway activation.