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.

Referral Networks, Racial Inequity, and Hospital Quality for Open Heart Surgery.

Background: Differences in the quality of hospitals where Black and White patients receive coronary artery bypass grafting (CABG) surgery have been documented. We examined the contributions of physician networks to the gap.

Methods: This was a cross-sectional study of all Medicare fee-for-service Black and White patients undergoing elective CABG during 2017 to 2019; the primary care physicians and cardiologists treating them for 12 months before surgery (the patients' physician network); and CABG-performing hospitals within 100 miles of each patient.

Assessing healthcare cost changes associated with transitioning away from cigarette smoking using healthcare claims data: an exploratory study among adult male patients with COPD.

Background: The assessment of potential health effects of switching from cigarette smoking to non-combustible tobacco products has important implications for public health and regulatory decisions. Robust epidemiological evidence requires long-term follow-up of a large number of individuals. Real-world evidence derived from health records has the potential to help fill the gap in the interim.

Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis.

Background: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.

Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.

Scalable production of ultraflat and ultraflexible diamond membrane.

Diamond is an exceptional material with great potential across various fields owing to its interesting properties. However, despite extensive efforts over the past decades, producing large quantities of desired ultrathin diamond membranes for widespread use remains challenging. Here we demonstrate that edge-exposed exfoliation using sticky tape is a simple, scalable and reliable method for producing ultrathin and transferable polycrystalline diamond membranes.

Maternal Hypertension Aggravates Vascular Dysfunction After Injury in Male Adult Offspring Through Transgenerational Transmission of N-Methyladenosine.

Background: Whether maternal hypertension contributes to the enhanced susceptibility to vascular remodeling in adult offspring through epigenetic mechanisms remains unclear. We aimed to address this gap in the literature using a transgenerational mouse model.

Methods: Gestational hypertension was induced in pregnant mice using chronic angiotensin II infusion.

Computational evaluation of interactive dynamics for a full transcatheter aortic valve device in a patient-specific aortic root.

Transcatheter aortic valve implantation (TAVI) has become a key treatment for severe aortic stenosis, especially for patients unsuitable for surgery. Since its introduction in 2002, TAVI has advanced significantly due to improvements in imaging, operator skills, and device engineering. Despite these innovations, challenges in device sizing and positioning remain, complicating outcome predictions.

Pulsed Field Ablation of Paroxysmal Supraventricular Tachycardia: A Prospective Multicenter Single-Arm Study in China.

Background: Pulsed field ablation (PFA) has gained attention in cardiac electrophysiology, but data on its application to paroxysmal supraventricular tachycardia are limited. This study aimed to assess the feasibility and safety of PFA and its combination with radiofrequency ablation for treating paroxysmal supraventricular tachycardia.

Methods: A prospective, multicenter, single-arm study was conducted across 8 centers in China.

Validation and psychometric properties of the bipolar prodrome symptom interview and scale-full prospective Chinese version to assess individuals at risk for bipolar disorder.

Background: Bipolar disorder (BD) is a chronic, severe mental illness with a significant socio-economic burden. The early recognition of BD requires reliable and valid instruments.

Objective: We evaluated the psychometric attributes of the Bipolar Prodrome Symptom Interview and Scale-Full Prospective (BPSS-FP)-Chinese version.

Targeted Degradation of Receptor-Interacting Protein Kinase 1 to Modulate the Necroptosis Pathway.

Necroptosis is a highly regulated form of necrotic cell death that plays an essential role in pathogen defense and tissue homeostasis. Abnormal regulation of the necroptotic pathway has been implicated in the pathogenesis of various human diseases, including cancer, inflammatory, and neurodegenerative diseases. Receptor-interacting protein kinase 1 (RIPK1) serves as a crucial regulator of the necroptotic signaling pathway and has been identified as a potential therapeutic target.

Spin Bias Is Common in the Abstracts and Main Body of Systematic Reviews and Meta-analyses of Hip Arthroscopy in the Setting of Borderline Hip Dysplasia.

Purpose: To assess the quality and presence of spin bias in the abstracts of systematic reviews and meta-analyses that evaluated the outcomes of using hip arthroscopy for the treatment of hip pathology in the setting of borderline hip dysplasia.

Methods: PubMed and Embase were searched using the terms "borderline hip dysplasia" and "systematic review" or "meta-analysis." Forty-one initial studies were identified, and 12 met the inclusion criteria.

Enhanced removal of fluoride ions using lanthanum-doped coconut shell biochar in PVDF ultrafiltration membranes.

Fluoride contamination in surface and ground water poses significant health risks, necessitating a low-energy, cost-effective removal method. Herein, an ultrafiltration (UF) adsorptive membrane doped with lanthanum (La)-based coconut shell biochar was synthesized to effectively remove fluoride ions. Based on the results of adsorption and membrane separation performance, it was found that La-based biochar showed a significantly higher adsorption capacity (126.

Deep generative design of RNA aptamers using structural predictions.

RNAs represent a class of programmable biomolecules capable of performing diverse biological functions. Recent studies have developed accurate RNA three-dimensional structure prediction methods, which may enable new RNAs to be designed in a structure-guided manner. Here, we develop a structure-to-sequence deep learning platform for the de novo generative design of RNA aptamers.

Novel Anti-Trop2 Nanobodies Disrupt Receptor Dimerization and Inhibit Tumor Cell Growth.

Trop2 (trophoblast cell-surface antigen 2) is overexpressed in multiple malignancies and is closely associated with poor prognosis, thus positioning it as a promising target for pan-cancer therapies. Despite the approval of Trop2-targeted antibody-drug conjugates (ADCs), challenges such as side effects, drug resistance, and limited efficacy persist. Recent studies have shown that the dimeric forms of Trop2 are crucial for its oncogenic functions, and the binding epitopes of existing Trop2-targeted drugs lie distant from the dimerization interface, potentially limiting their antitumor efficacy.

A systematic review of generalization research in medical image classification.

Numerous Deep Learning (DL) classification models have been developed for a large spectrum of medical image analysis applications, which promises to reshape various facets of medical practice. Despite early advances in DL model validation and implementation, which encourage healthcare institutions to adopt them, a fundamental questions remain: how can these models effectively handle domain shift? This question is crucial to limit DL models performance degradation. Medical data are dynamic and prone to domain shift, due to multiple factors.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.