Mutability and hypermutation antagonize immunoglobulin codon optimality.

The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.

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.

Thermoresponsive gel embedding extracellular vesicles from adipose stromal cells improves the healing of colonic anastomoses following irradiation in rats.

Anastomotic leak occurrence is a severe complication after colorectal surgery. Considering the difficulty of treating these leaks and their impact on patient care, there is a strong need for an efficient prevention strategy. We evaluated a combination of extracellular vesicles (EVs) from rat adipose-derived stromal cells with a thermoresponsive gel, Pluronic® F127 (PF-127) to prevent anastomotic leaks.

The First Case of Serogroup Y and An Expanded Investigation of Healthy Carriers - Shijiazhuang City, Hebei Province, China, 2023.

What Is Already Known About This Topic?: (Nm) is a bacterial pathogen that causes meningococcal disease. Serogroups A, B, C, W, X, and Y account for the vast majority of cases. However, invasive meningococcal disease (IMD) caused by NmY is rare in China and has been reported only in Tianjin, Guangdong, Shanghai, and Hunan provinces and cities.

Socioeconomic Status and Stroke: A Review of the Latest Evidence on Inequalities and Their Drivers.

The latest research on socioeconomic status (SES) and stroke continues to demonstrate that individuals with low SES are at a higher risk of stroke, receive lower-quality care, and experience poorer outcomes. Despite growing evidence on the impact of SES on stroke, gaps remain in understanding the underlying mechanisms and the influence of SES in different contexts, particularly in low- and middle-income countries. This narrative review builds upon our previous reviews from 2006 to 2015, focusing on studies published since 2015 to update on the influence of SES on stroke.

Engineering bacteria for cancer immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response.

Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face significant challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing (L-Trp CB) strain that can colonize tumors strictly following systemic administration.

Uncovering latent infections in kidneys: A novel molecular approach for differential detection.

Leptospirosis, a re-emerging zoonotic disease caused by spp., poses significant global health and veterinary challenges. Long-term colonization of renal tubules by in asymptomatic hosts highlights the need for sensitive detection methods.

Quantitative Coronary Angiography Guidance for Drug-Eluting Stent Implantation: A Narrative Review.

Background: Percutaneous coronary intervention (PCI) using drug-eluting stents is an established strategy for the treatment of significant obstructive coronary artery disease. Evidence supports that intravascular imaging-guided PCI offers advantages over conventional angiography-guided PCI, though its use is limited, likely due to high costs. Angiography-guided PCI relies on visual estimation, leading to inter- and intra-observer variability and suboptimal outcomes.

Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.

This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified , a highly brain penetrant and selective mGlu NAM which displayed moderate potency against both human and rat mGlu.

Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged ≥75 Years in STREAM-1 and 2.

Background: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment-elevation myocardial infarction presenting within <3 hours, compared with primary percutaneous coronary intervention (PCI). We prespecified evaluating the efficacy and safety of a half-dose versus full-dose pharmaco-invasive strategy and compared the half-dose pharmaco-invasive strategy to primary PCI in patients aged ≥75 years.

Computer-aided endoscopic diagnostic system modified with hyperspectral imaging for the classification of esophageal neoplasms.

Introduction: The early detection of esophageal cancer is crucial to enhancing patient survival rates, and endoscopy remains the gold standard for identifying esophageal neoplasms. Despite this fact, accurately diagnosing superficial esophageal neoplasms poses a challenge, even for seasoned endoscopists. Recent advancements in computer-aided diagnostic systems, empowered by artificial intelligence (AI), have shown promising results in elevating the diagnostic precision for early-stage esophageal cancer.

mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

The Relationship of Pork Meat Consumption with Nutrient Intakes, Diet Quality, and Biomarkers of Health Status in Korean Older Adults.

Background: Pork meat is a widely consumed protein food with the potential to differentially affect health and nutritional status across social and cultural contexts.

Objectives: We evaluated the association between pork meat consumption and nutrient intake, diet quality, and biomarkers of health among older adults (age ≥ 65 years) in Korea.

Methods: Our analyses utilized dietary and health examination data from the 2016-2020 Korean National Health and Nutrition Examination Survey ( = 2068).

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Women's cellphone access and ownership in rural Uganda: implications for self-care interventions.

Background: The World Health Organization (WHO) call for cervical cancer elimination includes increasing global cervical screening coverage. HPV-based self-collection (HPV-SC) is a promising screening model for low- and middle-income countries (LMICs), and while digital technology, such as cellphones, can be used to streamline HPV-SC, there is limited data on digital technology penetration in LMICs. Determining women's cellphone access is critical to understanding the feasibility of using cellphones to support HPV-SC.

Precise kilobase-scale genomic insertions in mammalian cells using PASTE.

Programmable gene integration technologies are an emerging modality with exciting applications in both basic research and therapeutic development. Programmable addition via site-specific targeting elements (PASTE) is a programmable gene integration approach for precise and efficient programmable integration of large DNA sequences into the genome. PASTE offers improved editing efficiency, purity and programmability compared with previous methods for long insertions into the mammalian genome.

Quadrivalent meningococcal tetanus toxoid-conjugate booster vaccination in children aged 10-12 years: phase III randomized trial complementary analysis of immune persistence 3-6 years after priming.

Immune persistence following primary vaccination with a single dose of meningococcal quadrivalent conjugate vaccines, MenACYW-TT/MCV4-CRM, at age 10-12 years was demonstrated. Most participants primed with MenACYW-TT and MCV4-CRM maintained seroprotective titers against all serogroups, suggesting continued protection. Priming with MenACYW-TT resulted in higher persistent titers for serogroups C, W, and Y than MCV4-CRM.

Prescribing patterns in older people with advanced chronic kidney disease towards the end of life.

Background: Advancing age and chronic kidney disease (CKD) are risk factors for polypharmacy. Polypharmacy is associated with negative healthcare outcomes. Deprescribing, the systematic rationalization of potentially inappropriate medications, is a proposed way of addressing polypharmacy.

3D electron microscopy for analyzing nanoparticles in the tumor endothelium.

Delivering medical agents to diseased tissues has been challenging, leading researchers to study the in vivo transport process in the body for improving delivery. Many imaging techniques exist for mapping the distribution of medical agent-carrying nanoparticles in tissues, but they cannot capture the three-dimensional context of tissues with single nanoparticle resolution. Here, we developed 3DEM-NPD, a three-dimensional electron microscopy (3D EM) machine learning strategy to image and map single nanoparticle distributions (NPD) in tissues.

Gender issues in myopia: a changing paradigm in generations.

Myopia is becoming an important cause of visual impairment. Determining risk profiles will help to develop targeted prevention strategies. This study aims to explore the difference in myopia development between genders in two cohorts representing different generations, and to assess whether hypothetical interventions targeting education or lifestyle factors would reduce a gender gap.