Antibody Responses to mRNA COVID-19 Vaccine Among Healthcare Workers in Outpatient Clinics in Japan.

Background: This study aimed to assess the antibody response to SARS-CoV-2 vaccines among healthcare workers (HCWs) from multiple outpatient clinics in Japan, examining the effects of baseline characteristics (e.g., sex, age, underlying condition, smoking history, occupation) and prior infections.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

PREVENT and Pooled Cohort Equations in Mortality Risk Prediction: National Health and Nutrition Examination Survey.

Background: The Predicting Risk of CVD Events (PREVENT) equations were developed to address limitations of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) risk. The comparative effectiveness of the PREVENT equations versus the PCEs in predicting mortality risk remains unknown.

Objectives: The purpose of this study was to compare the risk discrimination value of the PREVENT equations with the PCEs for predicting mortality.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Prognostic Significance of Computed Tomography-Derived Fractional Flow Reserve for Long-Term Outcomes in Individuals With Coronary Artery Disease.

Background: Data on the predictive value of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) for long-term outcomes are limited.

Methods And Results: A retrospective pooled analysis of individual patient data was performed. Deep-learning-based CT-FFR was calculated.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Clonal Integration Promotes the Photosynthesis of Clonal Plant Under Heterogeneous Pb and/or Pyrene Stress.

Clonal plants can support the growth of their ramets in heterogeneous environments through clonal integration between the ramets. However, the role of clonal integration in modulating ramet photosynthesis under toxic stress, especially combined stress, is unclear. This study examines the impact of clonal integration on under three heterogeneous stresses (Pb, pyrene, and Pb+Pyrene) with two stolon connection conditions (connected and disconnected).

Iridium-Catalyzed Highly Selective 1,4-Reduction of α,β-Unsaturated Carbonyl Compounds.

In this study, an iridium-catalyzed selective 1,4-reduction of α,β-unsaturated carbonyl compounds is realized, with water as a solvent and formic acid as a hydride donor. The new efficient iridium catalyst features a 2-(4,5-dihydroimidazol-2-yl)quinoline ligand. The chemoselectivity and catalyst efficiency are highly dependent on the electronic and steric properties of the substrates.

Large-Scale Plasma Proteomics Improves Prediction of Peripheral Artery Disease in Individuals With Type 2 Diabetes: A Prospective Cohort Study.

Objective: Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction.

Research Design And Methods: This cohort study included 1,859 individuals with T2D from the UK Biobank.

Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.

The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points.

Engineered S. cerevisiae-pYD1-ScFv-AFB1 mitigates aflatoxin B1 toxicity via bio-binding and intestinal microenvironment repair.

The highly toxic aflatoxin B1 (AFB1) is considered one of the primary risk factors for hepatocellular carcinoma, while effective measures after AFB1 exposure remain to be optimized. This study utilized cell-surface-display technique to construct an engineered S. cerevisiae-pYD1-ScFv-AFB1 (S.

Deciphering the N-substituent effects on biodegradation of sulfonamides: Novel insights revealed from molecular biology and computational chemistry approaches.

Elucidating biodegradation mechanisms and predicting pollutant reactivities are essential for advancing the application of biodegradation engineering to address the challenge of thousands of emerging contaminants. Molecular biology and computational chemistry are powerful tools for this purpose, enabling the investigation of biochemical reactions at both the gene and atomic levels. This study employs the biodegradation of ten sulfonamide antibiotics as a case study to demonstrate the integration of genomics and quantum chemistry approaches in exploring the biodegradation behavior of emerging contaminants.

Exploring Immune-Mediated Brain Function Abnormalities in Systemic Lupus Erythematosus: Neuroimaging Evidence of the Impact of Anti-Ribosomal P Protein Antibodies.

Rationale And Objectives: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most severe complications of systemic lupus erythematosus (SLE), and its early biomarkers and immune mechanisms remain unclear. This study utilizes Resting-State functional magnetic resonance imaging (rs-fMRI) to explore early neuroimaging biomarkers and potential immune mechanisms of brain injury in SLE, with a particular focus on anti-ribosomal P protein antibody (ARPA).

Materials And Methods: A total of 47 SLE patients and 33 healthy controls (HCs) underwent rs-fMRI.

Genetic analysis of patients with low-frequency non-syndromic hearing loss.

Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate.

Single-Bundle Posterior Cruciate Ligament Reconstruction With Suture Tape Augmentation and Transtibial Tubercle Fixation.

The posterior cruciate ligament (PCL) is the strongest ligament of the knee and plays an important role in stabilizing the knee joint posteriorly. PCL tears are common injuries in sports injuries and traffic accidents; however, clinical outcomes after PCL reconstruction have not yet met clinicians' expectations, with a high postsurgery failure rate reported. Suture tape augmentation and supplementary fixation have shown ideal biomechanical properties in early studies.

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.

Preoperative prediction of Ki-67 expression in hepatocellular carcinoma by spectral imaging on dual-energy computed tomography (DECT).

Background: The Ki-67 expression level, which represents the proliferation status of cells, serves as a prognostic marker for hepatocellular carcinoma (HCC); however, the immunochemistry method currently used to evaluate Ki-67 is invasive and is not suitable for patients who have lost the chance for surgery, such as those with advanced tumors or those with other serious organic diseases. This study aimed to investigate the value of quantitative dual-energy computed tomography (DECT) parameters in predicting the expression level of Ki-67 in HCC.

Methods: This study analyzed the data of 123 consecutive patients with HCC who underwent both Ki-67 immunohistochemistry analysis and two-phase contrast-enhanced DECT imaging.

Association between high-density lipoprotein cholesterol and risk of abdominal aortic aneurysm among males and females aged 60 years and over.

Objective: Whether high-density lipoprotein cholesterol (HDL-C) has a protective role against abdominal aortic aneurysm (AAA) development in both older males and females remains uncertain. This study aims to assess the sex-specific association between HDL-C and incident AAA in older adults from the UK Biobank.

Methods: This cohort study included 86,184 males and 95,682 females aged ≥60 years from the UK biobank.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Effects of Quartz Sand on the Electromagnetic Wave Absorption of Cementitious Materials.

The roles of dielectric materials in adjusting the electromagnetic wave (EMW) absorption performance of an EMW absorber are as crucial as the EMW absorbents. The commonly used cement-based materials, such as mortar, are typical composites of multiple dielectric materials, such as quartz sand and air in the pores. This study investigates the EMW-absorption performances within the frequency range of 2 GHz to 18 GHz of cement paste and mortar samples with different sand-to-cement ratios (S/C), water-to-cement ratios (W/C), and thicknesses.

Elemental Sulfur/Selenium-Mediated Metal-Free Phosphinothioation and Phosphinoselenoation of Vinylsulfonium Salts with P-H Bonds.

An efficient and facile method has been developed for the construction of novel P-S-C and P-Se-C bonds by facilitating the three-component cross-coupling reaction of P-H bonds with elemental sulfur/selenium and vinylsulfonium salts, utilizing sodium bicarbonate as a base. This approach eliminates the need for the use of toxic and odorous active sulfur/selenium reagents and noble metals, thereby offering a new pathway for synthesizing -phosphinothioates and -phosphinoselenoates via the organic conversion of inorganic sources. The reaction has showcased remarkable versatility in terms of substrate applicability, particularly for organophosphorus compounds containing P-H bonds and vinylsulfonium salt derivatives.

Bidirectional high-speed optical wireless communication with tunable large field of view assisted by liquid crystal metadevice.

Beam-steered infrared (IR) light communication has gained tremendous attention as one of the solutions of congested wireless communication traffic. High performance active beam-steering devices play a crucial role in data allocation and exchange. Conventional beam-steering devices such as spatial light modulator (SLM) and micro-electrical mechanical system (MEMS) mirror and the current emerging nonmechanical beam-steering metasurface-based devices are challenging to realize a large tunable steering angle beyond several degrees, which significantly hinders the spatial application of optical wireless communications (OWC).