Bioengineered Human Arteries for the Repair of Vascular Injuries.

Importance: Vascular injuries require urgent repair to minimize loss of limb and life. Standard revascularization relies on autologous vein or synthetic grafts, but alternative options are needed when adequate vein is not feasible and when clinical conditions preclude safe use of synthetic materials.

Objective: To evaluate the performance of the acellular tissue engineered vessel (ATEV) in the repair of arterial injuries.

Immunogenicity and safety of BNT162b2 mRNA vaccine in Chinese adults: A phase 2 randomised clinical trial.

Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited.

Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart.

Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer.

Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). This analysis of 38 patients treated with the regimen demonstrated no treatment-related serious adverse events.

Immune Persistence and Safety After SARS-CoV-2 BNT162b1 mRNA Vaccination in Chinese Adults: A Randomized, Placebo-Controlled, Double-Blind Phase 1 Trial.

Introduction: BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified mRNA SARS-CoV-2 vaccine. Here, we report safety and immune persistence data following a primary two-dose vaccination schedule administered 21 days apart.

Methods: Immune persistence was determined at month 3 in 72 younger participants (aged 18-55 years) and at month 6 in 70 younger and 69 older participants (aged 65-85 years).

Combined TCR Repertoire Profiles and Blood Cell Phenotypes Predict Melanoma Patient Response to Personalized Neoantigen Therapy plus Anti-PD-1.

T cells use highly diverse receptors (TCRs) to identify tumor cells presenting neoantigens arising from genetic mutations and establish anti-tumor activity. Immunotherapy harnessing neoantigen-specific T cells to target tumors has emerged as a promising clinical approach. To assess whether a comprehensive peripheral mononuclear blood cell analysis predicts responses to a personalized neoantigen cancer vaccine combined with anti-PD-1 therapy, we characterize the TCR repertoires and T and B cell frequencies in 21 patients with metastatic melanoma who received this regimen.

A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed.

Bayesian longitudinal low-rank regression models for imaging genetic data from longitudinal studies.

To perform a joint analysis of multivariate neuroimaging phenotypes and candidate genetic markers obtained from longitudinal studies, we develop a Bayesian longitudinal low-rank regression (L2R2) model. The L2R2 model integrates three key methodologies: a low-rank matrix for approximating the high-dimensional regression coefficient matrices corresponding to the genetic main effects and their interactions with time, penalized splines for characterizing the overall time effect, and a sparse factor analysis model coupled with random effects for capturing within-subject spatio-temporal correlations of longitudinal phenotypes. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm.

Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer.

Purpose: Preclinical evidence suggests that both docetaxel and enzalutamide target androgen receptor translocation and signaling. This phase Ib study assessed the safety, tolerability, and pharmacokinetics of docetaxel when administered with enzalutamide as first-line systemic chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC).

Experimental Methods: Docetaxel-naïve patients received 21-day cycles of docetaxel (75 mg/m(2)).

Bayesian Generalized Low Rank Regression Models for Neuroimaging Phenotypes and Genetic Markers.

We propose a Bayesian generalized low rank regression model (GLRR) for the analysis of both high-dimensional responses and covariates. This development is motivated by performing searches for associations between genetic variants and brain imaging phenotypes. GLRR integrates a low rank matrix to approximate the high-dimensional regression coefficient matrix of GLRR and a dynamic factor model to model the high-dimensional covariance matrix of brain imaging phenotypes.

The Bayesian Covariance Lasso.

Estimation of sparse covariance matrices and their inverse subject to positive definiteness constraints has drawn a lot of attention in recent years. The abundance of high-dimensional data, where the sample size () is less than the dimension (), requires shrinkage estimation methods since the maximum likelihood estimator is not positive definite in this case. Furthermore, when is larger than but not sufficiently larger, shrinkage estimation is more stable than maximum likelihood as it reduces the condition number of the precision matrix.

DNA-methylation profiling distinguishes malignant melanomas from benign nevi.

DNA methylation, an epigenetic alteration typically occurring early in cancer development, could aid in the molecular diagnosis of melanoma. We determined technical feasibility for high-throughput DNA-methylation array-based profiling using formalin-fixed paraffin-embedded tissues for selection of candidate DNA-methylation differences between melanomas and nevi. Promoter methylation was evaluated in 27 common benign nevi and 22 primary invasive melanomas using a 1505 CpG site microarray.

Treatment of pain after initial archwire placement: a noninferiority randomized clinical trial comparing over-the-counter analgesics and bite-wafer use.

Introduction: Pain is a major concern of patients before orthodontic treatment. Currently, the most frequently recommended treatments for pain after archwire placement or appliance adjustment are over-the-counter (OTC) analgesics. Although the overuse of OTC medications and their potential side effects are concerns, particularly for children, no study to date has investigated a nonpharmacologic option for pain management as an alternative for these analgesics.

Temporal differences in DNA replication during the S phase using single fiber analysis of normal human fibroblasts and glioblastoma T98G cells.

We have recently shown that replication forks pause near origins in normal human fibroblasts (NHF1-hTERT) but not glioblastoma T98G cells. This observation led us to question whether other differences in the replication program may exist between these cell types that may relate to their genetic integrity. To identify differences, we detected immunoflourescently the sequential incorporation of the nucleotide analogs IdU and CldU into replicating DNA at the start of every hour of a synchronized S phase.