Spherical implantable collamer lens with postoperative adjunctive LASIK in the treatment of high compound hyperopic astigmatism.

Objective: To assess refractive and visual outcomes of a spherical Implantable Collamer Lens (ICL) followed by planned postoperative adjunctive laser-assisted in situ keratomileusis (LASIK) in the treatment of high compound hyperopic astigmatism.

Methods: In this prospective, multi-center, multi-surgeon, single-arm trial, eyes with ≥ 3.50 D hyperopia and ≥ 2.

Aryl-hydrocarbon receptor in smooth muscle cells protect against dioxin induced adverse remodeling of atherosclerosis.

Introduction: Environmental exposure to dioxin has been linked to increased myocardial infarction. Smooth muscle cells (SMC) in the coronary vasculature play a critical role in atherosclerotic plaque remodeling due to their phenotypic plasticity, however, the detailed mechanism linking dioxin exposure to adverse SMC modulation is not well understood.

Methods: Single-cell RNA and ATAC sequencing and histological analyses were performed on the aorta from mouse models of atherosclerosis exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or control.

Comprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics.

Evasion of apoptosis promotes tumor survival and contributes to resistance to cancer therapeutics in head and neck squamous cell carcinoma (HNSCC). Our recent work has demonstrated that HNSCC's highly express pro-survival anti-apoptotic proteins Bcl-xL and Mcl-1. Nevertheless, the mechanism of HNSCC to evade apoptosis is still not well understood.

Uncovering individualised treatment effects for educational trials.

Large-scale Randomised Controlled Trials (RCTs) are widely regarded as "the gold standard" for testing the causal effects of school-based interventions. RCTs typically present the statistical significance of the average treatment effect (ATE), which captures the effect an intervention has had on average for a given population. However, key decisions in child health and education are often about individuals who may be very different from those averages.

Prognostic Value of Circulating Fibrosis Biomarkers in Dilated Cardiomyopathy (DCM): Insights into Clinical Outcomes.

Background: Dilated cardiomyopathy (DCM) involves myocardial remodeling, characterized by significant fibrosis and extracellular matrix expansion. These changes impair heart function, increasing the risk of heart failure and sudden cardiac death. This study investigates the prognostic value of circulating fibrosis biomarkers as a less invasive method in DCM patients.

A cell and transcriptome atlas of the human arterial vasculature.

Vascular beds show different propensities for different vascular pathologies, yet mechanisms explaining these fundamental differences remain unknown. We sought to build a transcriptomic, cellular, and spatial atlas of human arterial cells across multiple different arterial segments to understand this phenomenon. We found significant cell type-specific segmental heterogeneity.

Smooth muscle expression of RNA editing enzyme controls activation of RNA sensor MDA5 in atherosclerosis.

Unlabelled: Mapping the genomic architecture of complex disease has been predicated on the understanding that genetic variants influence disease risk through modifying gene expression. However, recent discoveries have revealed that a significant burden of disease heritability in common autoinflammatory disorders and coronary artery disease is mediated through genetic variation modifying post-transcriptional modification of RNA through adenosine-to-inosine (A-to-I) RNA editing. This common RNA modification is catalyzed by ADAR enzymes, where ADAR1 edits specific immunogenic double stranded RNA (dsRNA) to prevent activation of the double strand RNA (dsRNA) sensor MDA5 ( ) and stimulation of an interferon stimulated gene (ISG) response.

Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment.

Cancer cells show altered antioxidant defense systems, dysregulated redox signaling, and increased generation of reactive oxygen species (ROS). Targeting cancer cells through ROS-mediated mechanisms has emerged as a significant therapeutic strategy due to its implications in cancer progression, survival, and resistance. Extensive research has focused on selective generation of HO in cancer cells for selective cancer cell killing by employing various strategies such as metal-based prodrugs, photodynamic therapy, enzyme-based systems, nano-particle mediated approaches, chemical modulators, and combination therapies.

Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus.

Objective: Cardiovascular disease (CVD) risk is increased in SLE and underestimated by general population prediction algorithms. We aimed to develop a novel SLE-specific prediction tool, SLECRISK, to provide a more accurate estimate of CVD risk in SLE.

Methods: We studied patients in the Brigham and Women's Hospital SLE cohort.

Design and sample size determination for multiple-dose randomized phase II trials for dose optimization.

The U.S. Food and Drug Administration (FDA) has launched Project Optimus to shift dose selection from the maximum tolerated dose (MTD) to the dose that produces the optimal risk-benefit tradeoff.

Challenges and Lessons Learned in Autologous Chimeric Antigen Receptor T-Cell Therapy Development from a Statistical Perspective.

Chimeric antigen receptor (CAR) T-cell therapy is a human gene therapy product where T cells from a patient are genetically modified to enable them to recognize desired target antigen(s) more effectively. In recent years, promising antitumor activity has been seen with autologous CAR T cells. Since 2017, six CAR T-cell therapies for the treatment of hematological malignancies have been approved by the Food and Drug Administration (FDA).

Short-term Comparison of Survivorship and Functional Outcomes for Metaphyseal Cones with Short and Long Stems in Revision Total Knee Arthroplasty.

Printed porous titanium metaphyseal cones have become a mainstay for managing bone loss in revision total knee arthroplasty (rTKA). A short or long stem is routinely used when implanting a cone to augment fixation and offload stresses. This retrospective analysis compared the short-term survivorships and functional outcomes for use of a short or long stem with a metaphyseal cone.

A patient-specific circle of Willis blood flow model in predicting outcomes of balloon test occlusion.

Background And Purpose: Balloon test occlusion (BTO) evaluates cerebral ischemic tolerance before internal carotid artery (ICA) sacrifice but carries risks like dissection and thrombosis. This study introduces a new approach using a patient-specific circle of Willis (COW) blood flow model, based on non-invasive quantitative MR angiography (qMRA) measurements, to predict the outcomes of BTO.

Methods: We developed individualized COW blood flow models for 43 patients undergoing BTO.

Accelerating drug development at Bristol Myers Squibb through innovation.

This paper focuses on the use of novel technologies and innovative trial designs to accelerate evidence generation and increase pharmaceutical Research and Development (R&D) productivity, at Bristol Myers Squibb. We summarize learnings with case examples, on how we prepared and continuously evolved to address the increasing cost, complexities, and external pressures in drug development, to bring innovative medicines to patients much faster. These learnings were based on review of internal efforts toward accelerating R&D focusing on four key areas: adopting innovative trial designs, optimizing trial designs, leveraging external control data, and implementing novel methods using artificial intelligence and machine learning.

Characterization of a Diverse Set of Conditionally Reprogrammed Head and Neck Cancer Cell Cultures.

Objective: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR).

Methods: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR methods. Tumor and blood samples were collected and clinical information was recorded.