Loss of Macrophage mTORC2 Drives Atherosclerosis via FoxO1 and IL-1β Signaling.

Background: The mTOR (mechanistic target of rapamycin) pathway is a complex signaling cascade that regulates cellular growth, proliferation, metabolism, and survival. Although activation of mTOR signaling has been linked to atherosclerosis, its direct role in lesion progression and in plaque macrophages remains poorly understood. We previously demonstrated that mTORC1 (mTOR complex 1) activation promotes atherogenesis through inhibition of autophagy and increased apoptosis in macrophages.

Corvis Biomechanical Factor Facilitates the Detection of Primary Angle Closure Glaucoma.

Purpose: To characterize the corneal biomechanical properties of primary angle closure glaucoma (PACG) and to investigate the diagnostic performance of combining corneal biomechanical parameters and anterior segment parameters in detecting PACG.

Methods: This retrospective cross-sectional study evaluated 79 and 81 eyes of normal controls and patients with PACG, respectively. Corvis Biomechanical Factor (CBiF) and anterior chamber volume (ACV) were measured using the Corvis ST and Pentacam, respectively.

SZN-413, a FZD4 Agonist, as a Potential Novel Therapeutic for the Treatment of Diabetic Retinopathy.

Purpose: There remains a high unmet need for therapies with new mechanisms of action to achieve reperfusion of ischemic retina in diabetic retinopathy. We examined whether a novel frizzled class receptor 4 (FZD4) agonist could promote regeneration of functional blood vessels in animal models of retinopathy.

Methods: We developed a novel Norrin mimetic (SZN-413-p) targeting FZD4 and low-density lipoprotein receptor-related protein 5 (LRP5) and examined its effect on retinal and brain endothelial cells in vitro.

Serum levels of copeptin predict adverse outcomes and improve risk prediction of TRISS and MGAP scores in patients with multiple trauma: A single-center prospective cohort study.

Background: Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma.

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial.

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.

Analysis of HFMD Transmissibility Among the Whole Population and Age Groups in a Large City of China.

Background: Hand-Foot-and-Mouth-Disease (HFMD) has been widely spread in Asia, and has result in a high disease burden for children in many countries. However, the dissemination characteristics intergroup and between different age groups are still not clear. In this study, we aim to analyze the differences in the transmissibility of HFMD, in the whole population and among age groups in Shenzhen city, by utilizing mathematical models.

Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.

Background: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time.

Death of a Child and the Risk of Stroke: A Binational Cohort Study from Denmark and Sweden.

Background And Objectives: The death of a child is an extreme life event with potentially long-term health consequences. Accumulating evidence suggests that parents who lost a child have increased risks of cardiovascular diseases, including ischemic heart disease and atrial fibrillation. Whether bereaved parents have an increased risk of stroke is unclear and was investigated in this study.

A Monoclonal Antibody for Malaria Prevention.

Background: Additional interventions are needed to reduce the morbidity and mortality caused by malaria.

Methods: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with . Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria.

The facilitators and barriers to physical activity scale for people with mental illness in Taiwan: development and validation.

Purpose: The purposes of this study were to develop a new measure, the Facilitators and Barriers to Physical Activity Scale for People with Mental Illness (FBPAS-MI) and to validate the psychometrics.

Methods: This study included two phases. In Phase I, a literature review and five focus groups were conducted to develop an item bank.

Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias.

Selective targeting of BCL-2 with the BH3-mimetic venetoclax has been a transformative treatment for patients with various leukemias. TP-53 controls apoptosis upstream of where BCL-2 and its prosurvival relatives, such as MCL-1, act. Therefore, targeting these prosurvival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status.

Keratoconus Screening Based on Deep Learning Approach of Corneal Topography.

Purpose: To develop and compare deep learning (DL) algorithms to detect keratoconus on the basis of corneal topography and validate with visualization methods.

Methods: We retrospectively collected corneal topographies of the study group with clinically manifested keratoconus and the control group with regular astigmatism. All images were divided into training and test datasets.

Edge of Scotoma Sensitivity as a Microperimetry Clinical Trial End Point in Retinopathy.

Purpose: Microperimetry is commonly used to assess retinal function. We perform cross-sectional and longitudinal analysis on microperimetry parameters in retinopathy and explore end points suitable for future clinical trials.

Methods: Microperimetry was performed using two grids, Grid 1 (18° diameter) and Grid 2 (6° diameter).

Association of common genetic variants with brain microbleeds: A genome-wide association study.

Objective: To identify common genetic variants associated with the presence of brain microbleeds (BMBs).

Methods: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel.

Pharmacological Properties of -Opioid Receptor-Mediated Behaviors: Agonist Efficacy and Receptor Reserve.

δ-Opioid receptor (-receptor) agonists produce antihyperalgesia, antidepressant-like effects, and convulsions in animals. However, the role of agonist efficacy in generating different -receptor-mediated behaviors has not been thoroughly investigated. To this end, efficacy requirements for -receptor-mediated antihyperalgesia, antidepressant-like effects, and convulsions were evaluated by comparing the effects of the partial agonist BU48 and the full agonist SNC80 and changes in the potency of SNC80 after -receptor elimination.

Smoking Paradox in Stroke Survivors?: Uncovering the Truth by Interpreting 2 Sets of Data.

Background and Purpose- The observation that smokers with stroke could have better outcome than nonsmokers led to the term "smoking paradox." The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists.

Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations.

Epigenome-wide association study of lung function level and its change.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries.

Biosynthesis of Coenzyme Q in the Phytopathogen Xanthomonas campestris via a Yeast-Like Pathway.

Coenzyme Q (CoQ) is a lipid-soluble membrane component found in organisms ranging from bacteria to mammals. The biosynthesis of CoQ has been intensively studied in Escherichia coli, where 12 genes (ubiA, -B, -C, -D, -E, -F, -G, -H, -I, -J, -K, and -X) are involved. In this study, we first investigated the putative genes for CoQ8 biosynthesis in the phytopathogen Xanthomonas campestris pv.

Deciphering the Role of Lipid Droplets in Cardiovascular Disease: A Report From the 2017 National Heart, Lung, and Blood Institute Workshop.

Lipid droplets (LDs) are distinct and dynamic organelles that affect the health of cells and organs. Much progress has been made in understanding how these structures are formed, how they interact with other cellular organelles, how they are used for storage of triacylglycerol in adipose tissue, and how they regulate lipolysis. Our understanding of the biology of LDs in the heart and vascular tissue is relatively primitive in comparison with LDs in adipose tissue and liver.

A flexible plasma-treated silver-nanowire electrode for organic light-emitting devices.

Silver nanowires (AgNWs) are a promising candidate to replace indium tin oxide (ITO) as transparent electrode material. However, the loose contact at the junction of the AgNWs and residual surfactant polyvinylpyrrolidone (PVP) increase the sheet resistance of the AgNWs. In this paper, an argon (Ar) plasma treatment method is applied to pristine AgNWs to remove the PVP layer and enhance the contact between AgNWs.

An immunogenic personal neoantigen vaccine for patients with melanoma.

Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules.