Genetically reprogrammed exosomes for immunotherapy of acute myeloid leukemia.

Current treatments for acute myeloid leukemia (AML) remain challenging and are characterized by poor clinical outcomes. Exosomes, cell-derived membranous vesicles, have been emerging as a new modality of therapy. Here, we designed and generated genetically reprogrammed exosomes with surface-displayed antibodies and immunoregulatory proteins, namely programmed immune-engaging exosomes (PRIME Exos).

Nicotinamide Riboside and CD38: Covalent Inhibition and Live-Cell Labeling.

Nicotinamide adenine dinucleotide (NAD) is required for a myriad of metabolic, signaling, and post-translational events in cells. Its levels in tissues and organs are closely associated with health conditions. The homeostasis of NAD is regulated by biosynthetic pathways and consuming enzymes.

Predictive value of quality of life as measured by KCCQ in heart failure patients: A meta-analysis.

Background: Studies on the predictive ability of disease-specific health quality of life (QoL) in patients with heart failure (HF) have produced conflicting results. To address these gaps in knowledge, we conducted a meta-analysis to evaluate the predictive value of QoL measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with HF.

Materials And Methods: We searched PubMed, and Embase databases to identify studies investigating the predictive utility of baseline QoL measured by the KCCQ in HF patients.

miR-1268a Regulates Fatty Acid Metabolism by Targeting CD36 in Angiotensin II-induced Heart Failure.

Multiple RNAs have been involved in the progress of heart failure. However, the role of miR-1268a in heart failure is still unclear. The differentially expressed miRNAs in heart failure was analyzed based on GEO dataset GSE104150.

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a meta-analysis of randomized controlled trials.

Background: COVID-19 induces a pro-coagulant state with thrombotic events. This meta-analysis explores the efficacy and safety of antiplatelet-based therapy in COVID-19 patients through randomized controlled trials (RCTs).

Materials And Methods: A systematic literature search until March 10, 2023, identified 7 RCTs involving 23,415 inpatients.

Rational design of humanized antibody inhibitors for cathepsin S.

Cathepsin S (CTSS) is involved in pathogenesis of many human diseases. Inhibitors blocking its protease activity hold therapeutic potential. In comparison to small-molecule inhibitors, monoclonal antibodies capable of inhibiting CTSS enzymatic activity may possess advantageous pharmacological properties.

The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC.

Purpose: To explore the association of the effective dose to immune cells (EDIC) with disease control, lymphopenia, and toxicity in patients with non-small cell lung cancer (NSCLC) and identify methods to reduce EDIC.

Methods: We abstracted data from all patients with locally advanced NSCLC treated with chemoradiation with or without consolidative immunotherapy over a ten-year period. Associations between EDIC and progression-free survival (PFS) and overall survival (OS) were modeled with Cox proportional hazards and Kaplan-Meier method.

A meta-analysis of randomized controlled trials of statin-based therapy in patients with COVID-19.

Background: Previous observational studies and meta-analyses have suggested that statins could be beneficial in reducing the risk of adverse clinical outcomes. This study is the first to conduct a meta-analysis of recently published randomized controlled clinical trials investigating the potential therapeutic benefits of statins for COVID-19.

Materials And Methods: A thorough search was conducted using databases such as PubMed and Embase until May 2023 to identify randomized controlled clinical trials investigating the use of statins in patients with COVID-19.

Cisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans.

Cisplatin kills proliferating cells via DNA damage but also has profound effects on post-mitotic cells in tumors, kidneys, and neurons. However, the effects of cisplatin on post-mitotic cells are still poorly understood. Among model systems, C.

A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.

Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes.

Death without progression as an endpoint to describe cardiac radiation effects in locally advanced non-small cell lung cancer.

Background And Purpose: Prior studies have examined associations of cardiovascular substructure dose with overall survival (OS) or cardiac events after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC). Herein, we investigate an alternative endpoint, death without cancer progression (DWP), which is potentially more specific than OS and more sensitive than cardiac events for understanding CRT toxicity.

Materials And Methods: We retrospectively reviewed records of 187 patients with locally advanced or oligometastatic NSCLC treated with definitive CRT from 2008 to 2016 at a single institution.

Identification of C. elegans ASNA-1 domains and tissue requirements that differentially influence platinum sensitivity and growth control.

ASNA1 plays an essential role in cisplatin chemotherapy response, type 2 diabetes, and heart disease. It is also an important biomarker in the treatment response of many diseases. Biochemically, ASNA1 has two mutually exclusive redox-modulated roles: a tail-anchored protein (TAP) targeting function in the reduced state and a holdase/chaperone function in the oxidized state.

pyTCR: A comprehensive and scalable solution for TCR-Seq data analysis to facilitate reproducibility and rigor of immunogenomics research.

T cell receptor (TCR) studies have grown substantially with the advancement in the sequencing techniques of T cell receptor repertoire sequencing (TCR-Seq). The analysis of the TCR-Seq data requires computational skills to run the computational analysis of TCR repertoire tools. However biomedical researchers with limited computational backgrounds face numerous obstacles to properly and efficiently utilizing bioinformatics tools for analyzing TCR-Seq data.

MicroRNA-126 and VEGF enhance the function of endothelial progenitor cells in acute myocardial infarction.

Previous studies have found that microRNA-126 (miR-126) overexpression can exert beneficial effects on endothelial function and angiogenesis. The role of miR-126 was previously reported to be by directly limiting the activities of negative regulators of the vascular endothelial growth factor (VEGF) pathway, such as PI3K regulation subunit 2 (PIK3R2). The aim of the present study was to investigate the role of the miR-126/PIK3R2/VEGF axis in endothelial progenitor cells (EPCs) under hypoxic conditions.

Integration of Deep Learning Radiomics and Counts of Circulating Tumor Cells Improves Prediction of Outcomes of Early Stage NSCLC Patients Treated With Stereotactic Body Radiation Therapy.

Purpose: We develop a deep learning (DL) radiomics model and integrate it with circulating tumor cell (CTC) counts as a clinically useful prognostic marker for predicting recurrence outcomes of early-stage (ES) non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT).

Methods And Materials: A cohort of 421 NSCLC patients was used to train a DL model for gleaning informative imaging features from computed tomography (CT) data. The learned imaging features were optimized on a cohort of 98 ES-NSCLC patients treated with SBRT for predicting individual patient recurrence risks by building DL models on CT data and clinical measures.

Multidisciplinary Care for Refractory Pediatric Functional Abdominal Pain Decreases Emergency and Inpatient Utilization.

Children with refractory functional abdominal pain (FAP) experience functional disability and may utilize emergency department (ED) and/or inpatient services. Whether multidisciplinary programs which help care for children with refractory FAP affect acute healthcare utilization is unknown. A retrospective chart review of children initially evaluated by the outpatient Multidisciplinary Abdominal Pain Program (MAPP) from October 2016 to May 2019 was completed.

Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes.

Background: Myocarditis, an inflammatory disease of the myocardium, is a serious hazard to human life due to the expansion of inflammatory lesions in the myocardium. The aim of this study was to investigate the role of hypoxia-inducible transcription factor (HIF)-1α and its inhibitor topotecan in the pathogenesis of myocarditis.

Methods: H9c2 cardiomyoblasts was stimulated with lipopolysaccharide (LPS) to simulate myocarditis model in vitro.

Alternative redox forms of ASNA-1 separate insulin signaling from tail-anchored protein targeting and cisplatin resistance in C. elegans.

Cisplatin is a frontline cancer therapeutic, but intrinsic or acquired resistance is common. We previously showed that cisplatin sensitivity can be achieved by inactivation of ASNA-1/TRC40 in mammalian cancer cells and in Caenorhabditis elegans. ASNA-1 has two more conserved functions: in promoting tail-anchored protein (TAP) targeting to the endoplasmic reticulum membrane and in promoting insulin secretion.

Multiblock Discriminant Analysis of Integrative F-FDG-PET/CT Radiomics for Predicting Circulating Tumor Cells in Early-Stage Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Purpose: The main objective of the present study was to integrate F-FDG-PET/CT radiomics with multiblock discriminant analysis for predicting circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT).

Methods: Fifty-six patients with stage I NSCLC treated with SBRT underwent F-FDG-PET/CT imaging pre-SBRT and post-SBRT (median, 5 months; range, 3-10 months). CTCs were assessed via a telomerase-based assay before and within 3 months after SBRT and dichotomized at 5 and 1.

Personal and Prognostic: Tissue and Liquid Biomarkers of Radiotherapeutic Response in Non-Small Cell Lung Cancer.

Recent treatment advances have improved outcomes for patients with non-small cell lung cancer (NSCLC), often utilizing tumor molecular characterization to identify targetable mutations. This is further enhanced by advancements in "liquid biopsies", using peripheral blood for noninvasive, serial sampling of tumor biology. While tumor genomic alterations have established therapeutic implications in metastatic NSCLC, research is also ongoing to develop applications for tissue and liquid biomarkers in earlier stage disease, such as patients treated with radiation for early stage or locoregional NSCLC.

The Pain of Invisibility: A Perspective on the Treatment of Pediatric Chronic Pain.

Although chronic pain can be debilitating and severely impacting, it can also be an affliction many take on privately. For many chronic pain patients and their families, the toll of symptom invisibility is often a prominent concern. The article expounds upon the theme of "symptom invisibility" and the need for and practice of developing a validating provider-family relationship in the treatment of children and adolescents with chronic pain.

Integration of Risk Survival Measures Estimated From Pre- and Posttreatment Computed Tomography Scans Improves Stratification of Patients With Early-Stage Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Purpose: To predict overall survival of patients receiving stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (ES-NSCLC), we developed a radiomic model that integrates risk of death estimates and changes based on pre- and posttreatment computed tomography (CT) scans. We hypothesize this innovation will improve our ability to stratify patients into various oncologic outcomes with greater accuracy.

Methods And Materials: Two cohorts of patients with ES-NSCLC uniformly treated with SBRT (a median dose of 50 Gy in 4-5 fractions) were studied.

Arts and crafts as an educational strategy and coping mechanism for Republic of Korea and United States parents during the COVID-19 pandemic.

The COVID-19 pandemic and ensuing stay-at-home orders have shifted family lives worldwide. Government regulations about social distancing and isolation have resulted in parents/carers and children spending most of their time together in private spaces. During the northern hemisphere spring 2020 semester, most childcare and school systems closed and parents had to dramatically modify their balance between work and home life.

ENPL-1, the homolog of GRP94, promotes insulin secretion via regulation of proinsulin processing and maturation.

Insulin/IGF signaling in is crucial for proper development of the dauer larva and growth control. Mutants disturbing insulin processing, secretion and downstream signaling perturb this process and have helped identify genes that affect progression of type 2 diabetes. Insulin maturation is required for its proper secretion by pancreatic β cells.

Men and Women's Different Dreams on the Future of the Gendered Division of Paid Work and Household Work after COVID-19 in South Korea.

Men's long hours of paid work and minimal commitment to household work, combined with the comparably low-level of women's labor force participation, characterize the gendered division of work and family in South Korea. Can the changes in work and family arrangements brought on by the COVID-19 pandemic alter the persevering gendered division of paid work and household work in Korea? Along with school closures and the increased number of employees working from home during COVID-19, do Korean men and women anticipate more equal sharing of paid work and household work? We collected data from 1000 Korean adults during the period of July 3-6, 2020, and asked their predictions about various dimensions of social changes, including the gendered division, after COVID-19. Although a substantial share of both men and women anticipate a reduction in the gendered division of paid work and household work after COVID-19, Korean women are not as optimistic as their male counterparts about this potential reduction.