Endothelial Immunosuppression in Atherosclerosis : Translational Control by Elavl1/HuR.

Atherosclerotic plaques are defined by the accumulation of lipids and immune cells beneath the endothelium of the arterial intima. CD8 T cells are among the most abundant immune cell types in plaque, and conditions linked to their activation correlate with increased levels of cardiovascular disease. As lethal effectors of the immune response, CD8 T cell activation is suppressed at multiple levels.

Using Recurrent Neural Networks to Extract High-Quality Information From Lung Cancer Screening Computerized Tomography Reports for Inter-Radiologist Audit and Feedback Quality Improvement.

Purpose: Lung cancer screening programs generate a high volume of low-dose computed tomography (LDCT) reports that contain valuable information, typically in a free-text format. High-performance named-entity recognition (NER) models can extract relevant information from these reports automatically for inter-radiologist quality control.

Methods: Using LDCT report data from a longitudinal lung cancer screening program (8,305 reports; 3,124 participants; 2006-2019), we trained a rule-based model and two bidirectional long short-term memory (Bi-LSTM) NER neural network models to detect clinically relevant information from LDCT reports.

Association of post-treatment longitudinal symptom severity clusters with subsequent survival in oropharyngeal cancer.

Background: Patients with cancer often experience multiple symptoms concurrently. We identified patient clusters based on longitudinal symptom severity trajectories in oropharyngeal cancer (OPC) and evaluated the potential clinical utility of this approach.

Methods: A retrospective OPC patient cluster analysis using 6 months of symptom severity data from radiotherapy initiation.

Exploring social-emotional learning, school climate, and social network analysis.

There is currently limited research on student peer leadership in the social-emotional literature. This paper used exploratory methods of social network analysis to understand the structure of school peer relationships, peer leadership, and school climate. Self-report measures of perceptions of peer leadership and climate were given to students during the 2016-2017 school year.

Oncolytic viruses in melanoma.

Malignant melanoma recurrence remains heterogeneous in presentation, ranging from locoregional disease (i.e., local recurrence, satellites, in transit disease) to distant dermal and visceral metastases.

Longitudinal Assessment of Health Utility Scores, Symptoms and Toxicities in Patients with Small Cell Lung Cancer Using Real World Data.

Introduction: Recent advances in small cell lung cancer (SCLC) treatments necessitate a better understanding of real-world health utility scores (HUS) in patients treated under current standards to facilitate robust pharmaco-economic assessments.

Methods: In this single institution cohort observational study, HUS were evaluated in patients with SCLC through EQ-5D questionnaires at outpatient visits (encounters). In addition, patients completed questionnaires relating to treatment toxicities and cancer symptoms.

Combined EZH2 Inhibition and IKAROS Degradation Leads to Enhanced Antitumor Activity in Diffuse Large B-cell Lymphoma.

Purpose: The efficacy of EZH2 inhibition has been modest in the initial clinical exploration of diffuse large B-cell lymphoma (DLBCL), yet EZH2 inhibitors are well tolerated. Herein, we aimed to uncover genetic and pharmacologic opportunities to enhance the clinical efficacy of EZH2 inhibitors in DLBCL.

Experimental Design: We conducted a genome-wide sensitizing CRISPR/Cas9 screen with tazemetostat, a catalytic inhibitor of EZH2.

Endoscopic resection with adjuvant treatment versus esophagectomy for early-stage esophageal cancer.

Objective: To evaluate the outcome following the strategy of endoscopic R0 resection (ER) plus adjuvant treatment (AT) versus esophagectomy for esophageal squamous cell cancer in T1a invading muscularis mucosa (M3)-T1b stage.

Methods: We evaluated the outcomes of 46 esophageal squamous cell cancer (ESCC) patients with T1aM3-T1b stage who underwent ER + AT from the Esophageal Cancer Endoscopic Therapy Consortium (ECETC) and compared these outcomes to 92 patients who underwent esophagectomy. Propensity score matching (1:2) was used, with overall survival (OS) and relapse-free survival (RFS) being compared between the two groups.

Costimulation Induces CD4 T Cell Antitumor Immunity via an Innate-like Mechanism.

Chronic exposure to tumor-associated antigens inactivates cognate T cells, restricting the repertoire of tumor-specific effector T cells. This problem was studied here by transferring TCR transgenic CD4 T cells into recipient mice that constitutively express a cognate self-antigen linked to MHC II on CD11c-bearing cells. Immunotherapeutic agonists to CD134 plus CD137, "dual costimulation," induces specific CD4 T cell expansion and expression of the receptor for the Th2-associated IL-1 family cytokine IL-33.

Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci.

Effector CD8 T cells infiltrate atherosclerotic lesions and are correlated with cardiovascular events, but the mechanisms regulating their recruitment and retention are not well understood. CD137 (4-1BB) is a costimulatory receptor induced on immune cells and expressed at sites of human atherosclerotic plaque. Genetic variants associated with decreased CD137 expression correlate with carotid-intimal thickness and its deficiency in animal models attenuates atherosclerosis.

Activated T-effector seeds: cultivating atherosclerotic plaque through alternative activation.

Atherosclerosis is a chronic inflammatory pathology that precipitates substantial morbidity and mortality. Although initiated by physiological patterns of low and disturbed flow that differentially prime endothelial cells at sites of vessel branch points and curvature, the chronic, smoldering inflammation of atherosclerosis is accelerated by comorbidities involving inappropriate activation of the adaptive immune system, such as autoimmunity. The innate contributions to atherosclerosis, especially in the transition of monocyte to lipid-laden macrophage, are well established, but the mechanisms underpinning the infiltration, persistence, and effector dynamics of CD8 T cells in particular are not well understood.

T cell-directed IL-17 production by lung granular γδ T cells is coordinated by a novel IL-2 and IL-1β circuit.

Immune-mediated lung is considered the result of an exacerbated innate injury immune response, although a role for adaptive lymphocytes is emerging. αβ T cells specific for S. aureus enterotoxin A orchestrate a Tγδ17 response during lung injury.

Macrophage polarization and meta-inflammation.

Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed "meta-inflammation," this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues.

Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation.

The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive.

Patient preferences for testing for pulmonary embolism in the ED using a shared decision-making model.

Introduction: Shared decision making (SDM) is a process whereby patients and clinicians work together to make informed medical decisions that incorporate patient values. Recent data suggest that, for patients with low pretest probability of pulmonary embolism (PE), doubling the standard d-dimer cutoff may reduce the need for imaging with minimal increase in missed PE diagnoses. We used an SDM approach to determine patient preferences regarding this diagnostic approach.