IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.

Background: Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).

Methods: To determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.

Long-term impact of artificial intelligence on colorectal adenoma detection in high-risk colonoscopy.

Background: Improved adenoma detection rate (ADR) has been demonstrated with artificial intelligence (AI)-assisted colonoscopy. However, data on the real-world application of AI and its effect on colorectal cancer (CRC) screening outcomes is limited.

Aim: To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or symptoms.

The molecular immune modulator adenosine deaminase-1 enhances HIV specific humoral and cellular responses to a native-like HIV envelope trimer DNA vaccine.

There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines.

Characteristics of Drug Poisonings Seen in the Emergency Department of an Urban Hospital.

Background: Drug poisoning, either intentional or non-intentional, is a frequent diagnosis in the emergency department (ED), necessitating patient management from multiple services.

Objective: To describe the drug poisonings seen in the ED of a large academic urban hospital.

Methods: This retrospective descriptive study used 3 years of data (2018-2020) abstracted from the hospital's electronic medical record system and linked to validated, coded extracts from the Canadian Institute for Health Information Discharge Abstract Database.

Translating and applying a simulation model to enhance understanding of grassland management.

Each new generation of grassland managers could benefit from an improved understanding of how modification of nitrogen application and harvest dates in response to different weather and soil conditions will affect grass yields and quality. The purpose of this study was to develop a freely available grass yield simulation model, validated for England and Wales, and to examine its strengths and weaknesses as a teaching tool for improving grass management. The model, called LINGRA-N-Plus, was implemented in a Microsoft Excel spreadsheet and iteratively evaluated by students and practitioners (farmers, consultants, and researchers) in a series of workshops across the UK over 2 years.

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies.

A Rare Case of Esophageal Carcinoma Cuniculatum Palliated by Esophageal and Endobronchial Stenting.

Carcinoma cuniculatum is a rare variant of well-differentiated squamous cell carcinoma. To date, there are less than 30 cases of esophageal carcinoma cuniculatum reported. It is frequently a diagnostic challenge: A definitive diagnosis typically cannot be made before esophagectomy.

Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling.

The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor.

Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma.

Background: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance.

Aims: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort.

Using the power of innate immunoprofiling to understand vaccine design, infection, and immunity.

In the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay between genetic, epigenetic, and environmental factors. Significant progress has been made in understanding the innate immune response, including cell players and critical signaling pathways, but many questions remain unanswered, including how the innate immune response dictates host/pathogen responses and responses to vaccines. To complicate things further, it is becoming increasingly clear that the innate immune response is not a linear pathway but is formed from complex networks and interactions.

Long-Term Outcomes and Risk of Pancreatic Cancer in Intraductal Papillary Mucinous Neoplasms.

Importance: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC).

Objective: To fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC.

Low Risk for Ross River Virus Infection in Expeditionary Forces Training in Australia Demonstrated by a Serological Survey of Marine Rotational Force-Darwin, 2012-2018.

On an annual basis, approximately 2,500 U.S. Marines and Sailors deploy to Australia on 6-month training rotations.

The Epigenetic Reader Protein SP140 Regulates Dendritic Cell Activation, Maturation and Tolerogenic Potential.

SP140 is an epigenetic reader protein expressed predominantly in immune cells. GWAS studies have shown an association between single nucleotide polymorphisms (SNPs) and diverse autoimmune and inflammatory diseases, suggesting a possible pathogenic role for SP140 in immune-mediated diseases. We previously demonstrated that treatment of human macrophages with the novel selective inhibitor of the SP140 protein (GSK761) reduced the expression of endotoxin-induced cytokines, implicating a role of SP140 in the function of inflammatory macrophages.

Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge.

Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, various patient populations, including the aged can have suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in aged mice.

COVID-19, the Gut, and Nutritional Implications.

Purpose Of Review: Our goal is to provide the most recent and accurate scientific evidence available regarding COVID-19's interaction with the human gut and the role of nutrition/nutritional supplementation in the prevention and treatment of the disease.

Recent Findings: Gastrointestinal symptoms of COVID-19 are common and often persist even after classically defined illness resolution. Nutritional status and content have been shown to impact infection risk and severity.

Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals.

Herein, we studied the impact of empty LNP (eLNP), component of mRNA-based vaccine, on anti-viral pathways and immune function of cells from young and aged individuals. eLNP induced maturation of monocyte derived dendritic cells (MDDCs). We further show that eLNP upregulated CD40 and induced cytokine production in multiple DC subsets and monocytes.

Shifting students toward testing: impact of instruction and context on self-regulated learning.

Much of the learning that college students engage in today occurs in unsupervised settings, making effective self-regulated learning techniques of particular importance. We examined the impact of task difficulty and supervision on whether participants would follow written instructions to use repeated testing over restudying. In Study 1, we found that when supervised, instructions to test resulted in changes in the self-regulated learning behaviors such that participants tested more often than they studied, relative to participants who were unsupervised during learning.

Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals.

Despite the overwhelming success of mRNA-based vaccine in protecting against SARS-CoV-2 infection and reducing disease severity and hospitalization, little is known about the role lipid nanoparticles (LNP) play in initiating immune response. In this report we studied the adjuvantive impact of empty LNP with no mRNA cargo (eLNP) on anti-viral pathways and immune function of cells from young and aged individuals. We found that eLNP induced maturation of monocyte derived dendritic cells by measuring the expression of CD40, CD80, HLA-DR and production of cytokines including IFN-α,IL-6, IFN-γ, IL-12, and IL-21.

A BET Protein Inhibitor Targeting Mononuclear Myeloid Cells Affects Specific Inflammatory Mediators and Pathways in Crohn's Disease.

Background: Myeloid cells are critical determinants of the sustained inflammation in Crohn's Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities.

Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.

The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described.

Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals.

CAR T cell therapy for solid tumors: Fatal attraction requires adhesion.

Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy against solid tumors in clinical studies in contrast to hematological malignancies. In a paper recently published in Nature, Larson et al. report that CAR T cell activity against solid tumors depends on cell adhesion mediated by IFNγ signaling, opening the prospect of improving their clinical activity in the future.