Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer.

Purpose: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data link cigarette smoke as a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity.

The Domain-Specific Neural Basis of Auditory Statistical Learning in 5-7-Year-Old Children.

Statistical learning (SL) is the ability to rapidly track statistical regularities and learn patterns in the environment. Recent studies show that SL is constrained by domain-specific features, rather than being a uniform learning mechanism across domains and modalities. This domain-specificity has been reflected at the neural level, as SL occurs in regions primarily involved in processing of specific modalities or domains of input.

The mARS complex: a critical mediator of immune regulation and homeostasis.

Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions.

Multifactoral immune modulation potentiates durable remission in multiple models of aggressive malignancy.

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single-agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the non-immunogenic 4T-1 model of TNBC, the aggressive MOC-2 model of HNSCC, and the high-risk MYCN-amplified model of neuroblastoma.

Artificial intelligence-powered discovery of small molecules inhibiting CTLA-4 in cancer.

Background/objectives: Checkpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4.

Immunomodulatory proteins from hookworms reduce cardiac inflammation and modulate regulatory responses in a mouse model of chronic infection.

Introduction: Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4 + Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite , the causative agent of Chagas disease, leads to chronic inflammation in tissues.

Defining the distance between the His bundle and first septal perforator: implications for left bundle branch pacing.

Background: Left bundle branch pacing (LBBP) is a developing method of native conduction pacing, but cases of injury to the septal perforator arteries during implantation have been reported. Knowing the distance between the His bundle and the first septal perforator artery can help operators implant LBBP leads more safely.

Methods: Using previously performed coronary CT angiography (CCTA) studies, the distance between the His bundle and the first septal perforator was measured.

Glutathione peroxidase 2 is a metabolic driver of the tumor immune microenvironment and immune checkpoint inhibitor response.

Background: The existence of immunologically 'cold tumors' frequently found across a wide spectrum of tumor types represents a significant challenge for cancer immunotherapy. Cold tumors have poor baseline pan-leukocyte infiltration, including a low prevalence of cytotoxic lymphocytes, and not surprisingly respond unfavorably to immune checkpoint (IC) inhibitors. We hypothesized that cold tumors harbor a mechanism of immune escape upstream and independent of ICs that may be driven by tumor biology rather than differences in mutational neoantigen burden.

How to assess the risks associated with the usage of a medical device based on predictive modeling: the case of an anemia control model certified as medical device.

Background: The successful application of Machine Learning (ML) to many clinical problems can lead to its implementation as a medical device (MD), which is important to assess the associated risks.

Methods: An anemia control model (ACM), certified as MD, may face adverse events as a result of wrong predictions that are translated into suggestions of doses of erythropoietic stimulating agents to dialysis patients. Risks are assessed as the combination of severity and probability of a given hazard.

Effect of body size and enhanced helmet systems on risk for motorsport drivers.

Objective: Computational modeling has been shown to be a useful tool for simulating representative motorsport impacts and analyzing data for relative injury risk assessment. Previous studies have used computational modeling to analyze the probability of injury in specific regions of a 50th percentile male driver. However, NASCAR drivers can represent a large range in terms of size and female drivers are becoming increasingly more common in the sport.

Papillary Muscle Rupture Complicating Acute Myocardial Infarction: A Tale of Teamwork.

A 52-year-old man presented with acute onset of chest pain and was found to have an inferolateral ST-segment elevation myocardial infarction and acute mitral regurgitation due to papillary muscle rupture. This case describes a rare, potentially fatal mechanical complication of acute myocardial infarction. ().

Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations.

Background: Neoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination.

Methods: We report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies, including surgery, radiation, chemotherapy, and tyrosine kinase inhibitors (TKIs).

A subset of cytotoxic effector memory T cells enhances CAR T cell efficacy in a model of pancreatic ductal adenocarcinoma.

In humans, the natural killer (NK) cell marker CD161 identifies several subsets of T cells, including a polyclonal CD8 αβ T cell receptor-expressing subset with characteristic specificity for tissue-localized viruses. This subset also displays enhanced cytotoxic and memory phenotypes. Here, we characterized this unique T cell subset and determined its potential suitability for use in chimeric antigen receptor (CAR) T cell therapy.

Development of the Elective Outpatient Percutaneous Coronary Intervention Episode-Based Cost Measure.

Background: The Merit-Based Incentive Payment System adjusts clinician payments based on a performance score that includes cost measures. With the Centers for Medicare & Medicaid Services, we developed a novel cost measure that compared interventional cardiologists on a targeted set of costs related to elective percutaneous coronary intervention (PCI). We describe the measure and compare it to a hypothetical version including all expenditures post-PCI.

CD8CD161 T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential.

NK1.1 and its human homolog CD161 are expressed on NK cells, subsets of CD4 and CD8 T cells, and NKT cells. While the expression of NK1.

Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types.

The immune response consists of a finely-tuned program, the activation of which must be coupled with inhibitory mechanisms whenever initiated. This ensures tight control of beneficial anti-pathogen and anti-tumor responses while preserving tissue integrity, promoting tissue repair, and safeguarding against autoimmunity. A cogent example of this binary response is in the mobilization of co-stimulatory and co-inhibitory signaling in regulating the strength and type of a T-cell response.

Finite element reconstruction of a vehicle-to-pedestrian impact.

Objective: This study aims to reconstruct a real-world Crash Injury Research and Engineering Network vehicle-to-pedestrian impact to supplement the determination of pedestrian kinematics and injury causation.

Methods: A case involving a 46-year-old male pedestrian with a height of 163 cm and mass of 100 kg that was impacted by a 2019 Dodge Charger Pursuit police cruiser at an approximate velocity of 20.1 m/s was reconstructed.

Simulation-based assessment of injury risk for an average male motorsport driver.

Objective: While well-protected through a variety of safety countermeasures, motorsports drivers can be exposed to a large variety of crash modes and severities. Computational human body models (HBMs) are currently used to assess occupant safety for the general driving public in production vehicles. The purpose of this study was to incorporate a HBM into a motorsport environment using a simulation-based approach and provide quantitative data on relative risk for on-track motorsport crashes.

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain.

Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans.

MHC class I and II peptide homology regulates the cellular immune response.

Mammalian immune responses are initiated by "danger" signals--immutable molecular structures known as PAMPs. When detected by fixed, germline encoded receptors, pathogen-associated molecular pattern (PAMPs) subsequently inform the polarization of downstream adaptive responses depending upon identity and localization of the PAMP. Here, we report the existence of a completely novel "PAMP" that is not a molecular structure but an antigenic pattern.

Correction to: Development and Multi-Scale Validation of a Finite Element Football Helmet Model.

This correction is to add the middle initials of all authors, which were inadvertently omitted from the original article.

Development and Multi-Scale Validation of a Finite Element Football Helmet Model.

Head injury is a growing concern within contact sports, including American football. Computational tools such as finite element (FE) models provide an avenue for researchers to study, and potentially optimize safety tools, such as helmets. The goal of this study was to develop an accurate representative helmet model that could be used in further study of head injury to mitigate the toll of concussions in contact sports.

Evaluation of finite element human body models for use in a standardized protocol for pedestrian safety assessment.

Finite element human body models (HBMs) must be certified for use within the EuroNCAP pedestrian safety assessment protocol. We demonstrate that the Global Human Body Model Consortium (GHBMC) simplified pedestrian series of HBMs meet all criteria set forth in Technical Bulletin (TB) 024 (v 1.1 Jan.