Application of novel CAR technologies to improve treatment of autoimmune disease.

Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success has spurred research into CAR T cell therapies for other diseases, including solid tumor cancers and autoimmune diseases. Notably, the development of CAR-based treatments for autoimmune diseases has shown great progress recently. Clinical trials for anti-CD19 and anti-BCMA CAR T cells in treating severe B cell-mediated autoimmune diseases, like systemic lupus erythematosus (SLE), have shown lasting remission thus far.

Thyroid Disease of Fishes.

The paraphyletic group referred to as fishes represents several extant and extinct classes that demonstrate the greatest diversity and abundance of any of the vertebrates on the Earth. Anatomically and physiologically, the systems of fish are comparable to those of other vertebrates and the thyroid and hypothalamic-pituitary-thyroid (HPT) axis are no exceptions. This article reviews the current literature on thyroid endocrinology of elasmobranch and teleost fishes with an emphasis on relevance to clinical management and highlights some of the anatomic and physiologic differences of the HPT axis in fishes.

A Novel Application of Spinning Disk Technology to Collect Plasma from Whole Blood Prior to Quantifying Plasma RNA.

The spinning disk technology has previously been utilized to isolate bacterial components from blood in hours instead of days. We hypothesized that this platform could be applied as an alternative approach to isolating plasma RNA from a whole blood sample. We consequently tested the efficacy of the spinning disk technology to extract plasma from whole blood upstream of RNA isolation and analysis.

The Role of Atypical Chemokine Receptors in Neuroinflammation and Neurodegenerative Disorders.

Neuroinflammation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation provides protection in acute situations but results in significant damage to the nervous system if chronic. Overexpression of chemokines within the brain results in the recruitment and activation of glial and peripheral immune cells which can propagate a cascading inflammatory response, resulting in neurodegeneration and the onset of neurodegenerative disorders.

Daytime, evening, and overnight: the 24-h radiology cycle and impact on interpretative accuracy.

Purpose: To assess the influence of time of day when a study is interpreted on discrepancy rates for common and advanced studies performed in the acute community setting.

Methods: This retrospective study used the databank of a U.S.

Radiologist age and diagnostic errors.

Purpose: Previous investigations into the causes of error by radiologists have addressed work schedule, volume, shift length, and sub-specialization. Studies regarding possible associations between radiologist errors and radiologist age and timing of residency training are lacking in the literature, to our knowledge. The aim of our study was to determine if radiologist age and residency graduation date is associated with diagnostic errors.

Interleukin-10 enhances activity of ventral tegmental area dopamine neurons resulting in increased dopamine release.

Dopamine transmission from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) regulates important aspects of motivation and is influenced by the neuroimmune system. The neuroimmune system is a complex network of leukocytes, microglia and astrocytes that detect and remove foreign threats like bacteria or viruses and communicate with each other to regulate non-immune (e.g neuronal) cell activity through cytokine signaling.

Characterizing the Interplay of Lymphocytes in Graves' Disease.

Graves' disease (GD) is a thyroid-specific autoimmune disease with a high prevalence worldwide. The disease is primarily mediated by B cells, which produce autoantibodies against the thyroid-stimulating hormone receptor (TSHR), chronically stimulating it and leading to high levels of thyroid hormones in the body. Interest in characterizing the immune response in GD has motivated many phenotyping studies.

Immunomodulatory role of oral microbiota in inflammatory diseases and allergic conditions.

In recent years, the interplay between oral microbiota and systemic disease has gained attention as poor oral health is associated with several pathologies. The oral microbiota plays a role in the maintenance of overall health, and its dysbiosis influences chronic inflammation and the pathogenesis of gum diseases. Periodontitis has also been associated with other diseases and health complications such as cancer, neurogenerative and autoimmune disorders, chronic kidney disease, cardiovascular diseases, rheumatic arthritis, respiratory health, and adverse pregnancy outcomes.

A Chromosome-length Assembly of the Black Petaltail (Tanypteryx hageni) Dragonfly.

We present a chromosome-length genome assembly and annotation of the Black Petaltail dragonfly (Tanypteryx hageni). This habitat specialist diverged from its sister species over 70 million years ago, and separated from the most closely related Odonata with a reference genome 150 million years ago. Using PacBio HiFi reads and Hi-C data for scaffolding we produce one of the most high-quality Odonata genomes to date.

Phaeohyphomycosis due to in Aquarium-Housed Lumpfish (): Clinical Diagnosis and Description.

Phaeohyphomycosis caused by species represents an important disease of concern for farmed and aquarium-housed fish. The objective of this study was to summarize the clinical findings and diagnosis of infections in aquarium-housed . Clinical records and postmortem pathology reports were reviewed for 15 individuals from 5 public aquaria in the United States and Canada from 2007 to 2015.

Bioaerosol and microbial exposures from residential evaporative coolers and their potential health outcomes: A review.

Evaporative cooling is an energy efficient form of air conditioning in dry climates that functions by pulling hot, dry outdoor air across a wet evaporative pad. While evaporative coolers can help save energy, they also have the potential to influence human health. Studies have shown residential evaporative coolers may pull outdoor air pollutants into the home or contribute to elevated levels of indoor bioaerosols that may be harmful to health.

Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer.

For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs.

Meta-Analysis of Two Human RNA-seq Datasets to Determine Periodontitis Diagnostic Biomarkers and Drug Target Candidates.

Periodontitis is a chronic inflammatory oral disease that affects approximately 42% of adults 30 years of age or older in the United States. In response to microbial dysbiosis within the periodontal pockets surrounding teeth, the host immune system generates an inflammatory environment in which soft tissue and alveolar bone destruction occur. The objective of this study was to identify diagnostic biomarkers and the mechanistic drivers of inflammation in periodontitis to identify drugs that may be repurposed to treat chronic inflammation.

CD5 Deficiency Alters Helper T Cell Metabolic Function and Shifts the Systemic Metabolome.

Metabolic function plays a key role in immune cell activation, destruction of foreign pathogens, and memory cell generation. As T cells are activated, their metabolic profile is significantly changed due to signaling cascades mediated by the T cell receptor (TCR) and co-receptors found on their surface. CD5 is a T cell co-receptor that regulates thymocyte selection and peripheral T cell activation.

Selection of human single domain antibodies (sdAb) against thymidine kinase 1 and their incorporation into sdAb-Fc antibody constructs for potential use in cancer therapy.

Thymidine Kinase 1 (TK1) is primarily known as a cancer biomarker with good prognostic capabilities for both hematological and solid malignancies. However, recent studies targeting TK1 at protein and mRNA levels have shown that TK1 may be useful as a therapeutic target. In order to examine the use of TK1 as a therapeutic target, it is necessary to develop therapeutics specific for it.

Interpretations of Examinations Outside of Radiologists' Fellowship Training: Assessment of Discrepancy Rates Among 5.9 Million Examinations From a National Teleradiology Databank.

In community settings, radiologists commonly function as multispecialty radiologists, interpreting examinations outside of their area of fellowship training. The purpose of this article was to compare discrepancy rates for preliminary interpretations of acute community-setting examinations that are concordant versus discordant with interpreting radiologists' area of fellowship training. This retrospective study used the databank of a U.

Alphaviruses: Host pathogenesis, immune response, and vaccine & treatment updates.

Human pathogens belonging to the genus, in the family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas.

Radiologist errors by modality, anatomic region, and pathology for 1.6 million exams: what we have learned.

Purpose: To evaluate the feasibility of adding pathology to recent radiologist error characterization schemes of modality and anatomic region and the potential of this data to more specifically inform peer review and peer learning.

Methods: Quality assurance data originating from 349 radiologists in a national teleradiology practice were collected for 2019. Interpretive errors were simply categorized as major or minor.

CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.

CD4 T cells are crucial for effective repression and elimination of cancer cells. Despite a paucity of CD4 T cell receptor (TCR) clinical studies, CD4 T cells are primed to become important therapeutics as they help circumvent tumor antigen escape and guide multifactorial immune responses. However, because CD8 T cells directly kill tumor cells, most research has focused on the attributes of CD8 TCRs.

Phaeohyphomycosis due to Veronaea botryosa in cultured white sturgeon (Acipenser transmontanus Richardson) from California USA during 2006 to 2015.

Infection with Veronaea botryosa can result in rare cutaneous or disseminated, granulomatous to pyogranulomatous phaeohyphomycosis in humans, although disease due to the fungus has also been reported in non-mammalian vertebrates. This report documents disease due to V. botryosa in captive, juvenile to subadult or young adult white sturgeon (Acipenser transmontanus Richardson) from California USA and complements a previous report of the disease in captive Siberian sturgeon (Acipenser baerii) from Florida USA.

Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function.

Immune memory is a defining characteristic of adaptive immunity, but recent work has shown that the activation of innate immunity can also improve responsiveness in subsequent exposures. This has been coined "trained immunity" and diverges with the perception that the innate immune system is primitive, non-specific, and reacts to novel and recurrent antigen exposures similarly. The "exposome" is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.

Atypical chemokine receptor ACKR2-V41A has decreased CCL2 binding, scavenging, and activation, supporting sustained inflammation and increased Alzheimer's disease risk.

A recent genome-wide association study (GWAS) of 59 cerebrospinal fluid (CSF) proteins with a connection to Alzheimer's disease (AD) demonstrated an association between increased levels of chemokine ligand 2 (CCL2) with an atypical chemokine receptor chemokine-binding protein 2 variant V41A (ACKR2-V41A; rs2228467). High levels of CCL2 are associated with increased risk of AD development as well as other inflammatory diseases. In this study we characterized the biological function of the ACKR2-V41A receptor compared to the wild type allele by measuring its ligand binding affinity, CCL2 scavenging efficiency, and cell activation sensitivity.