Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.

Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.

Whole genome sequencing analysis of enteropathogenic from human and companion animals in Korea.

Importance: This study is essential for comprehending the zoonotic transmission, antimicrobial resistance, and genetic diversity of enteropathogenic (EPEC).

Objective: To improve our understanding of EPEC, this study focused on analyzing and comparing the genomic characteristics of EPEC isolates from humans and companion animals in Korea.

Methods: The whole genome of 26 EPEC isolates from patients with diarrhea and 20 EPEC isolates from companion animals in Korea were sequenced using the Illumina HiSeq X (Illumina, USA) and Oxford Nanopore MinION (Oxford Nanopore Technologies, UK) platforms.

Primary gastric T-cell lymphoma presenting with perforation: a case report and review of the literature.

Primary gastric T-cell lymphomas (PGTL) are exceedingly rare with an estimated incidence of 0.0091 per 100,000 person-years, affecting mainly elderly males. PGTL can present with a variety of gastrointestinal symptoms, but patients only rarely present with perforation.

Hiding in plain sight: eating disorders in diverse populations - a case for comprehensive medical education.

Background: Training gaps regarding the diagnosis and management of eating disorders in diverse populations, including racial, ethnic, sexual, and gender minoritized groups, have not been thoroughly examined.

Objective: This study aimed to examine resident physicians' knowledge and attitudes regarding eating disorders in diverse populations, with a focus on areas for improved training and intervention.

Methods: Ninety-two resident physicians in internal medicine, emergency medicine, obstetrics/gynecology, psychiatry, and surgery at an academic center completed an online survey from 12/1/2020-3/1/2021, which comprised multiple choice and vignette-style open-ended questions to assess knowledge and attitudes toward the management and clinical presentations of eating disorders.

Survival Distinctions for Cases Representing Immunologically Cold Tumors via Intrinsic Disorder Assessments for Blood-Sourced TRB Variable Regions.

T cell receptor beta (TRB) sequences were recovered from the Cancer Genome Atlas Uveal Melanoma blood exome files. Intrinsic disorder scores for amino acid (AA) sequences of the entire TRB variable region were obtained and evaluated as potentially representative of overall survival (OS) distinctions, i.e.

Triel Bonds with Methyl Groups as Electron Donors. A Pentacoordinate Carbon Atom.

The triel bond (TrB) formed between Be(CH)/Mg(CH) and TrX (Tr=B, Al, and Ga; X=H, F, Cl, Br, and I) is investigated via the MP2/aug-cc-pVTZ(PP) quantum chemical protocol. The C atoms of the methyl groups in M(CH) are characterized by a negative electrostatic potential and act as an electron donor in a triel bond with the π-hole above the Tr atom of planar TrX. The interaction energy spans a wide range between -2 and -69 kcal/mol.

Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR.

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here, we present a novel algorithm for extrasensitive and specific variable (V) and joining (J) gene allele inference, allowing the reconstruction of individual high-quality gene segment libraries.

Interpretable GWAS by linking clinical phenotypes to quantifiable immune repertoire components.

Bridging the gap between genotype and phenotype in GWAS studies is challenging. A multitude of genetic variants have been associated with immune-related diseases, including cancer, yet the interpretability of most variants remains low. Here, we investigate the quantitative components in the T cell receptor (TCR) repertoire, the frequency of clusters of TCR sequences predicted to have common antigen specificity, to interpret the genetic associations of diverse human diseases.

Chemical Complementarity of Blood-Sourced, Breast Cancer-Related TCR CDR3s and the CMV UL29 and IE1 Antigens is Associated with Worse Overall Survival.

Cytomegalovirus (CMV) infection is common and becomes a particular concern in immunocompromised patients. Understanding the potential role CMV plays in breast cancer patients' disease progression is important for providing more patient-specific treatments. In this study, we analyzed whether a breast cancer patient's blood-sourced T-cell receptor (TCR) complementarity determining-3 (CDR3) amino acid (AA) sequences could provide an indication of the impact of a systemic CMV infection.

Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation.

Epstein-Barr virus (EBV) infection has long been associated with the development of multiple sclerosis (MS). MS patients have elevated titers of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Regarding CD8+ T-cells, an elevated but ineffective response to EBV was suggested in MS patients, who present with a broader MHC-I-restricted EBV-specific T-cell receptor beta chain (TRB) repertoire compared to controls.

Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.

Human type 1 diabetes (T1D) is caused by autoimmune attack on the insulin-producing pancreatic beta cells by islet antigen-reactive T cells. How human islet antigen-reactive (IAR) CD4+ memory T cells from peripheral blood affect T1D progression in the pancreas is poorly understood. Here, we aim to determine if IAR T cells in blood could be detected in pancreas.

2023 EULAR classification criteria for hand osteoarthritis.

Objectives: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features.

Methods: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls.

Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis? Data from the IMI-APPROACH cohort.

Objective: To determine the association between joint structure and gait in patients with knee osteoarthritis (OA).

Methods: IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS).

Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis.

Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways.

High-throughput RNA sequencing of the T cell receptor alpha and beta chains for simultaneous clonality and biological analyses in Sezary syndrome.

Background: Previous investigations pointed out a role for antigen stimulation in Sezary syndrome (SS). High-throughput sequencing of the T cell receptor (TR) offers several applications beyond diagnostic purposes, including the study of T cell pathogenesis.

Methods: We performed high-throughput RNA sequencing of the TR alpha (TRA) and beta (TRB) genes focusing on the complementarity-determining region 3 (CDR3) in 11 SS and one erythrodermic mycosis fungoides (MF) patients.

What We Should Expect from an Innovative Intra-Articular Hyaluronic Acid Product: Expert Opinion Based on a Comprehensive Review of the Literature.

Background: Intra-articular hyaluronic acid (IAHA) products are often used in the treatment of adults with mild-to-moderate knee osteoarthritis (KOA). The International Symposium on Intra-Articular Treatment (ISIAT) convened a multidisciplinary technical expert panel to define characteristics for an innovative IAHA product that should answer unmet needs in the clinical management of adults with mild-to-moderate KOA.

Methods: An initial set of evidence-based statements was developed based on data extracted from articles identified through a comprehensive literature search.

Novel bimodal TRBD1-TRBD2 rearrangements with dual or absent D-region contribute to TRB V-(D)-J combinatorial diversity.

T-cell receptor (TR) diversity of the variable domains is generated by recombination of both the alpha (TRA) and beta (TRB) chains. The textbook process of TRB chain production starts with TRBD and TRBJ gene rearrangement, followed by the rearrangement of a TRBV gene to the partially rearranged D-J gene. Unsuccessful V-D-J TRB rearrangements lead to apoptosis of the cell.

Protein Coronas on Functionalized Nanoparticles Enable Quantitative and Precise Large-Scale Deep Plasma Proteomics.

Background: The wide dynamic range of circulating proteins coupled with the diversity of proteoforms present in plasma has historically impeded comprehensive and quantitative characterization of the plasma proteome at scale. Automated nanoparticle (NP) protein corona-based proteomics workflows can efficiently compress the dynamic range of protein abundances into a mass spectrometry (MS)-accessible detection range. This enhances the depth and scalability of quantitative MS-based methods, which can elucidate the molecular mechanisms of biological processes, discover new protein biomarkers, and improve comprehensiveness of MS-based diagnostics.

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1.

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear.