T cell receptor beta germline variability is revealed by inference from repertoire data.

Background: T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance.

Novel clonality assays for T cell lymphoma in cats targeting the T cell receptor beta, T cell receptor delta, and T cell receptor gamma loci.

Background: T cell clonality assays in veterinary medicine currently target only the T cell receptor gamma (TRG) locus. Existing assays have suboptimal sensitivity because of insufficient primer coverage of all possible rearrangements.

Objective: Develop higher sensitivity clonality assays targeting the TRG, delta (TRD), and beta (TRB) loci in cats.

Neuropathic pain in the IMI-APPROACH knee osteoarthritis cohort: prevalence and phenotyping.

Objectives: Osteoarthritis (OA) patients with a neuropathic pain (NP) component may represent a specific phenotype. This study compares joint damage, pain and functional disability between knee OA patients with a likely NP component, and those without a likely NP component.

Methods: Baseline data from the Innovative Medicines Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway knee OA cohort study were used.

Real-world evidence in a national health service: results of the UK CardioMEMS HF System Post-Market Study.

Aims: The CardioMEMS HF System Post-Market Study (COAST) was designed to evaluate the safety, effectiveness, and feasibility of haemodynamic-guided heart failure (HF) management using a small sensor implanted in the pulmonary artery of New York Heart Association (NYHA) Class III HF patients in the UK, Europe, and Australia.

Methods And Results: COAST is a prospective, international, multicentre, open-label clinical study (NCT02954341). The primary clinical endpoint compares annualized HF hospitalization rates after 1 year of haemodynamic-guided management vs.

Next-generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides.

Background: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population.

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

Background: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.

Methods: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.

Are outpatient transperineal prostate biopsies without antibiotic prophylaxis equivalent to standard transrectal biopsies for patient safety and cancer detection rates?A retrospective cohort study in 222 patients.

Background: To describe our experience with outpatient transperineal biopsy (TPB) without antibiotics compared to transrectal biopsy (TRB) with antibiotics and bowel preparation. The literature elicits comparable cancer detection, time, and cost between the two. As antibiotic resistance increases, antimicrobial stewardship is imperative.

A comparison of immune receptor recombination databases sourced from tumour exome or RNAseq files: Verifications of immunological distinctions between primary and metastatic melanoma.

It became apparent several years ago that RNAseq and exome files prepared from tissue could be mined for adaptive immune receptor (IR) recombinations, which has given extra value to datasets originally intended for gene expression or mutation studies. For example, recovery of IR recombination reads from tumour specimen genomics files can correlate with survival rates. In particular, many benchmarking processes have been applied to the two sets of the IR recombination reads obtained from the cancer genome atlas files, but these two sets have never been directly compared.

Association between redundant endometrium and endometrial polyps: a pilot study.

Background: The aim of this study was to explore the organic features of redundant endometrium (RE), we examined the expression of different endometrial hormone receptors, oncogenes, and cell replication markers, in normal endometrium (NE), endometrial polyps (EP) and RE specimens.

Methods: This was an experimental study examining endometrial tissue expression of estrogen receptors (ER1 and 2), progesterone receptors (PR-A+B), androgen receptor (AR), insulin receptor (Insulin-R), insulin-like growth factor receptor 1 (IGFR-1), thyroid hormone receptor (TH-RB), B-cell lymphoma 2 (Bcl-2), Ki67, HOXA10, in women with NE, EP and RE, of women undergoing hysteroscopy for benign gynecologic pathology. Specimens were separated in 3 groups: NE, EP, RE.

Psychometric Properties of the Copenhagen Burnout Inventory in a Sample of Medical Students in Kazakhstan.

Background: The Copenhagen Burnout Inventory (CBI) has demonstrated good psychometric properties among different populations, but there is no known data on its validity among Russian-speaking medical students. The CBI-Student Survey focuses only on fatigue, but measures exhaustion in four different life domains: Personal Burnout (PB), Studies-Related Burnout (SRB), Colleague-Related Burnout (CRB), and Teacher-Related Burnout (TRB).

Objective: To investigate the psychometric properties of the Russian version of the Copenhagen Burnout Inventory-Student Survey (R-CBI-S).

Aspirin, Statins, and Primary Prevention: Opportunities for Shared Decision Making in the Face of Uncertainty.

Purpose Of Review: The utility of aspirin and statins for primary prevention of atherosclerotic cardiovascular disease remains ambiguous in older adults. Current guidelines and recent data are vague and inconclusive. This review seeks to summarize the landscape of primary prevention of cardiovascular disease in older adults and explore the role of shared decision making.

A putative "chemokine switch" that regulates systemic acute inflammation in humans.

Systemic inflammation is complex and likely drives clinical outcomes in critical illness such as that which ensues following severe injury. We obtained time course data on multiple inflammatory mediators in the blood of blunt trauma patients. Using dynamic network analyses, we inferred a novel control architecture for systemic inflammation: a three-way switch comprising the chemokines MCP-1/CCL2, MIG/CXCL9, and IP-10/CXCL10.

Racial and Ethnic Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: An Analysis of 45 States and the District of Columbia.

The coronavirus disease 2019 (COVID-19) epidemic in the United States has disproportionately impacted communities of color across the country. Focusing on COVID-19-attributable mortality, we expand upon a national comparative analysis of years of potential life lost (YPLL) attributable to COVID-19 by race/ethnicity (Bassett et al., 2020), estimating percentages of total YPLL for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, non-Hispanic Asians, and non-Hispanic American Indian or Alaska Natives, contrasting them with their respective percent population shares, as well as age-adjusted YPLL rate ratios-anchoring comparisons to non-Hispanic Whites-in each of 45 states and the District of Columbia using data from the National Center for Health Statistics as of 30 December 2020.

Subcutaneous tanezumab for osteoarthritis: Is the early improvement in pain and function meaningful and sustained?

Background: To evaluate if early improvements in pain and function with subcutaneous tanezumab are meaningful and sustained over 24 weeks.

Methods: Patients with moderate-to-severe osteoarthritis (hip or knee) in Europe and Japan were randomized to placebo, tanezumab 2.5 mg or tanezumab 5 mg (baseline, Week 8 and Week 16).

Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle.

Background: Currently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect.

Safe and rapid radial hemostasis achieved using a novel topical hemostatic patch: Results of a first-in-human pilot study using hydrophobically modified polysaccharide-chitosan.

Background: The transradial approach (TRA) for catheter interventions decreases vascular complications and bleeding versus transfemoral approach. Reducing time to hemostasis and preventing radial artery occlusion (RAO) following TRA are important and incompletely realized aspirations.

Objectives: This first-in-human study sought to evaluate the efficacy of a novel, topically applied compound (hydrophobically modified polysaccharide-chitosan, hm-P) plus minimal required pneumatic compression, to achieve rapid radial arterial hemostasis in post-TRA procedures compared with de facto standards.

Weak σ-Hole Triel Bond between C H Tr (Tr=B, Al, Ga) and Haloethyne: Substituent and Cooperativity Effects.

The replacement of a CH group of benzene by a triel (Tr) atom places a positive region of electrostatic potential near the Tr atom in the plane of the aromatic ring. This σ-hole can interact with an X lone pair of XCCH (X=F, Cl, Br, and I) to form a triel bond (TrB). The interaction energy between C H Tr and FCCH lies in the range between 2.

Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence.

Primary melanomas >1 mm thickness are potentially curable by resection, but can recur metastatically. We assessed the prognostic value of T cell fraction (TCFr) and repertoire T cell clonality, measured by high-throughput-sequencing of the T cell receptor beta chain (TRB) in T2-T4 primary melanomas (n=199). TCFr accurately predicted progression-free survival (PFS) and was independent of thickness, ulceration, mitotic rate, or age.

Defining Dry Eye from a Clinical Perspective.

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe.

The SPPL3-Defined Glycosphingolipid Repertoire Orchestrates HLA Class I-Mediated Immune Responses.

HLA class I (HLA-I) glycoproteins drive immune responses by presenting antigens to cognate CD8 T cells. This process is often hijacked by tumors and pathogens for immune evasion. Because options for restoring HLA-I antigen presentation are limited, we aimed to identify druggable HLA-I pathway targets.

Cutaneous T-cell lymphomas with pathogenic somatic mutations and absence of detectable clonal T-cell receptor gene rearrangement: two case reports.

Background: Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin lymphomas for which diagnosis can be challenging given the potential for overlap with inflammatory dermatoses. Current diagnostic criteria for CTCL incorporate clinical and histopathologic findings as well as results of T-cell receptor (TCR) gene sequencing. Molecular interrogation of TCR genes, TRG and TRB, has proven to be a critical tool for confirming diagnoses of CTCL and for disease tracking after initiation of therapy or after stem cell transplant.

Benchmarking of T cell receptor repertoire profiling methods reveals large systematic biases.

Monitoring the T cell receptor (TCR) repertoire in health and disease can provide key insights into adaptive immune responses, but the accuracy of current TCR sequencing (TCRseq) methods is unclear. In this study, we systematically compared the results of nine commercial and academic TCRseq methods, including six rapid amplification of complementary DNA ends (RACE)-polymerase chain reaction (PCR) and three multiplex-PCR approaches, when applied to the same T cell sample. We found marked differences in accuracy and intra- and inter-method reproducibility for T cell receptor α (TRA) and T cell receptor β (TRB) TCR chains.