Belimumab efficacy in mucocutaneous lupus erythematosus: a large post-hoc analysis from five phase III clinical trials.

Objective: To determine the efficacy of belimumab on mucocutaneous manifestations of systemic lupus erythematosus (SLE) in a large integrative analysis.

Methods: Using data from five phase III clinical trials (BLISS-52; BLISS-76; BLISS-NEA; EMBRACE; BLISS-SC; N = 3086), we investigated the effect of belimumab vs placebo on top of standard therapy on inducing improvement in mucocutaneous British Isles Lupus Assessment Group (mcBILAG) and mucocutaneous SLE Disease Activity Index 2000 (mcSLEDAI-2K), and on preventing mcBILAG flares. We employed logistic and Cox regression analysis, adjusting for trial variance.

Holistic approaches in systemic lupus erythematosus: do physicians avoid addressing difficult-to-treat but highly relevant symptoms?

Despite advancements in the management of systemic lupus erythematosus (SLE), patients experience poor health-related quality of life (hrQoL) and premature death due to disease severity and treatment side effects. Achieving remission offers substantial benefits, including improved hrQoL and reduced mortality, yet the complexity of SLE, with its diverse underlying immune mechanisms and clinical manifestations, hampers progress. Involvement of the central nervous system with symptoms like fatigue, pain and brain fog often goes unaddressed due to limited evidence-based guidance and measurement tools.

Virtual Patient Simulations Using Social Robotics Combined With Large Language Models for Clinical Reasoning Training in Medical Education: Mixed Methods Study.

Background: Virtual patients (VPs) are computer-based simulations of clinical scenarios used in health professions education to address various learning outcomes, including clinical reasoning (CR). CR is a crucial skill for health care practitioners, and its inadequacy can compromise patient safety. Recent advancements in large language models (LLMs) and social robots have introduced new possibilities for enhancing VP interactivity and realism.

Time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model uncovers ECM homoeostasis-related translationally relevant genes.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential.

High DNA methylation age deceleration defines an aggressive phenotype with immunoexclusion environments in endometrial carcinoma.

Like telomere shortening, global DNA hypomethylation occurs progressively with cellular divisions or aging and functions as a mitotic clock to restrain malignant transformation/progression. Several DNA-methylation (DNAm) age clocks have been established to precisely predict chronological age using normal tissues, but show DNAm age drift in tumors, which suggests disruption of this mitotic clock during carcinogenesis. Little is known about DNAm age alterations and biological/clinical implications in endometrial cancer (EC).

promoter mutations and methylation for telomerase activation in urothelial carcinomas: New mechanistic insights and clinical significance.

Telomerase, an RNA-dependent DNA polymerase synthesizing telomeric TTAGGG sequences, is primarily silent in normal human urothelial cells (NHUCs), but widely activated in urothelial cell-derived carcinomas or urothelial carcinomas (UCs) including UC of the bladder (UCB) and upper track UC (UTUC). Telomerase activation for telomere maintenance is required for the UC development and progression, and the key underlying mechanism is the transcriptional de-repression of the , a gene encoding the rate-limiting, telomerase catalytic component. Recent mechanistic explorations have revealed important roles for TERT promoter mutations and aberrant methylation in activation of transcription and telomerase in UCs.

Thyroid carcinoma-featured telomerase activation and telomere maintenance: Biology and translational/clinical significance.

Background: Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co-factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes.

Phenotypic and HLA-DRB1 allele characterization of Swedish cardiac sarcoidosis patients.

Background: Early detection and initiation of treatment in cardiac sarcoidosis (CS) is believed to be crucial to reduce morbidity and mortality. The diagnosis of CS is challenging, especially in isolated CS (ICS). Certain human leukocyte antigen (HLA-DRB1) alleles associate with different phenotypes of sarcoidosis.

The association of telomere maintenance and TERT expression with susceptibility to human papillomavirus infection in cervical epithelium.

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection.

DNA Methylation Age Drift Is Associated with Poor Outcomes and De-Differentiation in Papillary and Follicular Thyroid Carcinomas.

Alterations in global DNA methylation play a critical role in both aging and cancer, and DNA methylation (DNAm) age drift has been implicated in cancer risk and pathogenesis. In the present study, we analyzed the TCGA cohort of papillary and follicular thyroid carcinoma (PTC and FTC) for their DNAm age and association with clinic-pathological features. In 54 noncancerous thyroid (NT) samples, DNAm age was highly correlated with patient chronological age (R = 0.

Bronchoalveolar lavage fluid cell subsets associate with the disease course in Löfgren's and non-Löfgren's sarcoidosis patients.

Background: Sarcoidosis is a multisystem granulomatous inflammatory disorder, that predominantly involves the lungs. Patients with Löfgren's syndrome (LS) are characterized by acute onset and usually have the HLA-DRB1*03 (DR3) allele and a good prognosis. Non-LS patients are usually DR3 and are more likely to develop chronic disease.

Regulatory region mutations of , and genes as urinary biomarkers in upper tract urothelial carcinomas.

The hotspot regulatory region mutations of the TERT, PLEKHS1 and GPR126 genes have been shown to occur frequently in urothelial bladder carcinoma (UBC). However, it is currently unclear whether these mutations are all present in upper tract urothelial carcinomas (UTUC) including renal pelvic carcinoma (RPC) and ureter carcinoma (UC), although TERT promoter mutations were previously observed in these malignancies. The hotspot mutations of TERT and PLEKHS1 promoters and GPR126 intron 6 (enhancer) in tumors derived from 164 patients with UTUC were determined using Sanger sequencing, and the obtained results were further compared with the mutation frequency in 106 UBCs.

Telomerase reverse transcriptase promoter mutations in thyroid carcinomas: implications in precision oncology-a narrative review.

Telomerase is a ribonucleoprotein enzyme with telomerase reverse transcriptase (TERT) as a catalytic component. In normal human follicular thyroid cells or thyrocytes, telomerase is silent due to the gene being tightly repressed. However, during the formation of thyroid carcinoma (TC), telomerase becomes activated via TERT induction.

TERT promoter mutations and GABP transcription factors in carcinogenesis: More foes than friends.

The transcriptional de-repression of the telomerase reverse transcriptase (TERT) gene and subsequent activation of telomerase is a prerequisite step in malignant transformation and progression. Recently, the gain-of-function mutation of the TERT promoter was identified in many types of human malignancies, and the mutated promoter acquires de novo ETS binding motifs through which the TERT transcription is activated. The ETS family transcription factors GABPA and GABPB1 have been shown to act as master drivers for the mutant TERT promoter activity.

Lung CD4+ Vα2.3+ T-cells in sarcoidosis cohorts with Löfgren's syndrome.

Background: Sarcoidosis is diagnosed by a combination of typical clinical and radiological findings together with biopsy proof of non-caseating epithelioid cell granulomas in affected tissues and/or the cell distribution in bronchoalveolar lavage fluid (BALF). We aimed at investigating the usefulness of measuring the proportion of T-cell receptor (TCR) CD4+ Vα2.3+ T-cells in BALF as an additive marker to CD4/CD8-ratio to confirm the diagnosis.

Subpopulations of cells from bronchoalveolar lavage can predict prognosis in sarcoidosis.

http://bit.ly/2Mta0Cs

Publisher Correction: Sarcoidosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sarcoidosis.

Sarcoidosis is an inflammatory disorder of unknown cause that is characterized by granuloma formation in affected organs, most often in the lungs. Patients frequently suffer from cough, shortness of breath, chest pain and pronounced fatigue and are at risk of developing lung fibrosis or irreversible damage to other organs. The disease develops in genetically predisposed individuals with exposure to an as-yet unknown antigen.

Disease activity in rheumatoid arthritis is inversely related to cerebral TSPO binding assessed by [C]PBR28 positron emission tomography.

Reumatoid Arthritis (RA) is an autoimmune disorder characterized by peripheral joint inflammation. Recently, an engagement of the brain immune system has been proposed. The aim with the current investigation was to study the glial cell activation marker translocator protein (TSPO) in a well characterized cohort of RA patients and to relate it to disease activity, peripheral markers of inflammation and autonomic activity.

The TERT locus genotypes of rs2736100-CC/CA and rs2736098-AA predict shorter survival in renal cell carcinoma.

Objectives: The single nucleotide polymorphisms (SNPs) at the TERT rs2736100 and rs2736098 are associated with multicancer susceptibility, however, published findings regarding renal cell carcinoma (RCC) risk are conflicting. In addition, the potential of these SNPs to predict outcomes in RCC remains unclear. The present study is designed to address these questions.

Soluble epoxide hydrolase derived lipid mediators are elevated in bronchoalveolar lavage fluid from patients with sarcoidosis: a cross-sectional study.

Background: Sarcoidosis is a systemic inflammatory multi-organ disease almost always affecting the lungs. The etiology remains unknown, but the hallmark of sarcoidosis is formation of non-caseating epithelioid cells granulomas in involved organs. In Scandinavia, > 30% of sarcoidosis patients have Löfgren's syndrome (LS), an acute disease onset mostly indicating a favorable prognosis.

An LC-MS/MS workflow to characterize 16 regio- and stereoisomeric trihydroxyoctadecenoic acids.

Trihydroxyoctadecenoic acids (TriHOMEs) are linoleic acid-derived oxylipins with potential physiological relevance in inflammatory processes as well as in maintaining an intact skin barrier. Due to the high number of possible TriHOME isomers with only subtle differences in their physicochemical properties, the stereochemical analysis is challenging and usually involves a series of laborious analytical procedures. We herein report a straightforward analytical workflow that includes reversed-phase ultra-HPLC-MS/MS for rapid quantification of 9,10,13- and 9,12,13-TriHOME diastereomers and a chiral LC-MS method capable of resolving all sixteen 9,10,13-TriHOME and 9,12,13-TriHOME regio- and stereoisomers.

TERT rs2736100 genotypes are associated with differential risk of myeloproliferative neoplasms in Swedish and Chinese male patient populations.

The telomerase reverse transcriptase (TERT) gene rs2736100_C allele has recently been shown to be associated with an increased risk for myeloproliferative neoplasms (MPNs) among Caucasians. However, it is unknown if this association is present in other ethnical populations and whether rs2736100 allele frequencies mirror the incidence of MPNs in a population. Here we genotyped TERT rs2736100 variants in 126 Swedish and 101 Chinese MPN patients and their age-, sex-, and ethnically-matched healthy controls.

Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications.

The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization.