Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage.
View Article and Find Full Text PDFCirculating extracellular vesicles and particles (EVPs) are being investigated as potential biomarkers for early cancer detection, prognosis, and disease monitoring. However, the suboptimal purity of EVPs isolated from peripheral blood plasma has posed a challenge of in-depth analysis of the EVP proteome. Here, we compared the effectiveness of different methods for isolating EVPs from healthy donor plasma, including ultracentrifugation (UC)-based protocols, phosphatidylserine-Tim4 interaction-based affinity capture (referred to as "PS"), and several commercial kits.
View Article and Find Full Text PDFSummary: Subcluster analysis is a powerful means to improve clustering and characterization of single cell RNA-Seq data. However, there are no existing tools to systematically integrate results from multiple subclusters, which creates hurdles for accurate data quantification, visualization, and interpretation in downstream analysis. To address this issue, we developed Ragas, an R package that integrates multi-level subclustering objects for streamlined analysis and visualization.
View Article and Find Full Text PDFOne of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment.
View Article and Find Full Text PDFOur study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.
View Article and Find Full Text PDFPneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct.
View Article and Find Full Text PDFInfants necessitate vaccinations to prevent life-threatening infections. Our understanding of the infant immune responses to routine vaccines remains limited. We analyzed two cohorts of 2-month-old infants before vaccination, one week, and one-month post-vaccination.
View Article and Find Full Text PDFInflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19).
View Article and Find Full Text PDFSystemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN . Thus, defective removal of mitochondria from mature red blood cells (Mito RBCs), a feature of SLE, contributes to IFN production by myeloid cells .
View Article and Find Full Text PDFPneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax) and a conjugated polysaccharide vaccine PCV13 (Prevnar) are used to prevent these infections, yet underlying responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13.
View Article and Find Full Text PDFIn the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance.
View Article and Find Full Text PDFAutoreactive B cells and interferons are central players in systemic lupus erythematosus (SLE) pathogenesis. The partial success of drugs targeting these pathways, however, supports heterogeneity in upstream mechanisms contributing to disease pathogenesis. In this review, we focus on recent insights from genetic and immune monitoring studies of patients that are refining our understanding of these basic mechanisms.
View Article and Find Full Text PDFComput Methods Programs Biomed
February 2023
Background And Objective: Age-related macular degeneration (AMD) is an eye disease that happens when ageing causes damage to the macula, and it is the leading cause of blindness in developed countries. Screening retinal fundus images allows ophthalmologists to early detect, diagnose and treat this disease; however, the manual interpretation of images is a time-consuming task. In this paper, we aim to study different deep learning methods to diagnose AMD.
View Article and Find Full Text PDFStill's disease is a severe inflammatory syndrome characterized by fever, skin rash and arthritis affecting children and adults. Patients with Still's disease may also develop macrophage activation syndrome, a potentially fatal complication of immune dysregulation resulting in cytokine storm. Here we show that mTORC1 (mechanistic target of rapamycin complex 1) underpins the pathology of Still's disease and macrophage activation syndrome.
View Article and Find Full Text PDFThe incorporation of a healthy diet, regular physical exercise and smoking cessation are the initial measures to reduce cardiovascular risk in patients with atherogenic dyslipidemia. In these patients, the nutritional quality of their diet should be improved, replacing foods with a greater atherogenic effect for others with a healthier effect. There is strong evidence that plant-based dietary patterns, low in saturated fatty acids, cholesterol and sodium, with a high content of fiber, potassium and unsaturated fatty acids, are beneficial and reduce the expression of cardiovascular risk factors.
View Article and Find Full Text PDFObjectives: Risk perception of the COVID-19 pandemic may affect chronic disease outcomes among patients with rheumatic diseases (RD). To describe and compare the perception of risk and effects of the COVID-19 pandemic on patients with RD from two health care centers compared with a control group.
Methods: A retrospective case-control study was conducted.
One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated.
View Article and Find Full Text PDFJ Stroke Cerebrovasc Dis
February 2022