Template-Based Information Extraction System for Detection of Events on Twitter

With the number of prosecutions for crimes on online social networks rising each year combined with the volume, velocity and variety of the data produced on these online social networks, it is almost impossible to effectively discover instances of crime or criminal behavior manually. Past work has been conducted in the area of event detection using Twitter, including TEDAS (Li, et al., 2012) and Jasmine (Watanabe, et al., 2011). This paper proposes a novel solution allowing for real-time monitoring of geo-tagged posts on Twitter using information extraction techniques to discover relevant information. This approach has had promising results, returning a number of relevant results from within the data set used in the evaluation

Absence of Epstein-Barr virus DNA in anti-citrullinated protein antibody-expressing B cells of patients with rheumatoid arthritis

Objective: Rheumatoid arthritis (RA) is characterized by the presence of disease-specific autoreactive B cell responses, in particular those generating anti-citrullinated protein antibodies (ACPA). For many years, Epstein-Barr virus (EBV) has been implicated in disease pathogenesis, possibly by facilitating the development and persistence of autoreactive B cells. To test this hypothesis, the presence of EBV episomes in ACPA-expressing B cells was analyzed.Methods: ACPA-expressing B cells derived from peripheral blood (PB) of seven EBV-seropositive RA patients, and synovial fluid (SF) of one additional EBV-seropositive RA patient, were isolated by flow cytometry. PB cells were expanded for 11-12 days, after which supernatant was harvested and analyzed for cyclic citrullinated-peptide (CCP)2 reactivity. SF cells were isolated directly in a lysis buffer. DNA was isolated and qPCR reactions were performed to determine the EBV status of the cells. EBV-immortalized B cell lymphoblastoid-cell lines (EBV blasts) served as standardized controls.Results: Two hundred ninety-six PB and 60 SF ACPA-expressing B cells were isolated and divided over 16 and 3 pools containing 10-20 cells, respectively. Supernatants of all 16 cultured PB pools contained CCP2-Ig. DNA of all pools was used for qPCR analysis. While EBV-blast analysis showed sensitivity to detect EBV DNA in single B cells, no EBV DNA was detected in any of the ACPA-expressing B cell pools.Conclusion: ACPA-expressing B cells are not enriched for EBV-DNA-containing clones. These results do not support the hypothesis that EBV infection of autoreactive B cells causes or maintains autoreactive B cell populations in RA. Instead, other mechanisms might explain the association between positive EBV serology and RA.Pathophysiology and treatment of rheumatic disease

Addressing the key issue: Antigen-specific targeting of B cells in autoimmune diseases

Autoimmune diseases are heterogeneous pathologies characterized by a breakdown of immunological tolerance to self, resulting in a chronic and aberrant immune response to self-antigens. The scope and extent of affected tissues can vary greatly per autoimmune disease and can involve multiple organs and tissue types. The patho-genesis of most autoimmune diseases remains unknown but it is widely accepted that a complex interplay be-tween (autoreactive) B and T cells in the context of breached immunological tolerance drives autoimmune pathology. The importance of B cells in autoimmune disease is exemplified by the successful use of B cell tar-geting therapies in the clinic. For example, Rituximab, a depleting anti-CD20 antibody, has shown favorable results in reducing the signs and symptoms of multiple autoimmune diseases, including Rheumatoid Arthritis, Anti-Neutrophil Cytoplasmic Antibody associated vasculitis and Multiple Sclerosis. However, Rituximab depletes the entire B cell repertoire, leaving patients susceptible to (latent) infections. Therefore, multiple ways to target autoreactive cells in an antigen-specific manner are currently under investigation. In this review, we will lay out the current state of antigen-specific B cell inhibiting or depleting therapies in the context of autoimmune diseases.NWONWO-024.002.009Pathophysiology and treatment of rheumatic disease

Autoreactive B cells in rheumatoid arthritis include mainly activated CXCR3+memory B cells and plasmablasts

Many autoimmune diseases (AIDs) are characterized by the persistence of autoreactive B cell responses, which have been directly implicated in disease pathogenesis. How and why these cells are generated or how they are maintained for years is largely unknown. Rheumatoid arthritis (RA) is among the most common AIDs and is characterized by autoantibodies recognizing proteins with posttranslational modifications (PTMs). This PTM-directed autoreactive B cell compartment is ill defined. Here, we visualized the B cell response against the three main types of PTM antigens implicated in RA by spectral flow cytometry. Our results showed extensive cross-reactivity of PTM-directed B cells against all three PTM antigens (citrulline, homocitrulline, and acetyllysine). Unsupervised clustering revealed several distinct memory B cell (mBC) populations. PTM-directed cells clustered with the most recently activated class-switched mBC phenotype, with high CD80, low CD24, and low CD21 expression. Notably, patients also harbored large fractions of PTM-directed plasmablasts (PBs). Both PTM-directed mBCs and PBs showed high expression of CXCR3, a receptor for chemokines present in abundance in arthritic joints. Together, our data provide detailed insight into the biology of B cell autoreactivity and its remarkable, seemingly exhaustless persistence in a prominent human AID. Pathophysiology and treatment of rheumatic disease

Autoreactive B cells in rheumatoid arthritis consist of activated CXCR3+ memory B cells and plasmablasts

Many autoimmune diseases (AIDs) are characterized by persistence of autoreactive B cell responses which is often directly implicated in disease pathogenesis. How and why these cells are generated or how they are maintained for years is largely unknown. Rheumatoid arthritis is among the most common AIDs and characterized by autoantibodies recognizing proteins with post-translational modifications (PTMs). This PTM-directed, autoreactive B cell compartment is ill defined. Here, we visualized the B cell response against the three main types of PTM antigens implicated in RA by spectral flow cytometry. Our results show extensive cross-reactivity of autoreactive B cells against all three PTM antigens (citrulline, homocitrulline and acetyllysine). Unsupervised clustering revealed several distinct memory B cell (mBC) populations. Autoreactive cells clustered with the most recently activated, class-switched mBC phenotype, expressing high CD80, low CD24 and low CD21. Notably, patients also harbored large fractions of autoreactive plasmablasts (PB). Both PTM-directed mBC and PB showed high expression of CXCR3, a receptor for chemokines abundantly present in arthritic joints. Together, our data provide novel, detailed insight into the biology of B cell autoreactivity and its remarkable, seemingly exhaustless persistence in a prominent human AID. Pathophysiology and treatment of rheumatic disease

Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

BACKGROUND: /st> Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. OBJECTIVE: /st> To analyse the effect of the 6q23 region on the rate of joint destruction. METHODS: /st> Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. RESULTS: /st> Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. CONCLUSIONS: /st> These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.Pathophysiology and treatment of rheumatic disease

Рідке мило на основі соапстоків після нейтралізації олій та жирів в нейтралізуючому розчині, що містить етанол

Development and application of statistical models for medical scientific researc

Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis

Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course