Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic analysis of synovial signalling and gene expression in animal models of arthritis

Background Animal models of arthritis are frequently used to evaluate novel therapeutic agents. However, their ability to predict responses in humans is variable. Objective To examine the time course of signalling molecule and gene expression in two models of arthritis to assist with selection of the model and timing of drug administration. Methods The passive K/BxN serum transfer and collagen-induced arthritis (CIA) models were studied. Activation of MAP kinase and interferon (IFN)-response pathways was evaluated by quantitative PCR and western blot analysis of ankle joints at various time points during the models. Results The kinetics of gene expression and kinase phosphorylation were strikingly different in passive K/BxN and CIA. All three MAP kinases (ERK, JNK and p38) and upstream kinases were activated within days in passive K/BxN and declined as arthritis severity decreased. Surprisingly, IFN-regulated genes, including IRF7, were not induced in the model. In CIA, activation of ERK and JNK was surprisingly low and p38 phosphorylation mainly peaked late in the disease. IFN-response genes were activated during CIA, with especially prominent peaks at the onset of clinical arthritis. Conclusions Timing of treatment and selection of CIA or passive K/BxN might have an important impact on therapeutic response. p38, in particular, increases during the late stages of CIA. ERK and JNK patterns are similar in passive K/BxN and rheumatoid arthritis (RA), while IFN-response genes in CIA and RA are similar. The dichotomy between RA and animal models could help explain the poor correlation between efficacy in RA and preclinical studies.
Evaluation of several ultrasonography scoring systems for synovitis and comparison to clinical examination: results from a prospective multicentre study of rheumatoid arthritis

Objectives To evaluate different global ultrasonographic (US) synovitis scoring systems as potential outcome measures of rheumatoid arthritis (RA) according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) filter. Methods To study selected global scoring systems, for the clinical, B mode and power Doppler techniques, the following joints were evaluated: 28 joints (28-joint Disease Activity Score (DAS28)), 20 joints (metacarpophalangeals (MCPs) + metatarsophalangeals (MTPs)) and 38 joints (28 joints + MTPs) using either a binary (yes/no) or a 0–3 grade. The study was a prospective, 4-month duration follow-up of 76 patients with RA requiring anti-tumour necrosis factor (TNF) therapy (complete follow-up data: 66 patients). Intraobserver reliability was evaluated using the intraclass correlation coefficient (ICC), construct validity was evaluated using the Cronbach α test and external validity was evaluated using level of correlation between scoring system and C reactive protein (CRP). Sensitivity to change was evaluated using the standardised response mean. Discriminating capacity was evaluated using the standardised mean differences in patients considered by the doctor as significantly improved or not at the end of the study. Results Different clinimetric properties of various US scoring systems were at least as good as the clinical scores with, for example, intraobserver reliability ranging from 0.61 to 0.97 versus from 0.53 to 0.82, construct validity ranging from 0.76 to 0.89 versus from 0.76 to 0.88, correlation with CRP ranging from 0.28 to 0.34 versus from 0.28 to 0.35 and sensitivity to change ranging from 0.60 to 1.21 versus from 0.96 to 1.36 for US versus clinical scoring systems, respectively. Conclusion This study suggests that US evaluation of synovitis is an outcome measure at least as relevant as physical examination. Further studies are required in order to achieve optimal US scoring systems for monitoring patients with RA in clinical trials and in clinical practice.
Electromyographic comparison of the mid-vastus and sub-vastus approaches to total knee arthroplasty

Background To date there has been no study using robust surface electromyographic methods to compare the effect of sub-vastus and mid-vastus approaches to total knee arthroplasty on quadriceps activity. This study was done to ascertain if the sub-vastus technique would result in greater postoperative muscle activity than a vastus splitting approach as measured by electromyography and an earlier achievement of a straight leg raise. Methods This was a prospective comparative study of the sub-vastus and mid-vastus approaches on vastus medialis and vastus lateralis muscle activity measured by electromyography and time to straight leg raise in 18 patients (7 men and 11 women) after a primary total knee arthroplasty. Results A statistically significant difference in the number of days taken to achieve straight leg was noted between the mid-vastus and sub-vastus groups (mid-vastus = 2.0 days, 95% CI, 1.43 to 2.56; sub-vastus = 1.25 days, 95% CI, 0.93 to 1.57; P = 0.045). There were no statistical differences (P > 0.05) between the two techniques in electromyography or any of the secondary outcomes at 5 days, 6 weeks and 3 months after surgery. There was no significant correlation (P > 0.05) between the earlier return of straight leg raise in the sub-vastus technique and increased quadriceps activation. Conclusions This study did not find any statistically significant differences in electromyographic data between the two approaches, suggesting no evidence of denervation of the vastus medialis, although the sub-vastus technique led to an earlier single-leg raise.
Impact of anti-tumour necrosis factor therapy on the weight of patients with rheumatoid arthritis

The role of tumour necrosis factor α (TNFα) in cachexia is established.1 More recent studies have found that adipocytes of obese animals and humans express higher levels of TNF than controls2 3; in this phenotype higher concentrations of TNFα are thought to limit further fat accumulation.4 5 We observed weight gain was becoming an increasing problem in some of our patients with rheumatoid arthritis (RA) given anti-TNF therapy. Several patients had raised this concern at review appointments and one even elected to discontinue anti-TNF treatment owing to weight gain. The authors therefore undertook a longitudinal retrospective review of …
Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population

Objective Variations in gene copy number (CNV) have been recognised as a hereditable source of susceptibility in human complex diseases. Recent studies have shown that Tlr7 gene dosage has a significant contribution in the autoimmune-enhancing effect in mouse models of systemic lupus erythematosus (SLE). A study was therefore performed to investigate whether CNVs in TLR7 contribute to the genetic component of childhood-onset SLE. Methods A case–control association study was performed in 328 Mexican children with SLE and 403 healthy controls. Determination of CNVs of TLR7 was achieved by real-time PCR using the ΔΔCt method. Expression levels of TLR7 and interferon α (IFNα) were determined in 23 patients. In addition, a stratification analysis was performed to investigate the association of TLR7 gene copy number (CN) with lupus nephritis. Results A significant increase was found in the relative TLR7 gene CN in females patients with SLE compared with female controls (p<0.0001). However, logistic regression analysis by gender showed a higher OR (OR 6.61, p=0.005) in male patients with >1 copy of TLR7 than in female patients with >2 copies (OR 3.07, p<0.0001). This association was not observed with lupus nephritis. TLR7 mRNA levels correlated significantly with TLR7 CN and with IFNα mRNA levels. Conclusion These results show that an increase in TLR7 CN is a risk factor for childhood-onset SLE and provide new evidence for a role for X-linked gene dosage in SLE susceptibility. There is also evidence to suggest that TLR7 may be involved in the pathogenesis of SLE through the induction of IFNα.
Circulating levels of frizzled-related protein (FRZB) are increased in patients with early rheumatoid arthritis and decrease in response to disease-modifying antirheumatic drugs

Products of the secreted frizzled-related protein (FRZB) families have crucial roles in the development and maintenance of bone, cartilage and joints, mainly by inhibiting the wnt and/β catenin pathway.1 In particular, while several important studies have associated FRZB (also known as sFRP3) with an increased susceptibility to the development of osteoarthritis,2,–,4 no information is available on the potential role of circulating FRZB in early rheumatoid arthritis (ERA). We have measured the serum levels of FRZB by ELISA (R&D Systems, Minneapolis, Minnesota, USA) in a cohort of patients presenting with ERA, defined as previously described.5 Serological signs of inflammation (raised erythrocyte sedimentation rate or C reactive …
Serum urate and its relationship with alcoholic beverage intake in men and women: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort

Objective To investigate if beer, liquor (spirits), wine and total alcohol intakes have different associations with serum urate (SU) concentrations at different ages in a cohort of young men and women. Methods Data from 3123 participants at baseline and follow-up at 20 years were used, with balanced proportions of Caucasians and African Americans. The relationships of SU with categories of beer, liquor, wine and total alcohol intake referent to no intake were examined in sex-specific, cross-sectional analyses. Results Mean age (SD) at the beginning of follow-up was 25.1 (3.6) years. Compared with non-drinkers, significant associations between higher SU concentrations and greater beer intake were observed among men and women, with more pronounced and consistent associations for women. An association between greater liquor intake and higher SU concentrations was only seen for men at the year 20 evaluation. Wine intake was not associated with SU in either sex and total alcohol was associated with higher SU concentrations in both men and women. The magnitude of the associations between alcoholic beverages intake and SU was modest (≤0.03 mg/dl/alcoholic beverage serving). Conclusion An association between higher SU concentrations and greater beer intake was consistent and pronounced among women, but also present in men. Despite the small magnitude of the increases in SU associated with alcohol intake, clinical implications in conditions such as cardiovascular disease and gout in young adults who are moderate and heavy drinkers cannot be ruled out.
Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis

Objective To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA). Methods The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death. Results There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74). Conclusion TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.
The Sexual Assault and Secondary Victimization of Female Veterans: Help-Seeking Experiences with Military and Civilian Social Systems

A sample of predominantly low-income, African American female veterans and reservists seeking health care in a Veterans' Administration medical clinic was screened for a history of sexual assault since age 18. Overall, 39% had been sexually assaulted in adulthood. Those who had been sexually victimized were asked to describe one assault incident in detail: 38% described an assault that occurred during military service and 62% described one that occurred before or after military service. This study also examined victims' postassault help-seeking experiences and the degree to which they encountered “secondary victimization” (i.e., victim-blaming behaviors and practices engaged in by legal and medical personnel, which exacerbates victims' trauma). Most victims who sought help from the legal or medical systems (military or civilian) reported that this contact made them feel guilty, depressed, anxious, distrustful of others, and reluctant to seek further help. Secondary victimization was significantly positively correlated with posttraumatic stress symptomatology.
(cid:1) 2 (cid:2) 1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell–speciﬁc manner

To deﬁne the role of the (cid:1) 2 (cid:2) 1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and (cid:1) 2-null mice. Our ﬁndings reveal that the (cid:1) 2 (cid:2) 1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F10 melanoma cells, mice lacking (cid:1) 2 (cid:2) 1 integrin expression exhibit increased tumor angiogenesis associated with up-regulated VEGFR1 expression. In contrast, there was no (cid:1) 2 (cid:2) 1 integrin-dependent difference in the angiogenic response to Lewis lung carcinoma (LLC) cells. Interestingly, whereas B16F10 cells secrete high levels of placental growth factor (PLGF), LLC cells produce high levels of VEGF, but low levels of PLGF. The (cid:1) 2 (cid:2) 1 integrin-dependentdifferenceinangiogenesiswas restored to LLC cells by expression of PLGF, strongly suggesting that the angiogenic phenotype and tumor growth in the (cid:1) 2-null host is dependent on speciﬁc interactions between the tumor cell and the genetically deﬁned integrin repertoire of the host microenvironment. Thus integrin (cid:1) 2-null mice represent an example of genetic alterations of “the soil” determining response to the “seed. ” (Blood. 111:1980-1988)
Adiponectin and leptin increase IL-8 production in human chondrocytes

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two of the most frequent articular diseases. Recently, adipokines have been proposed as relevant mediators of cartilage degeneration in both OA and RA.1 Our group has previously demonstrated that RA patients have elevated serum levels of leptin and adiponectin,2 while others have shown positive associations between serum levels of leptin and hip-radiographic OA,3 and of adiponectin and erosive OA.4 Thus, several studies have suggested that adipokines can modulate the …
Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study

Objective To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee. Methods Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade ≥2 (range 0–3) and effusion synovitis as any grade ≥2 (range 0–3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders. Results Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis. Conclusions Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.
The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type I interferon

Objectives The objective of this study was to investigate the effect of the novel Janus kinase inhibitor CP-690,550 in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). Methods RA FLSs were isolated from tissue obtained by arthroplasty, cultured and serum-starved 48 h prior to stimulation. Messenger RNA and protein levels were determined by quantitative PCR and ELISA or multiplex bead assay, respectively. Phosphorylation of STAT (signal transducers and activators of transcription) proteins was determined by western blot. Results Interleukin-6-induced phosphorylation of STAT1 and STAT3 was inhibited by CP-690,550 with IC50 values of 23 and 77 nM, respectively. Unexpectedly, although tumour necrosis factor (TNF) did not induce immediate phosphorylation of either STAT, CP-690,550 inhibited TNF-induced expression of several chemokines (IP-10, RANTES and MCP1) at the messenger RNA and protein levels. Chemokine expression was inhibited by cycloheximide, implying a need for de novo protein synthesis, and cycloheximide abolished the effect of CP-690,550 (tofacitinib). TNF induced early interferon (IFN) β expression and STAT1 phosphorylation beginning at 3 h, which was blocked by CP-690,550. The dependence of TNF-induced chemokine expression on type I IFN was confirmed in FLSs from mice lacking type I IFN receptors (IFNARs) and in RA FLSs using an IFNAR blocking antibody. Conclusions The Janus kinase/STAT pathway in FLS is indirectly activated by TNF through autocrine expression of type I IFN, resulting in IFNAR engagement and production of T cell chemokines. These findings illuminate a novel role of CP-690,550 in the treatment of RA: the reduction of chemokine synthesis by FLS, thereby limiting recruitment of T cells and other infiltrating leucocytes.
Do patients with psoriatic arthritis who present early fare better than those presenting later in the disease?

Background This investigation aimed to determine whether patients presenting to a psoriatic arthritis (PsA) clinic early in the course of the disease had less severe disease at presentation, and whether disease duration at presentation predicts progression of joint damage. Methods Patients followed prospectively in a specialised clinic were divided into those first seen within 2 years of diagnosis (group 1) and those seen with more than 2 years of disease (group 2). The groups were compared with regard to demographics and disease characteristics at presentation. A multivariate analysis using a negative binomial model was conducted to determine whether patients with early disease had less progression of joint damage. Results 436 patients were identified in group 1 and 641 patients in group 2. Patients in group 2 were older, had longer duration of psoriasis and PsA, more joint damage and were less likely to be treated with disease-modifying antirheumatic drugs, but had similar level of education and degree of psoriasis severity. After adjusting for age, sex, education level, clinical joint damage at first visit and treatment, group 2 had significantly greater rate of clinical damage progression compared with group 1. Conclusions Disease progression is more marked in patients presenting with established disease of more than 2 years' duration. These results suggest that patients with PsA should be treated earlier in the course of their disease.
Use of anthelmintics in sheep

ANTHELMINTICS are used both prophylactically and therapeutically for the management of helminth infections in sheep, but the rationale behind some of the anthelmintic strategies employed on farms remains questionable. This article reviews the spectrum of activity of the principle groups of anthelmintic drugs and emphasises the importance of combining strategic anthelmintic usage with grassland management in order to achieve effective worm control and reduce the risk of anthelmintic resistance.
Performance enhancement of smith-waterman algorithm using hybrid model: Comparing the MPI and hybrid programming paradigm on SMP clusters

Nowadays, database pattern searching is the most heavily used operation in computational biology. Indeed, sequence alignment algorithm plays an important role to find the homologous groups of sequences which may help to determine the function of new sequences. Meanwhile Smith-Waterman algorithm is one of the most prominent pattern matching algorithms. However, it cost the large quantity of time and resource power. By the aid of parallel hardware and software architecture it becomes more feasible to get the fast and accurate result in efficient time. In this paper, Smith-Waterman algorithm is parallelized base on various types of parallel programming, pure MPI, pure OpenMP and Hybrid MPI-OpenMP model. In addition, based on the experiments it will be proved that hybrid programming which employ the coarse grain and fine grain parallelization, is more efficient compare with pure MPI and pure OpenMP in cluster of SMP machines.
A field level architecture for reconfigurable real-time automation systems

Rapidly changing customer demands lead to a paradigm shift from mass production to mass customization within the manufacturing industry. However, todays production systems are of a very static nature. Changing the manufacturing process requires a high amount of expensive human resources and is quite error prone. Hence, reconfigurability will become a key factor in the manufacturing industry and industrial automation systems must provide suitable solutions to support this new paradigm. Service-oriented architectures (SOAs) are a potential technology which can provide the requested capability of automatic reconfiguration. Originating from the IT world, the adaptation of SOAs to industrial automation systems has to face several difficulties - especially real-time requirements must be met. This paper proposes an innovative solution approach for the integration of a SOA into real-time systems for industrial automation.