Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry

Objective: Etanercept monotherapy has been studied and approved for treatment of polyarticular juvenile idiopathic arthritis (JIA). The following study evaluates the safety and efficacy of combination therapy of etanercept and methotrexate compared to etanercept monotherapy in JIA. Methods: We perfomed an open, non-randomised study on patients who had previously failed to respond to at least one disease-modifying antirheumatic drug (DMARD). A total of 722 patients with JIA in whom at least 1 item of follow-up data was recorded were identified; of these, 118 patients treated with further slow acting drugs were excluded. In all, 504 patients were treated with a combination of etanercept and methotrexate. A total of 100 patients treated with etanercept only were in the control group. Efficacy was calculated using the American College of Rheumatology paediatric scores for 30, 50 and 70% improvement (PedACR30/50/70). Adverse events (AEs) and serious adverse events (SAEs) were reported. Results: After 12 months 55 patients in the monotherapy group and 376 patients in the etanercept and methotrexate group were available for comparison. For the intention to treat analysis, 65 patients discontinuing treatment prematurely were included. All activity parameters decreased significantly in both treatment groups. After 12 months 81%/74%/62% of patients of the etanercept and methotrexate group and 70%/63%/45% of patients of the etanercept monotherapy group achieved PedACR30/50/70 scores, respectively (p<0.05 for PedACR30, p<0.01 for PedACR70). The likelihood of achieving a PedACR70 increased with combination therapy with an odds ratio of 2.1 (95% CI 1.2 to 3.5). In total, 25 infectious and 23 non-infectious SAEs including 3 malignancies occurred in the etanercept and methotrexate group, and 1 infectious and 3 non-infectious SAEs occurred in the single etanercept group. Conclusions: The patients’ disease activity improved during etanercept monotherapy and etanercept and methotrexate combination therapy. Tolerability in both treatment groups was comparable.
Pretreatment serum levels of anti-cyclic citrullinated peptide antibodies are associated with the response to methotrexate in recent-onset arthritis

To direct individual treatment decisions in recent-onset rheumatoid arthritis (RA), predictors of treatment response to methotrexate (MTX) need to be identified. Disease activity at baseline, gender and genetic polymorphisms have already been found to be associated with the effect of MTX treatment, but the predictive value of autoimmune antibody status remains less clear.1 2 It has been shown, however, that both the presence and level of anti-cyclic citrullinated peptide antibodies (ACPA) are strongly associated with a worse disease course.3 Therefore, we investigated the potential predictive effect of levels of ACPA in ACPA-positive patients for the response to MTX treatment. As observations from our cohort and others indicate that ACPA levels decrease …
Complement activation in patients with primary antiphospholipid syndrome

Objective: To investigate the significance of complement activation in patients with primary antiphospholipid syndrome (APS). Methods: Thirty-six patients with primary APS, 42 control patients with non-systemic lupus erythematosus (SLE) connective tissue diseases, and 36 healthy volunteers were analysed retrospectively. Serum complement levels (C3, C4, CH50) and anaphylatoxins (C3a, C4a, C5a) were examined in all subjects, and serum complement regulatory factors (factor H and factor I) were measured in patients with primary APS. Plasma anticoagulant activity was determined in a mixing test using the activated partial thromboplastin time. Results: Serum complement levels were significantly lower in patients with primary APS than in patients with non-SLE connective tissue diseases (mean (SD) C3: 81.07 (17.86) vs 109.80 (22.76) mg/dl, p<0.001; C4: 13.04 (8.49) vs 21.70 (6.96) mg/dl, p<0.001; CH50: 31.32 (8.76) vs 41.40 (7.70) U/ml, p<0.001) or healthy volunteers. Only two healthy subjects with low serum C4 levels showed hypocomplementaemia, whereas most patients with primary APS showed raised serum C3a and C4a. No subjects showed raised C5a. Patients with primary APS with low serum C3 or C4 had significantly higher levels of C3a or C4a than healthy controls. No patients had low serum complement regulatory factors. Among patients with primary APS, hypocomplementaemia was significantly more common in those with high anticoagulant activity than in those with low or normal activity. Conclusion: Hypocomplementaemia is common in patients with primary APS, reflecting complement activation and consumption, and was correlated with anticoagulant activity, suggesting that antiphospholipid antibodies may activate monocytes and macrophages via anaphylatoxins produced in complement activation.
The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events

Objective: To evaluate the safety of biological treatments for rheumatoid arthritis (RA) using results from randomised controlled trials (RCT). Methods: The literature was searched to December 2007 for RCT evaluating inhibitors of tumour necrosis factor alpha (anti-TNF) for RA. Safety data were abstracted and risk estimates were calculated using three approaches, meta-analysis with and without adjustment for exposure and simple exposure-adjusted pooling. Results: Eighteen randomised trials involving 8808 RA subjects were included. Treatment with recommended doses of anti-TNF found no increase in the odds of death (odds ratio (OR) 1.39; 95% CI 0.74 to 2.62), serious adverse events (OR 1.11; 95% CI 0.94 to 1.32), serious infection (OR 1.21; 95% CI 0.89 to 1.63), lymphoma (OR 1.26; 95% CI 0.52 to 3.06), non-melanoma skin cancers (OR 1.27; 95% CI 0.67 to 2.42) or the composite endpoint of non-cutaneous cancers plus melanomas (OR 1.31; 95% CI 0.69 to 2.48) when evaluated using the unadjusted meta-analytic method. Risk estimates were similar with the other methods. For subjects who received two to three times the recommended doses of anti-TNF the risk of serious infection was increased with the unadjusted meta-analytic and pooled analysis, (OR 2.07; 95% CI 1.31 to 3.26) and (risk ratio (RR) 1.83; 95% CI 1.18 to 2.85), respectively, but not increased in the exposure-adjusted meta-analysis (RR 1.99; 95% CI 0.90 to 4.37). Meta-regression identified that the risk of serious infection with anti-TNF therapy decreases with increasing trial duration (p = 0.035). Conclusion: Meta-analytic and exposure-adjusted pooled analyses on over 8800 RA subjects in RCT treated over an average of 0.8 years did not identify an increased risk of serious adverse events with recommended doses. High-dose anti-TNF therapy was associated with a twofold increase in the risk of serious infections.
Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study

The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. Objective: To establish the prevalence and incidence of SSc and its pulmonary complications. Methods: Detailed information on patients in the POEMAS registry, “Pulmonary Hypertension Screening, a Multidisciplinary Approach in Scleroderma”, consisting of 819 patients, was combined with a nationwide questionnaire. Results: By combining the two sources the prevalence of SSc was found to be 8.9 per 100 000 adults. The incidence was 0.77 patients per 100 000 per year. PAH was diagnosed in 9.9% of SSc patients. The prevalence of interstitial lung disease in SSc varied from 19% to 47% depending on the definition used. Conclusion: This study clarifies the epidemiology of SSc in The Netherlands and confirms the frequent occurrence of pulmonary complications, based on 654 cases. This can and will be studied further in the ongoing POEMAS study.
Porcine Small Intestine Submucosal Grafts for Post-tumor Resection Orbital Reconstruction

Objectives: With sinonasal malignancy, removal of the medial orbital wall for tumor involvement is required to obtain complete oncologic resection. However, orbital fat herniation can produce significant morbidity, including enophthalmos and diplopia. The purpose of the current study was to evaluate outcomes following use of porcine small intestine submucosa (SIS) grafts for orbital reconstruction following extirpation of sinonasal malignancies. Methods: Review of prospectively collected data regarding orbital reconstruction using SIS was performed. Demographics, tumor histology, size of orbital defect, adjuvant treatment, clinical status, and complications were recorded. Results: Seventeen patients (average age 58, range 27-82) had SIS grafting of the medial orbital wall over a five year period at our tertiary academic institution. Average orbital wall defect size was 1.6 x 2.1 cm (height vs. length). Tumor histopathology included esthesioneuroblastoma (n=5), squamous cell carcinoma (n=4), adenocarcinoma (n=2), sinonasal undifferentiated carcinoma (n=2), melanoma (n=3), and neuroendocrine carcinoma (n=1). Surgical goals were curative intent in all patients. Ten patients had postoperative radiation therapy, while 5 individuals had surgical extirpation following neoadjuvant chemotherapy and radiation. All patients had complete locoregional control at last clinical follow-up (average 16 months, range 2-54), although three patients developed distant metastases. The only orbital complications noted were enophthalmos (n=1), periorbital cellulitis (n=1), and orbital wall crusting (n=1). Conclusions: SIS reconstruction of orbital wall defects was effective in the current series of patients with only one patient developing noticeable enophthalmos and a low incidence of surgical complications.
A Qualitative Evaluation of Problem-Based Learning Curriculum by Students' Perceptions

Purpose: Recently established in 1997, Sungkyunkwan University School of Medicine was the first medical school in Korea to adopt problem-based learning (PBL) as a core curriculum from the very beginning. The purpose of this study was to evaluate the PBL curriculum from the viewpoint of the medical students. Methods: This study used a qualitative approach to understand students' perceptions of the positive aspects of PBL. A total of 22 second-year medical students at Sungkyunkwan medical school were surveyed. Student perceptions were obtained from questionnaires and face-to-face interviews. The interview was designed to evoke more personal and in-depth responses. Results: Students' perceptions of the effects of PBL were found to be very favorable. Most students showed positive responses on issues of more active learning attitude, self-directed learning, motivation to study, improved problem solving, and integrated learning. Conclusion: The results of this study demonstrated that the students had a good understanding of PBL and experienced its positive aspects. It might be concluded that PBL was successfully implemented into the curriculum and the specific and expected effects of PBL accomplished.
Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis

Objective: To investigate the influence of age on the effectiveness and tolerance of antitumour necrosis factor alpha (TNFα) therapy in rheumatoid arthritis (RA). Methods: 730 patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) register were categorised into three groups according to their age at initiation of anti-TNFα therapy (<45, 45–65 and >65 years). Effectiveness of anti-TNFα therapy was primarily assessed by longitudinal analysis of the DAS28 during the first 12 months of treatment. Results: Improvement in disease activity and physical functioning was significantly less in elderly patients, correcting for relevant confounders. Elderly patients reached the EULAR categories of good responders and remission less often than younger patients. Drug survival, co-medication use and tolerance were comparable between the three age groups. Conclusion: Anti-TNFα therapy significantly reduced disease activity in all age groups of patients; however, it appeared less effective in elderly compared with younger RA patients.
Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus

Interleukin 17 (IL17)-producing T helper (Th17) cells, a new effector T cell subset, appear to play an essential role in autoimmune diseases.1 It has been shown that IL22 is another Th17 cytokine in mice and IL23 is critical for Th17 development.2–5 Increased plasma IL17 levels have been reported in systemic lupus erythematosus (SLE). 6 We analysed Th17-related cytokine profiles in the plasma of patients with SLE. A total of 45 patients with SLE were studied. All patients received glucocorticoids (2.5–50 mg/day). There were 24 patients with active (SLE Disease Activity Index (SLEDAI) score of ⩾6; 22 female; mean (SD) age 37.3 (12.1)) and 21 with inactive …
On Vibration and Noise Dissipation in Ship and FPSO Structures with Smart Systems

Ships and floating structure production systems are widely deployed for deep and ultradeep waters operation. Active vibration reduction and noise control in such structures can significantly improve their hydrodynamic performance and stability during navigation, exploration, and exploitation activities. One way to minimise or reduce the transmission of vibration in these moving offshore structures is to exploit the mechanism of interfacial slip in press fit joints or layered structural laminates in their internal hull configurations to dissipate vibration energy. In this paper, slip damping with heterogeneous sandwich composite viscoelastic beam-plate smart systems as a model for dissipation of vibration and active noise control mechanism in ship and floating structures is investigated. For this problem, a boundary value partial differential equation is formulated for the case of linear and nonlinear hydrodynamic wave loadings. In particular, the effect of pressure distribution variation at the interface of the layered smart system on the energy dissipation, logarithmic damping decrement, and spatial transfer function is analyzed and presented for design application and selection of appropriate stabilizers.
Cardiac magnetic resonance imaging in patients with systemic lupus erythematosus

Objectives: To delineate the cardiac magnetic resonance (MR) appearances of cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE), in comparison with transthoracic echocardiographs. Methods: Cardiac MR was performed on 22 patients with SLE—11 with previous CVD and 11 matched controls—using late gadolinium contrast enhancement (LGE) to identify areas of myocardial scarring; Transthoracic echocardiography (TTE) was performed on the same day. Results: Twenty female and two male patients participated. LGE was seen in 5/11 subjects in the CVD group (4/5 with previous myocardial infarction) and 1/11 in the control group. TTE detected myocardial abnormalities in 2/6 patients with LGE. Conclusion: The cardiac MR appearance of CVD in these patients with SLE was suggestive of coronary disease, rather than cumulative inflammatory muscle damage. Cardiac MR detected more abnormalities than TTE. Further studies of cardiac MR in patients with SLE are warranted to investigate these preliminary findings.
Exiting Homelessness Without a Voucher: A Comparison of Independently Housed and Other Homeless Veterans

Studies that have shown the superiority of housing voucher programs over standard care for homeless adults with mental illness have also incidentally shown that many are able to obtain independent housing without subsidies. The current study examined how individuals obtain housing without a voucher and whether greater employment earnings or better clinical outcomes were associated with such housing success. Data from an experimental evaluation of the Housing and Urban Development-Veterans Affairs Supportive Housing program were used for an observational study that compared participants who, at 3 months, were: (1) Independently Housed Without a Voucher (n 96), (2) Independently Housed With a Voucher (n 93), (3) Housed In Another Individual’s Place (n 60), or (4) Not Yet Housed (n 170). Participants who obtained independent housing without a voucher worked more days and had higher employment income than those who did use a voucher, but they were less satisfied with their housing. About a third of participants who lived in independent housing without a voucher had others living with them. Homeless veterans with mental illness are able to use employment and shared housing as naturalistic ways to obtain independent housing.
Automatic Defect Categorization

Defects are prevalent in software systems. In order to understand defects better, industry practitioners often categorize bugs into various types. One common kind of categorization is the IBM's Orthogonal Defect Classification (ODC). ODC proposes various orthogonal classification of defects based on much information about the defects, such as the symptoms and semantics of the defects, the root cause analysis of the defects, and many more. With these category labels, developers can better perform post-mortem analysis to find out what the common characteristics of the defects that plague a particular software project are. Albeit the benefits of having these categories, for many software systems, these category labels are often missing. To address this problem, we propose a text mining solution that can categorize defects into various types by analyzing both texts from bug reports and code features from bug fixes. To this end, we have manually analyzed the data about 500 defects from three software systems, and classified them according to ODC. In addition, we propose a classification-based approach that can automatically classify defects into three super-categories that are comprised of ODC categories: control and data flow, structural, and non-functional. Our empirical evaluation shows that the automatic classification approach is able to label defects with an average accuracy of 77.8% by using the SVM multiclass classification algorithm.
Multiple Toxic Effects of Phenylbutazone

easy to explore the common bile duct and, in the average case, to pass the standard Desjardins forceps down this duct. For a barrel-chested patient with a high liver I have a more curved pair of Desjardins forceps available. Should more room be required medially the incision is extended tbrough the linea alba into the left rectus sheath. As the incision lies between the eighth and ninth intercostal nerves, these nerves are in no danger of injury and do not have to be identified (Fig. 1). Should the lateral margin of the incision be made a little low the ninth intercostal nerve is seen lying on the posterior layer of the recfus sheath near its lateral margin. The direction of the ninth nerve at this point is that taken by the ninth rib in the axilla (Fig. 1).
The natural soluble form of IL-18 receptor β exacerbates collagen-induced arthritis via modulation of T-cell immune responses

Objective: IL-18 is a pluripotent cytokine that has been implicated in the development of rheumatoid arthritis. A soluble form of the IL-18 receptor accessory protein (sIL-18Rβ) with unknown function has recently been identified. This study examined the ability of sIL-18Rβ to inhibit IL-18 biological activities and to modulate immune responses during collagen-induced arthritis (CIA). Methods: Adenoviruses encoding sIL-18Rβ were administered intravenously in type II collagen-immunised DBA/1 mice. Humoral responses were analysed by determining anti-bovine collagen type II (BCII) antibody levels by ELISA. Cytokine production by splenic T cells and cytokine levels in serum were measured by Luminex multi-analyte technology. CD4+CD25+Foxp3+ regulatory T cells (Treg) were measured by flow cytometry. Results: Intravenous delivery of Ad5.sIL-18Rβ in collagen-immunised mice led to enhanced transgene expression in splenic antigen-presenting cells (APC). A co-culture of these sIL-18Rβ-transduced APC with purified splenic CD3+ T cells led to a marked inhibition of IL-18-induced IFNγ, IL-4 and IL-17 production by CD3+ T cells. Remarkably, systemic treatment with Ad5.sIL-18Rβ caused an exacerbation of arthritis, and histological evaluation of knee joints showed increased cartilage and bone erosion. No significant differences were observed in anti-BCII antibodies, but the aggravation was accompanied by decreased IFNγ (−30%) and IL-4 (−44%) and increased IL-17 (+84%) production by splenic CD3+ T cells. In addition, reduced circulating levels of CD4+CD25+Foxp3+ Treg and anti-inflammatory IL-10 were shown. Conclusion: This study identifies sIL-18Rβ as a novel IL-18 inhibitor, which promotes CIA after intravenous overexpression by affecting Treg levels and supporting a T helper type 17 response.
Hipertensão como fator associado à perda auditiva

OBJETIVO: Identificar possivel associacao entre hipertensao arterial e perda auditiva. Foi realizado um estudo do tipo caso-controle nao pareado, na Universidade Norte do Parana, no Sul do Brasil. MATERIAL E METODO: 154 casos e 154 controles, de ambos os sexos com idade variando de 45 a 64 anos foram incluidos na pesquisa apos o calculo da amostra. A hipertensao foi verificada por medicao da pressao arterial e de questionario sistematizado sobre hipertensao e uso de medicamentos para pressao arterial. A audicao foi avaliada por audiometria e anamnese audiologica. A tecnica de regressao logistica nao-condicional foi utilizada com o objetivo de controlar a possivel acao de confusao ou modificacao de efeito exercida por outras variaveis sobre as associacoes de interesse. RESULTADOS : Pode-se verificar que existe associacao significativa entre hipertensao arterial e presenca de perda auditiva e que a perda auditiva observada nesta populacao sugere que a hipertensao arterial age como fator de aceleracao da degeneracao do aparelho auditivo proveniente da idade. CONCLUSOES: Os resultados da presente pesquisa, atraves da constatacao da associacao entre hipertensao e perda auditiva, servirao de base a uma integracao entre cardiologistas, nefrologistas, otorrinolaringologistas, fonoaudiologos e outros profissionais da area de com alteracoes provenientes da hipertensao.
Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study

Objective: To examine the effect of infliximab plus methotrexate (MTX) compared with placebo plus MTX on bone loss in patients with early rheumatoid arthritis (RA) in a double-blind randomised study design. Further, to explore the associations between bone loss and markers of RA disease. Methods: All 20 patients with RA (10 patients in each treatment group) had active, early RA. Bone mineral density (BMD) was assessed at the hand, lumbar spine (L2–4) and hip by dual energy x-ray absorptiometry at baseline and 12 months’ follow-up. Clinical data were collected at regular visits. Results: BMD loss was significantly reduced in the infliximab group compared with the placebo group at the femoral neck (−0.35% vs −3.43%, p = 0.01) and total hip (−0.23% vs −2.62%, p = 0.03) but not at the hand (−2.09% vs −2.82%, p = 0.82) and spine (−0.75% vs −1.77%, p = 0.71). Measures of disease process and joint damage were found to be independently associated with bone loss. Conclusions: This study provides strong evidence of a causal link between inflammation and bone loss in RA. The anti-inflammatory effect of infliximab was potent enough to arrest inflammatory bone loss at the hip but not at the spine and hand.