Miracle-dz/UniFAR-FTUs huggingface dataset:
Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes

Objective To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). Methods The AGREE was a 2-year phase IIIb multinational study in early (≤2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. Results Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. Conclusions The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. Trial Registration: NCT00122382
Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study

Objective To prospectively explore the short-term efficacy and safety of abatacept in patients with ankylosing spondylitis (AS). Methods In this prospective open-label pilot study, abatacept (10 mg/kg) was administered intravenously on days 1, 15, 29 and every 28 days thereafter up to week 24 in 15 tumour necrosis factor α (TNFα)-inhibitor naive patients (group 1) and 15 patients with inadequate response to TNFα inhibitors (group 2) with active AS. The primary end point was the proportion of patients with 40% improvement according to the Assessment of SpondyloArthritis international Society criteria (ASAS40) in both groups at week 24. Results At week 24, ASAS40 was reached by 13% of group 1 and 0% of group 2; 20% improvement (ASAS20) was reached by 27% and 20%, respectively. There was no significant change of Bath Ankylosing Spondylitis Disease Activity Index score, patient global assessment or C reactive protein. Overall, abatacept was well tolerated. Conclusions In this pilot open-label AS study a major response was not observed.
Characterization of an In Vitro Platelet Function Analyzer, PFA-100™

A new in vitro system for the evaluation of platelet function, PFA-100 (currently under evaluation) is characterized. The system monitors platelet aggrega tion on a collagen-epinephrine-coated membrane as whole blood sample is aspirated under controlled flow conditions through a microscopic aperture cut into the membrane. The time required for the platelet plug to oc clude the aperture (closure time) is indicative of the plate let function in the sample. Incubation of normal blood samples with antibodies to glycoprotein (GP) Ib, GPIIb- IIIa, von Willebrand factor, or with the peptide Arg-Gly- Asp-Ser, resulted in a concentration-dependent prolonga tion in closure time. An anti-fibrinogen antibody did not impact the closure time. Closure time was also prolonged when the hematocrit or the platelet count was lowered to pathological values. The study indicates that PFA-100 could detect defects in platelet adhesion or aggregation. The simplicity of the test makes PFA-100 unique for rapid screening of a variety of platelet dysfunction.
Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis

Objectives This project was undertaken to assess the risk of malignancy in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors (TNFi) in clinical practice, as recorded in prospective, observational studies. Methods The authors undertook comprehensive searches of MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and American College of Rheumatology, European League against Rheumatism and British Society for Rheumatology conference abstracts according to a prespecified protocol. Results The searches identified 2039 full-text papers and 1979 conference abstracts, of which 21 full texts and eight abstracts met the inclusion criteria. The pooled estimate for the risk of all-site malignancy from seven studies was 0.95 (95% CI 0.85 to 1.05). Two studies reported there was no evidence that longer exposure to TNFi agents increased the risk of malignancy. In patients with previous malignancies there was a higher risk of a new/recurring malignancy. This risk was not increased further by exposure to TNFi, although CI were wide. Results from four studies showed that patients treated with TNFi have a significantly increased risk of developing a non-melanoma skin cancer (1.45, 95% CI 1.15 to 1.76). In addition, patients are at an increased risk of developing melanoma, as the pooled estimate from two studies was 1.79 (95% CI 0.92 to 2.67). The pooled estimate for the risk of lymphoma was 1.11 (95% CI 0.70 to 1.51). Conclusions This systematic review and meta-analysis shows that TNFi treatments do not increase the risk of malignancy, particularly lymphoma. However, they do appear to increase the risk of skin cancer, including melanoma.
A phase II trial of weekly high dose continuous infusion 5‐fluorouracil plus oral leucovorin in patients with advanced colorectal cancer

Background. In a previous Phase II trial, the authors showed that a weekly continuous infusion of 5‐fluorouracil (5‐FU) at a dose of 3.5 g/m2 for 48 hours is an active treatment for advanced colorectal cancer. The overall response rate was 38.5%, and the median survival was 12 months. These data were comparable to those achieved by biochemical modulation of 5‐FU with leucovorin. To study the modulation of this weekly, high dose, continuous infusion 5‐FU with oral leucovorin, a new Phase II trial was planned.
Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes

Objective Longer-term effects of prolonged selective interleukin-1β blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date. Methods Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels. Results Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the normal range thereafter. Median treatment duration was 414 days (29–687 days). Upward adjustments of dose or frequency were needed in 24.1% patients; mostly children and those with severe CAPS. Predominant adverse events (AE) were infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18 patients (10.8%) were mainly infections and were responsive to standard treatment. The majority of patients (92%) reported having no injection-site reactions and only 8% patients reported mild-to-moderate reactions. Patients receiving vaccination (15%) showed normal immune response. Conclusions Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE. Trial registration number: NCT00685373 (clinicaltrials.gov)
Model Checking Pervasive Context-Aware Systems

Many approaches on context-aware systems specification have been proposed in the literature. However, the absence or poor representation of contextual information and its relationships with system entities in these approaches usually leads to low-precision and irrelevant results. The aim of this paper is to promote the ability to specify and verify context-aware systems. Our proposed modeling methodology exploits Maude reflection and meta-programming to define a domain specific language for context-aware systems specification and adopts Maude model checker to verify system inherent properties. Moreover, a runtime environment implementing the proposed model is developed for pervasive context-aware systems execution.
Rheumatoid arthritis near remission: clinical rather than laboratory inflammation is associated with radiographic progression

Background Disease activity in rheumatoid arthritis (RA) can be measured clinically (eg, swollen joint count (SJC)) or systemically (eg, C reactive protein (CRP)). In general, both contribute to the progression of joint damage, but the relevance of residual inflammation in patients near remission is unclear. Objective To determine the independent contribution of SJC and CRP to progression of joint damage in patients near remission. Methods Data from methotrexate monotherapy arms of the ASPIRE, ERA, Leflunomide, PREMIER and TEMPO trials (n=1184) were pooled and the average SJC and CRP values from visits at 6, 9 and 12 months were determined. The two variables were then dichotomised into active and inactive, where inactive was defined as a mean. Radiographic outcomes were assessed according to these definitions. Results The greatest progression was seen in patients in whom both SJC and CRP were active and the smallest in those in whom both were inactive. If SJC was inactive, radiographic progression was not different between those with inactive or active CRP (0.7±4.3/year and 0.8±5.4/year, respectively, p=0.19). However, if CRP was inactive (<1 mg/dl), SJC status still determined radiographic progression (0.7±4.3/year and 1.8±5.6/year, for inactive and active SJC, respectively, p=0.004). The importance of SJC in patients with inactive CRP was also shown in a linear model (p=0.019), while CRP was not significantly different in patients with inactive SJC (p=0.40). Conclusion In patients with RA who are near remission, the amount of joint swelling appears to be more predictive of radiographic progression than the amount of CRP.
Blood pressure and nutrient intake in the United States

A data base of the National Center for Health Statistics, Health and Nutrition Examination Survey I (HANES I), was used to perform a computer-assisted, comprehensive analysis of the relation of 17 nutrients to the blood pressure profile of adult Americans. Subjects were 10,372 individuals, 18 to 74 years of age, who denied a history of hypertension and intentional modification of their diet. Significant decreases in the consumption of calcium, potassium, vitamin A, and vitamin C were identified as the nutritional factors that distinguished hypertensive from normotensive subjects. Lower calcium intake was the most consistent factor in hypertensive individuals. Across the population, higher intakes of calcium, potassium, and sodium were associated with lower mean systolic blood pressure and lower absolute risk of hypertension. Increments of dietary calcium were also negatively correlated with body mass. Even though these correlations cannot be accepted as proof of causation, they have implications for future studies of the association of nutritional factors and dietary patterns with hypertension in America.
Characterization of a Trpc6 Transgenic Mouse Associated with Early Onset FSGS

Rationale: Mutations in Transient Receptor Potential Channel 6 (TRPC6) gene are associated with autosomal dominant focal and segmental glomerulosclerosis (FSGS). The majority of the identified mutations affect the ion channel function. Since calcium channels are promising candidate drug targets, there is an an urgent need for a mouse model to assess new therapeutic drugs and to help delineate the pathogenic process leading to FSGS. We have previously reported the generation of three independent transgenic mouse lines carrying different Trpc6 mutations that display a glomerular disease comparable to the phenotype presented by individuals with FSGS. However, the utility of these models for drug testing is dampened by the late-onset of the presentation and the mild phenotypic manifestations. Methodology: In order to obtain a time-effective mouse model for Trpc6-associated FSGS we generated a new transgenic mutant Trpc6 mouse model emulating the amino acid change carried by the first pediatric patient of FSGS associated with a TRPC6 mutation: M132T. Results: Mice carrying the orthologous Trpc6 M131T transgene showed early onset proteinuria and early signs of FSGS. When exploring molecular consequences of the overexpression of this mutated form of Trpc6 in podocytes, differences in expression levels of Axin2 and β-catenin were found in glomeruli from transgenic Trpc6 M131T mice. These data supports the proposed molecular mechanisms related to the activation of calcineurin-NFAT/Wnt signaling, as outcome of the increased calcium influx caused by the mutated form of Trpc6. Conclusion: Given that the Trpc6 M131T mouse develops an early onset of FSGS-like phenotypes it represents a promising model for studying the pathogenesis of FSGS caused by TRpC6, facilitating the assessment of new drugs as treatments and allowing further studies to understand underlying molecular pathways involved in the development of the TRPC6 mediated disease.
Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma.

Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase 1 trial of ATO in children (median age 13 y, range, 2-19) with refractory leukemia. ATO was administered intravenously over 2 hours, 5 d/wk for 20 doses/cycle. Patients with APL (n=13) received 0.15 mg/kg per day, and patients with other types of leukemia received 0.15 mg/kg per day (n=2) or 0.2 mg/kg per day (n=4). Nineteen of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg per day, 2 of 15 patients experienced dose-limiting corrected QT interval (QTc) prolongation, pneumonitis, or neuropathic pain. At 0.2 mg/kg per day, 2 of 4 patients had dose-limiting QTc prolongation or pancreatitis. Non-dose-limiting toxicities included elevated serum transaminases, nausea, vomiting, abdominal pain, constipation, electrolyte imbalance, hyperglycemia, dermatitis, and headache. At 0.15 mg/kg per day, the median (range) plasma arsenic maximum concentration (Cmax) was 0.28 microM (0.11-0.37 microM) and at 0.2 mg/kg per day, Cmax was 0.40 and 0.46 microM; area under the concentration times time curve (AUC0-24) was 2.50 microM-hr (1.28-3.85 microM-hr) and 4.37 microM-hr and 4.69 microM-hr, respectively. Morphologic complete response (CR) was achieved in 85% of patients with APL; no responses were observed in non-APL patients. ATO is well-tolerated in children at the recommended dose of 0.15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 at www.ClinicalTrials. gov.
Knowledge of Radiation Protection and the Recognition and Performance of Radiation Protection Behavior among Perioperative Nurses

Purpose: The purpose of this descriptive study was to investigate the knowledge of radiation protection and the recognition and performance of radiation protection behaviors among perioperative nurses. This study was intended to yield basic data for the development of nursing interventions aimed at improving the nurses’ radiation protection behaviors. Methods: One hundred and thirty-seven nurses working in the operating room participated in a survey from September 1 to 30, 2011. The data was analyzed using t-test, ANOVA, and Pearson’s correlation with the SPSS/WIN 19.0 program. Results: The average score of radiation protection knowledge was 7.57±3.45 out of 16. The average score for the recognition and performance of radiation protection behaviors was 4.32±0.23. The knowledge of radiation protection was significantly correlated with the recognition and performance of radiation protection behaviors. Conclusion: Expanding the knowledge of radiation protection could lead to the increase of the recognition and performance of radiation protection behaviors. Therefore, promoting the performance of radiation protection behaviors by improving perioperative nurses’ knowledge of radiation protection through reinforcing radiation-related education hereafter could be an important part of nursing.
Change in health‐related quality of life of opiate users in low‐threshold methadone programs

Aim: To assess changes in the health‐related quality of life (HRQOL) among opiate users in the first 6 months upon entering a low‐threshold methadone treatment program. Changes were evaluated from the perspectives of both statistical and clinical significance. Design: A prospective cohort study of low‐threshold methadone participants who had completed interviews at baseline and 6 months post enrollment. Participants: 183 opiate users who started low‐threshold methadone treatment between December 2000 and January 2004. Measurements: Data on HRQOL were collected by a trained interviewer using the SF‐36 instrument to determine baseline and 6 months post treatment scale scores. Findings: Statistically significant improvements were found in the study group for seven out of ten SF‐36 scales: role physical, bodily pain, vitality, social functioning, role emotional, mental health and the mental health component summary scale. At an individual patient level, clinically significant improvements were most commonly observed with the mental health scale, the vitality scale and the mental health component summary scales. Conclusions: Enrolment in low‐threshold methadone treatment programs is associated with improved HRQOL, particularly in the mental health domains of the SF‐36 during the first 6 months of treatment. Further follow‐up of this cohort will allow us to determine if a levelling or reversal in HRQOL occurs, permitting an evaluation of the potential long‐terms benefits of low‐threshold methadone programs.
Reconceptualising drug markets and drug dealers — the need for change

This paper outlines how, in many ways, the drug market is not what it is commonly assumed to be and that, as such, we need to reconceptualise how we understand both the drug market and the drug dealer. It briefly reviews the research showing that many of the core activities thought to characterise drug markets and drug dealing are unreasonably exaggerated or even essentially fallacious. It then seeks to demonstrate that the drug market doesn't even look the way it is assumed to look, in terms of its shape, structure and personnel. The issue of social supply is held up as an example of how unhelpful the current view is, particularly around cannabis and young people, and as evidence that the ‘house of cards’ that is the current conceptualisation of the drug market and the drug dealer needs reappraisal along with policy that is currently insufficiently nuanced to respond appropriately.
WE-Safe: A wearable IoT sensor node for safety applications via LoRa

This paper presents a wearable Internet of Things (IoT) sensor node aimed at monitoring harmful environmental conditions for safety applications via LoRa wireless technology. The proposed sensor node is low-power and supports multiple environmental sensors. A LoRa based gateway is used to connect sensors to the Internet. We mainly focus on monitoring carbon monoxide, carbon dioxide, ultraviolet, and some general environmental parameters. Poor environment quality could cause severe health problems to individuals. Therefore, surrounding environmental data is gathered by the wearable node in a real-time manner and then transmitted to a remote cloud server. The data can then be displayed to authorized users through a web-based application located in the cloud server and the device will give alert to the user via mobile application when an emergency condition occurs. The experimental results indicate that our safety monitoring network can work reliably with low power consumption.
Physical training in elderly men with special reference to quadriceps muscle strength and morphology

Summary. Physical training, including strength training of the lower extremities, was performed three times per week for 12 weeks by twelve 69–74-year-old men with no cardiovascular or locomotor symptoms. Only body weight was used as resistance. The training was considered to be moderately intense for this age-group. After training, the heart rate was significantly lower at submaximal loads, demonstrating a conditioning effect of the training programme. The static and dynamic (isokinetic) muscle strength in the quadriceps muscle increased significantly with the training. Muscle biopsies were obtained from the vastus lateralis muscle for fibre, capillary and enzyme activity analysis. The fibre composition was altered after training, with a significantly higher proportion of Type II fibres, mainly due to an increase of Type II A fibres. The relative area of the Type IIA fibres increased significantly with training. There was no change in total body cell mass or capillarization. There was also enzymatic evidence of training adaptation, with a significant increment in myokinase activity. It is concluded that the ageing human skeletal muscle remains trainable and that the training response is similar to that seen in younger age-groups.
Using traditional horizontal-vertical illusion figures and single lines to directly compare haptics and vision

The horizontal-vertical illusion (HVI) is the tendency for a vertical line to be perceived as longer than a horizontal line of the same length. The HVI is commonly reported and investigated as a visual phenomenon. It has, however been found to occur haptically. The comparatively small number of haptic HVI papers paired with varied stimuli and measures make it problematic to directly compare visual and haptic forms of the illusion. The current paper reports a study in which the visual and haptic HVIs were directly compared. Three sets of stimuli were used in an attempt to resolve previous limitations: L-figures, inverted T-figures, and separated horizontal and vertical lines. These stimuli were presented in two lengths: 3 and 9 cm. The dependent variable was percentage error between the horizontal and vertical - no error represents an absence of illusion. As expected, inverted T-figures produced an illusion significantly stronger than both the L-figures and single lines, which did not differ from each other. Stimuli of 9 cm produced stronger illusions than those that measured 3 cm, and stimulus size interacted with modality. The consequences of these findings for earlier research are discussed and suggestions are offered as to what causes this and other illusions.