Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis

Objective To evaluate tofacitinib's effect upon pneumococcal and influenza vaccine immunogenicity. Methods We conducted two studies in patients with rheumatoid arthritis using the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and the 2011–2012 trivalent influenza vaccine. In study A, tofacitinib-naive patients were randomised to tofacitinib 10 mg twice daily or placebo, stratified by background methotrexate and vaccinated 4 weeks later. In study B, patients already receiving tofacitinib 10 mg twice daily (with or without methotrexate) were randomised into two groups: those continuing (‘continuous’) or interrupting (‘withdrawn’) tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation. In both studies, titres were measured 35 days after vaccination. Primary endpoints were the proportion of patients achieving a satisfactory response to pneumococcus (twofold or more titre increase against six or more of 12 pneumococcal serotypes) and influenza (fourfold or more titre increase against two or more of three influenza antigens). Results In study A (N=200), fewer tofacitinib patients (45.1%) developed satisfactory pneumococcal responses versus placebo (68.4%), and pneumococcal titres were lower with tofacitinib (particularly with methotrexate). Similar proportions of tofacitinib-treated and placebo-treated patients developed satisfactory influenza responses (56.9% and 62.2%, respectively), although fewer tofacitinib patients (76.5%) developed protective influenza titres (≥1:40 in two or more of three antigens) versus placebo (91.8%). In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively). Conclusions Among patients starting tofacitinib, diminished responsiveness to PPSV-23, but not influenza, was observed, particularly in those taking concomitant methotrexate. Among existing tofacitinib users, temporary drug discontinuation had limited effect upon influenza or PPSV-23 vaccine responses. Trial registration numbers NCT01359150, NCT00413699.
CASE OF THE MONTH: February 1999 ‐ 54 Year Old Man with Severe Muscle Weakness

A 54 year old man developed rhabdomyolysis one year after beginning treatment with a combination of lovastatin (an HMGCoA reductase inhibitor) and niacin. Muscle biopsy showed a severe necrotizing myopathy affecting both fibre types. Recovery occured gradually with cessation of medication. The spectrum of cholesterol lowering agent myopathy may include delayed cases of unusual severity.
Structure/Function Analysis of Four Core ESCRT‐III Proteins Reveals Common Regulatory Role for Extreme C‐Terminal Domain

Endosomal sorting complex required for transport‐III (ESCRT‐III) is a large complex built from related ESCRT‐III proteins involved in multivesicular body biogenesis. Little is known about the structure and function of this complex. Here, we compare four human ESCRT‐III proteins – hVps2‐1/CHMP2a, hVps24/CHMP3, hVps20/CHMP6, and hSnf7‐1/CHMP4a – to each other, studying the effects of deleting predicted α‐helical domains on their behavior in transfected cells. Surprisingly, removing ∼40 amino acids from the C‐terminus of each protein unmasks a common ability to associate with endosomal membranes and assemble into large polymeric complexes. Expressing these truncated ESCRT‐III proteins in cultured cells causes ubiquitinated cargo to accumulate on enlarged endosomes and inhibits viral budding, while expressing full‐length proteins does not. hVps2‐1/CHMP2a lacking its C‐terminal 42 amino acids further fails to bind to the AAA+ adenosine triphosphatase VPS4B/SKD1, indicating that C‐terminal sequences are important for interaction of ESCRT‐III proteins with VPS4. Overall, our study supports a model in which ESCRT‐III proteins cycle between a default ‘closed’ state and an activated ‘open’ state under control of sequences at their C‐terminus and associated factors.
[Influence on pubertal reproductive function in female rats by immune challenge in early life].

OBJECTIVE To investigate the long-term programming effects on pubertal reproductive function by immunological challenge in early life. METHODS Female Sprague-Dawley rats were administered by endotoxin (lipopolysaccharide, LPS) at a dosage of 50 µg/kg and saline intraperitoneally on postnatal day 3 and 5. Body weight was measured weekly. Puberty onset (vaginal opening) and oestrous cyclicity were monitored from postnatal day 30. At the age of 6 weeks, bilateral ovariectomy was performed. The histological and morphological change of the ovaries (the thickness of the theca interna and the number of different kinds of follicles) were observed and the immunoreactivity of the ovarian sympathetic nerve markers (low affinity receptor of nerve growth factor, p75NGFR) was evaluated by immune staining. RESULTS Immunological challenge (exposed to LPS) in early life delayed vaginal opening significantly [LPS-treated (40.6 ± 0.7) days versus controls (38.6 ± 0.5) days, P < 0.05], decreased the percentage of normal oestrous cyclicity (LPS-treated 26.1% versus controls 66.8%, P < 0.05), decreased the total number of different types of follicles (primordial follicles: LPS-treated 610 ± 47 versus controls 1181 ± 57, P < 0.05; primary follicles: LPS-treated 624 ± 41 versus controls 960 ± 30, P < 0.05; preantral follicles: LPS-treated 183 ± 16 versus controls 260 ± 14, P < 0.05; antral follicles: LPS-treated 32 ± 4 versus controls 79 ± 7, P < 0.05) and increased the thickness of the theca interna [LPS-treated (15.8 ± 0.4) µm versus controls (11.4 ± 0.3) µm, P < 0.05]. The immunostaining of p75NGFR was obviously enhanced in the LPS-treated ovaries when compared with that of controls (P < 0.05). CONCLUSIONS Immunological stress during early critical developmental windows could have long dysfunctional effects on the pubertal reproductive function. It delayed puberty onset, reduced the percentage of the normal oestrous cycles, decreased follicles reserve and increased the thickness of the theca interna which might involve the up-regulation of the local ovarian sympathetic nerve activity.
Thermal optimization of a tubular permanent magnet linear synchronous motor

For motor working in high load condition, such as electromagnetic launch motor, the phenomenon of the local overheating exists easily. It makes the thermal capacity of the motor itself reduce, and the efficiency of the traditional water cooling or forced air cooling systems in the iron decline. Against the issue, this paper researched a small proportion of tubular permanent magnet linear synchronous motor (TPMLSM). The temperature calculation model was established combing the methods of thermal circuit and temperature field. The heating and cooling process and their regularity were analyzed. And the optimization of thermal conductivity was obtained by optimizing the insulation to reduce the temperature gradient inside the motor and improve the cooling rate. The temperature rises of the TPMLSM when the methods of the optimization of thermal conductivity, forced cooling and reducing the loss were used. And the effect of reducing temperature rise were comparing, which were expected to be useful for the thermal optimization and reasonable application for the motor in different working condition.
A multimedia big data retrieval framework to detect dyslexia among children

In this paper we present a tablet-based and big data-based multimedia environment, which uses text, audio, video, and gaze movement to detect a set of symptoms of having dyslexia among children of age both less than 10 and greater than 10. Multi-modal screening test modules have been developed, which gives indications of further dyslexia diagnosis. The multimedia framework is envisioned to accelerate and ease the process of testing dyslexia at the global level, and to identify and auto assess potential Dyslexic patterns and to accumulate huge collection of multimedia test data for in-depth dyslexia pattern analysis. Categories and Subject Descriptors H.1. 2 [User/Machine Systems]: Human Factors. General Terms K.4. 2 [Social Issues]: Assistive technologies for persons with disabilities.
Atrial tachycardia: mechanisms and management

Atrial tachycardias comprise a heterogeneous group of arrhythmias that include focal atrial tachycardia, typical atrial flutter and atypical atrial flutter. Focal atrial tachyardias arise from automatic, triggered or microreentrant mechanisms, while typical and atypical flutters are macroreentrant in nature. Typical flutter describes a reentrant circuit that is dependant on the cavotricuspid isthmus in the right atrium while atypical flutter includes various lesional and de novo macroreentrant circuits in the right and left atria. Electrocardiographic criteria have been proposed to distinguish these mechanisms of tachycardia, but they are not specific; whereas adenosine often aids in the diagnosis. Management of focal atrial tachyardias and macroreentry centers around rate control, antiarrhythmic therapy, ablation and anticoagulation. Success rates for ablation are highest for typical atrial flutter and higher than antiarrhythmic therapy for most atrial tachycardias.
Telerehabilitation after arthroscopic subacromial decompression is effective and not inferior to standard practice: Preliminary results

Background Telerehabilitation promises to improve quality, increase patient access and reduce costs in health care. Physiotherapy with exercises is generally recommended to restore function after surgery in patients with chronic subacromial syndrome. Relatively few studies have investigated the feasibility of telerehabilitation interventions in musculoskeletal and orthopaedic disorders. The aim of this study was to evaluate the feasibility and effectiveness of a customizable telerehabilitation intervention and compare with traditional care. Methods This research includes 18 consecutive patients with subacromial impingement who underwent arthroscopic subacromial decompression in a controlled clinical prospective study. Patients were randomized to either a 12-week telerehabilitation programme or the usual face-to-face physical therapy for immediate postoperative rehabilitation. We have developed a telerehabilitation system to provide services to patients who have undergone shoulder arthroscopy. An independent blinded observer performed postoperative follow-up after 4, 8, and 12 weeks. Results The preliminary efficacy of this telerehabilitation programme in terms of both physical and functional objective outcome measures was assessed on eight patients. Using the Constant–Murley score to evaluate functional outcome, patients in the telerehabilitation group were shown to have improved from a mean 43.50 ± 3.21 points to a mean 68.50 ± 0.86 points after 12 weeks. The physical and functional improvements in the telerehabilitation group were similar to those in the control group (p = 0.213). There was a non-significant trend for greater improvements in the telerehabilitation group for most outcome measurements. Conclusion The results of this study provide evidence for the efficacy of telerehabilitation after shoulder arthroscopy in shoulder impingement syndrome. A telerehabilitation programme with range of motion, strengthening of the rotator cuff and scapula stabilizers exercises seems to be similar and not inferior to traditional face-to-face physiotherapy after subacromial arthroscopic decompression. Through this study, we are developing our preliminary dataset to evaluate the efficacy of telerehabilitation programmes following surgical procedures in musculoskeletal injuries and for comparison with more traditional interventions.
Macrophage function during Trypanosoma musculi infection in mice

Quantitative and functional changes in peritoneal macrophages from mice infected with Trypanosoma musculi were investigated. Increase in the number and size and in the protein content of peritoneal macrophages and the presence of parasites in the peritoneal activity were observed during the course of parasitemia. Induced releases of H2O2 by macrophages were increased during parasitemia, but H2O2 release returned to normal after infection. A correlation was also observed between parasitemia and 99mTc colloidal uptake by peritoneal macrophages. These changes in macrophage function may indicate an activation of these cells.
Single mothers and family formation in Suurbraak: a mixed methods study

ii OPSOMMING . iii ACKNOWLEDGEMENTS . iv LIST OF TABLES . viii LIST OF FIGURES . ix LIST OF ABBREVIATIONS . x CHAPTER 1: INTRODUCTION . 1 1.
Widespread Bordetella parapertussis Infections-Wisconsin, 2011-2012: Clinical and Epidemiologic Features and Antibiotic Use for Treatment and Prevention.

BACKGROUND During October 2011-December 2012, concurrent with a statewide pertussis outbreak, 443 Bordetella parapertussis infections were reported among Wisconsin residents. We examined clinical features of patients with parapertussis and the effect of antibiotic use for treatment and prevention. METHODS Patients with polymerase chain reaction results positive for B. parapertussis reported during October 2011-May 2012 were interviewed regarding presence and durations of pertussis-like symptoms and receipt of azithromycin treatment. Data regarding acute cough illnesses and receipt of azithromycin prophylaxis among parapertussis patient household members (HHMs) were also collected. Using multivariate repeated measures log-binomial regression analysis, we examined associations of treatment receipt by the HHM with the earliest illness onset and prophylaxis receipt among other HHMs with the presence of any secondary cough illnesses in the household. RESULTS Among 218 patients with parapertussis, pertussis-like symptoms were frequently reported. Illness durations were significantly shorter among patients with treatment initiated 0-6 days after cough onset, compared with nonrecipients (median durations: 10 vs 19 days, P = .002). Among 361 HHMs from 120 households, compared with nonrecipients, prompt prophylaxis of HHMs was associated with no secondary cough illnesses (relative risk: 0.16; 95% confidence interval, .04-.69). CONCLUSIONS Bordetella parapertussis infection causes pertussis-like illness that might be misclassified as pertussis if B. parapertussis testing is not performed. Prompt treatment might shorten illness duration, and prompt HHM prophylaxis might prevent secondary illnesses. Further study is needed to evaluate antibiotic effectiveness for preventing parapertussis and to determine risks and benefits of antibiotic use.
Characterization and localization of the genes for mouse proteinase-3 (Prtn3) and neutrophil elastase (Ela2)

Proteinase-3 (PR-3) and neutrophil elastase (NE) are polymorphonuclear leukocyte serine proteinases that degrade extracellular matrix proteins including elastin and appear to be involved in the pathogenesis of several diseases characterized by tissue destruction most notably emphysema and Wegener’s granulomatosis. In this report we characterize and compare the mouse PR-3 and NE genes and establish by FISH analysis a common location on mouse chromosome 10C2. Each gene consists of five exons and four introns conserving the typical granule-associated serine proteinase gene structure. The mouse PR-3 gene (Prtn3) is approximately 3.7 kb and is within 2.2 kb of the smaller (1.7 kb) NE gene (Ela2). The larger size of Prtn3 is accounted for by differences in intron sizes. A comparison between the mouse and human PR-3 cDNA reveals 73% homology, however, this drops to 60% when the amino acid sequences are compared. Homology between the mouse and human NE cDNA is 77% for both the cDNA and amino acid sequences. The catalytic triad and its placement are conserved among the four genes. The proximal promoter of mouse Prtn3 contains a TATA box, c-myb and an ets transcriptional site. As these are functional elements in the mouse Ela2 promoter they may also be important in the expression of Prtn3.
A Systematic Literature Review of University Technology Transfer from a Quadruple Helix Perspective: Toward a Research Agenda

Within recent years, there has been a rapid expansion of the University's role in economic development. This has resulted in University Technology Transfer (UTT) taking place within an increasingly complex network of regional stakeholders. This complexity has resulted in quadruple helix models where the triple helix model of academia, industry and regional government now includes societal based innovation users as a fourth helix. Despite this development, extant research is fragmented and lacks coherent frameworks and conceptualisations which fully depict the dynamic and evolving nature of UTT. Accordingly, this article reviews Mode 2 UTT from a quadruple helix perspective to identify key themes to develop a research agenda which reflects progression from a triple into a quadruple helix ecosystem.
Small-Molecule Inhibitors of the Protein Methyltransferase SET7/9 Identified in a High-Throughput Screen

Aberrant expression of chromatin-modifying enzymes (CMEs) is associated with a range of human diseases, including cancer. CMEs are now an important target area in drug discovery. Although the role that histone and protein (lysine) methyltransferases (PMTs) play in the regulation of transcription and cell growth is increasingly recognized, few small-molecule inhibitors of this class of enzyme have been reported. Here we describe an assay suitable for primary compound screening for the identification of PMT inhibitors. The assay followed the methylation of histones in the presence of the PMT SET7/9 and the radioactive cofactor S-adenosyl-methionine using scintillating microplates (FlashPlate) and was used to screen approximately 65 000 compounds (% coefficient of variation = 10%; Z′ = 0.6). The hits identified from a library of more than 63 000 diverse small molecules included a series of rhodanine compounds with micromolar activity. A screen of the National CancerInstitute Diversity Set (2000 compounds) identified an orsein derivative that inhibited SET7/9 (~20 µM) and showed modest growth inhibition associated with the expected cellular phenotype of reduced histone methylation in a human tumor cell line. The assay represents a useful tool for the identification of inhibitors of PMT activity.
Contribution of energy systems during a Wingate power test.

Six men performed a total of 23 modified Wingate power tests against 5.5 kp (53.9 N) resistance on a Monark 864 ergometer. Breath-by-breath VO2 was measured using a SensorMedics 4400 metabolic cart. Peak anaerobic power (highest 5 s; mean(s.e.m.)) was 819(16) W (11.1(0.6) W kg-1) and anaerobic capacity (work in 30 s; mean(s.e.m.)) was 18.2(0.2) kJ (248(11) J kg-1). Contributions of ATP-PC, glycolytic and aerobic systems each 5 s were estimated. ATP-PC power (mean(s.e.m.)) peaked at 750(14) W (10.2(0.6) W kg-1) in the first 5 s; glycolytic power (mean(s.e.m.] peaked at 497(11) W (6.8(0.7) W kg-1) between 10 and 15 s into the test; aerobic power (mean(s.e.m.)) peaked at 157(5) W (2.1(0.3) W kg-1) during the last 5 s of the test, and VO2 exceeded 90% VO2peak Over the entire 30 s, aerobic contribution was 16%, glycolytic contribution was 56%, and ATP-PC contribution was 28%. It is concluded that glycolytic power peaks within the first 15 s of high power exercise; also, aerobic metabolism responds quickly during 'anaerobic' exercise and makes a significant contribution to the work performed.
Computing Special Values of Motivic L-Functions

We present an algorithm to compute values L(s) and derivatives L (k) (S) of L-functions of motivic origin numerically to required accuracy. Specifically, the method applies to any L-serieswhose Γ-factor is of the form AS with d arbitrary and complex λ j , not necessarily distinct. The algorithm relies on the known (or conjectural) functional equation for L(s).
KAJIAN PERAN ELIT POLITIK DALAM KEBIJAKAN PANGAN: JEBAKAN IMPOR PANGAN PASCA REFORMASI

This study aimed to unwrap the dynamic in policy making of food import, focusing in political elitess’ interest during the period of 1999-2009. Every period was analized emphasizing the main characters of nepotism and rent seeking: (a) the general character of food policy, (b) regulation in prolonging its activity, and (c) policy actors/elites and the political party dominating the policy sector. Result of this reseach were mainly the difference of focus and characters on policy in 3 periods. Explanation of research finally answered as followed: (1) government elites are the main actors and they are mostly the policy makers from food institution, (2) the actors came from different political party and bring about the different agenda to be supported with regulation, and (3) food institution determined the rent-seeking activity through the same actors that also dominate the import area. The important evidence of this point was the “three pairs of name” that affiliated with (the same) political party, executed importing processes, and also influenced the regulation in very the same time. Keywords: political economy, food import policy, policy elites, incremental policy.
Bridging the gap between science and public health: taking advantage of tobacco control experience in Brazil to inform policies to counter risk factors for non-communicable diseases.

AIMS AND DESIGN The historical and economic involvement of Brazil with tobacco, as a major producer and exporter, was considered an insurmountable obstacle to controlling the consumption of this product. Nevertheless, the country was able to achieve significant progress in implementing public policies and to take an international leadership position, meeting its constitutional commitment to protect public health. In this paper we provide a brief historical overview of tobacco control (TC) in Brazil, and analyse the factors that contributed to the major decline in tobacco consumption in the country over the last 20 years, as well as identify the challenges that had to be overcome and those still at play. FINDINGS The Brazilian case demonstrates how cross-sectorial collaborations among health-related groups that capitalize on their respective strengths and capacities can help to influence public policy and overcome industry and population resistance to change. Although Brazil still lags behind some leading TC nations, the country has an extensive collaborative TC network that was built over time and continues to focus upon this issue. CONCLUSIONS The tobacco experience can serve as an example for other fields, such as alcoholic beverages, of how networks can be formed to influence the legislative process and the development of public policies. Brazilian statistics show that problems related to non-communicable diseases are a pressing public health issue, and advocacy groups, policy-makers and government departments can benefit from tobacco control history to fashion their own strategies.
Combination of multiple classifiers by minimizing the upper bound of bayes error rate for unconstrained handwritten numeral recognition

In order to raise a class discrimination power by the combination of multiple classifiers, the upper bound of Bayes error rate which is bounded by the conditional entropy of a class and decisions should be minimized. Based on the minimization of the upper bound of the Bayes error rate, Wang and Wong proposed only a tree dependence approximation scheme of a high-dimensional probability distribution composed of a class and patterns. This paper extends such a tree dependence approximation scheme to higher order dependency for improving the classification performance and thus optimally approximates the high-dimensional probability distribution with a product of low-dimensional distributions. And then, a new combination method by the proposed approximation scheme is presented and evaluated with classifiers recognizing unconstrained handwritten numerals.