Miracle-dz/UniFAR-FTUs huggingface dataset:
Educational session as a tool to increase patient satisfaction of switching etanercept from the prefilled syringe to the autoinjection pen

Objective: To assess patients' acceptability of switching etanercept from the prefilled syringe to the autoinjection pen in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis patients. Methods: A two-phase cross-sectional study was designed. First phase: consisted of a 2 h information/education session to present the pen and learning its use. At the end of the session, patients completed a self-administered questionnaire regarding the meeting usefulness. Second phase: eight single-use prefilled Enbrel® Pen Myclic were provided. Results: The number of patients included were 104 (rheumatoid arthritis 58, psoriatic arthritis 31, ankylosing spondylitis 15). Attendees showed a high satisfaction degree with the meeting. A high percentage of patients (74.4 – 95.1%) rated the items of the questionnaire as ‘very much'. Patients reported > 95% adherence to etanercept autoinjection pen. The percentage of patients self-administering etanercept increased from 66 to 94% and the percentage of those attending primary care for injection decreased from 23 to 2%. It produced important cost savings, in our study represents > 22.000 euros/year. Pain at the injection site was significantly reduced with the use of autoinjection pen. Ninty seven (93%) patients considered that the use of the autoinjection pen was easier than the syringe and 94.2% chose the pen as their preferred delivery system. Conclusions: The autoinjection pen is an advantageous delivery option for etanercept. This study provides further evidence to support that the education strategy is a valid method for switching anti-TNF-α drugs from syringe to pen in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.
Epidemiology of hodgkin's lymphoma

The epidemiology of Hodgkin’s Lymphoma (HL) varies with age at clinical onset. In developing countries, the disorder appears predominantly during childhood and its incidence decreases with age, while in industrialized countries, the incidence rate increase with age. There has long been a view that the differences in descriptive epidemiology of Hodgkin’s Lymphoma around the world, and also between children, young adults and older adults may reflect differences in etiology between them. Hodgkin’s Lymphoma has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), as a causal agent. The etiology of EBV-negative cases remains obscure. Epidemiological investigation of the etiology of Hodgkin’s Lymphoma is making steady progress, and it leads to a better understanding and hence prevention. This review considers in detail the descriptive and the etiological epidemiology of Hodgkin’s Lymphoma.
Modality-specific changes in P300 parameters in patients with dementia of the Alzheimer type.

BACKGROUND The relationship between the parameters of the P300 potential and the degree or profile of cognitive decline remains controversial. The aim of our study was to evaluate parameters of auditory and visual P300 in patients with mild and moderate dementia of the Alzheimer type (DAT) and to correlate these with neuropsychological test results. MATERIAL/METHODS The study group comprised 13 patients with DAT and 13 healthy, age-matched controls. Auditory and visual event-related potentials were evoked using a basic oddball paradigm. P300 latency and amplitude were compared in patients with DAT and controls and between subgroups of patients with mild and moderate DAT. Correlations between P300 parameters and the results of the Mini-Mental State Examination (MMSE), the Global Deterioration Score (GDS), and the Alzheimer's Disease Assessment Scale (ADAS-cog) were also analyzed. RESULTS The mean latency of auditory P300 was significantly prolonged, and the mean amplitude of visual P300 was significantly lower in the DAT patients. 4 patients with DAT (31%) had a prolonged latency of auditory P300. No significant differences in P300 parameters were found between mildly demented and controls or between mildly and moderately demented. A positive correlation was found between MMSE score and auditory P300 latency in Fz and visual P300 amplitude in Cz. CONCLUSIONS P300 parameters undergo significant, modality-specific changes in patients with DAT. However, they are not sensitive enough to differentiate early dementia from normal aging.
Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide

Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3′,5′-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator–activated receptor γ coactivator 1α, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS–/–) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide–cGMP–dependent pathway controls mitochondrial biogenesis and body energy balance.
Changes in the relative population size of selected ruminal bacteria following an induced episode of acidosis in beef heifers receiving viable and non‐viable active dried yeast

To characterize the changes in the relative population size (RPS) of select ruminal bacteria and rumen fermentation variables in beef heifers supplemented with a strain of Saccharomyces cerevisiae as viable active dried (ADY) or killed dried (KDY) yeast following an induced episode of ruminal acidosis.
An evidence-based approach to red blood cell transfusions in asymptomatically anaemic patients.

INTRODUCTION Surgeons and physicians encounter blood transfusions on a daily basis but a robust evidence-based strategy on indications and timing of transfusion in asymptomatic anaemic patients is yet to be determined. For judicious use of blood products, the risks inherent to packed red blood cells, the patient's co-morbidities and haemoglobin (Hb)/haematocrit levels should be considered. This review critiques and summarises the latest available evidence on the indications for transfusions in healthy and cardiac disease patients as well as the timing of transfusions relative to surgery. METHODS An electronic literature search of the MEDLINE(®), Google Scholar™ and Trip databases was conducted for articles published in English between January 2006 and January 2015. Studies discussing timing and indications of transfusion in medical and surgical patients were retrieved. Bibliographies of studies were checked for other pertinent articles that were missed by the initial search. FINDINGS Six level 1 studies (randomised controlled trials or systematic reviews) and six professional society guidelines were included in this review. In healthy patients without cardiac disease, a restrictive transfusion trigger of Hb 70-80g/l is safe and appropriate whereas in cardiac patients, the trigger is Hb 80-100g/l. The literature on timing of transfusions relative to surgery is limited. For the studies available, preoperative transfusions were associated with a decreased incidence of subsequent transfusions and timing of transfusions did not affect the rates of colorectal cancer recurrence.
Application of near-infrared spectroscopy to predict sweetpotato starch thermal properties and noodle quality

Sweetpotato starch thermal properties and its noodle quality were analyzed using a rapid predictive method based on near-infrared spectroscopy (NIRS). This method was established based on a total of 93 sweetpotato genotypes with diverse genetic background. Starch samples were scanned by NIRS and analyzed for quality properties by reference methods. Results of statistical modelling indicated that NIRS was reasonably accurate in predicting gelatinization onset temperature (To) (standard error of prediction SEP=2.014 °C, coefficient of determination RSQ=0.85), gelatinization peak temperature (Tp) (SEP=1.371 °C, RSQ=0.89), gelatinization temperature range (Tr) (SEP=2.234 °C, RSQ=0.86), and cooling resistance (CR) (SEP=0.528, RSQ=0.89). Gelatinization completion temperature (Tc), enthalpy of gelatinization (ΔH), cooling loss (CL) and swelling degree (SWD), were modelled less well with RSQ between 0.63 and 0.84. The present results suggested that the NIRS based method was sufficiently accurate and practical for routine analysis of sweetpotato starch and its noodle quality.
Two pharmacologically and kinetically distinct transient potassium currents in cultured embryonic mouse hippocampal neurons

Transient potassium currents in mammalian central neurons influence both the repolarization of single action potentials and the timing of repetitive action potential generation. How these currents are integrated into neuronal function will depend on their specific properties: channel availability at the resting potential, activation threshold, inactivation rate, and current density. We here report on the voltage-gated transient potassium currents in embryonic mouse hippocampal neurons dissected at embryonic days 15–16 and grown in dissociated cell culture for up to 3 d. Two transient potassium currents, A-current and D-current, were isolated based on steady state inactivation and sensitivity to 4-aminopyridine (4-AP) and dendrotoxin (DTx). A-current had an activation threshold of approximately -50 mV and was half-inactivated at approximately -81 mV. A-current relaxations at voltages between -40 and +40 mV could be fit by single exponential functions with time constants of 20–25 msec; these time constants showed little sensitivity to voltage. In contrast, D-current had an activation threshold of between -40 and -30 mV and was half-inactivated at approximately -22 mV. D-current inactivation was voltage dependent; time constants of fitted exponential functions ranged from approximately 7 sec at -40 mV to 200 msec at +40 mV. A slower component of inactivation was also evident. D-current was preferentially blocked by 4-AP (100 microM) and DTx (1 microM). Operationally, A- and D- currents could be cleanly separated based on conditioning pulse potential and 4-AP sensitivity. Total transient potassium current amplitude increased during the time that neurons were in culture (recordings were made between 2 hr after dissociation and 3 d in culture). When normalized for cell capacitance (an index of membrane area), A-current density (pA/pF) decreased and D-current density increased, even during a period between days 1 and 3 when total transient current density remained constant. This observation suggests that A- and D-currents may be reciprocally modulated. Since blockade of D-current (with 100 microM 4-AP) increased both action potential duration and repetitive firing in response to constant current stimulation, long-term modulation of the A-current:D-current ratio may affect the excitability of hippocampal neurons.
Drug-stimulated ATPase Activity of Human P-glycoprotein Requires Movement between Transmembrane Segments 6 and 12*

Transmembrane segments (TM) 6 and 12 are directly connected to the ATP-binding domain in each homologous half of P-glycoprotein and are postulated to be important for drug-protein interactions. Cysteines introduced into TM6 (L332C, F343C, G346C, and P350C) were oxidatively cross-linked to cysteines introduced into TM12 (L975C, M986C, G989C, and S993C, respectively). The pattern of cross-linking was consistent with a left-handed coiled coil arrangement of the two helices. To detect conformational changes between the helices during drug-stimulated ATPase activity, we tested the effects of substrates and ATP on cross-linking. Cyclosporin A, verapamil, vinblastine, and colchicine inhibited cross-linking of mutants F343C/M986C, G346C/G989C, and P350C/S993C. By contrast, ATP promoted cross-linking between only L332C/L975C. Enhanced cross-linking between L332C/L975C was due to ATP hydrolysis, since cross-linked product was not observed in the presence of ATP and vanadate, ADP, ADP and vanadate, or AMP-PNP. Cross-linking between P350C/S993C inhibited verapamil-stimulated ATPase activity by about 75%. Drug-stimulated ATPase activity, however, was fully restored in the presence of dithiothreitol. These results show that TM6 and TM12 undergo different conformational changes upon drug binding or during ATP hydrolysis, and that movement between these two helices is essential for drug-stimulated ATPase activity.
A Mechanistic Perspective on Process-Induced Changes in Glucosinolate Content in Brassica Vegetables: A Review

Brassica vegetables are consumed mostly after processing, which is expected to give beneficial effects on the vegetable properties, such as improved palatability and bioavailability of nutrients, or shelf life extension. But processing also results to various changes in the content of health promoting phytochemicals like glucosinolates. This paper reviews the effects of processing on the glucosinolates content by using a mechanism approach underlying processing method employed. Cultural differences between Eastern and Western preparation practices and their possible effect on glucosinolate retention are highlighted. Boiling and blanching considerably reduce the glucosinolate content mainly due to mechanisms of cell lysis, diffusion, and leaching, and partly due to thermal and enzymatic degradation. Steaming, microwave processing, and stir frying either retain or slightly reduce the glucosinolates content due to low degrees of leaching; moreover, these methods seem to enhance extractability of glucosinolates from the plant tissue. Fermentation reduces the glucosinolate content considerably, but the underlying mechanisms are not yet studied in detail. Studying the changes of glucosinolates during processing by a mechanistic approach is shown to be valuable to understand the impact of processing and to optimize processing conditions for health benefits of these compounds.
Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum*

Merozoites of the malaria parasite Plasmodium falciparum expose at their surface a large multiprotein complex, composed of proteolytically processed, noncovalently associated products of at least three genes, msp-1, msp-6, and msp-7. During invasion of erythrocytes, this complex is shed from the surface except for a small glycosylphosphatidylinositol-anchored portion originating from MSP-1. The proteolytic cleavage separating the C-terminal portion of MSP-1 is required for successful invasion. Little is known about the structure and function of the abundant and essential multipartite complex. Using heterologously produced MSP-1, MSP-6, and MSP-7 in precursor and with the exception of MSP-7 in processed form, we have studied in vitro the complex formation between the different proteins to identify the interaction partners within the complex. Both MSP-636 and MSP-7 bind only to MSP-1 subunits that are shed, but although MSP-636 contacts just subunit p38, MSP-7 interacts with p83, p30, and p38. The intact C-terminal region of MSP-6 is required for the association with p38 as well as for its multimerization into tetramers. Furthermore, our data suggest that only the processed form and not the precursor form of MSP-1 interacts with MSP-636. MSP-6- as well as MSP-7-specific rabbit antibodies inhibit parasite multiplication in vitro as shown previously for antibodies directed against MSP-1. Our findings raise interesting questions with regard to proteolysis-mediated mechanisms of maturation of the MSP-1-MSP-6-MSP-7 complex and to the mode by which antibodies directed against this complex interfere with parasite multiplication.
Adaptive Control for Nonlinear Teleoperators With Uncertain Kinematics and Dynamics

The problem of controlling bilateral teleoperation systems in the presence of uncertain kinematics and dynamics is studied in this paper. Control algorithms and adaptive laws are developed to address the impediment of imprecise measurement resulting from when the slave robot grips a tool with unknown grasping point and orientation. We first demonstrate that with the utilization of the proposed adaptive laws, the teleoperation system is stable and the position tracking is guaranteed even if there are dynamic and kinematic uncertainties. Due to the end-effector velocity being difficult to obtain, an alternative control algorithm that does not incorporate task-space velocity information is developed. The issue of asymmetric constant communication delays in the teleoperation system is studied by Lyapunov-Krasovskii theorem. In the presence of external forces, we prove that all signals in the proposed teleoperation systems are bounded, and that force feedback is proportional to the tracking errors. Numerical simulations and experiments are performed to demonstrate the efficacy of the developed teleoperation systems.
[Treatment of non-motor symptoms of Parkinson's disease patients of Gan-Shen deficiency syndrome by guling pa'an granule: a multi-center double-blinded randomized controlled trial].

OBJECTIVE To observe the therapeutic efficacy of guiling pa'an granule (GPG) in treating non-motor symptoms of Parkinson's disease (PD) patients of Gan-Shen deficiency syndrome (GSDS). METHODS A multi-center,third party-central online, network randomized, double-blinded, double-dummy, and placebo controlled clinical trial was conducted. Totally 121 patients with confirmed diagnosis of PD by Western medicine and of GSDS by syndrome typing were assigned to the control group and the treatment group. Under the premise of the same treatment baseline, the placebo and GPG at the same dose was respectively administered to patients in the control group and the treatment group. The therapeutic course was 6 months for all. The changes of 8 non-motor symptoms (including witless expression, seborrhea, sialorrhea, cognitive impairment, constipation, hyperhidrosis, insomnia and dreaminess, and psychosis) were observed in the two groups, when compared with the baseline. RESULTS Satisfactory effectiveness in the 8 non-motor symptoms of PD patients were obtained in the treatment group (P<0.01). Besides, less adverse reactions occurred. CONCLUSION GPG could improve the non-motor symptoms of PD patients.
Exudative lesions of Reinke's space. An anatomopathological correlation.

Few anatomopathological criteria for distinguishing vocal nodules, polyps or REINKE's edema have been established in previously published studies. In order to study this issue, 163 samples (from 119 patients) were examined by an experienced anatomopathologist, without her prior knowledge of the macroscopic or microscopic diagnosis. In all the cases, the presence of exudative phenomena in REINKE's space proved to be the determining factors, with four outstanding stages of evolution: edema, fibrosis, deposits of fibrin and development of vascular ectasia. Although each of the three entities were seen to have their specific characteristics, a large number of lesions showed histological features which were not very specific, and were dominated by edema. Furthermore, the coexistence of different anatomopathological features makes each group heterogeneous. We propose a model which groups all the exudative lesions of REINKE's space by insisting, on the one hand, on the evolution of the anomalies and, on the other hand, the etiological factors (vocal misuse, tobacco, alcohol acute, vocal trauma .) which determine the onset of either one or other lesion.
Background selection as null hypothesis in population genomics: insights and challenges from Drosophila studies

The consequences of selection at linked sites are multiple and widespread across the genomes of most species. Here, I first review the main concepts behind models of selection and linkage in recombining genomes, present the difficulty in parametrizing these models simply as a reduction in effective population size (Ne) and discuss the predicted impact of recombination rates on levels of diversity across genomes. Arguments are then put forward in favour of using a model of selection and linkage with neutral and deleterious mutations (i.e. the background selection model, BGS) as a sensible null hypothesis for investigating the presence of other forms of selection, such as balancing or positive. I also describe and compare two studies that have generated high-resolution landscapes of the predicted consequences of selection at linked sites in Drosophila melanogaster. Both studies show that BGS can explain a very large fraction of the observed variation in diversity across the whole genome, thus supporting its use as null model. Finally, I identify and discuss a number of caveats and challenges in studies of genetic hitchhiking that have been often overlooked, with several of them sharing a potential bias towards overestimating the evidence supporting recent selective sweeps to the detriment of a BGS explanation. One potential source of bias is the analysis of non-equilibrium populations: it is precisely because models of selection and linkage predict variation in Ne across chromosomes that demographic dynamics are not expected to be equivalent chromosome- or genome-wide. Other challenges include the use of incomplete genome annotations, the assumption of temporally stable recombination landscapes, the presence of genes under balancing selection and the consequences of ignoring non-crossover (gene conversion) recombination events. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Phase-shifted full bridge converter featuring ZVS over the full load range

A new full-bridge circuit which can achieve zero voltage switching (ZVS) for all the primary side switches over the full load range and a wide input voltage range is proposed. The ZVS is achieved by the energy stored in the auxiliary inductor and the magnetizing inductance of the transformer. Because the leakage inductance is relatively small, there is no severe duty ratio loss or severe voltage ringing across the output rectifier. As the assistant current for achieving ZVS is almost the same for any duty ratio, the conduction losses at light load are reduced. The principal operation of the converter is described, and the optimal design is discussed. Finally, the operation of the converter is verified on a 1kW prototype.
Sphingosine 1-Phosphate Inhibits Activation of Caspases that Cleave Poly(ADP-ribose) Polymerase and Lamins during Fas- and Ceramide-mediated Apoptosis in Jurkat T Lymphocytes*

Ceramide, a sphingolipid generated by the hydrolysis of membrane-associated sphingomyelin, appears to play a role as a gauge of apoptosis. A further metabolite of ceramide, sphingosine 1-phosphate (SPP), prevents ceramide-mediated apoptosis, and it has been suggested that the balance between intracellular ceramide and SPP levels may determine the cell fate (Cuvillier, O., Pirianov, G, Kleuser, B., Vanek, P. G., Coso, O. A., Gutkind, J. S., and Spiegel, S. (1996) Nature 381, 800–803). Here, we investigated the role of SPP and the protein kinase C activator, phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), in the caspase cascade leading to the proteolysis of poly(ADP-ribose) polymerase (PARP) and lamins. In Jurkat T cells, Fas ligation or addition of exogenous C2-ceramide induced activations of caspase-3/CPP32 and caspase-7/Mch3 followed by PARP cleavage, effects that can be blocked either by SPP or TPA. Furthermore, both SPP and TPA inhibit the activation of caspase-6/Mch2 and subsequent lamin B cleavage. Ceramide, in contrast to Fas ligation, did not induce activation of caspase-8/FLICE and neither SPP nor TPA were able to prevent this activation. Thus, SPP, likely generated via protein kinase C-mediated activation of sphingosine kinase, suppresses the apoptotic pathway downstream of FLICE but upstream of the executioner caspases, caspase-3, -6, and -7.