Miracle-dz/UniFAR-FTUs huggingface dataset:
Capsaicin Combined with Local Anesthetics Preferentially Prolongs Sensory/Nociceptive Block in Rat Sciatic Nerve

Background: Transient receptor potential vanilloid 1 channels integrate nociceptive stimuli and are predominantly expressed by unmyelinated C-fiber nociceptors, but not low-threshold mechanoreceptive sensory or motor fibers. A recent report showed that the transient receptor potential vanilloid 1 channel agonist capsaicin allows a hydrophilic quaternary ammonium derivative of lidocaine, QX-314, to selectively block C fibers without motor block. The authors tested whether a similar differential block would be produced using amphipathic N-methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, either alone or together with 0.05% capsaicin, in a rat sciatic nerve block model. Methods: Rats (n = 8/group) were anesthetized with sevoflurane, and 0.2 ml of drug was injected either alone or with capsaicin (simultaneously or 10 min later) next to the sciatic nerve in the sciatic notch. Motor function was assessed by the extensor postural thrust. Nociception was evaluated by the nocifensive withdrawal reflex and vocalization evoked by pinch of a skin fold over the lateral metatarsus (cutaneous pain) with a serrated forceps. Results: N-Methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, followed by injection of capsaicin 10 min later, each elicited a predominantly nociceptive-specific blockade. In comparison, simultaneous application of each local anesthetic with capsaicin did not elicit a clinically significant differential block, with the exception of N-methyl amitriptyline. Conclusions: Both tertiary amine local anesthetics and their quaternary ammonium derivatives can elicit a predominantly sensory/nociceptor selective block when followed by injection of capsaicin. The combined application of transient receptor potential vanilloid 1 channel agonists and various local anesthetics or their quaternary ammonium derivatives is an appealing strategy to achieve a long-lasting differential block in regional analgesia.
Letter to the Editor: Comments on ‘Is there an excess of significant findings in published studies of psychotherapy for depression?’

Flint and colleagues make use of a powerful statistical approach to suggest that there is significant positive bias in the expected distribution of published trials of psychotherapy (Flint et al. 2014). They draw a parallel with the bias we know exists in the drug treatment literature and imply that it is again publication bias that explains the finding. In other words, withholding publication has deflated the number of non-significant results. Indeed, for drug trials conducted by companies (the majority), we know this is the case because the results of negative trials are submitted to the regulatory authorities and can be identified if they are not published. Much has been made of this in previous reviews (Turner, 2013). However, publication bias is not necessarily the explanation for the findings in psychotherapy trials. We know that the quality of most psychotherapy trials falls far short of what is normal in drug trials (Huhn et al. 2014). Thus, a variety of biases operate to inflate the number of significant results in psychotherapy trials before publication. These include strong allegiance bias, single blind designs and a flexible approach to statistical treatment of outcomes. The result may well be the distorted distribution of results that Flint and colleagues identify in the published literature. A simple prediction is that significant numbers of unpublished negative studies simply do not exist for psychotherapies. In conclusion, if bias distorts the generation of data rather than simply its reporting, we are presumably uncertain what a true effect size is for psychotherapy.
Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study.

OBJECTIVE To obtain preliminary information about the effectiveness of intra-articular injections of an autologous preparation rich in growth factors (PRGF) for knee OA treatment to be explored further in future studies. METHODS We have characterized PRGF treatment by platelet count and concentration of relevant growth factors (TGF-Beta1, PDGF-AB, VEGF-A; HGF and IGF-I) involved in healing mechanisms. We have performed an observational retrospective cohort study using hyaluronan injections as a control. Each group included 30 patients with OA of the knee, matched according to age, sex, body mass index and radiographic severity. Both treatments were based on three weekly injections. Clinical outcome was examined using the WOMAC questionnaires prior to treatment and at 5 weeks after treatment. RESULTS The observed success rates by week 5 for the pain subscale reached 33.4% for the PRGF group and 10% for the hyaluronan group. The difference was attributed exclusively to the treatment modality, p = 0.004. The percent reductions in the physical function subscale and overall WOMAC at 5 weeks were also associated solely with treatment modality in favour of PRGF, p = 0.043 and p = 0.010 respectively. CONCLUSIONS Although these preliminary results need to be evaluated in a randomized clinical trial, they provide useful infomration about the safety of PRGF and open new perspectives on autologous treatments for joint diseases.
Distribution System State Estimation Model Using a Reduced Quasi-Symmetric Impedance Matrix

This paper presents a novel formulation of the Distribution System State Estimation (DSSE) optimization model. For a given electric three-phase circuit feeder, network models are built using a quasi-symmetric impedance matrix TRX representing the entire structure and topology of the radial network. As a key contribution, the state variables of demands and generators connected to large-scale distribution grids are obtained by using a convenient matrix reduction technique. As a result, the size of the optimization problem is considerably reduced with respect to the jacobian formulation by considering radial and weakly meshed exploitation and elimination of interconnecting nodes. Results and comparative analysis are presented using the IEEE 4-, 13-, 37-, 123-, and 8500-node test systems.
A diagnostic test pattern generation algorithm

The authors present a novel ATPG (automatic test pattern generation) algorithm, based on PODEM, that makes diagnostic test pattern generation feasible for medium-sized combinational circuits described at the gate level with the single-stuck-at-fault assumption. The input to the ATPG is a couple of faults, and either the output is a test pattern that distinguishes them or they are tagged as indistinguishable. The need to consider the fault-free circuit and the two faulty circuits at the same time required the extension of the algebra to encompass two additional values, Delta and delta . A Delta appears on the nodes of the circuit whenever a difference between the two faulty circuits exists. The presence of a delta marks the locations where a difference might exist if the X values on one or both faulty circuits were suitably set. The algorithm excites and propagates Delta s onto the primary outputs and is thus called the Delta -algorithm. Preliminary results on a set of benchmark circuits are reported. <<ETX>>
Evolution of pharmacological obesity treatments: focus on adverse side‐effect profiles

Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity‐associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine‐induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non‐fatal cardiovascular events (sibutramine), and neuro‐psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti‐obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk–benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight‐reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post‐marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post‐marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti‐obesity pharmacotherapy and consider how the history of high‐profile toxicity issues has shaped the current regulatory landscape for new and future weight‐reducing drugs.
IDENTIDADE IURDIANA EM TEMPOS LÍQUIDOS:QUESTÕES SOBRE DIFERENÇA E TRADUÇÃO NA FORMAÇÃO IDENTITÁRIA DA IURD

Este Artigo faz reflexoes sobre a construcao indenitaria da Igreja Universal do Reino de Deus (IURD), empregando as categorias da “diferenca” e “traducao” propostas por Stuart Hall e Kathryn Woodard. Um componente importante nesta construcao e a “diferenca”, pois a IURD edifica sua identidade ressaltando sua diferenca em relacao a outros grupos religiosos. No entanto, a “traducao” trata da forma como a IURD tomou emprestado parte do corpo de tradicoes, doutrinas e rituais de grupos religiosos que ela mesma critica, fazendo uma reelaboracao criativa e radical. Para empreender esta tarefa utilizamos dados obtidos de observacoes de cultos da IURD, de literatura produzida pela instituicao, livros de pesquisadores e dados oriundos de entrevistas que realizamos.
Advances, Nuances, and Potential Pitfalls When Exploiting the Therapeutic Potential of RNA Interference

The discovery of RNA interference (RNAi) holds the potential to alter the paradigm of medical therapeutics. With the ability to selectively silence the function of a gene, RNAi not only provides an indispensable research tool for determining the function of a gene, but also offers potential for the development of novel therapeutics that will inhibit specific genes involved in disease. New concepts in therapeutics have been uncovered through the study of RNAi. Nuances have emerged. For instance, global RNAi pathways can be affected by somatic mutations in cancer and cellular stress, such as hypoxia. Also, viral gene therapy can have unexpected effects on endogenous short noncoding RNA pathways. Therefore, it is important to understand where RNAi therapeutics enter the processing pathways. We highlight the evolving use of RNAi as a new class of therapeutics, such as for amyloidosis, and address some of the anticipated challenges associated with its clinical application.
Wavelet denoising and ANN/SVM decoding of a self-paced forelimb movement based on multi-unit intra-cortical signals in rats

Brain-computer interfacing (BCI) has the potential to rehabilitate patients suffering from severe motor deficits. A key element in the success of BCI systems is the availability of sophisticated signal processing techniques for decoding intended movements. The first objective of the present work was to investigate the usefulness of ANN/SVM techniques to decode a self-paced forelimb movement based on multi-unit intracortical recordings in rats. The second objective was to evaluate if wavelet denoising of the raw intra-cortical signals had a positive effect on the decoding. Four rats were first trained to hit a response paddle. Multiple recording sessions where performed after implanting a 16ch microwire array in the M1. An artificial neural network (ANN) and a support vector machine (SVM) were designed for decoding the intra-cortical signals, i.e. to detect if a `Hit' had occurred. The results showed that denoising of the intra-cortical recordings consistently yielded a lower misclassification error rate (statistically different). We also found that the ANN and the SVM resulted in similar classification results (no significant difference). The classification error rate showed variability between days and between rats (average between 23% - 31% (ANN) and 23% - 30% (SVM)). Our results indicate that the non-linear decoding methods both perform equally well, and as such, the quality of intra-cortical signals is of high importance in the design of a robust and reliable BCI system.
Rumen epithelial cell proliferation accelerated by rapid increase in intraruminal butyrate.

Two pairs of adult castrated male sheep were given intraruminally 2 g/kg body weight per day of sodium n-butyrate rapidly 10 s at noon or slowly over 20 to 24 h from noon in four trials in which they received only mixed minerals and water ad libitum. Their ruminal papillae were biopsied just before each administration and 24 h after the final administration. Mitotic indices of the epithelial cells were observed. Mitotic indices were lower than . 48% before butyrate administration. In sheep rapidly administered butyrate, mitotic indices increased to 1.29%, 2.33%, 2.65%, and 1.84% in 1 day after the first administration in four trials and tended to decline on later days. In sheep slowly administered butyrate, mitotic indices stayed lower than . 50% and did not show significant fluctuations. Our data support our hypothesis that an increase in the rate of intraruminal production of volatile fatty acids promotes proliferation of epithelial cells of the organ.
Diagnosis and Management of Thyrotoxicosis

Background: thyrotoxicosis is a hypermetabolic state due to excessive amounts of thyroid hormone in the circulation. There are several causes and the worst presentation is a thyroid storm, which is an endocrinal emergency. Clinically, thyrotoxicosis can present vaguely leading to misdiagnosis and mismanagement. Aim of the work: this study aimed to understand the clinical presentation of thyrotoxicosis, its diagnosis and ways of management. Methodology: we conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE from January 1987 to March 2017. Conclusion: due to its vague presentation, thyrotoxicosis can be misdiagnosed and managed wrongly, leading to life threatening condition called thyroid storm. Health care physicians must keep a high degree of suspicion in order to provide prompt therapeutic measures to avoid complications as well as death of patient.
Single-phase active power filter for selective harmonic elimination based on synchronous frame control system

In this paper is presented a synchronous reference frame control strategy for single-phase active power filter. The presented system is based on a selective harmonic elimination approach and allows for the fundamental reactive power compensation and harmonic elimination. The control system is carried out on a synchronous frame, which brings robustness and simplicity to the whole system.
Multiple mechanisms of transcription inhibition by ppGpp at the lambdap(R) promoter.

General stress conditions in bacterial cells cause a global cellular response called the stringent response. The first event in this control is production of large amounts of a regulatory nucleotide, guanosine-3',5'-(bis)pyrophospahte (ppGpp). It was proposed recently that ppGpp acts by decreasing stability of open complexes at promoters that make short-lived open complexes, e.g. the rRNA promoters. However, here we report that the bacteriophage lambdap(R) promoter, which forms long-lived open complexes, is inhibited by ppGpp in vitro as observed in vivo. We performed a systematic investigation of the ppGpp-specific inhibition of transcription initiation at lambdap(R) and found that ppGpp does decrease stability of open complexes at lambdap(R), but only slightly. Likewise the equilbrium binding constant and rate of open complex formation by RNA polymerase at lambdap(R) are only slightly affected by ppGpp. The major effect of ppGpp-mediated inhibition is to decrease the rate of promoter escape. We conclude that ppGpp-mediated inhibition of transcription initiation is not restricted to promoters that make short-lived open complexes. Rather we conclude that the initial catalytic step of transcript formation is affected by ppGpp, specifically formation of the first phosphodiester bond is inhibited by ppGpp at lambdap(R).
On the Key Generation From Correlated Wireless Channels

This letter investigates the secret key capacity of key generation from correlated wireless channels in a source model. We systematically study a practical scenario by taking into account all relevant parameters including sampling delay, eavesdroppers’ location, qualities of legitimate and eavesdropping channels, Doppler spread, and pilot length. Our findings indicate that secret key capacity is determined by the cross correlation of the channel measurements, and a better legitimate channel is not necessary when the correlation between legitimate channels is higher than correlation between legitimate and eavesdropping channels. We also find that it is possible to tune the secret key capacity by carefully designing the sampling delay, pilot length, and channel qualities. This letter offers practical design guidelines on secure key generation systems.
Cytoplasmic Dynein Moves Through Uncoordinated Stepping of the AAA+ Ring Domains

Doing the Side Step The molecular motor, dynein, contains two ring domains responsible for its movement along the microtubule. However, how the rings move relative to each other during processive motility and whether dynein processivity requires interhead coordination are unclear. To directly observe how dynein “walks” along microtubules, DeWitt et al. (p. 221, published online 8 December) performed advanced fluorescence-imaging studies to follow both motor domains of a single dynein motor at nanometer resolution. The data suggest that the two heads do not cooperate during movement, which suggests a fundamentally different mechanism of motility from that observed for other microtubule-based motors. The molecular motor dynein moves each of its two heads independently along the microtubule. Cytoplasmic dynein is a homodimeric AAA+ motor that transports a multitude of cargos toward the microtubule minus end. How the two catalytic head domains interact and move relative to each other during processive movement is unclear. Here, we tracked the relative positions of both heads with nanometer precision and directly observed the heads moving independently along the microtubule. The heads remained widely separated, and their stepping behavior varied as a function of interhead separation. One active head was sufficient for processive movement, and an active head could drag an inactive partner head forward. Thus, dynein moves processively without interhead coordination, a mechanism fundamentally distinct from the hand-over-hand stepping of kinesin and myosin.
A General Framework for the Parametrization of Hierarchical Models

In this paper, we describe centering and noncentering methodology as complementary techniques for use in parametrization of broad classes of hierarchical models, with a view to the construction of effective MCMC algorithms for exploring posterior distributions from these models. We give a clear qualitative understanding as to when centering and noncentering work well, and introduce theory concerning the convergence time complexity of Gibbs samplers using centered and noncentered parametrizations. We give general recipes for the construction of noncentered parametrizations, including an auxiliary variable technique called the state-space expansion technique. We also describe partially noncentered methods, and demonstrate their use in constructing robust Gibbs sampler algorithms whose convergence properties are not overly sensitive to the data.
Pattern of p53 protein expression is predictive for survival in chemoradiotherapy-naive esophageal adenocarcinoma

Introduction TP53 mutations are considered to be the driving factor in the initiation of esophageal adenocarcinoma (EAC). However, the impact of this gene and its encoded protein as a prognostic marker has not been definitely established yet. Methods In total, 204 chemoradiotherapy (CRT)-naive patients with EAC were included for p53 protein expression evaluation by immunohistochemistry (IHC) on the resection specimens, categorized as overexpression, heterogeneous or loss of expression, and correlated with disease free survival (DFS) and overall survival (OS) using multivariable Cox regression analysis. In a subset representing all three IHC subgroups mutational status of selected candidate genes (n=33) and high throughput methylation profiling (n=16) was assessed. Results Compared to heterogeneous p53 expression, loss and overexpression were both independently predictive for adverse DFS and OS. TP53 mutational status significantly correlated with the IHC categories (p=0.035). Most of the EAC with loss- or overexpression harbored TP53 mutations (18/20, representing nonsense and missense mutations respectively). In contrast, 6/13 EAC with heterogeneous expression were TP53 wild type, of which two demonstrated MDM4 or MDM2 amplification. Combined genomic hypomethylation and high frequency of intra-chromosomal breaks was found in a selection of EAC without p53 overexpression. Conclusion P53 expression pattern is prognostic for DFS and OS in this historical cohort of CRT-naive EAC. P53 IHC is an informative readout for TP53 mutational status in EAC with either loss- or overexpression, but not in case of a heterogeneous p53 pattern. Different EAC pathogenesis might exist, related to p53 and other candidate gene status, DNA hypomethylation and intrachromosomal breaks.
Uncovering the Pre-Dispositional Roots of Job Satisfaction

Understanding the determinants of Job satisfaction has long been the main focus of academic research in various business fields including; marketing, human resource management and organizational psychology. Business managers consider job satisfaction as one of the most important employee attitudes because of its positive work-related outcomes such as enhanced employee’s job performance, organizational commitment and citizenship behaviour. In service-oriented firms, a satisfied employee may be the facilitator of customerorientation implementation. A number of studies have found a positive relationship between employee satisfaction and customer satisfaction. In this context, the positive emotions and attitudes towards an organization motivates the employee to kindly treat customers simply because they are the ultimate source of organization success.