Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.

The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1 alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 "shared epitope" (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.
Recent Advances in Urinary Tract Reconstruction for Neuropathic Bladder in Children

Neuropathic bladder usually causes several limitations to patients’ quality of life, including urinary incontinence, recurrent urinary tract infections, and upper urinary tract damage. Its management has significantly changed over the last few years. The aim of our paper is to address some salient features of recent literature dealing with reconstructive procedures in pediatric and adolescent patients with lower urinary tract dysfunction.
Novel therapy for Crohn’s disease targeting IL-6 signalling

The aetiology of Crohn’s disease (CD) remains unknown, however, the importance of pro-inflammatory cytokines including IL-6 has been shown. IL-6 can transduce its signal into the cells lacking membrane-bound receptors by forming a complex with soluble IL-6R (sIL-6R). To pursue the therapeutic potential of IL-6 signalling blockade for CD, anti-IL-6R monoclonal antibody (mAb) was introduced to experimental colitis, and successfully prevented and treated intestinal inflammation by suppressing vascular adhesion molecules and by inducing lamina propria T cell apoptosis. Based on these results, the clinical trial of humanised anti-IL-6R mAb, MRA, was carried out. Eighty per cent of the patients given twice-weekly MRA had a significantly better clinical response rate as compared to 31% of the placebo-treated patients. The response rate of the every-4-weeks regimen was 42%. The incidence of adverse events was similar in all groups. These data strongly suggest a therapeutic potential of MRA for CD.
Bacteriocin (Mutacin) Production by Streptococcus mutans Genome Sequence Reference Strain UA159: Elucidation of the Antimicrobial Repertoire by Genetic Dissection

ABSTRACT Streptococcus mutans UA159, the genome sequence reference strain, exhibits nonlantibiotic mutacin activity. In this study, bioinformatic and mutational analyses were employed to demonstrate that the antimicrobial repertoire of strain UA159 includes mutacin IV (specified by the nlm locus) and a newly identified bacteriocin, mutacin V (encoded by SMU.1914c).
American Urological Association ( AUA ) Guideline PEYRONIE ’ S DISEASE : AUA GUIDELINE

Methods: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates 1/1/1965 to 1/26/15) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of PD. The review yielded an evidence base of 303 articles after application of inclusion/ exclusion criteria. These publications were used to create the guideline statements. If sufficient evidence existed, then the body of evidence for a particular treatment was assigned a strength rating of A (high quality evidence; high certainty), B (moderate quality evidence; moderate certainty), or C (low quality evidence; low certainty); evidence-based statements of Strong, Moderate, or Conditional Recommendation, which can be supported by any body of evidence strength, were developed based on benefits and risks/burdens to patients. Additional information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed.
Service‐oriented middleware for financial Monte Carlo simulations on the cell broadband engine

Financial Monte Carlo simulations are computationally intensive applications that must meet tight deadlines in terms of job completion times. The completion time might have a huge impact on the financial profits made from decisions derived from the simulation results. Naturally, there is a huge interest in being able to simulate as fast as possible. While single simulations can be done on one machine, decisions often depend on portfolios of simulations. Distributing the workload among resources is crucial to achieve low latency. In this article we present a combination of a middleware with a high‐performance implementation of an Asian options evaluation code on the Cell Broadband Engine (CBE). We handle workload distribution with our PHASTGrid middleware and provide users with a web service interface to the whole infrastructure. The CBE is particularly suitable for Monte Carlo simulations. We implemented a well‐known algorithm on both the CBE and the Intel x86 multicore architectures. Both codes are integrated in our middleware, allowing a direct comparison of the performance and scalability. In addition to the Monte Carlo simulation, we also use different applications and compare our middleware with Globus. Copyright © 2009 John Wiley & Sons, Ltd.
Public Interest in Imaging-Based Cancer Screening Examinations in the United States: Analysis Using a Web-Based Search Tool.

OBJECTIVE The objective of this study was to identify geographic and temporal patterns related to the frequencies of online searches within the United States for information on imaging-based cancer screening tests. MATERIALS AND METHODS Google Trends, a web-based tool for identifying the frequency of online searches, was used to determine, on both a monthly and a geographic basis, the relative frequency of searches for imaging-based cancer screening tests in the United States from 2004 through 2014. Findings were evaluated qualitatively. RESULTS Searches for "mammography" decreased slightly overall, although they peaked in October (Breast Cancer Awareness Month) in most years and spiked in November 2009 (when the updated U.S. Preventive Services Task Force screening mammography guidelines were released). The frequency of searches for "tomosynthesis" increased rapidly from 2009 through 2014. On the other hand, the frequency of searches for "lung cancer screening" decreased slightly from 2006 through 2010, increased rapidly from 2011 through 2014, and exhibited a spike in November 2010 (when the results of the National Lung Screening Trial were released). Searches for "virtual colonoscopy" decreased substantially from 2004 through 2010, remained stable from 2011 through 2014, and spiked in months coinciding with the publication of the results of large relevant clinical trials and a press release announcing that the president of the United States was undergoing virtual colonoscopy. The frequency of searches for "prostate MRI" was stable from 2006 through 2010 and increased rapidly from 2011 through 2014. Searches for "prostate MRI biopsy" increased rapidly in 2013 and 2014. These searches occurred predominantly in densely populated areas (e.g., searches for "lung cancer screening," "prostate MRI," and "tomosynthesis" were highest in New York City). CONCLUSION Online search patterns indicate geographic and short- and long-term temporal variation in the interest in cancer screening examinations among the U.S. population. These trends may indicate pending shifts in the use of these examinations.
Virulence and molecular polymorphisms of the wheat leaf rust fungus Puccinia triticina in Canada from 1997 to 2007

Populations of Puccinia triticina, one of the casual agents of wheat leaf rust disease, in the pacific (British Columbia and Alberta), prairie (Manitoba and Saskatchewan), and eastern regions (Quebec and Ontario) of Canada from 1997 to 2007 were analyzed for virulence and genetic diversity by revealing expressed sequence tag derived simple sequence repeat (EST-SSR) polymorphisms. Since 1997, a significant shift in the virulence of P. triticina occurred across Canada. The diversity of P. triticina virulence phenotypes in Manitoba and Saskatchewan, as measured by Shannon and Simpson indexes, decreased due to the directional selection toward predominant virulence phenotypes, whereas it remained relatively constant in Quebec and Ontario. The clustering of P. triticina virulence phenotypes from 1997 to 2007 was similar to that found in previous years, and was correlated with virulence to leaf rust resistance genes Lr2a, Lr2c, and Lr17a. Distinct EST-SSR profiles were found in different groups of P. triticina v.
SEPARATION, WEAK EXOGENEITY, AND P-T DECOMPOSITION IN COINTEGRATED VAR SYSTEMS WITH COMMON FEATURES

ABSTRACT The aim of this paper is to study the concept of separability in multiple nonstationary time series displaying both common stochastic trends and common stochastic cycles. When modeling the dynamics of multiple time series for a panel of several entities such as countries, sectors, firms, imposing some form of separability and commonalities is often required to restrict the dimension of the parameter space. For this purpose we introduce the concept of common feature separation and investigate the relationships between separation in cointegration and separation in serial correlation common features. Loosely speaking we investigate whether a set of time series can be partitioned into subsets such that there are serial correlation common features within the sub-groups only. The paper investigates three issues. First, it provides conditions for separating joint cointegrating vectors into marginal cointegrating vectors as well as separating joint short-term dynamics into marginal short-term dynamics. Second, conditions for making permanent-transitory decompositions based on marginal systems are given. Third, issues of weak exogeneity are considered. Likelihood ratio type tests for the different hypotheses under study are proposed. An empirical analysis of the link between economic fluctuations in the United States and Canada shows the practical relevance of the approach proposed in this paper.
Inhibition of the allergic response by regulatory T cells

Purpose of reviewAllergic diseases are caused by the overdevelopment of T-helper type 2 biased immune responses in susceptible individuals. A number of recent studies indicate that regulatory T cells play an important role in controlling such T-helper type 2 biased responses not only in animal models, but in humans as well, and these will be reviewed in this article. Recent findingsA family of regulatory cells appears to be involved in regulating allergies. Both naturally occurring CD4+CD25+ regulatory T cells and inducible forms of antigen-specific regulatory T cells, both expressing the transcription factor foxp3, have been shown to inhibit the inappropriate immune responses involved in allergic diseases. Impaired expansion of natural or adaptive regulatory T cells is hypothesized to lead to the development of allergy, and treatment to induce allergen-specific regulatory T cells could provide curative therapies for allergy and asthma. SummaryAllergen-specific regulatory T cells play an important role in controlling the development of allergy and asthma.
Pre-Employment Integrity Testing across Multiple Industries

Despite the robust meta-analytic data available, very little comparative research exists on validities of integrity measures within specific industries. Among a sample of 2,456 Israeli job applicants, integrity scores were found to be significantly correlated with self-reported counterproductive work behaviors across eight different industries, with no evidence of adverse impact by gender, age, or national origin. These results are believed to be of practical importance to the diverse organizations administering integrity tests.
Spatial and temporal variability of diurnal wind forcing in the coastal ocean

Spatial and temporal variability of diurnal wind forcing and the coastal response is characterized for the New York Bight from February through May, 2005. This analysis demonstrates that diurnal wind forced motions are significant in the coastal ocean during the spring and summer months, near shore and as far as 100 km offshore. A doubling of diurnal current amplitudes is common in the spring compared to the winter months, associated with an increase in sea/land breeze days. Diurnal fluid motions due to sea/land breeze events can account for up 50% of the total kinetic energy during the spring.
Complications and results of 361 hysterectomies performed at laparoscopy.

BACKGROUND Before the appropriate use of laparoscopy in hysterectomy can be determined, it is necessary to evaluate the results, including complications. There must also be an accepted classification system to facilitate accurate comparison to total abdominal hysterectomy. STUDY DESIGN We retrospectively evaluated the charts of 361 women who underwent hysterectomy for various benign pathologic conditions. Intraoperative and postoperative complication rates for hysterectomy performed at operative laparoscopy were examined. The hysterectomies were classified as one of four types according to the number of steps performed laparoscopically. All women were candidates for total abdominal hysterectomy, but not vaginal hysterectomy. RESULTS The overall complication rate for hysterectomy performed at operative laparoscopy was 11.1 percent. Most complications were minor, including cystitis (1.66 percent), transient high fever (1.39 percent), abdominal wall ecchymosis (1.12 percent), and pneumonia and bronchitis (1.12 percent). There was no correlation between the type of laparoscopic hysterectomy performed and the complication rate. CONCLUSIONS Our rate of intraoperative and postoperative complications associated with laparoscopic hysterectomy compares favorably with published complication rates for vaginal and abdominal hysterectomy.
Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study

Objective To quantify the potential effect of reciprocal approval legislation on access to clinically impactful therapeutics in the USA. Design A cohort study. Setting New therapeutics approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and/or Health Canada between 2000 and 2010. Main outcome measures Characteristics of new therapeutics approved by the EMA and/or Health Canada before the FDA, including mechanistic novelty, likely clinical impact, size of the affected population and FDA review outcome. Results From 2001 to 2010, 282 drugs were approved in the USA, Europe or Canada, including 172 (61%) first approved in the USA, 24 (9%) never approved in the USA, and 86 (30%) approved in the USA after Europe and/or Canada. Of the 110 new drugs approved in Europe and/or Canada before the USA, 37 (34%) had a novel mechanisms of action compared with drugs already approved by the FDA, but only 10 (9%) were for conditions lacking alternate available therapies in the USA at the time of ex-US approval—of which the majority (9/10; 90%) were indicated for rare diseases. 12 of the 37 agents with novel mechanisms of action approved first in Europe and/or Canada (32%) had their initial FDA submissions rejected for safety reasons—including 2 drugs that were ultimately withdrawn from the market in Europe due to safety concerns. Conclusions If enacted, reciprocal approval legislation would most likely benefit only a small number of US patients receiving treatment for rare diseases, and the benefit may be somewhat mitigated by an increased exposure to harms.
Molecular Neurosteroid Access to the GABAA Receptor

GABAA receptors are a pivotal inhibitory influence in the nervous system, and modulators of the GABAA receptor are important anesthetics, sedatives, anticonvulsants, and anxiolytics. Current views of receptor modulation suggest that many exogenous drugs access and bind to an extracellular receptor domain. Using novel synthetic steroid analogs, we examined the access route for neuroactive steroids, potent GABAA receptor modulators also produced endogenously. Tight-seal recordings, in which direct aqueous drug access to receptor was prevented, demonstrated that steroids can reach the receptor either through plasma membrane lateral diffusion or through intracellular routes. A fluorescent neuroactive steroid accumulated intracellularly, but recordings from excised patches indicated that the intracellular reservoir is not necessary for receptor modulation, although it can apparently equilibrate with the plasma membrane within seconds. A membrane impermeant neuroactive steroid modulated receptor activity only when applied to the inner membrane leaflet, demonstrating that the steroid does not access an extracellular modulatory site. Thus, neuroactive steroids do not require direct aqueous access to the receptor, and membrane accumulation is required for receptor modulation.
Development of Specific Immunoglobulins G, M, and A Following Primary Toxoplasma gondii Infection in Pregnant Women

ABSTRACT The development of specific antibodies following primaryToxoplasma gondii infection during pregnancy was assessed by six different antibody assays: dye test, Platelia Toxo-IgG, Toxo-Screen DA IgG, Platelia Toxo-IgM, Toxo-ISAGA IgM, and Platelia Toxo-IgA. A total of 126 sera from 27 pregnant women, for whom the time of acquisition of infection could be estimated fairly accurately, were included. All tests showed great individual variation in the peak amounts of antibodies detected. The times elapsed after infection until the peak was reached also varied greatly from individual to individual: the ranges were 2 to 21 weeks for the dye test, 4 to 36 weeks for Platelia Toxo-IgG, 4 to 30 weeks for Toxo-Screen DA IgG, 2 to 18 weeks for Platelia Toxo-IgM, 1 to 6 weeks for Toxo-ISAGA IgM, and 2 to 21 weeks for Platelia Toxo-IgA. In the early phase of the infection the dye test and the specific-IgM tests were the most sensitive. Toxo-Screen DA IgG was more sensitive than Platelia Toxo-IgG in the acute phase, while Platelia Toxo-IgA was clearly the least sensitive assay. Of the sera collected 21 to 52 weeks after infection, all were positive by the dye test, all except one (which was negative by Platelia Toxo-IgG) were positive by the specific-IgG tests, approximately 80% were positive by the IgM tests, and 45% were positive by the IgA test. Due to the great individual variation it seems impossible to estimate when the infection occurred based on results obtained from a single serum, and it may even be difficult to assess when a titer increase in paired sera is detectable unless the first sample is only marginally positive. As a diagnostic criterion a dye test titer of ≥300 IU/ml has a low sensitivity for recent primary infection.
Motor Neuron-specific Disruption of Proteasomes, but Not Autophagy, Replicates Amyotrophic Lateral Sclerosis*

Background: It is not clear how protein degradation systems are involved in ALS pathogenesis. Results: Transgenic mice with motor neuron-specific knock-out of proteasomes, but not of autophagy showed ALS phonotypes. Conclusion: Dysfunction of proteasome may primarily contribute to the pathogenesis of ALS than that of autophagy. Significance: Modulation of proteasome function is a promising approach toward treatment of ALS. Evidence suggests that protein misfolding is crucially involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, controversy still exists regarding the involvement of proteasomes or autophagy in ALS due to previous conflicting results. Here, we show that impairment of the ubiquitin-proteasome system, but not the autophagy-lysosome system in motor neurons replicates ALS in mice. Conditional knock-out mice of the proteasome subunit Rpt3 in a motor neuron-specific manner (Rpt3-CKO) showed locomotor dysfunction accompanied by progressive motor neuron loss and gliosis. Moreover, diverse ALS-linked proteins, including TAR DNA-binding protein 43 kDa (TDP-43), fused in sarcoma (FUS), ubiquilin 2, and optineurin were mislocalized or accumulated in motor neurons, together with other typical ALS hallmarks such as basophilic inclusion bodies. On the other hand, motor neuron-specific knock-out of Atg7, a crucial component for the induction of autophagy (Atg7-CKO), only resulted in cytosolic accumulation of ubiquitin and p62, and no TDP-43 or FUS pathologies or motor dysfunction was observed. These results strongly suggest that proteasomes, but not autophagy, fundamentally govern the development of ALS in which TDP-43 and FUS proteinopathy may play a crucial role. Enhancement of proteasome activity may be a promising strategy for the treatment of ALS.
Does unbelted safety requirement affect protection for belted occupants?

ABSTRACT Objective: Federal regulations in the United States require vehicles to meet occupant performance requirements with unbelted test dummies. Removing the test requirements with unbelted occupants might encourage the deployment of seat belt interlocks and allow restraint optimization to focus on belted occupants. The objective of this study is to compare the performance of restraint systems optimized for belted-only occupants with those optimized for both belted and unbelted occupants using computer simulations and field crash data analyses. Methods: In this study, 2 validated finite element (FE) vehicle/occupant models (a midsize sedan and a midsize SUV) were selected. Restraint design optimizations under standardized crash conditions (U.S.-NCAP and FMVSS 208) with and without unbelted requirements were conducted using Hybrid III (HIII) small female and midsize male anthropomorphic test devices (ATDs) in both vehicles on both driver and right front passenger positions. A total of 10 to 12 design parameters were varied in each optimization using a combination of response surface method (RSM) and genetic algorithm. To evaluate the field performance of restraints optimized with and without unbelted requirements, 55 frontal crash conditions covering a greater variety of crash types than those in the standardized crashes were selected. A total of 1,760 FE simulations were conducted for the field performance evaluation. Frontal crashes in the NASS-CDS database from 2002 to 2012 were used to develop injury risk curves and to provide the baseline performance of current restraint system and estimate the injury risk change by removing the unbelted requirement. Results: Unbelted requirements do not affect the optimal seat belt and airbag design parameters in 3 out of 4 vehicle/occupant position conditions, except for the SUV passenger side. Overall, compared to the optimal designs with unbelted requirements, optimal designs without unbelted requirements generated the same or lower total injury risks for belted occupants depending on statistical methods used for the analysis, but they could also increase the total injury risks for unbelted occupants. Conclusions: This study demonstrated potential for reducing injury risks to belted occupants if the unbelted requirements are eliminated. Further investigations are necessary to confirm these findings.