Miracle-dz/UniFAR-FTUs huggingface dataset:
Patients treated with bivalirudin are still at higher risk of stent thrombosis: a comprehensive meta-analysis of randomised clinical trials of bivalirudin and heparin for percutaneous coronary interventions.

BACKGROUND Although the current practice guidelines recommend using both heparin and bivalirudin for percutaneous coronary interventions (PCI), the research data are ambiguous. AIM The aim of the study was to compare the impact of bivalirudin and heparin on major clinical endpoints in PCI patients with particular emphasis on periprocedural stent thrombosis. METHODS A total of 18 randomised clinical trials involving 41,752 subjects were included. The endpoints comprised: net adverse clinical event (NACE: death, myocardial infarction [MI], unscheduled revascularisation, major bleeding), major adverse cardiovascular event (MACE: death, MI, or stroke), and acute/subacute stent thrombosis (ST). A subanalysis for planned and provisional glycoprotein IIb/IIIa inhibitor (GPI) use with heparin was performed. Results were presented as risk ratios (RR) and 95% confidence intervals (CI). RESULTS Bivalirudin significantly reduced NACE risk (RR 0.85, 95% CI 0.76-0.96) and increased the incidence of MI (RR 1.09, 95% CI 1.01-1.18), ST (RR 1.50, 95% CI 1.13-1.99), and MACEs (RR 1.06, 95% CI 0.99-1.13). Comparing to heparin with provisional or planned GPI use, there was higher risk of acute ST with bivalirudin (RR 2.14, 95% CI 1.01-4.56 and RR 5.53, 95% CI 2.32-13.18, respectively). Comparing to heparin and provisional GPIs, bivalirudin failed to reduce NACEs and major bleeding. However, it decreased rates of NACEs (RR 0.81, 95% CI 0.69-0.96) and major bleeding (RR 0.64, 95% CI 0.48-0.85) compared with heparin and planned GPI use. CONCLUSIONS The advantages of bivalirudin are undoubtedly related to GPI use in the heparin arms. Bivalirudin-based regimens are more beneficial when compared with heparin and planned GPI use in terms of NACE and major bleedings; this was not observed when compared to heparin and provisional GPI use. Regardless of adjunctive GPI use, stent thrombosis episodes were significantly more common in bivalirudin-treated subjects. Therefore, the safety and economic issues may urge revision of this aspect of current clinical practice and guidelines.
Thermoplastic nanocomposites filled with wheat straw cellulose whiskers. Part I: Processing and mechanical behavior

Cellulose microcrystals with dimensions of ∼5 nm x 150-300 nm were obtained from wheat straw. To evaluate the reinforcing effect of these fillers within a thermoplastic matrix, composites with a weight fraction of cellulose ranging from 0 to 30 wt% were processed by freeze-drying and molding a mixture of aqueous suspensions of microcrystals and poly(styrene-co-butyl acrylate) latex. It was found that these microcrystals, or whiskers, bring a great reinforcing effect at temperatures higher than the glass transition temperature (T g ) of the matrix and improve the thermal stability of the composite. The relaxed modulus increased continuously with the filler content, and for a film containing 30 wt% of whiskers, it was more than a thousand times higher than that of the matrix. This effect is discussed with regard to theoretical calculations based on a mean field approach (Halpin-Kardos model). It is concluded that the great reinforcement observed seems to be due not only to the geometry and stiffness of the straw cellulose whiskers but also to the interactions of the microcrystals, their topological arrangement, and the probable formation of whisker clusters within the thermoplastic matrix, the cellulose fillers probably being linked through hydrogen bonds.
Gut microbiome diversity influenced more by the Westernized dietary regime than the body mass index as assessed using effect size statistic

Human gut microbiome dysbiosis has been associated with the onset of metabolic diseases and disorders. However, the critical factors leading to dysbiosis are poorly understood. In this study, we provide increasing evidence of the association of diet type and body mass index (BMI) and how they relatively influence the taxonomic structure of the gut microbiota with respect to the causation of gut microbiome dysbiosis. The study included randomly selected Alabama residents (n = 81), including females (n = 45) and males (n = 36). The demographics data included age (33 ± 13.3 years), height (1.7 ± 0.11 meters), and weight (82.3 ± 20.6 kg). The mean BMI was 28.3 ± 7.01, equating to an overweight BMI category. A cross‐sectional case–control design encompassing the newly recognized effect size approach to bioinformatics analysis was used to analyze data from donated stool samples and accompanying nutrition surveys. We investigated the microbiome variations in the Bacteroidetes‐Firmicutes ratio relative to BMI, food categories, and dietary groups at stratified abundance percentages of <20%, 20%, 30%, 40%, 50%, 60%, and ≥70%. We further investigated variation in the Firmicutes and Bacteroidetes phyla composition (at the genus and species level) in relation to BMI, food categories, and dietary groups (Westernized or healthy). The Pearson Correlation coefficient as an indication of effect size across Alpha diversity indices was used to test the hypothesis (H0): increased BMI has greater effect on taxonomic diversity than Westernized diet type, (Ha): increased BMI does not have a greater effect on taxonomic diversity than Westernized diet type. In conclusion, we rejected the (H0) as our results demonstrated that Westernized diet type had an effect size of 0.22 posing a greater impact upon the gut microbiota diversity than an increased BMI with an effect size of 0.16. This implied Westernized diet as a critical factor in causing dysbiosis as compared to an overweight or obese body mass index.
All-Trans Retinoic Acid Directs Urothelial Specification of Murine Embryonic Stem Cells via GATA4/6 Signaling Mechanisms

The urinary bladder and associated tract are lined by the urothelium, a transitional epithelium that acts as a specialized permeability barrier that protects the underlying tissue from urine via expression of a highly specific group of proteins known as the uroplakins (UP). To date, our understanding of the developmental processes responsible for urothelial differentiation has been hampered due to the lack of suitable models. In this study, we describe a novel in vitro cell culture system for derivation of urothelial cells from murine embryonic stem cells (ESCs) following cultivation on collagen matrices in the presence all trans retinoic acid (RA). Upon stimulation with micromolar concentrations of RA, ESCs significantly downregulated the pluripotency factor OCT-4 but markedly upregulated UP1A, UP1B, UP2, UP3A, and UP3B mRNA levels in comparison to naïve ESCs and spontaneously differentiating controls. Pan-UP protein expression was associated with both p63- and cytokeratin 20-positive cells in discrete aggregating populations of ESCs following 9 and 14 days of RA stimulation. Analysis of endodermal transcription factors such as GATA4 and GATA6 revealed significant upregulation and nuclear enrichment in RA-treated UP2-GFP+ populations. GATA4−/− and GATA6−/− transgenic ESC lines revealed substantial attenuation of RA-mediated UP expression in comparison to wild type controls. In addition, EMSA analysis revealed that RA treatment induced formation of transcriptional complexes containing GATA4/6 on both UP1B and UP2 promoter fragments containing putative GATA factor binding sites. Collectively, these data suggest that RA mediates ESC specification toward a urothelial lineage via GATA4/6–dependent processes.
Re-evaluating strategies to define the immunoregulatory roles miRNAs

MicroRNAs (miRNAs) play an important role in fine-tuning host immune homeostasis and responses through the regulation of messenger RNA (mRNA) stability and translation. Studies have demonstrated that miRNA-mediated regulation of gene expression has a profound impact on immune cell development, function and response to invading pathogens. As we continue to examine the mechanisms by which miRNAs maintain the balance between robust protective host immune responses and dysregulated responses that promote immune pathology, careful consideration of the complexity of post-transcriptional immune regulation is needed. Distinct tissue- and stimulus-specific RNA-RNA and RNA-protein interactions can modulate the functions of a given miRNA. Thus, new challenges emerge in the identification of post-transcriptional co-regulatory modules and the genetic factors that impact miRNA function. 3 ′ UTR through usage of alternative polyadenylation sites (pA) results in changes in the number of potential interaction sites/motifs for the previously mentioned post-transcriptional modulators, impacting mRNA stability. The development of novel molecular and computational tools provide means to understand global changes in post-transcriptional regulator expression, the identification of mRNA regulatory motifs, and changes in the sequence and structure of the 3 ′ UTR. Building a comprehensive post-transcriptional regulome will allow us to contextualize the function of miRNAs in the regulation of host gene expression during immune development, infection, and immunological disease.
Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

Novel subtypes of Asian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3. 4, such as H5N2, H5N5, H5N6, and H5N8, have been identified in China since 2008 and have since evolved into four genetically distinct clade 2.3. 4.4 groups (A–D). Since 2014, HPAI clade 2.3. 4.4 viruses have spread rapidly via migratory wild aquatic birds and have evolved through reassortment with prevailing local low pathogenicity avian influenza viruses. Group A H5N8 viruses and its reassortant viruses caused outbreaks in wide geographic regions (Asia, Europe, and North America) during 2014–2015. Novel reassortant Group B H5N8 viruses caused outbreaks in Asia, Europe, and Africa during 2016–2017. Novel reassortant Group C H5N6 viruses caused outbreaks in Korea and Japan during the 2016–2017 winter season. Group D H5N6 viruses caused outbreaks in China and Vietnam. A wide range of avian species, including wild and domestic waterfowl, domestic poultry, and even zoo birds, seem to be permissive for infection by and/or transmission of clade 2.3. 4.4 HPAI viruses. Further, compared to previous H5N1 HPAI viruses, these reassortant viruses show altered pathogenicity in birds. In this review, we discuss the evolution, global spread, and pathogenicity of H5 clade 2.3. 4.4 HPAI viruses.
Charles A. Dice Center for Research in Financial Economics Complex Times: Asset Pricing and Conditional Moments under Non-Affine Diffusions

Many applications in continuous-time financial economics require conditional moments or contingent claims prices, but such expressions are known in closed-form for only a few specific models. Power series (in the time variable) for these quantities are easily derived, but often fail to converge, even for very short time horizons. We characterize a large class of continuous-time non-affine conditional moment and contingent claim pricing problems with solutions that are analytic in the time variable, and that therefore can be represented by convergent power series. The ability to approximate solutions accurately and in closedform simplifies the estimation of latent variable models, since the state vector must be extracted from observed quantities for many different parameter vectors during a typical estimation procedure.
A Study of Connected Component Labeling Algorithms on the MPP

In this paper we consider the problem of labeling the connected components of a binary image. We descnbe three different algorithms and variations thereof which we implemented on NASA's MPP. These algoritluns include a simple label propagation algorithm. a version of Levialdi's algorithm, and an asymptotically optimal divide-and-eonquer algorithm. We discuss the perfonnance of these algorithms on the MPP and provide insight into how special hardware features of the lvIPP influence the design of parallel algorithms. We also address the issue of how to handle images that are larger than the processor array of the MPP (Le.; images larger ! ban 128xl28). This work was supponed by the Office of Naval Research under Contracts NOOOl4-84-K-OS02 and NOOO14-86.K-0689, and by the National Science Foundation lDldcr Gn! nt DMC.84-13496.
Semi-Cognitive Radio Networks: A Novel Dynamic Spectrum Sharing Mechanism

In conventional cognitive radio networks, channels that are in use by opportunistic secondary users (SUs) can be recaptured by the network’s licensed primary users (PUs) at will, thus interrupting the connectivity of the former. To compensate for this, we propose here a semi-cogntive radio network (SCRN) paradigm where PUs are constrained to first use all free channels in the network before being allowed to capture channels that are currently in use by SUs. By imposing a monetary (or other) penalty to the network’s secondary spectrum owners when opportunistic channel use becomes excessive, this additional constraint only induces a slight drop in the PUs’ performance while offering significant benefits to the network’s SUs. In this paper, we provide a game-theoretic analysis of such systems and we derive both centralized and decentralized adaptive algorithms that allow the system control process to converge to a stable equilibrium state. Our numerical results show that, with the same channel efficiency, SCRNs provide increased profits to the primary network and significantly reduced interruption rates to the secondary network.
Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin Hydrolase.

Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 °C increased T5010 over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete bioproduction of simvastatin at industrial scale.
Effect of antimitotic drugs on tubulin GTPase activity and self-assembly.

Microtubule inhibitors can be classified into two categories: 1) those which inhibit the polymerization-dependent GTPase activity of phosphocellulose-purified tubulin, but induce a significant polymerization-independent GTPase activity (e.g. colchicine, griseofulvine, daunorubicine); 2) those which inhibit the GTPase activity associated with tubulin polymerization and that induced by inhibitors of the first class (e.g. the vincaalkaloids and podophyllotoxin). The colchicine-stimulated GTPase activity of tubulin appears to be due to the tubulin.colchicine complex. This suggests that colchicine inhibits tubulin assembly by binding to a tubulin-tubulin interaction site required for the polymerization-dependent GTPase activity and induces by itself a tubulin conformational change that leads to polymerization-independent GTPase activity. Stoichiometry of inhibition by vinblastine of the colchicine-stimulated GTPase activity is 1:2. On the other hand, the inhibition by vinblastine of the tubulin self-assembly and of the polymerization-dependent GTPase activity is strongly substoichiometric at the beginning of the polymerization reaction, 1 vinblastine molecule inhibiting the ability of 10 tubulin dimers to polymerize and to hydrolyze the GTP. However, at the polymerization plateau, the inhibition effect by vinblastine appears to be lower, suggesting a selective action of vinblastine on the early stages of the polymerization reaction.
Automatic speech recognition with sparse training data for dysarthric speakers

We describe an unusual ASR application: recognition of command words from severely dysarthric speakers, who have poor control of their articulators. The goal is to allow these clients to control assistive technology by voice. While this is a small vocabulary, speaker-dependent, isolated-word application, the speech material is more variable than normal, and only a small amount of data is available for training. After training a CDHMM recogniser, it is necessary to predict its likely performance without using an independent test set,so that confusable words can be replaced by alternatives. We present a battery of measures of consistency and confusability, based on forced-alignment, which can be used to predict recogniser performance. We show how these measures perform, and how they are presented to the clinicians who are the users of the system.
Performance Specifications of Market Physiological Sensors for Efficient Driver Drowsiness Detection System

Significant advances in bio-sensors technologies hold promise to monitor human physiological signals in real time. In the context of driving safety, such devices are knowing notable research investigations to objectively detect early stages of driver drowsiness that impair driving performance under various conditions. Seeking for low-cost, compact yet reliable sensing technology that can provide a solution to drowsy state problem is challenging. The contribution of this paper is to study fundamental performance specifications required for the design of efficient physiological signals based driver drowsiness detection systems. Existing measurement products are then accessed and ranked following the discussed performance specifications. The finding of this work is to provide a tool to facilitate making the appropriate hardware choice to implement efficient yet low-cost drowsiness detection system using existing market physiological sensors products.
Popular Media Representations of Physical Activity Among Mothers

Purpose. Many mothers fail to meet the recommended guidelines for physical activity. Popular media magazines targeting mothers provide information about physical activity and health, but little is known about the framing and content of physical activity messages within these sources. The aim of this content analysis was to analyze the framing and content (i.e., benefits, consequences, and sources of self-efficacy) of physical activity messages directed toward mothers in popular magazines. Method. Ten popular magazines were selected for data analysis and coded independently by two researchers in NVivo Version 10.0 for gain- or loss-framed messages, benefits and consequences of physical activity, and sources of self-efficacy. Results. Most of the 164 articles encouraged physical activity by presenting benefits associated with physical activity. These benefits primarily focused on weight loss and fitness gains and few articles used self-efficacy messages to enhance confidence in physical activity participation. Conclusions. It is promising that popular media magazines used gain-framed messages about the benefits of physical activity for mothers. Future research should focus on finding ways of using popular media outlets to promote a more comprehensive set of physical activity benefits, enhance physical activity self-efficacy, and determine the impact of such messages on physical activity participation.
The incident user design in comparative effectiveness research

Comparative effectiveness research includes cohort studies and registries of interventions. When investigators design such studies, how important is it to follow patients from the day they initiated treatment with the study interventions? Our article considers this question and related issues to start a dialogue on the value of the incident user design in comparative effectiveness research. By incident user design, we mean a study that sets the cohort's inception date according to patients' new use of an intervention. In contrast, most epidemiologic studies enroll patients who were currently or recently using an intervention when follow‐up began. We take the incident user design as a reasonable default strategy because it reduces biases that can impact non‐randomized studies, especially when investigators use healthcare databases. We review case studies where investigators have explored the consequences of designing a cohort study by restricting to incident users, but most of the discussion has been informed by expert opinion, not by systematic evidence. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation

Additional sex combs like 1 (ASXL1) is frequently mutated in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP). Although loss of ASXL1 promotes hematopoietic transformation, there is growing evidence that ASXL1 mutations might confer an alteration of function. In this study, we identify that physiological expression of a C-terminal truncated Asxl1 mutant in vivo using conditional knock-in (KI) results in myeloid skewing, age-dependent anemia, thrombocytosis, and morphological dysplasia. Although expression of mutant Asxl1 altered the functions of hematopoietic stem cells (HSCs), it maintained their survival in competitive transplantation assays and increased susceptibility to leukemic transformation by co-occurring RUNX1 mutation or viral insertional mutagenesis. KI mice displayed substantial reductions in H3K4me3 and H2AK119Ub without significant reductions in H3K27me3, distinct from the effects of Asxl1 loss. Chromatin immunoprecipitation followed by next-generation sequencing analysis demonstrated opposing effects of wild-type and mutant Asxl1 on H3K4me3. These findings reveal that ASXL1 mutations confer HSCs with an altered epigenome and increase susceptibility for leukemic transformation, presenting a novel model for CHIP.
Antibody Repertoires Identify β-Tubulin as a Host Protective Parasite Antigen in Mice Infected With Trypanosoma cruzi

Few studies investigate the major protein antigens targeted by the antibody diversity of infected mice with Trypanosoma cruzi. To detect global IgG antibody specificities, sera from infected mice were immunoblotted against whole T. cruzi extracts. By proteomic analysis, we were able to identify the most immunogenic T. cruzi proteins. We identified three major antigens as pyruvate phosphate dikinase, Hsp-85, and β-tubulin. The major protein band recognized by host IgG was T. cruzi β-tubulin. The T. cruzi β-tubulin gene was cloned, expressed in E. coli, and recombinant T. cruzi β-tubulin was obtained. Infection increased IgG reactivity against recombinant T. cruzi β-tubulin. A single immunization of mice with recombinant T. cruzi β-tubulin increased specific IgG reactivity and induced protection against T. cruzi infection. These results indicate that repertoire analysis is a valid approach to identify antigens for vaccines against Chagas disease.