Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatty liver index and mortality: The cremona study in the 15th year of follow‐up

A fatty liver, which is a common feature in insulin‐resistant states, can lead to chronic liver disease. It has been hypothesized that a fatty liver can also increase the rates of non–hepatic‐related morbidity and mortality. Therefore, we wanted to determine whether the fatty liver index (FLI), a surrogate marker and a validated algorithm derived from the serum triglyceride level, body mass index, waist circumference, and γ‐glutamyltransferase level, was associated with the prognosis in a population study. The 15‐year all‐cause, hepatic‐related, cardiovascular disease (CVD), and cancer mortality rates were obtained through the Regional Health Registry in 2011 for 2074 Caucasian middle‐aged individuals in the Cremona study, a population study examining the prevalence of diabetes mellitus in Italy. During the 15‐year observation period, 495 deaths were registered: 34 were hepatic‐related, 221 were CVD‐related, 180 were cancer‐related, and 60 were attributed to other causes. FLI was independently associated with the hepatic‐related deaths (hazard ratio = 1.04, 95% confidence interval = 1.02‐1.05, P < 0.0001). Age, sex, FLI, cigarette smoking, and diabetes were independently associated with all‐cause mortality. Age, sex, FLI, systolic blood pressure, and fibrinogen were independently associated with CVD mortality; meanwhile, age, sex, FLI, and smoking were independently associated with cancer mortality. FLI correlated with the homeostasis model assessment of insulin resistance (HOMA‐IR), a surrogate marker of insulin resistance (Spearman's ρ = 0.57, P < 0.0001), and when HOMA‐IR was included in the multivariate analyses, FLI retained its association with hepatic‐related mortality but not with all‐cause, CVD, and cancer‐related mortality. Conclusion: FLI is independently associated with hepatic‐related mortality. It is also associated with all‐cause, CVD, and cancer mortality rates, but these associations appear to be tightly interconnected with the risk conferred by the correlated insulin‐resistant state. (HEPATOLOGY 2011;)
Evidence for expression of eosinophil-associated IL-12 messenger RNA and immunoreactivity in bronchial asthma.

BACKGROUND Eosinophils are a source of cytokines within the airways of asthmatic individuals that may exert an important immunoregulatory influence. OBJECTIVES We examined IL-12 messenger (m)RNA and protein expression in eosinophils from peripheral blood and bronchoalveolar lavage (BAL) fluid obtained from subjects with atopic asthma (n = 7), patients with chronic bronchitis (n = 5), and nonatopic healthy control subjects (n = 7). To further define this IL-12(+) population of eosinophils for the expression of other cytokines, we colocalized IL-12 and IL-5 within the peripheral blood eosinophils. METHODS To detect IL-12 mRNA and protein expression, we used in situ hybridization and immunocytochemistry techniques. The double-immunocytochemistry technique was used to localize IL-12 protein to BAL eosinophils and to colocalize IL-5 and IL-12 in peripheral blood eosinophils. RESULTS IL-12 mRNA and immunoreactive protein were localized to peripheral blood eosinophils. BAL fluid-derived eosinophils from asthmatic subjects were also reactive to IL-12. The percentage of peripheral blood eosinophils expressing mRNA for IL-12 was significantly lower in asthmatic subjects compared with that found in eosinophils obtained from patients with chronic bronchitis (P<.001) and control patients (P <.05). Colocalization studies demonstrated that the percentages of IL-12(+) eosinophils that are also IL-5(+) were 72% in asthmatic subjects and only 11% in control subjects (P<.001). CONCLUSION These results suggest that eosinophils are a potential source of IL-12. Eosinophil-derived IL-12 may contribute and modulate the local allergic inflammatory responses.
Cloning, expression, and functional characterization of cynomolgus monkey (Macaca fascicularis) CC chemokine receptor 1

The CC chemokine receptor 1 (CCR1) has emerged as a relevant factor contributing to inflammatory diseases such as allergic asthma. Commonly used animal models of allergic airway inflammation, especially murine models, have certain limitations. The elaborate, nonhuman, primate models of asthma display the highest comparability with the situation in humans. These models play an important role in the understanding of the pathogenesis of asthma. To improve the understanding in cynomolgus monkey models, we identified and characterized CCR1 in this nonhuman primate. Initially, we cloned the cynomolgus monkey CCR1 (cCCR1) gene, and the sequence analysis revealed high homology at the nucleotide (92%) and amino acid (88.4%) levels with its human counterpart. Human embryonic kidney 293 cells were stably transfected with cCCR1 and used in functional assays. Among those CCR1 ligands tested, CCL14(9‐74) was most potent in the induction of intracellular Ca2+ fluxes as observed for human CCR1 (hCCR1). Complete cross‐desensitization could be achieved between CCL14(9‐74) and CCL15. However, CCL3 could not fully abrogate the response to the potent ligand CCL14(9‐74). Competition‐binding studies with radiolabeled CCL3 concordantly showed that CCL14(9‐74) has a higher affinity to cCCR1 than hCCL3. Moreover, differential tissue‐specific expression of cCCR1 was investigated by real‐time quantitative polymerase chain reaction, displaying the highest levels in spleen. This study adds basic information needed for the evaluation of the role of CCR1 in the pathophysiology of asthma using the highly relevant cynomolgus monkey model and in addition, aids in the preclinical evaluation of potential novel drugs targeting CCR1.
Asthma as a risk factor for COPD in a longitudinal study.

BACKGROUND For several years, asthma and COPD have been regarded as distinct entities, with distinct clinical courses. However, despite distinctive physiologic features at the time of diagnosis, and different risk factors, the two diseases over time may develop features that are quite similar. STUDY OBJECTIVE To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ. DESIGN AND METHODS A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey. RESULTS Subjects with active asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156) or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17-times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83), and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84), even after adjusting for smoking history and other potential confounders. CONCLUSIONS Physician-diagnosed asthma is significantly associated with an increased risk for CB, emphysema, and COPD.
The U.S. Transuranium Registry report on the 241Am content of a whole body.

An analysis and evaluation of 241Am in the whole body of a donor to the U.S. Transuranium Registry (USTR) is presented in five parts. The USTR donor's pertinent medical history, autopsy findings and antemortem evaluations of intake and systemic burden are described in Parts I and II. The donor was a 49-yr-old male Caucasian radiochemist who died of metastic melanoma in 1979. His work with actinide elements began in 1952, and the greatest potential for intake of 241Am was when he used an unsealed 241Am source in his doctoral research (1952-54). The first indication that an intake had occurred was the detection of 241Am in a urine sample collected in 1958 as part of an internal dosimetry surveillance program. In-vivo estimates of the initial 241Am intake, based on sporadic urine samples and three sets of external photon measurements, ranged from 0.23-1.1 muCi depending on the calculational models and calibration factors used. No chelation therapy was applied. The time of intake was estimated to be approximately 25 yr before death. External photon measurements made on the donor's body and dissected bones, presented in Part III, have yielded new and more accurate calibration factors for external in-vivo measurement of the 60-keV gamma rays of 241Am and the 13.2- and 14-keV x rays of 239Pu and 238Pu. The symmetrical distribution of 241Am in the bones of the right and left sides of the body and the reliability of total skeletal 241Am estimated from external measurements of 241Am in the head were confirmed. The soft tissues and about one-half of the skeleton were weighed wet, ashed, reweighed and analyzed radiochemically for 241Am, as described in Part IV. The measured total 241Am in the body was 147.4 nCi, distributed as follows: soft tissues of left hand, 1.9%; liver, 6.3%; respiratory tract tissues, 1.5%; other organs, 0.9%; combined structural soft tissues (muscle, skin, connective tissue), 8.6%; mineralized tissues (bones, teeth), 80%. The expectations of similar 241Am concentrations in bones of grossly similar structure and also in parts of bones of similar microscopic structure were confirmed. (ABSTRACT TRUNCATED AT 400 WORDS)
Business angels: a research review and new agenda

Abstract This paper provides a structured literature review of 84 business angel articles published between 2000 and 2013, building on the 1999 review contacted by Mason and Harrison. The articles are classified according to the generational framework laid out by Mason and Harrison, which describes first and second generations of articles (prior to 1999) and calls for a third generation of research. We find that Mason and Harrison’s agenda has largely been met, with some notable gaps. We also find that the research is diverse, with many articles falling into what Mason and Harrison call first and second generations. Our paper outlines a new agenda for research focusing on six key areas. Finally, we conclude with a discussion of key implications for policy and practice.
The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate in C. elegans

The aryl hydrocarbon receptors (AHR) are bHLH-PAS domain containing transcription factors. In mammals, they mediate responses to environmental toxins such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Such functions of AHRs require a cofactor, the aryl hydrocarbon receptor nuclear translocator (ARNT), and the cytoplasmic chaperonins HSP90 and XAP2. AHR homologs have been identified throughout the animal kingdom. We report here that the C. elegans orthologs of AHR and ARNT, ahr-1 and aha-1, regulate GABAergic motor neuron fate specification. Four C. elegans neurons known as RMED, RMEV, RMEL and RMER express the neurotransmitter GABA and control head muscle movements. ahr-1 is expressed in RMEL and RMER neurons. Loss of function in ahr-1 causes RMEL and RMER neurons to adopt a RMED/RMEV-like fate, whereas the ectopic expression of ahr-1 in RMED and RMEV neurons can transform them into RMEL/RMER-like neurons. This function of ahr-1 requires aha-1, but not daf-21/hsp90. Our results demonstrate that C. elegans ahr-1 functions as a cell-type specific determinant. This study further supports the notion that the ancestral role of the AHR proteins is in regulating cellular differentiation in animal development.
Discovery of a Marine Bacterium Producing 4-Hydroxybenzoate and Its Alkyl Esters, Parabens

ABSTRACT Chemically synthesized 4-hydroxybenzoate (4HBA) is widely used in the chemical and electrical industries as a material for producing polymers such as those of the liquid crystal type. Its alkyl esters, called parabens, have been the most widely used preservatives by the food and cosmetic industries. We report here for the first time a microorganism, a marine bacterium, which biosynthesizes these petrochemical products. The marine bacterial strain, A4B-17, which was found to belong to the genus Microbulbifer on the basis of its rRNA and gyrB sequences, was isolated from an ascidian in the coastal waters of Palau. Strain A4B-17 was, surprisingly, found to produce 10 mg/liter of 4HBA, together with its butyl (24 mg/liter), heptyl (0.4 mg/liter), and nonyl (6 mg/liter) esters. We therefore characterized 23 other marine bacteria belonging to the genus Microbulbifer, which our institute had previously isolated from various marine environments, and found that these bacteria also produced 4HBA, although with low production levels (less than one-fifth of that produced by A4B-17). We also show that the alkyl esters of 4HBA produced by strain A4B-17 were effective in preventing the growth of yeasts, molds, and gram-positive bacteria.
Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling

De novo formation of blood vessels is a pivotal mechanism during cancer development. During the past few years, antiangiogenic drugs have been developed to target tumor vasculature. However, because of limitations and adverse effects observed with current therapies, there is a strong need for alternative antiangiogenic strategies. Using specific anti‐junctional adhesion molecule (JAM)‐B antibodies and Jam‐b‐deficient mice, we studied the role in antiangiogenesis of JAM‐B. We found that antibodies against murine JAM‐B, an endothelium‐specific adhesion molecule, inhibited microvessel outgrowth from ex vivo aortic rings and in vitro endothelial network formation. In addition, anti‐JAM‐B antibodies blocked VEGF signaling, an essential pathway for angiogenesis. Moreover, increased aortic ring branching was observed in aortas isolated from Jam‐b‐deficient animals, suggesting that JAM‐B negatively regulates proangiogenic pathways. In mice, JAM‐B expression was detected in de novo‐formed blood vessels of tumors, but anti‐JAM‐B antibodies unexpectedly did not reduce tumor growth. Accordingly, JAM‐B deficiency in vivo had no impact on blood vessel formation, suggesting that targeting JAM‐B in vivo may be offset by other proangiogenic mechanisms. In conclusion, despite the promising effects observed in vitro, targeting JAM‐B during tumor progression seems to be inefficient as a stand‐alone antiangiogenesis therapy. —Meguenani, M. , Miljkovic‐Licina, M. , Fagiani, E. , Ropraz, P., Hammel, P., Aurrand‐Lions, M. , Adams, R. H. , Christofori, G. , Imhof, B. A. , Garrido‐Urbani, S. Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling. FASEB J. 29, 3411‐3425 (2015). www.fasebj. org
Potential for Canadian Mosquitoes To Transmit Rift Valley Fever Virus1

Abstract The rapid spread of West Nile viral activity across North America since its discovery in 1999 illustrates the potential for an exotic arbovirus to be introduced and become widely established across North America. Rift Valley fever virus (RVFV) has been responsible for large outbreaks in Africa that have resulted in hundreds of thousands of human infections and major economic disruption due to loss of livestock and to trade restrictions. However, little is known about the potential for mosquitoes in Canada to transmit this virus, should it be introduced into North America. Therefore, we evaluated mosquito species captured near Winnipeg, Manitoba, Canada, for their ability to serve as potential vectors for RVFV. Mosquitoes were exposed to RVFV by allowing them to feed on adult hamsters inoculated the previous day with RVFV. These mosquitoes were tested for infection, dissemination, and the ability to transmit RVFV after incubation at 25°C for 14–18 days. Based on the detection of virus in saliva collected in capillary tubes, individual Culex tarsalis, Aedes sticticus, and Coquillettidia perturbans were able to transmit RVFV under laboratory conditions. These preliminary results suggest that these 3 species may be able to transmit RVFV, should this virus be introduced into Canada.
Shelf Life of Unbuffered Rapid Urease Test

Unbuffered rapid urease test (RUT) is an accurate and inexpensive method to detect Helicobacter pylori. However, the test is not always readily available because the reagents must be mixed freshly or stored at −20°C after mixing. From our experience, storage at 4°C for less than 6 days seemed to have no effect on the test’s accuracy. This prospective study was undertaken to evaluate the shelf life of our unbuffered RUT.
Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial.

CONTEXT Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treatment has been established. OBJECTIVE To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients (aged 8-17 years) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010. Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks. MAIN OUTCOME MEASURES The primary outcome was sustained reduction in alanine aminotransferase (ALT) defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures. RESULTS Sustained reduction in ALT level was similar to placebo (10/58; 17%; 95% CI, 9% to 29%) in both the vitamin E (15/58; 26%; 95% CI, 15% to 39%; P = .26) and metformin treatment groups (9/57; 16%; 95% CI, 7% to 28%; P = .83). The mean change in ALT level from baseline to 96 weeks was -35.2 U/L (95% CI, -56.9 to -13.5) with placebo vs -48.3 U/L (95% CI, -66.8 to -29.8) with vitamin E (P = .07) and -41.7 U/L (95% CI, -62.9 to -20.5) with metformin (P = .40). The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo (95% CI, -0.2 to 0.3) vs -0.5 with vitamin E (95% CI, -0.8 to -0.3; P = .006) and -0.3 with metformin (95% CI, -0.6 to -0.0; P = .04); and in NAFLD activity score, -0.7 with placebo (95% CI, -1.3 to -0.2) vs -1.8 with vitamin E (95% CI, -2.4 to -1.2; P = .02) and -1.1 with metformin (95% CI, -1.7 to -0.5; P = .25). Among children with NASH, the proportion who resolved at 96 weeks was 28% with placebo (95% CI, 15% to 45%; 11/39) vs 58% with vitamin E (95% CI, 42% to 73%; 25/43; P = .006) and 41% with metformin (95% CI, 26% to 58%; 16/39; P = .23). Compared with placebo, neither therapy demonstrated significant improvements in other histological features. CONCLUSION Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00063635.
Neuromodulation in Epilepsy

Neuromodulation strategies have been proposed to treat a variety of neurological disorders, including medication-resistant epilepsy. Electrical stimulation of both central and peripheral nervous systems has emerged as a possible alternative for patients who are not deemed to be good candidates for resective procedures. In addition to well-established treatments such as vagus nerve stimulation, epilepsy centers around the world are investigating the safety and efficacy of neurostimulation at different brain targets, including the hippocampus, thalamus, and subthalamic nucleus. Also promising are the preliminary results of responsive neuromodulation studies, which involve the delivery of stimulation to the brain in response to detected epileptiform or preepileptiform activity. In addition to electrical stimulation, novel therapeutic methods that may open new horizons in the management of epilepsy include transcranial magnetic stimulation, focal drug delivery, cellular transplantation, and gene therapy. We review the current strategies and future applications of neuromodulation in epilepsy.
Control of reactive power in double-fed machine based wind park

Different aspects of reactive power regulation problem in wind farms are presented in this paper. In the first part some background of the reactive power control in wind parks is presented, including motivations for its use and methods that can be used. In general, there are active (wind generator, compensator) and passive methods (L,C) of reactive power compensation. A simulation model of the wind park (model of doubly fed induction generator (DFIG) based wind turbines, transformers, cable lines between wind farm and PCC, control system). has been done to verify the efficacy of proposed methods. Conclusions about need and possibilities of reactive power control have been drawn From simulations in steady and transient state. Next features with special regards to limits of the DFIG working as wind generator are presented. In the final part of the paper selected methods of reactive power control are described and simulation results are presented.
Real-Time Measurement of Electronic Cigarette Aerosol Size Distribution and Metals Content Analysis.

INTRODUCTION Electronic cigarette (e-cigarette) use is increasing worldwide and is highest among both daily and nondaily smokers. E-cigarettes are perceived as a healthier alternative to combustible tobacco products, but their health risk factors have not yet been established, and one of them is lack of data on aerosol size generated by e-cigarettes. METHODS We applied a real-time, high-resolution aerosol differential mobility spectrometer to monitor the evolution of aerosol size and concentration during puff development. Particles generated by e-cigarettes were immediately delivered for analysis with minimal dilution and therefore with minimal sample distortion, which is critically important given the highly dynamic aerosol/vapor mixture inherent to e-cigarette emissions. RESULTS E-cigarette aerosols normally exhibit a bimodal particle size distribution: nanoparticles (11-25nm count median diameter) and submicron particles (96-175nm count median diameter). Each mode has comparable number concentrations (10(7)-10(8) particles/cm(3)). "Dry puff" tests conducted with no e-cigarette liquid (e-liquid) present in the e-cigarette tank demonstrated that under these conditions only nanoparticles were generated. Analysis of the bulk aerosol collected on the filter showed that e-cigarette emissions contained a variety of metals. CONCLUSIONS E-cigarette aerosol size distribution is different from that of combustible tobacco smoke. E-cigarettes generate high concentrations of nanoparticles and their chemical content requires further investigation. Despite the small mass of nanoparticles, their toxicological impact could be significant. Toxic chemicals that are attached to the small nanoparticles may have greater adverse health effects than when attached to larger submicron particles. IMPLICATIONS The e-cigarette aerosol size distribution is different from that of combustible tobacco smoke and typically exhibits a bimodal behavior with comparable number concentrations of nanoparticles and submicron particles. While vaping the e-cigarette, along with submicron particles the user is also inhaling nano-aerosol that consists of nanoparticles with attached chemicals that has not been fully investigated. The presence of high concentrations of nanoparticles requires nanotoxicological consideration in order to assess the potential health impact of e-cigarettes. The toxicological impact of inhaled nanoparticles could be significant, though not necessarily similar to the biomarkers typical of combustible tobacco smoke.