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INTRODUCTION Angioedema is a subcutaneous swelling typically affecting the face, larynx or pharynx. It is a known adverse drug reaction (ADR) of ACE inhibitors (ACEi), angiotensin-II-receptor blockers (ARBs) and aliskiren (renin inhibitor). Several studies have reported pathophysiological mechanisms and risk factors of ACEi-associated angioedemas, whereas little is known for ARBs and aliskiren. The aim of the study was to analyze comparatively ACEi versus ARBs and aliskiren angioedema reports contained in the European ADR database EudraVigilance with regard to reported risk factors and clinical phenotypes. METHODS All spontaneous angioedema reports received between 01/2010-06/2017 reporting either an ACEi, ARB, or aliskiren as "suspected/interacting" drug were identified using the Standardized MedDRA Query "angioedema (narrow)". In order to perform a comparative analysis, odds ratios (ORs) were calculated for angioedema reports of ACEi (n = 3.194) versus ARBs (n = 687) and aliskiren (n = 162). RESULTS More pafirm our observation and elucidate the underyling causes.[This corrects the article DOI 10.1371/journal.pone.0227341.].INTRODUCTION Smoking is a strong risk factor for disease severity in Crohn's disease (CD) and cessation improves outcomes. The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy varenicline doubles cessation over nicotine replacement therapy (NRT) for "normal", but not "slow" metabolizers. Varenicline side effects are heightened in slow metabolizers. Methods using NMR to optimize cessation pharmacotherapy have not been evaluated in CD. AIMS We aim to determine the prevalence of smoking in a CD population and then assess these smokers' attitudes toward a personalized metabolism-informed care (MIC) approach to cessation. AY-22989 mw METHODS In this observational study, we surveyed 1098 patients visiting an inflammatory bowel disease center about their smoking history. We then evaluated a subgroup of individuals with CD (n = 32) who participated in a randomized controlled trial of smoking cessation using MIC versus usual care. For MIC, medication selection was informed by the NMR (normal ≥0.31 vs. slow less then 0.31). The primary outcomes were intervention satisfaction and match rates between NMR and medication choice. RESULTS The baseline prevalence of smoking in our CD population was 13%. Intervention participants reported high rates of satisfaction (85%) and chose a medication that matched their NMR result more often in the MIC group (100% vs. 64%, p = 0.01). Six of 16 (37.5%) patients prescribed varenicline discontinued due to side effects. CONCLUSION MIC produced high rates of satisfaction and matching between NMR and medication in CD patients, supporting patient acceptance and feasibility of precision smoking cessation in this population. To reduce smoking in CD, therapies such as MIC are needed to maximize efficacy and minimize side effects.The quantitative understanding of human behavior is a key issue in modern science. Recently, inhomogeneous human activities have been described by bursts (consecutive activities separated by long periods of inactivity) and characterized by fat-tailed inter-event time (interval between two activities) distributions. However, the dynamics between number of activities and activity duration are still unclear. In this study, we analyzed 133 million toll-free call records from China to study the dynamics between call frequency and call duration. We confirmed that both call frequency and call duration exhibit circadian cycles and weekly cycles. By analyzing intraday patterns of these two metrics, we found the opposite volatility and clustered distributions. Results of clustering analysis showed that calling activity to toll-free numbers can be clustered into four clusters. In the "Work" cluster, the distribution of call duration was significantly different from that in the other clusters. The corresponding time of "Work" cluster was much shorter than estimates based on common sense. Intraday patterns and clustering results showed that both call frequency and call duration are primarily related to circadian cycles, the nature of human beings, and that work is a secondary factor that affects these variables. Moreover, we found a strong positive correlation between call frequency and call duration, as well as polarization of joint probability. The polarization indicates two extremes in inhomogeneous calling activity to toll-free numbers, i.e., either people are very busy or very idle. The empirical probability of the extreme was approximately four times that of random probability. Our findings may have great usage for studying the dynamics of inhomogeneous human behavior.The innovation value chain is an effective tool for analysing innovation activities and reflects the process of value creation and increase in innovation activities. From the perspective of innovation value chains, we divided patent innovation activities into three stages knowledge innovation stage, applied research stage and patent commercialization stage. The panel data from 64 universities directly managed by the Ministry of Education from 2009 to 2017 were used and several conclusions were drawn 1) In the initial stage of knowledge innovation, the fundamental research fund plays a crucial promoting role, and knowledge innovation achievements are mainly published academic papers. 2) In the applied research stage, the knowledge innovation in the early stage and the fund investment in R&D activities have a significant positive effect on the patent output of universities, but the personnel investment has a negative effect. 3) In the final stage of patent commercialization, preliminary research results have a positive impact on patent commercialization, whose marginal effect depends on the industry-university-research relationship, external competition and reputation of the university. The evidence showed that there is a feedback channel between university patent commercialization and knowledge innovation, and new knowledge generated by the interaction with the outside world in the process of patent commercialization was transmitted to the subject of knowledge innovation through this channel, forming a virtuous dynamic cycle. By analysing the driving factors of the value chain of patent innovation in colleges and universities, we provided empirical evidence for the operation mechanism and policy formulation of college patents in China.BACKGROUND Small sample sizes combined with multiple correlated endpoints pose a major challenge in the statistical analysis of preclinical neurotrauma studies. The standard approach of applying univariate tests on individual response variables has the advantage of simplicity of interpretation, but it fails to account for the covariance/correlation in the data. In contrast, multivariate statistical techniques might more adequately capture the multi-dimensional pathophysiological pattern of neurotrauma and therefore provide increased sensitivity to detect treatment effects. RESULTS We systematically evaluated the performance of univariate ANOVA, Welch's ANOVA and linear mixed effects models versus the multivariate techniques, ANOVA on principal component scores and MANOVA tests by manipulating factors such as sample and effect size, normality and homogeneity of variance in computer simulations. Linear mixed effects models demonstrated the highest power when variance between groups was equal or variance ratio wore treatment effect patterns without formal hypothesis testing.Ecology studies showed that esophageal and gastric cancers are directly correlated with the consumption of processed foods. The carcinogenicity of traditional Chinese fermented foods such as douchi (fermented black beans or fermented black soybeans) is due to the presence of carcinogenic N-nitroso compounds, which are derived from biogenic amines. Among the various biogenic amines that can act as precursors of N-nitroso compounds, histamine and tyramine are considered to be the most toxic and are of public health concern when present in food. We have examined some douchi products on the market, and significant amounts of histamine and tyramine were found. The use of fermentation starters generated by subculturing fermented products with unknown microbiota would induce the risk of biogenic amines. As the microbiota used in fermentation is a crucial factor in determining the biogenic amines of fermented food, it is hypothesized that the possible harmful effects of douchi can be minimized through the use of fermentation starters composed of probiotic bacteria. This is the first study to investigate the potential of using probiotic bacteria in manufacturing douchi. Lactobacillus rhamnosus GG (LGG), Lactobacillus casei Shirota (LcS) and Escherichia coli Nissle 1917 (EcN) were used to ferment black beans in this study, and no tyramine was detected in black bean samples incubated with these three strains anaerobically at 37°C or 20°C. The starter culture strains, temperature and presence of oxygen during the incubation period were found to be critical to the generation of biogenic amines. The findings of this study can provide evidence-based insights and warrant further investigations on the potential of reducing the harmful compounds in food fermented with probiotic bacteria as well as the sensory evaluation of douchi fermented with probiotic bacteria.BACKGROUND It is unclear if the intakes of different types of protein have changed over time. OBJECTIVE We delineated trends in types of protein (beef, pork, lamb or goat, chicken, turkey, fish, dairy, eggs, legumes, and nuts and seeds) in US children (2- less then 12 years) and adolescents (12-19 years) from 1999 to 2010. METHODS We used 6 repeated cross-sectional surveys (National Health and Nutrition Examination Survey 1999-2010, n≥1,665 for children; n≥1,156 for adolescents) to test for linear trends in the intake of types of protein (grams per kilogram of body weight) among children and adolescents, and according to sociodemographic groups and participation in food assistance programs. RESULTS Among children, pork intake (0.76 to 0.51 g/kg) decreased, but chicken (0.98 to 1.28 g/kg), all poultry (1.18 to 1.55 g/kg), egg (0.63 to 0.69 g/kg), and legume (0.35 to 0.54 g/kg) intake increased (all P less then 0.05). Among adolescents, beef intake decreased (0.92 to 0.67 g/kg) whereas chicken (0.59 to 0.74 g/kg) and all poultry (0.72 to 0.86 g/kg) intake increased from 1999 to 2010 (all P less then 0.01). Participants of the Women, Infants, and Children (WIC) increased the intake of chicken and dairy (all P less then 0.05) over time whereas no significant trend was observed for income-eligible non-participants. Fish intake did not change in any age group, and recommended types of protein (poultry, fish, nuts and seeds) declined among children of lower socioeconomic status. CONCLUSIONS Intake of recommended types of protein increased among children, adolescents and WIC participants. However, subgroup analyses suggest socioeconomic disparities.The roles of microRNAs (miRNAs) in liver cancer have attracted much attention in recent years. link2 In this study, we demonstrate that miR-520b is downregulated in MHCC-97H cells, a liver cancer cell line with high potential of metastasis, compared with MHCC-97L cells which has a low potential of metastasis. link3 Furthermore, the enhanced expression of miR-520b could inhibit liver cancer cell migration, while silencing its expression resulted in increased migration. Mixed lineage kinase 3 (MLK3) was identified as a direct and functional new target of miR-520b. This regulation was also confirmed by luciferase reporter assays. In addition, our results showed that overexpression of the MLK3 expression partially reversed the effect of miR-520b on liver cancer cell migration, indicating that MLK3 contributes to the migration in liver cancer. The newly identified miR-520b/MLK3 axis partially elucidates the molecular mechanism of liver cancer cell migration and represents a new potential therapeutic target for liver cancer treatment.
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