| 1. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 2. |
- El-Seedi, Hesham, et al.
(författare)
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Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids
- 2012
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 60:44, s. 10877-10895
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Forskningsöversikt (refereegranskat)abstract
- Hydroxycinnamic acids are the most widely distributed phenolic acids in plants. Broadly speaking, they can be defined as compounds derived from cinnamic acid. They are present at high concentrations in many food products, including fruits, vegetables, tea, cocoa, and wine. A diet rich in hydroxycinnamic acids is thought to be associated with beneficial health effects such as a reduced risk of cardiovascular disease. The impact of hydroxycinnamic acids on health depends on their intake and pharmacokinetic properties. This review discusses their chemistry, biosynthesis, natural sources, dietary intake, and pharmacokinetic properties.
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| 3. |
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| 4. |
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| 5. |
- Langerth, A, et al.
(författare)
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Late Complications following Endoscopic Sphincterotomy for Choledocholithiasis: A Swedish Population-Based Study
- 2014
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Ingår i: Diagnostic and therapeutic endoscopy. - : Hindawi Limited. - 1070-3608 .- 1029-0516. ; 2014, s. 745790-
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Tidskriftsartikel (refereegranskat)abstract
- In order to assess the risk of long-term complications following endoscopic sphincterotomy (ES) for common bile duct stones (CBDS), we conducted a cohort study. The study included 1,113 patients who underwent ES for CBDS in six different hospitals in central Sweden between 1977 and 1990. Through the use of the Swedish population registry, each patient was assigned five population-based controls matched for sex and age. Linkage to the Inpatient Registry yielded information on morbidity and mortality for the patients as well as for the controls. After one year of washout, there were 964 patients available for follow-up. The mean age was 70.6 years, 57% were women, and the mean length of follow-up was 8.9 years. The patients’ overall morbidity was significantly higher and we observed a tendency towards increased mortality as well. Recurrent CBDS was diagnosed in 4.1% of the patients. Acute cholangitis with a hazard ratio (HR) of 36 (95%CI 11–119.4) was associated with recurrent CBDS in 39% of the patients. HR for acute pancreatitis was 6.2 (95%CI 3.4–11.3) and only one patient had CBDS at the same time. In conclusion, we consider acute pancreatitis and cholangitis both as probable long-term complications after ES.
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| 6. |
- Wiegerinck, W., et al.
(författare)
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BOVINOSE : Pheromone-based sensor system for detecting estrus in dairy cows
- 2011
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Ingår i: Procedia Comput. Sci.. - : Elsevier BV. ; , s. 340-342
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Konferensbidrag (refereegranskat)abstract
- The BOVINOSE project (www.bovinose.eu) aims to develop an electronic nose to detect estrus in a dairy cow, and thus to determine the optimal timing of artificial insemination. The physical principle is based on detection of sex pheromones that are secreted by the cow, exclusively during estrus. These pheromones are the natural olfactory signal for the bull that the cow is in heat. This technology aims to help the dairy farmers in the EU, the vast majority being micro-enterprises run as family businesses.
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| 7. |
- Ballantyne, C. M., et al.
(författare)
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Efficacy, safety and effect on biomarkers related to cholesterol and lipoprotein metabolism of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg vs. simvastatin 40 or 80 mg plus ezetimibe 10 mg in high-risk patients: Results of the GRAVITY randomized study
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 232:1, s. 86-93
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Combination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent. Methods: Adult patients (n = 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks. Results: Significantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of < 100 mg/dl and < 70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced w10-14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced beta-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A(2) mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable. Conclusion: Co-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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| 9. |
- Ehrlén, Johan, et al.
(författare)
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Selection on plant optical traits and floral scent : Effects via seed development and antagonistic interactions
- 2012
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Ingår i: Basic and Applied Ecology. - : Elsevier BV. - 1439-1791 .- 1618-0089. ; 13:6, s. 509-515
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Tidskriftsartikel (refereegranskat)abstract
- Evolutionary explanations of plant reproductive traits have usually emphasized optical characteristics of plants and selection mediated by pollinators. In recent years, studies have been broadened by incorporating also interactions with antagonists and by studying plant fragrant cues. Here, we examined if optical and fragrance traits of the perennial herb Primula veris correlated with reproductive success, in terms of fruit and seed set, and with avoidance of seed predators. Selection path analysis showed that both optical and fragrance traits influenced total seed production, and effects occurred both via fruit and seed set and via predator avoidance. In one case the same trait, inflorescence height, influenced total seed production both positively and negatively through effects on different components of fitness. Our results lend support to the notion that selection by mutualists and antagonists simultaneously acts on optical and fragrance traits.
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| 10. |
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