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Sökning: WFRF:(Bell J) > Linköpings universitet

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  • Kurilshikov, Alexander, et al. (författare)
  • Large-scale association analyses identify host factors influencing human gut microbiome composition
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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  • Kalman, L. V., et al. (författare)
  • Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
  • 2016
  • Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
  • Tidskriftsartikel (refereegranskat)abstract
    • This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
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  • Brennan, R.M., et al. (författare)
  • Strains of Epstein-Barr virus infecting multiple sclerosis patients
  • 2010
  • Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 16:6, s. 643-651
  • Tidskriftsartikel (refereegranskat)abstract
    • Both epidemiological and experimental studies have indicated that the ubiquitous herpesvirus Epstein-Barr virus (EBV) plays a role in the pathogenesis of multiple sclerosis (MS). Some features of MS epidemiology, such as the decline in risk among migrants from high to low MS prevalence areas, suggest the presence of variant EBV strains that increase MS risk. The objective of this study was to investigate whether genetic variability in EBV is associated with MS. Genes encoding for two EBV antigens (EBNA1 and BRRF2) were sequenced in EBV isolates from 40 MS patients and a similar number of control subjects. These viral antigens were chosen for analysis because they are known to stimulate atypical immune responses in MS. Extensive sequence polymorphism was observed within the EBNA1 and BRRF2 genes in isolates from both MS patients and controls. Interestingly, several single nucleotide polymorphisms within the EBNA1 gene, and one within the BRRF2 gene, were found to occur at marginally different frequencies in EBV strains infecting MS patients versus controls. Although this study does not find a simple causal relationship between EBV strains and the occurrence of MS, the existence of haplotypes that occur at different frequencies in MS patients versus controls may provide an area for future study of the role of EBV strain variation in multiple sclerosis.
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6.
  • ODonnell, Michael, et al. (författare)
  • Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
  • 2018
  • Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
  • Tidskriftsartikel (refereegranskat)abstract
    • Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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  • Bell, Katy J. L., et al. (författare)
  • Prognostic impact of systolic blood pressure variability in people with diabetes
  • 2018
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes.Methods: We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models.Results: BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000–0.003 in all models).Conclusions: Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP.
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  • Patnaik, Samarjit, et al. (författare)
  • Structure-Activity Relationship of Imidazopyridinium Analogues as Antagonists of Neuropeptide S Receptor
  • 2013
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:22, s. 9045-9056
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery and characterization of a novel chemical series of phosphorothioyl-containing imidazopyridines as potent neuropeptide S receptor antagonists is presented. The synthesis of analogues and their structure-activity relationship with respect to the Gq, Gs, and ERK pathways is detailed. The pharmacokinetics and in vivo efficacy of a potent analogue in a food intake rodent model are also included, underscoring its potential therapeutic value for the treatment of sleep, anxiety, and addiction disorders.
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  • Prowle, John R., et al. (författare)
  • Postoperative acute kidney injury in adult non-cardiac surgery : joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative
  • 2021
  • Ingår i: Nature Reviews Nephrology. - : Springer Nature. - 1759-5061 .- 1759-507X. ; 17:9, s. 605-618
  • Forskningsöversikt (refereegranskat)abstract
    • The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI. Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.
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10.
  • Vicente Perez-Giron, J., et al. (författare)
  • Selective binding of oligonucleotide on TiO2 surfaces modified by swift heavy ion beam lithography
  • 2014
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier. - 0168-583X .- 1872-9584. ; 339, s. 67-74
  • Tidskriftsartikel (refereegranskat)abstract
    • We have used swift heavy-ion beam based lithography to create patterned bio-functional surfaces on rutile TiO2 single crystals. The applied lithography method generates a permanent and well defined periodic structure of micrometre sized square holes having nanostructured TiO2 surfaces, presenting different physical and chemical properties compared to the surrounding rutile single crystal surface. On the patterned substrates selective binding of oligonucleotides molecules is possible at the surfaces of the holes. This immobilisation process is only being controlled by UV light exposure. The patterned transparent substrates are compatible with fluorescence detection techniques, are mechanically robust, have a high tolerance to extreme chemical and temperature environments, and apparently do not degrade after ten cycles of use. These qualities make the patterned TiO2 substrates useful for potential biosensor applications.
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