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Sökning: WFRF:(Olesen Ole F)

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1.
  • Chen, H.Y., et al. (författare)
  • Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
  • 2023
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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  • Harandi, Ali M, 1968, et al. (författare)
  • Vaccine adjuvants: scientific challenges and strategic initiatives.
  • 2009
  • Ingår i: Expert review of vaccines. - : Informa UK Limited. - 1744-8395 .- 1476-0584. ; 8:3, s. 293-8
  • Forskningsöversikt (refereegranskat)abstract
    • The majority of vaccine antigens currently under investigation represent recombinant molecules or subunits of pathogens with little or no inherent immunostimulatory property. The development of safe and potent immunologic adjuvants that can increase and direct vaccine-specific immunity is, therefore, required urgently. At the same time, the discovery of Toll-like receptors and other innate immune receptors with the ability to bridge innate immune responses and adaptive immunity is offering unprecedented opportunities for the development of novel adjuvants. However, research on vaccine adjuvants has so far received little attention as an independent scientific priority from most of the main research-funding agencies and policy makers. Further, adjuvant research and development is currently spread over a wide number of highly diverse organizations, including large commercial companies, small biotech enterprises as well as publicly funded research organizations and academia. More efforts are, therefore, needed to highlight the importance of vaccine adjuvants on the global research agenda and to encourage collaboration and flow of information between different stakeholders. This article attempts to underline scientific challenges and strategic priorities in the development of vaccine adjuvants for human use.
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