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- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Lu, Yingchang, et al.
(författare)
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A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
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Tidskriftsartikel (refereegranskat)abstract
- .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
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- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 6. |
- Shu, Xiang, et al.
(författare)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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- Bedri, Sahl Khalid, et al.
(författare)
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Plasma protein profiling reveals candidate biomarkers for multiple sclerosis treatment
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment.
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| 10. |
- Bergström, Lena, et al.
(författare)
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Report of the ICES/HELCOM Working Group on Integrated Assessments of the Baltic Sea (WGIAB)
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The ICES/HELCOM Working Group on Integrated Assessments of the Baltic Sea(WGIAB) was established in 2007 as a forum for developing and combining ecosystembasedmanagement efforts for the Baltic Sea. The group intends to serve as a scientificcounterpart and support for the ICES Baltic Fisheries Assessment Working Group(WGBFAS) as well as for efforts and projects related to Integrated Ecosystem Assessments(IEA) within ICES and HELCOM. The group works in cooperation with similargroups within the ACOM/SCICOM Steering Group on Integrated Ecosystem Assessments(SSGIEA).The 2015 WGIAB meeting was held in Cádiz, Spain, from 9–13 March, back-to-backwith the meeting of its counterpart in the Working Group on Ecosystem Assessmentof Western European Shelf Seas (WGEAWESS). The meetings had joint sessions as wellas WG specific work, and some participants effectively participated in both meetings.The WGIAB meeting was attended by 27 participants from nine countries. The meetingwas chaired by Christian Möllmann, Germany, Laura Uusitalo, Finland and Lena Bergström,Sweden.This was the last year of the ongoing three-year Terms of Reference (ToR) for WGIAB.The main working activities in 2015 were to i) conduct studies on Baltic Sea ecosystemfunctioning with the goal to publish case studies from different parts of the Baltic Seain peer-reviewed journals, ii) work on the demonstration exercise to develop ecosystem-based assessment and advice for Baltic fish stocks focusing on cod (DEMO) withmultiple approaches, iii) plan further how to integrate the social and economic aspectsmore tightly in the WGIAB work, and iv) discuss the future focus and format of theWGIAB work.The Baltic ecosystem functioning activity focused on identifying and exploring keytrends and linkages in the Baltic Sea foodweb. This was pursued by presentation andfurther discussion of ongoing intersessional work on foodweb modelling and integratedanalyses, and by exercises to develop conceptual models Baltic Sea foodwebsand the links to ecosystem function. Long-term monitoring datasets on the abiotic andbiotic parts of the Baltic Sea Proper ecosystem were updated for use in the continuedwork to develop environmental indicators for fisheries and marine management.The focus of the DEMO 3 (DEMOnstration exercise for Integrated Ecosystem Assessmentand Advice of Baltic Sea cod) was on finding a way to use the results from theDEMO1 and DEMO2 workshops in short and midterm projections/scenarios of Balticcod dynamics based on different types of modelling, as well as designing methodologyand modelling data for practical implementation of Integrated Advice for Baltic cod.The WGIAB was positively inclined towards including social and economic aspectsinto the integrated assessment. Openings to this path were provided by presentationon ongoing project work, and discussing their linkages to ecological aspects. It wasseen as crucial that experts on social and economic analysis should be included andtake an active part in the future work of the group.The group concluded that its upcoming work should focus more closely on functionaldiversity, which was identified as a recurring issue in the Baltic Sea. This approach wasalso identified as a useful connection point between scientific and management aspectsin order for the group to continue serving as a forum for developing ecosystem-basedmanagement efforts in the Baltic Sea. A focus on functional diversity was also seen as2 | ICES WGIAB REPORT 2015a potentially feasible way of bringing together management aspects for different sectors,by linking to ecosystem services concepts.The group proposed Saskia Otto, Germany and Martin Lindegren, Denmark as newincoming Chairs, together with Lena Bergström, Sweden and Laura Uusitalo, Finland.Having four Chairs is justified due to the wide scope of the group's work, as well asthe increased work load due to the planned new foci.
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