| 1. |
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| 2. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 3. |
- Forrest, ARR, et al.
(författare)
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A promoter-level mammalian expression atlas
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Adam, A, et al.
(författare)
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Abstracts from Hydrocephalus 2016.
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 9. |
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| 10. |
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| 11. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 12. |
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| 13. |
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| 14. |
- Inagaki-Kawata, Y, et al.
(författare)
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Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
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Tidskriftsartikel (refereegranskat)abstract
- The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
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| 15. |
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| 16. |
- Kerkhof, H. J. M., et al.
(författare)
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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 17. |
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| 18. |
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| 19. |
- Takahashi, H., et al.
(författare)
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A thermal-neutron detector with a phoswich system of LiCaAlF6 and BGO crystal scintillators onboard PoGOLite
- 2010
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Ingår i: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference, NSS/MIC 2010 and 17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors, RTSD 2010. ; , s. 32-37
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Konferensbidrag (refereegranskat)abstract
- To measure the flux of atmospheric neutrons and study the neutron contribution to the background of the main detector of the PoGOLite (Polarized Gamma-ray Observer) balloon-borne experiment, a thermal-neutron detector with a phoswich system of LiCaAlF6 (Eu) and BGO crystal scintillators is developed. The performance to separate thermal-neutron events from those of gamma-rays and charged particles is validated with 252Cf on ground. The detector is attached to the PoGOLite instrument and is launched in 2011 from the Esrange facility in the North of Sweden. Although the emission wavelength of the LiCaAlF6 (Ce) is 300 nm and overlaps with the absorption wavelength of the BGO, the phoswich capability of the LiCaAlF6 (Ce) with the BGO is also confirmed with installing a waveform shifter.
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| 20. |
- Feron, Romain, et al.
(författare)
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RADSex : A computational workflow to study sex determination using restriction site-associated DNA sequencing data
- 2021
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Ingår i: Molecular Ecology Resources. - : John Wiley & Sons. - 1755-098X .- 1755-0998. ; 21:5, s. 1715-1731
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Tidskriftsartikel (refereegranskat)abstract
- The study of sex determination and sex chromosome organization in nonmodel species has long been technically challenging, but new sequencing methodologies now enable precise and high-throughput identification of sex-specific genomic sequences. In particular, restriction site-associated DNA sequencing (RAD-Seq) is being extensively applied to explore sex determination systems in many plant and animal species. However, software specifically designed to search for and visualize sex-biased markers using RAD-Seq data is lacking. Here, we present RADSex, a computational analysis workflow designed to study the genetic basis of sex determination using RAD-Seq data. RADSex is simple to use, requires few computational resources, makes no prior assumptions about the type of sex-determination system or structure of the sex locus, and offers convenient visualization through a dedicated R package. To demonstrate the functionality of RADSex, we re-analysed a published data set of Japanese medaka, Oryzias latipes, where we uncovered a previously unknown Y chromosome polymorphism. We then used RADSex to analyse new RAD-Seq data sets from 15 fish species spanning multiple taxonomic orders. We identified the sex determination system and sex-specific markers in six of these species, five of which had no known sex-markers prior to this study. We show that RADSex greatly facilitates the study of sex determination systems in nonmodel species thanks to its speed of analyses, low resource usage, ease of application and visualization options. Furthermore, our analysis of new data sets from 15 species provides new insights on sex determination in fish.
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| 21. |
- Flores, H., et al.
(författare)
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Impact of climate change on Antarctic krill
- 2012
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Ingår i: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 458, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Antarctic krill Euphausia superba (hereafter 'krill') occur in regions undergoing rapid environmental change, particularly loss of winter sea ice. During recent years, harvesting of krill has in creased, possibly enhancing stress on krill and Antarctic ecosystems. Here we review the overall impact of climate change on krill and Antarctic ecosystems, discuss implications for an ecosystem-based fisheries management approach and identify critical knowledge gaps. Sea ice decline, ocean warming and other environmental stressors act in concert to modify the abundance, distribution and life cycle of krill. Although some of these changes can have positive effects on krill, their cumulative impact is most likely negative. Recruitment, driven largely by the winter survival of larval krill, is probably the population parameter most susceptible to climate change. Predicting changes to krill populations is urgent, because they will seriously impact Antarctic ecosystems. Such predictions, however, are complicated by an intense inter-annual variability in recruitment success and krill abundance. To improve the responsiveness of the ecosystem-based management approach adopted by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), critical knowledge gaps need to be filled. In addition to a better understanding of the factors influencing recruitment, management will require a better understanding of the resilience and the genetic plasticity of krill life stages, and a quantitative understanding of under-ice and benthic habitat use. Current precautionary management measures of CCAMLR should be maintained until a better understanding of these processes has been achieved. [GRAPHICS] .
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| 22. |
- Kawaguchi, K., et al.
(författare)
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Detection of HF Toward PKS 1830-211, Search for Interstellar H2F+, and Laboratory Study of H2F+ and H2Cl+ Dissociative Recombination
- 2016
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 822:2, s. Art. no. 115-
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Tidskriftsartikel (refereegranskat)abstract
- We report extragalactic observations of two fluorine-bearing species, hydrogen fluoride (HF) and fluoronium (H2F+), in the z = 0.89 absorber in front of the lensed blazar PKS 1830-211 with the Atacama Large Millimeter/submillimeter Array. HF was detected toward both southwest and northeast images of the blazar, with column densities >3.4 × 1014 cm-2 and 0.18 × 1014 cm-2, respectively. H2F+ was not detected, down to an upper limit (3?) of 8.8 × 1011 cm-2 and an abundance ratio of [H2F+]/[HF] 1/386. We also searched for H2F+ toward the Galactic sources NGC 6334 I and W51C, and toward Galactic center clouds with the Herschel HIFI spectrometer.6 The upper limit on the column density was derived to be 2.5 × 1011 cm-2 in NGC 6334 I, which is 1/68 of that for H2Cl+. In constrast, the ortho transition of H2Cl+ is detected toward PKS 1830-211. To understand the small abundance of interstellar H2F+, we carried out laboratory experiments to determine the rate constants for the ion-electron recombination reaction by infrared time-resolved spectroscopy. The constants determined are ke(209 K) = (1.1 ± 0.3) ×10-7 cm3 s-1 and (0.46 ± 0.05) ×10-7 cm3 s-1 for H2F+ and H2Cl+, respectively. The difference in the dissociative recombination rates between H2F+ and H2Cl+ by a factor ?2 and the cosmic abundance ratio [F]/[Cl] ? 1/6 are not enough to explain the much smaller abundance of H2F+. The difference in the formation mechanism of H2F+ and H2Cl+ in interstellar space would be a major factor in the small abundance of H2F+.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Aglago, Elom K., et al.
(författare)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 27. |
- Aihara, Aya, et al.
(författare)
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A Vibration Estimation Method for Wind Turbine Blades
- 2017
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Ingår i: Experimental mechanics. - : Springer Science and Business Media LLC. - 0014-4851 .- 1741-2765. ; 57:8, s. 1213-1224
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the development of a vibration monitoring system for wind turbine blades. This system is used to estimate the deflection at the tip blade on a wind turbine tower. Technical accidents of wind turbine blades have become increasingly common. Thus, regular monitoring of the blades is very important to prevent breakdowns, especially in cases when the blades begin to vibrate excessively. The monitoring system developed in this study satisfies two main objectives for practicality. First, our system is easy to install on existing wind turbines. Second, blade deflection is measured in real time. Our system can be operated using a few strain gages attached at the blade root, and the deflection is calculated based on the monitored stress. Thus, direct measurement of deflection at the blade tip is unnecessary. An estimation algorithm for this purpose is adopted based on the experimental modal analysis. This paper focuses on the evaluation of the estimation algorithm to investigate the feasibility of our system. Basic experiments were conducted using a simple blade model of a 300 W scaled wind turbine under rotation. Signals from the strain gages were acquired by a sensor network and sent to a computer through a wireless connection. The results show that the estimation accuracy is acceptably high. Therefore, we conclude that our proposed system is practical.
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| 28. |
- Carreras-Torres, Robert, et al.
(författare)
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Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 315-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.IMPACT: These findings can guide potential prevention treatments.
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| 29. |
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| 30. |
- Drew, David A., et al.
(författare)
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Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
- 2024
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:22
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Tidskriftsartikel (refereegranskat)abstract
- Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
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| 31. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 32. |
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| 33. |
- Inoue T, T, et al.
(författare)
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Autofluorescence imaging videoendoscopy in the diagnosis of chronic atrophic fundal gastritis
- 2010
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Ingår i: Journal of Gastroenterology. - : Springer Science and Business Media LLC. - 0944-1174 .- 1435-5922. ; 45:1, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Diagnosis of chronic atrophic fundal gastritis (CAFG) is important to understand the pathogenesis of gastric diseases and assess the risk of gastric cancer. Autofluorescence imaging videoendoscopy (AFI) may enable the detection of mucosal features not apparent by conventional white-light endoscopy. The purpose of this study was to estimate the diagnostic ability of AFI in CAFG. Methods: A total of 77 patients were enrolled. Images of the gastric body in AFI and white-light mode were taken to assess the extent of gastritis, and biopsies were taken from green (n = 119) and purple (n = 146) mucosa in AFI images. The diagnostic accuracy of green mucosa for CAFG was investigated according to the Sydney system. Results: In per-patient analysis, the accuracy of green mucosa in patients with activity, inflammation, atrophy and intestinal metaplasia was 64, 93, 88 and 81%, respectively. In per-biopsy analysis, the accuracy for activity, inflammation, atrophy and intestinal metaplasia was 55, 62, 76 and 76%, respectively. Green areas in the gastric body exhibited more inflammation (p\0.001), atrophy (p\0.001) and intestinal metaplasia (p\0.001), whereas purple areas rarely contained atrophy or intestinal metaplasia. The kappa statistics for inter- and intra-observer agreement of AFI on assessing the extent of CAFG were 0.66 and 0.47, while those for white-light endoscopy were 0.56 and 0.39. Conclusions: AFI could diagnose the extent of CAFG as a green area in the gastric body, with higher reproducibility compared with white-light endoscopy. Therefore, AFI may be a useful adjunct to endoscopy to identify patients at high risk of developing gastric cancer.
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| 34. |
- Ito, Y, et al.
(författare)
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Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma
- 2002
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 76:3, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate whether c-Src is involved in carcinogenesis and progression of breast carcinoma, we examined the expression of activated c-Src in tissue sections from surgically resected human breast specimens. First, we confirmed the specificity of the antibody against activated c-Src (Clone 28) using six cell lines established from human breast carcinomas by western blotting. As expected, activated c-Src was detected as a 60 kDa band in all cell lines tested. Immunofluorescence analysis demonstrated that the activated c-Src was mainly observed in cytoplasms of these cells. Then, we designed an immunohistochemical study with 73 human breast carcinoma tissues. Glandular epithelial and myoepithelial cells in normal mammary glands adjacent to carcinoma nests and infiltrating stromal cells were negative for activated c-Src. In contrast, 37 of the 73 breast carcinoma tested (50.7%) were positive for activated c-Src, and this positive staining was inversely correlated with Ki-67 labeling index (p <0.0001), TNM stage (p <0.0001), tumor size (p < 0.0001), and histological grade (p = 0.0002). These results strongly suggest that the activation of c-Src would be related to the progression of breast carcinomas with low aggressiveness.
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| 35. |
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| 36. |
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| 37. |
- Kole, Merlin, et al.
(författare)
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Neutron background detection for a hard X-ray balloon-borne polarimeter
- 2014
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Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
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Konferensbidrag (refereegranskat)abstract
- PoGOLite is a balloon-borne hard X-ray polarimeter. It determines polarisation by measuring the azimuthal angular distribution of Compton scattered photons in a plastic scintillator array. The use of an all-plastic target yields a relatively large, low-mass detection area. The dominant source of background for these measurements has been shown, through Geant4 simulations, to originate from high energy (MeV range) atmospheric neutrons. Neutrons can pass the instrument's Bismuth Germanium Oxide (BGO) anti-coincidence shield undetected and subsequently scatter between plastic scintillator elements to produce a polarisation signature. A passive 15 cm thick polyethylene shield surrounding the polarimeter reduces the neutron induced background by an order of magnitude. The background level remains however significant, prompting the need for active monitoring of the continuously changing neutron flux. For this purpose PoGOLite makes use of a phoswich scintillator cell. The phoswich cell consists of a 5 mm thick Lithium Calcium Aluminium Fluoride (LiCAF) scintillator, used for neutron detection. The LiCAF is surrounded by a BGO anti-coincidence system. This small light weight detector can therefore be used to measure the neutron flux even in high radiation environments. This type of neutron detector was tested on a separate dedicated stratospheric balloon mission in March 2013, called PoGOLino, prior to the PoGOLite flight which took place in July 2013. Results from the test flight and implications for the measurements performed on the PoGOLite flight will be discussed.
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| 38. |
- McAlindon, T E, et al.
(författare)
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OARSI guidelines for the non-surgical management of knee osteoarthritis.
- 2014
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 22:3, s. 363-388
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Tidskriftsartikel (refereegranskat)abstract
- To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide.
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| 39. |
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| 40. |
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| 41. |
- Muller, Sebastien, 1976, et al.
(författare)
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Detection of extragalactic CF+ toward PKS 1830-211 Chemical differentiation in the absorbing gas
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 589, s. Art. no. L5-
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Tidskriftsartikel (refereegranskat)abstract
- We report the first extragalactic detection of the fluoromethylidynium ion CF+ in the z = 0.89 absorber toward PKS 1830-211. We estimate an abundance of similar to 3 x 10(-10) relative to H-2 and that similar to 1% of fluorine is captured in CF+. The absorption line profile of CF+ is found to be markedly different from that of other species observed within the same tuning, and is notably anticorrelated with CH3OH. On the other hand, the CF+ profile resembles that of [CI]. Our results are consistent with expected fluorine chemistry and point to chemical differentiation in the column of absorbing gas.
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| 42. |
- 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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| 43. |
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| 44. |
- Papavero, Luca, et al.
(författare)
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Degenerative Cervical Myelopathy : A 7-Letter Coding System That Supports Decision-Making for the Surgical Approach
- 2020
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Ingår i: Neurospine. - : The Korean Spinal Neurosurgery Society. - 2586-6583 .- 2586-6591. ; 17:1, s. 164-171
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To validate with a prospective study a decision-supporting coding system for the surgical approach for multilevel degenerative cervical myelopathy.METHODS: Ten cases were presented on an internet platform, including clinical and imaging data. A single-approach (G1), a choice between 2 (G2), or 3 approaches (G3) were options. Senior and junior spine surgeons analyzed 7 parameters: location and extension of the compression of the spinal cord, C-spine alignment and instability, general morbidity and bone diseases, and K-line and multilevel corpectomy. For each parameter, an anterior, posterior, or combined approach was suggested. The most frequent letter or the last letter (if C) of the resulting 7-letter code (7LC) suggested the surgical approach. Each surgeon performed 2 reads per case within 8 weeks.RESULTS: G1: Interrater reliability between junior surgeons improved from the first read (κ = 0.40) to the second (κ = 0.76, p < 0.001) but did not change between senior surgeons (κ = 0.85). The intrarater reliability was similar for junior (κ = 0.78) and senior (κ = 0.71) surgeons. G2: Junior/senior surgeons agreed completely (58%/62%), partially (24%/23%), or did not agree (18%/15%) with the 7LC choice. G3: junior/senior surgeons agreed completely (50%/50%) or partially (50%/50%) with the 7LC choice.CONCLUSION: The 7LC showed good overall reliability. Junior surgeons went through a learning curve and converged to senior surgeons in the second read. The 7LC helps less experienced surgeons to analyze, in a structured manner, the relevant clinical and imaging parameters influencing the choice of the surgical approach, rather than simply pointing out the only correct one.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Tian, Yu, et al.
(författare)
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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
- 2024
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130:10, s. 1687-1696
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Tidskriftsartikel (refereegranskat)abstract
- Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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| 49. |
- Tsukahara, T., et al.
(författare)
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Turbulence stripe in transitional channel flow with/without system rotation
- 2010
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Ingår i: 7th IUTAM Symposium on Laminar-Turbulent Transition. - Dordrecht : Springer Science+Business Media B.V.. ; , s. 421-426
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Konferensbidrag (refereegranskat)abstract
- We report direct numerical simulations and experiments conducted in two types of plane channel flows-plane Poiseuille flow and plane Couette flows without/ with system rotation-considering the subcritical-transition regime with using large aspect-ratio computational domains and channels. Both flows give rise to coexisting laminar and turbulent equilibrium regions in the form of oblique stripes, which are tilted by a certain angle with respect to the mean flow. When subjected to a stabilizing rotation, the Couette turbulence is locally quenched and exhibits the stripe pattern as similar to non-rotating cases. In this context, the turbulence stripe can be seen as an intrinsic phenomenon in the reverse transition in a channel flow.
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