| 1. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 2. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 9. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 10. |
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| 11. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 12. |
- Achterberg, A., et al.
(författare)
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Detection of atmospheric muon neutrinos with the IceCube 9-string detector
- 2007
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:2, s. 027101-
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of live time, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst)+/- 14.5(stat) events from atmospheric neutrinos.
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| 13. |
- Achterberg, A., et al.
(författare)
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Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II
- 2007
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:4, s. 042008-
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Tidskriftsartikel (refereegranskat)abstract
- A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E-2 Phi(90%C.L.)< 7.4x10(-8) GeV cm(-2) s(-1) sr(-1) is placed on the diffuse flux of muon neutrinos with a Phi proportional to E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Phi proportional to E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Phi proportional to E-2.
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| 14. |
- Gustavsson, Larisa, et al.
(författare)
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Resistance to Neonectria ditissima in apple : insights from metabolomics and lipidomics analyses
- 2023
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Ingår i: Xxxi international horticultural congress (ihc2022). - : International Society for Horticultural Science. - 9789462613614 ; , s. 329-335, s. 329-336
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Konferensbidrag (refereegranskat)abstract
- European canker, caused by the necrotrophic fungus Neonectria ditissima, is the most serious disease in apple production in Sweden. The disease is favored by a relatively cool and rainy climate. The canker damages have a significant economic impact due to reduced bearing surface and increased orchard management costs. The possibilities for chemical and biological control are very limited. Therefore, directed breeding for new resistant cultivars is urgently needed. Knowledge of inheritance of canker resistance and understanding of molecular mechanisms involved in resistant and susceptible responses to fungal attacks would facilitate breeding. In this study, we evaluated the tempo-spatial differences in plant-pathogen interactions in a set of partially resistant and susceptible cultivars by conducting metabolomic and lipidomic analyses. The major trends in metabolomics and lipidomic profiles were common among cultivars, irrespective of the degree of susceptibility. Several metabolites and lipids varied with time point and cultivar under N. ditissima infection. Putative key metabolites such as suberic acid and jasmonic acid were upregulated in all cultivars upon infection. Additionally, several lipids exhibited changes 30 to 45 days post-inoculation. Thus, the approach used seems to have resulted in a rich data set to be further analyzed in light of ongoing QTL-mapping efforts.
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| 15. |
- Lesseur, Corina, et al.
(författare)
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Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:12, s. 1544-1550
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
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| 16. |
- Stacey, Simon N, et al.
(författare)
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Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.
- 2010
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Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 6:7, s. e1001029-
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Tidskriftsartikel (refereegranskat)abstract
- We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.
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| 17. |
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| 18. |
- Bing, Zhao, 1990, et al.
(författare)
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Unconventional Charge–Spin Conversion in Weyl-Semimetal WTe2
- 2020
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 32:38
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Tidskriftsartikel (refereegranskat)abstract
- An outstanding feature of topological quantum materials is their novel spin topology in the electronic band structures with an expected large charge-to-spin conversion efficiency. Here, a charge-current-induced spin polarization in the type-II Weyl semimetal candidate WTe2 and efficient spin injection and detection in a graphene channel up to room temperature are reported. Contrary to the conventional spin Hall and Rashba–Edelstein effects, the measurements indicate an unconventional charge-to-spin conversion in WTe2, which is primarily forbidden by the crystal symmetry of the system. Such a large spin polarization can be possible in WTe2 due to a reduced crystal symmetry combined with its large spin Berry curvature, spin–orbit interaction with a novel spin-texture of the Fermi states. A robust and practical method is demonstrated for electrical creation and detection of such a spin polarization using both charge-to-spin conversion and its inverse phenomenon and utilized it for efficient spin injection and detection in the graphene channel up to room temperature. These findings open opportunities for utilizing topological Weyl materials as nonmagnetic spin sources in all-electrical van der Waals spintronic circuits and for low-power and high-performance nonvolatile spintronic technologies.
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| 19. |
- Claeson, Anna-Sara, 1974-, et al.
(författare)
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A standardized protocol for comparable analysis of GSH/GSSG by UHPLC-ESI-MSMS for human plasma
- 2019
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Ingår i: Journal of chromatography. B. - : Elsevier. - 1570-0232 .- 1873-376X. ; 1104, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Variability in the levels of GSH and GSSG in plasma is suggested to derive from inadequate pre-processing methods. The aim of this study was to develop a protocol for comparable and reliable measurements of GSH/GSSG. Venous blood from 8 healthy individuals were collected and divided into 7 different pre-processing procedures. For three of the samples an extraction mixture was added after 0 (baseline), 4 and 8 min and for three of the samples the extraction mixture was added at different times during defrost. A worst case scenario where a sample was left in a cool box during 6 h was also included. The samples were analyzed with UHPLC-ESIMSMS. A large difference in the levels of GSH and GSSG were identified and it was clearly associated with the sample handling procedures. A sample left untreated for 4 min will have significantly reduced amount of GSH. Stability tests showed that the level of GSH was reduced after 3 months in -80 degrees C.
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| 20. |
- Diamanti, Riccardo, et al.
(författare)
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Comparative structural analysis provides new insights into the function of R2-like ligand-binding oxidase
- 2022
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Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 596:12, s. 1600-1610
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Tidskriftsartikel (refereegranskat)abstract
- R2-like ligand-binding oxidase (R2lox) is a ferritin-like protein that harbours a heterodinuclear manganese–iron active site. Although R2lox function is yet to be established, the enzyme binds a fatty acid ligand coordinating the metal centre and catalyses the formation of a tyrosine–valine ether cross-link in the protein scaffold upon O2 activation. Here, we characterized the ligands copurified with R2lox by mass spectrometry-based metabolomics. Moreover, we present the crystal structures of two new homologs of R2lox, from Saccharopolyspora erythraea and Sulfolobus acidocaldarius, at 1.38 Å and 2.26 Å resolution, respectively, providing the highest resolution structure for R2lox, as well as new insights into putative mechanisms regulating the function of the enzyme.
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| 21. |
- Green, Alanna C., et al.
(författare)
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Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells
- 2023
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5:4, s. 642-659
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase–cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a ‘folate trap’. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.
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| 22. |
- Hubert, Madlen, et al.
(författare)
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Lipid accumulation controls the balance between surface connection and scission of caveolae.
- 2020
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae are bulb-shaped invaginations of the plasma membrane (PM) that undergo scission and fusion at the cell surface and are enriched in specific lipids. However, the influence of lipid composition on caveolae surface stability is not well described or understood. Accordingly, we inserted specific lipids into the cell PM via membrane fusion and studied their acute effects on caveolae dynamics. We demonstrate that sphingomyelin stabilizes caveolae to the cell surface, whereas cholesterol and glycosphingolipids drive caveolae scission from the PM. Although all three lipids accumulated specifically in caveolae, cholesterol and sphingomyelin were actively sequestered, whereas glycosphingolipids diffused freely. The ATPase EHD2 restricts lipid diffusion and counteracts lipid-induced scission. We propose that specific lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not restrained by EHD2 at the caveolae neck. This work provides a mechanistic link between caveolae and their ability to sense the PM lipid composition.
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| 23. |
- Janson Fagring, Annika, 1949, et al.
(författare)
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Unexplained chest pain in relation to psychosocial factors and health-related quality of life in men and women.
- 2007
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Ingår i: European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 6:4, s. 329-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Unexplained chest pain is a frequent and increasingly common complaint among patients admitted to Emergency Departments. Previous studies have defined unexplained chest pain as non-cardiac or non-coronary artery disease, i.e. patients with other organic causes explaining the chest pain could be included. To increase the knowledge of unexplained chest pain, this study only includes patients without any known explanation for their chest pain. AIM: To analyze gender differences regarding pain characteristics, psychosocial factors and health-related quality of life among patients diagnosed unexplained chest pain. METHODS AND RESULTS: The results are based on 179 patients (101 men, 78 women) between 16 and 69 years old (mean age 45.3) consecutively admitted to Emergency Department. Pain characteristics were assessed by Pain-O-Meter. Social relationships, depression, anxiety, and health-related quality of life were measured by a self-administered questionnaire. There were no gender differences regarding chest pain intensity; however women described their pain as burning (p<0.01) and frightening (p<0.03) more often than men. Men reported less depression (p<0.01) and less trait anxiety (p=0.01) than women. Chest pain intensity did not significantly impact health-related quality of life except physical functioning in men (p=0.05). CONCLUSION: Gender differences were few. Chest pain intensity did not significantly impact health-related quality of life.
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| 24. |
- Jerlock, Margaretha, 1946, et al.
(författare)
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Psychosocial profile in men and women with unexplained chest pain
- 2008
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Ingår i: J Intern Med. - : Wiley-Blackwell. ; 264:3, s. 265-274
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVE: The aim of this study was to compare men and women with unexplained chest pain (UCP) to a randomly selected population sample free of clinical heart disease with regard to sleep problems, mental strain at work, stress at home, negative life events and health-related quality of life (HRQOL). DESIGN AND SUBJECTS: The study was conducted at a university hospital in Sweden including 231 patients aged 25-69 without any organic cause for chest pain. As a reference group, 1069 participants, were recruited from the INTERGENE population-based study. RESULTS: Patients with UCP had more sleep problems (OR = 1.8, P < 0.0001), were almost three times more worried about stress at work (OR = 2.9, P < 0.0001), or had more stress at home (OR = 2.8, P < 0.0001), and were twice as likely to have negative life events (OR = 2.1, P < 0.0001). Women, but not men, with UCP, had a higher prevalence of cardiovascular risk factors (obesity, smoking, diabetes and hypertension) compared with references. With regard to HRQOL, UCP patients scored significantly lower than references in all dimensions of the SF-36. CONCLUSIONS: In comparison with a healthy reference group, patients with UCP reported more sleep problems, mental strain at work, stress at home and negative life events and had lower health-related quality of life. Aside from immigration the strongest independent psychosocial factors were mental strain at work and negative life events last year in men and stress at home in women.
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| 25. |
- Jiye, A, et al.
(författare)
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Extraction and GC/MS analysis of the human blood plasma metabolome
- 2005
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Ingår i: ANALYTICAL CHEMISTRY. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:24, s. 8086-94
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of the entire set of low molecular weight compounds (LMC), the metabolome, could provide deeper insights into mechanisms of disease and novel markers for diagnosis. In the investigation, we developed an extraction and derivatization protocol, using experimental design theory (design of experiment), for analyzing the human blood plasma metabolome by GC/MS. The protocol was optimized by evaluating the data for more than 500 resolved peaks using multivariate statistical tools including principal component analysis and partial least-squares projections to latent structures (PLS). The performance of five organic solvents (methanol, ethanol, acetonitrile, acetone, chloroform), singly and in combination, was investigated to optimize the LMC extraction. PLS analysis demonstrated that methanol extraction was particularly efficient and highly reproducible. The extraction and derivatization conditions were also optimized. Quantitative data for 32 endogenous compounds showed good precision and linearity. In addition, the determined amounts of eight selected compounds agreed well with analyses by independent methods in accredited laboratories, and most of the compounds could be detected at absolute levels of similar to 0.1 pmol injected, corresponding to plasma concentrations between 0.1 and 1 mu M. The results suggest that the method could be usefully integrated into metabolomic studies for various purposes, e.g., for identifying biological markers related to diseases.
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| 26. |
- Johansson, Emil, et al.
(författare)
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Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection
- 2022
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 11:19
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Tidskriftsartikel (refereegranskat)abstract
- Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.
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| 27. |
- Johansson, M., et al.
(författare)
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Few fathers-to-be prefer caesarean section for the birth of their baby
- 2010
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 117:6, s. 761-764
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate prospective fathers' preferences for caesarean section and associated factors. Data were collected by means of a questionnaire given in mid-pregnancy to 1105 fathers-to-be in northern Sweden. In total, 6.4% of fathers preferred a caesarean section. The factors associated with a preference for caesarean section were a wish to plan the date of the baby's birth [prevalence ratio (PR) 6.0], a previous negative birth experience (PR 8.6) and previous experience of a caesarean section (PR 5.7).
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| 28. |
- Jonsson, Pär, et al.
(författare)
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High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses
- 2005
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:17, s. 5635-5642
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Tidskriftsartikel (refereegranskat)abstract
- In metabolomics, the objective is to identify differences in metabolite profiles between samples. A widely used tool in metabolomics investigations is gas chromatography-mass spectrometry (GC/MS). More than 400 compounds can be detected in a single analysis, if overlapping GC/ MS peaks are deconvoluted. However, the deconvolution process is time-consuming and difficult to automate, and additional processing is needed in order to compare samples. Therefore, there is a need to improve and automate the data processing strategy for data generated in GC/MS-based metabolomics; if not, the processing step will be a major bottleneck for high-throughput analyses. Here we describe a new semiautomated strategy using a hierarchical multivariate curve resolution approach that processes all samples simultaneously. The presented strategy generates (after appropriate treatment, e.g., multivariate analysis) tables of all the detected metabolites that differ in relative concentrations between samples. The processing of 70 samples took similar time to that of the GC/TOFMS analyses of the samples. The strategy has been validated using two different sets of samples: a complex mixture of standard compounds and Arabidopsis samples.KeyWords Plus: CHROMATOGRAPHY MASS-SPECTROMETRY; PRINCIPAL COMPONENT ANALYSIS; SYSTEMS BIOLOGY; ARABIDOPSIS-THALIANA; CHEMOMETRIC ANALYSIS; 2-WAY DATA; MS; REGRESSION; RESOLUTION; ALIGNMENT
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| 29. |
- Jägerbrand, Annika K., et al.
(författare)
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Uppdatering och nya effektsamband i effektmodellen för viltolyckor
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Viltolyckor i Sverige är ett växande problem som leder till dödade och skadade personer, liksom skador på fordon och dödade djur. Viltolyckor har samhällsekonomiska kostnader som behöver kvantifieras för att man ska kunna räkna ut kostnadsnyttan av åtgärder som förebygger viltolyckor, såsom exempelvis viltstängsel eller passager. Effektmodellen för viltolyckor utvecklades under 1980-talet och ingår i EVA (effekter vid väganalyser) men är idag till vissa delar föråldrad på grund av utvecklingen som skett avseende trafiksäkerhet, viltolyckssammansättning, datasystem, kunskap och forskning. Den existerande effektmodellen bygger på risk för viltolyckor per km väg per län i tre trafikflödesklasser för älg och summerat ihop för rådjur/ren. Detta projekt har haft som mål att uppdatera effektmodellen för viltolyckor genom att inkludera aktuella data på viltolycksfördelningar och mörkertal, beakta flera viltslag (älg, rådjur, hjort och vildsvin) och involvera flera variabler som kan vara av betydelse för olyckorna: t.ex. viltets populationsstorlek, vägstandard, trafikarbete, hastighet, viltstängsel, landskapstyp och viltets populationsstorlek. Arbetet har delats upp i tre huvudsakliga delar. Den första delen omfattade att ta fram ny kunskap om sambanden mellan viltolyckor, trafikarbete, och viltpopulationer där också landskapsvariabler ingår samt kostnadsberäkningar baserat på olika typer av prognoser på längre sikt. En annan del omfattade att ta fram ny viltolycksstatistik baserat på GIS-analyser för uppdaterade effektsamband för viltolyckor (olycksfrekvens per km väg), ÅDT1 , vägstandard och stängsel samt nya skattningar av mörkertal. Den tredje delen omfattade att ta fram nya värden för skadeföljd och skadekonsekvenser för olika viltslag för 2010–2016. Resultaten från första delen av projektet visar att utifrån ett oförändrat jakttryck kommer viltolyckorna att öka med 12% från 2015 fram till 2030, mestadels på grund av en fördubbling av vildsvinsolyckor medan risken för olycka med älg och rådjur minskar något. Vid minskat jakttryck under samma period visar resultaten att det är teoretiskt möjligt att viltolyckorna istället kommer att öka med 50%. Beräknade kostnader för viltolyckor år 2030 (ASEK 6) varierar mellan 1 707 och 7 556 miljoner kronor beroende på antaganden om jakttryck och skadekostnader. Olyckor med rådjur svarar för den största delen av olyckorna under hela perioden, men olyckor med vildsvin ökar mest under samtliga scenarier. Prognos för kostnadsberäkningar av viltolyckor för Västra Götaland och Skåne inkluderas som exempel. Data från 2010–2016 visar att viltolyckorna ökat mer eller mindre konstant sen 2003 och att ökningen i olyckstal över åren sker med snabbare takt än ökningen i trafikarbetet. På mindre vägar tilltar olycksfrekvenser med ökande trafikarbete fram till en genomsnittlig trafikvolym av omkring 5 000 ÅDT. På större vägar avtar däremot olycksfrekvensen med stigande trafik. Olycksfrekvensen är högst på mellanstora vägar men avtar på trafiktunga vägar och på vägar med hög hastighet. Uppdaterade värden för skadeföljd och skadekonsekvens baserades på uttag ur STRADA2 och NVR3 2010–2016 och endast polisrapporterade olyckor (förutom för RPMI4 värden där även sjukhusrapporter ingick). Skadeföljden visar att dödade och skadade personer i älg- och rådjur/hjortolyckor har minskat och justeringar i de nya värdena har gjorts. För skadekonsekvenser föreslås nya värden för älgolyckor medan föregående värden behållits för rådjur/hjort och även föreslås för vildsvin. Nya värden för skadeföljd föreslås för rådjur/hjort och vildsvin. Slutligen diskuteras antagande i effektmodellen och resultat utifrån trafiksäkerhetsutvecklingen, relevanta viltolycksfrågor, samt några utvalda aspekter inför effektmodellens implementering.
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| 30. |
- Long, Maeve, et al.
(författare)
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DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion
- 2022
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 41
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Tidskriftsartikel (refereegranskat)abstract
- Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated with deferiprone, a therapeutic iron chelator that stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling of lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurred several hours before mitochondrial clearance, with lipid droplets bordering mitochondria upon iron chelation. We demonstrate that DGAT1 inhibition restricts mitophagy in vitro, with impaired lysosomal homeostasis and cell viability. Importantly, genetic depletion of DGAT1 in vivo significantly impaired neuronal mitophagy and locomotor function in Drosophila. Our data define iron depletion as a potent signal that rapidly reshapes metabolism and establishes an unexpected synergy between lipid homeostasis and mitophagy that safeguards cell and tissue integrity.
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| 31. |
- Mansour, Mohammed S.I., et al.
(författare)
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Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer
- 2021
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Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- PD-L1 expression assessed by immunohistochemical staining is used for the selection of immunotherapy in non-small cell lung cancer (NSCLC). Appropriate validation of PD-L1 expression in cytology specimens is important as cytology is often the only diagnostic material in NSCLC. In a previous study comprising two different cohorts of paired biopsies and cytological specimens, we found a fairly good cyto-histological correlation of PD-L1 expression in one, whereas only a moderate correlation was found in the other cohort. Therefore, that cohort with additional new cases was now further investigated for the impact of preanalytical factors on PD-L1 concordance in paired biopsies and cytological specimens. A total of 100 formalin-fixed paraffin-embedded cell blocks from 19 pleural effusions (PE), 17 bronchial brushes (BB), and 64 bronchoalveolar lavage (BAL) and concurrent matched biopsies from 80 bronchial biopsies and 20 transthoracic core biopsies from NSCLC patients were stained using the PD-L1 28-8 assay. Using the cutoffs & GE;1%, & GE;5%, & GE;10%, and & GE;50% positive tumour cells, the overall agreement between histology and cytology was 77-85% (kappa 0.51-0.70) depending on the applied cutoff value. The concordance was better for BALs (kappa 0.53-0.81) and BBs (kappa 0.55-0.85) than for PEs (kappa -0.16-0.48), while no difference was seen for different types of biopsies or histological tumour type. A high number of tumour cells (> 500) in biopsies was associated with better concordance at the & GE;50% cutoff. In conclusion, the study results suggest that PEs may be less suitable for evaluation of PD-L1 due to limited cyto-histological concordance, while a high amount of tumour cells in biopsies may be favourable when regarding cyto-histological PD-L1 concordance.
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| 32. |
- Nordin, Viviann, et al.
(författare)
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Gangliosides in cerebrospinal fluid in children with autism spectrum disorders.
- 1998
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 40:9, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.
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| 33. |
- Sjölander, Johan, et al.
(författare)
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Circadian clock components control growth and gibberellin metabolism in Populus trees
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This study investigates the role of the circadian clock in the regulation of gibberellin (GA) metabolism and growth in hybrid aspen (Populus tremula x P. tremuloides (Ptt)). We revealed a conserved function of the clock homolog PttEARLY BIRD1 (PttEBI1), but also implicated its rolein controlling tree growth. GA metabolite profiling and transcriptomic analysis in hybrid aspenlines with modulated expression of PttEBI1 or the core clock homologs PttLATE ELONGATED HYPOCOTYLs (PttLHYs) revealed significant changes in GA metabolism. These alterations werelinked to the differential expression of PttGA2ox8, a gene encoding an enzyme with both GA2-oxidase and GA20-oxidase activities. Our results indicate that modifications to circadian clockcomponents can significantly influence both GA metabolism and tree growth, providing potential strategies for improving tree biomass production.
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| 34. |
- Vandenput, Liesbeth, 1974, et al.
(författare)
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Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan
- 2022
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:10, s. 2103-2136
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Forskningsöversikt (refereegranskat)abstract
- Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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| 35. |
- Wallner, Fredrik K., et al.
(författare)
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Solid-phase synthesis of serine-based glycosphingolipid analogues for preparation of glycoconjugate arrays
- 2005
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Ingår i: Organic and biomolecular chemistry. - London : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 3:2, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic glycolipids with defined structures are important tools in the study of glycolipid biology. In this paper we describe a solid-phase synthesis of three galactosylated serine-based glycosphingolipid analogues using the novel linker 2-fluoro-4-(hydroxymethyl)-phenoxyacetic acid. Gel-phase 19F-NMR spectroscopy was used to measure the yield and stereochemical outcome of the solid-phase glycosylations. Under NIS–TfOH promotion, α- and β-selective glycosylations were performed at room temperature with thioglycoside donors carrying fluorine labelled protective groups. Finally, the glycolipids were covalently linked to microtiter plates and labelled lectins with different selectivity for α- and β-galactosides could bind to the glycolipid arrays.
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| 36. |
- Yammine, S.G., et al.
(författare)
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Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition
- 2023
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Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons.Results: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5−Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk.Conclusion: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
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| 37. |
- Yannuzzi, M., et al.
(författare)
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TEFIS: A Single Access Point for Conducting Multifaceted Experiments on Heterogeneous Test Facilities
- 2014
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Ingår i: Computer Networks. - : Elsevier BV. - 1389-1286 .- 1872-7069. ; 63, s. 147-172
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Tidskriftsartikel (refereegranskat)abstract
- A few years ago, an experimental facility composed of networking gear and simulation tools was sufficient for testing the main features of a prototype before the final product could be launched to the Internet market. This paradigm has certainly changed, but the lack of platforms enabling the realistic assessment of the different facets of a product, including cross-cutting trials across different testbeds, poses strong limitations for researchers and developers. In light of this, we present an open platform that offers a versatile combination of heterogeneous experimental facilities called “TEstbed for Future Internet Services” (TEFIS). TEFIS provides a single access point for conducting cutting-edge experiments on testbeds that supply different capabilities, including testbeds dedicated to network performance, software performance, grid computing, and living labs. We shall show that TEFIS covers the entire life-cycle of a multifaceted experiment, with the advantage that a single testrun can seamlessly execute across different experimental facilities. In order to demonstrate the potential and versatility of the TEFIS platform, we describe the deployment of four distinct experiments and provide a set of results highlighting the benefits of using TEFIS. The experiments described in this article cover: i) the experimentation with an open API called OPENER (which is an open and programmable environment for managing experimentation with SDN applications); ii) an application for skiers and tourists at the Megève ski resort in France; iii) an application that can dynamically adapt the Quality of Experience (QoE) of multimedia services for mobile users; and iv) an augmented reality workspace for remote education and learning purposes based on videoconferencing.
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