| 1. |
- Graff, M., et al.
(author)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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In: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Journal article (peer-reviewed)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 2. |
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| 3. |
- Wang, Z., et al.
(author)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Journal article (peer-reviewed)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 4. |
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| 5. |
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| 6. |
- Willems, S. M., et al.
(author)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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| 7. |
- Scott, Robert A, et al.
(author)
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No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
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In: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
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Journal article (peer-reviewed)abstract
- Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
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| 8. |
- Speakman, John R., et al.
(author)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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In: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Journal article (other academic/artistic)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 9. |
- Ekelund, U., et al.
(author)
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Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women : the EPIC-InterAct Study
- 2012
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:7, s. 1944-1952
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Journal article (peer-reviewed)abstract
- We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.
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| 10. |
- Garcia, L, et al.
(author)
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Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies
- 2023
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In: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 57:15, s. 979-
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Journal article (peer-reviewed)abstract
- To estimate the dose–response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population.DesignSystematic review and cohort-level dose-response meta-analysis.Data sourcesPubMed, Scopus, Web of Science and reference lists of published studies.Eligibility criteriaProspective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney).Results196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted.ConclusionsInverse non-linear dose–response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults.PROSPERO registration numberCRD42018095481.
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| 11. |
- Thomassen, Mads, et al.
(author)
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Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
- 2022
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 43:12, s. 1921-1944
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Journal article (peer-reviewed)abstract
- Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
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| 12. |
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| 13. |
- Brito, Ema C, 1961-, et al.
(author)
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PPARGC1A sequence variation and cardiovascular risk-factor levels : a study of the main genetic effects and gene x environment interactions in children from the European youth heart study
- 2009
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 52:4, s. 609-613
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription factors involved in cellular energy metabolism and vascular stasis. In the present study, we genotyped 35 tagging polymorphisms to capture all common PPARGC1A nucleotide sequence variations and tested for association with metabolic and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the European Youth Heart Study, a multicentre school-based cross-sectional cohort study. METHODS: Fasting plasma glucose concentrations, anthropometric variables and blood pressure were measured. Habitual physical activity and aerobic fitness were objectively assessed using uniaxial accelerometry and a maximal aerobic exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted models, nominally significant associations were observed for BMI (rs10018239, p = 0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p = 0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose concentrations (rs11724368, p = 0.045). Stronger associations were observed for aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose concentrations (rs7657071, p = 0.002). None remained significant after correcting for the number of statistical comparisons. We proceeded by testing for gene x physical activity interactions for the polymorphisms that showed nominal evidence of association in the main effect models. None of these tests was statistically significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence several metabolic traits in this European paediatric cohort. However, variation at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic health in these children.
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| 14. |
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| 15. |
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| 16. |
- Franks, Paul, et al.
(author)
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Physical activity energy expenditure may mediate the relationship between plasma leptin levels and worsening insulin resistance independently of adiposity.
- 2007
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In: J Appl Physiol. - : American Physiological Society. - 8750-7587. ; 102:5, s. 1921-6
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Journal article (peer-reviewed)abstract
- Leptin regulates a constellation of neuroendocrine processes that control energy homeostasis. The infusion of leptin in rodents lacking endogenous leptin promotes physical activity energy expenditure (PAEE) and improves insulin signaling, whereas hyperleptinemia is associated with physical inactivity and insulin resistance (IR). We tested whether baseline leptin levels predict changes in PAEE and IR over time, independent of obesity. We also assessed whether the relationship between leptin and change in IR is mediated by PAEE. The population consisted of 288 nondiabetic UK Caucasian adults (mean age: 49.4 yr; SD: 0.7 yr), in whom leptin, insulin, glucose, PAEE (via heart rate monitoring with individual calibration by indirect calorimetry), and anthropometric characteristics had been measured at baseline and 5 yr later. In linear regression models, baseline leptin levels inversely predicted follow-up PAEE ( P = 0.033). On average, individuals with low leptin levels (below sex-specific median) increased their daily activity 35% more during the 5-yr follow-up period than those with above-median leptin levels. Baseline leptin level also predicted worsening IR (fasting, 30-min, and 2-h insulins, and homeostasis model assessment-IR; all P < 0.01). Associations were independent of potential confounders, such as adiposity, age, and sex. Including baseline PAEE as a cofactor in the leptin-insulin models reduced the strength (1–4% reduction) and significance of the associations, suggesting that PAEE mediates the leptin-insulin relationships. Hyperleptinemia predicts a relative decline in PAEE and worsening insulin resistance, possibly via shared molecular pathways.
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| 17. |
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| 18. |
- Goharian, T S, et al.
(author)
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Examining the causal association of fasting glucose with blood pressure in healthy children and adolescents: a Mendelian randomization study employing common genetic variants of fasting glucose.
- 2015
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In: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 29:3, s. 179-184
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Journal article (peer-reviewed)abstract
- The aim of the study was to determine whether genetically raised fasting glucose (FG) levels are associated with blood pressure (BP) in healthy children and adolescents. We used 11 common genetic variants of FG discovered in genome-wide association studies (GWAS), including the rs560887 single-nucleotide polymorphism (SNP) located in the G6PC2 locus found to be robustly associated with FG in children and adolescents, as an instrument to associate FG with resting BP in 1506 children and adolescents from the European Youth Heart Study (EYHS). Rs560887 was associated with increased FG levels corresponding to an increase of 0.08 mmol l(-1) (P=2.4 × 10(-8)). FG was associated with BP, independent of other important determinants of BP in conventional multivariable analysis (systolic BP z-score: 0.32 s.d. per increase in mmol l(-1) (95% confidence interval (CI) 0.20-0.44, P=1.9 × 10(-7)), diastolic BP z-score: 0.13 s.d. per increase in mmol l(-1) (95% CI 0.04-0.21, P=3.2 × 10(-3)). This association was not supported by the Mendelian randomization approach, neither from instrumenting FG from all 11 variants nor from the rs560887, where non-significant associations of glucose with BP were observed. The results of this study could not support a causal association between FG and BP in healthy children and adolescents; however, it is possible that rs560887 has pleiotropic effects on unknown factors with a BP lowering effect or that these results were due to a lack of statistical power.Journal of Human Hypertension advance online publication, 31 July 2014; doi:10.1038/jhh.2014.63.
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| 19. |
- Guo, X. L., et al.
(author)
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Calculations with spectroscopic accuracy for the ground configuration (3d(9)) forbidden transition in Co-like ions
- 2016
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In: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 93:1
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Journal article (peer-reviewed)abstract
- We present systematic and large-scale calculations for the fine-structure energy splitting and transition rate between the 3d(9) D-2(3/2,5/2) levels of Co-like ions with 28 <= Z <= 100. Two different fully relativistic approaches are used, based on the multiconfiguration Dirac-Hartree-Fock (MCDHF) theory and the relativistic many-body-perturbation theory (RMBPT). Especially the former gives results of similar accuracy as experiments for a large range of ions. Our calculations are therefore accurate enough to probe Breit and quantum-electro-dynamic effects. To obtain spectroscopic accuracy, we show that it is important to include deep core-valence correlation, down to and including the n = 2 shell. We estimate that the uncertainties of our wavelengths are within the uncertainty of experiments, i.e., 0.02%. We also show that the frequently used flexible atomic code has an inaccurate treatment of the self-energy (SE) contribution and of the M1-transition properties for lower-Z ions. After correcting for the SE calculation, the resulting RMBPT transition energies are in good agreement with the MCDHF ones, especially for the high-Z end of the Co-like sequence.
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| 20. |
- Koivula, Robert W., et al.
(author)
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The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes : an IMI DIRECT study
- 2020
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In: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 63:4, s. 744-756
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.
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| 21. |
- Olsen, Rikke K J, et al.
(author)
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ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.
- 2007
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 130:Pt 8, s. 2045-54
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Journal article (peer-reviewed)abstract
- Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid, amino acid and choline metabolism that can result from defects in two flavoproteins, electron transfer flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETF:QO). Some patients respond to pharmacological doses of riboflavin. It is unknown whether these patients have defects in the flavoproteins themselves or defects in the formation of the cofactor, FAD, from riboflavin. We report 15 patients from 11 pedigrees. All the index cases presented with encephalopathy or muscle weakness or a combination of these symptoms; several had previously suffered cyclical vomiting. Urine organic acid and plasma acyl-carnitine profiles indicated MADD. Clinical and biochemical parameters were either totally or partly corrected after riboflavin treatment. All patients had mutations in the gene for ETF:QO. In one patient, we show that the ETF:QO mutations are associated with a riboflavin-sensitive impairment of ETF:QO activity. This patient also had partial deficiencies of flavin-dependent acyl-CoA dehydrogenases and respiratory chain complexes, most of which were restored to control levels after riboflavin treatment. Low activities of mitochondrial flavoproteins or respiratory chain complexes have been reported previously in two of our patients with ETF:QO mutations. We postulate that riboflavin-responsive MADD may result from defects of ETF:QO combined with general mitochondrial dysfunction. This is the largest collection of riboflavin-responsive MADD patients ever reported, and the first demonstration of the molecular genetic basis for the disorder.
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| 22. |
- Ridgway, C. L., et al.
(author)
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Fat-free mass mediates the association between birth weight and aerobic fitness in youth
- 2011
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In: International Journal of Pediatric Obesity. - : Informa UK Limited. - 1747-7166 .- 1747-7174. ; 6:2-2, s. E590-E596
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Journal article (peer-reviewed)abstract
- Objective. To investigate whether birth weight acts as a biological determinant of later aerobic fitness, and whether fat-free mass may mediate this association. Methods. The European Youth Heart Study (EYHS) is a population-based cohort of two age groups (9 and 15 years) from Denmark, Portugal, Estonia and Norway. Children with parentally reported birth weight >1.5 kg were included (n = 2 749). Data were collected on weight, height, and skinfold measures to estimate fat mass and fat-free mass. Aerobic fitness (peak power, watts) was assessed using a maximal, progressive cycle ergometer test. Physical activity was collected in a subset (n = 1 505) using a hip-worn accelerometer and defined as total activity counts/wear time, all children with >600 minutes/day for >= 3 days of wear were included. Results. Lower birth weight was associated with lower aerobic fitness, after adjusting for sex, age group, country, sexual maturity and socio-economic status (beta = 5.4; 95% CI: 3.5, 7.3 W per 1 kg increase in birth weight, p < 0.001). When fat-free mass was introduced as a covariate in the model, the association between birth weight and aerobic fitness was almost completely attenuated (p = 0.7). Birth weight was also significantly associated with fat-free mass (beta = 1.4; 95% CI: 1.1, 1.8, p < 0.001) and fat-free mass was significantly associated with aerobic fitness (beta = 3.6; 95% CI: 3.4, 3.7, p < 0.001). Further adjustment for physical activity did not alter the findings. Conclusion. Birth weight may have long-term influences on fat-free mass and differences in fat-free mass mediate the observed association between birth weight and aerobic fitness.
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| 23. |
- Svedman, F. C., et al.
(author)
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Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
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Journal article (peer-reviewed)abstract
- Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Meth-ods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients’ baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20–1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08–3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25–4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 24. |
- Tobin, N. P., et al.
(author)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Journal article (peer-reviewed)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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| 25. |
- Watts, Eleanor L., et al.
(author)
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Observational and genetic associations between cardiorespiratory fitness and cancer : a UK Biobank and international consortia study
- 2024
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130, s. 114-124
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Journal article (peer-reviewed)abstract
- Background: The association of fitness with cancer risk is not clear.Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
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| 26. |
- Allesøe, Rosa Lundbye, et al.
(author)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
-
In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
-
Journal article (peer-reviewed)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 27. |
- Andersson, Lena, 1965, et al.
(author)
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Can access to psychiatric health care explain regional differences in disability pension with psychiatric disorders?
- 2007
-
In: Soc Psychiatry Psychiatr Epidemiol. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 42:5, s. 366-71
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Psychiatric disorders are a serious public health problem, especially as many psychiatric disorders begin early in life. Disability pension (DP) with psychiatric diagnoses has, since the mid 1990s, increased in several European countries and regional differences within countries have emerged. It is not clear whether these regional differences are associated with differences in access to psychiatric health care. AIM: The aim of this study was to investigate whether regional differences in DP with psychiatric diagnoses in Norway were associated with differences in psychiatric service provision (the number of staff employed and psychiatric beds available). METHOD: The study population consisted of individuals aged 16-67 years living in Norway (n = 4,348,410) and six southern regions. Included cases were individuals who were granted a DP with a psychiatric diagnosis between 1 January and 31 December 1990, 1995 or 2000. Mental retardation was excluded. Data on cases were collected from the National Insurance Administration and data on psychiatric health care staff and beds was collected from Specialist Health Service, Statistics Norway. Regression models were used to calculate incidence rate ratios (IRR) with 95% confidence intervals (CI) using Norway as reference. RESULTS: Staffing levels (per 10,000 inhabitants) did not differ substantially between the regions, with the exception of Oslo that had about 70% higher numbers of staff employed. In regression analyses controlling for numbers of psychiatric staff and beds, regional differences in DP remained. Both men and women in the semi rural regions Aust-Agder and Vest-Agder were significantly more likely to receive a DP with a psychiatric diagnosis, while the IRR for DP was reduced in Ostfold. Different psychiatric staff groups were associated with increased or decreased rates of DP. The adjusted IRR between number of psychiatric staff (man-years of staff per 10,000 inhabitants) and DP with psychiatric diagnoses were: 1.23 (1.18-1.29) for psychologists, 1.13 (1.04-1.23) for physicians, 1.03 (1.00-1.07) for nurses and 0.84 (0.80-0.88) for auxiliary nurses. Furthermore, increased numbers of beds were associated with DP with a psychiatric diagnosis (IRR 2.86 (2.03-4.05) for 100 beds/10,000 population). CONCLUSION: Psychiatric provision (in terms of both staff and beds) was associated with the incidence of DP with psychiatric diagnoses but regional differences in provision did not explain the regional differences in DP with a psychiatric diagnosis. Future work needs to examine whether differences in case detection and case management are associated with regional differences in DP with psychiatric diagnoses.
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| 28. |
- Andersson, Lena, 1965, et al.
(author)
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Disability pension for psychiatric disorders: Regional differences in Norway 1988-2000
- 2006
-
In: Nord J Psychiatry. ; 60:4, s. 255-62
-
Journal article (peer-reviewed)abstract
- The aim of this study was to describe regional differences in the incidence of disability pensions (DPs) with psychiatric diagnoses, and to determine whether these differences were related to age and/or gender. We compared the incidence rates of new DPs including all diagnoses, with DP with psychiatric diagnoses in Norwegian regions from 1988 to 2000. The population at risk was all individuals aged 16-67 in each year. Individuals already on DP were excluded. Cases were collected from the Norwegian National Insurance Administration. The results showed that the incidence rate ratio (IRR; Norway reference) for DP with psychiatric diagnoses was most elevated for men 1.41 (95% CI 1.27-1.58) and women 1.48 (95% CI 1.34-1.64) living in the most rural region. Men in the urban area had a higher IRR, 1.33 (95% CI 1.26-1.40), than urban women, 1.02 (95% CI 0.96-1.07). The incidence more than doubled in the youngest age group (16-29 years) and decreased in the oldest age group (60-67 years) between 1988 and 2000. The findings conclude that individuals living in semi-rural regions of Norway are more likely to receive a DP with a psychiatric diagnosis than those living in urban areas. Large gender differences were found in the urban area. Further research is needed to investigate the impact of the psychiatric healthcare system and access to rehabilitation on psychiatric disability.
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| 29. |
- Azimi, A, et al.
(author)
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Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in melanoma cells
- 2017
-
In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 8:8, s. e3029-
-
Journal article (peer-reviewed)abstract
- A majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines. In addition, increased levels of the previously reported resistance mediators, receptor tyrosine kinase ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were also identified. The expression of these proteins was assessed in matched tumor samples from melanoma patients obtained before BRAFi and after disease progression. MET was overexpressed in all progression samples while the expression of the other candidates varied between the individual patients. Targeting CD13/ANPEP by a blocking antibody induced apoptosis in both parental A375- and BRAFi-resistant daughter cells as well as in melanoma cells with intrinsic BRAFi resistance and led to dephosphorylation of EPHA2 on S897, previously demonstrated to cause inhibition of the migratory capacity. AKT and RSK, both reported to induce EPHA2 S897 phosphorylation, were also dephosphorylated after inhibition of CD13/ANPEP. FLI1 silencing also caused decreases in EPHA2 S897 phosphorylation and in total MET protein expression. In addition, silencing of FLI1 sensitized the resistant cells to BRAFi. Furthermore, we show that BRAFi in combination with the multi kinase inhibitor dasatinib can abrogate BRAFi resistance and decrease both EPHA2 S897 phosphorylation and total FLI1 protein expression. This is the first report presenting CD13/ANPEP and FLI1 as important mediators of resistance to BRAF inhibition with potential as drug targets in BRAFi refractory melanoma.
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| 30. |
- Azimi, Alireza, et al.
(author)
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Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors
- 2018
-
In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 14:3
-
Journal article (peer-reviewed)abstract
- Novel therapies are undergoing clinical trials, for example, the Hsp90 inhibitor, XL888, in combination with BRAF inhibitors for the treatment of therapy-resistant melanomas. Unfortunately, our data show that this combination elicits a heterogeneous response in a panel of melanoma cell lines including PDX-derived models. We sought to understand the mechanisms underlying the differential responses and suggest a patient stratification strategy. Thermal proteome profiling (TPP) identified the protein targets of XL888 in a pair of sensitive and unresponsive cell lines. Unbiased proteomics and phosphoproteomics analyses identified CDK2 as a driver of resistance to both BRAF and Hsp90 inhibitors and its expression is regulated by the transcription factor MITF upon XL888 treatment. The CDK2 inhibitor, dinaciclib, attenuated resistance to both classes of inhibitors and combinations thereof. Notably, we found that MITF expression correlates with CDK2 upregulation in patients; thus, dinaciclib would warrant consideration for treatment of patients unresponsive to BRAF-MEK and/or Hsp90 inhibitors and/or harboring MITF amplification/overexpression.
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| 31. |
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| 32. |
- Bizzotto, Roberto, et al.
(author)
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Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study
- 2021
-
In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:2, s. 511-518
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Dussex, Nicolas, et al.
(author)
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Adaptation to the High-Arctic island environment despite long-term reduced genetic variation in Svalbard reindeer
- 2023
-
In: iScience. - 2589-0042. ; 26:10
-
Journal article (peer-reviewed)abstract
- Typically much smaller in number than their mainland counterparts, island populations are ideal systems to investigate genetic threats to small populations. The Svalbard reindeer (Rangifer tarandus platyrhynchus) is an endemic subspecies that colonized the Svalbard archipelago ca. 6,000–8,000 years ago and now shows numerous physiological and morphological adaptations to its arctic habitat. Here, we report a de-novo chromosome-level assembly for Svalbard reindeer and analyze 133 reindeer genomes spanning Svalbard and most of the species’ Holarctic range, to examine the genomic consequences of long-term isolation and small population size in this insular subspecies. Empirical data, demographic reconstructions, and forward simulations show that long-term isolation and high inbreeding levels may have facilitated the reduction of highly deleterious—and to a lesser extent, moderately deleterious—variation. Our study indicates that long-term reduced genetic diversity did not preclude local adaptation to the High Arctic, suggesting that even severely bottlenecked populations can retain evolutionary potential.
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| 37. |
- Fei, Z., et al.
(author)
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Forbidden-line spectroscopy of the ground-state configuration of Cd-like W
- 2014
-
In: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 90:5
-
Journal article (peer-reviewed)abstract
- only using electric-dipole forbidden emission lines, in what we label forbidden-line spectroscopy, we identified several energy levels in cadmium-like tungsten, W26+. The spectrum was recorded at the Shanghai permanentmagnet electron beam ion trap in the visible region. The identifications were supported by large-scale multiconfiguration Dirac-Hartree-Fock calculations which involved careful investigations of core-valence and core-core correlation effects, and by relativistic many-body perturbation theory calculations. With this novel method we identified in all seven lines and measured their wavelengths. From this we can determine the relative position of seven energy levels. Due to the close degeneracy of two levels, we give alternative energies for three of the levels.
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| 38. |
- Fortuin-de Smidt, Melony C., et al.
(author)
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Physical activity attenuates but does not eliminate coronary heart disease risk amongst adults with risk factors : EPIC-CVD case-cohort study
- 2022
-
In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 29:12, s. 1618-1629
-
Journal article (peer-reviewed)abstract
- AIMS: This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors.METHODS AND RESULTS: EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal).Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32-64%] and 21% (95%CI 2-44%), with hypercholesterolaemia were 80% (95%CI 55-108%) and 48% (95%CI 22-81%), with hypertension were 80% (95%CI 65-96%) and 49% (95%CI 28-74%), with diabetes were 142% (95%CI 63-260%), and 100% (95%CI 32-204%), and amongst smokers were 152% (95%CI 122-186%) and 109% (95%CI 74-150%).CONCLUSIONS: In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.
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| 39. |
- Haapala, E. A., et al.
(author)
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Associations of physical activity, sedentary time, and diet quality with biomarkers of inflammation in children
- 2022
-
In: European Journal of Sport Science. - : Informa UK Limited. - 1746-1391 .- 1536-7290. ; 22:6, s. 906-915
-
Journal article (peer-reviewed)abstract
- We investigated the associations of physical activity (PA), sedentary time (ST), and diet quality with biomarkers of inflammation in 390 children (192 girls, 198 boys) aged 6–8 years. PA energy expenditure (PAEE), light PA, moderate PA (MPA), vigorous PA (VPA), moderate-to-vigorous PA (MVPA), and ST were assessed by combined movement and heart rate sensor. Finnish Children Healthy Eating Index was calculated using data from 4 d food records. Body fat percentage (BF%) was measured by dual-energy X-ray absorptiometry. High-sensitivity C-reactive protein (Hs-CRP), leptin, interleukin-6 (IL-6), adiponectin, tumour necrosis factor-α, and glycoprotein acetyls were measured from fasting blood samples. PAEE, MPA, VPA, and MVPA were inversely associated with hs-CRP (β=−191 to −139, 95% CI=−0.294 to −0.024), leptin (β=−0.409 to −0.301, 95% CI=−0.499 to −0.107), IL-6 (β=−0.136 to −0.104, 95% CI=−0.240 to −0.001) and PAEE, MPA, and MVPA were inversely associated with glycoprotein acetyls (β=−0.117 to −0.103, 95% CI=−0.213 to −0.001). ST was directly associated with hs-CRP (β=0.170, 95% CI=0.070–0.269), leptin (β=0.355, 95% CI=0.265–0.445), and IL-6 (β=0.105, 95% CI=0.005–0.205). VPA was inversely associated with hs-CRP, leptin, and IL-6 in children with higher BF% (β=−0.344 to −0.181, 95% CI=−0.477 to −0.033) but not among children with lower BF% (β=−0.007–0.033, 95% CI=−0.183–0.184). In conclusion, PA was inversely and ST directly associated with circulating levels of biomarkers of inflammation among children. Furthermore, we observed that PA was inversely associated with these biomarkers for inflammation in children with a higher BF%. Highlights Systemic inflammation, as indicated by increased circulating concentrations of biomarkers for inflammation, may be important in causal pathways leading to insulin resistance, sub-clinical atherosclerosis, and eventually clinical manifestations of cardiovascular diseases. Higher levels of physical activity and lower levels of sedentary time were associated with more favourable inflammatory profile. Body fat percentage modified these associations and especially vigorous intensity physical activity was inversely associated with biomarkers of inflammation on children with higher body fat percentage but not in children with lower body fat percentage.
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| 40. |
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| 41. |
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| 42. |
- Hensing, Gunnel, 1956, et al.
(author)
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Increase in sickness absence with psychiatric diagnosis in Norway: a general population-based epidemiologic study of age, gender and regional distribution
- 2006
-
In: BMC Med. - : Springer Science and Business Media LLC. - 1741-7015. ; 4
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to assess the incidence of sickness absence with psychiatric diagnoses from 1994-2000, and the distribution across gender, age groups, diagnostic groups and regions in a general population. METHODS: The population at risk was defined as all individuals aged 16-66 years who were entitled to sickness benefits in 1994, 1996, 1998 and 2000 (n = 2,282,761 in 2000). All individuals with a full-time disability pension were excluded. The study included approximately 77% of the Norwegian population aged 16-66 years. For each year, the study base started on 1 January and ended on 31 December. Individuals that were sick-listed for more than 14/16 consecutive days with a psychiatric diagnosis on their medical certificate were selected as cases. Included in this study were data for Norway, the capital city Oslo and five regions in the southeast of the country. RESULTS: Sickness absence with psychiatric diagnoses increased in all age groups, in women and men, and in all regions. At the national level, the cumulative incidence increased in women from 1.7% in 1994 to 4.6% in 2000, and in men from 0.8% in 1994 to 2.2% in 2000. The highest cumulative incidence was found in middle-aged women and men (30-59 years). Women had a higher incidence than men in all stratification groups. The cumulative incidences in 2000 varied between 4.6% to 5.6% in women in the different regions, and for men the corresponding figures were 2.1% to 3.2%. Throughout the four years studied, women in Oslo had more than twice as high incidence levels of sickness absence with alcohol and drug diagnoses as the country as a whole. There were some differences between regions in sickness absence with specific psychiatric diagnoses, but they were small and most comparisons were non-significant. CONCLUSION: Sickness absence with psychiatric diagnoses increased between 1994 and 2000 in Norway. The increase was highest in the middle-aged, and in women. Few regional differences were found. That the increase pervaded all stratification groups supports general explanations of the increase, such as changes in attitudes to psychiatric disorders in both patients and doctors, and increased mental distress probably associated with societal changes at a more structural level.
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| 43. |
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| 44. |
- Ihlebaek, C., et al.
(author)
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Prevalence of low back pain and sickness absence: a "borderline" study in Norway and Sweden
- 2006
-
In: Scand J Public Health. - 1403-4948. ; 34:5, s. 555-8
-
Journal article (peer-reviewed)abstract
- AIMS: Low back pain (LBP) is a major public health problem in both Norway and Sweden. The aim of the study was to estimate the prevalence of LBP and sickness absence due to LBP in two neighbouring regions in Norway and Sweden. The two areas have similar socioeconomic status, but differ in health benefit systems. METHODS: A representative sample of 1,988 adults in Norway and 2,006 in Sweden completed questionnaires concerning LBP during 1999 and 2000. For this study only individuals in part or full time jobs, (n = 1,158 in Norway and n = 1,129 in Sweden) were included. RESULTS: In Norway the lifetime prevalence was 60.7% and in Sweden 69.6%, the one-year prevalence was 40.5% and 47.2%, and the point prevalence 13.4% and 18.2% respectively. There was a significantly higher risk of reporting LBP in Sweden, even after controlling for gender, age, education, and physical workload. There was no difference in risk of self-certified short-term sickness absence (1-3 days), but it was a 40% lower risk of sickness absence with medical sickness certification in Sweden compared with Norway. CONCLUSION: The prevalence of LBP was higher in the Swedish area than in the Norwegian. The risk of self-certified sickness absence, however, showed no differences and the risk of medically certified sickness absence was lower in the Swedish area. This contradiction might partly be explained by the economical "disincentives" in the Swedish health compensation system.
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| 45. |
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| 46. |
- Keenan, FP, et al.
(author)
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The O IV and S IV intercombination lines in the ultraviolet spectra of astrophysical sources
- 2002
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 337:3, s. 901-909
-
Journal article (peer-reviewed)abstract
- New electron density diagnostic line ratios are presented for the O IV 2s(2)2p P-2-2s2p(24)P and S IV 3s(2)3p P-2-3s3p(24)P intercombination lines around 1400 Angstrom comparison of these with observational data for the symbiotic star RR Telescopii (RR Tel), obtained with the Space Telescope Imaging Spectrograph (STIS), reveals generally very good agreement between theory and observation. However the S IV P-2(3/2)-P-4(1/2) transition at 1423.824 Angstrom is found to be blended with an unknown feature at 1423.774 Angstrom. The linewidth for the latter indicates that the feature arises from a species with a large ionization potential. In addition, the S IV P-2(1/2)-P-4(3/2) transition at 1398.044 Angstrom is identified for the first time (to our knowledge) in an astrophysical source other than the Sun, and an improved wavelength of 1397.166 Angstrom is measured for the O IV P-2(1/2)-P-4(3/2) line. The O IV and S IV line ratios in a sunspot plume spectrum, obtained with the Solar Ultraviolet Measurements of the Emitted Radiation (SUMER) instrument on the Solar and Heliospheric Observatory, are found to be consistent, and remove discrepancies noted in previous comparisons of these two ions.
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| 47. |
- Kilpeläinen, Tuomas O, et al.
(author)
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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
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In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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| 48. |
- Kohli, S, et al.
(author)
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Childhood leukaemia in areas with different radon levels : A spatial and temporal analysis using GIS
- 2000
-
In: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 54:11, s. 822-826
-
Journal article (peer-reviewed)abstract
- Objectives-To evaluate the relation between exposure to ground radon levels and leukaemia among children using existing population and disease registers. Design-Ecological correlation study. Setting-The county of Ostergotland in Sweden. Methods-Every child born in the county between 1979 and 1992 was mapped to the property centroid coordinates by linking addresses in the population and property registers. Population maps were overlaid with radon maps and exposure at birth and each subsequent year was quantified as high, normal, low or unknown. This was analysed with data from the tumour registry. Standardised mortality ratios (SMRs) were calculated using the age and sex specific rates for Sweden for the year 1995. Results-90 malignancies occurred among 53 146 children (498 887 person years) who formed the study population. SMRs for acute lymphatic leukemia (ALL) among children born in high, normal and low risk areas were 1.43, 1.17 and 0.25 respectively. The relative risk for the normal risk group and high risk group as compared with the low risk group was 4.64 (95% CI 1.29, 28.26) and 5.67 (95% CI 1.06, 42.27). The association between ALL and continued residence at normal or high risk areas showed a similar trend. No association between radon risk levels and any other malignancy was seen. Conclusion-Children born in and staying at areas where the risk from ground radon has been classified as low are less likely to develop ALL than those born in areas classified as normal and high risk.
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| 49. |
- Kristiansson, Moa K., et al.
(author)
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Experimental and theoretical studies of excited states in Ir
- 2021
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In: Physical Review A. - : American Physical Society. - 2469-9926 .- 2469-9934. ; 103:6
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Journal article (peer-reviewed)abstract
- The properties of atomic negative ions are to a large extent determined by electron-electron correlation which makes them an ideal testing ground for atomic many-body physics. In this paper, we present a detailed experimental and theoretical study of excited states in the negative ion of iridium. The ions were stored at cryogenic temperatures using the double electrostatic ion ring experiment facility at Stockholm University. Laser photodetachment was used to monitor the relaxation of three bound excited states belonging to the [Xe] 4f(14)5d(8)6s(2) ionic ground configuration. Our measurements show that the first excited state has a lifetime much longer than the ion-beam storage time of 1230 +/- 100 s. The binding energy of this state was measured to be 1.045 +/- 0.002 eV. The lifetimes of the second and third excited states were experimentally determined to be 133 +/- 10 and 172 +/- 35 ms, respectively. Multiconfiguration Dirac-Hartree-Fock calculations were performed in order to extract binding energies and lifetimes. These calculations predict the existence of the third excited bound state that was detected experimentally. The computed lifetimes for the three excited bound states agree well with the experimental results and allow for a clear identification of the detected levels.
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| 50. |
- Li, W., et al.
(author)
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Investigation of M1 transitions of the ground-state configuration of In-like tungsten
- 2016
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In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 49:10
-
Journal article (peer-reviewed)abstract
- Three visible lines of M1 transitions from In-like tungsten were recorded using the Shanghai Permanent Magnet Electron Beam Ion Trap. The experimental wavelengths were measured as 493.84 ± 0.15, 226.97 ± 0.13 and 587.63 ± 0.23 nm (vacuum wavelengths). These results are in good agreement with theoretical predictions obtained using the large-scale relativistic many-body perturbation theory, in the form of the flexible atomic code.
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