| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 4. |
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| 5. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 6. |
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| 7. |
- Sakatani, N., et al.
(författare)
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Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
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Ingår i: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Laguzzi, F., et al.
(författare)
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Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease : Pooled De Novo Results From 15 Observational Studies
- 2024
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 149:4, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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| 14. |
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| 15. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 16. |
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| 17. |
- Vissers, L.E.T., et al.
(författare)
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Milk intake and incident stroke and coronary heart disease in populations of European descent : a mendelian randomization study
- 2022
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 128:9, s. 1789-1797
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Tidskriftsartikel (refereegranskat)abstract
- Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.
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| 18. |
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| 19. |
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| 20. |
- Harris, WS, et al.
(författare)
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Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2329-
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Tidskriftsartikel (refereegranskat)abstract
- The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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| 21. |
- Ibsen, Daniel B, et al.
(författare)
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Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations : The EPIC-InterAct Study
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:11, s. 2660-2667
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.RESULTS: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat `(50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.CONCLUSIONS: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
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| 22. |
- Lai, Heidi T. M., et al.
(författare)
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Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes : Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE)
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:4, s. 854-863
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >= 18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P >= 0.1).CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.
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| 23. |
- O'Keefe, James H., et al.
(författare)
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Omega-3 Blood Levels and Stroke Risk : A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies
- 2024
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 55:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The effect of marine omega-3 PUFAs on risk of stroke remains unclear.METHODS:We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome.RESULTS:Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD.CONCLUSIONS:Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.
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| 24. |
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| 25. |
- Sobiecki, Jakub G., et al.
(författare)
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A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes : Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study
- 2023
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.Methods and findings: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22, 202 participants, of whom 9, 453 were T2D cases, with relevant biomarkers from an original case-cohort of 27, 779 participants sampled from a cohort of 340, 234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.Conclusions: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.
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| 26. |
- Steur, Marinka, et al.
(författare)
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Dietary Fatty Acids, Macronutrient Substitutions, Food Sources and Incidence of Coronary Heart Disease : Findings From the EPIC-CVD Case-Cohort Study Across Nine European Countries
- 2021
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 10:23
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain.Methods and Results: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88-0.99]), cheese (HR, 0.98 [95% CI, 0.96-1.00]), and fish (HR, 0.87 [95% CI, 0.75-1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02-1.12]) and butter (HR, 1.02 [95% CI, 1.00-1.04]).Conclusions: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.
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| 27. |
- Tamura, Yoichi, et al.
(författare)
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The 300 pc Resolution Imaging of a z=8.31 Galaxy : Turbulent Ionized Gas and Potential Stellar Feedback 600 Million Years after the Big Bang
- 2023
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 952:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of 300 pc resolution Atacama Large Millimeter/submillimeter Array imaging of the [O iii] 88 & mu;m line and dust continuum emission from a z = 8.312 Lyman-break galaxy MACS0416_Y1. The velocity-integrated [O iii] emission has three peaks that are likely associated with three young stellar clumps of MACS0416_Y1, while the channel map shows a complicated velocity structure with little indication of a global velocity gradient unlike what was found in [C ii] 158 & mu;m at a larger scale, suggesting random bulk motion of ionized gas clouds inside the galaxy. In contrast, dust emission appears as two individual clumps apparently separating or bridging the [O iii]/stellar clumps. The cross-correlation coefficient between dust and ultraviolet-related emission (i.e., [O iii] and ultraviolet continuum) is unity on a galactic scale, while it drops at <1 kpc, suggesting well-mixed geometry of multiphase interstellar media on subkiloparsec scales. If the cutoff scale characterizes different stages of star formation, the cutoff scale can be explained by gravitational instability of turbulent gas. We also report on a kiloparsec-scale off-center cavity embedded in the dust continuum image. This could be a superbubble producing galactic-scale outflows, since the energy injection from the 4 Myr starburst suggested by a spectral energy distribution analysis is large enough to push the surrounding media creating a kiloparsec-scale cavity.
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| 28. |
- Tong, Tammy Y. N., et al.
(författare)
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Dietary amino acids and risk of stroke subtypes : a prospective analysis of 356,000 participants in seven European countries
- 2024
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Ingår i: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 63, s. 209-220
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study.Methods: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants.Results: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing.Conclusion: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.
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| 29. |
- Zheng, Ju-Sheng, et al.
(författare)
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Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes : EPIC-InterAct case-cohort study in eight European countries
- 2020
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 370
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.Design: Prospective case-cohort study.Setting: Populations from eight European countries.Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measure: Incident type 2 diabetes.Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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| 30. |
- Zheng, Ju Sheng, et al.
(författare)
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Plasma Vitamin C and type 2 diabetes : Genome-wide association study and mendelian randomization analysis in European populations
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:1, s. 98-106
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS We identified 11 genomic regions associated with plasma vitamin C (P < 5 ☓ 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
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| 31. |
- Zheng, Ju-Sheng, et al.
(författare)
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The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations : A meta-analysis and Mendelian randomisation analysis
- 2020
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Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.Methods and findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
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