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| 14. |
- Gao, H, et al.
(författare)
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Genetic variation in CDH13 is associated with lower plasma adiponectin levels but greater adiponectin sensitivity in East Asian populations
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:12, s. 4277-4283
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Tidskriftsartikel (refereegranskat)abstract
- Variants in the CDH13 gene have been identified as determinants of blood levels of adiponectin, an insulin-sensitizing adipokine. However, their association with other metabolic risk factors remains unclear. We examined variants at CDH13 in relation to total and high-molecular-weight (HMW) adiponectin using data from a genome-wide association study performed in 2,434 Singaporean Chinese with replication in up to 3,290 Japanese and 1,610 Koreans. The top signal rs4783244 in CDH13 showed strong associations with total adiponectin (standardized β [β] = −0.34, 95% CI −0.38 to −0.30, P = 2.0 × 10−70), HMW adiponectin (β = −0.40, 95% CI −0.43 to −0.36, P = 1.1 × 10−117), and the HMW-to-total adiponectin ratio (β = −0.44, 95% CI −0.49 to −0.40, P = 3.2 × 10−83). In the replication study, this single nucleotide polymorphism explained 4.1% of total and 6.5% of HMW adiponectin levels. No association was observed between rs4783244 and metabolic traits associated with insulin resistance before adjustment for HMW adiponectin levels. After adjustment for HMW adiponectin levels, the minor allele was associated with lower BMI (β = −0.15, 95% CI −0.19 to −0.11, P = 3.5 × 10−14), homeostasis model assessment-insulin resistance index (β = −0.16, 95% CI −0.20 to −0.12, P = 9.2 × 10−16), and triglycerides (β = −0.16, 95% CI −0.19 to −0.12, P = 1.3 × 10−16) and with higher HDL (β = 0.16, 95% CI 0.12 to 0.19, P = 2.1 × 10−17). CDH13 variants strongly influence plasma total and HMW adiponectin levels in East Asian populations but appear to alter adiponectin sensitivity, resulting in better metabolic health than expected based on circulating adiponectin levels.
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| 15. |
- Gao, J, et al.
(författare)
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Monkeypox outbreaks in the context of the COVID-19 pandemic: Network and clustering analyses of global risks and modified SEIR prediction of epidemic trends
- 2023
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Ingår i: Frontiers in public health. - : Frontiers Media SA. - 2296-2565. ; 11, s. 1052946-
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Tidskriftsartikel (refereegranskat)abstract
- Ninety-eight percent of documented cases of the zoonotic disease human monkeypox (MPX) were reported after 2001, with especially dramatic global spread in 2022. This longitudinal study aimed to assess spatiotemporal risk factors of MPX infection and predict global epidemiological trends.MethodTwenty-one potential risk factors were evaluated by correlation-based network analysis and multivariate regression. Country-level risk was assessed using a modified Susceptible-Exposed-Infectious-Removed (SEIR) model and a risk-factor-driven k-means clustering analysis.ResultsBetween historical cases and the 2022 outbreak, MPX infection risk factors changed from relatively simple [human immunodeficiency virus (HIV) infection and population density] to multiple [human mobility, population of men who have sex with men, coronavirus disease 2019 (COVID-19) infection, and socioeconomic factors], with human mobility in the context of COVID-19 being especially key. The 141 included countries classified into three risk clusters: 24 high-risk countries mainly in West Europe and Northern America, 70 medium-risk countries mainly in Latin America and Asia, and 47 low-risk countries mainly in Africa and South Asia. The modified SEIR model predicted declining transmission rates, with basic reproduction numbers ranging 1.61–7.84 in the early stage and 0.70–4.13 in the current stage. The estimated cumulative cases in Northern and Latin America may overtake the number in Europe in autumn 2022.ConclusionsIn the current outbreak, risk factors for MPX infection have changed and expanded. Forecasts of epidemiological trends from our modified SEIR models suggest that Northern America and Latin America are at greater risk of MPX infection in the future.
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| 17. |
- Gao, YG, et al.
(författare)
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Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:5, s. 450-
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.
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| 21. |
- Huang, QW, et al.
(författare)
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Effects of inhaled nitric oxide and high-frequency ventilation in rabbits with meconium aspiration
- 1999
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 76:6, s. 374-382
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate effects of inhaled nitric oxide (iNO) in experimental meconium aspiration treated with high-frequency (HFV) or conventional mechanical ventilation (CMV). Ventilated adult rabbits had meconium instilled intratracheally resulting in respiratory failure as evidenced by more than 50% reduction of dynamic lung compliance (Cdyn) and increase in mean oxygenation index (OI) from 1 to 16. The animals were then allocated to 2 groups treated without (control) or with iNO at 20 ppm (NO). In each group the animals were initially ventilated with CMV or HFV mode for 3 h and then in a crossover fashion with HFV or CMV for another 3 h (CMV→HFV, HFV→CMV), respectively. In the first 3 h of treatment, the animals subjected to HFV-CMV in the control, and those with both HFV-CMV and CMV-HFV in the NO group had significantly reduced OI. In the subsequent 3 h, the animals in the control group with CMV-HFV did not improve in OI and those with HFV-CMV had deteriorated. In the NO group with both CMV-HFV and HFV-CMV moderate improvement of OI was observed. Platelet aggregation capability and counts were significantly decreased and bleeding time prolonged in animals receiving iNO treatment. These results suggest that both HFV alone and a combined treatment of iNO with either CMV or HFV are more effective in improving blood oxygenation than that of CMV in this animal model. The influence of iNO on platelet aggregation should be considered.
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| 22. |
- Jelenkovic, A, et al.
(författare)
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Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts
- 2016
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Ingår i: Scientific reports. - London, United Kingdom : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28496-
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Tidskriftsartikel (refereegranskat)abstract
- Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.
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| 23. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 25. |
- Ma, J, et al.
(författare)
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Climate Change Drives the Transmission and Spread of Vector-Borne Diseases: An Ecological Perspective
- 2022
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Ingår i: Biology. - : MDPI AG. - 2079-7737. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Climate change affects ecosystems and human health in multiple dimensions. With the acceleration of climate change, climate-sensitive vector-borne diseases (VBDs) pose an increasing threat to public health. This paper summaries 10 publications on the impacts of climate change on ecosystems and human health; then it synthesizes the other existing literature to more broadly explain how climate change drives the transmission and spread of VBDs through an ecological perspective. We highlight the multi-dimensional nature of climate change, its interaction with other factors, and the impact of the COVID-19 pandemic on transmission and spread of VBDs, specifically including: (1) the generally nonlinear relationship of local climate (temperature, precipitation and wind) and VBD transmission, with temperature especially exhibiting an n-shape relation; (2) the time-lagged effect of regional climate phenomena (the El Niño–Southern Oscillation and North Atlantic Oscillation) on VBD transmission; (3) the u-shaped effect of extreme climate (heat waves, cold waves, floods, and droughts) on VBD spread; (4) how interactions between non-climatic (land use and human mobility) and climatic factors increase VBD transmission and spread; and (5) that the impact of the COVID-19 pandemic on climate change is debatable, and its impact on VBDs remains uncertain. By exploring the influence of climate change and non-climatic factors on VBD transmission and spread, this paper provides scientific understanding and guidance for their effective prevention and control.
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| 26. |
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| 27. |
- Schlosser, P, et al.
(författare)
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Meta-analyses identify DNA methylation associated with kidney function and damage
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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| 29. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 33. |
- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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