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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Wang, HD, et al.
(författare)
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Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
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Tidskriftsartikel (refereegranskat)
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- Buhler, JL, et al.
(författare)
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The Association between Apparent Temperature and Hospital Admissions for Cardiovascular Disease in Limpopo Province, South Africa
- 2023
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular diseases (CVDs) have a high disease burden both globally and in South Africa. They have also been found to be temperature-sensitive globally. The association between temperature and CVD morbidity has previously been demonstrated, but little is known about it in South Africa. It is important to understand how changes in temperature in South Africa will affect CVD morbidity, especially in rural regions, to inform public health interventions and adaptation strategies. This study aimed to determine the short-term effect of apparent temperature (Tapp) on CVD hospital admissions in Mopani District, Limpopo province, South Africa. A total of 3124 CVD hospital admissions records were obtained from two hospitals from 1 June 2009 to 31 December 2016. Daily Tapp was calculated using nearby weather station measurements. The association was modelled using a distributed lag non-linear model with a negative binomial regression over a 21-day lag period. The fraction of morbidity attributable to non-optimal Tapp, i.e., cold (6–25 °C) and warm (27–32 °C) Tapp was reported. We found an increase in the proportion of admissions due to CVDs for warm and cold Tapp cumulatively over 21 days. Increasing CVD admissions due to warm Tapp appeared immediately and lasted for two to four days, whereas the lag-structure for the cold effect was inconsistent. A proportion of 8.5% (95% Confidence Interval (CI): 3.1%, 13.7%) and 1.1% (95% CI: −1.4%, 3.5%) of the total CVD admissions was attributable to cold and warm temperatures, respectively. Warm and cold Tapp may increase CVD admissions, suggesting that the healthcare system and community need to be prepared in the context of global temperature changes.
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- He, YQ, et al.
(författare)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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- 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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- Moller, J, et al.
(författare)
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Geriatric syndromes and subsequent health-care utilization among older community dwellers in Stockholm
- 2022
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Ingår i: European journal of ageing. - : Springer Science and Business Media LLC. - 1613-9372 .- 1613-9380. ; 19:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the long-term effect of geriatric syndromes on health-care utilization. This study aims to determine the association between geriatric syndromes and health-care utilization during a four-year period among older community dwellers. Based on the Stockholm Public Health Cohort study, a total number of 6700 community dwellers aged ≥65 years were included. From a baseline survey in 2006, geriatric syndromes were defined as having at least one of the following: insomnia, functional decline, urinary incontinence, depressive symptoms and vision impairment. Health-care utilization was identified by linkages at individual level with register data with a four-year follow-up. Cox regression was performed to estimate the associations. Compared to those without geriatric syndromes, participants with any geriatric syndromes had a higher prevalence of frequent hospitalizations, long hospital stays, frequent outpatient visits and polypharmacy in each of the follow-up years. After controlling for covariates, having any geriatric syndromes was associated with higher levels of utilization of inpatient and outpatient care as well as polypharmacy. The association was stable over time, and the fully adjusted hazard ratio (95% confidence interval) remained stable in frequent hospitalizations (from 1.89 [1.31, 2.73] in year 1 to 1.70 [1.23, 2.35] in year 4), long hospital stay (from 1.75 [1.41, 2.16] to 1.49 [1.24, 1.78]), frequent outpatient visits (from 1.40 [1.26, 1.54] to 1.33 [1.22, 1.46]) and polypharmacy (from 1.63 [1.46, 1.83] to 1.53 [1.37, 1.71]). Having any geriatric syndromes is associated with higher levels of health-care utilization among older community dwellers, and the impact of geriatric syndromes is stable over a four-year period.
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- Rissanen, R, et al.
(författare)
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Trajectories of sickness absence after road traffic injury: a Swedish register-based cohort study
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:7, s. e031132-
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Tidskriftsartikel (refereegranskat)abstract
- Despite much focus on the health impact of road traffic injury (RTI) on life, there is a lack of knowledge of the dynamic process of return to work following RTI and its related factors. The aim of this study was to identify longitudinal patterns of sickness absence (SA) following RTI, to examine the patterns’ interplay with health-related quality of life (HRQoL) and to determine if there are differences, regarding the patterns and interplay, according to injury severity.DesignA register-based prospective cohort study.SettingAdministrative data on RTI in Sweden from the Swedish Traffic Accident Data Acquisition System (STRADA) and Swedish Social Insurance data.ParticipantsIndividuals suffering an RTI (total n=4761) were identified in STRADA between 1 January 2007 and 31 December 2009. A total of 903 of these met the inclusion criteria for the current study and were included.Primary and secondary outcome measuresThe primary outcome measure was SA following RTI. The secondary outcome measure was HRQoL.ResultsThree distinct patterns of SA were identified; ‘Stable’, ‘Quick decrease’ and ‘Gradual decrease’. The patterns differed in the number of initial SA days and the rate of reduction of SA days. After 3 years, all three patterns had almost the same level of SA. Higher injury severity and a higher number of SA days had a negative interplay with HRQoL. Participants who initially had a higher number of SA days were more likely to report a low HRQoL, indicating that people with a slower return to work are more vulnerable.ConclusionThe study highlights the heterogeneity of return to work after an RTI. People with a more severe injury and slower pace of return to work seem to be more vulnerable with regards to HRQoL loss following RTI.
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- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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