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| 2. |
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| 3. |
- Lind, Lars, et al.
(author)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Journal article (peer-reviewed)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 4. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 8. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 11. |
- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 12. |
- Taddei, C, et al.
(author)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Journal article (peer-reviewed)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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| 13. |
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| 14. |
- Buchanan, E. M., et al.
(author)
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The Psychological Science Accelerator's COVID-19 rapid-response dataset
- 2023
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
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Journal article (peer-reviewed)abstract
- In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
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| 17. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 18. |
- Kang, E. Y., et al.
(author)
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MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma
- 2022
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In: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480, s. 855-871
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Journal article (peer-reviewed)abstract
- Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
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| 19. |
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| 20. |
- Kobel, M., et al.
(author)
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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
- 2023
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In: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
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Journal article (peer-reviewed)abstract
- Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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| 21. |
- Razavi-Shearer, Devin M., et al.
(author)
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Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
- 2024
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In: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
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Journal article (peer-reviewed)abstract
- Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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| 22. |
- Domingo-Pardo, C., et al.
(author)
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Advances and new ideas for neutron-capture astrophysics experiments at CERN n_TOF
- 2023
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In: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 59:1
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Journal article (peer-reviewed)abstract
- This article presents a few selected developments and future ideas related to the measurement of (n,γ) data of astrophysical interest at CERN n_TOF. The MC-aided analysis methodology for the use of low-efficiency radiation detectors in time-of-flight neutron-capture measurements is discussed, with particular emphasis on the systematic accuracy. Several recent instrumental advances are also presented, such as the development of total-energy detectors with γ-ray imaging capability for background suppression, and the development of an array of small-volume organic scintillators aimed at exploiting the high instantaneous neutron-flux of EAR2. Finally, astrophysics prospects related to the intermediate i neutron-capture process of nucleosynthesis are discussed in the context of the new NEAR activation area.
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| 23. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 24. |
- Lerendegui-Marco, J., et al.
(author)
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New perspectives for neutron capture measurements in the upgraded CERN-n_TOF Facility
- 2023
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In: 15th International Conference on Nuclear Data for Science and Technology, ND2022. - : EDP Sciences.
-
Conference paper (peer-reviewed)abstract
- The n_TOF facility has just undergone in 2021 a major upgrade with the installation of its third generation spallation target that has been designed to optimize the performance of the two n_TOF time-of-flight lines. This contribution describes the key features and limitations for capture measurements in the two beam lines prior to the target upgrade and presents first results of (n,gamma) measurements carried out as part of the commissioning of the upgraded facility. In particular, the energy resolution, a key factor for both increasing the signal-to background ratio and obtaining accurate resonance parameters, has been clearly improved for the 20 m long vertical beam-line with the new target design while keeping the remarkably high resolution of the long beamline n_TOF-EAR1. The improvements in the n_TOF neutron beam-lines need to be accompanied by improvements in the instrumentation. A review is given on recent detector R&D projects aimed at tackling the existing challenges and further improving the capabilities of this facility.
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| 25. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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