| 1. |
- Tran, K. B., et al.
(författare)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 2. |
- Bryazka, D., et al.
(författare)
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Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10347, s. 185-235
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Tidskriftsartikel (refereegranskat)abstract
- Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 3. |
- Ikuta, K. S., et al.
(författare)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Tidskriftsartikel (refereegranskat)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 10. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 14. |
- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 19. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 20. |
- van Setten, Jessica, et al.
(författare)
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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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| 21. |
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| 22. |
- Thiele, I., et al.
(författare)
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A community-driven global reconstruction of human metabolism
- 2013
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
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Tidskriftsartikel (refereegranskat)abstract
- Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
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| 23. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 24. |
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| 25. |
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| 26. |
- Tai, F, et al.
(författare)
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Abdominal Wall Miscellaneous
- 2015
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Ingår i: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S5-S12
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Tidskriftsartikel (refereegranskat)
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| 27. |
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| 28. |
- Alikhani, HK, et al.
(författare)
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Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications
- 2022
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Ingår i: Frontiers in cell and developmental biology. - : Frontiers Media SA. - 2296-634X. ; 10, s. 894800-
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Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is a common monogenic disease which is associated with high serum levels of low-density lipoprotein cholesterol (LDL-C) and leads to atherosclerosis and cardiovascular disease (CVD). Early diagnosis and effective treatment strategy can significantly improve prognosis. Recently, non-coding RNAs (ncRNAs) have emerged as novel biomarkers for the diagnosis and innovative targets for therapeutics. Non-coding RNAs have essential roles in the regulation of LDL-C homeostasis, suggesting that manipulation and regulating ncRNAs could be a promising theranostic approach to ameliorate clinical complications of FH, particularly cardiovascular disease. In this review, we briefly discussed the mechanisms and pathophysiology of FH and novel therapeutic strategies for the treatment of FH. Moreover, the theranostic effects of different non-coding RNAs for the treatment and diagnosis of FH were highlighted. Finally, the advantages and disadvantages of ncRNA-based therapies vs. conventional therapies were discussed.
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| 29. |
- Loyfer, N, et al.
(författare)
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A DNA methylation atlas of normal human cell types
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:79447943, s. 355-
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2–5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.
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| 30. |
- Osborn, D. P. S., et al.
(författare)
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Autosomal recessive cardiomyopathy and sudden cardiac death associated with variants in MYL3
- 2021
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:4, s. 787-792
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Variants in genes encoding sarcomeric proteins are the most common cause of inherited cardiomyopathies. However, the underlying genetic cause remains unknown in many cases. We used exome sequencing to reveal the genetic etiology in patients with recessive familial cardiomyopathy. Methods Exome sequencing was carried out in three consanguineous families. Functional assessment of the variants was performed. Results Affected individuals presented with hypertrophic or dilated cardiomyopathy of variable severity from infantile- to early adulthood-onset and sudden cardiac death. We identified a homozygous missense substitution (c.170C>A, p.[Ala57Asp]), a homozygous translation stop codon variant (c.106G>T, p.[Glu36Ter]), and a presumable homozygous essential splice acceptor variant (c.482-1G>A, predicted to result in skipping of exon 5). Morpholino knockdown of the MYL3 orthologue in zebrafish, cmlc1, resulted in compromised cardiac function, which could not be rescued by reintroduction of MYL3 carrying either the nonsense c.106G>T or the missense c.170C>A variants. Minigene assay of the c.482-1G>A variant indicated a splicing defect likely resulting in disruption of the EF-hand Ca2+ binding domains. Conclusions Our data demonstrate that homozygous MYL3 loss-of-function variants can cause of recessive cardiomyopathy and occurrence of sudden cardiac death, most likely due to impaired or loss of myosin essential light chain function.
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| 31. |
- Azangou-Khyavy, M, et al.
(författare)
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National, sub-national, and risk-attributed burden of thyroid cancer in Iran from 1990 to 2019
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 13231-
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Tidskriftsartikel (refereegranskat)abstract
- An updated exploration of the burden of thyroid cancer across a country is always required for making correct decisions. The objective of this study is to present the thyroid cancer burden and attributed burden to the high Body Mass Index (BMI) in Iran at national and sub-national levels from 1990 to 2019. The data was obtained from the GBD 2019 study estimates. To explain the pattern of changes in incidence from 1990 to 2019, decomposition analysis was conducted. Besides, the attribution of high BMI in the thyroid cancer DALYs and deaths were obtained. The age-standardized incidence rate of thyroid cancer was 1.57 (95% UI: 1.33–1.86) in 1990 and increased 131% (53–191) until 2019. The age-standardized prevalence rate of thyroid cancer was 30.19 (18.75–34.55) in 2019 which increased 164% (77–246) from 11.44 (9.38–13.85) in 1990. In 2019, the death rate, and Disability-adjusted life years of thyroid cancer was 0.49 (0.36–0.53), and 13.16 (8.93–14.62), respectively. These numbers also increased since 1990. The DALYs and deaths attributable to high BMI was 1.91 (0.95–3.11) and 0.07 (0.04–0.11), respectively. The thyroid cancer burden and high BMI attributed burden has increased from 1990 to 2019 in Iran. This study and similar studies’ results can be used for accurate resource allocation for efficient management and all potential risks’ modification for thyroid cancer with a cost-conscious view.
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| 34. |
- Majdi, Saman, et al.
(författare)
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High Performance Temperature Sensors using SC-CVD Diamond Schottky Diodes
- 2012
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Ingår i: Applied Physics Letters. - 0003-6951 .- 1077-3118.
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of new materials for thermal IR detection has been an intensive research area during the recent years. Among the new materials, diamond has the ability to function under high temperature, high power, and high radiation conditions, which enables large performance enhancements to a wide variety of systems and applications, e.g. electric vehicles, space exploration and nuclear energy reactors. In this study, diamond Schottky diodes (with boron concentrations in the range 1×1015 - 3×1016 cm-3) are presented as candidates for IR sensors with an excellent temperature coefficient of resistance (-16 %/K) and noise levels around 1.8×10-14 (V2/Hz).
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| 35. |
- Nilsson, Emma C, et al.
(författare)
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Sialic acid is a cellular receptor for coxsackievirus A24 variant, an emerging virus with pandemic potential
- 2008
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Ingår i: Journal of Virology. - Baltimore : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 82:6, s. 3061-3068
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Tidskriftsartikel (refereegranskat)abstract
- Binding to target cell receptors is a critical step in the virus life cycle. Coxsackievirus A24 variant (CVA24v) has pandemic potential and is a major cause of acute hemorrhagic conjunctivitis, but its cellular receptor has hitherto been unknown. Here we show that CVA24v fails to bind to and infect CHO cells defective in sialic acid expression. Binding of CVA24v to and infection of corneal epithelial cells are efficiently inhibited by treating cells with a sialic acid-cleaving enzyme or sialic acid-binding lectins and by treatment of the virus with soluble, multivalent sialic acid. Protease treatment of cells efficiently inhibited virus binding, suggesting that the receptor is a sialylated glycoprotein. Like enterovirus type 70 and influenza A virus, CVA24v can cause pandemics. Remarkably, all three viruses use the same receptor. Since several unrelated viruses with tropism for the eye use this receptor, sialic acid-based antiviral drugs that prevent virus entry may be useful for topical treatment of such infections.
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| 36. |
- Oldfors Hedberg, Carola, 1969, et al.
(författare)
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Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 28:11, s. 1919-1929
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Tidskriftsartikel (refereegranskat)abstract
- Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.
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| 37. |
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| 38. |
- Andersson, P, et al.
(författare)
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Youth with severe mental illness and complex non-somatic motor abnormalities: conflicting conceptualizations and unequal treatment
- 2022
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Ingår i: Npj mental health research. - : Springer Science and Business Media LLC. - 2731-4251. ; 1:1, s. 13-
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Tidskriftsartikel (refereegranskat)abstract
- Two emerging diagnostic concepts promote distinct treatments for youth with acute-onset motor abnormalities and severe concurrent psychiatric symptoms: Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric catatonia. Both have institutional approval in parts of Europe and in the USA, meriting an unconditional comparison of supporting evidence. Here we report results of qualitative and quantitative analyses of literature and Swedish National Registry Data suggesting that (1) catatonic patients are liable to fulfilling diagnostic criteria for PANS, (2) three conservatively assessed PANS case-reports present with possible unrecognized catatonia, (3) lithium and electroconvulsive therapy usage frequencies in Swedish minors (exclusively recommended for severe mental illness) are strongly intercorrelated and unequally distributed across Swedish counties, (4) established severe mental disorders are rarely overtly considered amongst PANS-specific research and (5) best-available evidence treatments appear markedly superior for pediatric catatonia compared to PANS in both childhood and adolescence. Prioritizing treatments for pediatric catatonia in concerned subjects could markedly improve treatment outcomes.
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| 39. |
- Danaei, Goodarz, et al.
(författare)
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Iran in transition
- 2019
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 393:10184, s. 1984-2005
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Forskningsöversikt (refereegranskat)abstract
- Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.
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| 40. |
- Filieri, Antonio, et al.
(författare)
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Control Strategies for Self-Adaptive Software Systems
- 2017
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Ingår i: ACM Transactions on Autonomous and Adaptive Systems. - : Association for Computing Machinery (ACM). - 1556-4665 .- 1556-4703. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- The pervasiveness and growing complexity of software systems are challenging software engineering to design systems that can adapt their behavior to withstand unpredictable, uncertain, and continuously changing execution environments. Control theoretical adaptation mechanisms have received growing interest from the software engineering community in the last few years for their mathematical grounding, allowing formal guarantees on the behavior of the controlled systems. However, most of these mechanisms are tailored to specific applications and can hardly be generalized into broadly applicable software design and development processes.This article discusses a reference control design process, from goal identification to the verification and validation of the controlled system. A taxonomy of the main control strategies is introduced, analyzing their applicability to software adaptation for both functional and nonfunctional goals. A brief extract on how to deal with uncertainty complements the discussion. Finally, the article highlights a set of open challenges, both for the software engineering and the control theory research communities.
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| 41. |
- Filieri, Antonio, et al.
(författare)
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Software Engineering Meets Control Theory
- 2015
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Ingår i: 2015 10th International Symposium on Software Engineering for Adaptive and Self-Managing Systems. - Piscataway, NJ, USA : IEEE Press. - 9780769555676 ; , s. 71-82
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Konferensbidrag (refereegranskat)abstract
- The software engineering community has proposed numerous approaches for making software self-adaptive. These approaches take inspiration from machine learning and control theory, constructing software that monitors and modifies its own behavior to meet goals. Control theory, in particular, has received considerable attention as it represents a general methodology for creating adaptive systems. Control-theoretical software implementations, however, tend to be ad hoc. While such solutions often work in practice, it is difficult to understand and reason about the desired properties and behavior of the resulting adaptive software and its controller. This paper discusses a control design process for software systems which enables automatic analysis and synthesis of a controller that is guaranteed to have the desired properties and behavior. The paper documents the process and illustrates its use in an example that walks through all necessary steps for self-adaptive controller synthesis.
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| 42. |
- Jamshidi, Asghar, et al.
(författare)
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Growth of GeSnSiC layers for photonic applications
- 2013
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 230, s. 106-110
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Tidskriftsartikel (refereegranskat)abstract
- This work presents epitaxial growth of intrinsic and doped GeSnSiC layers using Ge2H6, SnCl4, CH3SiH3, B2H6, PH3 and Si2H6 deposited at 290-380 degrees C on strain relaxed Ge buffer layer or Si substrate by using reduced pressure chemical vapor deposition (RPCVD) technique. The GeSnSi layers were compressively strained on Ge buffer layer and strain relaxed on Si substrate. It was demonstrated that the quality of epitaxial layers is dependent on the growth parameters and that the Sn content in epi-layers could be tailored by growth temperature. The Sn segregation caused surface roughness which was decreased by introducing Si and Si-C into Ge layer. less thanbrgreater than less thanbrgreater thanThe Sn content in GeSn was carefully determined from the mismatch, both parallel and perpendicular, to the growth direction when the Poisson ratio was calculated for a certain Ge-Sn composition. The X-ray results were excellently consistent with Rutherford Backscattered Spectroscopy (RBS). Strain relaxed GeSn layers were also used as virtual substrate to grow tensile-strained Ge layers. The Ge cap layer had low defect density and smooth surface which makes it a viable candidate material for future photonic applications.
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| 43. |
- Jamshidi, K., et al.
(författare)
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Magma storage and plumbing of adakite-type post-ophiolite intrusions in the Sabzevar ophiolitic zone, northeast Iran
- 2015
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Ingår i: Solid Earth. - : Copernicus GmbH. - 1869-9510 .- 1869-9529. ; 6:1, s. 49-72
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Tidskriftsartikel (refereegranskat)abstract
- Subduction-related adakite-type intrusive rocks emplaced into the late Cretaceous-Paleocene Sabzevar ophiolite zone, northeast Iran, range from Mg-andesite to rhyodacite in composition. Here we investigate the magma supply system to these subvolcanic intrusive rocks by applying thermobarometric mineral and mineral-melt equilibrium models, including amphibole thermobarometry, plagioclase-melt thermobarometry and clinopyroxene-melt barometry. Based on the results of these thermobarometric models, plagioclase crystallized dominantly at pressures of similar to 350 (130 to 468) MPa, while amphiboles record both low pressures (similar to 300 MPa) and very high pressures (> 700 MPa) of crystallization. The latter is supported by the calculated pressures for clinopyroxene crystallization (550 to 730 MPa). The association of amphibole with clinopyroxene and no plagioclase in the most primitive samples (Mg-andesites) is consistent with amphibole fractionation from very hydrous magmas at deep crustal levels of the plumbing system, which may have been a key process in intensifying adakite-type affinities in this rock suite. Barometry, combined with frequent disequilibrium features such as oscillatory-zoned and sieve-textured plagioclase crystals with An-rich overgrowths in more evolved samples, implies that final magma differentiation occurred in an open upper crustal magma system that developed progressively stronger compositional modifications during high-level magma storage.
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| 44. |
- Jamshidi, Mahboubeh, et al.
(författare)
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Copper(I) Iodide Thin Films: Deposition Methods and Hole-Transporting Performance
- 2024
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Ingår i: Molecules. - : Multidisciplinary Digital Publishing Institute (MDPI). - 1431-5157 .- 1420-3049. ; 29:8
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Forskningsöversikt (refereegranskat)abstract
- The pursuit of p-type semiconductors has garnered considerable attention in academia and industry. Among the potential candidates, copper iodide (CuI) stands out as a highly promising p-type material due to its conductivity, cost-effectiveness, and low environmental impact. CuI can be employed to create thin films with >80% transparency within the visible range (400–750 nm) and utilizing various low-temperature, scalable deposition techniques. This review summarizes the deposition techniques for CuI as a hole-transport material and their performance in perovskite solar cells, thin-film transistors, and light-emitting diodes using diverse processing methods. The preparation methods of making thin films are divided into two categories: wet and neat methods. The advancements in CuI as a hole-transporting material and interface engineering techniques hold promising implications for the continued development of such devices.
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| 45. |
- Jamshidi, Mahboubeh, et al.
(författare)
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Photoluminescent copper(I) iodide alkylpyridine thin films as sensors for volatile halogenated compounds
- 2023
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The paper presents the fabrication and characterization of [CuI(L)]n thin films, where L represents various alkylpyridine ligands including 4-methylpyridine, 3-methylpyridine, 2-methylpyridine, 4-tbutylpyridine, 3,4-dimethylpyridine, and 3,5-dimethylpyridine. The thin films were synthesized by exposing the corresponding ligands to CuI thin films through vapor deposition. The coordination reactions occurring on the films were investigated using PXRD and time-dependent photoluminescence spectroscopy, and a comparison was made between the structures of the thin films and the corresponding powder phases. The films showed primarly blue emission (λem = 457–515 nm) and polymeric structures with excited state lifetimes ranging from 0.6 to 5.5 μs. Significantly, the studied compounds exhibited fast reversible luminescence quenching when exposed to vapors of dichloromethane and dibromomethane (15 and 30 min respectively), and the luminescence was restored upon re-exposure to the alkylpyridine ligand (after 20 min). These findings indicate that these thin films hold promise for applications as sensors (with sensitive and reversible detection capability) for volatile halogen-based compounds (VHC).
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Mistry, Nitesh, et al.
(författare)
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Coxsackievirus A24 variant uses aialic acid-containing O-Linked glycoconjugates as cellular receptors on human ocular cells
- 2011
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Ingår i: Journal of Virology. - Baltimore : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 85:21, s. 11283-11290
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Tidskriftsartikel (refereegranskat)abstract
- Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection. Previously it has been suggested that CVA24v uses sialic acid-containing glycoconjugates as attachment receptors on corneal cells, but the nature of these receptors is poorly described. Here, we set out to characterize and identify the cellular components serving as receptors for CVA24v. Binding and infection experiments using corneal cells treated with deglycosylating enzymes or metabolic inhibitors of de novo glycosylation suggested that the receptor(s) used by CVA24v are constituted by sialylated O-linked glycans that are linked to one or more cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mock-transfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v. Finally, binding competition experiments using a library of mono- and oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to Neu5Ac alpha 2,3Gal disaccharides (Neu5Ac is N-acetylneuraminic acid). These results provide further insights into the early steps of the CVA24v life cycle.
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