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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Tran, K. B., et al.
(author)
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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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In: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Journal article (peer-reviewed)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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- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Abbas, S., et al.
(author)
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Synthesis and Structural Characterization of Bioactive Ferrocenyl Substituted Hydrazones
- 2021
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In: Russian journal of coordination chemistry. - 1070-3284 .- 1608-3318. ; 47:12, s. 891-902
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Journal article (peer-reviewed)abstract
- A series of ferrocenyl substituted hydrazones (I–VII) derived from ferrocene carboxaldehyde and substituted hydrazides have been prepared and characterized by FTIR, 1H NMR spectroscopy, and crystallographic studies. The single-crystal X-ray analysis for III·0.5H2O·0.5CH3CN (CIF file CCDC no. 1968937) further authenticates the structural motif of the synthesized compounds. The C(11) of ferrocene carboxaldehyde is linked with N(1) of the hydrazide moiety with a bond length of 1.283(5) Å, confirming the binding of the two structural units present in the final product. They were preliminarily screened for their antimicrobial activity and demonstrate good results. The free radical scavenging activity for the compounds (III, IV) has been found to be more than 90% when compared with the ascorbic acid. The total antioxidant capacity and total reducing power assays for VI show significant activity whereas the data for the other compounds are also encouraging. Quantum chemical calculations at the DFT level predict that compound II is the softest while VII is the hardest within the series, resultantly II can be used as a synthon for further chemical reactions.
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- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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- Mehmood, M. A., et al.
(author)
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Automating Test Data Generation for Testing Context-Aware Applications
- 2018
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In: Proceedings of the IEEE International Conference on Software Engineering and Service Sciences, ICSESS. - : IEEE Computer Society. - 9781538665640 ; , s. 104-108
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Conference paper (peer-reviewed)abstract
- Context-aware applications are emerging applications in the modern era of computing. These applications can determine and adapt to situational context to provide better user experience. Testing these applications is not straightforward and poses several challenges such as developing context-aware test cases and generating test data etc. However, by employing model based testing technique, testing process for context-aware applications can be automated. To achieve maximum degree of automation, it is necessary to automate model transformation, test data generation and test cases execution. To execute test cases, test data is required and developing test data for context-aware applications is a challenging task. The aim of this study is to address this issue; thus, we propose automated test data generation for functional testing of context-aware applications. This automated test data generation can reduce testing time and cost, thus enabling test engineers to execute more testing cycles to attain higher degree of test coverage.
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- Mehmood, M. A., et al.
(author)
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Transforming context-aware application development model into a testing model
- 2017
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In: Proceedings of the IEEE International Conference on Software Engineering and Service Sciences, ICSESS. - : IEEE Computer Society. - 9781538645703 ; , s. 177-182
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Conference paper (peer-reviewed)abstract
- Software testing aims at ensuring the quality of a software product. Context-aware applications are emerging applications that are capable to sense their environment and adapt to situational context to provide better user experience. Context-aware applications pose many challenges for software testing such as defining test adequacy criteria, generating test data, developing context-aware test cases etc. Test case generation process for context-aware applications can be automated using a model based testing technique. To attain this goal with maximum degree of automation, it is required to transform development model into a test model automatically. In this study, we propose a typecast of activity node of UML activity diagram, called Context-Aware Activity for modelling context-aware applications. We have also developed an approach for automatic transformation of the development model i.e., UML activity diagram with Context-aware Activity typecast into a testing model i.e. function nets. This testing model is used to automate test case generation and we have illustrated how to generate context-aware test cases using our proposed approach.
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- Mohammed, Abbas, et al.
(author)
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The Role of High-Altitude Platforms (HAPs) in the Global Wireless Connectivity
- 2011
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In: Proceedings of the IEEE. - : IEEE (The Institution of Electrical & Electronics Engineering). - 0018-9219 .- 1558-2256. ; 99:11, s. 1939-1953
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Journal article (peer-reviewed)abstract
- Since 1990s, the investigations of aerospace communication segment have not only been concerned with satellites, but increasingly with lower altitude repeaters flying in the stratosphere. They are the so-called high-altitude platforms (HAPs) with important advantages with respect to satellites in terms of reduced cost of implementation, deployment, and launch. However, HAPs are characterized by a reduced coverage, as compared with satellites. Nevertheless, in recent literature, HAPs are not regarded as competitors of the satellite technology. On the contrary, the emphasis is on the effective and seamless integration among heterogeneous aerospace segments (GEO, LEO, and HAP) and aerospace segments with terrestrial wireless networks in order to globally extend the broadband wireless connectivity. This paper is focused on the role of HAPs in providing global connectivity in future communication systems and services. Potentialities, enabling technologies, and challenges are presented from the perspective of the integrated terrestrial/HAPs/satellite communications infrastructure.
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- Zhang, F. P., et al.
(author)
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Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
- 2019
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Journal article (peer-reviewed)abstract
- Androgen receptor (AR) is regulated by SUMOylation at its transactivation domain. In vitro, the SUMOylation is linked to transcriptional repression and/or target gene-selective regulation. Here, we generated a mouse model (ArKl) in which the conserved SUMO acceptor lysines of AR are permanently abolished (Ar-K381R, (K500R)) ArKl males develop normally, without apparent defects in their systemic androgen action in reproductive tissues. However, the ArKl males are infertile. Their spermatogenesis appears unaffected, but their epididymal sperm maturation is defective, shown by severely compromised motility and fertilization capacity of the sperm. Fittingly, their epididymal AR chromatin-binding and gene expression associated with sperm maturation and function are misregulated. AR is SUMOylated in the wild-type epididymis but not in the testis, which could explain the tissue-specific response to the lack of AR SUMOylation. Our studies thus indicate that epididymal AR SUMOylation is essential for the post-testicular sperm maturation and normal reproductive capability of male mice.
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