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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)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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- Abudurexiti, A, et al.
(författare)
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Taxonomy of the order Bunyavirales: update 2019
- 2019
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Ingår i: Archives of virology. - : Springer Science and Business Media LLC. - 1432-8798 .- 0304-8608. ; 164:7, s. 1949-1965
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Tidskriftsartikel (refereegranskat)
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- Li, SY, et al.
(författare)
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Incidental findings on brain MRI among Chinese at the age of 55-65 years: the Taizhou Imaging Study
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 464-
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Tidskriftsartikel (refereegranskat)abstract
- Asymptomatic brain abnormalities are common incidental findings on brain MRI in the elderly population and can be regarded as imaging markers of early stroke and dementia. We initiated the Taizhou Imaging Study (TIS) to examine the prevalence and correlates of incidental findings using brain MRI among an elderly population residing in a rural area of China. A total of 562 individuals, at the age of 55 to 65 years, participated in the TIS study with a response rate of 90%. The prevalence of lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMB), perivascular space, and intracranial arterial stenosis was 26.69%, 10.68%, 18.51%, 27.76%, and 12.81%, respectively. Age and hypertension were the major correlates of these incidental findings. Per each year increase in age, the risks of WMH and CMB increased by 15% and 14%. Compared to individuals with normal blood pressure, individuals with hypertension had an increased risk of all incidental findings, with the adjusted odds ratios of 2.28 to 5.45. Correlations of age, gender and body mass index with brain gray matter fraction were also observed. The high prevalence of these findings indicates a need of preventative strategy to help prevent future stroke and dementia in this population.
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