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- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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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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- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Niu, XR, et al.
(författare)
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Bilateral Dysfunction of Otolith Pathway in Patients With Unilateral Idiopathic BPPV Detected by ACS-VEMPs
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13, s. 921133-
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Tidskriftsartikel (refereegranskat)abstract
- To observe the functional status of the otolith pathway in patients with unilateral idiopathic benign paroxysmal positional vertigo (BPPV) by combining air-conducted sound elicited cervical vestibular-evoked myogenic potential (ACS-cVEMP) and ocular vestibular-evoked myogenic potential (ACS-oVEMP).MethodsOne hundred and eighty patients with BPPV were recruited for conventional cVEMP and oVEMP tests. The abnormal rates of VEMPs were compared between BPPV patients and control participants.ResultsThe abnormal rates of cVEMP and oVEMP in BPPV patients were 46.7% (84/180) and 57.2% (103/180) in affected ears, respectively, and 45.0% (81/180) and 56.7% (102/180) in unaffected ears, respectively; both were significantly higher than the abnormal rates of cVEMP and oVEMP in normal control ears. Compared with normal subjects, the cVEMP response rate was lower in affected and unaffected ears in BPPV patients. The abnormal rates of cVEMP and oVEMP were 48.1% (76/158) and 57.6% (91/158) in patients with posterior semicircular canal BPPV, and 36.4% (8/22) and 54.5% (12/22) in lateral semicircular canal BPPV. There was no significant difference in VEMP abnormalities between posterior semicircular canal BPPV and lateral semicircular canal BPPV.ConclusionThe prevalence of abnormal cVEMPs and oVEMPs in both affected and unaffected ears of patients with BPPV was significantly higher than that observed in the control group. The pathological mechanism of unilateral idiopathic BPPV may be associated with bilateral degeneration of otolith pathways.
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- Wang, HD, et al.
(författare)
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Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
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