| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
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| 6. |
- 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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| 7. |
- Aubert, S, et al.
(författare)
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Global Matrix 4.0 Physical Activity Report Card Grades for Children and Adolescents: Results and Analyses From 57 Countries
- 2022
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Ingår i: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 19:11, s. 700-728
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children’s and adolescents’ (5–17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. Methods: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders’ top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. Results: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. Conclusions: The Global Matrix 4.0 represents the largest compilation of children’s and adolescents’ PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.
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| 12. |
- Trajkovska, V., et al.
(författare)
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BDNF downregulates 5-HT2A receptor protein levels in hippocampal cultures
- 2009
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Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186. ; 55:7, s. 697-702
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Tidskriftsartikel (refereegranskat)abstract
- Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT2A) have been related to depression pathology. Specific 5-HT2A receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT2A receptor level. Here we show a direct effect of BDNF on 5-HT2A receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT2A receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50 ng/mL BDNF resulted in downregulation of 5-HT2A, but not of 5-HT1A, receptor protein levels. The BDNF-associated downregulation of 5-HT2A receptor levels was also observed in mature hippocampal organotypic cultures, excluding confounding effects of BDNF on immature tissue. BDNF +/- mice showed significant increased 5-HT2A receptor levels in hippocampus confirming the association between 5-HT2A receptor and BDNF levels in vivo. In conclusion, our results point to a regulatory role of BDNF on 5-HT2A receptor levels. This interaction may be an important mechanism in the role of BDNF in affective disorders emphasizing the need for further elucidating the specificity and the mechanism behind this regulation. (C) 2009 Elsevier Ltd. All rights reserved.
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| 13. |
- Gasic, D., et al.
(författare)
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Retrospective estimation of heart and lung doses in pediatric patients treated with spinal irradiation
- 2018
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 128:2, s. 209-213
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The purpose of this study was to investigate whether treatment information from medical records can be used to estimate radiation doses to heart and lungs retrospectively in pediatric patients receiving spinal irradiation with conventional posterior fields. Material and methods: An algorithm for retrospective dosimetry in children treated with spinal irradiation was developed in a cohort of 21 pediatric patients with available CT-scans and treatment plans. We developed a multivariable linear regression model with explanatory variables identifiable in case note review for retrospective estimation of minimum, maximum, mean and V-10%-V-80% doses to the heart and lungs. Doses were estimated for both linear accelerator (Linac) and Co-60 radiation therapy modalities. Results: Age and spinal field width were identified as statistically significant predictors of heart and lung doses in multivariable analyses (p < 0.01 in all models). Models showed excellent predictive performance with R-2 = 0.70 for mean heart dose and 0.79 for mean lung dose, for Linac plans. In leave-one-out cross-validation analysis the average difference between predicted and actual mean heart dose was 6.7% and 7.6% of the prescription dose for Linac and Co-60 plans, respectively, and 5.2% and 4.9% for mean lung dose. Due to the small sample size and large inter-patient variation in heart and lung dose, prospective studies validating these findings are highly warranted. Conclusions: The models presented here provide retrospective estimates of heart and lung doses for historical cohorts of pediatric patients, thus facilitating studies of long-term adverse effects of radiation. (C) 2018 Elsevier B.V. All rights reserved.
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| 14. |
- Kreibich, Heidi, et al.
(författare)
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Panta Rhei benchmark dataset : Socio-hydrological data of paired events of floods and droughts
- 2023
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Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 15:5, s. 2009-2023
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Tidskriftsartikel (refereegranskat)abstract
- As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions, and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e. two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed and in the quantity of socio-hydrological data. The benchmark dataset comprises (1) detailed review-style reports about the events and key processes between the two events of a pair; (2) the key data table containing variables that assess the indicators which characterize management shortcomings, hazard, exposure, vulnerability, and impacts of all events; and (3) a table of the indicators of change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators of change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses, e.g. focused on causal links between risk management; changes in hazard, exposure and vulnerability; and flood or drought impacts. The data can also be used for the development, calibration, and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al., 2023, 10.5880/GFZ.4.4.2023.001).
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| 15. |
- Kreibich, Heidi, et al.
(författare)
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The challenge of unprecedented floods and droughts in risk management
- 2022
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 608:7921, s. 80-86
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Tidskriftsartikel (refereegranskat)abstract
- Risk management has reduced vulnerability to floods and droughts globally, yet their impacts are still increasing. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change.
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| 20. |
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| 21. |
- Tehrani, Nima Fotouhi, et al.
(författare)
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Coffee extract residue for production of ethanol and activated carbons
- 2015
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 91, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Biomass as a waste product in the form coffee extract residue (CER) has been shown to have potential for the dual purpose of ethanol production and preparation of activated carbons. A straightforward method of direct hydrolysis and fermentation (DHF) is considered as the main option utilized in this study for the generation of fuel ethanol from the biomass waste. Factors such as loadings of saccharomyces cerevisiae, temperatures (21 and 30 degrees C) and substrate content were investigated to maximize the yield of ethanol. Ethanol production rates between 1.1 g and 0.70 g h(-1) kg(-1) without pretreatment and 2.7 and 23 g h(-1) kg(-1) dry substance with mild treatment were obtained, respectively. The CER was also used to prepare activated carbons using both chemical and physical activation methods. The effects of process parameters such as temperatures and concentrations of acid were varied and determined as to the yield, BET-surface areas and porosities of the final product. H3PO4 treatment at 600 degrees C and steam treatment at 700 degrees C show maximum surface area of >640 m(2) g(-1) with increased total pore and micropore volumes. (C) 2014 Elsevier Ltd. All rights reserved.
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