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- Fabian, ID, et al.
(author)
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Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
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In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
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Journal article (peer-reviewed)abstract
- The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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- Bölükbas, D. A., et al.
(author)
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Fine-tuning lung cancer nanotherapy using closed cardiopulmonary circulation
- 2019
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In: Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium : 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence - 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence. - 9781510883901 ; 40
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Conference paper (peer-reviewed)abstract
- Statement of Purpose: Lung cancer is the leading cause of cancer-related deaths and efficient therapies remain elusive. One emerging approach is to use nanoparticles (NPs) that are designed to specifically target malignant cells (1). Such targeting increases on-site drug doses and reduces systemic side effects. A common target in lung tumors is epidermal growth factor receptor (EGFR). Here, we explored the targeting efficacy of EGFR-targeted mesoporous silica nanoparticles (MSN GE11 ) for lung cancer treatment. Though specifically taken up by cancer cells in vitro, when administered intravenously or intratracheally in lung cancer mouse models, the NPs could not reach the depths of solid tumors and often strayed away from their target. This raises concerns whether NPs are suitable for therapeutically targeting lung tumors and challenges translational value of current approaches. To circumvent physiological barriers of solid lung tumors and consequent systemic clearance of NPs, we extended our analysis to a treatment strategy where the NPs are administered intravenously in a closed cardiopulmonary (CP) circulation loop. This approach not only makes the therapy more local, but also eliminates confounding factors for NP delivery such as liver/spleen deposition of NPs in vivo.
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- Dybe, S., et al.
(author)
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Design and experimental characterization of a swirl-stabilized combustor for low calorific value gaseous fuels
- 2020
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In: Proceedings of the ASME Turbo Expo. - : American Society of Mechanical Engineers (ASME).
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Conference paper (peer-reviewed)abstract
- Low calorific value (LCV) gaseous fuels are generated as by-products in many commercial sectors, e.g. as mine gas or biogas. Their efficient exploitation can be a considerable source of primary energy. Typically, product gases from biomass are characterized by low lower heating values (LHV) due to their high concentration of inert gases and steam. At the same time, their composition varies strongly based on the initial feedstock and may contain unwanted components in the form of tars and ammonia. These properties make the design of appropriate combustion systems very challenging and issues such as ignition, flame stability, emission control, and combustion efficiency must be accounted for. By employing a proprietary gas turbine burner at the TU Berlin, the combustion of an artificial LCV gas mixture at stoichiometric conditions has been successfully demonstrated for a broad range of steam content in the fuel. The current work presents the stability maps and emissions measured with the swirl-stabilized burner at premixed conditions. It was shown that the flame location and shape primarily depend on the steam content of the LCV gas. The steam content in the fuel was increased until flame blow-out occurred at LHVs well below the target condition of 2.87 MJ/kg (2.7 MJ/m3N). The exhaust gas is analyzed in terms of the pollutants NOx and CO for different fuel compositions, moisture contents, and thermal powers. Finally, OH∗ measurements have been carried out in the flame. A simple reactor network simulation was used to confirm the feasibility of the experimental results.
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- Dybe, S., et al.
(author)
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Design and Experimental Characterization of a Swirl-Stabilized Combustor for Low Calorific Value Gaseous Fuels
- 2021
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In: Journal of engineering for gas turbines and power. - : ASME International. - 0742-4795 .- 1528-8919. ; 144:2
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Journal article (peer-reviewed)abstract
- Low calorific value (LCV) gaseous fuels are generated as by-products in many commercial sectors, e.g., as mine gas or biogas. Their efficient exploitation can be a considerable source of primary energy. Typically, product gases from biomass are characterized by low lower heating values (LHVs) due to their high concentration of inert gases and steam. At the same time, their composition varies strongly based on the initial feedstock and may contain unwanted components in the form of tars and ammonia. These properties make the design of appropriate combustion systems very challenging and issues such as ignition, flame stability, emission control, and combustion efficiency must be accounted for. By employing a proprietary gas turbine burner at the TU Berlin, the combustion of an artificial LCV gas mixture at stoichiometric conditions has been successfully demonstrated for a broad range of steam content in the fuel. This work presents the stability maps and emissions measured with the swirl-stabilized burner at premixed conditions. It was shown that the flame location and shape primarily depend on the steam content of the LCV gas. The steam content in the fuel was increased until flame blow-out occurred at LHVs well below the target condition of 2.87 MJ/kg (2.7 MJ/m3NmN3). The exhaust gas is analyzed in terms of the pollutants NOx and CO for different fuel compositions, moisture contents, and thermal powers. Finally, OH* measurements have been carried out in the flame. A simple reactor network simulation was used to confirm the feasibility of the experimental results.
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- Marazioti, Antonia, et al.
(author)
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KRAS signaling in malignant pleural mesothelioma
- 2022
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In: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 14:2
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Journal article (peer-reviewed)abstract
- Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.
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