| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Govaere, O., et al.
(författare)
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Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
- 2022
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:5, s. 1001-1012
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1-/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. © 2021 The Authors
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| 4. |
- Elkadeem, M. R., et al.
(författare)
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Agrivoltaic systems potentials in Sweden : A geospatial-assisted multi-criteria analysis
- 2024
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Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- Agrivoltaic systems represent an intelligent solution combining electricity production from solar photovoltaic technology with agricultural production to avoid land use conflicts. Geographic Information System technologies can support the implementation and spread of agrivoltaic systems by identifying the most suitable areas using useful spatially explicit information concerning techno-agro-socio-economic criteria. In this study, we have developed a procedure to identify and classify suitable areas for agrivoltaic systems in Sweden. An Ordinal Priority Approach based multi-criteria decision-making algorithm is established to calculate the weights of the selected evaluation criteria through expert interviews. The land use data refers to the Corine Land Cover 2018 product. The results show that about 8.6% of the Swedish territory, approximately 38,485 km2, is suitable for installing agrivoltaic systems. Among this area, about 0.2% is classified as “excellent”, about 15% as “very good”, about 72% as “good”, about 13% as “moderate”, and about 0.1% as “poor”. Most “excellent”-classified areas are in Kalmar, Skåne, and Gotland. In contrast, most “very good” sites are in Skåne, Kalmar, and Östergötland. By deploying vertically mounted agrivoltaic systems with bifacial photovoltaic modules, the total potential installed capacity for “excellent” areas is about 2.5 GWp, while for areas classified “excellent” and “very good” is about 221 GWp. The total “excellent” areas can potentially supply about 2.4 TWh of electricity against the electricity consumption in 2021 of about 143 TWh. On the other hand, the land classified as “excellent” and “very good” could potentially provide about 207 TWh. The County of Västra Götaland shows the greatest potentials in terms of total potential electricity supply from agrivoltaic systems with about 227 TWh, followed by Skåne with a total potential of 206 TWh.
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| 5. |
- Hardy, Timothy, et al.
(författare)
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The European NAFLD Registry : A real-world longitudinal cohort study of nonalcoholic fatty liver disease
- 2020
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Ingår i: Contemporary Clinical Trials. - : Elsevier. - 1551-7144 .- 1559-2030. ; 98
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Tidskriftsartikel (refereegranskat)abstract
- Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS Liver Investigation: Testing Marker Utility in Steatohepatitis consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
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| 6. |
- Elkadeem, M. R., et al.
(författare)
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Geospatial-assisted multi-criterion analysis of solar and wind power geographical-technical-economic potential assessment
- 2022
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Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 322
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Tidskriftsartikel (refereegranskat)abstract
- Amid the increasing electricity demand, energy crisis and pollution, the transition to renewable energy (RE) is becoming a preoccupation and major global challenge due to the multidimensional and intricate problem of RE planning. In Egypt, about 90% of gross power generation comes from carbon-intensive power plants (natural gas and coal). Here, we propose a novel geospatial-decision-making model aimed at geographical-technical–economic potential mapping and assessment of solar photovoltaic (PV) and onshore wind turbine (WT) power plants at a high level of resolution (1 km2) in Egypt. We identify the locations suitable for PV and WT development considering sixteen restrictive and contradictory evaluation criteria. These locations have been further analyzed to estimate how much energy generation is available and at what energy cost. The analysis identifies Middle-Upper Egypt and Suez Canal as hosting the majority of highly suitable locations for PV and WT power plants, respectively. Our finding reveals that the proper planning on RE projects at the proposed optimum locations could support the country's energy mix with a sizable 32% share of the projected country's electricity consumption from PV and 50% share from WT, by 2030. Furthermore, we show that the investment opportunities of PV and WT generation are potentially attractive with affordable competitive prices estimated at 57.84 $/MWh and 32.36 $/MWh, respectively, against conventional generation for today and the future. We anticipate that our results will provide valuable support in realizing Egypt's vision for sustainable electricity generation and in keeping abreast of the global transformation in power systems being witnessed. Ultimately, the method's relevance extends beyond the geographical boundaries of the present territory; it features a strategic, clear and reproducible approach that may be applied to a larger area or continent, provided the necessary input data and criteria are introduced.
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| 7. |
- Govaere, Olivier, et al.
(författare)
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Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis
- 2020
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Ingår i: Science Translational Medicine. - Washington, DC, United States : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 12:572
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms that drive nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This large multicenter study characterized the transcriptional changes that occur in liver tissue across the NAFLD spectrum as disease progresses to cirrhosis to identify potential circulating markers. We performed high-throughput RNA sequencing on a discovery cohort comprising histologically characterized NAFLD samples from 206 patients. Unsupervised clustering stratified NAFLD on the basis of disease activity and fibrosis stage with differences in age, aspartate aminotransferase (AST), type 2 diabetes mellitus, and carriage of PNPLA3 rs738409, a genetic variant associated with NAFLD. Relative to early disease, we consistently identified 25 differentially expressed genes as fibrosing steatohepatitis progressed through stages F2 to F4. This 25-gene signature was independently validated by logistic modeling in a separate replication cohort (n = 175), and an integrative analysis with publicly available single-cell RNA sequencing data elucidated the likely relative contribution of specific intrahepatic cell populations. Translating these findings to the protein level, SomaScan analysis in more than 300 NAFLD serum samples confirmed that circulating concentrations of proteins AKR1B10 and GDF15 were strongly associated with disease activity and fibrosis stage. Supporting the biological plausibility of these data, in vitro functional studies determined that endoplasmic reticulum stress up-regulated expression of AKR1B10, GDF15, and PDGFA, whereas GDF15 supplementation tempered the inflammatory response in macrophages upon lipid loading and lipopolysaccharide stimulation. This study provides insights into the pathophysiology of progressive fibrosing steatohepatitis, and proof of principle that transcriptomic changes represent potentially tractable and clinically relevant markers of disease progression.
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| 8. |
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| 9. |
- Armandi, Angelo, et al.
(författare)
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Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease
- 2024
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Ingår i: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288.
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Tidskriftsartikel (refereegranskat)abstract
- Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 mu g/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 mu g/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 mu g/L and 272 mu g/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices>0.71) and overall mortality (C-indices>0.65). Conclusions This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.
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| 10. |
- Elkadeem, M. R., et al.
(författare)
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Sustainable siting and design optimization of hybrid renewable energy system : A geospatial multi-criteria analysis
- 2021
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Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 295
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Tidskriftsartikel (refereegranskat)abstract
- The use of hybrid renewable energy system (HRES) holds great promise for sustainable electrification and support countries reaching their energy access goals. The site selection and design of HRES are strategic stages towards ensuring an affordable, sustainable, and well-performing project. However, both are multidimensional and intricate issues that involve multiple conflicting assessment criteria and alternatives, which are not yet investigated comprehensively and simultaneously in many of the existing literature. In this context, the paper aims to develop a systematic and conceptual decision-making framework for site suitability and optimal design of HRESs, with an application on a regional scale in Kenya, Sub-Saharan Africa. The suggested framework is applied through three consecutive phases. First, a geographical information system (GIS) is combined with Best Worst Method (BWM) decision-making approach to spatially investigate and analyze the potential sites of solar, wind, and hybrid solar/wind systems. Within the spatial investigation, 9 different climatology, environment, location, and orography criteria are considered. Second, energy-economy-ecology (E3) design optimization is conducted to determine the list of feasible alternatives among grid-extension, autonomous HRES, and stand-alone diesel genset electrification schemes for powering a representative remote rural village in Kenya. Third, a post-optimality multi-criteria decision-making (MCDM) analysis is applied to decide and assess the optimal energy access design against 12 key sustainability indicators. In the third phase, the BWM is employed to define the weights of each indicator. Then, the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and the VIšekriterijumsko KOmpromisno Rangiranje (VIKOR) decision making approaches are used for the final ranking of feasible alternatives. The obtained site suitability maps of Kenya show that 0.91% (5322 km2) and 1.5% (8828.4 km2) of the land is highly suitable, 10.25% (59687 km2) and 33.04% (192360 km2) is suitable, and 80.5% (470313 km2) and 65% (378407 km2) is permanently unsuitable for establishing solar and wind systems, respectively. Also, E3-MCDM results indicate that the development of solar/wind/diesel/battery HRES is the best sustainable solution to supply the studied region as compared to other feasible alternatives. The system does not only guarantee a reliable operation with an unmet load of 552 kWh/yr, but it also has the lowest net present and energy costs at 2.6 M$ and 0.28 $/kWh, respectively, meanwhile avoiding annual CO2 of 804 tons compared with diesel system.
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