| 1. |
- 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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| 2. |
- Donati, Benedetta, et al.
(författare)
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Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease.
- 2017
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Ingår i: Cancer medicine. - : Wiley. - 2045-7634. ; 6:8, s. 1930-1940
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Tidskriftsartikel (refereegranskat)abstract
- In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD-PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over-expressing protein variants in HEK-293 cells. We found that telomere length was reduced in individuals with NAFLD-HCC versus those with cirrhosis (P=0.048) and healthy controls (P=0.0006), independently of age and sex. We detected an enrichment of hTERT mutations in NAFLD-HCC, that was confirmed when we further considered a larger cohort of NAFLD-PLC, and was more marked in female patients (P=0.03). No mutations were found in cirrhosis and local controls, and only one in 503 healthy Europeans from the 1000 Genomes Project (allelic frequency=0.025 vs. <0.001; P=0.0005). Mutations with predicted functional impact, including the frameshift Glu113Argfs*79 and missense Glu668Asp, cosegregated with liver disease in two families. Three patients carried missense mutations (Ala67Val in homozygosity, Pro193Leu and His296Pro in heterozygosity) in the N-terminal template-binding domain (P=0.037 for specific enrichment). Besides Glu668Asp, the Ala67Val variant resulted in reduced intracellular protein levels. In conclusion, we detected an association between shorter telomeres in peripheral blood and rare germline hTERT mutations and NAFLD-HCC.
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| 3. |
- Grieco, Rebecca, et al.
(författare)
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A significantly improved polymer||Ni(OH) 2 alkaline rechargeable battery using anthraquinone-based conjugated microporous polymer anode
- 2022
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Ingår i: Materials Today Energy. - : Elsevier BV. - 2468-6069. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- Alkaline rechargeable batteries (ARBs) are predicted to be an attractive solution for large-scale electrochemical energy storage applications. However, their advancement is greatly hindered by the lack of high-performance and sustainable anode that can stably operate in less-corroding, low electrolyte concentration. Herein, we report the first example of polymer ARB able to operate in low concentrate electrolyte (1м potassium hydroxide [KOH]) due to the employment of a robust anthraquinone-based conjugated microporous polymer (IEP-11) as anode. The assembled IEP-11||Ni(OH)2 achieves high cell voltage (0.98 V), high gravimetric/areal capacities (150 mAh/g/7.2 mAh/cm2 at 3.5 and 65 mg/cm2, respectively), long cycle life (22,730 cycles, 960 h, 75% capacity retention at 20C), excellent rate performance (75 mAh/g at 50C) and low temperature operativity (75 mAh/g at −10 °C). Furthermore, rate capability, low-temperature performance and ability to prepare high mass loading anodes, along with low self-discharge is improved compared to conventional linear poly (anthraquinone sulfide) (PAQS) in commonly used 10 м KOH. This overall performance for IEP-11||Ni(OH)2 is not only far superior to that of PAQS||Ni(OH)2 owing to porous polymer's high specific surface area, combined micro-/mesoporosity and robust and mechanically stable three-dimensional (3D) architecture compared to the linear PAQS, but also surpass most of the reported organic||nickel [Ni]/cobalt [Co]/manganese [Mn] alkaline rechargeable batteries (ARBs).
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| 4. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- López-Ballesteros, Ana, et al.
(författare)
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Towards a feasible and representative pan-African research infrastructure network for GHG observations
- 2018
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- There is currently a lack of representative, systematic and harmonised greenhouse gas (GHG) observations covering the variety of natural and human-altered biomes that occur in Africa. This impedes the long-term assessment of the drivers of climate change, in addition to their impacts and feedback loops at the continental scale, but also limits our understanding of the contribution of the African continent to the global carbon (C) cycle. Given the current and projected transformation of socio-economic conditions in Africa (i.e. the increasing trend of urbanisation and population growth) and the adverse impacts of climate change, the development of a GHG research infrastructure (RI) is needed to support the design of suitable mitigation and adaptation strategies required to assure food, fuel, nutrition and economic security for the African population. This paper presents the initial results of the EU-African SEACRIFOG project, which aims to design a GHG observation RI for Africa. The first stages of this project included the identification and engagement of key stakeholders, the definition of the conceptual monitoring framework and an assessment of existing infrastructural capacity. Feedback from stakeholder sectors was obtained through three Stakeholder Consultation Workshops held in Kenya, Ghana and Zambia. Main concerns identified were data quality and accessibility, the need for capacity building and networking among the scientific community, and adaptation to climate change, which was confirmed to be a priority for Africa. This feedback in addition to input from experts in the atmospheric, terrestrial and oceanic thematic areas, facilitated the selection of a set of 'essential variables' that need to be measured in the future environmental RI. An inventory of 47 existing and planned networks across the continent allowed for an assessment of the current RIs needs and gaps in Africa. Overall, the development of a harmonised and standardised pan-African RI will serve to address the continent's primary societal and scientific challenges through a potential cross-domain synergy among existing and planned networks at regional, continental and global scales.
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| 6. |
- Merbold, Lutz, et al.
(författare)
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Opportunities for an African greenhouse gas observation system
- 2021
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Ingår i: Regional Environmental Change. - : Springer Science and Business Media LLC. - 1436-3798 .- 1436-378X. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- Global population projections foresee the biggest increase to occur in Africa with most of the available uncultivated land to ensure food security remaining on the continent. Simultaneously, greenhouse gas emissions are expected to rise due to ongoing land use change, industrialisation, and transport amongst other reasons with Africa becoming a major emitter of greenhouse gases globally. However, distinct knowledge on greenhouse gas emissions sources and sinks as well as their variability remains largely unknown caused by its vast size and diversity and an according lack of observations across the continent. Thus, an environmental research infrastructure—as being setup in other regions—is more needed than ever. Here, we present the results of a design study that developed a blueprint for establishing such an environmental research infrastructure in Africa. The blueprint comprises an inventory of already existing observations, the spatial disaggregation of locations that will enable to reduce the uncertainty in climate forcing’s in Africa and globally as well as an overall estimated cost for such an endeavour of about 550 M€ over the next 30 years. We further highlight the importance of the development of an e-infrastructure, the necessity for capacity development and the inclusion of all stakeholders to ensure African ownership.
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| 7. |
- Pelusi, Serena, et al.
(författare)
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Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n=181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p=0.024), and likely pathogenic variants (p=1.9*10-6), particularly in APOB (p=0.047). APOB variants were associated with lower circulating triglycerides and higher HDL cholesterol (p<0.01). A genetic risk score predicted NAFLD-HCC (OR 4.96, 3.29-7.55; p=5.1*10-16), outperforming the diagnostic accuracy of common genetic risk variants, and of clinical risk factors (p<0.05). In conclusion, rare pathogenic variants in genes involved in liver disease and cancer predisposition are associated with NAFLD-HCC development.
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