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| 2. |
- Meroni, Marica, et al.
(författare)
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Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 52
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Tidskriftsartikel (refereegranskat)abstract
- Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation.Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes.In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammation and MBOAT7 genotype. Hepatic MBOAT7 levels were reduced in murine models of fatty liver, and by hyper-insulinemia. In wild-type mice, Mboat7 was down-regulated by refeeding and insulin, concomitantly with insulin signalling activation. Acute hepatic Mboat7 silencing promoted hepatic steatosis in vivo and enhanced expression of fatty acid transporter Fatp1. MBOAT7 deletion in hepatocytes reduced the incorporation of arachidonic acid into phosphatidylinositol, consistently with decreased enzymatic activity, determining the accumulation of saturated triglycerides, enhanced lipogenesis and FATP1 expression, while FATP1 deletion rescued the phenotype.MBOAT7 down-regulation by hyper-insulinemia contributes to hepatic fat accumulation, impairing phosphatidylinositol remodelling and up-regulating FATP1.LV was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02,364,358, Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; LV and AG received funding from the European Union Programme Horizon 2020 (No. 777,377) for the project LITMUS-"Liver Investigation: Testing Marker Utility in Steatohepatitis". MM was supported by Fondazione Italiana per lo Studio del Fegato (AISF) 'Mario Coppo' fellowship.
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| 3. |
- Biancari, Fausto, et al.
(författare)
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Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation : Systematic Review and Individual Patient Data Meta-Analysis
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:24
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Forskningsöversikt (refereegranskat)abstract
- Background: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. Results: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08–1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04–1.76, I2 21%). Conclusions: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.
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| 4. |
- Biancari, Fausto, et al.
(författare)
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Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation
- 2024
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Ingår i: International Journal of Artificial Organs. - 0391-3988 .- 1724-6040. ; 47:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. Methods: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. Results: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients’ risk profile. Conclusions: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.
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| 5. |
- Biancari, Fausto, et al.
(författare)
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Multicenter study on postcardiotomy venoarterial extracorporeal membrane oxygenation
- 2020
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 159:5, s. 1844-1854
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to identify the risk factors associated with early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. Methods: This is an analysis of the postcardiotomy extracorporeal membrane oxygenation registry, a retrospective multicenter cohort study including 781 patients aged more than 18 years who required venoarterial extracorporeal membrane oxygenation for cardiopulmonary failure after cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. Results: After a mean venoarterial extracorporeal membrane oxygenation therapy of 6.9 ± 6.2 days, hospital and 1-year mortality were 64.4% and 67.2%, respectively. Hospital mortality after venoarterial extracorporeal membrane oxygenation therapy for more than 7 days was 60.5% (P = .105). Centers that had treated more than 50 patients with postcardiotomy venoarterial extracorporeal membrane oxygenation had a significantly lower hospital mortality than lower-volume centers (60.7% vs 70.7%, adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.82). The postcardiotomy extracorporeal membrane oxygenation score was derived by assigning a weighted integer to each independent pre–venoarterial extracorporeal membrane oxygenation predictors of hospital mortality as follows: female gender (1 point), advanced age (60-69 years, 2 points; ≥70 years, 4 points), prior cardiac surgery (1 point), arterial lactate 6.0 mmol/L or greater before venoarterial extracorporeal membrane oxygenation (2 points), aortic arch surgery (4 points), and preoperative stroke/unconsciousness (5 points). The hospital mortality rates according to the postcardiotomy extracorporeal membrane oxygenation score was 0 point, 45.6%; 1 point, 40.5%; 2 points, 51.1%; 3 points, 57.8%; 4 points, 70.7%; 5 points, 68.3%; 6 points, 77.5%; and 7 points or more, 89.7% (P < .0001). Conclusions: Age, female gender, prior cardiac surgery, preoperative acute neurologic events, aortic arch surgery, and increased arterial lactate were associated with increased risk of early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. Center experience with postcardiotomy venoarterial extracorporeal membrane oxygenation may contribute to improved results.
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| 7. |
- Fuzzi, Sandro, et al.
(författare)
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Overview of the inorganic and organic composition of size-segregated aerosol in Rondonia, Brazil, from the biomass-burning period to the onset of the wet season
- 2007
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 112:D1
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Tidskriftsartikel (refereegranskat)abstract
- The aerosol characterization experiment performed within the Large-Scale Biosphere-Atmosphere Experiment in Amazonia-Smoke, Aerosols, Clouds, Rainfall and Climate (LBA-SMOCC) field experiment carried out in Rondonia, Brazil, in the period from September to November 2002 provides a unique data set of size-resolved chemical composition of boundary layer aerosol over the Amazon Basin from the intense biomass-burning period to the onset of the wet season. Three main periods were clearly distinguished on the basis of the PM10 concentration trend during the experiment: (1) dry period, with average PM10 well above 50 mu g m(-3); (2) transition period, during which the 24-hour-averaged PM10 never exceeded 40 mu g m(-3) and never dropped below 10 mg m(-3); (3) and wet period, characterized by 48-hour-averaged concentrations of PM10 below 12 mu g m(-3) and sometimes as low as 2 mu g m(-3). The trend of PM10 reflects that of CO concentration and can be directly linked to the decreasing intensity of the biomass- burning activities from September through November, because of the progressive onset of the wet season. Two prominent aerosol modes, in the submicron and supermicron size ranges, were detected throughout the experiment. Dry period size distributions are dominated by the fine mode, while the fine and coarse modes show almost the same concentrations during the wet period. The supermicron fraction of the aerosol is composed mainly of primary particles of crustal or biological origin, whereas submicron particles are produced in high concentrations only during the biomass-burning periods and are mainly composed of organic material, mostly water-soluble, and similar to 10% of soluble inorganic salts, with sulphate as the major anion. Size-resolved average aerosol chemical compositions are reported for the dry, transition, and wet periods. However, significant variations in the aerosol composition and concentrations were observed within each period, which can be classified into two categories: (1) diurnal oscillations, caused by the diurnal cycle of the boundary layer and the different combustion phase active during day (flaming) or night (smouldering); and (2) day-to-day variations, due to alternating phases of relatively wet and dry conditions. In a second part of the study, three subperiods representative of the conditions occurring in the dry, transition, and wet periods were isolated to follow the evolution of the aerosol chemical composition as a function of changes in rainfall rate and in the strength of the sources of particulate matter. The chemical data set provided by the SMOCC field experiment will be useful to characterize the aerosol hygroscopic properties and the ability of the particles to act as cloud condensation nuclei.
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| 8. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 9. |
- Pundrich, Gabriel, et al.
(författare)
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Corporate Bankruptcy and Directors' Reputation: An Empirical Analysis of the Effects on Public Debt Contracts
- 2023
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Ingår i: Journal of Accounting, Auditing and Finance. - : Sage. - 2160-4061 .- 0148-558X. ; 38:4, s. 777-803
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Tidskriftsartikel (refereegranskat)abstract
- This article investigates the link between board members' past professional experiences and the terms and conditions of the debt contracts of their current firms. In particular, we examine whether directors' past bankruptcy experience affects the pricing and nonpricing terms of public debt contracts. Using a sample of 8,142 bond issues in the United States in the period 1995 to 2015, we document higher credit spreads and smaller bond sizes for firms with such directors, suggesting that bondholders are concerned about past bankruptcy experience. Our results remain robust to different model specifications. This effect is moderated for bankruptcies that are likely driven by macroeconomic shocks such as the dotcom bubble and the global financial crisis. We also show that our findings are not explained by bond issuers with an elevated risk of default and seem instead to be driven by directors serving on key monitoring committees, indicating that prior bankruptcy experience raises concerns about the company's corporate governance. Finally, mediation analysis offers some evidence of a limited negative indirect effect of prior bankruptcy experience on the terms of debt contracts through the firm's financial and investment policies. Overall, our findings suggest that lenders incorporate information about past professional experiences of directors into public debt contracting.
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| 10. |
- Sarneel, Judith M., et al.
(författare)
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Reading tea leaves worldwide : decoupled drivers of initial litter decomposition mass-loss rate and stabilization
- 2024
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Ingår i: Ecology Letters. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
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| 11. |
- Sarneel, Judith M., et al.
(författare)
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Reading tea leaves worldwide: Decoupled drivers of initial litter decomposition mass-loss rate and stabilization
- 2024
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Ingår i: ECOLOGY LETTERS. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
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