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- Del Chiaro, M, et al.
(författare)
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European evidence-based guidelines on pancreatic cystic neoplasms
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:5, s. 789-804
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
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- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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- Moschini, M, et al.
(författare)
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Open Versus Robotic Cystectomy: A Propensity Score Matched Analysis Comparing Survival Outcomes
- 2019
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.
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- Balaz, M., et al.
(författare)
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Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation
- 2019
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 29:4
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Tidskriftsartikel (refereegranskat)abstract
- Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modulating brown adipocyte functionality and systemic metabolism.
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| 17. |
- Canelas, A.B., et al.
(författare)
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Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains
- 2010
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 1:9
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Tidskriftsartikel (refereegranskat)abstract
- The field of systems biology is often held back by difficulties in obtaining comprehensive, high-quality, quantitative data sets. In this paper, we undertook an interlaboratory effort to generate such a data set for a very large number of cellular components in the yeast Saccharomyces cerevisiae, a widely used model organism that is also used in the production of fuels, chemicals, food ingredients and pharmaceuticals. With the current focus on biofuels and sustainability, there is much interest in harnessing this species as a general cell factory. In this study, we characterized two yeast strains, under two standard growth conditions. We ensured the high quality of the experimental data by evaluating a wide range of sampling and analytical techniques. Here we show significant differences in the maximum specific growth rate and biomass yield between the two strains. On the basis of the integrated analysis of the high-throughput data, we hypothesize that differences in phenotype are due to differences in protein metabolism.
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- Fantin, F, et al.
(författare)
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Impaired subendocardial perfusion in patients with metabolic syndrome
- 2021
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Ingår i: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 18:6, s. 14791641211047135-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic Syndrome (MS) is associated to vascular damage, increased arterial stiffness, and impaired myocardial perfusion. Subendocardial viability ratio (SEVR) is a noninvasive estimation of myocardial workload, oxygen supply, and perfusion. The aim of the study was to describe the relation between arterial stiffness, SEVR, and cardio-metabolic risk factors. Methods A cohort of 55 patients, aged 59.9 ± 10.8 years, was studied; 28 subjects (50.9%) had metabolic syndrome. All patients underwent a clinical evaluation and blood venous sampling, to assess glico-lipid profile. Applanation tonometry was performed, to obtain pulse wave analysis and SEVR values. Results In the overall study population, SEVR showed negative associations with mean (r = −0.301; p = 0.026) and systolic (borderline relation, r = −0.257; p = 0.058) arterial pressure. Metabolic syndrome patients presented lower level of SEVR ( p = 0.012), even after adjusting for age, sex, and mean arterial pressure ( p = 0.040). Subdividing the study population by the number of metabolic syndrome components, SEVR significantly decreased as the number of Metabolic Syndrome components increased ( p for trend 0.005). In a logistic backward regression analysis, both metabolic syndrome and mean arterial pressure resulted significant predictors of SEVR, accounting for 18% of variance. Conclusion The reduced SEVR in metabolic syndrome patients could be an important pathophysiological determinant of the increased cardiovascular risk.
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| 22. |
- Fantin, F, et al.
(författare)
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Weight Loss and Hypertension in Obese Subjects
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Arterial hypertension is strongly related to overweight and obesity. In obese subjects, several mechanisms may lead to hypertension such as insulin and leptin resistance, perivascular adipose tissue dysfunction, renal impairment, renin-angiotensin-aldosterone-system activation and sympathetic nervous system activity. Weight loss (WL) seems to have positive effects on blood pressure (BP). The aim of this review was to explain the mechanisms linking obesity and hypertension and to evaluate the main studies assessing the effect of WL on BP. We analysed studies published in the last 10 years (13 studies either interventional or observational) showing the effect of WL on BP. Different WL strategies were taken into account—diet and lifestyle modification, pharmacological intervention and bariatric surgery. Although a positive effect of WL could be identified in each study, the main difference seems to be the magnitude and the durability of BP reduction over time. Nevertheless, further follow-up data are needed: there is still a lack of evidence about long term effects of WL on hypertension. Hence, given the significant results obtained in several recent studies, weight management should always be pursued in obese patients with hypertension.
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| 26. |
- Posati, Tamara, et al.
(författare)
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Polydopamine Nanoparticle-Coated Polysulfone Porous Granules as Adsorbents for Water Remediation
- 2019
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 4:3, s. 4839-4847
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Tidskriftsartikel (refereegranskat)abstract
- Water purification technologies possibly based on eco-sustainable, low cost, and multifunctional materials are being intensively pursued to resolve the current water scarcity and pollution. In this scenario, polysulfone hollow porous granules (PS-HPGs) prepared from scraps of the industrial production of polysulfone hollow fiber membranes were recently introduced as adsorbents and filtration materials for water and air treatment. Here, we report the functionalization of PS-HPGs with polydopamine (PD) nanoparticles for the preparation of a new versatile and efficient adsorbent material, namely, PSPD-HPGs. The in situ growth of PD under mild alkaline oxidative polymerization allowed us to stably graft PD on polysulfone granules. Enhanced removal efficiency of ofloxacin, an antibiotic drug, with an improvement up to 70% with respect to the pristine PS-HPGs, and removal of Zn(II) and Ni(II) were also observed after PD modification. Remarkably, removal of Cu(II) ions with an efficiency up to 80% was observed for PSPD-HPGs, whereas no adsorption was found for the PD-free precursor. Collectively, these data show that modification with a biocompatible polymer such as PD provides a simple and valuable tool to enlarge the field of application of polysulfone hollow granules for water remediation from both organic and metal cation contaminants.
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| 28. |
- van der Kolk, Birgitta W., et al.
(författare)
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Molecular pathways behind acquired obesity : Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI
- 2021
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Ingår i: Cell Reports Medicine. - : Elsevier BV. - 2666-3791. ; 2:4, s. 100226-
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Tidskriftsartikel (refereegranskat)abstract
- Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity.
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