| 1. |
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Ambros, I. M., et al.
(författare)
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Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:31
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEFor localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODSDiagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTSPatients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] standard deviation [SD], 95% +/- 2%; 5-year overall survival [OS], 99% +/- 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS +/- SD, 84% +/- 3% in patients < 18 months of age and 75% 7% in patients >= 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS +/- SD in < 18months and 18months, 96% +/- 2% and 81% +/- 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS SD in patients 1p loss and no 1p loss, 62% +/- 13% and 87% +/- 3%, respectively; P = .019) but not OS (5-year OS +/- SD, 92% +/- 8% and 97% +/- 2%, respectively). In patients >= 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS +/- SD, 48% +/- 16% and 85% +/- 7%, P = .033; 5-year OS +/- SD, 46% +/- 22% and 92% +/- 6%, P = .038).CONCLUSIONGenomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
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| 10. |
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| 11. |
- Azevedo, Josué, et al.
(författare)
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Museums and cradles of diversity are geographically coincident for narrowly distributed Neotropical snakes
- 2020
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Ingår i: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 43:2, s. 328-339
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Tidskriftsartikel (refereegranskat)abstract
- Factors driving the spatial configuration of centres of endemism have long been a topic of broad interest and debate. Due to different eco-evolutionary processes, these highly biodiverse areas may harbour different amounts of ancient and recently diverged organisms (paleo- and neo-endemism, respectively). Patterns of endemism still need to be measured at distinct phylogenetic levels for most clades and, consequently, little is known about the distribution, the age and the causes of such patterns. Here we tested for the presence of centres with high phylogenetic endemism (PE) in the highly diverse Neotropical snakes, testing the age of these patterns (paleo- or neo-endemism), and the presence of PE centres with distinct phylogenetic composition. We then tested whether PE is predicted by topography, by climate (seasonality, stability, buffering and relictualness), or biome size. We found that most areas of high PE for Neotropical snakes present a combination of both ancient and recently diverged diversity, which is distributed mostly in the Caribbean region, Central America, the Andes, the Atlantic Forest and on scattered highlands in central Brazil. Turnover of lineages is higher across Central America, resulting in more phylogenetically distinct PE centres compared to South America, which presents a more phylogenetically uniform snake fauna. Finally, we found that elevational range (topographic roughness) is the main predictor of PE, especially for paleo-endemism, whereas low paleo-endemism levels coincide with areas of high climatic seasonality. Our study highlights the importance of mountain systems to both ancient and recent narrowly distributed diversity. Mountains are both museums and cradles of snake diversity in the Neotropics, which has important implications for conservation in this region.
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| 12. |
- Defferrari, R., et al.
(författare)
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Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:2, s. 290-295
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. Methods: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. Results: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P = 0.04). A significant correlation (P = 0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS = 46% vs 75%, P = 0.023; OS = 66.8% vs 100%, P = 0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P = 0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P = 0.018). Conclusions: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.
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| 13. |
- Passariello, A., et al.
(författare)
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Constitutional 11q14-q22 chromosome deletion syndrome in a child with neuroblastoma MYCN single copy
- 2013
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212. ; 56:11, s. 626-634
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Tidskriftsartikel (refereegranskat)abstract
- Constitutional 11q deletion is a chromosome imbalance possibly found in MCA/MR patients analyzed for chromosomal anomalies. Its role in determining the phenotype depends on extension and position of deleted region. Loss of heterozygosity of 11q (region 11q23) is also associated with neuroblastoma, the most frequent extra cranial cancer in children. It represents one of the most frequent cytogenetic abnormalities observed in the tumor of patients with high-risk disease even if germline deletion of 11q in neuroblastoma is rare. Hereby, we describe a 18 months old girl presenting with trigonocephaly and dysmorphic facial features, including hypotelorism, broad depressed nasal bridge, micrognathia, synophrys, epicanthal folds, and with a stage 4 neuroblastoma without MYCN amplification, carrying a germline 11q deletion (11q14.1-q22.3), outside from Jacobsen syndrome and from neuroblastoma 11q critical regions. The role of 11q deletion in determining the clinical phenotype and its association with neuroblastoma development in the patient are discussed. (C) 2013 Elsevier Masson SAS. All rights reserved.
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| 14. |
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| 15. |
- Gamble, LD, et al.
(författare)
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A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.
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| 16. |
- Valencia-Montoya, Wendy A., et al.
(författare)
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Evolutionary trade-offs between male secondary sexual traits revealed by a phylogeny of the hyperdiverse tribe Eumaeini (Lepidoptera: Lycaenidae)
- 2021
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 288:1950
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Tidskriftsartikel (refereegranskat)abstract
- Male butterflies in the hyperdiverse tribe Eumaeini possess an unusually complex and diverse repertoire of secondary sexual characteristics involved in pheromone production and dissemination. Maintaining multiple sexually selected traits is likely to be metabolically costly, potentially resulting in trade-offs in the evolution of male signals. However, a phylogenetic framework to test hypotheses regarding the evolution and maintenance of male sexual traits in Eumaeini has been lacking. Here, we infer a comprehensive, time-calibrated phylogeny from 379 loci for 187 species representing 91% of the 87 described genera. Eumaeini is a monophyletic group that originated in the late Oligocene and underwent rapid radiation in the Neotropics. We examined specimens of 818 of the 1096 described species (75%) and found that secondary sexual traits are present in males of 91% of the surveyed species. Scent pads and scent patches on the wings and brush organs associated with the genitalia were probably present in the common ancestor of Eumaeini and are widespread throughout the tribe. Brush organs and scent pads are negatively correlated across the phylogeny, exhibiting a trade-off in which lineages with brush organs are unlikely to regain scent pads and vice versa. In contrast, scent patches seem to facilitate the evolution of scent pads, although they are readily lost once scent pads have evolved. Our results illustrate the complex interplay between natural and sexual selection in the origin and maintenance of multiple male secondary sexual characteristics and highlight the potential role of sexual selection spurring diversification in this lineage.
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| 17. |
- Vomiero, Alberto, et al.
(författare)
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Structural properties of reactively sputtered W-Si-N thin films
- 2007
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 102:3
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Tidskriftsartikel (refereegranskat)abstract
- Tungsten-silicon-nitrogen, W-Si-N, ternary thin films have been reactively sputter deposited from W5 Si3 and W Si2 targets using several nitrogen partial pressures. The films have been thermal annealed in the 600-1000 °C temperature range and a wide region of the W-Si-N ternary phase diagram has been explored by changing the N2 Ar ratio during the deposition. Multitechnique approach was adopted for the analysis of the samples. Composition has been determined via ion beam analysis; chemical states were investigated using x-ray photoelectron spectroscopy (XPS); crystalline structure was studied using transmission electron microscopy (TEM) and x-ray diffraction (XRD) and surface morphology by scanning electron microscope. The films deposited in pure argon atmosphere are tungsten rich and approach the target contents as N2 Ar ratio is varied during deposition. Tungsten enrichment in the films is caused by resputtering of silicon which can be inhibited by the formation of silicon nitride, allowing films with SiW ratio closer to the target compositions. The higher capability to form nitrides with silicon than with tungsten favors enhancement of nitrogen content in samples deposited from the silicon rich target (W Si2). The samples with excess nitrogen content have shown losses of this element after thermal treatment. XPS measurements show a break of W-N bonds caused by thermal instability of tungsten nitrides. TEM and XRD revealed the segregation of tungsten in form of metallic or silicide nanoclusters in samples with low nitrogen content (W58 Si21 N21 and W24 Si42 N34). High amounts of nitrogen were revealed to be highly effective in inhibiting metallic cluster coalescence. Measurements of electrical resistivity of as deposited films were performed using four point probe technique. They were found to lie in the range between 0.4 and 79 m cm depending on sample composition. © 2007 American Institute of Physics.
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| 18. |
- Spagnuolo, M. S., et al.
(författare)
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A Short-Term Western Diet Impairs Cholesterol Homeostasis and Key Players of Beta Amyloid Metabolism in Brain of Middle Aged Rats
- 2020
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Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 64:16
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Tidskriftsartikel (refereegranskat)abstract
- Scope Cholesterol homeostasis is crucial for brain functioning. Unhealthy nutrition can influence cerebral physiology, but the effect of western diets on brain cholesterol homeostasis, particularly at middle age, is unknown. Given the link between brain cholesterol alteration and beta amyloid production, the aim is to evaluate whether a diet rich in fat and fructose affects the protein network implicated in cholesterol synthesis and shuttling between glial cells and neurons, as well as crucial markers of beta amyloid metabolism. Methods and results Middle aged rats are fed a high fat-high fructose (HFF) or a control diet for 4 weeks. Inflammatory markers and cholesterol levels significantly increase in hippocampus of HFF rats. A higher activation of 3-hydroxy 3-methylglutaryl coenzyme-A reductase, coupled with lower levels of apolipoprotein E, LXR-beta, and lipoproteins receptors is measured in hippocampus from HFF rats. The alteration of critical players of cholesterol homeostasis is associated with increased level of amyloid precursor protein, presenilin 1, and nicastrin, and decreased level of insulin degrading enzyme. Conclusions Overall these data show that a western diet is associated with perturbation of cholesterol homeostasis in middle aged rats, mostly in hippocampus. This might trigger molecular events involved in the onset of neurodegenerative diseases.
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| 19. |
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| 20. |
- Tonini, C., et al.
(författare)
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The fundamental manifold of spiral galaxies: ordered versus random motions and the morphology dependence of the Tully-Fisher relation
- 2014
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 438:4, s. 3332-3339
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the morphology dependence of the Tully-Fisher (TF) relation, and the expansion of the relation into a three-dimensional manifold defined by luminosity, total circular velocity and a third dynamical parameter, to fully characterize spiral galaxies across all morphological types. We use a full semi-analytic hierarchical model (based on Croton et al.), built on cosmological simulations of structure formation, to model galaxy evolution and build the theoretical TF relation. With this tool, we analyse a unique data set of galaxies for which we cross-match luminosity with total circular velocity and central velocity dispersion. We provide a theoretical framework to calculate such measurable quantities from hierarchical semi-analytic models. We establish the morphology dependence of the TF relation in both model and data. We analyse the dynamical properties of the model galaxies and determine that the parameter Sigma/V-C, i.e. the ratio between random and total motions defined by velocity dispersion and circular velocity, accurately characterizes the varying slope of the TF relation for different model galaxy types. We apply these dynamical cuts to the observed galaxies and find indeed that such selection produces a differential slope of the TF relation. The TF slope in different ranges of Sigma/V-C is consistent with that for the traditional photometric classification in Sa, Sb and Sc. We conclude that Sigma/V-C is a good parameter to classify galaxy type, and we argue that such classification based on dynamics more closely mirrors the physical properties of the observed galaxies, compared to visual (photometric) classification. We also argue that dynamical classification is useful for samples where eye inspection is not reliable or impractical. We conclude that Sigma/V-C is a suitable parameter to characterize the hierarchical assembly history that determines the disc-to-bulge ratio, and to expand the TF relation into a three-dimensional manifold, defined by luminosity, circular velocity and Sigma/V-C.
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| 21. |
- Ussia, A., et al.
(författare)
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Laparoscopic appendectomy as an index procedure for surgical trainees: clinical outcomes and learning curve
- 2021
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Ingår i: Updates in Surgery. - : Springer Science and Business Media LLC. - 2038-131X .- 2038-3312. ; 73, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Surgical training is essential to maintain safety standards in healthcare. The aim of this study is to evaluate learning curves and short-term postoperative outcomes of laparoscopic appendectomy (LA) performed by trainees (TRN) and attendings (ATT). The present study included the medical records of patients with acute appendicitis who underwent a fully LA in our department between January 2013 and December 2018. Cases were divided into trainees (TRN and ATT groups based on the experience of the operating surgeon. The primary outcome measures were 30-day morbidity and mortality. Preoperative patients' clinical characteristics, intraoperative findings, operative times, and postoperative hospitalization were compared. Operative times were used to extrapolate learning curves and evaluate the effects of changes in faculty using CUSUM charts. A propensity score matching analysis was performed to reduce differences between cohorts regarding both preoperative characteristics and intraoperative findings. A total of 1173 patients undergoing LA for acute appendicitis were included, of whom 521 (45%) in the TRN group and 652 (55%) in the ATT group. No significant differences were found between the two groups in terms of complication rates, operative times and length of hospital stay. However, CUSUM chart analysis showed decreased operating times in the TRN group. Operative times improved more quickly for advanced cases. The results of this study indicate that LA can be performed by trainees without detrimental effects on clinical outcomes, procedural safety, and operative times. However, the learning curve is longer than previously acknowledged.
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| 22. |
- Vomiero, Alberto, et al.
(författare)
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Composition and resistivity changes of reactively sputtered W-Si-N thin films under vacuum annealing
- 2006
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 88:3, s. 1-3
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Tidskriftsartikel (refereegranskat)abstract
- W-Si-N layers about 200 nm thick with different nitrogen content were reactively sputtered from a W5 Si3 target on oxidized silicon substrates. The thermal stability of the films' composition and resistivity was studied with ion beam analysis and four-point probe measurements. Upon vacuum annealing from 600 to 980 °C for 1.5 h, a sample with an initial 56 at. % of nitrogen gradually loses nitrogen down to 36%. This composition lies close to the W- Si3 N4 tie line. Concurrently, the room temperature resistivity decreases from 4.7 to about 2 mΩ cm. The composition changes only a little for a sample whose initial composition is near the W- Si3 N4 tie line and the resistivity changes significantly less than for the nitrogen-rich film. Interpretations are discussed. © 2006 American Institute of Physics.
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