| 1. |
- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 5. |
- Arevalo-Martinez, D. L., et al.
(författare)
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Ideas and perspectives: Land-ocean connectivity through groundwater
- 2023
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 20:3, s. 647-662
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Tidskriftsartikel (refereegranskat)abstract
- For millennia, humans have gravitated towards coastlines for theirresource potential and as geopolitical centres for global trade. A basicrequirement ensuring water security for coastal communities relies on adelicate balance between the supply and demand of potable water. Theinteraction between freshwater and saltwater in coastal settings is,therefore, complicated by both natural and human-driven environmentalchanges at the land-sea interface. In particular, ongoing sea-level rise,warming and deoxygenation might exacerbate such perturbations. In thiscontext, an improved understanding of the nature and variability ofgroundwater fluxes across the land-sea continuum is timely yet remains outof reach. The flow of terrestrial groundwater across the coastal transitionzone and the extent of freshened groundwater below the present-dayseafloor are receiving increased attention in marine and coastal sciencesbecause they likely represent a significant yet highly uncertain componentof (bio)geochemical budgets and because of the emerging interest in thepotential use of offshore freshened groundwater as a resource. At the sametime, "reverse" groundwater flux from offshore to onshore is of prevalentsocio-economic interest, as terrestrial groundwater resources arecontinuously pressured by over-pumping and seawater intrusion in many coastalregions worldwide. An accurate assessment of the land-ocean connectivitythrough groundwater and its potential responses to future anthropogenicactivities and climate change will require a multidisciplinary approachcombining the expertise of geophysicists, hydrogeologists, (bio)geochemistsand modellers. Such joint activities will lay the scientific basis forbetter understanding the role of groundwater in societally relevant issuessuch as climate change, pollution and the environmental status of thecoastal oceans within the framework of the United Nations SustainableDevelopment Goals. Here, we present our perspectives on future researchdirections to better understand land-ocean connectivity through groundwater,including the spatial distributions of the essential hydrogeologicalparameters, highlighting technical and scientific developments and brieflydiscussing the societal relevance of that connectivity in rapidly changing coastal oceans.
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| 9. |
- Voronina, N, et al.
(författare)
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The age of adult pilocytic astrocytoma cells
- 2021
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 40:16, s. 2830-2841
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Tidskriftsartikel (refereegranskat)abstract
- Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been unclear whether adult PAs arise early in life and remain asymptomatic until adulthood, or whether they develop during adulthood. We sought to determine the age and origin of adult human PAs using two types of “marks” in the genomic DNA. First, we analyzed the DNA methylation patterns of adult and pediatric PAs to distinguish between PAs of different anatomic locations (n = 257 PA and control brain tissues). Second, we measured the concentration of nuclear bomb test-derived 14C in genomic DNA (n = 14 cases), which indicates the time point of the formation of human cell populations. Our data suggest that adult and pediatric PAs developing in the infratentorial brain are closely related and potentially develop from precursor cells early in life, whereas supratentorial PAs might show age and location-specific differences.
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| 10. |
- Elsir, T., et al.
(författare)
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PROX1 is a predictor of survival for gliomas WHO grade II
- 2011
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 104:11, s. 1747-1754
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Tidskriftsartikel (refereegranskat)abstract
- Background:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.Methods:A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Results:Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.Conclusion:PROX1 is a novel predictor of survival for grade II gliomas.
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| 11. |
- Soffietti, R, et al.
(författare)
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Management of Low-Grade Gliomas
- 2011. - 2
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Ingår i: European Handbook of Neurological Management. - Oxford, UK : Blackwell Publishing Ltd. - 9781405185349 - 9781444346268 ; , s. 213-223
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Bokkapitel (refereegranskat)
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| 13. |
- Edsjö, Anders, et al.
(författare)
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Precision cancer medicine : Concepts, current practice, and future developments
- 2023
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Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 294:4, s. 455-481
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Forskningsöversikt (refereegranskat)abstract
- Precision cancer medicine is a multidisciplinary team effort that requires involvement and commitment of many stakeholders including the society at large. Building on the success of significant advances in precision therapy for oncological patients over the last two decades, future developments will be significantly shaped by improvements in scalable molecular diagnostics in which increasingly complex multilayered datasets require transformation into clinically useful information guiding patient management at fast turnaround times. Adaptive profiling strategies involving tissue- and liquid-based testing that account for the immense plasticity of cancer during the patient's journey and also include early detection approaches are already finding their way into clinical routine and will become paramount. A second major driver is the development of smart clinical trials and trial concepts which, complemented by real-world evidence, rapidly broaden the spectrum of therapeutic options. Tight coordination with regulatory agencies and health technology assessment bodies is crucial in this context. Multicentric networks operating nationally and internationally are key in implementing precision oncology in clinical practice and support developing and improving the ecosystem and framework needed to turn invocation into benefits for patients. The review provides an overview of the diagnostic tools, innovative clinical studies, and collaborative efforts needed to realize precision cancer medicine.
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| 15. |
- Keck, Michaela Kristina, et al.
(författare)
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Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
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| 16. |
- Northcott, Paul A, et al.
(författare)
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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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| 17. |
- Soffietti, R., et al.
(författare)
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Guidelines on management of low-grade gliomas : report of an EFNS-EANO* Task Force
- 2010
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 17:9, s. 1124-1133
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDDiffuse infiltrative low-grade gliomas of the cerebral hemispheres in the adult are a group of tumors with distinct clinical, histological and molecular characteristics, and there are still controversies in management.METHODSThe scientific evidence of papers collected from the literature was evaluated and graded according to EFNS guidelines, and recommendations were given accordingly.RESULTS AND CONCLUSIONSWHO classification recognizes grade II astrocytomas, oligodendrogliomas and oligoastrocytomas. Conventional MRI is used for differential diagnosis, guiding surgery, planning radiotherapy and monitoring treatment response. Advanced imaging techniques can increase the diagnostic accuracy. Younger age, normal neurological examination, oligodendroglial histology and 1p loss are favorable prognostic factors. Prophylactic antiepileptic drugs are not useful, whilst there is no evidence that one drug is better than the others. Total/near total resection can improve seizure control, progression-free and overall survival, whilst reducing the risk of malignant transformation. Early post-operative radiotherapy improves progression-free but not overall survival. Low doses of radiation are as effective as high doses and better tolerated. Modern radiotherapy techniques reduce the risk of late cognitive deficits. Chemotherapy can be useful both at recurrence after radiotherapy and as initial treatment after surgery to delay the risk of late neurotoxicity from large-field radiotherapy. Neurocognitive deficits are frequent and can be caused by the tumor itself, tumor-related epilepsy, treatments and psychological distress.
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| 18. |
- Strauss, Jens, et al.
(författare)
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Deep Yedoma permafrost : A synthesis of depositional characteristics and carbon vulnerability
- 2017
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Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 172, s. 75-86
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Tidskriftsartikel (refereegranskat)abstract
- Permafrost is a distinct feature of the terrestrial Arctic and is vulnerable to climate warming. Permafrost degrades in different ways, including deepening of a seasonally unfrozen surface and localized but rapid development of deep thaw features. Pleistocene ice-rich permafrost with syngenetic ice-wedges, termed Yedoma deposits, are widespread in Siberia, Alaska, and Yukon, Canada and may be especially prone to rapid-thaw processes. Freeze-locked organic matter in such deposits can be re-mobilized on short time-scales and contribute to a carbon-cycle climate feedback. Here we synthesize the characteristics and vulnerability of Yedoma deposits by synthesizing studies on the Yedoma origin and the associated organic carbon pool. We suggest that Yedoma deposits accumulated under periglacial weathering, transport, and deposition dynamics in non-glaciated regions during the late Pleistocene until the beginning of late glacial warming. The deposits formed due to a combination of aeolian, colluvial, nival, and alluvial deposition and simultaneous ground ice accumulation. We found up to 130 gigatons organic carbon in Yedoma, parts of which are well-preserved and available for fast decomposition after thaw. Based on incubation experiments, up to 10% of the Yedoma carbon is considered especially decomposable and may be released upon thaw. The substantial amount of ground ice in Yedoma makes it highly vulnerable to disturbances such as thermokarst and thermo-erosion processes. Mobilization of permafrost carbon is expected to increase under future climate warming. Our synthesis results underline the need of accounting for Yedoma carbon stocks in next generation Earth-System-Models for a more complete representation of the permafrost-carbon feedback.
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