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  • Flores-Morales, Amilcar, et al. (författare)
  • Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer
  • 2019
  • Ingår i: Clinical Cancer Research. - American Association for Cancer Research. - 1078-0432. ; 25:2, s. 595-608
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood. Experimental Design: We applied mass spectrometry–based proteomics to a unique set of 17 prostate cancer patient–derived xenografts (PDX) to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas. Genome-wide profiling of REST-occupied regions in prostate cancer cells was correlated to the expression changes in vivo to investigate the role of the transcriptional repressor REST in castration-induced NEPC differentiation. Results: An average of 4,881 proteins were identified and quantified from each PDX. Proteins related to neurogenesis, cell-cycle regulation, and DNA repair were found upregulated and elevated in NEPC, while the reduced levels of proteins involved in mitochondrial functions suggested a prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin bound regions with expression changes indicated a direct role of REST in regulating neuronal gene expression in prostate cancer cells. Mechanistically, depletion of REST led to cell-cycle arrest in G1, which could be rescued by p53 knockdown. Finally, the expression of the REST-regulated gene secretagogin (SCGN) correlated with an increased risk of suffering disease relapse after radical prostatectomy. Conclusions: This study presents the first deep characterization of the proteome of NEPC and suggests that concomitant inhibition of REST and the p53 pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in prostate cancer.
  • Guiomar, N., et al. (författare)
  • Typology and distribution of small farms in Europe : Towards a better picture
  • 2018
  • Ingår i: Land use policy. - 0264-8377 .- 1873-5754. ; 75, s. 784-798
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The contribution of small farms to local food supply, food security and food sovereignty is widely acknowledged at a global level. In the particular case of Europe, they often are seen as an alternative to large and specialised farms. Assessing the real role of small farms has been limited by a lack of information, as small farms are frequently omitted from agricultural censuses and national statistics. It is also well acknowledged that small farms differ widely, and are distributed according to different spatial patterns across Europe, fulfilling different roles according to the agriculture and territorial characteristics of each region. This paper presents the result of a novel classification of small farms at NUTS-3 level in Europe, according to the relevance of small farms in the agricultural and territorial context of each region, and based on a typology of small farms considering different dimensions of farm size. The maps presented result from an extensive data collection and variables selected according to European wide expert judgement, analysed with advanced cluster procedures. The results provide a fine grained picture of the role of small farms at the regional level in Europe today, and are expected to support further data analysis and targeted policy intervention.</p>
  • Gülfe, Anders, et al. (författare)
  • Efficacy and drug survival of anti-tumour necrosis factor-alpha therapies in patients with non-radiographic axial spondyloarthritis: an observational cohort study from Southern Sweden.
  • 2014
  • Ingår i: Scandinavian Journal of Rheumatology. - Taylor & Francis. - 1502-7732. ; 43:6, s. 493-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the efficacy and drug survival of anti-tumour necrosis factor (anti-TNF) therapy in non-radiographic axial spondyloarthritis (nr-axSpA) patients treated in clinical practice in Southern Sweden. Method: In this cohort study we prospectively included 112 patients with nr-axSpA and high disease activity as well as inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) receiving their first course of anti-TNF therapy. Patients fulfilling modified New York criteria for ankylosing spondylitis (AS) were excluded. The Assessment of SpondyloArthritis International Society (ASAS) criteria for axial SpA were fulfilled by 77% (n = 86) of the included patients. Results: At baseline, the median age of the cohort was 38 years, 59% were males, 79% of the patients had imaging suggestive of sacroiliitis (primarily inflammation on magnetic resonance imaging, MRI), 71% were HLA-B27 positive, and the median disease duration was 6 years and 10 months. At 6 months of follow-up, the median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.6 to 3.2 (p = 0.002), the Bath Ankylosing Spondylitis Functional Index (BASFI) decreased from 3.9 to 1.8 (p = 0.005), and C-reactive protein (CRP) level decreased from 4.4 to 1.7 mg/L (p = 0.001). After 1 year of treatment the Kaplan-Meier estimated drug survival was 76%, and at 2 years of follow-up this value decreased to 65%. Patients with inflammatory MRI findings at baseline had significantly better drug survival [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.10-0.55, p = 0.001]. Male sex was also associated with higher drug survival (HR 0.45, 95% CI 0.24-0.85, p = 0.011). CRP level at baseline was not associated with drug survival. Conclusions: Anti-TNF treatment of patients with nr-axSpA in clinical practice resulted in reduced BASDAI and BASFI scores and good drug survival. The results from this study suggest that male gender and positive imaging at baseline are associated with a favourable treatment course.
  • Gülfe, Anders, et al. (författare)
  • Rapid and sustained health utility gain in anti-TNF treated inflammatory arthritis. Observational data during seven years in southern Sweden.
  • 2010
  • Ingår i: Annals of the Rheumatic Diseases. - British Medical Association. - 1468-2060. ; 69:2, s. 352-357
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and other spondylarthritides (SpA) impose great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry independent health economic studies should complement studies sponsored by industry. OBJECTIVE: To study secular trends in baseline health utilities in patients commencing TNF blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures, and to compare them across diagnostic entities. METHODS: /B> EuroQoL 5 Dimensions (EQ-5D) utility data were collected from a structured clinical follow-up program of anti-TNF treated patients with RA (N=2554), PsA (N=574) or SpA (N=586). Time trends were calculated. Completer analysis was used. RESULTS: /B> There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and SpA. Maximum gain in utilities occurred already after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. First and second anti-TNF courses performed similarly. CONCLUSIONS: Utilities at inclusion remained largely unchanged for RA, PsA and SpA over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and SpA. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.
  • Gülfe, Anders, et al. (författare)
  • Six and 12 Weeks Treatment Response Predicts Continuation of Tumor Necrosis Factor Blockade in Rheumatoid Arthritis: An Observational Cohort Study from Southern Sweden.
  • 2009
  • Ingår i: Journal of Rheumatology. - J Rheumatol Publ Co. - 0315-162X. ; 36, s. 517-521
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate if treatment response predicts continuation of anti-tumor necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: We investigated if treatment response and/or achieving a certain activity state at 6 weeks or 3 months predicts continuation of treatment in an observational cohort of 1789 anti-TNF-naive patients with established RA disease from southern Sweden. RESULTS: Response to treatment at 6 weeks at overall/American College of Rheumatology (ACR20) or good/major level (except ACR70) significantly predicted drug continuation. Response according to all criteria sets at overall/ACR20 and at good/major/ACR70 level predicted drug continuation at 3 months, as did achieving low disease activity at 3 months irrespective of activity index applied. Remaining in a high disease activity state predicted drug discontinuation at both timepoints and according to all criteria sets. CONCLUSION: Response criteria may be useful aids in deciding on continuation of TNF blockade in RA as early as after 6 weeks of treatment. The various criteria sets perform similarly.
  • Gülfe, Anders, et al. (författare)
  • Utility-based outcomes made easy: The number needed per QALY gained (NNQ). Observational cohort study from Southern Sweden of TNF blockade in inflammatory arthritis.
  • 2010
  • Ingår i: Arthritis Care and Research. - John Wiley and Sons Inc.. - 2151-4658. ; 62:10, s. 1399-1406
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE.: To introduce a novel, simple, utility based outcome measure, the Number Needed per Quality adjusted life year (QALY) gained (NNQ), and to apply it in clinical practice in anti-TNF treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylarthritis (SpA). METHODS.: The NNQ is the number of patients one has to treat in order to gain 1 QALY. It is calculated as the inverted value of the utility gain (area under curve) over 1 year in a cohort subjected to an intervention. EuroQoL-5-dimensions (EQ-5D) utility data from the South Swedish Arthritis Treatment Register was used. RESULTS.: 1001 RA, 241 PsA, and 255 SpA patients were eligible for the study. First, 2(nd) and 3(rd) treatment courses were studied. For RA, NNQ was 4.5, 6.4 and 5.2 for 1(st), 2(nd) and 3(rd) courses, respectively. For PsA and SpA, NNQ was 4.2-4.5 irrespective of treatment order. Treatment groups with N<50 were not analysed. During the study period 2002-2007, there were no secular trends of utility gains. CONCLUSION.: The NNQ is an easily derived and understandable, utility based outcome measure that may be useful for stakeholders, decision makers as well as for clinicians. It was readily applied in this study of TNF blockade across 3 arthritis diagnoses. NNQ varied little over diagnoses and treatment course order, with a possible exception in 2(nd) treatment course in RA.
  • Hallberg, Håkan, et al. (författare)
  • Modeling of Continuous Dynamic Recrystallization in Aluminum
  • 2009
  • Ingår i: DCE Technical Memorandum No. 11. - Aalborg University, Department of Civil Engineering. - 1901-7278. ; 11, s. 59-62
  • Konferensbidrag (refereegranskat)abstract
    • A constitutive model is presented, considering grain size refinement through continuous dynamic recrystallization together with an evolving dislocation density. The grain refinement is allowed to influence both the evolution of the dislocation density and the rate dependence of the material. The model is calibrated against experimental data on aluminum and numerical simulations of equal channel angular pressing (ECAP) material processing illustrates the capabilities of the model.
  • Hansen, Lea B.S., et al. (författare)
  • A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
  • 2018
  • Ingår i: Nature Communications. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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