| 1. |
- Correa, D. F., et al.
(författare)
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Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates
- 2023
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 32:1, s. 49-69
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period Tree-inventory plots established between 1934 and 2019. Major taxa studied Trees with a diameter at breast height (DBH) >= 9.55 cm. Location Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types.
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| 2. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 4. |
- Michelsen, B., et al.
(författare)
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Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration
- 2020
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries. METHODS: Real-life data from 13 European registries participating in the European Spondyloarthritis Research Collaboration Network were pooled. Kaplan-Meier with log-rank test, Cox regression, χ² and logistic regression analyses were performed to assess 6-month and 12-month secukinumab retention, inactive disease/low-disease-activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <2/<4, Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3/<2.1) and response rates (BASDAI50, Assessment of Spondyloarthritis International Society (ASAS) 20/40, ASDAS clinically important improvement (ASDAS-CII) and ASDAS major improvement (ASDAS-MI)). RESULTS: We included 1860 patients initiating secukinumab as part of routine care. Overall 6-month/12-month secukinumab retention rates were 82%/72%, with significant (p<0.001) differences between the registries (6-month: 70-93%, 12-month: 53-86%) and across number of previous b/tsDMARDs (b/tsDMARD-naïve: 90%/73%, 1 prior b/tsDMARD: 83%/73%, ≥2 prior b/tsDMARDs: 78%/66%). Overall 6-month/12-month BASDAI<4 were observed in 51%/51%, ASDAS<1.3 in 9%/11%, BASDAI50 in 53%/47%, ASAS40 in 28%/22%, ASDAS-CII in 49%/46% and ASDAS-MI in 25%/26% of the patients. All rates differed significantly across number of previous b/tsDMARDs, were numerically higher for b/tsDMARD-naïve patients and varied significantly across registries. Overall, time since diagnosis was not associated with secukinumab effectiveness. CONCLUSIONS: In this study of 1860 patients from 13 European countries, we present the first comprehensive real-life data on effectiveness of secukinumab in patients with axSpA. Overall, secukinumab retention rates after 6 and 12months of treatment were high. Secukinumab effectiveness was consistently better for bionaïve patients, independent of time since diagnosis and differed across the European countries. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 5. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 6. |
- Lindström, Ulf, et al.
(författare)
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Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1410-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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| 7. |
- Ortigoza-Escobar, J. D., et al.
(författare)
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Thiamine deficiency in childhood with attention to genetic causes: Survival and outcome predictors
- 2017
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134. ; 82:3, s. 317-330
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Tidskriftsartikel (refereegranskat)abstract
- Primary and secondary conditions leading to thiamine deficiency have overlapping features in children, presenting with acute episodes of encephalopathy, bilateral symmetric brain lesions, and high excretion of organic acids that are specific of thiamine-dependent mitochondrial enzymes, mainly lactate, alpha-ketoglutarate, and branched chain keto-acids. Undiagnosed and untreated thiamine deficiencies are often fatal or lead to severe sequelae. Herein, we describe the clinical and genetic characterization of 79 patients with inherited thiamine defects causing encephalopathy in childhood, identifying outcome predictors in patients with pathogenic SLC19A3 variants, the most common genetic etiology. We propose diagnostic criteria that will aid clinicians to establish a faster and accurate diagnosis so that early vitamin supplementation is considered. Ann Neurol 2017;82:317–330. © 2017 American Neurological Association
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| 8. |
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| 9. |
- Michelsen, B., et al.
(författare)
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Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis
- 2020
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 59:9, s. 2455-2461
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (Delta PEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. Methods. Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by chi(2) test and by logistic regression across quartiles of baseline Delta PEG, separately in female and male PsA and axSpA patients. Results. We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline Delta PEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P < 0.001), with 6/12/24-months' BASDAI < 2 (P <= 0.002) and ASDAS < 1.3 (P <= 0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P <= 0.04) and DAPSA28 <= 4 (P <= 0.01), but not DAS28CRP(3)<2.6 (P >= 0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. Conclusion. High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.
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