| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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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. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 9. |
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| 10. |
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| 11. |
- Schmied, C., et al.
(författare)
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Community-developed checklists for publishing images and image analyses
- 2024
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Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 21:2
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Tidskriftsartikel (refereegranskat)abstract
- Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However, for scientists wishing to publish obtained images and image-analysis results, there are currently no unified guidelines for best practices. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here, we present community-developed checklists for preparing light microscopy images and describing image analyses for publications. These checklists offer authors, readers and publishers key recommendations for image formatting and annotation, color selection, data availability and reporting image-analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby to heighten the quality and explanatory power of microscopy data. Community-developed checklists offer best-practice guidance for biologists preparing light microscopy images and describing image analyses for publications.
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| 12. |
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| 13. |
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| 14. |
- Mohr, S., et al.
(författare)
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The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
- 2021
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Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 25:16, s. 8047-8061
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
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| 15. |
- Ramonet, M., et al.
(författare)
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The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
- 2020
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Tidskriftsartikel (refereegranskat)abstract
- During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 16. |
- Thambawita, V., et al.
(författare)
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SinGAN-Seg: Synthetic training data generation for medical image segmentation
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5 May
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Tidskriftsartikel (refereegranskat)abstract
- Analyzing medical data to find abnormalities is a time-consuming and costly task, particularly for rare abnormalities, requiring tremendous efforts from medical experts. Therefore, artificial intelligence has become a popular tool for the automatic processing of medical data, acting as a supportive tool for doctors. However, the machine learning models used to build these tools are highly dependent on the data used to train them. Large amounts of data can be difficult to obtain in medicine due to privacy reasons, expensive and time-consuming annotations, and a general lack of data samples for infrequent lesions. In this study, we present a novel synthetic data generation pipeline, called SinGAN-Seg, to produce synthetic medical images with corresponding masks using a single training image. Our method is different from the traditional generative adversarial networks (GANs) because our model needs only a single image and the corresponding ground truth to train. We also show that the synthetic data generation pipeline can be used to produce alternative artificial segmentation datasets with corresponding ground truth masks when real datasets are not allowed to share. The pipeline is evaluated using qualitative and quantitative comparisons between real data and synthetic data to show that the style transfer technique used in our pipeline significantly improves the quality of the generated data and our method is better than other state-of-the-art GANs to prepare synthetic images when the size of training datasets are limited. By training UNet++ using both real data and the synthetic data generated from the SinGAN-Seg pipeline, we show that the models trained on synthetic data have very close performances to those trained on real data when both datasets have a considerable amount of training data. In contrast, we show that synthetic data generated from the SinGAN-Seg pipeline improves the performance of segmentation models when training datasets do not have a considerable amount of data. All experiments were performed using an open dataset and the code is publicly available on GitHub.
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| 17. |
- Babic, M, et al.
(författare)
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NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells
- 2020
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:8
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Tidskriftsartikel (refereegranskat)abstract
- NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. Despite its established role as a potent activator of the immune system, NKG2D-driven regulation of CD4+ T helper (Th) cell–mediated immunity remains unclear. In this study, we demonstrate that NKG2D modulates Th1 and proinflammatory T-bet+ Th17 cell effector functions in vitro and in vivo. In particular, NKG2D promotes higher production of proinflammatory cytokines by Th1 and T-bet+ Th17 cells and reinforces their transcription of type 1 signature genes, including Tbx21. Conditional deletion of NKG2D in T cells impairs the ability of antigen-specific CD4+ T cells to promote inflammation in vivo during antigen-induced arthritis and experimental autoimmune encephalomyelitis, indicating that NKG2D is an important target for the amelioration of Th1- and Th17-mediated chronic inflammatory diseases.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Smedsrud, P. H., et al.
(författare)
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Kvasir-Capsule, a video capsule endoscopy dataset
- 2021
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) is predicted to have profound effects on the future of video capsule endoscopy (VCE) technology. The potential lies in improving anomaly detection while reducing manual labour. Existing work demonstrates the promising benefits of AI-based computer-assisted diagnosis systems for VCE. They also show great potential for improvements to achieve even better results. Also, medical data is often sparse and unavailable to the research community, and qualified medical personnel rarely have time for the tedious labelling work. We present Kvasir-Capsule, a large VCE dataset collected from examinations at a Norwegian Hospital. Kvasir-Capsule consists of 117 videos which can be used to extract a total of 4,741,504 image frames. We have labelled and medically verified 47,238 frames with a bounding box around findings from 14 different classes. In addition to these labelled images, there are 4,694,266 unlabelled frames included in the dataset. The Kvasir-Capsule dataset can play a valuable role in developing better algorithms in order to reach true potential of VCE technology.
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| 22. |
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| 23. |
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| 24. |
- Barsoe, S, et al.
(författare)
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RT-qPCR assay for detection of mink astrovirus in outbreaks of diarrhea on Danish mink farms
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5, s. e0252022-
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Tidskriftsartikel (refereegranskat)abstract
- Diarrhea in mink kits is a major cause of disease and mortality in the mink production. The etiology remains unknown in most outbreaks due to a lack of diagnostic assays. In the current study we present an RT-qPCR method to detect mink astrovirus in fecal samples from mink kits with diarrhea. All sampled animals were classified based on age and patoanatomical evaluation as having pre-weaning diarrhea, diarrhea in the growth period or as having no macroscopic signs of diarrhea. Fecal samples were analyzed for MiAstV with RT-qPCR, next generation sequencing and electron microscopy in parallel. Mink astrovirus was detected with RT-qPCR in 92 out of 203 samples. This detection was confirmed by next generation sequencing in a high proportion of samples (22/27), and by visualization of astrovirus particles with EM in some of the samples. Mink astrovirus was highly prevalent (68%) among kits in the outbreaks of pre-weaning diarrhea, in particular outbreaks from May, while less prevalent in outbreaks in June. Mink astrovirus was detected in outbreaks of diarrhea in the growth period, though in a much lesser extent than in the pre-weaning period. The role of mink astrovirus in the diarrhea disease complex of mink remain to be investigated, and for that purpose this sensitive and robust RT-qPCR can be a valuable tool in the future.
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| 25. |
- Ben Avraham, Binyamin, et al.
(författare)
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HFA of the ESC Position paper on the management of LVAD supported patients for the non LVAD specialist healthcare provider : Part 1: Introduction and at the non-hospital settings in the community
- 2021
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 4394-4408
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Tidskriftsartikel (refereegranskat)abstract
- The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the destination therapy indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patients pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.
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| 26. |
- Ben Gal, Tuvia, et al.
(författare)
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Guidance on the management of left ventricular assist device (LVAD) supported patients for the non-LVAD specialist healthcare provider: executive summary
- 2021
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Ingår i: European Journal of Heart Failure. - : Wiley-Blackwell. - 1388-9842 .- 1879-0844. ; 23:10, s. 1597-1609
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Tidskriftsartikel (refereegranskat)abstract
- The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD supported patients. Device-related, and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of LVAD implanting centres. The probability of an LVAD supported patient presenting with medical emergency to a local ambulance team, emergency department medical team and internal or surgical wards in a non-LVAD implanting centre is increasing. The purpose of this paper is to supply the immediate tools needed by the non-LVAD specialized physician - ambulance clinicians, emergency ward physicians, general cardiologists, and internists - to comply with the medical needs of this fast-growing population of LVAD supported patients. The different issues discussed will follow the patients pathway from the ambulance to the emergency department, and from the emergency department to the internal or surgical wards and eventually back to the general practitioner.
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| 27. |
- Borgli, H, et al.
(författare)
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HyperKvasir, a comprehensive multi-class image and video dataset for gastrointestinal endoscopy
- 2020
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1, s. 283-
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Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence is currently a hot topic in medicine. However, medical data is often sparse and hard to obtain due to legal restrictions and lack of medical personnel for the cumbersome and tedious process to manually label training data. These constraints make it difficult to develop systems for automatic analysis, like detecting disease or other lesions. In this respect, this article presents HyperKvasir, the largest image and video dataset of the gastrointestinal tract available today. The data is collected during real gastro- and colonoscopy examinations at Bærum Hospital in Norway and partly labeled by experienced gastrointestinal endoscopists. The dataset contains 110,079 images and 374 videos, and represents anatomical landmarks as well as pathological and normal findings. The total number of images and video frames together is around 1 million. Initial experiments demonstrate the potential benefits of artificial intelligence-based computer-assisted diagnosis systems. The HyperKvasir dataset can play a valuable role in developing better algorithms and computer-assisted examination systems not only for gastro- and colonoscopy, but also for other fields in medicine.
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| 28. |
- Brodin, N, et al.
(författare)
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Self-report and device-based physical activity measures and adherence to physical activity recommendations: a cross-sectional survey among people with inflammatory joint disease in four European countries
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:2, s. e064278-
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Tidskriftsartikel (refereegranskat)abstract
- Self-monitoring of physical activity (PA) has the potential to contribute to successful behaviour change in PA interventions in different populations, including people with inflammatory joint diseases (IJDs). The objectives of this study were to describe the use and knowledge of self-report-based and device-based PA measures in people with IJDs in four European countries, and to explore if the use of such devices, sociodemographic or disease-related variables were associated with adherence to the recommendations of at least 150 min of moderate to vigorous PA per week.SettingCross-sectional survey, performed in 2015–2016.ParticipantsPeople with IJDs in Belgium, Denmark, Ireland and Sweden.Primary and secondary outcome measuresUse of self-report and device-based PA measures, receipt of instructions how to use PA measures, confidence in using them, adherence to PA recommendations and associated factors for adherence to PA recommendations.ResultsOf the 1305 respondents answering questions on PA measures, 600 (46%) reported use of any kind of self-report or device-based measures to self-monitor PA. Between country differences of 34%–58% was observed. Six per cent and four per cent received instructions from health professionals on how to use simple and complex devices, respectively. Independent associated factors of fulfilment of recommendations of PA were living in Ireland (OR=84.89, p<0.001) and Sweden (OR=1.68, p=0.017) compared with living in Denmark, not perceiving activity limitations in moderate activities (OR=1.92, p<0.001) and using a device to measure PA (OR=1.56, p<0.001). Those living in Belgium (OR=0.21, p<0.001) were less likely to fulfil recommendations of PA.ConclusionsAlmost half of the participants with IJDs used self-report-based or deviced-based PA measures, although few used wearable devices regularly. The results indicate that participants meeting public PA health guidelines were engaged in self-monitoring of PA.
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| 29. |
- Brodin, N, et al.
(författare)
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Self-report and device-based physical activity measures and adherence to physical activity recommendations: a cross-sectional survey among people with inflammatory joint disease in four European countries
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:2, s. e064278-
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Tidskriftsartikel (refereegranskat)abstract
- Self-monitoring of physical activity (PA) has the potential to contribute to successful behaviour change in PA interventions in different populations, including people with inflammatory joint diseases (IJDs). The objectives of this study were to describe the use and knowledge of self-report-based and device-based PA measures in people with IJDs in four European countries, and to explore if the use of such devices, sociodemographic or disease-related variables were associated with adherence to the recommendations of at least 150 min of moderate to vigorous PA per week.SettingCross-sectional survey, performed in 2015–2016.ParticipantsPeople with IJDs in Belgium, Denmark, Ireland and Sweden.Primary and secondary outcome measuresUse of self-report and device-based PA measures, receipt of instructions how to use PA measures, confidence in using them, adherence to PA recommendations and associated factors for adherence to PA recommendations.ResultsOf the 1305 respondents answering questions on PA measures, 600 (46%) reported use of any kind of self-report or device-based measures to self-monitor PA. Between country differences of 34%–58% was observed. Six per cent and four per cent received instructions from health professionals on how to use simple and complex devices, respectively. Independent associated factors of fulfilment of recommendations of PA were living in Ireland (OR=84.89, p<0.001) and Sweden (OR=1.68, p=0.017) compared with living in Denmark, not perceiving activity limitations in moderate activities (OR=1.92, p<0.001) and using a device to measure PA (OR=1.56, p<0.001). Those living in Belgium (OR=0.21, p<0.001) were less likely to fulfil recommendations of PA.ConclusionsAlmost half of the participants with IJDs used self-report-based or deviced-based PA measures, although few used wearable devices regularly. The results indicate that participants meeting public PA health guidelines were engaged in self-monitoring of PA.
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| 30. |
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| 31. |
- Gustafsson, Finn, et al.
(författare)
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HFA of the ESC position paper on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider : Part 3: at the hospital and discharge
- 2021
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Ingår i: ESC Heart Failure. - : Wiley Periodicals Inc. - 2055-5822. ; 8:6, s. 4425-4443
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Tidskriftsartikel (refereegranskat)abstract
- The growing population of left ventricular assist device (LVAD)-supported patients increases the probability of an LVAD- supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient-device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD-supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non-cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end-of-life approaches are described.
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| 32. |
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| 33. |
- Haroun-Izquierdo, Alvaro, et al.
(författare)
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Adaptive single-KIR(+)NKG2C(+) NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
- 2022
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:11, s. e005577-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNatural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)(+)NKG2C(+) adaptive NK cells to maximize missing-self reactivity.MethodsWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ResultsADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45(dim) blast subtypes.ConclusionsThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
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| 34. |
- Haugaard-Kedström, Linda M., et al.
(författare)
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A High-Affinity Peptide Ligand Targeting Syntenin Inhibits Glioblastoma
- 2021
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:3, s. 1423-1434
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Tidskriftsartikel (refereegranskat)abstract
- Despite the recent advances in cancer therapeutics, highly aggressive cancer forms, such as glioblastoma (GBM), still have very low survival rates. The intracellular scaffold protein syntenin, comprising two postsynaptic density protein-95/discslarge/zona occludens-1 (PDZ) domains, has emerged as a novel therapeutic target in highly malignant phenotypes including GBM. Here, we report the development of a novel, highly potent, and metabolically stable peptide inhibitor of syntenin, KSL-128114, which binds the PDZ1 domain of syntenin with nanomolar affinity. KSL-128114 is resistant toward degradation in human plasma and mouse hepatic microsomes and displays a global PDZ domain selectivity for syntenin. An X-ray crystal structure reveals that KSL128114 interacts with syntenin PDZ1 in an extended noncanonical binding mode. Treatment with KSL-128114 shows an inhibitory effect on primary GBM cell viability and significantly extends survival time in a patient-derived xenograft mouse model. Thus, KSL-128114 is a novel promising candidate with therapeutic potential for highly aggressive tumors, such as GBM.
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| 35. |
- Kear, Benjamin P., 1975-, et al.
(författare)
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Earliest Triassic ichthyosaur fossils push back oceanic reptile origins
- 2023
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:5, s. R178-R179
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Tidskriftsartikel (refereegranskat)abstract
- Reptiles first radiated into oceanic environments after the cataclysmic end-Permian mass extinction (EPME)1, 251.9 million years (Ma) ago. The geologically oldest fossils evincing this adaptive transition have been recovered from upper-Lower Triassic (lower Spathian) strata, ∼248.8 Ma2, and postdate a landmark turnover of amphibian-dominated to reptile-dominated marine ecosystems spanning the late Smithian crisis (LSC)3, ∼249.6 Ma4 —less than ∼2.3 Ma after the EPME. Here, we report ichthyopterygian (the group including ‘fish-shaped’ ichthyosaurians1) remains from the Arctic island of Spitsbergen that predate the LSC in later-middle to early-late Smithian5 deposits up to ∼250 Ma. Unexpectedly, however, their large size and spongy internal bone structure indicate a fully pelagic ichthyopterygian1,6. Given this unambiguous occurrence ∼2 Ma after the EPME, these pioneering seagoing tetrapods can now be feasibly recast as mass extinction survivors instead of ecological successors2,3 within the earliest Mesozoic marine predator communities.
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| 36. |
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| 37. |
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| 38. |
- Milicic, Davor, et al.
(författare)
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Heart Failure Association of the European Society of Cardiology position paper on the management of left ventricular assist device-supported patients for the non-left ventricular assist device specialist healthcare provider : Part 2: at the emergency department
- 2021
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 4409-4424
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Tidskriftsartikel (refereegranskat)abstract
- The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the destination therapy indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.
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| 39. |
- Mulrooney, Elisabeth, et al.
(författare)
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Hand osteoarthritis phenotypes based on a biopsychosocial approach, and their associations with cross-sectional and longitudinal pain
- 2024
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Ingår i: Osteoarthritis and Cartilage. - 1063-4584.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hand osteoarthritis (OA) pain is characterized as heterogeneous and multifactorial. Differences in pain may be explained by underlying phenotypes, which have not been previously explored Design: Latent class analysis determined classes of participants with hand OA from the Nor-Hand study baseline examination (2016–17) based on a biopsychosocial framework. Outcomes were hand and overall bodily pain intensity (Numeric Rating Scale, 0–10) at baseline and follow-up (2019–21), The relations of the classes to pain outcomes at baseline, follow-up, and change over time were analysed in separate models by linear regression, using the overall healthiest class as reference. Results: Five classes differing in radiographic hand OA burden and OA burden in the lower extremities by ultrasound, demographic factors, psychosocial burden and pain sensitization was identified. Persons with the least severe OA but higher burden of biopsychosocial factors reported the most hand pain (beta 3.65, 95% CI 2.53, 4.75). Pain was less pronounced in persons with the most severe hand OA but low burden of biopsychosocial factors (beta 1.03, 95% CI 0.41, 1.65). Results were similar for overall bodily pain and at follow-up. Changes in pain were small, but the association between a separate class defined by higher levels of biopsychosocial burden and pain changes was significant. Conclusion: The five hand OA phenotypes were associated with pain at baseline and 3.5 years later. The phenotype with the least OA severity, but higher burden of biopsychosocial factors reported more pain than the phenotype with the most severe OA, reflecting the symptom-structure discordance of the hand OA pain experience.
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- Scarpellini, E., et al.
(författare)
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International consensus on the diagnosis and management of dumping syndrome
- 2020
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Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 16:8, s. 448-466
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Tidskriftsartikel (refereegranskat)abstract
- Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose. Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.
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| 42. |
- Teixeira, Pedro P.C., et al.
(författare)
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Decoding the rhizodeposit-derived carbon's journey into soil organic matter
- 2024
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Ingår i: Geoderma. - 0016-7061. ; 443
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Tidskriftsartikel (refereegranskat)abstract
- Net rhizodeposition corresponds to the portion of living root carbon (C) that remains in the soil after microbial processing and partial decomposition. Although it is assumed that this C input exerts an important role in the formation of soil organic matter (SOM), its contribution to distinct SOM pools is still not fully understood. In this study, we aimed to (i) quantify the retention of net rhizodeposition C in the different SOM fractions and in reactive Al and Fe mineral phases and (ii) investigate how rhizodeposition drives the spatial distribution of microbial communities in the rhizosphere. To track the transfer of net rhizodeposition into the soil, we used artificially labeled eucalypt (Eucalyptus spp.) seedlings under a 13C-CO2 atmosphere (multiple-pulse labeling). Combining physical SOM fractionation and the chemical extraction of aluminum (Al) and iron (Fe) reactive phases, we studied the distribution of net rhizodeposition into different soil fractions. We also assessed the 13C incorporation into microbial phospholipid fatty acids (PLFAs) at different distances from the roots. Our results show that 76 % of the net rhizodeposition 13C was retained within the mineral-associated organic matter (MAOM) fraction. About 28 % of net rhizodeposition 13C within the MAOM fraction was retained within the Al and Fe reactive phases, indicating that this is a sizeable mechanism for the retention of net rhizodeposition in soil. Rhizodeposition increased the abundance of microbial PLFAs exclusively in the soil close to the roots (0–4 mm), with prominent incorporation of net rhizodeposition 13C into fungal biomarkers. Overall, our findings underscore the importance of mineral associations for the retention of net rhizodeposition in the soil. We also highlight the role of fungi in transferring the root-derived C beyond the root vicinity and promoting the formation of occluded SOM.
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| 43. |
- Vasilatou, K., et al.
(författare)
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Extending traceability in airborne particle size distribution measurements beyond 10 µm : Counting efficiency and unit-to-unit variability of four aerodynamic particle size spectrometers
- 2023
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Ingår i: Aerosol Science and Technology. - : Taylor and Francis Ltd.. - 0278-6826 .- 1521-7388. ; 57:1, s. 24-34
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to establish traceable number concentration measurements of airborne particles beyond 10 μm in particle size. To this end, the primary standards for particle number concentration at the National Metrology Institutes of Switzerland and Japan were further developed to extend their measurement capabilities. Details on the upgraded setup are provided. An inter-comparison of the two primary standards using an optical particle counter as transfer standard showed that these agree well within the stated uncertainties at polystyrene (PS) equivalent optical diameter of 15 µm. Subsequently, four Model 3321 (TSI Inc., USA) aerodynamic particle size spectrometers (APS) were calibrated against the primary standard of Switzerland using size-certified PS spheres with optical/aerodynamic diameter up to 20 µm as test aerosols. The counting efficiency profile and unit-to-unit variability of the APS units were determined. The results presented here can be useful for the analysis and interpretation of data collected by the different atmospheric aerosol networks worldwide. The outlined methodology can also be applied in the calibration of automated bio-aerosol monitors. © 2022 The Author(s).
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