| 6381. |
- Skenteris, Nikolaos T, et al.
(författare)
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Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification
- 2022
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 12:2, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context.METHODS AND RESULTS: In patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α-SMA+ cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE-/- mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFβ1, phosphate and β-glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues.CONCLUSION: We report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α-SMA+ regions of calcified cardiovascular tissues, induced by pro-inflammatory and pro-osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification.
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| 6382. |
- Skoglund, Elisabeth, et al.
(författare)
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Skeletal muscle morphology, satellite cells, and oxidative profile in relation to physical function and lifelong endurance training in very old men
- 2023
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 134:2, s. 264-275
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Tidskriftsartikel (refereegranskat)abstract
- In the current study, we compared muscle morphology in three advanced aging cohorts that differed in physical function, includ-ing a unique cohort of lifelong endurance athletes. Biopsies from the vastus lateralis muscle of seven lifelong endurance athletes (EAs) aged 82-92 yr, and 19 subjects from the Uppsala Longitudinal Study of Adult Men (ULSAM) aged 87-91 yr were analyzed. ULSAM subjects were divided into high-(n = 9, HF) and low-(n = 10, LF) function groups based on strength and physical function tests. The analysis included general morphology, fiber type and cross-sectional area, capillarization, deficient cytochrome c oxi-dase (COX) activity, number of myonuclei and satellite cells, and markers of regeneration and denervation. Fibers with central nuclei and/or nuclear clumps were observed in all groups. EA differed from LF and HF by having a higher proportion of type I fibers, 52% more capillaries in relation to fiber area, fewer COX-negative fibers, and less variation in fiber sizes (all P < 0.05). There were no differences between the groups in the number of myonuclei and satellite cells per fiber, and no significant differ-ences between LF and HF (P > 0.05). In conclusion, signs of aging were evident in the muscle morphology of all groups, but neither endurance training status nor physical function influenced signs of regeneration and denervation processes. Lifelong en-durance training, but not higher physical function, was associated with higher muscle oxidative capacity, even beyond the age of 80.NEW & NOTEWORTHY Here we show that lifelong endurance training, but not physical function, is associated with higher mus-cle oxidative capacity, even beyond the age of 80 yr. Neither endurance training status nor physical function was significantly associated with satellite cells or markers of regeneration and denervation in muscle biopsies from these very old men.
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| 6383. |
- Skoglund, Martin A.
(författare)
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Visual Inertial Navigation and Calibration
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Processing and interpretation of visual content is essential to many systems and applications. This requires knowledge of how the content is sensed and also what is sensed. Such knowledge is captured in models which, depending on the application, can be very advanced or simple. An application example is scene reconstruction using a camera; if a suitable model of the camera is known, then a model of the scene can be estimated from images acquired at different, unknown, locations, yet, the quality of the scene model depends on the quality of the camera model. The opposite is to estimate the camera model and the unknown locations using a known scene model. In this work, two such problems are treated in two rather different applications.There is an increasing need for navigation solutions less dependent on external navigation systems such as the Global Positioning System (GPS). Simultaneous Localisation and Mapping (slam) provides a solution to this by estimating both navigation states and some properties of the environment without considering any external navigation systems.The first problem considers visual inertial navigation and mapping using a monocular camera and inertial measurements which is a slam problem. Our aim is to provide improved estimates of the navigation states and a landmark map, given a slam solution. To do this, the measurements are fused in an Extended Kalman Filter (ekf) and then the filtered estimates are used as a starting solution in a nonlinear least-squares problem which is solved using the Gauss-Newton method. This approach is evaluated on experimental data with accurate ground truth for reference.In Augmented Reality (ar), additional information is superimposed onto the surrounding environment in real time to reinforce our impressions. For this to be a pleasant experience it is necessary to have a good models of the ar system and the environment.The second problem considers calibration of an Optical See-Through Head Mounted Display system (osthmd), which is a wearable ar system. We show and motivate how the pinhole camera model can be used to represent the osthmd and the user’s eye position. The pinhole camera model is estimated using the Direct Linear Transformation algorithm. Results are evaluated in experiments which also compare different data acquisition methods.
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| 6384. |
- Skov, Morten W., et al.
(författare)
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Risk prediction of atrial fibrillation based on electrocardiographic interatrial block
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Background--The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. Methods and Results--Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. Conclusions--IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.
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| 6385. |
- Skov, Vibe, et al.
(författare)
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A 7-gene signature depicts the biochemical profile of early prefibrotic myelofibrosis
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that a large proportion of patients classified as essential thrombocythemia (ET) actually have early primary prefibrotic myelofibrosis (prePMF), which implies an inferior prognosis as compared to patients being diagnosed with so-called genuine or true ET. According to theWorld Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between themmay be challenging and several studies have not been able to distinguish between them.Most lately, it has been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH.Whole blood gene expression profiling was performed in 17 and 9 patients diagnosed with ET and PMF, respectively. Using elevated LDH obtained at the time of diagnosis as a marker of prePMF, a 7-gene signature was identified which correctly predicted the prePMF group with a sensitivity of 100%and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, andMMP8, which are genes known to be involved in inflammation, cell adhesion, differentiation and proliferation. Evaluation of bone marrow biopsies and the 7-gene signature showed a concordance rate of 71%, 79%, 62%, and 38%. Our 7-gene signature may be a useful tool to differentiate between genuine ET and prePMF but needs to be validated in a larger cohort of "ET" patients.
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| 6386. |
- Skrimizea, Eirini, et al.
(författare)
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Sustainable agriculture : Recognizing the potential of conflict as a positive driver for transformative change
- 2020. - 1
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Ingår i: The Future of Agricultural Landscapes, Part I. - London : Academic Press. - 9780128220177 ; , s. 255-311
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Bokkapitel (refereegranskat)abstract
- Transformative changes in agriculture at multiple scales are needed to ensure sustainability, i.e. achieving food security while fostering social justice and environmental integrity. These transformations go beyond technological fixes and require fundamental changes in cognitive, relational, structural and functional aspects of agricultural systems. However, research on agricultural transformations fails to engage deeply with underlying social aspects such as differing perceptions of sustainability, uncertainties and ambiguities, politics of knowledge, power imbalances and deficits in democracy. In this paper, we suggest that conflict is one manifestation of such underlying social aspects. We present an original conceptualization and analytical framework, wherein conflict is recognized as an important motor for redistribution of power and leverage for social learning that-if addressed through a conflict transformation process-could potentially create a step-change in agricultural transformation towards greater sustainability. Our analysis, building on an extensive literature review and empirical case studies from around the world, suggests a novel approach to guide future transdisciplinary research that can support agricultural transformations towards sustainability.
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| 6387. |
- Skripcak, Tomas, et al.
(författare)
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Creating a data exchange strategy for radiotherapy research : Towards federated databases and anonymised public datasets
- 2014
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 113:3, s. 303-309
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Tidskriftsartikel (refereegranskat)abstract
- Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate 'translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within "Big Data". Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology.
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| 6388. |
- Sliwa, Karen, et al.
(författare)
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Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy.
- 2021
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 23:4, s. 527-540
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Tidskriftsartikel (refereegranskat)abstract
- This position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogenous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non-classified cardiomyopathies, left ventricular non-compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo-/radiotherapy for cancer or hematological malignancies need specific pre-, during and post-pregnancy assessment and counseling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the fetus. This position paper assists in balancing benefits and detrimental effects.
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| 6389. |
- Slodownik, Miriam A., et al.
(författare)
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Reassessment of the Early Triassic trematosaurid temnospondyl Tertrema acuta from the Arctic island of Spitsbergen
- 2021
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Ingår i: Journal of Vertebrate Paleontology. - : Informa UK Limited. - 0272-4634 .- 1937-2809. ; 41:1
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Tidskriftsartikel (refereegranskat)abstract
- Trematosaurids were globally distributed Early Triassic temnospondyl amphibians characterized by elongate ‘crocodile-like’ skulls. Some of the most famous trematosaurid fossils were discovered on the island of Spitsbergen in the Arctic Svalbard archipelago. Among these, the short-snouted trematosaurine, Tertrema acuta, is one of the few taxa represented by virtually complete cranial remains. Unusually, however, the type specimens comprise only natural molds that were historically used to reconstruct three-dimensional casts. Here, we re-assess these restorations using the original impressions to phylogenetically analyze and re-diagnose the taxon. Unexpectedly, our first-hand scores differ markedly from previous literature-sourced interpretations and yield conflicting tree topologies that nest T. acuta with long-snouted lonchorhynchines, thus destabilizing the long-favored sub-division of trematosaurids based on their skull shape. We attribute this result to character state conflict and suggest that the traditional classification of trematosaurids may mask more complex evolutionary relationships, as well as possible trophic partitioning, and eco-morphological plasticity.
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| 6390. |
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