| 1. |
- Flockhart, Mikael, et al.
(författare)
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Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.
- 2023
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Ingår i: Redox Biology. - : Elsevier. - 2213-2317. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.
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| 2. |
- Garvanska, Dimitriya H., et al.
(författare)
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The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions
- 2024
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Ingår i: EMBO Reports. - : Springer Nature. - 1469-221X .- 1469-3178. ; 25:2, s. 902-926
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Tidskriftsartikel (refereegranskat)abstract
- Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.
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| 3. |
- Hammaréus, Filip, et al.
(författare)
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Wall shear stress measured with 4D flow CMR correlates with biomarkers of inflammation and collagen synthesis in mild-to-moderate ascending aortic dilation and tricuspid aortic valves
- 2024
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Ingår i: European Heart Journal Cardiovascular Imaging. - : OXFORD UNIV PRESS. - 2047-2404 .- 2047-2412.
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Tidskriftsartikel (refereegranskat)abstract
- Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter >= 40 mm) and 50 sex-and age-matched controls (diameter < 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I alpha 1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P < 0.001), and maximum oscillatory shear index and collagen type I alpha 1 chain (r = -0.575, P < 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.
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| 4. |
- Kruse, Thomas, et al.
(författare)
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Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
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| 5. |
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| 6. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 7. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 8. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 9. |
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| 10. |
- Ammirati, Enrico, et al.
(författare)
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Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device : Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA)
- 2021
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 324
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Tidskriftsartikel (refereegranskat)abstract
- Background: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. Methods: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. Results: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. Conclusions: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.
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| 11. |
- Andersen, Kasper Winther, et al.
(författare)
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Disentangling white-matter damage from physiological fibre orientation dispersion in multiple sclerosis
- 2020
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:2, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis leads to diffuse damage of the central nervous system, affecting also the normal-appearing white matter. Demyelination and axonal degeneration reduce regional fractional anisotropy in normal-appearing white matter, which can be routinely mapped with diffusion tensor imaging. However, the standard fractional anisotropy metric is also sensitive to physiological variations in orientation dispersion of white matter fibres. This complicates the detection of disease-related damage in large parts of cerebral white matter where microstructure physiologically displays a high degree of fibre dispersion. To resolve this ambiguity, we employed a novel tensor-valued encoding method for diffusion MRI, which yields a microscopic fractional anisotropy metric that is unaffected by regional variations in orientation dispersion. In 26 patients with relapsing-remitting multiple sclerosis, 14 patients with primary-progressive multiple sclerosis and 27 age-matched healthy controls, we compared standard fractional anisotropy mapping with the novel microscopic fractional anisotropy mapping method, focusing on normal-appearing white matter. Mean microscopic fractional anisotropy and standard fractional anisotropy of normal-appearing white matter were significantly reduced in both patient groups relative to healthy controls, but microscopic fractional anisotropy yielded a better reflection of disease-related white-matter alterations. The reduction in mean microscopic fractional anisotropy showed a significant positive linear relationship with physical disability, as reflected by the expanded disability status scale. Mean reduction of microscopic fractional anisotropy in normal-appearing white matter also scaled positively with individual cognitive dysfunction, as measured with the symbol digit modality test. Mean microscopic fractional anisotropy reduction in normal-appearing white matter also showed a positive relationship with total white-matter lesion load as well as lesion load in specific tract systems. None of these relationships between normal-appearing white-matter microstructure and clinical, cognitive or structural measures emerged when using mean fractional anisotropy. Together, the results provide converging evidence that microscopic fractional anisotropy mapping substantially advances the assessment of cerebral white matter in multiple sclerosis by disentangling microstructure damage from variations in physiological fibre orientation dispersion at the stage of data acquisition. Since tensor-valued encoding can be implemented in routine diffusion MRI, microscopic fractional anisotropy mapping bears considerable potential for the future assessment of disease progression in normal-appearing white matter in both relapsing-remitting and progressive forms of multiple sclerosis as well as other white-matter-related brain diseases.
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| 12. |
- Backman, Filip, 1991-, et al.
(författare)
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The development of the NNBAR experiment
- 2022
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- The NNBAR experiment for the European Spallation Source will search for free neutrons converting to antineutrons with a sensitivity improvement of three orders of magnitude compared to the last such search. This paper describes progress towards a conceptual design report for NNBAR. The design of a moderator, neutron reflector, beamline, shielding and annihilation detector is reported. The simulations used form part of a model which will be used for optimisation of the experiment design and quantification of its sensitivity.
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| 13. |
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| 14. |
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| 15. |
- Bjursten, Henrik, et al.
(författare)
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Particle separation using ultrasound can be used with human shed mediastinal blood.
- 2005
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Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 20:1, s. 39-43
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Tidskriftsartikel (refereegranskat)abstract
- Shed mediastinal blood collected by cardiotomy suction has been shown to be a large contributor to lipid microemboli ending up in different organs. The aim of this study was to test the separation efficiency on human shed blood of a new separation method developed to meet this demand. METHODS: Shed mediastinal blood collected from the pericardial cavity of 13 patients undergoing cardiac surgery with cardiopulmonary bypass was collected. The blood was processed in an eight-channel parallel PARSUS separator, and separation efficiency was determined. RESULTS: Erythrocyte recovery, in terms of a separation ratio, varied between 68% and 91%. Minor electrolyte changes took place, where levels of sodium increased and levels of potassium and calcium decreased. CONCLUSION: This study demonstrates that PARSUS technology can be used on human shed mediastinal blood with good separation efficiency. The technology is, thereby, suggested to have future clinical relevance.
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| 16. |
- Brabec, Jan, et al.
(författare)
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Coregistered histology sections with diffusion tensor imaging data at 200 µm resolution in meningioma tumors
- 2023
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Ingår i: Data in Brief. - 2352-3409. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- A significant problem in diffusion MRI (dMRI) is the lack of understanding regarding which microstructural features account for the variability in the diffusion tensor imaging (DTI) parameters observed in meningioma tumors. A common assumption is that mean diffusivity (MD) and fractional anisotropy (FA) from DTI are inversely proportional to cell density and proportional to tissue anisotropy, respectively. Although these associations have been established across a wide range of tumors, they have been challenged for interpreting within-tumor variations where several additional microstructural features have been suggested as contributing to MD and FA.To facilitate the investigation of the biological underpinnings of DTI parameters, we performed ex-vivo DTI at 200 µm isotropic resolution on 16 excised meningioma tumor samples. The samples exhibit a variety of microstructural features because the dataset includes meningiomas of six different meningioma types and two different grades. Diffusion-weighted signal (DWI) maps, DWI maps averaged over all directions for given b-value, signal intensities without diffusion encoding (S0) as well as DTI parameters: MD, FA, in-plane FA (FAIP), axial diffusivity (AD) and radial diffusivity (RD), were coregistered to Hematoxylin & Eosin- (H&E) and Elastica van Gieson-stained (EVG) histological sections by a non-linear landmark-based approach.Here, we provide DWI signal and DTI maps coregistered to histology sections and describe the pipeline for processing the raw DTI data and the coregistration. The raw, processed, and coregistered data are hosted by Analytic Imaging Diagnostics Arena (AIDA) data hub registry, and software tools for processing are provided via GitHub. We hope that data can be used in research and education concerning the link between the meningioma microstructure and parameters obtained by DTI.
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| 17. |
- Brabec, Jan, et al.
(författare)
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Histogram analysis of tensor-valued diffusion MRI in meningiomas : Relation to consistency, histological grade and type
- 2022
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preoperative radiological assessment of meningioma characteristics is of value for pre- and post-operative patient management, counselling, and surgical approach.PURPOSE: To investigate whether tensor-valued diffusion MRI can add to the preoperative prediction of meningioma consistency, grade and type.MATERIALS AND METHODS: 30 patients with intracranial meningiomas (22 WHO grade I, 8 WHO grade II) underwent MRI prior to surgery. Diffusion MRI was performed with linear and spherical b-tensors with b-values up to 2000 s/mm2. The data were used to estimate mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and its components-the anisotropic and isotropic kurtoses (MKA and MKI). Meningioma consistency was estimated for 16 patients during resection based on ultrasonic aspiration intensity, ease of resection with instrumentation or suction. Grade and type were determined by histopathological analysis. The relation between consistency, grade and type and dMRI parameters was analyzed inside the tumor ("whole-tumor") and within brain tissue in the immediate periphery outside the tumor ("rim") by histogram analysis.RESULTS: Lower 10th percentiles of MK and MKA in the whole-tumor were associated with firm consistency compared with pooled soft and variable consistency (n = 7 vs 9; U test, p = 0.02 for MKA 10 and p = 0.04 for MK10) and lower 10th percentile of MD with variable against soft and firm (n = 5 vs 11; U test, p = 0.02). Higher standard deviation of MKI in the rim was associated with lower grade (n = 22 vs 8; U test, p = 0.04) and in the MKI maps we observed elevated rim-like structure that could be associated with grade. Higher median MKA and lower median MKI distinguished psammomatous type from other pooled meningioma types (n = 5 vs 25; U test; p = 0.03 for MKA 50 and p = 0.03 and p = 0.04 for MKI 50).CONCLUSION: Parameters from tensor-valued dMRI can facilitate prediction of consistency, grade and type.
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| 18. |
- Brabec, Jan, et al.
(författare)
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Meningioma microstructure assessed by diffusion MRI : An investigation of the source of mean diffusivity and fractional anisotropy by quantitative histology
- 2023
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mean diffusivity (MD) and fractional anisotropy (FA) from diffusion MRI (dMRI) have been associated with cell density and tissue anisotropy across tumors, but it is unknown whether these associations persist at the microscopic level.PURPOSE: To quantify the degree to which cell density and anisotropy, as determined from histology, account for the intra-tumor variability of MD and FA in meningioma tumors. Furthermore, to clarify whether other histological features account for additional intra-tumor variability of dMRI parameters.MATERIALS AND METHODS: We performed ex-vivo dMRI at 200 μm isotropic resolution and histological imaging of 16 excised meningioma tumor samples. Diffusion tensor imaging (DTI) was used to map MD and FA, as well as the in-plane FA (FA IP). Histology images were analyzed in terms of cell nuclei density (CD) and structure anisotropy (SA; obtained from structure tensor analysis) and were used separately in a regression analysis to predict MD and FA IP, respectively. A convolutional neural network (CNN) was also trained to predict the dMRI parameters from histology patches. The association between MRI and histology was analyzed in terms of out-of-sample (R 2 OS) on the intra-tumor level and within-sample R 2 across tumors. Regions where the dMRI parameters were poorly predicted from histology were analyzed to identify features apart from CD and SA that could influence MD and FA IP, respectively. RESULTS: Cell density assessed by histology poorly explained intra-tumor variability of MD at the mesoscopic level (200 μm), as median R 2 OS = 0.04 (interquartile range 0.01-0.26). Structure anisotropy explained more of the variation in FA IP (median R 2 OS = 0.31, 0.20-0.42). Samples with low R 2 OS for FA IP exhibited low variations throughout the samples and thus low explainable variability, however, this was not the case for MD. Across tumors, CD and SA were clearly associated with MD (R 2 = 0.60) and FA IP (R 2 = 0.81), respectively. In 37% of the samples (6 out of 16), cell density did not explain intra-tumor variability of MD when compared to the degree explained by the CNN. Tumor vascularization, psammoma bodies, microcysts, and tissue cohesivity were associated with bias in MD prediction based solely on CD. Our results support that FA IP is high in the presence of elongated and aligned cell structures, but low otherwise. CONCLUSION: Cell density and structure anisotropy account for variability in MD and FA IP across tumors but cell density does not explain MD variations within the tumor, which means that low or high values of MD locally may not always reflect high or low tumor cell density. Features beyond cell density need to be considered when interpreting MD.
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| 19. |
- Brabec, Jan, et al.
(författare)
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Separating Glioma Hyperintensities From White Matter by Diffusion-Weighted Imaging With Spherical Tensor Encoding
- 2022
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tumor-related hyperintensities in high b-value diffusion-weighted imaging (DWI) are radiologically important in the workup of gliomas. However, the white matter may also appear as hyperintense, which may conflate interpretation.Purpose: To investigate whether DWI with spherical b-tensor encoding (STE) can be used to suppress white matter and enhance the conspicuity of glioma hyperintensities unrelated to white matter.Materials and Methods: Twenty-five patients with a glioma tumor and at least one pathology-related hyperintensity on DWI underwent conventional MRI at 3 T. The DWI was performed both with linear and spherical tensor encoding (LTE-DWI and STE-DWI). The LTE-DWI here refers to the DWI obtained with conventional diffusion encoding and averaged across diffusion-encoding directions. Retrospectively, the differences in contrast between LTE-DWI and STE-DWI, obtained at a b-value of 2,000 s/mm2, were evaluated by comparing hyperintensities and contralateral normal-appearing white matter (NAWM) both visually and quantitatively in terms of the signal intensity ratio (SIR) and contrast-to-noise ratio efficiency (CNReff).Results: The spherical tensor encoding DWI was more effective than LTE-DWI at suppressing signals from white matter and improved conspicuity of pathology-related hyperintensities. The median SIR improved in all cases and on average by 28%. The median (interquartile range) SIR was 1.9 (1.6 - 2.1) for STE and 1.4 (1.3 - 1.7) for LTE, with a significant difference of 0.4 (0.3 -0.5) (p < 10-4, paired U-test). In 40% of the patients, the SIR was above 2 for STE-DWI, but with LTE-DWI, the SIR was below 2 for all patients. The CNReff of STE-DWI was significantly higher than of LTE-DWI: 2.5 (2 - 3.5) vs. 2.3 (1.7 - 3.1), with a significant difference of 0.4 (-0.1 -0.6) (p < 10-3, paired U-test). The STE improved CNReff in 70% of the cases. We illustrate the benefits of STE-DWI in three patients, where STE-DWI may facilitate an improved radiological description of tumor-related hyperintensity, including one case that could have been missed out if only LTE-DWI was inspected.Conclusion: The contrast mechanism of high b-value STE-DWI results in a stronger suppression of white matter than conventional LTE-DWI, and may, therefore, be more sensitive and specific for assessment of glioma tumors and DWI-hyperintensities.
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| 20. |
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| 21. |
- Brynolfsson, Patrik, et al.
(författare)
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Tensor-valued diffusion magnetic resonance imaging in a radiotherapy setting
- 2022
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 24, s. 144-151
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeDiagnostic information about cell density variations and microscopic tissue anisotropy can be gained from tensor-valued diffusion magnetic resonance imaging (MRI). These properties of tissue microstructure have the potential to become novel imaging biomarkers for radiotherapy response. However, tensor-valued diffusion encoding is more demanding than conventional encoding, and its compatibility with MR scanners that are dedicated to radiotherapy has not been established. Thus, our aim was to investigate the feasibility of tensor-valued diffusion MRI with radiotherapy dedicated MR equipment.Material and methodsA tensor-valued diffusion protocol was implemented, and five healthy volunteers were scanned with different resolutions using conventional head coil and radiotherapy coil setup with fixation masks. Signal-to-noise-ratio (SNR) was evaluated to assess the risk of signal bias due to rectified noise floor. We also evaluated the repeatability and reproducibility of the microstructure parameters. One patient with brain metastasis was scanned to investigate the image quality and the transferability of the setup to diseased tissue.ResultsA resolution of 3×3×3 mm3 provided images with SNR>3 for 93% of the voxels using radiotherapy coil setup. The parameter maps and repeatability characteristics were comparable to those observed with a conventional head coil. The patient evaluation demonstrated successful parameter analysis also in tumor tissue, with SNR>3 for 93% of the voxels.ConclusionWe demonstrate that tensor-valued diffusion MRI is compatible with radiotherapy fixation masks and coil setup for investigations of microstructure parameters. The reported reproducibility may be used to plan future investigations of imaging biomarkers in brain cancer radiotherapy.
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| 22. |
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| 23. |
- Chakwizira, Arthur, et al.
(författare)
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Diffusion MRI with free gradient waveforms on a high-performance gradient system : Probing restriction and exchange in the human brain
- 2023
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Ingår i: NeuroImage. - 1053-8119. ; 283
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Tidskriftsartikel (refereegranskat)abstract
- The dependence of the diffusion MRI signal on the diffusion time carries signatures of restricted diffusion and exchange. Here we seek to highlight these signatures in the human brain by performing experiments using free gradient waveforms designed to be selectively sensitive to the two effects. We examine six healthy volunteers using both strong and ultra-strong gradients (80, 200 and 300 mT/m). In an experiment featuring a large set of 150 gradient waveforms with different sensitivities to restricted diffusion and exchange, our results reveal unique and different time-dependence signatures in grey and white matter. Grey matter was characterised by both restricted diffusion and exchange and white matter predominantly by restricted diffusion. Exchange in grey matter was at least twice as fast as in white matter, across all subjects and all gradient strengths. The cerebellar cortex featured relatively short exchange times (115 ms). Furthermore, we show that gradient waveforms with tailored designs can be used to map exchange in the human brain. We also assessed the feasibility of clinical applications of the method used in this work and found that the exchange-related contrast obtained with a 25-minute protocol at 300 mT/m was preserved in a 4-minute protocol at 300 mT/m and a 10-minute protocol at 80 mT/m. Our work underlines the utility of free waveforms for detecting time dependence signatures due to restricted diffusion and exchange in vivo, which may potentially serve as a tool for studying diseased tissue.
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| 24. |
- Chakwizira, Arthur, et al.
(författare)
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Diffusion MRI with pulsed and free gradient waveforms : effects of restricted diffusion and exchange
- 2023
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring time-dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted diffusion and exchange have opposite effects on the diffusion-weighted signal, which can lead to errors in parameter estimates. In this work, we propose a signal representation that incorporates the effects of both restricted diffusion and exchange up to second order in b-value and is compatible with gradient waveforms of arbitrary shape. The representation features mappings from a gradient waveform to two scalars that separately control the sensitivity to restriction and exchange. We demonstrate that these scalars span a two-dimensional space that can be used to choose waveforms that selectively probe restricted diffusion or exchange, eliminating the correlation between the two phenomena. We found that waveforms with specific but unconventional shapes provide an advantage over conventional pulsed and oscillating gradient acquisitions. We also show that parametrisation of waveforms into a two-dimensional space can be used to understand protocols from other approaches that probe restricted diffusion and exchange. For example, we found that the variation of mixing time in filter-exchange imaging corresponds to variation of our exchange-weighting scalar at a fixed value of the restriction-weighting scalar. The proposed signal representation was evaluated using Monte Carlo simulations in identical parallel cylinders with hexagonal and random packing as well as parallel cylinders with gamma-distributed radii. Results showed that the approach is sensitive to sizes in the interval 4 - 12 μm and exchange rates in the simulated range of 0 to 20 s -1 , but also that there is a sensitivity to the extracellular geometry. The presented theory constitutes a simple and intuitive description of how restricted diffusion and exchange influence the signal as well as a guide to protocol design capable of separating the two effects.
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| 25. |
- Cottaar, Michiel, et al.
(författare)
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Improved fibre dispersion estimation using b-tensor encoding
- 2020
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119. ; 215
-
Tidskriftsartikel (refereegranskat)abstract
- Measuring fibre dispersion in white matter with diffusion magnetic resonance imaging (MRI) is limited by an inherent degeneracy between fibre dispersion and microscopic diffusion anisotropy (i.e., the diffusion anisotropy expected for a single fibre orientation). This means that estimates of fibre dispersion rely on strong assumptions, such as constant microscopic anisotropy throughout the white matter or specific biophysical models. Here we present a simple approach for resolving this degeneracy using measurements that combine linear (conventional) and spherical tensor diffusion encoding. To test the accuracy of the fibre dispersion when our microstructural model is only an approximation of the true tissue structure, we simulate multi-compartment data and fit this with a single-compartment model. For such overly simplistic tissue assumptions, we show that the bias in fibre dispersion is greatly reduced (~5x) for single-shell linear and spherical tensor encoding data compared with single-shell or multi-shell conventional data. In in-vivo data we find a consistent estimate of fibre dispersion as we reduce the b-value from 3 to 1.5 ms/μm2, increase the repetition time, increase the echo time, or increase the diffusion time. We conclude that the addition of spherical tensor encoded data to conventional linear tensor encoding data greatly reduces the sensitivity of the estimated fibre dispersion to the model assumptions of the tissue microstructure.
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| 26. |
- de Almeida Martins, João P., et al.
(författare)
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Neural networks for parameter estimation in microstructural MRI : Application to a diffusion-relaxation model of white matter
- 2021
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119. ; 244
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Tidskriftsartikel (refereegranskat)abstract
- Specific features of white matter microstructure can be investigated by using biophysical models to interpret relaxation-diffusion MRI brain data. Although more intricate models have the potential to reveal more details of the tissue, they also incur time-consuming parameter estimation that may converge to inaccurate solutions due to a prevalence of local minima in a degenerate fitting landscape. Machine-learning fitting algorithms have been proposed to accelerate the parameter estimation and increase the robustness of the attained estimates. So far, learning-based fitting approaches have been restricted to microstructural models with a reduced number of independent model parameters where dense sets of training data are easy to generate. Moreover, the degree to which machine learning can alleviate the degeneracy problem is poorly understood. For conventional least-squares solvers, it has been shown that degeneracy can be avoided by acquisition with optimized relaxation-diffusion-correlation protocols that include tensor-valued diffusion encoding. Whether machine-learning techniques can offset these acquisition requirements remains to be tested. In this work, we employ artificial neural networks to vastly accelerate the parameter estimation for a recently introduced relaxation-diffusion model of white matter microstructure. We also develop strategies for assessing the accuracy and sensitivity of function fitting networks and use those strategies to explore the impact of the acquisition protocol. The developed learning-based fitting pipelines were tested on relaxation-diffusion data acquired with optimal and sub-optimal acquisition protocols. Networks trained with an optimized protocol were observed to provide accurate parameter estimates within short computational times. Comparing neural networks and least-squares solvers, we found the performance of the former to be less affected by sub-optimal protocols; however, model fitting networks were still susceptible to degeneracy issues and their use could not fully replace a careful design of the acquisition protocol.
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| 27. |
- Edén, Arvid, 1975, et al.
(författare)
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Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.
- 2010
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Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40
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Tidskriftsartikel (refereegranskat)abstract
- Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
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| 28. |
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| 29. |
- Flockhart, Mikael, et al.
(författare)
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A simple model for diagnosis of maladaptations to exercise training
- 2022
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Ingår i: Sports Medicine Open. - : Springer. - 2198-9761 .- 2199-1170. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The concept of overreaching and super compensation is widely in use by athletes and coaches seeking to maximize performance and adaptations to exercise training. The physiological aspects of acute fatigue, overreaching and non-functional overreaching are, however, not well understood, and well-defined negative physiological outcomes are missing. Instead, the concept relies heavily on performance outcomes for differentiating between the states. Recent advancements in the field of integrated exercise physiology have associated maladaptations in muscular oxidative function to high loads of exercise training.Method: Eleven female and male subjects that exercised regularly but did not engage in high-intensity interval training (HIIT) were recruited to a 4-week long training intervention where the responses to different training loads were studied. Highly monitored HIIT sessions were performed on a cycle ergometer in a progressive fashion with the intent to accomplish a training overload. Throughout the intervention, physiological and psychological responses to HIIT were assessed, and the results were used to construct a diagnostic model that could indicate maladaptations during excessive training loads.Results: We here use mitochondrial function as an early marker of excessive training loads and show the dynamic responses of several physiological and psychological measurements during different training loads. During HIIT, a loss of mitochondrial function was associated with reduced glycolytic, glucoregulatory and heart rate responses and increased ratings of perceived exertion in relation to several physiological measurements. The profile of mood states was highly affected after excessive training loads, whereas performance staled rather than decreased. By implementing five of the most affected and relevant measured parameters in a diagnostic model, we could successfully, and in all the subjects, identify the training loads that lead to maladaptations.Conclusions: As mitochondrial parameters cannot be assessed without donating a muscle biopsy, this test can be used by coaches and exercise physiologists to monitor adaptation to exercise training for improving performance and optimizing the health benefits of exercise. Clinical trial registry number NCT04753021 . Retrospectively registered 2021-02-12.
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| 30. |
- Flockhart, Mikael, et al.
(författare)
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Dose-response relationship between exercise load and mitochondrial function
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Dose-response relationship between exercise load and mitochondrial functionFlockhart M, Nilsson L, Bergman K, Apro W, Ekblom B, Larsen FJA dose-dependent relationship exists between exercise load and muscular adaptation. Mitochondria adapt to the increased ATP-demand by alterations in mass and/or quality. How mitochondrial mass and quality changes as a function of exercise load is not well investigated and we have previously found mitochondrial dysfunction after short-term intensive exercise. We therefore aimed to study mitochondrial function by altering exercise load during a three week interval training regimen to understand the dose-response relationship between exercise load and mitochondrial function. We took four muscle biopsies throughout the study, and as expected, mitochondrial function was positively affected during the first two weeks. After the third week, a dramatic mitochondrial dysfunction was evident as mitochondrial intrinsic respiration was reduced by 26% despite a 32% increase in mitochondrial yield. We hereby present evidence of a striking exercise-induced reduction in mitochondrial function after a period of very intense interval training.
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| 31. |
- Flockhart, Mikael, et al.
(författare)
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Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers.
- 2021
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Ingår i: Cell Metabolism. - : Cell Press. - 1550-4131 .- 1932-7420. ; 33:5, s. 957-970
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training positively affects metabolic health through increased mitochondrial oxidative capacity and improved glucose regulation and is the first line of treatment in several metabolic diseases. However, the upper limit of the amount of exercise associated with beneficial therapeutic effects has not been clearly identified. Here, we used a training model with a progressively increasing exercise load during an intervention over 4 weeks. We closely followed changes in glucose tolerance, mitochondrial function and dynamics, physical exercise capacity, and whole-body metabolism. Following the week with the highest exercise load, we found a striking reduction in intrinsic mitochondrial function that coincided with a disturbance in glucose tolerance and insulin secretion. We also assessed continuous blood glucose profiles in world-class endurance athletes and found that they had impaired glucose control compared with a matched control group.
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| 32. |
- Flockhart, Mikael, et al.
(författare)
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Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.
- 2023
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 238:4
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms.METHODS: Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO2 max (PE) or 5 × 4 min at ~95% of VO2 max (HIIT) on a cycle ergometer.RESULTS: Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON.CONCLUSION: Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.
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| 33. |
- Flockhart, Mikael, et al.
(författare)
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THREE HOURS OF MODERATE INTENSITY EXERCISE TRAINING REDUCES GLUCOSE TOLERANCE IN ENDURANCE TRAINED ATHLETES
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUNDIt is well accepted that exercise training improves glucose uptake and insulin sensitivity, and that endurance trained athletes in general show a high capacity for these parameters and excellent metabolic control. However, some studies fail to observe positive effects on glucose regulation in healthy, trained subjects the day after exercise. These, often unexpected, results have been postulated to be caused by excessive training loads, muscle damage, energy deficit, differences in glucose uptake in the exercised and non-exercised musculature and a metabolic interaction through increased fatty acid metabolism which suppresses glucose oxidation and uptake. The mode or volume of exercise that can lead to glucose intolerance in trained athletes as well as mechanistic insights and its relevance for health and performance are, however, not fully understood.AIMWe studied the metabolic response to a glucose load the day after a session of high intensity interval training (HIIT) or three hours of continuous exercise (3h) in endurance trained athletes and compared the results with measurements during rest.METHODNine endurance trained athletes (5 females, 4 males) underwent oral glucose tolerance tests (OGTT) after rest and ~14 hours after exercise on a cycle ergometer (HIIT 5x4 minutes at ~95% of VO2max or 3h at 65% of VO2max). Venous blood was sampled at 15-minute intervals for 120 minutes and concentrations of glucose, insulin, free fatty acids (FFA) and ketones (β-hydroxybutyrate) were measured. Statistical analysis was performed using a RM one-way ANOVA with the Giesser-Greenhouse correction and Dunnett’s test was used to compare the exercise conditions to the resting condition.RESULTSThe area under the curve (AUC) during the OGTT increased greatly after 3h (668±124 mM · min) (p<0.01) compared to rest (532±89) but was found to be unchanged after HIIT (541±96). Resting values of FFA and ketones were increased after 3h (p<0.01 and p<0.05, respectively) but not after HIIT. Insulin was found to be unaltered during all conditions.CONCLUSIONS AND RELEVANCEHere, we show manifestation of glucose intolerance in endurance trained athletes together with concomitant increases in plasma concentrations of FFA and ketones the day after a session of prolonged exercise training but not after HIIT. This could be a protective response for securing glucose delivery to the brain and therefore have a positive effect on endurance. It also has the potential to reduce the recovery of glycogen depots, glucose uptake during exercise and performance at higher work rates.
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| 34. |
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| 35. |
- Flyckt, Jonatan, et al.
(författare)
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Detecting ditches using supervised learning on high-resolution digital elevation models
- 2022
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Ingår i: Expert systems with applications. - : Elsevier Ltd. - 0957-4174 .- 1873-6793. ; 201
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Tidskriftsartikel (refereegranskat)abstract
- Drained wetlands can constitute a large source of greenhouse gas emissions, but the drainage networks in these wetlands are largely unmapped, and better maps are needed to aid in forest production and to better understand the climate consequences. We develop a method for detecting ditches in high resolution digital elevation models derived from LiDAR scans. Thresholding methods using digital terrain indices can be used to detect ditches. However, a single threshold generally does not capture the variability in the landscape, and generates many false positives and negatives. We hypothesise that, by combining the digital terrain indices using supervised learning, we can improve ditch detection at a landscape-scale. In addition to digital terrain indices, additional features are generated by transforming the data to include neighbouring cells for better ditch predictions. A Random Forests classifier is used to locate the ditches, and its probability output is processed to remove noise, and binarised to produce the final ditch prediction. The confidence interval for the Cohen's Kappa index ranges [0.655, 0.781] between the evaluation plots with a confidence level of 95%. The study demonstrates that combining information from a suite of digital terrain indices using machine learning provides an effective technique for automatic ditch detection at a landscape-scale, aiding in both practical forest management and in combatting climate change. © 2022 The Authors
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| 36. |
- Gallardo, Rodrigo, et al.
(författare)
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De novo design of a biologically active amyloid
- 2016
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 354:6313, s. 720-
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Tidskriftsartikel (refereegranskat)abstract
- Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional-determined by VEGFR2 loss of function in a biological context in which target protein function is essential.
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| 37. |
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| 38. |
- Gustafsson, Jan, et al.
(författare)
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APSI - svår autoimmun sjukdom med endokrina och icke-endokrina symtom
- 2004
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:24, s. 2096-2103
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.
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| 39. |
- Haghighatafshar, Salar, et al.
(författare)
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Microsieving coupled with O3 or ClO2 for treatment and disinfection of combined sewer overflows
- 2018
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Ingår i: Vatten: tidskrift för vattenvård /Journal of Water Management and research. - 0042-2886. ; 74:3, s. 123-134
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Tidskriftsartikel (refereegranskat)abstract
- A compact combined sewer overflow (CSO) treatment unit is set up and evaluated in pilot-scale. The pilotplant consisted of flocculation, coagulation and a microsieving system followed by a disinfection unit with either O3 or ClO2. Efficiency of the pilot-plant was evaluated with respect to reduction of Escherichia coli, coliform bacteria and intestinal enterococci as well as removal of biocides. Results showed that 10 mg L-1 of ClO2 as disinfectant was sufficient to meet the European Union (EU) requirements as per Bathing Water Directive (2006/7 EC) while the same results were only achieved when higher O3 dose (20 mg O3 L-1) was applied. This study revealed that chlorine dioxide was the most effective disinfectant agent in reducing the number of bacteria to below the limits set by the EU Bathing Water Directive and that the pre-treatment used was highly efficient. Regarding biocides, the efficiency of the removal was highly dependent on the type of substance. However, ozone was found to be able to remove a broader range of the investigated biocides.
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| 40. |
- Hammaréus, Filip, 1998-, et al.
(författare)
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Plasma type I collagen α1 chain in relation to coronary artery disease : findings from a prospective population-based cohort and an acute myocardial infarction prospective cohort in Sweden.
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the association between type I collagen α1 chain (COL1α1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1α1 to clinical characteristics and circulating markers of collagen metabolism.DESIGN: Life conditions, Stress and Health (LSH) study: prospective cohort study, here with a nested case-control design.Assessing Platelet Activity in Coronary Heart Disease (APACHE) study: prospective cohort study.SETTING: LSH: primary care setting, southeast Sweden.APACHE: cardiology department, university hospital, southeast Sweden.PARTICIPANTS: LSH: 1007 randomly recruited individuals aged 45-69 (50% women). Exclusion criteria was serious disease. After 13 years of follow-up, 86 cases with primary endpoint were identified and sex-matched/age-matched to 184 controls.APACHE: 125 patients with myocardial infarction (MI), 73 with ST-elevation MI and 52 with non-ST-elevation MI.EXCLUSION CRITERIA: Intervention study participation, warfarin treatment and short life expectancy.PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association between baseline COL1α1 and first-time major event of CAD, defined as fatal/non-fatal MI or coronary revascularisation after 13 years. Secondary outcomes were the association between the collagen biomarkers PRO-C1 (N-terminal pro-peptide of type I collagen)/C1M (matrix metalloproteinase-mediated degradation of type I collagen) and CAD; temporal change of COL1α1 after acute MI up to 6 months and lastly, correlates between COL1α1 and patient characteristics along with circulating markers of collagen metabolism.RESULTS: COL1α1 levels were associated with CAD, both unadjusted (HR=0.69, 95% CI=0.56 to 0.87) and adjusted (HR=0.55, 95% CI=0.41 to 0.75). PRO-C1 was associated with CAD, unadjusted (HR=0.62, 95% CI=0.47 to 0.82) and adjusted (HR=0.61, 95% CI=0.43 to 0.86), while C1M was not. In patients with MI, COL1α1 remained unchanged up to 6 months. COL1α1 was correlated to PRO-C1, but not to C1M.CONCLUSIONS: Plasma COL1α1 was independently and inversely associated with CAD. Furthermore, COL1α1 appeared to reflect collagen synthesis but not degradation. Future studies are needed to confirm whether COL1α1 is a clinically useful biomarker of CAD.
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| 41. |
- Hellstrand, Sophie, et al.
(författare)
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Dietary Data in the Malmö Offspring Study : Reproducibility, Method Comparison and Validation against Objective Biomarkers
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Irregular dietary intakes impairs estimations from food records. Biomarkers and method combinations can be used to improve estimates. Our aim was to examine reproducibility from two assessment methods, compare them, and validate intakes against objective biomarkers. We used the Malmö Offspring Study (55% women, 18-71 y) with data from a 4-day food record (4DFR) and a short food frequency questionnaire (SFFQ) to compare (1) repeated intakes (n = 180), (2) intakes from 4DFR and SFFQ (n = 1601), and (3) intakes of fatty fish, fruits and vegetables, and citrus with plasma biomarkers (n = 1433) (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid [CMPF], β-carotene and proline betaine). We also combined 4DFR and SFFQ estimates using principal component analysis (PCA). Moderate correlations were seen between repeated intakes (4DFR median ρ = 0.41, SFFQ median ρ = 0.59) although lower for specific 4DFR-items, especially fatty/lean fish (ρ ≤ 0.08). Between-method correlations (median ρ = 0.33) were higher for intakes of overall food groups compared to specific foods. PCA scores for citrus (proline betaine ρ = 0.53) and fruits and vegetables (β-carotene: ρ = 0.39) showed the highest biomarker correlations, whereas fatty fish intake from the SFFQ per se showed the highest correlation with CMPF (ρ = 0.46). To conclude, the reproducibility of SFFQ data was superior to 4DFR data regarding irregularly consumed foods. Method combination could slightly improve fruit and vegetable estimates, whereas SFFQ data gave most valid fatty fish intake.
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| 42. |
- Holmstrom, Jesper, et al.
(författare)
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Do we Read what we Share? Analyzing the Click Dynamic of News Articles Shared on Twitter
- 2019
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Ingår i: PROCEEDINGS OF THE 2019 IEEE/ACM INTERNATIONAL CONFERENCE ON ADVANCES IN SOCIAL NETWORKS ANALYSIS AND MINING (ASONAM 2019). - New York, NY, USA : Institute of Electrical and Electronics Engineers (IEEE). - 9781450368681 ; , s. 420-425
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Konferensbidrag (refereegranskat)abstract
- News and information spread over social media can have big impact on thoughts, beliefs, and opinions. It is therefore important to understand the sharing dynamics on these forums. However, most studies trying to capture these dynamics rely only on Twitters open APIs to measure how frequently articles are shared/retweeted, and therefore do not capture how many users actually read the articles linked in these tweets. To address this problem, in this paper, we first develop a novel measurement methodology, which combines the Twitter steaming API, the Bitly API, and careful sample rate selection to simultaneously collect and analyze the timeline of both the number of retweets and clicks generated by news article links. Second, we present a temporal analysis of the news cycle based on five-day-long traces (containing both clicks and retweet over time) for the news article links discovered during a seven-day period. Among other things, our analysis highlights differences in the relative timelines observed for clicks and retweets (e.g., retweet data often lags and underestimates the bias towards reading popular links/articles), and helps answer important questions regarding differences in how age-based biases and churn affect how frequently news articles shared on Twitter are accessed over time.
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| 43. |
- Johansson, Madeleine, et al.
(författare)
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PLASMA METABOLOMIC PROFILING PREDICTS AORTIC STIFFNESS AND RISK OF INCIDENT CARDIOVASCULAR DISEASE AND MORTALITY AFTER 16 YEARS OF FOLLOW-UP IN THE GENERAL POPULATION
- 2023
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Ingår i: Journal of Hypertension. - 1473-5598. ; 41:Suppl 3, s. 60-60
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Konferensbidrag (refereegranskat)abstract
- Objective: The mechanisms and metabolomic profile underlying early vascular ageing have not been explored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular ageing) and associated risk of incident cardiovascular disease and mortality in the general population.Design and method: We analysed 108 metabolites in plasma of 5172 individuals from two prospective population-based cohorts with over 16 years of follow-up. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Metabolite-predicted PWV was calculated in the older population based on the LASSO regression model by randomly assigning a training set (80%) and validation set (20%) in the younger cohort. Correlations between metabolite-predicted PWV and traditional cardiovascular risk factors were assessed by Spearman. Cox regression was used to calculate risk of incident cardiovascular disease and mortality, and all-cause mortality. All models were adjusted for age, sex and traditional cardiovascular risk factors.Results: Study characteristics are displayed in Table 1. Aortic stiffness was positively associated with following metabolites: long-chain acyl carnitines (C16:0, C16:1 and C13:0), dimethylguanidino valeric acid (DMGV), glutamate and cysteine, while serine was negatively associated with aortic stiffness (Figure 1A). The plasma metabolome predicted aortic stiffness in the validation cohort with good accuracy (R2 0.25, Figure 1B). Metabolite-predicted aortic stiffness was significantly correlated with age (r = 0.68), SBP (r = 0.49), BMI (r = 0.43), and sex (r = 0.20) in both cohorts cross-sectionally. During an average follow-up of 16 years, aortic stiffness predicted by baseline metabolites was associated with increased risk of incident coronary artery disease, incident stroke, cardiovascular mortality, and all-cause mortality in the older population (Figure 1C).Conclusions: For the first time, we show that aortic stiffness (vascular ageing) is predicted by altered metabolism of glutamate, acylcarnitine, cysteine, serine, and DMGV in the general population. These metabolic disturbances precede aortic stiffness by several years and are also associated with increased cardiovascular risk factor burden, and future risk of coronary artery disease, stroke, cardiovascular mortality, and all-cause mortality. Our results highlight the relevance of investigating the molecular pathways related to aortic stiffness. Further metabolomics studies are warranted to verify these findings in independent populations.
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| 44. |
- Khodaparast, Ladan, et al.
(författare)
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Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Buildup of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates of Escherichia coli and Acinetobacter baumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy.
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| 45. |
- Korduner, Johan, et al.
(författare)
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Proteomic and Metabolomic Characterization of Metabolically Healthy Obesity: : A Descriptive Study from a Swedish Cohort
- 2021
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Ingår i: Journal of Obesity. - : Hindawi Limited. - 2090-0708 .- 2090-0716. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims. Obesity is a well-established risk factor for the development of numerous chronic diseases. However, there is a small proportion of obese individuals that seem to escape these aforementioned conditions—Metabolically Healthy Obesity (MHO). Our aim was to do a metabolic and biomarker profiling of MHO individuals. Method. Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study—Cardiovascular arm (MDCS-CV, n = 3,443). They were further divided into MHO (n = 143) and MUO (n = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC, n = 3,027). Two distinctive principle components (PL2, PP5) were discovered with a significant difference and thus further investigated through their main loadings. Results. MHO individuals had a more metabolically favorable lipid and glucose profile than MUO subjects, that is, lower levels of traditional blood glucose and triglycerides, as well as a trend of lower metabolically unfavorable lipid biomarkers. PL2 (lipidomics, ) showed stronger associations of triacylglycerides with MUO, whereas phospholipids correlated with MHO. PP5 (proteomics, ) included interleukin-1 receptor antagonist (IL-1ra) and leptin with positive relations to MUO and galanin that correlated positively to MHO. The group differences in metabolite profiles were to a large extent explained by factors included in the metabolic syndrome. Conclusion. Compared to MUO individuals, corresponding MHO individuals present with a more favorable lipid metabolic profile, accompanied by a downregulation of potentially harmful proteomic biomarkers. This unique and extensive biomarker profiling presents novel data on potentially differentiating traits between these two obese phenotypes.
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| 47. |
- Lampinen, Björn, et al.
(författare)
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Neurite density imaging versus imaging of microscopic anisotropy in diffusion MRI : A model comparison using spherical tensor encoding
- 2017
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Ingår i: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119. ; 147, s. 517-531
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Tidskriftsartikel (refereegranskat)abstract
- In diffusion MRI (dMRI), microscopic diffusion anisotropy can be obscured by orientation dispersion. Separation of these properties is of high importance, since it could allow dMRI to non-invasively probe elongated structures such as neurites (axons and dendrites). However, conventional dMRI, based on single diffusion encoding (SDE), entangles microscopic anisotropy and orientation dispersion with intra-voxel variance in isotropic diffusivity. SDE-based methods for estimating microscopic anisotropy, such as the neurite orientation dispersion and density imaging (NODDI) method, must thus rely on model assumptions to disentangle these features. An alternative approach is to directly quantify microscopic anisotropy by the use of variable shape of the b-tensor. Along those lines, we here present the 'constrained diffusional variance decomposition' (CODIVIDE) method, which jointly analyzes data acquired with diffusion encoding applied in a single direction at a time (linear tensor encoding, LTE) and in all directions (spherical tensor encoding, STE). We then contrast the two approaches by comparing neurite density estimated using NODDI with microscopic anisotropy estimated using CODIVIDE. Data were acquired in healthy volunteers and in glioma patients. NODDI and CODIVIDE differed the most in gray matter and in gliomas, where NODDI detected a neurite fraction higher than expected from the level of microscopic diffusion anisotropy found with CODIVIDE. The discrepancies could be explained by the NODDI tortuosity assumption, which enforces a connection between the neurite density and the mean diffusivity of tissue. Our results suggest that this assumption invalid, which leads to a NODDI neurite density that is inconsistent between LTE and STE data. Using simulations, we demonstrate that the NODDI assumptions result in parameter bias that precludes the use of NODDI to map neurite density. With CODIVIDE, we found high levels of microscopic anisotropy in white matter, intermediate levels in structures such as the thalamus and the putamen, and low levels in the cortex and in gliomas. We conclude that accurate mapping of microscopic anisotropy requires data acquired with variable shape of the b-tensor.
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| 48. |
- Lampinen, Björn, et al.
(författare)
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Optimal experimental design for filter exchange imaging: Apparent exchange rate measurements in the healthy brain and in intracranial tumors.
- 2017
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 77:3, s. 1104-1114
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Filter exchange imaging (FEXI) is sensitive to the rate of diffusional water exchange, which depends, eg, on the cell membrane permeability. The aim was to optimize and analyze the ability of FEXI to infer differences in the apparent exchange rate (AXR) in the brain between two populations.METHODS: A FEXI protocol was optimized for minimal measurement variance in the AXR. The AXR variance was investigated by test-retest acquisitions in six brain regions in 18 healthy volunteers. Preoperative FEXI data and postoperative microphotos were obtained in six meningiomas and five astrocytomas.RESULTS: Protocol optimization reduced the coefficient of variation of AXR by approximately 40%. Test-retest AXR values were heterogeneous across normal brain regions, from 0.3 ± 0.2 s-1 in the corpus callosum to 1.8 ± 0.3 s-1 in the frontal white matter. According to analysis of statistical power, in all brain regions except one, group differences of 0.3-0.5 s-1 in the AXR can be inferred using 5 to 10 subjects per group. An AXR difference of this magnitude was observed between meningiomas (0.6 ± 0.1 s-1 ) and astrocytomas (1.0 ± 0.3 s-1 ).CONCLUSIONS: With the optimized protocol, FEXI has the ability to infer relevant differences in the AXR between two populations for small group sizes. Magn Reson Med 77:1104-1114, 2017.
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| 49. |
- Lampinen, Björn, et al.
(författare)
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Probing brain tissue microstructure with MRI: principles, challenges, and the role of multidimensional diffusion-relaxation encoding.
- 2023
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Ingår i: NeuroImage. - 1095-9572. ; 282
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Tidskriftsartikel (refereegranskat)abstract
- Diffusion MRI uses the random displacement of water molecules to sensitize the signal to brain microstructure and to properties such as the density and shape of cells. Microstructure modeling techniques aim to estimate these properties from acquired data by separating the signal between virtual tissue 'compartments' such as the intra-neurite and the extra-cellular space. A key challenge is that the diffusion MRI signal is relatively featureless compared with the complexity of brain tissue. Another challenge is that the tissue microstructure is wildly different within the gray and white matter of the brain. In this review, we use results from multidimensional diffusion encoding techniques to discuss these challenges and their tentative solutions. Multidimensional encoding increases the information content of the data by varying not only the b-value and the encoding direction but also additional experimental parameters such as the shape of the b-tensor and the echo time. Three main insights have emerged from such encoding. First, multidimensional data contradict common model assumptions on diffusion and T2 relaxation, and illustrates how the use of these assumptions cause erroneous interpretations in both healthy brain and pathology. Second, many model assumptions can be dispensed with if data are acquired with multidimensional encoding. The necessary data can be easily acquired in vivo using protocols optimized to minimize Cramér-Rao lower bounds. Third, microscopic diffusion anisotropy reflects the presence of axons but not dendrites. This insight stands in contrast to current 'neurite models' of brain tissue, which assume that axons in white matter and dendrites in gray matter feature highly similar diffusion. Nevertheless, as an axon-based contrast, microscopic anisotropy can differentiate gray and white matter when myelin alterations confound conventional MRI contrasts.
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| 50. |
- Lampinen, Björn, et al.
(författare)
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Searching for the neurite density with diffusion MRI : Challenges for biophysical modeling
- 2019
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:8, s. 2529-2545
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Tidskriftsartikel (refereegranskat)abstract
- In vivo mapping of the neurite density with diffusion MRI (dMRI) is a high but challenging aim. First, it is unknown whether all neurites exhibit completely anisotropic (“stick-like”) diffusion. Second, the “density” of tissue components may be confounded by non-diffusion properties such as T2 relaxation. Third, the domain of validity for the estimated parameters to serve as indices of neurite density is incompletely explored. We investigated these challenges by acquiring data with “b-tensor encoding” and multiple echo times in brain regions with low orientation coherence and in white matter lesions. Results showed that microscopic anisotropy from b-tensor data is associated with myelinated axons but not with dendrites. Furthermore, b-tensor data together with data acquired for multiple echo times showed that unbiased density estimates in white matter lesions require data-driven estimates of compartment-specific T2 values. Finally, the “stick” fractions of different biophysical models could generally not serve as neurite density indices across the healthy brain and white matter lesions, where outcomes of comparisons depended on the choice of constraints. In particular, constraining compartment-specific T2 values was ambiguous in the healthy brain and had a large impact on estimated values. In summary, estimating neurite density generally requires accounting for different diffusion and/or T2 properties between axons and dendrites. Constrained “index” parameters could be valid within limited domains that should be delineated by future studies.
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