| 61. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Cerebrospinal Fluid Microglial Markers in Alzheimer's Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid beta-plaques in Alzheimer's disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than controls and patients with stable mild cognitive impairment, consistent with the presence of activated microglial cells in AD brains, but with large overlaps between groups. CCL2 and YKL-40 concentrations did not differ among groups. Microglial markers are unlikely to be useful for AD diagnosis, but might be useful for identification of distinct subgroups of patients, and for the development and implementation of drugs targeting microglial pathology.
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| 62. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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| 63. |
- Meklesh, Viktoriia, et al.
(författare)
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Characterization of the Colloidal Properties of Dissolved Organic Matter From Forest Soils
- 2022
-
Ingår i: Frontiers in Soil Science. - : Frontiers Media SA. - 2673-8619.
-
Tidskriftsartikel (refereegranskat)abstract
- Components of dissolved organic matter (DOM) span from sub-nm molecules to colloidal aggregates of several hundred nm. The colloidal fraction is important for the transport of organic matter and associated elements in the environment, and for the stability of DOM constituents with respect to microbial decomposition. This study focuses on the colloidal properties of DOM extracted from spruce forest soils of a chronosequence. The DOM samples were obtained by common water extraction procedures at 21 and 100°C, respectively. We applied an experimental approach combining chemical analysis with light and X-ray scattering techniques that informed on the colloidal size, charge, and structure of DOM. Results showed that two main types of colloids were present: semi-flexible cylinders and fractal aggregates. The cylinders consisted of carbohydrates, presumably hemicelluloses, while the aggregates were a composite material containing a large fraction of carbohydrates together with aliphatics and clay particles. These fractal aggregates dominated the cold-water extracts whereas the strong increase in total organic carbon by hot-water extraction caused a concomitantly strong increase of semi-flexible cylinders, which became the predominant species. Comparison between the chronosequence soils showed that with increasing forest age, the amount of carbon extracted per gram of soil declined and the concentration of the semi-flexible cylinders decreased. Thus, the distribution between the fractal aggregates and cylinders in the forest soil DOM samples depends on the composition of the soil organic matter and the leaching temperature. Changes in this distribution may have important implications for the reactivity and stability of DOM colloids.
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| 64. |
- Mårild, Karl, 1982, et al.
(författare)
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Histological activity in inflammatory bowel disease and risk of serious infections : A nationwide study
- 2024
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 22:4, s. 831-846
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear.METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses.RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61).CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD.
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| 65. |
- Novakova, Lenka, et al.
(författare)
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Monitoring disease activity in multiple sclerosis using serum neurofilament light protein.
- 2017
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 89:22, s. 2230-2237
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Tidskriftsartikel (refereegranskat)abstract
- To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.In MS, the correlation between serum and CSF NFL was r = 0.62 (p < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p < 0.001 and p < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6-32.7) ng/L to 15.7 (IQR 9.6-22.7) ng/L (p < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission (p < 0.001) or those without new lesions on MRI (p < 0.001).Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.
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| 66. |
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| 67. |
- Olsson, Henrik, et al.
(författare)
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Askåterföring och biogasuppgradering med träbränsleaska
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Wood fuel ash is a resource that should be used for nutrient recycling to forest land andwhich also has the potential to be used for small-scale upgrading of biogas into CNG foruse as vehicle fuel. In the biogas upgrading process, carbon dioxide is fixed through acarbonation process. The carbonation process is also an important part of theconventional ash recycling process, since ash to be returned to forest is usually stabilizedby storing in a pile for a significant period of time to allow the carbon dioxide of the airto act on the ash. This project has explored the possibilities of developing a technicalsystem and business models that can lead to ash filter technology being used to processbiogas into vehicle fuel while at the same time contributing to more wood fuel ash beingreturn to forest land. Work has shown that the preconditions are good for the ashproducers existing infrastructure to be well suited for use in a future system where thebiogas plant replaces the role of the ash terminal for stabilizing the ash. Desirableproperties for ash used for biogas upgrading is that it has a high content of CaO and anability to hold water without creating backpressure in the ash bed, and that the biogasstabilized ash meets the limit values for heavy metals and nutrients for return to forest.Within the project tests were carried out with 10 tonnes of moistened ash involving shortterm storage of fresh ash, ash stabilization in biogas upgrading filters and subsequentreturn to forest land. The biogas stabilized ash had a very low conductivity in relation tothe limit value, showed a lowering of the pH value from close to 13 to below 10 and metthe limit values for heavy metals and plant nutrients for spreading on forest land. Thespreading trail with biogas stabilized ash to forest land showed an acceptable distributionpattern and did not cause any damage to the trees. A slightly higher moisture contentprobably would have further improved the distribution pattern. The tests were successfuland showed that there is good potential for biogas stabilized ashes to be spread with ashrecycling technology currently in use.In a system where biogas upgrading with ash filter technology is integrated into the ashrecycling chain, the biogas plant will act as a micro-terminal, where ash is handled closerto the ash producer and the distribution site compared to a conventional terminal. Inorder for this to be effective, one partner must be able to coordinate transportation ofash and ensure the ash quality, which in many cases can be an ash contractor. It is alsoof the utmost importance that forest operators and landowners are involved to secureend-users for the stabilized wood fuel ash. The economic calculations show that the costfor ash producers and forest owners would be in the same order of magnitude as for thecurrent ash recycling system. However, there is a potential that ash filter technology cancreate a product of a more uniform and higher quality while at the same time upgradingthe biogas to vehicle gas quality. The system will also contribute to local production ofvehicle fuel and an increased supply of biofuel in rural areas. Revenues from theupgraded biogas are expected to cover a large part of the costs incurred at the biogasplant linked to ash management. However, the cost of handling ash at a biogas plant isdependent on local conditions such as whether the ash is supplied dry or moistened andwhat carbon dioxide uptake capacity it has.In order to be able to handle ashes from smaller biomass energy plants and other ashproducers that currently deliver dry ash to end-users, it would be desirable to continuework on cost-effective methods for dust-free reception at biogas plants. Furthermore,there is a need for continued work linked to the storage of fresh ash. From a logisticalperspective there is a need to store the ash for shorter periods to get more efficienttransport and to be able to store ash from the winter season for use during the summer.For a long-term successful implementation of the developed system, it is important tocontinue to address the challenge linked to the forest owners’ interest in spreading ashin the future. For a smaller biogas plant that handles 500 tonnes / year of dry ash, acollaboration with up to 200-300 forest owners may be needed to find the distributionarea for the ash over time. The challenge of finding end users for the stabilized ash isshared by other players in the ash value chain and the project group sees opportunitiesthat local use of ash for production of vehicle gas to the community could provide apositive local connection that will aid in the work for increased ash recycling.
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| 68. |
- Olsson, Henrik, et al.
(författare)
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Estimating diagnostic uncertainty in artificial intelligence assisted pathology using conformal prediction
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Unreliable predictions can occur when an artificial intelligence (AI) system is presented with data it has not been exposed to during training. We demonstrate the use of conformal prediction to detect unreliable predictions, using histopathological diagnosis and grading of prostate biopsies as example. We digitized 7788 prostate biopsies from 1192 men in the STHLM3 diagnostic study, used for training, and 3059 biopsies from 676 men used for testing. With conformal prediction, 1 in 794 (0.1%) predictions is incorrect for cancer diagnosis (compared to 14 errors [2%] without conformal prediction) while 175 (22%) of the predictions are flagged as unreliable when the AI-system is presented with new data from the same lab and scanner that it was trained on. Conformal prediction could with small samples (N = 49 for external scanner, N = 10 for external lab and scanner, and N = 12 for external lab, scanner and pathology assessment) detect systematic differences in external data leading to worse predictive performance. The AI-system with conformal prediction commits 3 (2%) errors for cancer detection in cases of atypical prostate tissue compared to 44 (25%) without conformal prediction, while the system flags 143 (80%) unreliable predictions. We conclude that conformal prediction can increase patient safety of AI-systems.
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| 69. |
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| 70. |
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