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| 3. |
- Benkert, P., et al.
(författare)
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Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study
- 2022
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Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 21:3, s. 246-257
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI). Furthermore, we used the reference database to test the suitability of sNfL as an endpoint for group-level comparison of effectiveness across disease-modifying therapies. Methods: For derivation of a reference database of sNfL values, a control group was created, comprising participants with no evidence of CNS disease taking part in four cohort studies in Europe and North America. We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalised additive model for location, scale, and shape. We tested the reference database in participants with multiple sclerosis in the Swiss Multiple Sclerosis Cohort (SMSC). We compared the association of sNfL Z scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capacity. We validated these findings in an independent sample of individuals with multiple sclerosis who were followed up in the Swedish Multiple Sclerosis registry. Findings: We obtained 10 133 blood samples from 5390 people (median samples per patient 1 [IQR 1–2] in the control group). In the control group, sNfL concentrations rose exponentially with age and at a steeper increased rate after approximately 50 years of age. We obtained 7769 samples from 1313 people (median samples per person 6·0 [IQR 3·0–8·0]). In people with multiple sclerosis from the SMSC, sNfL percentiles and Z scores indicated a gradually increased risk for future acute (eg, relapse and lesion formation) and chronic (disability worsening) disease activity. A sNfL Z score above 1·5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3·15, 95% CI 2·35–4·23; p<0·0001) and in people considered stable with no evidence of disease activity (2·66, 1·08–6·55; p=0·034). Increased Z scores outperformed absolute raw sNfL cutoff values for diagnostic accuracy. At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the SMSC decreased to those seen in the control group with use of monoclonal antibodies (ie, alemtuzumab, natalizumab, ocrelizumab, and rituximab) and, to a lesser extent, oral therapies (ie, dimethyl fumarate, fingolimod, siponimod, and teriflunomide). However, longitudinal sNfL Z scores remained elevated with platform compounds (interferons and glatiramer acetate; p<0·0001 for the interaction term between treatment category and treatment duration). Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry. Interpretation: The use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials. Funding: Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, Roche. © 2022 Elsevier Ltd
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- Meier, S, et al.
(författare)
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Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis
- 2023
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:3, s. 287-297
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS).ObjectiveTo determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression.Design, Setting, and ParticipantsData were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022. The SMSC is a prospective, multicenter study performed in 8 centers in Switzerland. For this nested study, participants had to meet the following inclusion criteria: cohort 1, patients with MS and either stable or worsening disability and similar baseline Expanded Disability Status Scale scores with no relapses during the entire follow-up; and cohort 2, all SMSC study patients who had initiated and continued B-cell–depleting treatment (ie, ocrelizumab or rituximab).ExposuresPatients received standard immunotherapies or were untreated.Main Outcomes and MeasuresIn cohort 1, sGFAP and sNfL levels were measured longitudinally using Simoa assays. Healthy control samples served as the reference. In cohort 2, sGFAP and sNfL levels were determined cross-sectionally.ResultsThis study included a total of 355 patients (103 [29.0%] in cohort 1: median [IQR] age, 42.1 [33.2-47.6] years; 73 female patients [70.9%]; and 252 [71.0%] in cohort 2: median [IQR] age, 44.3 [33.3-54.7] years; 156 female patients [61.9%]) and 259 healthy controls with a median [IQR] age of 44.3 [36.3-52.3] years and 177 female individuals (68.3%). sGFAP levels in controls increased as a function of age (1.5% per year; P &lt; .001), were inversely correlated with BMI (−1.1% per BMI unit; P = .01), and were 14.9% higher in women than in men (P = .004). In cohort 1, patients with worsening progressive MS showed 50.9% higher sGFAP levels compared with those with stable MS after additional sNfL adjustment, whereas the 25% increase of sNfL disappeared after additional sGFAP adjustment. Higher sGFAP at baseline was associated with accelerated gray matter brain volume loss (per doubling: 0.24% per year; P &lt; .001) but not white matter loss. sGFAP levels remained unchanged during disease exacerbations vs remission phases. In cohort 2, median (IQR) sGFAP z scores were higher in patients developing future confirmed disability worsening compared with those with stable disability (1.94 [0.36-2.23] vs 0.71 [−0.13 to 1.73]; P = .002); this was not significant for sNfL. However, the combined elevation of z scores of both biomarkers resulted in a 4- to 5-fold increased risk of confirmed disability worsening (hazard ratio [HR], 4.09; 95% CI, 2.04-8.18; P &lt; .001) and PIRA (HR, 4.71; 95% CI, 2.05-9.77; P &lt; .001).Conclusions and RelevanceResults of this cohort study suggest that sGFAP is a prognostic biomarker for future PIRA and revealed its complementary potential next to sNfL. sGFAP may serve as a useful biomarker for disease progression in MS in individual patient management and drug development.
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- Mikeš, P., et al.
(författare)
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The Mass Production of Lignin Fibres by Means of Needleless Electrospinning
- 2021
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Ingår i: Journal of Polymers and the Environment. - : Springer. - 1566-2543 .- 1572-8919. ; 29:7, s. 2164-2173
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Lignin, a cheap renewable natural polymer, can be used as a precursor for the production of carbon fibres, its conversion into which is significantly faster than that of polyacrylonitrile. Lignin can be fractionated in various solvents via dissolution to decrease its polydispersity. Fractions with a higher molecular weight distribution can then be used in solvent-based spinning technologies such as electrospinning. We selected several solvent systems according to the Hansen solubility theory and subsequently tested them for solubility and electro-spinability. The selected solvent systems were then successfully tested for use in the needleless electrospinning process due to their potential for mass production. The solutions used in the electrospinning process needed high concentrations of lignin, which led to a high degree of viscosity. Therefore, we measured the relaxation times and viskosity for selected solutions, a factor that plays a pivotal role in terms of the production of smooth fibres. Finally, these solutions were tested for electrospinning using alternating current. This technology brings a new possibility in mass production of lignin fibres due to its high productivity and ease of use. Such materials can be used in a number of applications such as batteries, supercapacitors or for the production of composite materials. They provide a cheap and renewable natural polymer source which can easily be transformed into a carbon nanofibrous layer. Graphic Abstract: [Figure not available: see fulltext.].
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| 12. |
- Lindgren, K, et al.
(författare)
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Automation of cell line development
- 2009
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Ingår i: Cytotechnology. - : Springer Science and Business Media LLC. - 0920-9069 .- 1573-0778. ; 59:1, s. 1-10
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Lundmark, A., et al.
(författare)
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Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflamed areas of connective tissue, and non-inflamed areas of connective tissue. Moreover, 92 genes were identified as significantly up-regulated in inflamed areas of the gingival connective tissue compared to non-inflamed tissue. Among these, immunoglobulin lambda-like polypeptide 5 (IGLL5), signal sequence receptor subunit 4 (SSR4), marginal zone B and B1 cell specific protein (MZB1), and X-box binding protein 1 (XBP1) were the four most highly up-regulated genes. These genes were also verified as significantly higher expressed in gingival tissue of patients with periodontitis compared to healthy controls, using reverse transcription quantitative polymerase chain reaction. Moreover, the protein expressions of up-regulated genes were verified in gingival biopsies by immunohistochemistry. In summary, in this study, we report distinct gene expression signatures within periodontitis-affected gingival tissue, as well as specific genes that are up-regulated in inflamed areas compared to non-inflamed areas of gingival tissue. The results obtained from this study may add novel information on the genes and cell types contributing to pathogenesis of the chronic inflammatory disease periodontitis.
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- Alakalhunmaa, Suvi, et al.
(författare)
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Softwood-based sponge gels
- 2016
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Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 23:5, s. 3221-3238
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Tidskriftsartikel (refereegranskat)abstract
- Crosslinking-aided gelation was utilized to prepare hydrogels from softwood polysaccharides, with spruce galactoglucomannans (GGM)—a group of largely unexploited hemicelluloses—as the main component, aiming at conversion into sponge-like aerogels. Cellulose nanofibrils were used for the formation of a reinforcing network, which was further crosslinked together with a GGM matrix by ammonium zirconium carbonate, an inorganic salt that is regarded as safe for use in food packaging. The hydrogels were freeze-dried into stiff, low-density aerogels with 98 % of their volume composed of air-filled pores. When immersed in water, the aerogels absorbed water up to 37 times their initial weight, demonstrating elasticity and repeatable and reversible sponge capacity. The developed concept reassembles the wood polysaccharides in a new way, creating interesting possibilities for utilizing the abundant “green gold,†GGM. The obtained biobased materials could find application potential, for example, in the field of food packaging and could contribute in the reduction of the usage of petroleum-based plastics in the future.
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- Baker, Darren A., et al.
(författare)
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Opportunities in lignin based carbon fibre
- 2015
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Ingår i: NWBC 2015. - Espoo : VTT. - 9789513883539 ; , s. 244-251
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Konferensbidrag (refereegranskat)abstract
- Innventia AB's LignoBoost process enables the extraction of high purity lignin efficiently from the black liquor in kraft mills. A stream of black liquor is taken from the evaporation plant and the lignin is precipitated by acidification and filtered. The filter cake is redispersed and acidified and the resulting slurry is filtered and washed. High purity lignin can be produced at several scales, namely 10g, 1kg, 10kg and over 1,000kg. Innventia has invested significantly to demonstrate the potential of lignin as a viable feedstock for carbon fibre manufacture. Initially, the fibre melt spinning performance of the lignin is assessed using single filament melt extrusion and then melt spinning is performed at the multifilament scale, where fine fibres can be produced for conversion to carbon fibre. Oxidative thermostabilisation of the lignin fibres is carried out so that carbonisation can proceed. The effects of thermal treatment programmes and tensioning have been studied by using either thermomechanical analysis or by using test equipment specially designed to monitor carbonisation profiles with either stress or strain control. In addition, continuous processes for the conversion of lignin fibre to carbon fibre are being developed.
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- Bjurhager, Ingela, et al.
(författare)
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Ultrastructure and Mechanical Properties of Populus Wood with Reduced Lignin Content Caused by Transgenic Down-Regulation of Cinnamate 4-Hydroxylase
- 2010
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 11:9, s. 2359-2365
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Tidskriftsartikel (refereegranskat)abstract
- Several key enzymes in lignin biosynthesis of Populus have been down-regulated by transgenie approaches to investigate their role in wood lignification and to explore their potential for lignin modification. Cinnamate 4-hydroxylase is an enzyme in the early phenylpropanoid pathway that has not yet been functionally analyzed in Populus. This study shows that down-regulation of cinnamate 4-hydroxylase reduced Klason lignin content by 30% with no significant change in syringyl to guaiacyl ratio. The lignin reduction resulted in ultrastructural differences of the wood and a 10% decrease in wood density. Mechanical properties investigated by tensile tests and dynamic mechanical analysis showed a decrease in stiffness, which could be explained by the lower density. The study demonstrates that a large modification in lignin content only has minor influences on tensile properties of wood in its axial direction and highlights the usefulness of wood modified beyond its natural variation by transgene technology in exploring the impact of wood biopolymer composition and ultrastructure on its material properties.
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| 17. |
- Fernandes, Susana C. M., et al.
(författare)
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Transparent chitosan films reinforced with a high content of nanofibrillated cellulose
- 2010
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 81:2, s. 394-401
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the preparation and characterization of nanocomposite films based on different chitosan matrices and nanofibrillated cellulose (NFC) for the purpose of improving strength properties. The nanocomposite films were prepared by a simple procedure of casting a water-based suspension of chitosan and NFC, and were characterized by several techniques: namely SEM, X-ray diffraction, visible spectrophotometry, TGA, tensile and dynamic-mechanical analysis. The films obtained were shown to be highly transparent (transmittance varying between 90 and 20% depending on the type of chitosan and NFC content), flexible, displayed better mechanical properties, with a maximum increment on the Young's modulus of 78% and 150% for high molecular weight (HCH) and water-soluble high molecular weight (WSHCH) filled chitosans, respectively; and of 200% and 320% for low molecular weight (LCH) and water-soluble filled (WSLCH) chitosans, respectively. The filled films also showed increased thermal stability, with, for example, an increase in the initial degradation temperature (Td(i)) from 227 degrees C in the unfilled LCH film up to 271 degrees C in filled LCHNFC50% nanocomposite films, and a maximum degradation temperature (Tdi) raising from 304 degrees C to 313 degrees C for the same materials.
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| 18. |
- Penttilä, Paavo A., et al.
(författare)
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Xylan as limiting factor in enzymatic hydrolysis of nanocellulose
- 2013
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 129, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- The role of xylan as a limiting factor in the enzymatic hydrolysis of cellulose was studied by hydrolysing nanocellulose samples prepared by mechanical fibrillation of birch pulp with varying xylan content. Analyzing the nanocelluloses and their hydrolysis residues with dynamic FT-IR spectroscopy revealed that a certain fraction of xylan remained tightly attached to cellulose fibrils despite partial hydrolysis of xylan with xylanase prior to pulp fibrillation and that this fraction remained in the structure during the hydrolysis of nanocellulose with cellulase mixture as well. Thus, a loosely bound fraction of xylan was predicted to have been more likely removed by purified xylanase. The presence of loosely bound xylan seemed to limit the hydrolysis of crystalline cellulose, indicated by an increase in cellulose crystallinity and by preserved crystal width measured with wide-angle X-ray scattering. Removing loosely bound xylan led to a proportional hydrolysis of xylan and cellulose with the cellulase mixture.
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| 19. |
- Salmen, Lennart, et al.
(författare)
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On the origin of sorption hysteresis in cellulosic materials
- 2018
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 182, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- Moisture sorption and moisture sorption hysteresis of carbohydrates are phenomena which affect the utilisation of products made thereof. Although extensively studied, there is still no consensus regarding the mechanisms behind sorption hysteresis. Attempts have been made to link the behaviour to molecular properties, in particular to softening properties, and the moisture sorption hysteresis has therefore here been investigated by modifying cellulosic fibres to affect their softening properties. The results show that the moisture sorption hysteresis diminishes with decreasing softening temperature, and was even completely absent at the higher degrees of modification. The moisture sorption characteristics also changed from a type II sorption to a more type III sorption behaviour, a feature more prominent the higher the degree of modification and the higher the temperature. For the highest degree of modification studied the sorption characteristics changed from sorbing less water the higher the temperature to sorbing more water with increasing temperature.
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