| 1. |
- Lind, Lars, et al.
(författare)
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Comparison of four non-alcoholic fatty liver disease detection scores in a Caucasian population
- 2020
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Ingår i: World Journal of Hepatology. - : Baishideng Publishing Group Inc.. - 1948-5182. ; 12:4, s. 149-159
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is a common disorder, with an estimated prevalence ranging from 20% to 35% in the general population. Several scores based on easily measurable biochemical and clinical parameters, including the fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), and NAFLD liver fat score (LFS), have been developed for the detection of NAFLD. However, comparative information regarding the efficacy of these scores for predicting NAFLD in population-based samples comprising normal and high-risk individuals is lacking.AIMTo evaluate four NAFLD detection scores in two samples with different NAFLD risks.METHODSNAFLD screening was performed in a population-based sample of 50-year-old individuals in Uppsala, Sweden [n = 310; Prospective investigation of obesity, energy and metabolism (POEM) study] and a high-risk population comprising patients with a body mass index > 25 kg/m2 and either high plasma triglycerides (≥ 1.7 mmol/L) or type 2 diabetes (n = 310; EFFECT studies). NAFLD was defined as liver fat > 5.5% using magnetic resonance imaging-proton density fat fraction. FLI, HSI, LAP, and NAFLD LFS were assessed. A logistic regression model was used to evaluate the effectiveness of the different scores.RESULTSThe prevalence of NAFLD was 23% in POEM. FLI showed the highest receiver operating characteristic area under the curve (ROC AUC; 0.82) and was significantly better than the LAP score (P = 0.005 vs LAP, P = 0.08 vs LFS, P = 0.12 vs HSI) for detection of NAFLD. The other three indices performed equally in POEM (0.77-0.78). The prevalence of NAFLD was 74% in EFFECT; LFS performed best (ROC AUC 0.80) in this sample. The ROC AUC for LFS (0.80) was significantly higher than that for FLI (P = 0.0019) and LAP (P = 0.0022), but not HSI (P = 0.11). We performed a sensitivity analysis with stratification for the two high-risk subgroups (patients with diabetes or hypertriglyceridemia) from the EFFECT studies. LAP performed best in patients with hypertriglyceridemia. No major differences were observed between the other scores.CONCLUSIONThe four investigated NAFLD scores performed differently in the populationbased vs high-risk setting. FLI was preferable in the population-based setting, while LFS performed best in the high-risk setting.
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| 2. |
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| 3. |
- Lind, Lars, et al.
(författare)
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The Plasma Metabolomic Profile is Differently Associated with Liver Fat, Visceral Adipose Tissue, and Pancreatic Fat
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Lippincott Williams & Wilkins. - 0021-972X .- 1945-7197. ; 106:1, s. e118-e129
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Metabolic differences between ectopic fat depots may provide novel insights to obesity-related diseases.OBJECTIVE: To investigate the plasma metabolomic profiles in relation to visceral adipose tissue (VAT) volume and liver and pancreas fat percentages.DESIGN: Cross-sectional.SETTING: Multicenter at academic research laboratories.PATIENTS: Magnetic resonance imaging (MRI) was used to assess VAT volume, the percentage of fat in the liver and pancreas (proton density fat fraction [PDFF]) at baseline in 310 individuals with a body mass index ≥ 25 kg/m2 and with serum triglycerides ≥ 1.7 mmol/l and/or type 2 diabetes screened for inclusion in the 2 effect of omega-3 carboxylic acid on liver fat content studies.INTERVENTION: None.MAIN OUTCOME MEASURE: Metabolomic profiling with mass spectroscopy enabled the determination of 1063 plasma metabolites.RESULTS: Thirty metabolites were associated with VAT volume, 31 with liver PDFF, and 2 with pancreas PDFF when adjusting for age, sex, total body fat mass, and fasting glucose. Liver PDFF and VAT shared 4 metabolites, while the 2 metabolites related to pancreas PDFF were unique. The top metabolites associated with liver PDFF were palmitoyl-palmitoleoyl-GPC (16:0/16:1), dihydrosphingomyelin (d18:0/22:0), and betaine. The addition of these metabolites to the Liver Fat Score improved C-statistics significantly (from 0.776 to 0.861, P = 0.0004), regarding discrimination of liver steatosis.CONCLUSION: Liver PDFF and VAT adipose tissue shared several metabolic associations, while those were not shared with pancreatic PDFF, indicating partly distinct metabolic profiles associated with different ectopic fat depots. The addition of 3 metabolites to the Liver Fat Score improved the prediction of liver steatosis.
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| 4. |
- Mulder, Skander, et al.
(författare)
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A metabolomics-based molecular pathway analysis of how the sodium-glucose co-transporter-2 inhibitor dapagliflozin may slow kidney function decline in patients with diabetes
- 2020
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 22:7, s. 1157-1166
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate which metabolic pathways are targeted by the sodium-glucose co-transporter-2 inhibitor dapagliflozin to explore the molecular processes involved in its renal protective effects. Methods An unbiased mass spectrometry plasma metabolomics assay was performed on baseline and follow-up (week 12) samples from the EFFECT II trial in patients with type 2 diabetes with non-alcoholic fatty liver disease receiving dapagliflozin 10 mg/day (n = 19) or placebo (n = 6). Transcriptomic signatures from tubular compartments were identified from kidney biopsies collected from patients with diabetic kidney disease (DKD) (n = 17) and healthy controls (n = 30) from the European Renal cDNA Biobank. Serum metabolites that significantly changed after 12 weeks of dapagliflozin were mapped to a metabolite-protein interaction network. These proteins were then linked with intra-renal transcripts that were associated with DKD or estimated glomerular filtration rate (eGFR). The impacted metabolites and their protein-coding transcripts were analysed for enriched pathways. Results Of all measured (n = 812) metabolites, 108 changed (P < 0.05) during dapagliflozin treatment and 74 could be linked to 367 unique proteins/genes. Intra-renal mRNA expression analysis of the genes encoding the metabolite-associated proteins using kidney biopsies resulted in 105 genes that were significantly associated with eGFR in patients with DKD, and 135 genes that were differentially expressed between patients with DKD and controls. The combination of metabolites and transcripts identified four enriched pathways that were affected by dapagliflozin and associated with eGFR: glycine degradation (mitochondrial function), TCA cycle II (energy metabolism), L-carnitine biosynthesis (energy metabolism) and superpathway of citrulline metabolism (nitric oxide synthase and endothelial function). Conclusion The observed molecular pathways targeted by dapagliflozin and associated with DKD suggest that modifying molecular processes related to energy metabolism, mitochondrial function and endothelial function may contribute to its renal protective effect.
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| 5. |
- Akter, Shaheda T.
(författare)
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Experimental characterization and numerical modeling of compression perpendicular to the grain in wood and cross-laminated timber
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Compression perpendicular to the grain (CPG) of wood is a typical loading situation in timber structures. It has been an extensively studied research topic for decades, due to the highly ductile behavior of wood under such loading, the large variations in mechanical properties, and the relevance of these properties in structural design. Among others, the main influencing factors for CPG properties are stressed volume, load and support configurations, and annual ring orientations to the loading direction. After the innovation of the massive, engineered wood based product, cross-laminated timber (CLT) and its application in high rise buildings, CPG of wood has gained further importance. The development of a non-homogeneous, undesired and combined stress state under CPG in solid wood, due to the material anisotropy in the radial-tangential plane, can build up a complex multi-axial stress state in CLT. As a comparatively new product, the study of the influencing factors for CPG properties of CLT, and an understanding of the local material behavior under such loading, is essential for product characterization and for the development of design guidelines to ensure safe and efficient design.The main aim of the doctoral thesis is to establish a relationship betweenthe anisotropic behavior of clear wood in the transverse plane and the structural response of CLT under CPG loading. Both experimental and numerical studies were adopted herein, to enhance the understanding of the basic material behavior and the product and structural behavior. On the clear wood scale, the focus was on developing a test setup for uniaxial and biaxial loading in the radial-tangential(RT) plane. The potential of the developed test setup for the biaxial testing in the transverse plane was exploited for the investigation of the moisture and time dependent behavior of clear wood under radial compression and rolling shear loading. For data acquisition, in addition to the force and displacement data measured by the internal actuators of the testing machine and an external load cell,a contact-free digital image correlation (DIC) system was used in the experimental investigations. A numerical model was developed, which can describe the elasto-plastic behavior of wood under compression in the transverse plane and predict the structural behavior of solid wood and CLT. For that purpose, a novel Quadratic multi-surface (QMS) failure criterion and a simplified Hoffman failure criterion were implemented in a user-subroutine in the finite element software Abaqus®, and their suitability was compared with the Abaqus implemented Hill’s criterion.The validation of the material models was based on the experimental investigations of failure behavior of clear wood under stress perpendicular to the grain with rolling shear interaction. The material models were further utilized to predict the structural response of solid wood and CLT wall-to-floor connections under CPG loading. The predicted response of CLT connections under CPG by using the above-mentioned material models was compared with experiments, which investigated the influences of different connection types, wall and floor thicknesses, positions of walls, and outer deck layer orientations. The models were then applied to investigate the influence of the pith location in the boards, the number of layers and the thickness of walls and the floor on the stiffness and strength of CLT connections. Moreover, the CLT connection’s rotational rigidity as a consequence of compressive force from the upper floor in a multi-story building was studied by means of finite element calculations.The DIC measured strain fields from the experiments on clear wood confirmed the dependence of strain field on the curvature of the annual rings. As regards the material models, Hill’s model resulted in significantly higher force carrying capacity than experiments on clear wood, whereas Hoffman’s and QMS models predicted reasonably well the force-displacement relationships as found in experiments. The Hoffman’s and QMS models predicted stiffness was about 5–10% higher than corresponding experimental results on clear wood, and about 25% higher for CLT connections. The higher difference in the latter case is due to the difference in material properties of clear wood and structural timber, and the contact behavior between the structural members. The results from CLT wall-to-floor connections revealed a strong influence of loading and supporting configurations, wall thickness and pith locations on their stiffness and strength. A compressive loading on the CLT wall showed a positive effect on the rotational stiffness of CLT wall-to-floor connections, which considerably reduces the CLT floor mid-span deflection in comparison to a simply-supported floor.The thesis work contributes to an enhanced understanding of the anisotropic material behavior of wood in the RT-plane and of its effects on structural timber and CLT under CPG loading. The outcomes of the thesis are beneficial to the product design and standardization of CLT and can be applied in further product development and in optimized structural design.
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| 6. |
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| 7. |
- Bao, Kai, et al.
(författare)
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Extracellular Vesicle Subproteome Differences among Filifactor alocis Clinical Isolates
- 2022
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Filifactor alocis is a Gram-positive asaccharolytic, obligate anaerobic rod of the Firmicutes phylum, which has recently been implicated in oral infections. Extracellular vesicles (EVs) are crucial conveyors of microbial virulence in bacteria and archaea. Previously, in highly purified EVs from the F. alocis reference strain ATCC 35896 (CCUG 47790), 28 proteins were identified. The present study aimed to use label-free quantification proteomics in order to chart these EV proteins, in the reference strain, and in nine less-well-characterized clinical F. alocis isolates. In total, 25 of the EV proteins were identified and 24 were quantified. Sixteen of those were differentially expressed between the ten strains and the novel FtxA RTX toxin and one lipoprotein were among them. Consistent expression was observed among ribosomal proteins and proteins involved in L-arginine biosynthesis and type IV pilin, demonstrating a degree of EV protein expression preservation among strains. In terms of protein–protein interaction analysis, 21 functional associations were revealed between 19 EV proteins. Interestingly, FtxA did not display predicted interactions with any other EV protein. In conclusion, the present study charted 25 EV proteins in ten F. alocis strains. While most EV proteins were consistently identified among the strains, several of them were also differentially expressed, which justifies that there may be potential variations in the virulence potential among EVs of different F. alocis strains.
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| 8. |
- Bao, Kai, et al.
(författare)
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Proteomic Characterization of the Oral Pathogen Filifactor alocis Reveals Key Inter-Protein Interactions of Its RTX Toxin : FtxA
- 2022
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Ingår i: Pathogens. - : MDPI AG. - 2076-0817. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Filifactor alocis is a Gram-positive asaccharolytic, obligate anaerobic rod that has been isolated from a variety of oral infections including periodontitis, peri-implantitis, and odontogenic abscesses. As a newly emerging pathogen, its type strain has been investigated for pathogenic properties, yet little is known about its virulence variations among strains. We previously screened the whole genome of nine clinical oral isolates and a reference strain of F. alocis, and they expressed a novel RTX toxin, FtxA. In the present study, we aimed to use label-free quantification proteomics to characterize the full proteome of those ten F. alocis strains. A total of 872 proteins were quantified, and 97 among them were differentially expressed in FtxA-positive strains compared with the negative strains. In addition, 44 of these differentially expressed proteins formed 66 pairs of associations based on their predicted functions, which included clusters of proteins with DNA repair/mediated transformation and catalytic activity-related function, indicating different biosynthetic activities among strains. FtxA displayed specific interactions with another six intracellular proteins, forming a functional cluster that could discriminate between FtxA-producing and non-producing strains. Among them were FtxB and FtxD, predicted to be encoded by the same operon as FtxA. While revealing the broader qualitative and quantitative proteomic landscape of F. alocis, this study also sheds light on the deeper functional inter-relationships of FtxA, thus placing this RTX family member into context as a major virulence factor of this species.
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| 9. |
- Briggert, Andreas, 1984-
(författare)
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Modelling and strength grading of structural timber and glulam lamellae on the basis of optical scanning and dynamic excitation
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Machine strength grading of sawn timber is a sawmill process in which density, modulus of elasticity (MOE) and bending or tensile strength are predicted such that the timber can be assigned to strength classes. The predictions of these properties are performed using one or several so-called indicating properties (IPs), which represent a board property, or combination of board properties, measured non-destructively. A limitation of today’s strength grading is that the IPs applied in the industry for prediction of strength, in general, are based on rather weak statistical relationships between IPs and strength properties, which in turn results in poor material utilisation. It is well known that the strength of sawn timber is associated with the presence of knots and their surrounding fibre disorientations. Local fibre direction at surfaces of softwood can be determined by means of the light scattering that occur when a wood surface is illuminated by a dot-laser, i.e. by application of the so-called tracheid effect. Lately, IPs based on such measurements have been developed, and some of the suggested IPs have a strong statistical relationship to bending strength. The purposes of the research presented in this thesis are to contribute with knowledge of possibilities and limitations of the tracheid effect and of data of fibre directions in the vicinity of knots, to evaluate if information of fibre directions at surfaces of Norway spruce sawn timber can be used to achieve a better material utilisation of glulam lamellae and finger-jointed timber, and to provide insight regarding the grading regulations in Europe. Results presented herein show that knots and fibre direction within the interior of boards can be modelled on the basis of data obtained by means of the tracheid effect, but also that a previously proposed method to determine out-of-plane fibre angles gives poor accuracy. As regards grading of glulam lamellae, an IP based on fibre directions and dynamic MOE is proposed for prediction of tensile strength. The latter is used when grading glulam lamellae. Application of the proposed IP resulted in substantially increased yield in strength classes. It is also shown that this IP is applicable for boards with sawn as well as with planed surface finish. Regarding current regulations for machine strength grading in Europe, results indicate that grading based on global board properties give higher yield than what is appropriate.
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| 10. |
- Briggert, Andreas, 1984-, et al.
(författare)
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Prediction of tensile strength of sawn timber : models for calculation of yield in strength classes
- 2020
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Ingår i: Materials and Structures. - : Springer. - 1359-5997 .- 1871-6873. ; 53:3, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- In Europe, strength classes for structural timber and glulam lamellae are defined by minimum requirements of characteristic values of the grade determining properties (GDPs). To fulfill these minimum requirements of characteristic values in the daily production at sawmills, indicating properties (IPs) to GDPs are calculated for each board and based on predetermined limits of the IPs (settings) boards are assigned to the graded class, or rejected. The aims of this paper is to address and discuss two different grading procedures/models that can be applied when settings for IPs that reflects a local board property are derived and to show how the yield in different T-classes depend on the model applied. It is not always that a board’s weakest cross-section is evaluated in a destructive test. An IP representing a local board property can therefore be determined either as the lowest property of the tested part of the board or as the lowest property along the whole board when applied to derive settings. Results presented in this paper show that too low settings and too large yields are obtained when the latter IP is employed. Similarly, IPs reflecting a global board property, like axial dynamic MOE, also give too low settings and too high yield in strength classes. This paper is the second and closing part of a series of two paper on prediction of GDPs and procedures for grading sawn timber into T-classes.
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