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- Brunius, Carl, 1974, et al.
(författare)
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Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
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| 2. |
- Malmodin, Daniel, 1974, et al.
(författare)
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NMR Spectroscopic Analysis to Evaluate the Quality of Insulin: Concentration, Variability, and Excipient Content.
- 2020
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Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 14:1, s. 180-184
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Tidskriftsartikel (refereegranskat)abstract
- Known and consistent bioactivity between samples of insulin is essential to correctly estimate the dose. Insulin concentration is not the same thing as bioactivity, however, and methods to correctly determine both are required. Here we show that one dimensional nuclear magnetic resonance (1D NMR), in contrast to, for example, reverse phase high pressure liquid chromatography, can be used to determine both insulin concentration as well as confirm the structural integrity required for activity. In response to the report by Carter and Heinemann, we decided to investigate insulin intended for public use. Insulin from several manufacturers was investigated. Correct insulin concentrations were found in all tested samples although the general sample variability, which possibly could influence the bioactivity, varied depending on insulin type and manufacturer.
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| 3. |
- Martin, W. P., et al.
(författare)
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Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2‐year follow‐up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary1H‐NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6‐month follow‐up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host–microbial co‐metabolites (N‐phenylacetylglycine, trimethylamine N‐oxide, and 4‐ aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched‐chain amino acids (BCAAs) and related catabolites (valine, leucine, 3‐hydroxyisobutyrate, 3‐hydroxyisovalerate, and 3‐methyl‐ 2‐oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 4. |
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| 5. |
- Rådjursöga, Millie, 1977, et al.
(författare)
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Nutritional metabolomics: Postprandial response of meals relating to vegan, lacto-ovo vegetarian, and omnivore diets
- 2018
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics provide an unbiased tool for exploring the modulation of the human metabolome in response to food intake. This study applied metabolomics to capture the postprandial metabolic response to breakfast meals corresponding to vegan (VE), lacto ovo-vegetarian (LOV), and omnivore (OM) diets. In a cross over design 32 healthy volunteers (16 men and 16 females) consumed breakfast meals in a randomized order during three consecutive days. Fasting and 3 h postprandial serum samples were collected and then subjected to metabolite profiling using1 H-nuclear magnetic resonance (NMR) spectroscopy. Changes in concentration of identified and discriminating metabolites, between fasting and postprandial state, were compared across meals. Betaine, choline, and creatine displayed higher concentration in the OM breakfast, while 3-hydroxyisobutyrate, carnitine, proline, and tyrosine showed an increase for the LOV and unidentified free fatty acids displayed a higher concentration after the VE breakfast. Using1 H NMR metabolomics it was possible to detect and distinguish the metabolic response of three different breakfast meals corresponding to vegan, lacto-ovo vegetarian, and omnivore diets in serum. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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| 6. |
- Rådjursöga, Millie, 1977, et al.
(författare)
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The H-1 NMR serum metabolomics response to a two meal challenge: a cross-over dietary intervention study in healthy human volunteers
- 2019
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolomics represents a powerful tool for exploring modulation of the human metabolome in response to food intake. However, the choice of multivariate statistical approach is not always evident, especially for complex experimental designs with repeated measurements per individual. Here we have investigated the serum metabolic responses to two breakfast meals: an egg and ham based breakfast and a cereal based breakfast using three different multivariate approaches based on the Projections to Latent Structures framework. Methods: In a cross over design, 24 healthy volunteers ate the egg and ham breakfast and cereal breakfast on four occasions each. Postprandial serum samples were subjected to metabolite profiling using H-1 nuclear magnetic resonance spectroscopy and metabolites were identified using 2D nuclear magnetic resonance spectroscopy. Metabolic profiles were analyzed using Orthogonal Projections to Latent Structures with Discriminant Analysis and Effect Projections and ANOVA-decomposed Projections to Latent Structures. Results: The Orthogonal Projections to Latent Structures with Discriminant Analysis model correctly classified 92 and 90% of the samples from the cereal breakfast and egg and ham breakfast, respectively, but confounded dietary effects with inter-personal variability. Orthogonal Projections to Latent Structures with Effect Projections removed inter-personal variability and performed perfect classification between breakfasts, however at the expense of comparing means of respective breakfasts instead of all samples. ANOVA-decomposed Projections to Latent Structures managed to remove inter-personal variability and predicted 99% of all individual samples correctly. Proline, tyrosine, and N-acetylated amino acids were found in higher concentration after consumption of the cereal breakfast while creatine, methanol, and isoleucine were found in higher concentration after the egg and ham breakfast. Conclusions: Our results demonstrate that the choice of statistical method will influence the results and adequate methods need to be employed to manage sample dependency and repeated measurements in cross-over studies. In addition, H-1 nuclear magnetic resonance serum metabolomics could reproducibly characterize postprandial metabolic profiles and identify discriminatory metabolites largely reflecting dietary composition.
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| 7. |
- Tham, Wilhelm, 1951-, et al.
(författare)
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A listeriosis patient infected with two different Listeria monocytogenes strains
- 2002
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Ingår i: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 128:1, s. 105-106
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Tidskriftsartikel (refereegranskat)abstract
- Normally, only one isolate of Listeria monocytogenes from a case of listeriosis is subjected to characterization. Here we show that two isolates from different sites of the body were not the same strain. Such a phenomenon may not have any clinical relevance, although it may confuse the epidemiologist trying to match infection source with infection target.
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