| 1. |
- Abdellah, Tebani, et al.
(author)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 2. |
- Bengtsson-Palme, Johan, 1985, et al.
(author)
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Strategies to improve usability and preserve accuracy in biological sequence databases
- 2016
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 16:18, s. 2454-2460
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Journal article (peer-reviewed)abstract
- Biology is increasingly dependent on large-scale analysis, such as proteomics, creating a requirement for efficient bioinformatics. Bioinformatic predictions of biological functions rely upon correctly annotated database sequences, and the presence of inaccurately annotated or otherwise poorly described sequences introduces noise and bias to biological analyses. Accurate annotations are, for example, pivotal for correct identifications of polypeptide fragments. However, standards for how sequence databases are organized and presented are currently insufficient. Here, we propose five strategies to address fundamental issues in the annotation of sequence databases: (i) to clearly separate experimentally verified and unverified sequence entries; (ii) to enable a system for tracing the origins of annotations; (iii) to separate entries with high-quality, informative annotation from less useful ones; (iv) to integrate automated quality-control software whenever such tools exist; and (v) to facilitate post-submission editing of annotations and metadata associated with sequences. We believe that implementation of these strategies, for example as requirements for publication of database papers, would enable biology to better take advantage of large-scale data.
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| 3. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Assessing the human gut microbiota in metabolic diseases.
- 2013
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:10, s. 3341-9
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Journal article (peer-reviewed)abstract
- Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.
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| 4. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Gut metagenome in European women with normal, impaired and diabetic glucose control
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 498:7452, s. 99-103
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Journal article (peer-reviewed)abstract
- Type 2 diabetes (T2D) is a result of complex gene-environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence(1). Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity(2,3), diabetes(4) and cardiovascular disease(5). Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort(4) and show that the discriminant metagenomicmarkers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.
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| 5. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Symptomatic atherosclerosis is associated with an altered gut metagenome
- 2012
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3
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Journal article (peer-reviewed)abstract
- Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of β-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.
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| 6. |
- Mobini, Reza, 1965, et al.
(author)
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Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial
- 2017
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 19:4, s. 579-589
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Journal article (peer-reviewed)abstract
- Aims: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. Materials and methods: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (10(8) CFU/d) or high dose (10(10) CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. Results: Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. Conclusions: Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.
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| 7. |
- Tremaroli, Valentina, 1978, et al.
(author)
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Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation
- 2015
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 22:2, s. 228-238
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Journal article (peer-reviewed)abstract
- Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls. By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery.
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| 8. |
- Chalangar, Ebrahim, 1984-, et al.
(author)
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Influence of morphology on electrical and optical properties of graphene/Al-doped ZnO-nanorod composites
- 2018
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In: Nanotechnology. - Bristol : Institute of Physics Publishing (IOPP). - 0957-4484 .- 1361-6528. ; 29:41
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Journal article (peer-reviewed)abstract
- The development of future 3D-printed electronics relies on the access to highly conductive inexpensive materials that are printable at low temperatures (<100 C). The implementation of available materials for these applications are, however, still limited by issues related to cost and printing quality. Here, we report on the simple hydrothermal growth of novel nanocomposites that are well suited for conductive printing applications. The nanocomposites comprise highly Al-doped ZnO nanorods grown on graphene nanoplatelets (GNPs). The ZnO nanorods play the two major roles of (i) preventing GNPs from agglomerating and (ii) promoting electrical conduction paths between the graphene platelets. The effect of two different ZnO-nanorod morphologies with varying Al-doping concentration on the nanocomposite conductivity and the graphenedispersity are investigated. Time-dependent absorption, photoluminescence and photoconductivity measurements show that growth in high pH solutions promotes a better graphene dispersity, higher doping levels and enhanced bonding between the graphene and the ZnO nanorods. Growth in low pH solutions yields samples characterized by a higher conductivity and a reduced number of surface defects. These samples also exhibit a large persistent photoconductivity attributed to an effective charge separation and transfer from the nanorods to the graphene platelets. Our findings can be used to tailor the conductivity of novel printable composites, or for fabrication of large volumes of inexpensive porous conjugated graphene-semiconductor composites. © 2018 IOP Publishing Ltd.
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| 9. |
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| 10. |
- Davidsson, Sabina, 1972-, et al.
(author)
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Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
- 2016
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In: Infectious Agents and Cancer. - London, United Kingdom : BioMed Central (BMC). - 1750-9378. ; 11
-
Journal article (peer-reviewed)abstract
- Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.
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| 11. |
- Eklund, Elisabeth, 1988-, et al.
(author)
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Perceived articulatory precision in patients with Parkinson’s disease after deep brain stimulation of subthalamic nucleus and caudal zona incerta
- 2015
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In: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 29:2, s. 150-166
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Journal article (peer-reviewed)abstract
- The effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and caudal zona incerta (cZi) on speech articulation in patients with Parkinson’s disease (PD) was investigated. Read speech samples were collected from nine patients with STN-DBS and ten with cZi-DBS. The recordings were made preoperatively and 12 months postoperatively with stimulator on and off (on medication). Blinded, randomized, repeated perceptual assessments were performed on words and isolated fricatives extracted from the recordings to assess 1) overall articulatory quality ratings, 2) frequency of occurrence of misarticulation patterns, and 3) fricative production. Statistically significant worsening of articulatory measures on- compared with off-stimulation occurred in the cZi-DBS group, with deteriorated articulatory precision ratings, increased presence of misarticulations (predominately altered realizations of plosives and fricatives) and a reduced accuracy in fricative production. A similar, but not significant, trend was found for the STN-DBS group.
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| 12. |
- El-Semman, Ibrahim, 1977, et al.
(author)
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Genome-scale metabolic reconstructions of Bifidobacterium adolescentis L2-32 and Faecalibacterium prausnitzii A2-165 and their interaction
- 2014
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In: BMC Systems Biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 8:41
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Journal article (peer-reviewed)abstract
- Background: The gut microbiota plays an important role in human health and disease by acting as a metabolic organ. Metagenomic sequencing has shown how dysbiosis in the gut microbiota is associated with human metabolic diseases such as obesity and diabetes. Modeling may assist to gain insight into the metabolic implication of an altered microbiota. Fast and accurate reconstruction of metabolic models for members of the gut microbiota, as well as methods to simulate a community of microorganisms, are therefore needed. The Integrated Microbial Genomes (IMG) database contains functional annotation for nearly 4,650 bacterial genomes. This tremendous new genomic information adds new opportunities for systems biology to reconstruct accurate genome scale metabolic models (GEMs). Results: Here we assembled a reaction data set containing 2,340 reactions obtained from existing genome-scale metabolic models, where each reaction is assigned with KEGG Orthology. The reaction data set was then used to reconstruct two genome scale metabolic models for gut microorganisms available in the IMG database Bifidobacterium adolescentis L2-32, which produces acetate during fermentation, and Faecalibacterium prausnitzii A2-165, which consumes acetate and produces butyrate. F. prausnitzii is less abundant in patients with Crohn's disease and has been suggested to play an anti-inflammatory role in the gut ecosystem. The B. adolescentis model, iBif452, comprises 699 reactions and 611 unique metabolites. The F. prausnitzii model, iFap484, comprises 713 reactions and 621 unique metabolites. Each model was validated with in vivo data. We used OptCom and Flux Balance Analysis to simulate how both organisms interact. Conclusions: The consortium of iBif452 and iFap484 was applied to predict F. prausnitzii's demand for acetate and production of butyrate which plays an essential role in colonic homeostasis and cancer prevention. The assembled reaction set is a useful tool to generate bacterial draft models from KEGG Orthology.
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| 13. |
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| 14. |
- Islam, Md Mafijul, et al.
(author)
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Towards benchmarking of functional safety in the automotive industry
- 2013
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In: Lecture Notes in Computr Science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 9783642387883 ; , s. 111-125
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Conference paper (peer-reviewed)abstract
- Functional safety is becoming increasingly important in the automotive industry to deal with the growing reliance on the electrical and/or electronic (E/E) systems and the associated complexities. The introduction of ISO 26262, a new standard for functional safety in road vehicles, has made it even more important to adopt a systematic approach of evaluating functional safety. However, standard assessment methods of benchmarking functional safety of automotive systems are not available as of today. This is where the BeSafe (Benchmarking of Functional Safety) project comes into the picture. BeSafe project aims to lay the foundation for benchmarking functional safety of automotive E/E systems. In this paper, we present a brief overview of the project along with the benchmark targets that we have identified as relevant for the automotive industry, assuming three abstraction layers (model, software, hardware). We then define and discuss a set of benchmark measures. Next, we propose a benchmark framework encompassing fault/error models, methods and the required tool support. This paper primarily focuses on functional safety benchmarking from the Safety Element out of Context (SEooC) viewpoint. Finally, we present some preliminary results and highlight potential future works.
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| 15. |
- Karakatsanis, Andreas, et al.
(author)
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Axillary Staging in the Setting of a Preoperative Diagnosis of Ductal Cancer In Situ (DCIS) : Results of an International Expert Panel and a Critical Guideline Performance Using Frequentist and Bayesian Analysis
- 2020
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In: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 27:Suppl. 2, s. S337-S338
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Journal article (other academic/artistic)abstract
- Background/Objective: Sentinel lymph node biopsy (SLNB) is not routine in DCIS. Guidelines suggest SLNB when there is high risk for underlying invasion (large size, high grade, symptomatic lesion) or for detection failure (e.g., after mastectomy). However, guidelines and current practice patterns are inconsistent. Moreover, whilst SLNB is thought to be feasible and accurate after wide local excision (WLE), there is less consensus to support its use after oncoplastic breast-conserving surgery (OPBCS), which can reduce the need for mastectomy (Mx) and is gradually adopted as standard of care. The study aim was to assess if guidelines or individualized assessment result in optimal selection of patients for upfront SLNB.Methods: A panel of 28 international experts (20 surgeons, 8 oncologists, Europe 20, USA 5, Asia/Australia 3) was formed, all blind to the identity of the others. They reviewed anonymized patient cases from the SentiNot study (n=184, m. age 60 years, DCIS m. size 4 cm, Grade 2/3= 36%/64%, mass lesions 13,4%, underlying invasion 24.5%) and answer if they would consider upfront SLNB and why. Consensus and majority were set to >75 and >50%. At the same time, 6 independent raters (4 surgeons, 2 oncologists) reviewed guidelines and assessed the same patient cases per each guideline. Accuracy in relation to underlying invasion was assessed by Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was reported. Agreement was investigated by kappa statistics and decision-making patterns by logistic multivariate regression and cluster analysis. To allow for flexibility and adaptation to current knowledge, both a frequentist and a Bayesian approach were undertaken. Priors were adjusted after a literature review regarding the factors that are commonly thought to be associated with higher risk for underlying invasion.Results: A total of 44,896 decisions were retrieved and analysed. The panel reached consensus/majority for upfront SLNB in 41.3/61.4%, whereas individual rates ranged from 11 to 100%. Agreement among panelists was low (kappa=0.37). In multivariate regression analysis for the entire panel, type of surgery was the most common determinant, (simple WLE=less, OPBCS=more and Mx=constant for SLNB), followed by symptomatic diagnosis and DCIS size. Most (26) members had a clear decision-making pattern regarding SLND, based mainly on DCIS size and type of surgery. Individual decision-making performed modestly in identifying patients with underlying invasion (AUC range 0,47-0,59), resulting mainly in overtreatment in 44-77% of patients. The panel performed similarly by majority (AUC 0,5) and by consensus (AUC 0,55) but “undertreated” 60-75% of patients with invasion, failing to identify them as "high-risk." After the recognition of different decision-making patterns, panelists were divided in subgroups with similar decision-making pattern. Analysis identified subgroups with difference in SLNB rate but not with better AUC. The disagreement among panelists in the same subgroups was significant, not only regarding which patients should undergo SLNB, but also on what factors that recommendation was based on. Eight guidelines with relevant recommendations were identified [USA (ASCO/NCCN), Europe (ESMO), Sweden, Denmark, UK, Netherlands and Italy, retrieval date May 2019]. Agreement among raters for each guideline separately varied (kappa: 0.23-0.9). Interpretation as to whether SLNB should be performed ranged widely (40-90%) and with varying concordance (32-88%). No guideline demonstrated accuracy (AUC range 0.45-0.55). Overtreatment risk was high (50-90%), whereas 10-50% of patients with invasion were not identified as “high- risk.” Agreement across guidelines was low (kappa=0.24), meaning that different patients had similar risk to be treated inaccurately, regardless of which guideline was examined.Conclusions: Individualized decision-making and guideline interpretation may be highly subjective and with low accuracy in terms of prediction of invasive disease, resulting in almost random risk for over- or undertreatment of the axilla in patients with DCIS. This suggests that current views and guidelines should be challenged. More accurate preoperative workup and novel techniques to allow for delayed SLNB may be of value in this setting.
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| 16. |
- Karlsson, Fredrik, 1984, et al.
(author)
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A Closer Look at Bacteroides: Phylogenetic Relationship and Genomic Implications of a Life in the Human Gut
- 2011
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In: Microbial Ecology. - : Springer Science and Business Media LLC. - 0095-3628 .- 1432-184X. ; 61:3, s. 473-485
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Journal article (peer-reviewed)abstract
- The human gut is extremely densely inhabited by bacteria mainly from two phyla, Bacteroidetes and Firmicutes, and there is a great interest in analyzing whole-genome sequences for these species because of their relation to human health and disease. Here, we do whole-genome comparison of 105 Bacteroidetes/Chlorobi genomes to elucidate their phylogenetic relationship and to gain insight into what is separating the gut living Bacteroides and Parabacteroides genera from other Bacteroidetes/Chlorobi species. A comprehensive analysis shows that Bacteroides species have a higher number of extracytoplasmic function sigma factors (ECF sigma factors) and two component systems for extracellular signal transduction compared to other Bacteroidetes/Chlorobi species. A whole-genome phylogenetic analysis shows a very little difference between the Parabacteroides and Bacteroides genera. Further analysis shows that Bacteroides and Parabacteroides species share a large common core of 1,085 protein families. Genome atlases illustrate that there are few and only small unique areas on the chromosomes of four Bacteroides/Parabacteroides genomes. Functional classification to clusters of othologus groups show that Bacteroides species are enriched in carbohydrate transport and metabolism proteins. Classification of proteins in KEGG metabolic pathways gives a detailed view of the genome's metabolic capabilities that can be linked to its habitat. Bacteroides pectinophilus and Bacteroides capillosus do not cluster together with other Bacteroides species, based on analysis of 16S rRNA sequence, whole-genome protein families and functional content, 16S rRNA sequences of the two species suggest that they belong to the Firmicutes phylum. We have presented a more detailed and precise description of the phylogenetic relationships of members of the Bacteroidetes/Chlorobi phylum by whole genome comparison. Gut living Bacteroides have an enriched set of glycan, vitamin, and cofactor enzymes important for diet digestion.
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| 17. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Metagenomic Data Utilization and Analysis (MEDUSA) and Construction of a Global Gut Microbial Gene Catalogue
- 2014
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In: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 10:7
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Journal article (peer-reviewed)abstract
- Metagenomic sequencing has contributed important new knowledge about the microbes that live in a symbiotic relationship with humans. With modern sequencing technology it is possible to generate large numbers of sequencing reads from a metagenome but analysis of the data is challenging. Here we present the bioinformatics pipeline MEDUSA that facilitates analysis of metagenomic reads at the gene and taxonomic level. We also constructed a global human gut microbial gene catalogue by combining data from 4 studies spanning 3 continents. Using MEDUSA we mapped 782 gut metagenomes to the global gene catalogue and a catalogue of sequenced microbial species. Hereby we find that all studies share about half a million genes and that on average 300 000 genes are shared by half the studied subjects. The gene richness is higher in the European studies compared to Chinese and American and this is also reflected in the species richness. Even though it is possible to identify common species and a core set of genes, we find that there are large variations in abundance of species and genes.
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| 18. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Prospects for systems biology and modeling of the gut microbiome
- 2011
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In: Trends in Biotechnology. - : Elsevier BV. - 0167-7799 .- 1879-3096. ; 29:6, s. 251-258
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Journal article (peer-reviewed)abstract
- Abundant microorganisms that inhabit the human intestine are implicated in health and disease. The gut microbiome has been studied with metagenomic tools, and over 3 million genes have been discovered, constituting a 'parts list' of this ecosystem; further understanding requires studies of the interacting parts. Mouse models have provided a glimpse into the microbiota and host interactions at metabolic and immunologic levels; however, to provide more insight, there is a need to generate mathematical models that can reveal genotype-phenotype relationships and provide scaffolds for integrated analyses. To this end, we propose the use of genome-scale metabolic models that have successfully been used in studying interactions between human hosts and microbes, as well as microbes in isolation and in communities.
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| 19. |
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| 20. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Utility of in vitro systems and preclinical data for the prediction of human intestinal first-pass metabolism during drug discovery and preclinical development
- 2013
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In: Drug Metabolism and Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-009X .- 0090-9556. ; 41:12, s. 2033-2046
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Journal article (peer-reviewed)abstract
- A growing awareness of the risks associated with extensive intestinal metabolism has triggered an interest in developing robust methods for its quantitative assessment. This study explored the utility of intestinal S9 fractions, human liver microsomes, and recombinant cytochromes P450 to quantify CYP3A-mediated intestinal extraction in humans for a selection of marketed drugs that are predominantly metabolized by CYP3A4. A simple competing rates model is used to estimate the fraction of drug escaping gut wall metabolism (f g ) from in vitro intrinsic clearance in humans. The f g values extrapolated from the three in vitro systems used in this study, together with literature-derived f g from human intestinal microsomes, were validated against f g extracted from human in vivo pharmacokinetic (PK) profiles using a generic whole-body physiologically-based pharmacokinetic (PBPK) model. The utility of the rat as a model for human CYP3A-mediated intestinal meta bolism was also evaluated. Human f g from PBPK compares well with that from the grapefruit juice method, justifying its use for the evaluation of human in vitro systems. Predictive performance of all human in vitro systems was comparable [root mean square error (RMSE) = 0.22-0.27; n = 10]. Rat f g derived from in vivo PK profiles using PBPK has the lowest RMSE (0.19; n = 11) for the prediction of human f g for the selected compounds, most of which have a fraction absorbed close to 1. On the basis of these evaluations, the combined use of f g from human in vitro systems and rats is recommended for the estimation of CYP3A4-mediated intestinal metabolism in lead optimization and preclinical development phases.
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| 21. |
- Karlsson, Markus, et al.
(author)
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Assessing Tissue Hydration Dynamics Based on Water/Fat Separated MRI
- 2023
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In: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 58:2, s. 652-660
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Journal article (peer-reviewed)abstract
- Background: Optimal fluid status is an important issue in hemodialysis. Clinical evaluation of volume status and different diagnostic tools are used to determine hydration status in these patients. However, there is still no accurate method for this assessment. Purpose: To propose and evaluate relative lean water signal (LWSrel) as a water–fat MRI-based tissue hydration measurement. Study Type: Prospective. Population: A total of 16 healthy subjects (56 ± 6 years, 0 male) and 11 dialysis patients (60.3 ± 12.3 years, 9 male; dialysis time per week 15 ± 3.5 hours, dialysis duration 31.4 ± 27.9 months). Field Strength/Sequence: A 3 T; 3D spoiled gradient echo. Assessment: LWSrel, a measurement of the water concentration of tissue, was estimated from fat-referenced MR images. Segmentations of total adipose tissue as well as thigh and calf muscles were used to measure LWSrel and tissue volumes. LWSrel was compared between healthy subjects and dialysis patients, the latter before and after dialysis. Bioimpedance-based body composition monitor over hydration (BCM OH) was also measured. Statistical Tests: T-tests were used to compare differences between the healthy subjects and dialysis patients, as well as changes between before and after dialysis. Pearson correlation was calculated between MRI and non-MRI biomarkers. A P value <0.05 was considered statistically significant. Results: The LWSrel in adipose tissue was significantly higher in the dialysis cohort compared with the healthy cohort (246.8% ± 60.0% vs. 100.0% ± 10.8%) and decreased significantly after dialysis (246.8 ± 60.0% vs. 233.8 ± 63.4%). Thigh and calf muscle volumes also significantly decreased by 3.78% ± 1.73% and 2.02% ± 2.50% after dialysis. There was a significant correlation between changes in adipose tissue LWSrel and ultrafiltration volume (r = 87), as well as with BCM OH (r = 0.66). Data Conclusion: MRI-based LWSrel and tissue volume measurements are sensitive to tissue hydration changes occurring during dialysis. Evidence Level: 2. Technical Efficacy: Stage 3.
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| 22. |
- Lindskog, Carin, 1965-
(author)
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Tensions experienced and balancing strategies used in Agile Software Development environments
- 2022
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Doctoral thesis (other academic/artistic)abstract
- To achieve efficiency in rapidly changing environments, working methods that promote change and flexibility are needed. Thus, the Agile ways of working (i.e. Agile values, principles, and frameworks) are today the most common approach to developing software and something that is currently spreading to many other industries and organizations outside of the traditional IT sector. However, it is challenging to combine the business-driven need for predictability and planning with the Agile ways of working, e.g. changeability, self-management and step-by-step development and delivery; therefore, several tensions can arise at the team and organizational levels. Tensions can, for example, be experienced if the team members’ experiences are rooted in traditional project environments with stable processes and predefined requirements based on detailed planning. This dissertation aims to contribute to our knowledge of Agile Software Development (ASD) by examining the contradictions and tensions in ASD environments, as well as how to balance and react to these tensions. The dissertation responds to the great need for conceptual development in the field of Information Systems. The target groups are both researchers and practitioners.The research reported on in this dissertation is based on one conceptual study and two empirical studies. The studies reported on in four appended papers jointly contribute toward answering three research questions (RQs):RQ 1: What is the nature of the tensions experienced in ASD environments?RQ 2: What are the sources of the tensions experienced in ASD environments?RQ 3: What ambidextrous strategies can be used to both balance and react to the tensions found in ASD environments?This dissertation brings together concepts from academic domains of knowledge (organizational theories of [paradoxical] tensions and ambidexterity and Activity Theory derived from socio-psychological theory) in order to provide a new insight into the complexity of ASD.This dissertation contributes by discussing and visualizing how patterns of contradictions, categorized tensions and ambidextrous (i.e. the ability to manage two seemingly contradictory activities) strategies have been compiled and connected. This dissertation also contributes by describing how three models that can be used to develop the concept of “shared mental models”, which is so important to team-based learning.
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| 23. |
- Sanli, Kemal, et al.
(author)
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FANTOM: Functional and taxonomic analysis of metagenomes
- 2013
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In: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 14
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Journal article (peer-reviewed)abstract
- Background Interpretation of quantitative metagenomics data is important for our understanding of ecosystem functioning and assessing differences between various environmental samples. There is a need for an easy to use tool to explore the often complex metagenomics data in taxonomic and functional context. Results Here we introduce FANTOM, a tool that allows for exploratory and comparative analysis of metagenomics abundance data integrated with metadata information and biological databases. Importantly, FANTOM can make use of any hierarchical database and it comes supplied with NCBI taxonomic hierarchies as well as KEGG Orthology, COG, PFAM and TIGRFAM databases. Conclusions The software is implemented in Python, is platform independent, and is available at http://www.sysbio.se/Fantom.
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| 24. |
- Shoaie, Saeed, 1985, et al.
(author)
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Understanding the interactions between bacteria in the human gut through metabolic modeling
- 2013
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 3
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Journal article (peer-reviewed)abstract
- The human gut microbiome plays an influential role in maintaining human health, and it is a potential target for prevention and treatment of disease. Genome-scale metabolic models (GEMs) can provide an increased understanding of the mechanisms behind the effects of diet, the genotype-phenotype relationship and microbial robustness. Here we reconstructed GEMs for three key species, (Bacteroides thetaiotamicron, Eubacterium rectale and Methanobrevibacter smithii) as relevant representatives of three main phyla in the human gut (Bacteroidetes, Firmicutes and Euryarchaeota). We simulated the interactions between these three bacteria in different combinations of gut ecosystems and compared the predictions with the experimental results obtained from colonization of germ free mice. Furthermore, we used our GEMs for analyzing the contribution of each species to the overall metabolism of the gut microbiota based on transcriptome data and demonstrated that these models can be used as a scaffold for understanding bacterial interactions in the gut.
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| 25. |
- Sundbom, Per, 1981-, et al.
(author)
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Sound analysis of the magnetically levitated left ventricular assist device HeartMate 3™
- 2019
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In: International Journal of Artificial Organs. - : Sagamore Publishing. - 0391-3988 .- 1724-6040. ; 42:12, s. 717-724
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The HeartMate 3™ has shown lower rates of adverse events compared to previous devices due to the design and absence of mechanical bearings. For previous devices, sound analysis emerged as a way to assess pump function. The aims of this study were to determine if sound analysis can be applied to the HeartMate 3 in vivo and in vitro and to evaluate an electronic stethoscope.METHOD: Sound recordings were performed with microphones and clinical accessible electronic stethoscope. The recordings were studied in both the time and the frequency domains. Recordings from four patients were performed to determine if in vivo and in vitro recordings are comparable.RESULTS: The results show that it is possible to detect sound from HeartMate 3 and the sound spectrum is clear. Pump frequency and frequency of the pulsatile mode are easily determined. Frequency spectra from in vitro and in vivo recordings have the same pattern, and the major proportion (96.7%) of signal power is located at the pump speed frequency ±40 Hz. The recordings from the patients show low inter-individual differences except from location of peaks originating from pump speed and harmonics. Electronic stethoscopes could be used for sound recordings, but the dedicated equipment showed a clearer sound spectrum.DISCUSSION: The results show that acoustic analysis can also be performed with the HeartMate 3 and that in vivo and in vitro sound spectrum is similar. The frequency spectra are different from previous devices, and methods for assessing pump function or thrombosis need further evaluation.
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