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Sökning: AMNE:(MEDICAL AND HEALTH SCIENCES Basic Medicine)

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41.
  • Zhang, C., et al. (författare)
  • The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
  • 2020
  • Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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42.
  • Krupic, Ferid, et al. (författare)
  • The Influence of Age, Gender and Religion on Willingness to be an Organ Donor: Experience of Religious Muslims Living in Sweden.
  • 2019
  • Ingår i: Journal of religion and health. - : Springer Science and Business Media LLC. - 1573-6571 .- 0022-4197. ; 58, s. 847-859
  • Tidskriftsartikel (refereegranskat)abstract
    • The transplantation of organs is one of the most successful medical advances in recent decades, and transplantation is the treatment of choice for severe organ failure worldwide. Despite this situation and the general acknowledgment of organ donation (OD) as a global priority, the demand for organs outstrips the supply in virtually every country in the world. The study aims to elucidate whether age, gender and religion influence decision-making about organ donation in religious Muslims living in Sweden Data were collected through three group interviews using open-ended questions and qualitative content analysis. Twenty-seven participants, 15 males and 12 females from four countries, participated in the focus group interviews. The analysis of the collected data resulted in three main categories: "Information and knowledge about organ donation," "The priorities when deciding about organ donation" and "The religious aspects of organ donation," including a number of subcategories. Good information about and knowledge of OD, priorities in OD, importance of the fact that religion must be studied and taught daily and religious education were only a few of the factors informants emphasized as predictors of the total and successful donation of organs. Age, gender or religion did not have an impact on organ donation. High levels of education through religious education and good information via various media, as well as a good knowledge of the Swedish language, are predictors of improved OD. In order to overcome religious ideology as a source of misinformation relating to OD and to promote increased OD in the future, specific intervention studies and the improved involvement of religious communities and education in schools and the healthcare system are vital and must be a starting point for improved OD.
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43.
  • Khoshnood, Ardavan (författare)
  • Prehospital Diagnosis and Oxygen Treatment in ST Elevation Myocardial Infarction
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • IntroductionPaper I: An Artificial Neural Network (ANN) was constructed to identify ST Elevation Myocardial Infarction (STEMI) and predict the need for Percutaneous Coronary Intervention (PCI). Paper II, III and IV: Studies suggest that O2 therapy may be harmful in STEMI patients. We therefore conducted the SOCCER study to evaluate the effects of O2 therapy in STEMI patients.MethodsPaper I: 560 ambulance ECGs sent to the Cardiac Care Unit (CCU), was together with the CCU physicians interpretation and decision of conducting an acute PCI or not collected, and compared with the interpretation and PCI decision of the ANN. Paper II, III, IV: Normoxic (≥94%) STEMI patients accepted for acute PCI were in the ambulance randomized to standard care with 10 L/min O2 or room air. A subset of the patients underwent echocardiography for determination of the Left Ventricular Ejection Fraction (LVEF) and the Wall Motion Score Index (WMSI). All patients had a Cardiac Magnetic Resonance Imaging (CMRI) to evaluate Myocardial area at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI).ResultsPaper I: The area under the ANN’s receiver operating characteristics curve for STEMI detection as well as predicting the need of acute PCI were very good.Paper II, III, IV: No significant differences could be shown in discussing MaR, MSI or IS between the O2 group (n=46) and the air group (n=49). Neither could any differences be shown for LVEF and WMSI at the index visit as well after six months between the O2 group (n=46) and the air group (n=41)ConclusionsPaper I: The results indicate that the number of ECGs sent to the CCU could be reduced with 2/3 as the ANN would safely identify ECGs not being STEMI.Paper II, III, IV: The results suggest that it is safe to withhold O2 therapy in normoxic, stable STEMI patients.
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44.
  • Rolfö, Linda, et al. (författare)
  • Predictors of Preference for the Activity-based Flexible Office
  • 2019
  • Ingår i: Human Systems Engineering and Design. - Cham : Springer. - 9783030020521 - 9783030020538 ; 876, s. 547-553
  • Konferensbidrag (refereegranskat)abstract
    • Activity-based Flexible Offices (A-FOs) are implemented with varying degree of success. Employees relocate from cell or open-plan offices, from different organizational backgrounds, varying design and implementation processes, and have different types of work tasks. This study aims at investigating whether preference for the A-FO correlate with these preconditions. The results from Chi-square tests and Spearman’s non-parametric correlation of post-relocation questionnaires distributed to 11 A-FO sites, showed that a high preference for the A-FO correlated strongest with an A-FO preference prior to relocation, being a former open-plan office occupier and with frequent performance of innovation. Low preference for the A-FO correlated with frequent performance of concentration demanding tasks. Working with tasks with high confidentiality did not predict the preference ratings.
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45.
  • Mamontov, Eugen, 1955 (författare)
  • Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
  • 2006
  • Ingår i: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
  • Konferensbidrag (refereegranskat)abstract
    • Advanced generalized-kinetic-theory (GKT) models for biological systems are developed for populations of active (or living) particles [1]-[5]. These particles are described with both the stochastic variables common in kinetic theory (such as time, the particle random location and velocity) and the stochastic variables related to the internal states of an active particle. Evolution of these states represents biological, ecological, or social properties of the particle behavior. Paper [6] analyzes a number of the well-known statistical-mechanics approaches and shows that the active-particle GKT (APGKT) is the only treatment capable of modelling living systems. Work [2] summarizes the significance of the notion of an active particle in kinetic models. This notion draws attention to the features distinguishing living matter from nonliving matter. They are discussed by many authors (e.g., [7]-[15], [1]-[3], [6], [16]-[18]). Work [11] considers a lot of differences between living and nonliving matters, and the limitations of the modelling approaches developed for nonliving matter. Work [6] mainly focuses on the comparison of a few theoretical mechanics treatments in terms of the key living-matter properties formulated in [15]. One of the necessary properties of the evolution of living systems is homeorhesis. It is, loosely speaking, a peculiar qualitative and quantitative insensitivity of a living system to the exogenous signals acting on it. The earlier notion, homeostasis, was introduced by W. B. Cannon in 1926 who discussed the phenomenon in detail later [7]. Homeorhesis introduced by C. H. Waddington [8, p. 32] generalizes homeostasis and is well known in biology [8], [9], [12]. It is an inherent part of mathematical models for oncogeny (e.g., [16]-[18], [6, Appendix]). Homeorhesis is also discussed in [3, Section 4] in connection with APGKT. Homeorhesis is documented in ecology (e.g., [11], [13, the left column on p. 675]) where it is one of the key notions of the strong Gaia theory, a version of the Gaia theory (e.g., [14, Chapter 8]). The strong Gaia theory “states that the planet with its life, a single living system, is regulated in certain aspects by that life” [14, p. 124]. The very origin of the name “Gaia” is related to homeorhesis or homeostasis [14, p. 118]. These notions are also used in psychology and sociology. If evolution of a system is not homeorhetic, the system can not be living. Work [6, Appendix] derives a preliminary mathematical formulation of homeorhesis in terms of the simplest dynamical systems, i.e. ordinary differential equations (ODEs). The present work complements, extended, and further specify the approach of [6, Appendix]. The work comprises the two main parts. The first part develops the sufficient conditions for ODE systems to describe homeorhesis, and suggests a fairly general structure of the ODE model. It regards homeorhesis as piecewise homeostasis. The model can be specified in different ways depending on specific systems and specific purposes of the analysis. An example of the specification is also noted (the PhasTraM nonlinear reaction-diffusion model for hyperplastic oncogeny [16]-[18]). The second part of the work discusses implementation of the above homeorhesis ODE model in terms of a special version [3] of APGKT (see above). The key feature of this version is that the components of a living population need not be discrete: the subdivision into the components is described with a general, continuous-discrete probability distribution (see also [6]). This enables certain properties of living matter noted in [15]. Moreover, the corresponding APGKT model presents a system of, firstly, a generalized kinetic equation for the conditional distribution function conditioned by the internal states of the population and, secondly, Ito's stochastic differential equations for these states. This treatement employs the results on nonstationary invariant diffusion stochastic processes [19]. The second part of the work also stresses that APGKT is substantially more important for the living-matter analysis than in the case of nonliving matter. One of the reasons is certain limitations in experimental sampling of the living-system modes presented with stochastic processes. A few directions for future research are suggested as well. REFERENCES: [1] Bellomo, N., Bellouquid, A. and Delitala, M., 2004, Mathematical topics on the modelling complex multicellular systems and tumor immune cells competition, Math. Models Methods Appl. Sci., 14, 1683-1733. [2] Bellomo, N., 2006, New hot Paper Comments, Essential Science Indicators, http://www.esi-topics.com/nhp/2006 /may- 06-NicolaBellomo.html. [3] Willander, M., Mamontov, E. and Chiragwandi, Z., 2004, Modelling living fluids with the subdivision into the components in terms of probability distributions, Math. Models Methods Appl. Sci. 14, 1495-1520. [4] Bellomo, N. and Maini, P.K., 2005, Preface and the Special Issue “Multiscale Cancer Modelling-A New Frontier in Applied Mathematics”, Math. Models Methods Appl. Sci., 15, iii-viii. [5] De Angelis, E. and Delitala, M., 2006, Modelling complex systems in applied sciences: Methods and tools of the mathematical kinetic theory for active particles. Mathl Comput. Modelling, 43, 1310-1328. [6] Mamontov, E., Psiuk-Maksymowicz, K. and Koptioug, A., 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, Article in Press, 13 pp. [7] Cannon, W.B., 1932, The Wisdom of the Body (New York: Norton). [8] Waddington, C.H., 1957, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (London, George Allen and Unwin). [9] Waddington, C.H., 1968, Towards a theoretical biology, Nature, 218, 525-527. [10] Cotnoir, P.-A., 1981, La compétence environnementale: Une affaire d’adaptation. Séminaire en écologie behaviorale, Univeristé du Québec, Montralé. Available online at: http://pac.cam.org/culture.doc . [11] O’Neill, R.V., DeAngelis, D.L., Waide, J.B. and Allen, T.F.H., 1986, A Hierarchical Concept of Ecosystems, Princeton: Princeton Univ. Press). [12] Sauvant, D., 1992, La modélisation systémique en nutrition, Reprod. Nutr. Dev., 32, 217-230. [13] Christensen, N.L., Bartuska, A.M., Brown, J.H., Carpenter, S., D'Antonio, C., Francis, R., Franklin, J.F., MacMahon, J.A., Noss, R.F., Parsons, D.J., Peterson, C.H., Turner, M.G. and Woodmansee, R.G., 1996, The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management, Ecological Applications, 6, 665-691. Available online at: http://www.esa.org/pao/esaPositions/Papers/ReportOfSBEM.php. [14] Margulis, L., 1998, Symbiotic Planet. A New Look at Evolution (Amherst: Sciencewriters). [15] Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W., 1999, From molecular to modular cell biology, Nature, 402, C47-C52. [16] Mamontov, E., Koptioug, A.V. and Psiuk-Maksymowicz, K., 2006, The minimal, phase-transition model for the cell- number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54, 44 pp., (no. 2, May-June, accepted). [17] Psiuk-Maksymowicz, K. and Mamontov, E., 2005, The time-slices method for rapid solving the Cauchy problem for nonlinear reaction-diffusion equations in the competition of homeorhesis with genotoxically activated hyperplasia, In: European Conference on Mathematical and Theoretical Biology - ECMTB05 (July 18-22, 2005) Book of Abstracts, Vol.1 (Dresden: Center for Information Services and High Performance Computing, Dresden Univ. Technol.), p. 429 (http://www.ecmtb05.org/). [18] Psiuk-Maksymowicz, K. and Mamontov, E., 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiation therapy, submitted. [19] Mamontov, E., 2005, Nonstationary invariant distributions and the hydrodynamic-style generalization of the Kolmogorov-forward/Fokker-Planck equation, Appl. Math. Lett. 18 (9) 976-982.
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46.
  • Benkel, Inger, et al. (författare)
  • Palliativ vård
  • 2016
  • Bok (övrigt vetenskapligt/konstnärligt)
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47.
  • Senkowski, Wojciech (författare)
  • High-throughput screening using multicellular tumor spheroids to reveal and exploit tumor-specific vulnerabilities
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • High-throughput drug screening (HTS) in live cells is often a vital part of the preclinical anticancer drug discovery process. So far, two-dimensional (2D) monolayer cell cultures have been the most prevalent model in HTS endeavors. However, 2D cell cultures often fail to recapitulate the complex microenvironments of in vivo tumors. Monolayer cultures are highly proliferative and generally do not contain quiescent cells, thought to be one of the main reasons for the anticancer therapy failure in clinic. Thus, there is a need for in vitro cellular models that would increase predictive value of preclinical research results. The utilization of more complex three-dimensional (3D) cell cultures, such as multicellular tumor spheroids (MCTS), which contain both proliferating and quiescent cells, has therefore been proposed. However, difficult handling and high costs still pose significant hurdles for application of MCTS for HTS.In this work, we aimed to develop novel assays to apply MCTS for HTS and drug evaluation. We also set out to identify cellular processes that could be targeted to selectively eradicate quiescent cancer cells. In Paper I, we developed a novel MCTS-based HTS assay and found that nutrient-deprived and hypoxic cancer cells are selectively vulnerable to treatment with inhibitors of mitochondrial oxidative phosphorylation (OXPHOS). We also identified nitazoxanide, an FDA-approved anthelmintic agent, to act as an OXPHOS inhibitor and to potentiate the effects of standard chemotherapy in vivo. Subsequently, in Paper II we applied the high-throughput gene-expression profiling method for MCTS-based drug screening. This led to discovery that quiescent cells up-regulate the mevalonate pathway upon OXPHOS inhibition and that the combination of OXPHOS inhibitors and mevalonate pathway inhibitors (statins) results in synergistic toxicity in this cell population. In Paper III, we developed a novel spheroid-based drug combination-screening platform and identified a set of molecules that synergize with nitazoxanide to eradicate quiescent cancer cells. Finally, in Paper IV, we applied our MCTS-based methods to evaluate the effects of phosphodiesterase (PDE) inhibitors in PDE3A-expressing cell lines.In summary, this work illustrates how MCTS-based HTS yields potential to reveal and exploit previously unrecognized tumor-specific vulnerabilities. It also underscores the importance of cell culture conditions in preclinical drug discovery endeavors.
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48.
  • Tedersoo, Leho, et al. (författare)
  • Response to Comment on “Global diversity and geography of soil fungi”
  • 2015
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6251
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Schadt and Rosling (Technical Comment, 26 June 2015, p. 1438) argue that primer-template mismatches neglected the fungal class Archaeorhizomycetes in a global soil survey. Amplicon-based metabarcoding of nine barcode-primer pair combinations and polymerase chain reaction (PCR)–free shotgun metagenomics revealed that barcode and primer choice and PCR bias drive the diversity and composition of microorganisms in general, but the Archaeorhizomycetes were little affected in the global study. We urge that careful choice of DNA markers and primers is essential for ecological studies using high-throughput sequencing for identification.
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49.
  • Stibrant Sunnerhagen, Katharina, 1957 (författare)
  • Reflecting the world report on disability: A report from Sweden
  • 2014
  • Ingår i: American Journal of Physical Medicine & Rehabilitation. - 0894-9115. ; 93:1 SUPPL.1
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: There is a range of statistics in Sweden regarding people with functional limitations available from different authorities presenting diverging information. Although healthcare and social welfare legislations aim for equal access and treatment, surveys about unmet needs show that opportunities for rehabilitation are unequal among diagnoses and around the country and insufficient in the long-term. There is also a law granting certain supports and services to those people who are considered to be in need of having someone to speak for them. Disability-related services are tax financed with a symbolic fee. Rehabilitation is performed by not only physical and rehabilitation medicine specialists. Rehabilitation research is mainly within healthcare science but also in social science. Disability services need better coordination, and an agency has recently been founded with this responsibility. More politicians should engage in disability-related issues, and more people with disability should get into politics. Copyright © 2013 by Lippincott Williams & Wilkins.
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50.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Introducing guidelines for publishing DNA-derived occurrence data through biodiversity data platforms
  • 2022
  • Ingår i: Metabarcoding and Metagenomics. - : Pensoft Publishers. - 2534-9708. ; 6, s. 239-244
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA sequencing efforts of environmental and other biological samples disclose unprecedented and largely untapped opportunities for advances in the taxonomy, ecology, and geographical distributions of our living world. To realise this potential, DNA-derived occurrence data (notably sequences with dates and coordinates) – much like traditional specimens and observations – need to be discoverable and interpretable through biodiversity data platforms. The Global Biodiversity Information Facility (GBIF) recently headed a community effort to assemble a set of guidelines for publishing DNA-derived data. These guidelines target the principles and approaches of exposing DNA-derived occurrence data in the context of broader biodiversity data. They cover a choice of terms using a controlled vocabulary, common pitfalls, and good practices, without going into platform-specific details. Our hope is that they will benefit anyone interested in better exposure of DNA-derived occurrence data through general biodiversity data platforms, including national biodiversity portals. This paper provides a brief rationale and an overview of the guidelines, an up-to-date version of which is maintained at https://doi.org/10.35035/doc-vf1a-nr22. User feedback and interaction are encouraged as new techniques and best practices emerge.
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