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- Björnsson, Bergthor, et al.
(författare)
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Digital twins to personalize medicine
- 2020
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
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| 2. |
- Burns, Georgette Leah, et al.
(författare)
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When the wildlife you watch becomes the food you eat : Exploring moral and ethical dilemmas when consumptive and non-consumptive tourism merge
- 2018
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Ingår i: Animals, food, and tourism. - New York : Routledge. - 9781138291607 - 9781315265209 ; , s. 25-35
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Bokkapitel (refereegranskat)abstract
- In the context of wildlife tourism, human experiences with other species are often divided into the binary categories of consumptive and non-consumptive interactions. What happens when the same person values a species, and interacts with it, in both categories? The aim of this chapter is to explore moral and ethical issues inherent in tourism experiences where tourists both watch and eat the same species. The work also seeks to contribute to filling an identified gap in the tourism literature concerning moral issues associated with the use of animals as food (Yudina & Fennell, 2013).Although the chapter is primarily a theoretical piece, two case studies examining whale watching and whale eating, and seal watching and seal eating, in Iceland are included. These provide practical examples of the decision-making dilemmas when consumptive and non-consumptive forms of wildlife tourism merge.
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| 3. |
- Gawel, Danuta, et al.
(författare)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 4. |
- Gawel, Danuta, et al.
(författare)
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An algorithm-based meta-analysis of genome- and proteome-wide data identifies a combination of potential plasma biomarkers for colorectal cancer
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects. Painstaking research has led to the identification of a large number of different types of biomarkers, few of which are in general clinical use. Here, we searched for highly accurate combinations of biomarkers by meta-analyses of genome- and proteome-wide data from CRC tumors. We focused on secreted proteins identified by the Human Protein Atlas and used our recently described algorithms to find optimal combinations of proteins. We identified nine proteins, three of which had been previously identified as potential biomarkers for CRC, namely CEACAM5, LCN2 and TRIM28. The remaining proteins were PLOD1, MAD1L1, P4HA1, GNS, C12orf10 and P3H1. We analyzed these proteins in plasma from 80 patients with newly diagnosed CRC and 80 healthy controls. A combination of four of these proteins, TRIM28, PLOD1, CEACAM5 and P4HA1, separated a training set consisting of 90% patients and 90% of the controls with high accuracy, which was verified in a test set consisting of the remaining 10%. Further studies are warranted to test our algorithms and proteins for early CRC diagnosis.
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| 5. |
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| 6. |
- Gervind, Elisabet, et al.
(författare)
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The influence of organizational models on the implementation of internet-based cognitive behavior therapy in primary care: A mixed methods study using the RE-AIM framework
- 2024
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: Internet-Based Cognitive Behavioral Therapy (iCBT) holds great potential in addressing mental health issues, yet its real-world implementation poses significant challenges. While prior research has predominantly focused on centralized care models, this study explores the implementation of iCBT in the context of decentralized organizational structures within the Swedish primary care setting, where all interventions traditionally are delivered at local Primary Care Centers (PCCs).Aim: This study aims to enhance our understanding of iCBT implementation in primary care and assess the impact of organizational models on the implementation's outcome using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework.Method: A mixed-methods research design was employed to identify the factors influencing iCBT implementation across different levels, involving patients, therapists and managers. Data spanning two years was collected and analyzed through thematic analysis and statistical tests. The study encompassed 104 primary care centers, with patient data (n = 1979) sourced from the Swedish National Quality Register for Internet-Based Psychological Treatment (SibeR). Additionally, 53 iCBT therapists and 50 PCC managers completed the Normalization Measure Development Questionnaire, and 15 leaders participated in interviews.Results: Our investigation identified two implementation approaches, one concentrated and one decentralized. Implementation effectiveness was evident through adherence rates suggesting that iCBT is a promising approach for treating mental ill-health in primary care, although challenges were observed concerning patient assessment and therapist drift towards unstructured treatment. Mandatory implementation, along with managerial and organizational support, positively impacted adoption. Results vary in terms of adherence to established protocols, with therapists working in concentrated model showing a significantly higher percentage of registration in the quality register SibeR (X2 (1, N = 2973) = 430.5774, p = 0.001). They also showed significantly higher means in cognitive participation (Z = - 2.179, p = 0.029) and in reflective monitoring (Z = - 2.548, p = 0.011). Discussion: Overall, the study results demonstrate that iCBT, as a complex and qualitatively different intervention from traditional psychological treatment, can be widely implemented in primary care settings. The study's key finding highlights the substantial advantages of the concentrated organizational model. This model has strengths in sustainability, encourages reflective monitoring among therapists, the use of quality registers, and enforces established protocols.Conclusion: In conclusion, this study significantly contributes to the understanding of the practical aspects associated with the implementation of complex internet interventions, particularly in the context of internetbased cognitive-behavioral therapy (iCBT). The study highlights that effective iCBT integration into primary care requires a multifaceted approach, taking into account organizational models, robust support structures, and a commitment to maintaining quality standards. By emphasizing these factors, our research aims to provide actionable insights that can enhance the practicability and real-world applicability of implementing iCBT in primary care settings.
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| 7. |
- Gervind, Elisabet, et al.
(författare)
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The transference of research results to practise: Organization and implementation outcomes of iCBT in primary care – a mixed methods study using the RE-AIM framework
- 2022
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Ingår i: SWESRII 2022.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Healthcare systems all over the world are working in dynamic and resource-constrained contexts. Implementation science plays a critical role in ensuring that costly research results are implemented and improve public health. Implementation of iCBT in regular care has given mixed results and has rarely been documented on the basis of a scientific framework for implementation research. Aim: The overall aim of the present study is to contribute to knowledge about how iCBT can be implemented and organized in primary care. The current study also explores naturalistic variability in two different organizational formats, concentrated and decentralized. Method: A mixed quantitative-qualitative design was used to identify factors that impact the implementation of iCBT across multiple levels, including patient, therapists, leaders and organization. The scientific framework RE-AIM with the dimensions reach (those in the target group participating in the program), effectiveness (effects after completion of the program), adoption (actors who accept the program), implementation (compliance with the program according to protocol), maintenance (sustainability over time) was used to evaluate the implementation. Results: 104 primary care centres participated in the study. Outcomes on patient-data (n=1979) were gathered between 2018 and 2021 from the quality register SibeR. Fifty-four iCBT-therapists, answered the NoMAD-questionnaire and fifteen leaders were interviewed. The materials are currently being analysed.
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| 8. |
- Jung Lee, Eun Jung, et al.
(författare)
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Analysis of expression profiling data suggests explanation for difficulties in finding biomarkers for nasal polyps
- 2020
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Ingår i: Rhinology. - : INT RHINOLOGIC SOC. - 0300-0729 .- 1996-8604. ; 58:4, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identification of clinically useful biomarkers for Nasal Polyposis in chronic rhinosinusitis (CRSwNP) has proven difficult. We analyzed gene expression profiling data to find explanations for this. Methods:We analyzed mRNA expression profiling data, GSE36830, of six uncinate tissues from healthy controls and six NP from CRSwNP patients. We performed Ingenuity Pathway Analysis (IPA) of differentially expressed genes to identify pathways and predicted upstream regulators. Results: We identified 1,608 differentially expressed genes and 177 significant pathways, of which Th1 and Th2 activation pathway and leukocyte extravasation signaling were most significant. We identified 75 upstream regulators whose activity was predicted to be upregulated.These included regulators of known pathogenic and therapeutic relevance, like IL-4. However, only seven of the 75 regulators were actually differentially expressed in NP, namely CSF1, TYROBP, CCL2, CCL11, SELP, ADORA3, ICAM1. Interestingly, these did not include IL-4, and four of the seven were receptors. This suggested a potential explanation for the discrepancy between the predicted and observed expression levels of the regulators, namely that the receptors, and not their ligands, were upregulated. Indeed, we found that 10 receptors of key predicted upstream regulators were upregulated, including IL4R. Conclusion: Our findings indicate that the difficulties in finding specific biomarkers for CRSwNP depend on the complex underlying mechanisms, which include multiple pathways and regulators, each of which may be subdivided into multiple components such as ligands, soluble and membrane-bound receptors. This suggests that combinations of biomarkers may be needed for CRSwNP diagnostics.
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| 9. |
- Jung Lee, Eun Jung, et al.
(författare)
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Bulk and single cell transcriptomic data indicate that a dichotomy between inflammatory pathways in peripheral blood and arthritic joints complicates biomarker discovery
- 2020
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Ingår i: Cytokine. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 1043-4666 .- 1096-0023. ; 127
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Tidskriftsartikel (refereegranskat)abstract
- Background: Unbiased studies using different genome-wide methods have identified several novel biomarkers for diagnosis and treatment response in Rheumatoid Arthritis (RA). However, clinical translation has proven difficult. Here, we hypothesized that one reason could be that inflammatory responses in peripheral blood are different from those in the arthritic joint. Methods: We performed meta-analysis of gene expression microarray data from synovium, whole blood cells (WBC), peripheral blood mononuclear cells (PBMC), and CD4+ T cells from patients with RA and healthy controls in order to identify overlapping pathways, upstream regulators and potential biomarkers. We also analyzed single cell RNA-sequencing (scRNA-seq) data from peripheral blood and whole joints from a mouse model of antigen-induced arthritis. Results: Analyses of two profiling data sets from synovium from RA patients and healthy controls all showed significant activation of pathways with known pathogenic relevance, such as the Th1 pathway, the role of NFAT in regulation of the immune response, dendritic cell maturation, iCOS-iCOSL signaling in T helper cells, Fc gamma receptor-mediated phagocytosis, interferon signaling, Cdc42 signaling, and cytotoxic T lymphocyte-mediated apoptosis. The most activated upstream regulators included TNF, an important drug target, as well as IFN-gamma and CD40LG, all of which are known to play important pathogenic roles in RA. The differentially expressed genes from synovium included several potential biomarkers, such as CCL5, CCL13, CCL18, CX3CL1, CXCL6, CXCL9, CXCL10, CXCL13, ILLS, IL32, IL1RN, SPP1, and TNFSF11. By contrast, microarray studies of WBC, PBMC and CD4+ T cells showed variable pathways and limited pathway overlap with synovium. Similarly, scRNA-seq data from a mouse model of arthritis did not support that inflammatory responses in peripheral blood reflect those in the arthritic joints. These data showed pathway overlap between mouse joint cells and synovium from patients with RA, but not with cells in peripheral blood. Conclusions: Our findings indicate a dichotomy between gene expression changes, pathways, upstream regulators and biomarkers in synovium and cell types in peripheral blood, which complicates identification of biomarkers in blood.
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