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- Martin-Almeida, M, et al.
(författare)
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Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma
- 2023
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10−8 were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood samples (coefficient= −0.015, p = 2.53 × 10−9) and nominally associated in nasal samples (coefficient = −0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.
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- Abdel-Aziz, MI, et al.
(författare)
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A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma
- 2021
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the “Systems Pharmacology Approach to Uncontrolled Pediatric Asthma” (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case–control study, moderate-to-severe asthmatic children (age; 6–17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.
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- Agres, K. R., et al.
(författare)
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Music, Computing, and Health : A Roadmap for the Current and Future Roles of Music Technology for Health Care and Well-Being
- 2021
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Ingår i: Music & Science. - : SAGE Publications. - 2059-2043. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The fields of music, health, and technology have seen significant interactions in recent years in developing music technology for health care and well-being. In an effort to strengthen the collaboration between the involved disciplines, the workshop “Music, Computing, and Health” was held to discuss best practices and state-of-the-art at the intersection of these areas with researchers from music psychology and neuroscience, music therapy, music information retrieval, music technology, medical technology (medtech), and robotics. Following the discussions at the workshop, this article provides an overview of the different methods of the involved disciplines and their potential contributions to developing music technology for health and well-being. Furthermore, the article summarizes the state of the art in music technology that can be applied in various health scenarios and provides a perspective on challenges and opportunities for developing music technology that (1) supports person-centered care and evidence-based treatments, and (2) contributes to developing standardized, large-scale research on music-based interventions in an interdisciplinary manner. The article provides a resource for those seeking to engage in interdisciplinary research using music-based computational methods to develop technology for health care, and aims to inspire future research directions by evaluating the state of the art with respect to the challenges facing each field.
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| 11. |
- Smets, N. J. J. M., et al.
(författare)
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Ontology-based situation awareness support for shared control : Extended abstract
- 2017
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Ingår i: ACM/IEEE International Conference on Human-Robot Interaction. - New York, NY, USA : IEEE Computer Society. - 9781450348850 ; , s. 289-290
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Konferensbidrag (refereegranskat)abstract
- Situation Awareness (SA) during tele-operation in robot-assisted disaster management has a major impact on the effectiveness and efficiency. Data perceived by the human and robot agents should be processed and shared in such a way that these agents can understand and direct the other agent's behaviors. E.g., for safe and effective tele-operation, the human (team leader and/or operator) and robot need to be aware of (1) the state, location, position and movement of the robot platform and its arms, and (2) the state of robot's environment (such as obstacles, ...). This paper presents an SA-ontology that formalizes the effects of SA-components on the shared control performance. It is based on literature research, interviews with subject matter experts and a field test during a disaster management exercise. The SA-ontology captured all information needs for the teleoperation, and provided further requirements for SA-support functions.
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| 13. |
- Abdel-Aziz, Mahmoud I., et al.
(författare)
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A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.
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| 14. |
- Kruijff-Korbayová, I, et al.
(författare)
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TRADR Project : Long-Term Human-Robot Teaming for Robot Assisted Disaster Response
- 2015
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Ingår i: Künstliche Intelligenz. - : Springer. - 0933-1875 .- 1610-1987. ; 29:2, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the project TRADR: Long-Term Human-Robot Teaming for Robot Assisted Disaster Response. Experience shows that any incident serious enough to require robot involvement will most likely involve a sequence of sorties over several hours, days and even months. TRADR focuses on the challenges that thus arise for the persistence of environment models, multi-robot action models, and human-robot teaming, in order to allow incremental capability improvement over the duration of a mission. TRADR applies a user centric design approach to disaster response robotics, with use cases involving the response to a medium to large scale industrial accident by teams consisting of human rescuers and several robots (both ground and airborne). This paper describes the fundamentals of the project: the motivation, objectives and approach in contrast to related work.
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| 15. |
- Marschall, Tobias, et al.
(författare)
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Computational pan-genomics : status, promises and challenges
- 2018
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 19:1, s. 118-135
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Tidskriftsartikel (refereegranskat)abstract
- Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.
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| 20. |
- Zurek, Birte, et al.
(författare)
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TRIM27 Negatively Regulates NOD2 by Ubiquitination and Proteasomal Degradation
- 2012
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Ingår i: PLOS ONE. - San fransisco, USA : Public Library of Science. - 1932-6203. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohns disease. We found that TRIM27 expression is increased in Crohns disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus. We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.
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