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  • Bousquet, J, et al. (author)
  • Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
  • 2020
  • In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
  • Journal article (peer-reviewed)abstract
    • There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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  • Bousquet, J., et al. (author)
  • Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
  • 2016
  • In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
  • Research review (peer-reviewed)abstract
    • Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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  • Bousquet, J., et al. (author)
  • Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
  • 2017
  • In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
  • Journal article (peer-reviewed)abstract
    • The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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  • Bousquet, J., et al. (author)
  • ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle
  • 2016
  • In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1
  • Research review (peer-reviewed)abstract
    • The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
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  • Snodgrass, C., et al. (author)
  • The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission
  • 2017
  • In: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2097
  • Journal article (peer-reviewed)abstract
    • We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/ Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies. This article is part of the themed issue 'Cometary science after Rosetta'.
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  • Buckley, Jeffrey, 1992-, et al. (author)
  • An assessment of the transparency of contemporary technology education research employing interview-based methodologies
  • 2021
  • In: International journal of technology and design education. - : Springer Nature. - 0957-7572 .- 1573-1804.
  • Journal article (peer-reviewed)abstract
    • A high level of transparency in reported research is critical for several reasons, such as ensuring an acceptable level of trustworthiness and enabling replication. Transparency in qualitative research permits the identification of specific circumstances which are associated with findings and observations. Thus, transparency is important for the repeatability of original studies and for explorations of the transferability of original findings. There has been no investigation into levels of transparency in reported technology education research to date. With a position that increasing transparency would be beneficial, this article presents an analysis of levels of transparency in contemporary technology education research studies which employed interviews within their methodologies, and which were published within the International Journal of Technology and Design Education and Design and Technology Education: An International Journal (n = 38). The results indicate room for improvement, especially in terms of documenting researcher positionality, determinations of data saturation, and how power imbalances were managed. A discussion is presented on why it is important to improve levels of transparency in reported studies, and a guide on areas to make transparent is presented for qualitative and quantitative research.
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  • Olff, M., et al. (author)
  • Screening for consequences of trauma–an update on the global collaboration on traumatic stress
  • 2020
  • In: European Journal of Psychotraumatology. - : Taylor and Francis Ltd.. - 2000-8198 .- 2000-8066. ; 11:1
  • Journal article (peer-reviewed)abstract
    • This letter provides an update on the activities of “The Global Collaboration on Traumatic Stress” (GC-TS) as first described by Schnyder et al. in 2017. It presents in further detail the projects of the first theme, in particular the development of and initial data on the Global Psychotrauma Screen (GPS), a brief instrument designed to screen for the wide range of potential outcomes of trauma. English language data and ongoing studies in several languages provide a first indication that the GPS is a feasible, reliable and valid tool, a tool that may be very useful in the current pandemic of the coronavirus disease 2019 (COVID-19). Further multi-language and cross-cultural validation is needed. Since the start of the GC-TS, new themes have been introduced to focus on in the coming years: a) Forcibly displaced persons, b) Global prevalence of stress and trauma related disorders, c) Socio-emotional development across cultures, and d) Collaborating to make traumatic stress research data “FAIR”. The most recent theme added is that of Global crises, currently focusing on COVID-19-related projects.
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  • Au, A. E., et al. (author)
  • Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Thrombopoietin (TPO) is the master cytokine regulator of megakaryopoiesis. In addition to regulation of megakaryocyte and platelet number, TPO is important for maintaining proper hematopoietic stem cell (HSC) function. It was previously shown that a number of lymphoid genes were upregulated in HSCs from Tpo(-/-)mice. We investigated if absent or enhanced TPO signaling would influence normal B-lymphopoiesis. Absent TPO signaling in Mpl(-/-)mice led to enrichment of a common lymphoid progenitor (CLP) signature in multipotential lineage-negative Sca-1(+)c-Kit(+) (LSK) cells and an increase in CLP formation. Moreover, Mpl(-/-)mice exhibited increased numbers of PreB2 and immature B-cells in bone marrow and spleen, with an increased proportion of B-lymphoid cells in the G1 phase of the cell cycle. Conversely, elevated TPO signaling in Tpo(Tg) mice was associated with reduced B-lymphopoiesis. Although at steady state, peripheral blood lymphocyte counts were normal in both models, Mpl(-/-)E mu-myc mice showed an enhanced preneoplastic phase with increased numbers of splenic PreB2 and immature B-cells, a reduced quiescent fraction, and augmented blood lymphocyte counts. Thus, although Mpl is not expressed on lymphoid cells, TPO signaling may indirectly influence B-lymphopoiesis and the preneoplastic state in Myc-driven B-cell lymphomagenesis by lineage priming in multipotential progenitor cells.
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  • Valiente-Dobon, JJ, et al. (author)
  • Evidence for nontermination of rotational bands in Kr-74
  • 2005
  • In: Physical Review Letters. - 1079-7114. ; 95:23
  • Journal article (peer-reviewed)abstract
    • Three rotational bands in Kr-74 were studied up to (in one case one transition short of) the maximum spin I-max of their respective single-particle configurations. Their lifetimes have been determined using the Doppler-shift attenuation method. The deduced transition quadrupole moments reveal a modest decrease, but far from a complete loss of collectivity at the maximum spin I-max. This feature, together with the results of mean field calculations, indicates that the observed bands do not terminate at I=I-max.
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  • Walsh, Naomi, et al. (author)
  • Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
  • 2019
  • In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 111:6
  • Journal article (peer-reviewed)abstract
    • Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
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  • McGowan, Eunike C., et al. (author)
  • A Bioinformatically Initiated Approach to Evaluate GATA1 Regulatory Regions in Samples with Weak D, Del, or D- Phenotypes Despite Normal RHD Exons
  • In: Transfusion Medicine and Hemotherapy. - 1660-3796.
  • Journal article (peer-reviewed)abstract
    • Introduction: With over 360 blood group antigens in systems recognized, there are antigens, such as RhD, which demonstrate a quantitative reduction in antigen expression due to nucleotide variants in the non-coding region of the gene that result in aberrant splicing or a regulatory mechanism. This study aimed to evaluate bioinformatically predicted GATA1-binding regulatory motifs in the RHD gene for samples presenting with weak or apparently negative RhD antigen expression but showing normal RHD exons. Methods: Publicly available open chromatin region data were overlayed with GATA1 motif candidates in RHD. Genomic DNA from weak D, Del or D- samples with normal RHD exons (n = 13) was used to confirm RHD zygosity by quantitative PCR. Then, RHD promoter, intron 1, and intron 2 regions were amplified for Sanger sequencing to detect potential disruptions in the GATA1 motif candidates. Electrophoretic mobility shift assay (EMSA) was performed to assess GATA1-binding. Luciferase assays were used to assess transcriptional activity. Results: Bioinformatic analysis identified five of six GATA1 motif candidates in the promoter, intron 1 and intron 2 for investigation in the samples. Luciferase assays showed an enhancement in transcription for GATA1 motifs in intron 1 and for intron 2 only when the R2 haplotype variant (rs675072G>A) was present. GATA1 motifs were intact in 12 of 13 samples. For one sample with a Del phenotype, a novel RHD c.1-110A>C variant disrupted the GATA1 motif in the promoter which was supported by a lack of a GATA1 supershift in the EMSA and 73% transcriptional activity in the luciferase assay. Two samples were D+/ D- chimeras. Conclusion: The bioinformatic predictions enabled the identification of a novel DEL allele, RHD c.1-110A>C, which disrupted the GATA1 motif in the proximal promoter. Although the majority of the samples investigated here remain unexplained, we provide GATA1 targets which may benefit future RHD regulatory investigations.
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  • Valiente-Dobon, JJ, et al. (author)
  • High-spin rotational structures in Kr-76
  • 2005
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 71:3
  • Journal article (peer-reviewed)abstract
    • High-spin states in Kr-76(36)40 have been populated in the Ca-40(Ca-40,4p)Kr-76 fusion-evaporation reaction at abeam energy of 165 MeV and studied using the Gammasphere and Microball multidetector arrays. The ground-state band and two signature-split negative parity bands of Kr-76 have been extended to similar to 30 (h) over bar. Lifetime measurements. using the Doppler-shift attenuation method show that the transition quadrupole moment of these three bands decrease as they approach their maximum-spin states. Two signatures of a new rotational structure with remarkably rigid rotational behavior have been identified. The high-spin properties of these rotational bands are analyzed within the framework of configuration-dependent cranked Nilsson-Strutinsky calculations.
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  • Valiente-Dobon, JJ, et al. (author)
  • Lifetimes of high-spin states in Kr-76
  • 2005
  • In: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 36:4, s. 1339-1342
  • Journal article (peer-reviewed)abstract
    • High-spin states in Kr-76(36)40 have been populated in the Ca-40 (Ca-40,4p) Kr-76 fusion-evaporation reaction at a beam energy of 165 MeV, and studied using the GAMMASPHERE and MICROBALL multi-detector arrays. The ground-state band and two signature-split negative-parity bands of Kr-76 have been extended to similar to 30h. Lifetime measurements using the Doppler-shift attenuation method indicate that the transition quadrupole moment of these three bands decrease as they approach their maximum-spin states.
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