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| 2. |
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| 3. |
- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Menditto, Enrica, et al.
(författare)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 5. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 6. |
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| 7. |
- Bousquet, J., et al.
(författare)
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ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle
- 2016
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1
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Forskningsöversikt (refereegranskat)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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| 8. |
- Bousquet, J., et al.
(författare)
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Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
- 2017
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Bousquet, J., et al.
(författare)
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MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY-BLACKWELL. - 0105-4538 .- 1398-9995. ; 70:11, s. 1372-1392
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Tidskriftsartikel (refereegranskat)abstract
- Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
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| 10. |
- Bousquet, J., et al.
(författare)
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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
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
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Forskningsöversikt (refereegranskat)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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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Bousquet, J, et al.
(författare)
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Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
- 2012
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Bousquet, J, et al.
(författare)
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CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis : A SUNFRAIL report
- 2017
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 7:1
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Forskningsöversikt (refereegranskat)abstract
- A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.
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| 22. |
- Bousquet, J., et al.
(författare)
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Daily allergic multimorbidity in rhinitis using mobile technology : A novel concept of the MASK study
- 2018
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 73:8, s. 1622-1631
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Forskningsöversikt (refereegranskat)abstract
- BackgroundMultimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. MethodsWe undertook a 1-year prospective observational study in which 4 210 users and 32585days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels 50/100 as "High" burden. ResultsVisual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis HighAsthma Low pattern. There were 1.7% days with a Rhinitis HighAsthma HighConjunctivitis Lowpattern. A novel Rhinitis HighAsthma HighConjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. ConclusionsIn a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.
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| 23. |
- Bousquet, J, et al.
(författare)
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MASK 2017 : ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence.
- 2018
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.
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| 24. |
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| 25. |
- Bosnic-Anticevich, S, et al.
(författare)
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ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy"
- 2019
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:7, s. 1219-1236
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Forskningsöversikt (refereegranskat)abstract
- Pharmacists are trusted health professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact of allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The ARIA-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses) and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of AR. However, the ARIA-pharmacy ICP should be adapted to local health care environments/situations as regional (national) differences exist in pharmacy care.
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| 26. |
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| 27. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 28. |
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| 31. |
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| 32. |
- Carrillo, I., et al.
(författare)
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Is the Milky Way still breathing? RAVE-Gaia streaming motions
- 2018
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 475:2, s. 2679-2696
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Tidskriftsartikel (refereegranskat)abstract
- We use data from the Radial Velocity Experiment (RAVE) and the Tycho-Gaia astrometric solution (TGAS) catalogue to compute the velocity fields yielded by the radial (V-R), azimuthal (V-phi), and vertical (V-z) components of associated Galactocentric velocity. We search in particular for variation in all three velocity components with distance above and below the disc midplane, as well as how each component of V-z (line-of-sight and tangential velocity projections) modifies the obtained vertical structure. To study the dependence of velocity on proper motion and distance, we use two main samples: a RAVE sample including proper motions from the Tycho-2, PPMXL, and UCAC4 catalogues, and a RAVE-TGAS sample with inferred distances and proper motions from the TGAS and UCAC5 catalogues. In both samples, we identify asymmetries in V-R and V-z. Below the plane, we find the largest radial gradient to be partial derivative V-R/partial derivative R = -7.01 +/- 0.61 km s(-1) kpc(-1), in agreement with recent studies. Above the plane, we find a similar gradient with partial derivative V-R/partial derivative R = -9.42 +/- 1.77 km s(-1) kpc(-1). By comparing our results with previous studies, we find that the structure in V-z is strongly dependent on the adopted proper motions. Using the Galaxia Milky Way model, we demonstrate that distance uncertainties can create artificial wave-like patterns. In contrast to previous suggestions of a breathing mode seen in RAVE data, our results support a combination of bending and breathing modes, likely generated by a combination of external or internal and external mechanisms.
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| 33. |
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| 35. |
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| 36. |
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| 37. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 38. |
- Liu, C, et al.
(författare)
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A DNA methylation biomarker of alcohol consumption.
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
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Tidskriftsartikel (refereegranskat)abstract
- The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
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| 39. |
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| 40. |
- Rosa, M. J., et al.
(författare)
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Identifying critical windows of prenatal particulate matter (PM2.5) exposure and early childhood blood pressure
- 2020
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Some evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 μm in diameter (PM2.5) exposure and children's BP at ages 4–6 years. Methods: Participants included 537 mother-child dyads enrolled in the Programming Research in Obesity, GRowth Environment, and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used distributed lag models (DLMs) to examine associations between daily PM2.5 exposure and systolic and diastolic BP (SBP and DBP), adjusting for child's age, sex and BMI, as well as maternal education, preeclampsia and indoor smoking report during the second and third trimester, seasonality and average postnatal year 1 PM2.5 exposure. Results: We found that PM2.5 exposure between weeks 11–32 of gestation (days 80–226) was significantly associated with children's increased SBP. Similarly, PM2.5 exposure between weeks 9–25 of gestation (days 63–176) was significantly associated with increased DBP. To place this into context, a constant 10 μg/m3 increase in PM2.5 sustained throughout this critical window would predict a cumulative increase of 2.6 mmHg (CI: 0.5, 4.6) in SBP and 0.88 mmHg (CI: 0.1, 1.6) in DBP at ages 4–6 years. In a stratified analysis by sex, this association persisted in boys but not in girls. Conclusions: Second and third trimester PM2.5 exposure may increase children's BP in early life. Further work investigating PM2.5 exposure with BP trajectories later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations, including pregnant women.
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| 41. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 42. |
- Sikdar, S, et al.
(författare)
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Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking
- 2019
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 11:13, s. 1487-1500
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.
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| 43. |
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- Adolf, A., et al.
(författare)
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Release of astroglial vimentin by extracellular vesicles: Modulation of binding and internalization of C3 transferase in astrocytes and neurons
- 2019
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Ingår i: Glia. - : Wiley. - 0894-1491. ; 67:4, s. 703-717
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Tidskriftsartikel (refereegranskat)abstract
- Clostridium botulinum C3 transferase (C3bot) ADP-ribosylates rho proteins to change cellular functions in a variety of cell types including astrocytes and neurons. The intermediate filament protein vimentin as well as transmembrane integrins are involved in internalization of C3bot into cells. The exact contribution, however, of these proteins to binding of C3bot to the cell surface and subsequent cellular uptake remains to be unraveled. By comparing primary astrocyte cultures derived from wild-type with Vim(-/-) mice, we demonstrate that astrocytes lacking vimentin exhibited a delayed ADP-ribosylation of rhoA concurrent with a blunted morphological response. This functional impairment was rescued by the extracellular excess of recombinant vimentin. Binding assays using C3bot harboring a mutated integrin-binding RGD motif (C3bot-G89I) revealed the involvement of integrins in astrocyte binding of C3bot. Axonotrophic effects of C3bot are vimentin dependent and postulate an underlying mechanism entertaining a molecular cross-talk between astrocytes and neurons. We present functional evidence for astrocytic release of vimentin by exosomes using an in vitro scratch wound model. Exosomal vimentin+ particles released from wild-type astrocytes promote the interaction of C3bot with neuronal membranes. This effect vanished when culturing Vim(-/-) astrocytes. Specificity of these findings was confirmed by recombinant vimentin propagating enhanced binding of C3bot to synaptosomes from rat spinal cord and mouse brain. We hypothesize that vimentin+ exosomes released by reactive astrocytes provide a novel molecular mechanism constituting axonotrophic (neuroprotective) and plasticity augmenting effects of C3bot after spinal cord injury.
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