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Sökning: WFRF:(Monti F)

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  • Bousquet, Jean, et al. (författare)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • 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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  • Menditto, Enrica, et al. (författare)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • 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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  • Panuzzo, P., et al. (författare)
  • Discovery of a dormant 33 solar-mass black hole in pre-release Gaia astrometry
  • 2024
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 686
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Gravitational waves from black-hole (BH) merging events have revealed a population of extra-galactic BHs residing in short-period binaries with masses that are higher than expected based on most stellar evolution models-And also higher than known stellar-origin black holes in our Galaxy. It has been proposed that those high-mass BHs are the remnants of massive metal-poor stars.Aims. Gaia astrometry is expected to uncover many Galactic wide-binary systems containing dormant BHs, which may not have been detected before. The study of this population will provide new information on the BH-mass distribution in binaries and shed light on their formation mechanisms and progenitors.Methods. As part of the validation efforts in preparation for the fourth Gaia data release (DR4), we analysed the preliminary astrometric binary solutions, obtained by the Gaia Non-Single Star pipeline, to verify their significance and to minimise false-detection rates in high-mass-function orbital solutions.Results. The astrometric binary solution of one source, Gaia BH3, implies the presence of a 32.70a ±a 0.82aM- BH in a binary system with a period of 11.6 yr. Gaia radial velocities independently validate the astrometric orbit. Broad-band photometric and spectroscopic data show that the visible component is an old, very metal-poor giant of the Galactic halo, at a distance of 590 pc.Conclusions. The BH in the Gaia BH3 system is more massive than any other Galactic stellar-origin BH known thus far. The low metallicity of the star companion supports the scenario that metal-poor massive stars are progenitors of the high-mass BHs detected by gravitational-wave telescopes. The Galactic orbit of the system and its metallicity indicate that it might belong to the Sequoia halo substructure. Alternatively, and more plausibly, it could belong to the ED-2 stream, which likely originated from a globular cluster that had been disrupted by the Milky Way.
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  • Bousquet, J, et al. (författare)
  • Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
  • 2020
  • Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
  • 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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  • Esposito, B., et al. (författare)
  • Progress of Design and Development for the ITER Radial Neutron Camera
  • 2022
  • Ingår i: Journal of fusion energy. - : Springer. - 0164-0313 .- 1572-9591. ; 41:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The paper presents an overview of the design status of the Radial Neutron Camera (RNC), that, together with the Vertical Neutron Camera, will provide, through reconstruction techniques applied to the measured line-integrated neutron fluxes, the time resolved measurement of the ITER neutron and alpha-source profile (i.e. neutron emissivity, neutrons emitted per unit time and volume). The RNC is composed of two subsystems, the In-Port RNC and Ex-Port RNC located, respectively, inside and outside the Plug of Equatorial Port #01. The In-Port subsystem is in a more advanced design stage since it has recently undergone the Final Design Review in the ITER procurement process. The paper describes the diagnostic layout, the interfaces, the measurement capabilities and the main challenges in its realization. Prototyping and testing of neutron detectors and electronics components were carried out and led to the choice of the component solutions that can match the environmental and operational constraints in terms radiation hardness, high temperature and electromagnetic compatibility. The performance of the RNC in terms of neutron emissivity measurement capability was assessed through 1D and 2D reconstruction analysis. It is proven that the neutron emissivity can be reconstructed in real-time within the measurement requirements: 10% accuracy, 10 ms time resolution and a/10 (a = plasma minor radius) space resolution.
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  • Bousquet, J, et al. (författare)
  • MASK 2017 : ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence.
  • 2018
  • Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 8
  • 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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  • Bédard, A., et al. (författare)
  • Treatment of allergic rhinitis during and outside the pollen season using mobile technology : A MASK study
  • 2020
  • Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 10:1
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundThe analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users.MethodsThe Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis.Results9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines.ConclusionsThis study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.
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  • Gurgel-Giannetti, J., et al. (författare)
  • A novel complex neurological phenotype due to a homozygous mutation in FDX2
  • 2018
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141, s. 2289-2298
  • Tidskriftsartikel (refereegranskat)abstract
    • Defects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leukoencephalopathy. Muscle biopsy demonstrated an unusual pattern of regional succinate dehydrogenase and cytochrome c oxidase deficiency with iron accumulation. The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c. 431C > T, p. P144L). The deleterious effect of the mutation was validated by real-time reverse transcription polymerase chain reaction and western blot analysis, which demonstrated normal expression of FDX2 mRNA but severely reduced expression of FDX2 protein in muscle tissue. This study describes a novel complex neurological phenotype with unusual MRI and muscle biopsy features, conclusively mapped to a mutation in FDX2, which encodes a ubiquitously expressed mitochondrial ferredoxin essential for early [Fe-S] cluster biogenesis.
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  • Paolucci, F., et al. (författare)
  • Interoperable multi-domain delay-aware provisioning using Segment Routing monitoring and BGP-LS advertisement
  • 2016
  • Ingår i: ECOC 2016 42th European Conference on Optical Communication Proceedings, September 18 - 22, 2016, Düsseldorf, Germany. - : Institute of Electrical and Electronics Engineers (IEEE). - 9783800742745 ; , s. 190-192
  • Konferensbidrag (refereegranskat)abstract
    • This paper demonstrates a multi-domain SDN orchestrator using delay information to provision network services using BGP-LS and a novel monitoring system enabled by Segment Routing. Moreover, it is the first implementation and interoperability of the BGP-LS extensions for TE metrics.
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  • Ardighieri, L, et al. (författare)
  • Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
  • 2021
  • Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 690201-
  • Tidskriftsartikel (refereegranskat)abstract
    • Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
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  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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  • Guerzoni, R., et al. (författare)
  • Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures : An architectural survey
  • 2017
  • Ingår i: Transactions on Emerging Telecommunications Technologies. - : Wiley-Blackwell. - 2161-5748 .- 2161-3915. ; 28:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the last couple of years, industry operators' associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This article provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi-operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation.
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  • Muhammad, Ajmal, et al. (författare)
  • On the Scalability of Connectivity Services in a Multi-Operator Orchestrator Sandbox
  • 2018
  • Ingår i: 2018 Optical Fiber Communications Conference and Exposition, OFC 2018 - Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781943580385
  • Konferensbidrag (refereegranskat)abstract
    • The paper investigates the performance of a multi-domain orchestrator (MdO) deployed in a real multi-domain European testbed. Results show how the MdO prototype scales well with the number of domains advertised and connectivity services provisioned.
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  • Padmanabhan, Sandosh, et al. (författare)
  • Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
  • 2010
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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  • Ravaioli, A, et al. (författare)
  • p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.
  • 2008
  • Ingår i: Annals of oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 19:4, s. 660-668
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.
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  • Ravaioli, F, et al. (författare)
  • DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome
  • 2022
  • Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 792165-
  • Tidskriftsartikel (refereegranskat)abstract
    • Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome.
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31.
  • Sgambelluri, Andrea, et al. (författare)
  • A multi-operator network service orchestration prototype : The 5G exchange
  • 2017
  • Ingår i: 2017 Optical Fiber Communications Conference and Exhibition, OFC 2017 - Proceedings. - : Institute of Electrical and Electronics Engineers Inc.. - 9781943580231
  • Konferensbidrag (refereegranskat)abstract
    • In the context of the 5GEx Project, a Multi-domain Orchestrator is in charge of creating, deploying, and terminating Network Services spanning across multiple-operators. This live demo showcases the main functionalities of the 5GEx system.
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  • Sgambelluri, A., et al. (författare)
  • Orchestrating QoS-based Connectivity Services in a Multi-Operator Sandbox
  • 2019
  • Ingår i: Journal of Optical Communications and Networking. - : OPTICAL SOC AMER. - 1943-0620 .- 1943-0639. ; 11:2, s. A196-A208
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the main features of 5G networks is the coordinated orchestration of both information technology (IT) and connectivity resources. This enables the deployment of a flexible and programmable architecture able to provision end-to-end services with different (and sometimes quite) stringent quality of service (QoS) constraints. In this paradigm, service orchestration may take place over single or multiple administrative domains. The 5G Exchange (5GEx) project, building on the software-defined network and the network function virtualization (NFV) concepts, targets the design and the implementation of a multi-domain orchestrator (MdO) prototype for the automatic provisioning of network service across multiple administrative domains. This paper presents an architectural solution, designed and implemented in the context of the 5GEx MdO prototype, that can be used to establish end-to-end connectivity tunnels with QoS constraints (i.e., bandwidth and/or end-to-end delay) connecting virtualized network functions deployed in remote data centers controlled by different providers by means of an innovative stateful backward recursive path-computation-element based computation procedure. The proposed solution has been experimentally validated in terms of scalability, reliability, and end-to-end workflow proof-of-concept. Results show how the designed solution permits the automatic establishment of QoS-based end-to-end tunnels spanning across multi-technology and multi-operator network domains. The orchestration scheme does not present scalability issues for either the advertisement of resources or for the provisioning of connectivity services. Moreover, no issues have been identified from the reliability point of view.
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34.
  • Sgambelluri, A., et al. (författare)
  • Orchestration of Network Services across multiple operators : The 5G Exchange prototype
  • 2017
  • Ingår i: EuCNC 2017 - European Conference on Networks and Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538638736
  • Konferensbidrag (refereegranskat)abstract
    • Future 5G networks will rely on the coordinated allocation of compute, storage, and networking resources in order to meet the functional requirements of 5G services as well as guaranteeing efficient usage of the network infrastructure. However, the 5G service provisioning paradigm will also require a unified infrastructure service market that integrates multiple operators and technologies. The 5G Exchange (5GEx) project, building heavily on the Software-Defined Network (SDN) and the Network Function Virtualization (NFV) functionalities, tries to overcome this market and technology fragmentation by designing, implementing, and testing a multi-domain orchestrator (MdO) prototype for fast and automated Network Service (NS) provisioning over multiple-technologies and spanning across multiple operators. This paper presents a first implementation of the 5GEx MdO prototype obtained by extending existing open source software tools at the disposal of the 5GEx partners. The main functions of the 5GEx MdO prototype are showcased by demonstrating how it is possible to create and deploy NSs in the context of a Slice as a Service (SlaaS) use-case, based on a multi-operator scenario. The 5GEx MdO prototype performance is experimentally evaluated running validation tests within the 5GEx sandbox. The overall time required for the NS deployment has been evaluated considering NSs deployed across two operators.
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35.
  • Sperduti, Andrea, et al. (författare)
  • Results of the first user program on the HOmogeneous Thermal NEutron Source HOTNES (ENEA/INFN)
  • 2017
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • The HOmogeneous Thermal NEutron Source (HOTNES) is a new type of thermal neutron irradiation assembly developed by the ENEA-INFN collaboration. The facility is fully characterized in terms of neutron field and dosimetric quantities, by either computational and experimental methods. This paper reports the results of the first "HOTNES users program", carried out in 2016, and covering a variety of thermal neutron active detectors such as scintillators, solid-state, single crystal diamond and gaseous detectors.
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36.
  • Bacalini, MG, et al. (författare)
  • Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer's disease and longevity in an Italian population
  • 2022
  • Ingår i: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 44:2, s. 881-896
  • Tidskriftsartikel (refereegranskat)abstract
    • Many physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.
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37.
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38.
  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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39.
  • Chiaraviglio, L., et al. (författare)
  • Impact of energy-efficient techniques on a device lifetime
  • 2014
  • Ingår i: 2014 IEEE Online Conference on Green Communications, OnlineGreenComm 2014. - : IEEE conference proceedings. - 9781479973842
  • Konferensbidrag (refereegranskat)abstract
    • This paper focuses on the impact that energyefficient techniques have on the component lifetime in optical backbone networks. The study presented in the paper considers in particular the influence that green routing strategies have on the failure rate of Erbium Doped Fiber Amplifiers (EDFAs), i.e., if their lifetime is positively or negatively impacted when putting them into sleep mode in order to reduce their energy consumption. To this end, the paper proposes a model that estimates the failure rate acceleration factor as a function of: (i) for how long and how frequently a device is switched into sleep mode, and (ii) hardware parameters that characterize the device. The proposed model is then evaluated by considering an energyefficient Routing and Wavelength Assignment (RWA) strategy that targets saving energy by putting EDFAs into sleep mode. The results presented in the paper show that energy-efficient techniques may have the potential to lower the failure rate of EDFAs. However, this is true only under specific conditions, i.e., an energy-efficient strategy needs to be carefully planned in order to avoid frequent power state transitions, which result in shortening the lifetime of an EDFA.
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40.
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41.
  • Codenotti, S, et al. (författare)
  • Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors
  • 2022
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:18
  • Tidskriftsartikel (refereegranskat)abstract
    • In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling.
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42.
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43.
  • Del Giudice, R, et al. (författare)
  • Autophagy Alteration in ApoA-I Related Systemic Amyloidosis
  • 2022
  • Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyloidoses are characterized by the accumulation and aggregation of misfolded proteins into fibrils in different organs, leading to cell death and consequent organ dysfunction. The specific substitution of Leu 75 for Pro in Apolipoprotein A-I protein sequence (ApoA-I; L75P-ApoA-I) results in late onset amyloidosis, where deposition of extracellular protein aggregates damages the normal functions of the liver. In this work, we describe that the autophagic process is inhibited in the presence of the L75P-ApoA-I amyloidogenic variant in stably transfected human hepatocyte carcinoma cells. The L75P-ApoA-I amyloidogenic variant alters the redox status of the cells, resulting into excessive mitochondrial stress and consequent cell death. Moreover, L75P-ApoA-I induces an impairment of the autophagic flux. Pharmacological induction of autophagy or transfection-enforced overexpression of the pro-autophagic transcription factor EB (TFEB) restores proficient proteostasis and reduces oxidative stress in these experimental settings, suggesting that pharmacological stimulation of autophagy could be a promising target to alleviate ApoA-I amyloidosis.
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44.
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45.
  • Gensous, N, et al. (författare)
  • A Targeted Epigenetic Clock for the Prediction of Biological Age
  • 2022
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic clocks were initially developed to track chronological age, but accumulating evidence indicates that they can also predict biological age. They are usually based on the analysis of DNA methylation by genome-wide methods, but targeted approaches, based on the assessment of a small number of CpG sites, are advisable in several settings. In this study, we developed a targeted epigenetic clock purposely optimized for the measurement of biological age. The clock includes six genomic regions mapping in ELOVL2, NHLRC1, AIM2, EDARADD, SIRT7 and TFAP2E genes, selected from a re-analysis of existing microarray data, whose DNA methylation is measured by EpiTYPER assay. In healthy subjects (n = 278), epigenetic age calculated using the targeted clock was highly correlated with chronological age (Spearman correlation = 0.89). Most importantly, and in agreement with previous results from genome-wide clocks, epigenetic age was significantly higher and lower than expected in models of increased (persons with Down syndrome, n = 62) and decreased (centenarians, n = 106; centenarians’ offspring, n = 143; nutritional intervention in elderly, n = 233) biological age, respectively. These results support the potential of our targeted epigenetic clock as a new marker of biological age and open its evaluation in large cohorts to further promote the assessment of biological age in healthcare practice.
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46.
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47.
  • Mandelli, GE, et al. (författare)
  • Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer
  • 2020
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy. Methods: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed. Results: Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T cells and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model. Conclusions: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.
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48.
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49.
  • Mello, D. A. A., et al. (författare)
  • Spectrally efficient fronthaul architectures for a cost-effective 5G C-RAN
  • 2016
  • Ingår i: International Conference on Transparent Optical Networks. - : IEEE Computer Society. - 9781509014675
  • Konferensbidrag (refereegranskat)abstract
    • In 5G wireless systems, centralized RAN (C-RAN) is an architectural choice where the signal waveforms received by Remote Radio Heads (RRH) are transparently forwarded to base band units (BBU), in many cases using an optical fronthaul. Although C-RAN highly simplifies the RRH, which is positive from the operational cost standpoint, much of the system complexity and cost is shifted towards the optical fronthaul. In this paper we show how a cost-effective C-RAN requires a spectrally-efficient optical fronthaul, and discuss the technological options to realize it.
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50.
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