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Sökning: WFRF:(Rossi Alessandra)

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1.
  • Filippou, Georgios, et al. (författare)
  • The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound : The STARTER study
  • 2018
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:9, s. 1283-1289
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation. Methods: A multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models. Results: 361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months. Conclusions: PD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.
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2.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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4.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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5.
  • Consiglio, Camila Rosat, et al. (författare)
  • The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19
  • 2020
  • Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 183:4, s. 968-981
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. Weapply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.
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6.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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7.
  • Perugia, Giulia, et al. (författare)
  • Gender Revealed : Evaluating the Genderedness of Furhat's Predefined Faces
  • 2021
  • Ingår i: Social Robotics, ICSR 2021. - Cham : Springer Nature. - 9783030905255 - 9783030905248 ; , s. 36-47
  • Konferensbidrag (refereegranskat)abstract
    • In this study, we employed Furhat to investigate how people attribute gender to a robot and whether the attribution of gender might elicit stereotypes already at a first impression. We involved 223 participants in an online study and asked them to rate 15 of Furhat's predefined faces in terms of femininity, masculinity, communion, and agency, and identify which facial cues they based their attribution of gender upon. Our results show that Furhat's predefined faces are attributed the same gender predicted by their names, except for one face which was perceived as androgynous. They disclose that feminine robots are perceived as less agentic than masculine robots already at a first impression, and reveal that vocal cues have higher relevance than facial cues in determining the gender attributed to a robot. Besides providing a complete account of the genderedness of Furhat's predefined faces, the present study also raises awareness of the importance of gender in the design of robots and provides a starting point to design more inclusive robotic technologies.
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8.
  • Rossi, Alessandra, et al. (författare)
  • Investigating Customers' Perceived Sensitivity of Information Shared with a Robot Bartender
  • 2021
  • Ingår i: Social Robotics, ICSR 2021. - Cham : Springer Nature. - 9783030905255 - 9783030905248 ; , s. 119-129
  • Konferensbidrag (refereegranskat)abstract
    • Personalised experiences with service robots positively affect people's perception of the robot and, consequently, foster the success of the interaction. This implies that people need to share their personal information with the robot, which could let people feel uneasy when such interactions happen in public spaces or in the presence of strangers. Therefore, it is difficult for a service robot to personalise a human-robot interaction (HRI) when this can lead to a breach of privacy. As a first step, the current study investigated people's perception of the sensitivity of various categories of potentially private personal information that are likely to be used by a service robot in a public business, such as a bar. We conducted a questionnaire-based study, where participants rated 15 personal information that they could share with either a human or robot bartender. The potentially private information was rated by participants according to their level of sensitivity. We analysed responses from 76 participants. We clearly identified information that are perceived as highly sensitive, such as those related to a person's identity (e.g. sexual orientation, political beliefs), and as low in sensitivity, such as those related to personal interests (e.g. sports, TV shows). Our findings also showed that older people consider sharing their preference of drinks more sensitive than younger people, especially when the bartender is a robot. We did not find significant differences in users' ratings due to their gender.
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9.
  • Falzarano, Maria Sofia, et al. (författare)
  • Urine-Derived Stem Cells Express 571 Neuromuscular Disorders Causing Genes, Making Them a Potential in vitro Model for Rare Genetic Diseases
  • 2021
  • Ingår i: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuromuscular disorders (NMDs) are a heterogeneous group of genetic diseases, caused by mutations in genes involved in spinal cord, peripheral nerve, neuromuscular junction, and muscle functions. To advance the knowledge of the pathological mechanisms underlying NMDs and to eventually identify new potential drugs paving the way for personalized medicine, limitations regarding the availability of neuromuscular disease-related biological samples, rarely accessible from patients, are a major challenge. & nbsp; Aim: We characterized urinary stem cells (USCs) by in-depth transcriptome and protein profiling to evaluate whether this easily accessible source of patient-derived cells is suitable to study neuromuscular genetic diseases, focusing especially on those currently involved in clinical trials. & nbsp; Methods: The global transcriptomics of either native or MyoD transformed USCs obtained from control individuals was performed by RNA-seq. The expression of 610 genes belonging to 16 groups of disorders () whose mutations cause neuromuscular diseases, was investigated on the RNA-seq output. In addition, protein expression of 11 genes related to NMDs including COL6A, EMD, LMNA, SMN, UBA1, DYNC1H1, SOD1, C9orf72, DYSF, DAG1, and HTT was analyzed in native USCs by immunofluorescence and/or Western blot (WB). & nbsp; Results: RNA-seq profile of control USCs shows that 571 out of 610 genes known to be involved in NMDs, are expressed in USCs. Interestingly, the expression levels of the majority of NMD genes remain unmodified following USCs MyoD transformation. Most genes involved in the pathogenesis of all 16 groups of NMDs are well represented except for channelopathies and malignant hyperthermia related genes. All tested proteins showed high expression values, suggesting consistency between transcription and protein representation in USCs. & nbsp; Conclusion: Our data suggest that USCs are human cells, obtainable by non-invasive means, which might be used as a patient-specific cell model to study neuromuscular disease-causing genes and that they can be likely adopted for a variety of in vitro functional studies such as mutation characterization, pathway identification, and drug screening.
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10.
  • Flex, Elisabetta, et al. (författare)
  • Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:16, s. 4315-4327
  • Tidskriftsartikel (refereegranskat)abstract
    • RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2(S2G) mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease.
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11.
  • Freidin, Maxim B., et al. (författare)
  • Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19
  • 2023
  • Ingår i: Inflammation Research. - 1023-3830. ; 72:5, s. 947-953
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective and design: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is the major symptom of the post-COVID syndrome (known colloquially as long-COVID). The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19. Subjects and methods: We analyzed pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19-positive and -negative participants were categorized based on SARS-CoV-2 antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale. Results: COVID-19-positive participants exhibited mild disease. Chronic fatigue was a prevalent symptom among this population and significantly higher in positive vs. negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in positive and negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in negative, but not positive individuals. Raised BMI was associated with chronic fatigue in positive participants. Conclusions: Pre-existing increased IL-6 levels may contribute to chronic fatigue symptoms, but there was no increased risk in individuals with mild COVID-19 compared with uninfected individuals. Elevated BMI also increased the risk of chronic fatigue in mild COVID-19, consistent with previous reports.
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12.
  • Ippoliti, Elena, et al. (författare)
  • An approach towards the construction of a Digital Atlas for the documentation of cloister and courtyards in Ascoli Piceno
  • 2011
  • Ingår i: International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, ISPRS, Trento, 2-4 March, 2011.. - Trento, Italy. ; , s. 231-238
  • Konferensbidrag (refereegranskat)abstract
    • The following article aims to present the results of a research experience that defines a geographic information system oriented at the architecture of closed areas of cloisters and courtyards of the historic center of Ascoli Piceno. This experimentation is part of the scenery of documentation's activities for the management and the enhancement of urban environmental improvements through the use of integrated technologies closed and open source. Therefore the main object of the analysis was the architectural one, in its different, articulated and individual features, but always considered in relation to the same geographical location, in this case the urban space, consequently focused not only on the object itself, but also on the relationship between this and any other similar ones. In this sense, the tested geographic information system is intentionally hybrid. We wanted to check the possibility of binding different shape and nature data to the "map" by structuring in a well organized manner different information – drawings, videos, photos, 3D, etc.. – in order to realize a GIS that would allow to analyze the architecture of cloisters and courtyards both in its relations to the urban context and in its specific spatial qualities.
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16.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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17.
  • Li, Jian-Yang, et al. (författare)
  • Ejecta from the DART-produced active asteroid Dimorphos
  • 2023
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 616, s. 452-456
  • Tidskriftsartikel (refereegranskat)abstract
    • Some active asteroids have been proposed to be formed as a result of impact events1. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA2, in addition to having successfully changed the orbital period of Dimorphos3, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions. Here we report the observations of the DART impact ejecta with the Hubble Space Telescope from impact time T + 15 min to T + 18.5 days at spatial resolutions of around 2.1 km per pixel. Our observations reveal the complex evolution of the ejecta, which are first dominated by the gravitational interaction between the Didymos binary system and the ejected dust and subsequently by solar radiation pressure. The lowest-speed ejecta dispersed through a sustained tail that had a consistent morphology with previously observed asteroid tails thought to be produced by an impact4,5. The evolution of the ejecta after the controlled impact experiment of DART thus provides a framework for understanding the fundamental mechanisms that act on asteroids disrupted by a natural impact1,6.
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18.
  • Morabito, Fortunato, et al. (författare)
  • Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients: A retrospective case-matched study
  • 2014
  • Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609. ; 89:4, s. 355-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2-microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients (P=0.007). After a median follow-up of 34 months (range, 1-92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52-0.82; P<0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32-0.59; P<0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients 75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control-case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT. Am. J. Hematol. 89:355-362, 2014. (c) 2013 Wiley Periodicals, Inc.
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19.
  • Perez-Nadales, Elena, et al. (författare)
  • Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
  • 2020
  • Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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20.
  • Policastro, Francesca, et al. (författare)
  • Adaptation, Validity, and Reliability of the Patient Health Questionnaire (PHQ-9) in the Kurdistan Region of Iraq
  • 2023
  • Ingår i: Healthcare. - : MDPI. - 2227-9032. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The Patient Health Questionnaire (PHQ-9) is widely used for detecting and screening depression in Iraq. However, no psychometric assessment has been performed on any Iraqi version. This study aims at studying the reliability and validity of the Iraqi Kurdish version of the PHQ-9 as tool for identifying depression. Methods: A cross-sectional study design was used; data were collected from 872 participants (49.3% female and 51.7% male) at Primary Health Care Centers (PHCCs) in the host community as well as from Internal Displaced Persons (IDPs) and refugee camps. Sociodemographic information was obtained; PHQ-9 for the diagnosis and screening of depression and Self Reporting Questionnaire 20 items (SRQ-20) for the screening of common mental illnesses were administered. Validity and reliability analyses were performed. Results: In total, 19% of the participants had a PHQ-9 total score equal to or higher than the clinical cut-off of 10 for diagnosing depressive disorder. The internal consistency of the PHQ-9 was good (Cronbach's alpha coefficient was 0.89). Good concurrent validity for PHQ-9 compared with SRQ-20 (71%, p < 0.001) was found. Conclusions: The PHQ-9 demonstrates good psychometric properties and proves to be a good tool for detecting and screening depression.
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21.
  • Policastro, Francesca, et al. (författare)
  • Motor Development of Children in the Kurdistan Region of Iraq : Parent Survey
  • 2024
  • Ingår i: Children. - : MDPI. - 2227-9067. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The actual literature highlights the importance of the socio-cultural context in the development of children. However, there is a lack of specific evidence about the middle East, especially regarding the development of Kurdish children who are living in a post-war scenario, in a country which is experiencing continuous instability due to the different crises. The main aim of this study is to identify the features of the motor development of Kurdish children according to parents' opinion. A comparison with Italian children is provided as a Western example, which reflects data from the literature. In the study, 331 parents of Kurdish and Italian children aged between 3 and 7 years were involved. Parents filled the questionnaire at kindergartens, after providing consent. The questionnaire was conceptualized, designed, tested and provided ad hoc for this study; it focused on the timing of development, concerning major milestones like head control, sitting and standing-up. The questionnaire consists of 15 questions and has not been standardized yet. A logistic regression showed several differences between Kurdish and Italian children, like head control (p = 0.007) or the manipulation of big objects (p < 0.0001). These results identify the effect of the socio-cultural context and the impact of the growing environment of the child. Moreover, the results of this survey show the need for introducing different adapted, translated and validated assessment tools for motor development, considering differences related to the socio-cultural context.
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  • Rossi, Rachele, et al. (författare)
  • A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma : Implications in DMD Diagnosis and Clinical Monitoring
  • 2023
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD.
  •  
24.
  • Rossi, Rachele, et al. (författare)
  • Circadian Genes as Exploratory Biomarkers in DMD : Results From Both the mdx Mouse Model and Patients
  • 2021
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Duchenne muscular dystrophy (DMD) is a rare genetic disease due to dystrophin gene mutations which cause progressive weakness and muscle wasting. Circadian rhythm coordinates biological processes with the 24-h cycle and it plays a key role in maintaining muscle functions, both in animal models and in humans. We explored expression profiles of circadian circuit master genes both in Duchenne muscular dystrophy skeletal muscle and in its animal model, the mdx mouse. We designed a customized, mouse-specific Fluidic-Card-TaqMan-based assay (Fluid-CIRC) containing thirty-two genes related to circadian rhythm and muscle regeneration and analyzed gastrocnemius and tibialis anterior muscles from both unexercised and exercised mdx mice. Based on this first analysis, we prioritized the 7 most deregulated genes in mdx mice and tested their expression in skeletal muscle biopsies from 10 Duchenne patients. We found that CSNK1E, SIRT1, and MYOG are upregulated in DMD patient biopsies, consistent with the mdx data. We also demonstrated that their proteins are detectable and measurable in the DMD patients' plasma. We suggest that CSNK1E, SIRT1, and MYOG might represent exploratory circadian biomarkers in DMD.
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25.
  • Ullah, Hammad, et al. (författare)
  • In Vitro Bioaccessibility and Anti-Inflammatory Activity of a Chemically Characterized Allium cepa L. Extract Rich in Quercetin Derivatives Optimized by the Design of Experiments
  • 2022
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 27:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Allium cepa L. is a highly consumed garden crop rich in biologically active phenolic and organosulfur compounds. This study aimed to assess the in vitro bioaccessibility and anti-inflammatory effect of a chemically characterized A. cepa extract rich in quercetin and its derivatives. Different varieties of A. cepa were studied; based on the highest total phenolic content, the “Golden” variety was selected. Its extracts, obtained from the tunicate bulb, tunic, and bulb, were subjected to determination of quercetin and its derivatives with LC-MS analysis and based on the highest total quercetin content, the tunic extract was utilized for further experiments. The extraction method was optimized through a design of experiment (DoE) method via full factorial design, which showed that 40% ethanol and 1 g tunic/20 mL solvent are the best extraction conditions. HPLC analysis of the optimized tunic extract identified 14 flavonols, including 10 quercetin derivatives. As far as in vitro bioaccessibility was concerned, the increases in some quercetin derivatives following the gastro-duodenal digestion process support the bioaccessibility of these bioactive compounds. Moreover, the extract significantly inhibited the production of PGE2 in stimulated J774 cell lines, while no effects of the tunic extract were observed against the release of IL-1β, TNF-α, and nitrites. The study provided insights into the optimized extraction conditions to obtain an A. cepa tunic extract rich in bioavailable quercetin derivatives with significant anti-inflammatory effects against PGE2.
  •  
26.
  • van der Zwaan, Irès (författare)
  • Characterisation of an in vitro dissolution method for assessment of novel pulmonary drug delivery systems : With a focus on controlled release systems
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Pulmonary drug delivery has been used for decades to treat local diseases like asthma. When using the pulmonary route to deliver drugs, several important lung features are being used, such as a large surface area available for absorption, high organ vascularization, and a thin blood-alveolar barrier. Pulmonary drug delivery systems on the market are formulations with a rapid release, which leads to a high drug concentration initially and a prompt decline in concentration shortly thereafter. This could cause unfavourable adverse effects or toxicity to the lung tissue at the onset of the release and could also result in decreased efficacy. To overcome these challenges, there is a need to develop controlled release drug delivery systems to improve the therapeutic effectiveness of inhaled drugs. When a drug is inhaled, the drug particles will deposit in the lung, and the drug needs to dissolve in the lung fluids before the drug is available for uptake locally or in the systemic circulation. The absorption inhaled drug thus depends on the dissolution of the drug particles in the lung fluid. As a result, it could be possible to prolong the duration of the drug effect, by prolonging the time it takes for the dissolution of the drug particles. Due to this, in vitro methods analysing the dissolution of the drug particles in the lung are of high relevance for the development of novel pulmonary drug delivery systems. It is therefore of high importance that the dissolution profiles that are measured are well understood. The overall aim of this thesis was to evaluate and characterise an in vitro dissolution method (Transwell system) for assessment of novel pulmonary drug delivery systems, with a focus on future controlled release systems. A developed mechanistic model was used to analyse experimental dissolution data and to predict which process was the rate limiting step in the obtained profiles. The developed mechanistic model provided the same rank order as the Weibull fit, however the model provided additional detailed understanding of the used dissolution process and setup. In addition, two novel controlled release drug delivery systems, mesoporous silica particles and hyaluronic based hydrogels, were successfully analysed using this in vitro dissolution system. Both delivery systems showed a promising aerosolization and control over the release profiles. Finally, the micellar contribution to diffusion of poorly soluble inhaled drugs during in vitro dissolution was defined and validated using the obtained in vitro dissolution profiles. Physiologically based biopharmaceutics modelling tools were successfully established for Bud, BDP and FP using the diffusivity values taking into account the micellar contribution of the surfactant.
  •  
27.
  • Velaga, Sitaram, et al. (författare)
  • Dry powder inhalers : An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products
  • 2018
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 113, s. 18-28
  • Tidskriftsartikel (refereegranskat)abstract
    • In vitro dissolution testing is routinely used in the development of pharmaceutical products. Whilst the dissolution testing methods are well established and standardized for oral dosage forms, i.e. tablets and capsules, there are no pharmacopoeia methods or regulatory requirements for testing the dissolution of orally inhaled powders. Despite this, a wide variety of dissolution testing methods for orally inhaled powders has been developed and their bio-relevance has been evaluated.The review provides an overview of the in vitro dissolution methodologies for dry inhalation products, with particular emphasis on dry powder inhaler, where the dissolution behavior of the respirable particles can have a role on duration and absorption of the drug. Dissolution mechanisms of respirable particles as well as kinetic models have been presented. A more recent bio-relevant dissolution set-ups and media for studying inhalation biopharmaceutics were also reviewed. In addition, factors affecting interplay between dissolution and absorption of deposited particles in the context of biopharmaceutical considerations of inhalation products were examined.
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