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5,218 results on '"Cavazzana A"'

1. Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project

Author

Spini A, L'Abbate L, Ingrasciotta Y, Pellegrini G, Carollo M, Ientile V, Leoni O, Zanforlini M, Ancona D, Stella P, Cavazzana A, Scapin A, Lopes S, Belleudi V, and Trifirò G

Subjects
immune-mediated inflammatory diseases, biological drugs, validation, claims data, meta-algorithm, indication for use., Infectious and parasitic diseases, RC109-216
Abstract

Andrea Spini,1 Luca L’Abbate,2 Ylenia Ingrasciotta,1 Giorgia Pellegrini,1 Massimo Carollo,1 Valentina Ientile,2 Olivia Leoni,3 Martina Zanforlini,4 Domenica Ancona,5 Paolo Stella,5 Anna Cavazzana,6 Angela Scapin,6 Sara Lopes,7 Valeria Belleudi,7 Gianluca Trifirò1 1Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 3Lombardy Regional Centre of Pharmacovigilance and Regional Epidemiologic Observatory, Milan, Italy; 4Azienda Regionale per l’Innovazione e gli Acquisti, S.p.A, Milan, Italy; 5Apulian Regional Health Department, Bari, Italy; 6Azienda Zero, Regione Veneto, Italy; 7Department of Epidemiology, Lazio Regional Health Service, Rome, ItalyCorrespondence: Gianluca Trifirò, Department of Diagnostics and Public Health, University of Verona, P. le L.A. Scuro 10, Verona, 37134, Italy, Tel +39 045 802 7679, Email gianluca.trifiro@univr.itPurpose: This research aimed to develop and validate a META-algorithm combining individual immune-mediated inflammatory disease (IMID)-specific algorithms to identify the exact IMID indications for incident biological drug users from claims data within the context of the Italian VALORE project.Methods and Patients: All subjects with at least one dispensing of TNF-alpha inhibitors, anti-interleukin agents, and selective immunosuppressants approved for IMIDs were identified from claims databases of Latium region in Italy (observation period: 2010– 2020). Validated coding algorithms for identifying individual IMIDs from claims databases were found from published literature and combined into a META-algorithm. Positive predictive value (PPV), sensitivity (Se), negative predictive value (NPV), specificity (Sp), and accuracy (Acc) were estimated for each indication against the electronic therapeutic plans (ETPs) of the Latium region as the reference standard. Lastly, the frequency of the indication of use across individual biologic drugs was compared with that reported in three other Italian regions (Lombardy, Apulia, and the Veneto region).Results: In total, 9755 incident biological drug users with a single IMID indication were identified. Using the newly developed META-algorithm, an indication of use was detected in 95% (n=9255) of the total cohort. The estimated Acc, Se, Sp, PPV, and NPV, against the reference standard were as follows: 0.96, 0.86, 0.97, 0.82, and 0.98 for Crohn’s disease, 0.96, 0.80, 0.98, 0.85, and 0.97 for ulcerative colitis, 0.93, 0.76, 0.99, 0.95, and 0.92 for rheumatoid arthritis, 0.97, 0.75, 0.99, 0.85, and 0.98 for spondylarthritis, and 0.91, 0.92, 0.91, 0.88, and 0.94 for psoriatic arthritis/psoriasis, respectively. Additionally, no substantial difference was observed in the frequency of indication of use by active ingredient among Latium and the other three Italian regions included in the study.Conclusion: The newly developed META-algorithm demonstrated high validity estimates in the Italian claims data and was capable of discriminating with good performance among the most frequent IMID indications.Plain Language Summary: In the claims database, the lack of information on the indication of use represents a well-known limitation for the conduct of observational studies. This study was conducted to develop and validate a META-algorithm that accurately identifies the exact indication for the use of biological drugs in treating various immune-mediated inflammatory diseases. Using claims databases from the Latium region, we developed and validated a META-algorithm. The META-algorithm combines disease-specific algorithms for different immune-mediated inflammatory diseases (ie, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriasis, and psoriatic arthritis) and was tested against a reference standard (electronic therapeutic plans of the Lazio region). The META-algorithm reported high validity estimates and was able to distinguish with a good performance among the most frequent IMIDs as indications for use. Applying this META-algorithm may facilitate post-marketing surveillance of biological drugs such as TNF-alpha inhibitors, anti-interleukin, and selective immunosuppressants in specific therapeutic areas in an Italian setting.Keywords: immune-mediated inflammatory diseases, biological drugs, validation, claims data, META-algorithm, indication for use

Published
2024

2. Comment on “Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project”. [Response to Letter]

Author

Spini A, L'Abbate L, Ingrasciotta Y, Pellegrini G, Carollo M, Ientile V, Leoni O, Zanforlini M, Ancona D, Stella P, Cavazzana A, Scapin A, Lopes S, Belleudi V, and Trifirò G

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Andrea Spini,1 Luca L’Abbate,2 Ylenia Ingrasciotta,1 Giorgia Pellegrini,1 Massimo Carollo,1 Valentina Ientile,2 Olivia Leoni,3 Martina Zanforlini,4 Domenica Ancona,5 Paolo Stella,5 Anna Cavazzana,6 Angela Scapin,6 Sara Lopes,7 Valeria Belleudi,7 Gianluca Trifirò1 1Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 3Lombardy Regional Centre of Pharmacovigilance and Regional Epidemiologic Observatory, Milan, Italy; 4Azienda Regionale per l’Innovazione e gli Acquisti, S.p.A, Milan, Italy; 5Apulian Regional Health Department, Bari, Italy; 6Azienda Zero, Regione Veneto, Italy; 7Department of Epidemiology, Lazio Regional Health Service, Rome, ItalyCorrespondence: Gianluca Trifirò, Department of Diagnostics and Public Health, University of Verona, P. le L.A. Scuro 10, Verona, 37134, Italy, Tel +39 045 802 7679, Email gianluca.trifiro@univr.it

Published
2024

5. Ovarian tissue cryopreservation for fertility preservation before hematopoietic stem cell transplantation in patients with sickle cell disease: safety, ovarian function follow-up, and results of ovarian tissue transplantation

Author

Missontsa, Mitawa Millin, Bernaudin, Françoise, Fortin, Anne, Dhédin, Nathalie, Pondarré, Corinne, Yakouben, Karima, Neven, Bénédicte, Castelle, Martin, Cavazzana, Marina, Lezeau, Harry, Peycelon, Matthieu, Paye-Jaouen, Annabel, Sroussi, Jeremy, Diesch-Furlanetto, Tamara, Barraud-Lange, Virginie, Sarnacki, Sabine, Fahd, Mony, Marchand, Isis, Delcour, Clémence, Vexiau, Dominique, Arlet, Jean-Benoît, Kamdem, Annie, Arnaud, Cécile, Dalle, Jean-Hugues, and Poirot, Catherine

Published
2024
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6. Lessons learned after three years of SPIDER operation and the first MITICA integrated tests

Author

Marcuzzi, D., Toigo, V., Boldrin, M., Chitarin, G., Bello, S. Dal, Grando, L., Luchetta, A., Pasqualotto, R., Pavei, M., Serianni, G., Zanotto, L., Agnello, R., Agostinetti, P., Agostini, M., Aprile, D., Barbisan, M., Battistella, M., Berton, G., Bigi, M., Brombin, M., Candela, V., Candeloro, V., Canton, A., Casagrande, R., Cavallini, C., Cavazzana, R., Cordaro, L., Cruz, N., Palma, M. Dalla, Dan, M., De Lorenzi, A., Delogu, R., De Muri, M., De Nardi, M., Denizeau, S., Fadone, M., Fellin, F., Ferro, A., Gaio, E., Gasparrini, C., Gnesotto, F., Jain, P., La Rosa, A., Lopez-Bruna, D., Lorenzini, R., Maistrello, A., Manduchi, G., Manfrin, S., Marconato, N., Mario, I., Martini, G., Milazzo, R., Patton, T., Peruzzo, S., Pilan, N., Pimazzoni, A., Poggi, C., Pomaro, N., Pouradier-Duteil, B., Recchia, M., Rigoni-Garola, A., Rizzetto, D., Rizzolo, A., Santoro, F., Sartori, E., Segalini, B., Shepherd, A., Siragusa, M., Sonato, P., Sottocornola, A., Spada, E., Spagnolo, S., Spolaore, M., Taliercio, C., Tinti, P., Tomsič, P., Trevisan, L., Ugoletti, M., Valente, M., Valisa, M., Veronese, F., Vignando, M., Zaccaria, P., Zagorski, R., Zaniol, B., Zaupa, M., Zuin, M., Cavenago, M., Boilson, D., Rotti, C., Decamps, H., Geli, F., Sharma, A., Veltri, P., Zacks, J., Simon, M., Paolucci, F., Garbuglia, A., Gutierrez, D., Masiello, A., Mico, G., Labate, C., Readman, P., Bragulat, E., Bailly-Maitre, L., Gomez, G., Kouzmenko, G., Albajar, F., Kashiwagi, M., Tobari, H., Kojima, A., Murayama, M., Hatakeyama, S., Oshita, E., Maejima, T., Shibata, N., Yamashita, Y., Watanabe, K., Singh, N. P., Singh, M. J., Dhola, H., Fantz, U., Heinemann, B., Wimmer, C., Wünderlich, D., Tsumori, K., Croci, G., Gorini, G., Muraro, A., Rebai, M., Tardocchi, M., Giacomelli, L., Rigamonti, D., Taccogna, F., Bruno, D., Rutigliano, M., Longo, S., Deambrosis, S., Miorin, E., Montagner, F., Tonti, A., and Panin, F.

Subjects
Physics - Plasma Physics, Physics - Accelerator Physics
Abstract

ITER envisages the use of two heating neutral beam injectors plus an optional one as part of the auxiliary heating and current drive system. The 16.5 MW expected neutral beam power per injector is several notches higher than worldwide existing facilities. A Neutral Beam Test Facility (NBTF) was established at Consorzio RFX, exploiting the synergy of two test beds, SPIDER and MITICA. SPIDER is dedicated to developing and characterizing large efficient negative ion sources at relevant parameters in ITER-like conditions: source and accelerator located in the same vacuum where the beam propagates, immunity to electromagnetic interferences of multiple radio-frequency (RF) antennas, avoidance of RF-induced discharges on the outside of the source. Three years of experiments on SPIDER have addressed to the necessary design modifications to enable full performances. The source is presently under a long shut-down phase to incorporate learnings from the experimental campaign. Parallelly, developments on MITICA, the full-scale prototype of the ITER NBI featuring a 1 MV accelerator and ion neutralization, are underway including manufacturing of in-vessel components, while power supplies and auxiliary plants are already under final testing and commissioning. Integration, commissioning and tests of the 1MV power supplies are essential for this first-of-kind system, unparalleled both in research and industry field. The integrated test to confirm 1MV output by combining invertor systems, DC generators and transmission lines extracted errors/accidents in some components. To realize a concrete system for ITER, solutions for the repair and the improvement of the system were developed. Hence, NBTF is emerging as a necessary facility, due to the large gap with existing injectors, effectively dedicated to identify issues and find solutions to enable successful ITER NBI operations in a time bound fashion.

Published
2023
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7. Numerical and experimental investigations of a microwave interferometer for the negative ion source SPIDER

Author

Agnello, R., Cavazzana, R., Furno, I., Jacquier, R., Pasqualotto, R., Sartori, E., and Serianni, G.

Subjects
Physics - Plasma Physics
Abstract

The electron density close to the extraction grids and the co-extracted electrons represent a crucial issue when operating negative ion sources for fusion reactors. An excessive electron density in the plasma expansion region can indeed inhibit the negative ion production and introduce potentially harmful electrons in the accelerator. Among the set of plasma and beam diagnostics proposed for SPIDER upgrade, a heterodyne microwave (mw) interferometer at 100 GHz is being explored as a possibility to measure electron density in the plasma extraction region. The major issue in applying this technique in SPIDER is the poor accessibility of the probing microwave beam through the source metal walls and the long distance of 4 m at which mw modules should be located outside the vacuum vessel. Numerical investigations in a full-scale geometry showed that the power transmitted through the plasma source apertures was sufficient for the microwave module sensitivity. An experimental proof-of-principle of the setup was then performed. The microwave system was tested on an experimental full-scale test-bench mimicking SPIDER viewports accessibility constraints, including the presence of a SPIDER-like plasma. The outcome of first tests revealed that, despite the geometrical constraints, in certain conditions, the electron density measurements are possible. The main issue arises from decoupling the one-pass signal from spurious multipaths generated by mw beam reflections, requiring signal cross correlation analysis. These preliminary tests demonstrate that despite the 4 m distance between the mw modules and the presence of metal walls, plasma density measurement is possible when the 80-mm diameter ports are available. In this contribution, we discuss the numerical simulations, the preliminary experimental tests and suggest design upgrades of the interferometric setup to enhance signal transmission.

Published
2023
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8. Measure of negative ion density in a large negative ion source using Langmuir probes

Author

Poggi, Carlo, Spolaore, Monica, Barbisan, Marco, Brombin, Matteo, Cavazzana, Roberto, Marconato, Nicolò, Pasqualotto, Roberto, Pimazzoni, Antonio, Sartori, Emanuele, and Serianni, Gianluigi

Subjects
Physics - Plasma Physics, Physics - Accelerator Physics
Abstract

Neutral Beam Injectors (NBIs) based on negative ions are the workhorses of future fusion reactors, such as ITER, which they are expected to provide with up to \SI{33}{MW} of power to heat the fusion plasma. The negative hydrogen ions are extracted from a RF plasma, in which a magnetic filter field cools down the electrons reaching the so-called expansion region and allows the formation of negative ions near the apertures in the plasma grid. To further improve the production of negative ions, cesium is usually evaporated inside the source and deposited onto the plasma walls, reducing the work function of the surfaces. This dramatically increases the density of negative hydrogen ions near the surfaces, causing the transition to an electronegative plasma in the vicinity of the plasma grid. This condition can be observed with Langmuir probes, which can then be used to provide a local meaurement of negative ion density in the ion source. In this paper we use the measurements provided by the Langmuir probe sensors embedded in the plasma grid of SPIDER, the prototype ion source of ITER NBIs, to determine the density of negative ions. A fitting method based on the determination of the collection area of the different plasma species is proposed and adapted to SPIDER experimental condition, taking into account the shape of the probes and the local topology of the magnetic field. The method is then applied to the experimental data, determining the densities of the positive and negative ions and of the electrons during a plasma pulse. Finally, a vertical array of four probes in the plasma grid is used to assess the vertical profile of plasma parameters., Comment: 12 pages, 7 figures, contributed paper to the NIBS 22 conference. Submitted to Journal of Instrumentation

Published
2023

13. Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries

Author

Bellomio, Veronica, Cavazzana, Ilaria, Khmelinskii, Nikita, Monticielo, Odirlei Andre, Portela Hernández, Margarita, Saavedra Salinas, Miguel Angel, Scolnik, Marina, Silva Montandon, Ana Carolina, Yilmaz, Esin, Zucchi, Dina, Bolla, Eleana, Semb, Anne Grete, Kerola, Anne M, Ikdahl, Eirik, Petri, Michelle, Pons-Estel, Guillermo J, Karpouzas, George A, Sfikakis, Petros P, Quintana, Rosana, Misra, Durga Prasanna, Borba, Eduardo Ferreira, Garcia-de la Torre, Ignacio, Popkova, Tatiana V, Artim-Esen, Bahar, Troldborg, Anne, Fragoso-Loyo, Hilda, Ajeganova, Sofia, Yazici, Ayten, Aroca-Martinez, Gustavo, Direskeneli, Haner, Ugarte-Gil, Manuel F, Mosca, Marta, Goyal, Mohit, Svenungsson, Elisabet, Macieira, Carla, Hoi, Alberta, Lerang, Karoline, Costedoat-Chalumeau, Nathalie, Tincani, Angela, Mirrakhimov, Erkin, Acosta Colman, Isabel, Danza, Alvaro, Massardo, Loreto, Blagojevic, Jelena, Yılmaz, Neslihan, Tegzová, Dana, Yavuz, Sule, Korkmaz, Cengiz, Hachulla, Eric, Moreno Alvarez, Mario J, Muñoz-Louis, Roberto, Pantazis, Nikos, and Tektonidou, Maria G

Published
2024
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14. Influence of low and medium intake supplements in the growing phase of steers grazing in the tropical pasture and finished in feedlot /Influência de suplementos de baixo e médio consumo na fase de crescimento de novilhos mantidos em pastagem tropical e terminados em confinamento

Author

Missio, Regis Luis, de Souza e Souza, Saimon, Paris, Wagner, Cavazzana, Jefferson Felipe, Severo, Marcelo Machado, Severo, Igor Kieling, Poggere, Julia Maria, Costa, Olmar Antônio Denardin, Borquis, Rusbel Raul Aspilcueta, and de Menezes, Luis Fernando Glasenapp

Published
2024
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16. A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence

Author

Bruschi, Maurizio, Angeletti, Andrea, Prunotto, Marco, Meroni, Pier Luigi, Ghiggeri, Gian Marco, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavalli, Andrea, Scapozza, Leonardo, Patel, Jigar J., Tan, John C., Lo, Ken C., Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Giannese, Domenico, Manfredi, Angelo, Ramirez, Giuseppe A., Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisan, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Mescia, Federica, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Ravelli, Angelo, Murtas, Corrado, Candiano, Giovanni, Caridi, Gianluca, La Porta, Edoardo, and Verrina, Enrico

Published
2024
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21. The Role of Tumor Microenvironment in Colon Cancer

Author

Fattorini, Caterina, Arganini, Marco, Cavazzana, Andrea, Ambrosio, Maria Raffaella, Rezaei, Nima, Series Editor, Ahmed, Atif A., Editorial Board Member, Aguiar, Rodrigo, Editorial Board Member, Ambrosio, Maria R., Editorial Board Member, Artac, Mehmet, Editorial Board Member, Augustine, Tanya N., Editorial Board Member, Bambauer, Rolf, Editorial Board Member, Bhat, Ajaz Ahmad, Editorial Board Member, Bertolaccini, Luca, Editorial Board Member, Bianchini, Chiara, Editorial Board Member, Cavic, Milena, Editorial Board Member, Chakrabarti, Sakti, Editorial Board Member, Cho, William C. S., Editorial Board Member, Czarnecka, Anna M., Editorial Board Member, Domingues, Cátia, Editorial Board Member, Eşkazan, A. Emre, Editorial Board Member, Fares, Jawad, Editorial Board Member, Fonseca Alves, Carlos E., Editorial Board Member, Fru, Pascaline, Editorial Board Member, Da Gama Duarte, Jessica, Editorial Board Member, García, Mónica C., Editorial Board Member, Gener, Melissa A.H., Editorial Board Member, Estrada Guadarrama, José Antonio, Editorial Board Member, Hargadon, Kristian M., Editorial Board Member, Holvoet, Paul, Editorial Board Member, Jurisic, Vladimir, Editorial Board Member, Kabir, Yearul, Editorial Board Member, Katsila, Theodora, Editorial Board Member, Kleeff, Jorg, Editorial Board Member, Liang, Chao, Editorial Board Member, Tan, Mei Lan, Editorial Board Member, Li, Weijie, Editorial Board Member, Prado López, Sonia, Editorial Board Member, Macha, Muzafar A., Editorial Board Member, Malara, Natalia, Editorial Board Member, Orhan, Adile, Editorial Board Member, Prado-Garcia, Heriberto, Editorial Board Member, Pérez-Velázquez, Judith, Editorial Board Member, Rashed, Wafaa M., Editorial Board Member, Sanguedolce, Francesca, Editorial Board Member, Sorrentino, Rosalinda, Editorial Board Member, Shubina, Irina Zh., Editorial Board Member, de Araujo, Heloisa Sobreiro Selistre, Editorial Board Member, Torres-Suárez, Ana Isabel, Editorial Board Member, Włodarczyk, Jakub, Editorial Board Member, Yeong, Joe Poh Sheng, Editorial Board Member, Toscano, Marta A., Editorial Board Member, Wong, Tak-Wah, Editorial Board Member, Yin, Jun, Editorial Board Member, and Yu, Bin, Editorial Board Member

Published
2023
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22. Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project

Author

Ingrasciotta, Ylenia, Spini, Andrea, L'Abbate, Luca, Fiore, Elena Sofia, Carollo, Massimo, Ientile, Valentina, Isgrò, Valentina, Cavazzana, Anna, Biasi, Valeria, Rossi, Paola, Ejlli, Lucian, Belleudi, Valeria, Poggi, Francesca, Sapigni, Ester, Puccini, Aurora, Ancona, Domenica, Stella, Paolo, Pollina Addario, Sebastiano, Allotta, Alessandra, Leoni, Olivia, Zanforlini, Martina, Tuccori, Marco, Gini, Rosa, and Trifirò, Gianluca

Published
2024
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25. Efficacy of COVID-19 mRNA vaccination in patients with autoimmune disorders: humoral and cellular immune response

Author

Federica Filippini, Mauro Giacomelli, Chiara Bazzani, Micaela Fredi, Paolo Semeraro, Cesare Tomasi, Franco Franceschini, Arnaldo Caruso, Ilaria Cavazzana, and Cinzia Giagulli

Subjects
COVID-19 vaccination, Autoimmune diseases, Abatacept, Rituximab, T cell, Interferon-γ, Medicine
Abstract

Abstract Background The impact of immunosuppressive therapies on the efficacy of vaccines to SARS-CoV-2 is not completely clarified. We analyzed humoral and T cell-mediated response after COVID-19 mRNA vaccine in immunosuppressed patients and patients with common variable immunodeficiency disease (CVID). Patients We enrolled 38 patients and 11 healthy sex- and age-matched controls (HC). Four patients were affected by CVID and 34 by chronic rheumatic diseases (RDs). All patients with RDs were treated by corticosteroid therapy and/or immunosuppressive treatment and/or biological drugs: 14 patients were treated with abatacept, 10 with rituximab, and 10 with tocilizumab. Methods Total antibody titer to SARS-CoV-2 spike protein was assessed by electrochemiluminescence immunoassay, CD4 and CD4-CD8 T cell-mediated immune response was analyzed by interferon-γ (IFN-γ) release assay, the production of IFN-γ-inducible (CXCL9 and CXCL10) and innate-immunity chemokines (MCP-1, CXCL8, and CCL5) by cytometric bead array after stimulation with different spike peptides. The expression of CD40L, CD137, IL-2, IFN-γ, and IL-17 on CD4 and CD8 T cells, evaluating their activation status, after SARS-CoV-2 spike peptides stimulation, was analyzed by intracellular flow cytometry staining. Cluster analysis identified cluster 1, namely the “high immunosuppression” cluster, and cluster 2, namely the “low immunosuppression” cluster. Results After the second dose of vaccine, only abatacept-treated patients, compared to HC, showed a reduced anti-spike antibody response (mean: 432 IU/ml ± 562 vs mean: 1479 IU/ml ± 1051: p = 0.0034), and an impaired T cell response, compared with HC. In particular, we found a significantly reduced release of IFN-γ from CD4 and CD4-CD8 stimulated T cells, compared with HC (p = 0.0016 and p = 0.0078, respectively), reduced production of CXCL10 and CXCL9 from stimulated CD4 (p = 0.0048 and p = 0.001) and CD4-CD8 T cells (p = 0.0079 and p = 0.0006). Multivariable General Linear Model analysis confirmed a relationship between abatacept exposure and impaired production of CXCL9, CXCL10, and IFN-γ from stimulated T cells. Cluster analysis confirms that cluster 1 (including abatacept and half of rituximab treated cases) showed a reduced IFN-γ response, as well as reduced monocyte-derived chemokines All groups of patients demonstrated the ability to generate specific CD4 T activated cells after spike proteins stimulation. After the third dose of vaccine, abatacept-treated patients acquired the ability to produce a strong antibody response, showing an anti-S titer significantly higher compared to that obtained after the second dose (p = 0.0047), and comparable with the anti-S titer of the other groups. Conclusions Patients treated with abatacept showed an impaired humoral immune response to two doses of COVID-19 vaccine. The third vaccine dose has been demonstrated to be useful to induce a more robust antibody response to balance an impaired T cell-mediated one. All patients, exposed to different immunosuppressive drugs, were able to produce specific CD4-activated T cells, after spike proteins stimulation. Trial registration Local Ethical Committee NP4187.

Published
2023
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26. Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies

Author

Mégane Brusson, Anne Chalumeau, Pierre Martinucci, Oriana Romano, Tristan Felix, Valentina Poletti, Samantha Scaramuzza, Sophie Ramadier, Cecile Masson, Giuliana Ferrari, Fulvio Mavilio, Marina Cavazzana, Mario Amendola, and Annarita Miccio

Subjects
MT: Non-coding RNAs, sickle cell disease, lentiviral vectors, gene silencing, gene therapy, microRNA, Therapeutics. Pharmacology, RM1-950
Abstract

Sickle cell disease (SCD) is due to a mutation in the β-globin gene causing production of the toxic sickle hemoglobin (HbS; α2βS2). Transplantation of autologous hematopoietic stem and progenitor cells (HSPCs) transduced with lentiviral vectors (LVs) expressing an anti-sickling β-globin (βAS) is a promising treatment; however, it is only partially effective, and patients still present elevated HbS levels. Here, we developed a bifunctional LV expressing βAS3-globin and an artificial microRNA (amiRNA) specifically downregulating βS-globin expression with the aim of reducing HbS levels and favoring βAS3 incorporation into Hb tetramers. Efficient transduction of SCD HSPCs by the bifunctional LV led to a substantial decrease of βS-globin transcripts in HSPC-derived erythroid cells, a significant reduction of HbS+ red cells, and effective correction of the sickling phenotype, outperforming βAS gene addition and BCL11A gene silencing strategies. The bifunctional LV showed a standard integration profile, and neither HSPC viability, engraftment, and multilineage differentiation nor the erythroid transcriptome and miRNAome were affected by the treatment, confirming the safety of this therapeutic strategy. In conclusion, the combination of gene addition and gene silencing strategies can improve the efficacy of current LV-based therapeutic approaches without increasing the mutagenic vector load, thus representing a novel treatment for SCD.

Published
2023
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28. Diagnostic data integration using deep neural networks for real-time plasma analysis

Author

Garola, A. Rigoni, Cavazzana, R., Gobbin, M., Delogu, R. S., Manduchi, G., Taliercio, C., and Luchetta, A.

Subjects
Physics - Computational Physics, Computer Science - Machine Learning, Nonlinear Sciences - Adaptation and Self-Organizing Systems, 60G35, I.2.1
Abstract

Recent advances in acquisition equipment is providing experiments with growing amounts of precise yet affordable sensors. At the same time an improved computational power, coming from new hardware resources (GPU, FPGA, ACAP), has been made available at relatively low costs. This led us to explore the possibility of completely renewing the chain of acquisition for a fusion experiment, where many high-rate sources of data, coming from different diagnostics, can be combined in a wide framework of algorithms. If on one hand adding new data sources with different diagnostics enriches our knowledge about physical aspects, on the other hand the dimensions of the overall model grow, making relations among variables more and more opaque. A new approach for the integration of such heterogeneous diagnostics, based on composition of deep variational autoencoders, could ease this problem, acting as a structural sparse regularizer. This has been applied to RFX-mod experiment data, integrating the soft X-ray linear images of plasma temperature with the magnetic state. However to ensure a real-time signal analysis, those algorithmic techniques must be adapted to run in well suited hardware. In particular it is shown that, attempting a quantization of neurons transfer functions, such models can be modified to create an embedded firmware. This firmware, approximating the deep inference model to a set of simple operations, fits well with the simple logic units that are largely abundant in FPGAs. This is the key factor that permits the use of affordable hardware with complex deep neural topology and operates them in real-time., Comment: Proceeding of the 22nd IEEE Real Time Conference

Published
2020
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29. Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase

Author

Clodoveo Ferri, Vincenzo Raimondo, Dilia Giuggioli, Laura Gragnani, Serena Lorini, Lorenzo Dagna, Silvia Laura Bosello, Rosario Foti, Valeria Riccieri, Serena Guiducci, Giovanna Cuomo, Antonio Tavoni, Rossella De Angelis, Fabio Cacciapaglia, Elisabetta Zanatta, Franco Cozzi, Giuseppe Murdaca, Ilaria Cavazzana, Nicoletta Romeo, Veronica Codullo, Roberta Pellegrini, Giuseppe Varcasia, Maria De Santis, Carlo Selmi, Giuseppina Abignano, Maurizio Caminiti, Massimo L'Andolina, Domenico Olivo, Ennio Lubrano, Amelia Spinella, Federica Lumetti, Giacomo De Luca, Piero Ruscitti, Teresa Urraro, Marcella Visentini, Silvia Bellando-Randone, Elisa Visalli, Davide Testa, Gabriella Sciascia, Francesco Masini, Greta Pellegrino, Francesca Saccon, Eugenia Balestri, Giusy Elia, Silvia Martina Ferrari, Antonio Tonutti, Francesca Dall’Ara, Giuseppa Pagano Mariano, Giorgio Pettiti, Giovanni Zanframundo, Raffaele Brittelli, Vincenzo Aiello, Ylenia Dal Bosco, Roberta Foti, Ilenia Di Cola, Daniela Scorpiniti, Enrico Fusaro, Tommaso Ferrari, Pietro Gigliotti, Corrado Campochiaro, Francesca Francioso, Carlo Iandoli, Virginia Caira, Anna Linda Zignego, Salvatore D'Angelo, Franco Franceschini, Marco Matucci-Cerinic, Roberto Giacomelli, Andrea Doria, Stefano Angelo Santini, Poupak Fallahi, Florenzo Iannone, and Alessandro Antonelli

Subjects
COVID-19, SARS-CoV-2, Systemic sclerosis, Scleroderma, Interstitial lung disease, COVID-19 vaccine, Immunologic diseases. Allergy, RC581-607
Abstract

Introduction: The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p

Published
2023
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31. Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study

Author

Tani, Chiara, Cardelli, Chiara, Depascale, Roberto, Gamba, Anna, Iaccarino, Luca, Doria, Andrea, Bandeira, Matilde, Dinis, Sara Paiva, Romão, Vasco C., Gotelli, Emanuele, Paolino, Sabrina, Cutolo, Maurizio, Di Giosaffatte, Niccolò, Ferraris, Alessandro, Grammatico, Paola, Cavagna, Lorenzo, Codullo, Veronica, Montecucco, Carlomaurizio, Longo, Valentina, Beretta, Lorenzo, Cavazzana, Ilaria, Fredi, Micaela, Peretti, Silvia, Guiducci, Serena, Matucci-Cerinic, Marco, Bombardieri, Stefano, Burmester, Gerd R., Fonseca, João E., Frank, Charissa, Galetti, Ilaria, Hachulla, Eric, Müller-Ladner, Ulf, Schneider, Matthias, Smith, Vanessa, Tamirou, Farah, Van Laar, Jacob M., Vieira, Ana, D'Urzo, Rossella, Cannizzo, Sara, Gaglioti, Andrea, Marinello, Diana, Talarico, Rosaria, and Mosca, Marta

Published
2023
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32. Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase

Author

Ferri, Clodoveo, Raimondo, Vincenzo, Giuggioli, Dilia, Gragnani, Laura, Lorini, Serena, Dagna, Lorenzo, Bosello, Silvia Laura, Foti, Rosario, Riccieri, Valeria, Guiducci, Serena, Cuomo, Giovanna, Tavoni, Antonio, De Angelis, Rossella, Cacciapaglia, Fabio, Zanatta, Elisabetta, Cozzi, Franco, Murdaca, Giuseppe, Cavazzana, Ilaria, Romeo, Nicoletta, Codullo, Veronica, Pellegrini, Roberta, Varcasia, Giuseppe, De Santis, Maria, Selmi, Carlo, Abignano, Giuseppina, Caminiti, Maurizio, L'Andolina, Massimo, Olivo, Domenico, Lubrano, Ennio, Spinella, Amelia, Lumetti, Federica, De Luca, Giacomo, Ruscitti, Piero, Urraro, Teresa, Visentini, Marcella, Bellando-Randone, Silvia, Visalli, Elisa, Testa, Davide, Sciascia, Gabriella, Masini, Francesco, Pellegrino, Greta, Saccon, Francesca, Balestri, Eugenia, Elia, Giusy, Ferrari, Silvia Martina, Tonutti, Antonio, Dall’Ara, Francesca, Pagano Mariano, Giuseppa, Pettiti, Giorgio, Zanframundo, Giovanni, Brittelli, Raffaele, Aiello, Vincenzo, Dal Bosco, Ylenia, Foti, Roberta, Di Cola, Ilenia, Scorpiniti, Daniela, Fusaro, Enrico, Ferrari, Tommaso, Gigliotti, Pietro, Campochiaro, Corrado, Francioso, Francesca, Iandoli, Carlo, Caira, Virginia, Zignego, Anna Linda, D'Angelo, Salvatore, Franceschini, Franco, Matucci-Cerinic, Marco, Giacomelli, Roberto, Doria, Andrea, Santini, Stefano Angelo, Fallahi, Poupak, Iannone, Florenzo, and Antonelli, Alessandro

Published
2023
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33. Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer

Author

Martini Leonardo, De Luca Filomena, Valsuani Chiara, Tartarelli Gianna, Puccetti Cheti, Siclari Olimpia, Viacava Paolo, Donati Sara, Camerini Andrea, Cavazzana Andrea, and Amoroso Domenico

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer. Methods HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors. Results Median time to progression and overall survival were 9 (range 2 - 54) and 20 (range 3 - 101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p = 0.05) and higher stage (p = 0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53 ± 10.21 vs 2.50 ± 4.12, p = 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p = 0.046). p53 expression was only associated with higher stage disease (p = 0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter. Conclusion Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.

Published
2011
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35. Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Author

Seidel, Markus G., Seppänen, Mikko R.J., Gennery, Andrew, Kanariou, Maria G., Tantou, Sofia, Grigoriadou, Sofia, Cericola, Gabriella, Hanitsch, Leif G., Scheibenbogen, Carmen, Hlaváčková, Eva O., Krivan, Gergely, McGuire, Frances K., Leahy, Timothy Ronan, Edgar, John David M., Bakhtiar, Shahrzad, Bader, Peter, Rohner, Geraldine Blanchard, Haerynck, Filomeen, Claes, Karlien, Lehmberg, Kai, Müller, Ingo, Farmand, Susan, Fasshauer, Maria, Graf, Dagmar, Neves, Joao Farela, Kostyuchenko, Larysa, Gonzalez-Granado, Luis Ignacio, Jeseňák, Miloš, Carrabba, Maria, Fabio, Giovanna, Pignata, Claudio, Giardino, Giuliana, Karadağ, Ilknur Kökçü, Yıldıran, Alişan, Hancioglu, Gonca, Králíčková, Pavlína, Steinmann, Sandra, Pietrucha, Barbara Maria, Gernert, Michael, Soomann, Maarja, Witte, Torsten, Markocsy, Adam, Wolska-Kusnierz, Beata, Randrianomenjanahary, Philippe, Rouger, Jérémie, Kostaridou, Stavroula, Zabara, Dariia V., Rodina, Yulia A., Shvets, Oksana A., Maccari, Maria Elena, Wolkewitz, Martin, Schwab, Charlotte, Lorenzini, Tiziana, Leiding, Jennifer W., Aladjdi, Nathalie, Abolhassani, Hassan, Abou-Chahla, Wadih, Aiuti, Alessandro, Azarnoush, Saba, Baris, Safa, Barlogis, Vincent, Barzaghi, Federica, Baumann, Ulrich, Bloomfield, Marketa, Bohynikova, Nadezda, Bodet, Damien, Boutboul, David, Bucciol, Giorgia, Buckland, Matthew S., Burns, Siobhan O., Cancrini, Caterina, Cathébras, Pascal, Cavazzana, Marina, Cheminant, Morgane, Chinello, Matteo, Ciznar, Peter, Coulter, Tanya I., D’Aveni, Maud, Ekwall, Olov, Eric, Zelimir, Eren, Efrem, Fasth, Anders, Frange, Pierre, Fournier, Benjamin, Garcia-Prat, Marina, Gardembas, Martine, Geier, Christoph, Ghosh, Sujal, Goda, Vera, Hammarström, Lennart, Hauck, Fabian, Heeg, Maximilian, Heropolitanska-Pliszka, Edyta, Hilfanova, Anna, Jolles, Stephen, Karakoc-Aydiner, Elif, Kindle, Gerhard R., Kiykim, Ayca, Klemann, Christian, Koletsi, Patra, Koltan, Sylwia, Kondratenko, Irina, Körholz, Julia, Krüger, Renate, Jeziorski, Eric, Levy, Romain, Le Guenno, Guillaume, Lefevre, Guillaume, Lougaris, Vassilios, Marzollo, Antonio, Mahlaoui, Nizar, Malphettes, Marion, Meinhardt, Andrea, Merlin, Etienne, Meyts, Isabelle, Milota, Tomas, Moreira, Fernando, Moshous, Despina, Mukhina, Anna, Neth, Olaf, Neubert, Jennifer, Neven, Benedicte, Nieters, Alexandra, Nove-Josserand, Raphaele, Oksenhendler, Eric, Ozen, Ahmet, Olbrich, Peter, Perlat, Antoinette, Pac, Malgorzata, Schmid, Jana Pachlopnik, Pacillo, Lucia, Parra-Martinez, Alba, Paschenko, Olga, Pellier, Isabelle, Sefer, Asena Pinar, Plebani, Alessandro, Plantaz, Dominique, Prader, Seraina, Raffray, Loic, Ritterbusch, Henrike, Riviere, Jacques G., Rivalta, Beatrice, Rusch, Stephan, Sakovich, Inga, Savic, Sinisa, Scheible, Raphael, Schleinitz, Nicolas, Schuetz, Catharina, Schulz, Ansgar, Sediva, Anna, Semeraro, Michaela, Sharapova, Svetlana O., Shcherbina, Anna, Slatter, Mary A., Sogkas, Georgios, Soler-Palacin, Pere, Speckmann, Carsten, Stephan, Jean-Louis, Suarez, Felipe, Tommasini, Alberto, Trück, Johannes, Uhlmann, Annette, van Aerde, Koen J., van Montfrans, Joris, von Bernuth, Horst, Warnatz, Klaus, Williams, Tony, Worth, Austen J.J., Ip, Winnie, Picard, Capucine, Catherinot, Emilie, Nademi, Zohreh, Grimbacher, Bodo, Forbes Satter, Lisa R., Kracker, Sven, Chandra, Anita, Condliffe, Alison M., and Ehl, Stephan

Published
2023
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36. The new vessel complex for the RFX-mod2 experiment: An effective synergy between fusion research and technological development

Author

Peruzzo, Simone, Aprile, Daniele, Dalla Palma, Mauro, Pavei, Mauro, Rizzetto, Dario, Rizzolo, Andrea, Abate, Domenico, Agostinetti, Piero, Agostini, Matteo, Andreani, Roberto, Anselmi, Fabrizio, Battistin, Flavio, Bernardi, Adriano, Bernardi, Marco, Berton, Giovanni, Bettini, Paolo, Bigi, Marco Angelo, Bonotto, Matteo, Brombin, Matteo, Canton, Alessandra, Carraro, Lorella, Cavazzana, Roberto, Cordaro, Luigi, Corniani, Giorgio, Dal Bello, Samuele, De Lorenzi, Antonio, De Masi, Gianluca, Degli Agostini, Fabio, Franchin, Luca, Franz, Paolo, Gambetta, Giulio, Gnesotto, Francesco, Grando, Luca, Innocente, Paolo, Laterza, Bruno, Lotto, Luca, Manfrin, Stefano, Marchiori, Giuseppe, Marconato, Nicolò, Marcuzzi, Diego, Marrelli, Lionello, Martines, Emilio, Moresco, Maurizio, Novella, Alberto, Piovan, Roberto, Pomaro, Nicola, Rossetto, Federico, Siragusa, Marco, Sonato, Piergiorgio, Spagnolo, Silvia, Spolaore, Monica, Taliercio, Cesare, Terranova, David, Tiso, Andrea, Trevisan, Lauro, Valente, Matteo, Valisa, Marco, Zaupa, Matteo, and Zuin, Matteo

Published
2023
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39. An Italian Multicenter Study on Anti-NXP2 Antibodies: Clinical and Serological Associations

Author

Fredi, Micaela, Cavazzana, Ilaria, Ceribelli, Angela, Cavagna, Lorenzo, Barsotti, Simone, Bartoloni, Elena, Benucci, Maurizio, De Stefano, Ludovico, Doria, Andrea, Emmi, Giacomo, Fabris, Martina, Fornaro, Marco, Furini, Federica, Giudizi, Maria Grazia, Govoni, Marcello, Ghirardello, Anna, Iaccarino, Luca, Iannone, Fiorenzo, Infantino, Maria, Isailovic, Natasa, Lazzaroni, Maria Grazia, Manfredi, Mariangela, Mathieu, Alessandro, Marasco, Emiliano, Migliorini, Paola, Montecucco, Carlomaurizio, Palterer, Boaz, Parronchi, Paola, Piga, Matteo, Pratesi, Federico, Riccieri, Valeria, Selmi, Carlo, Tampoia, Marilina, Tripoli, Alessandra, Zanframundo, Giovanni, Radice, Antonella, Gerli, Roberto, and Franceschini, Franco

Published
2022
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40. Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population

Author

Masala, Carla, Cavazzana, Annachiara, Sanna, Fabrizio, Cecchini, Maria Paola, Zanini, Alice, Gasperi, Flavia, Menghi, Leonardo, Endrizzi, Isabella, Borgogno, Monica, Drago, Serena, Cantone, Elena, Ciofalo, Andrea, Macchi, Alberto, Monti, Giulia, Parma, Valentina, Piochi, Maria, Pinna, Ilenia, Torri, Luisa, Cabrino, Giorgia, Ottaviano, Giancarlo, Pendolino, Alfonso Luca, Pignatelli, Angela, Pighin, Faride, Bochicchio, Vincenzo, Motta, Gaetano, Fontana, Giorgia, Pasquariello, Benedetta, Cavaliere, Carlo, Iacono, Valentina, and Hummel, Thomas

Published
2022
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41. RFX-mod2 diagnostic capability enhancements for the exploration of multi-magnetic-configurations

Author

Carraro, L, Zuin, M, Abate, D, Agostinetti, P, Agostini, M, Aprile, D, Barbisan, M, Belpane, A, Berton, G, Bonotto, M, Brombin, M, Cavazzana, R, Cinnirella, L, Ciufo, S, Croci, G, Cordaro, L, D'Isa, F, Dal Bello, S, Dal Molin, A, De Masi, G, Emma, G, Fadone, M, Fassina, A, Fiorucci, D, Franz, P, Grando, L, Guiotto, F, La Matina, M, Marchiori, G, Marconato, N, Mario, I, Marrelli, L, Milazzo, R, Molisani, S, Moresco, M, Muraro, A, Perelli Cippo, E, Peruzzo, S, Porcu, P, Pomaro, N, Puiatti, M, Putignano, O, Rigamonti, D, Rigoni Garola, A, Rizzolo, A, Ruffini, F, Scarin, P, Spagnolo, S, Spolaore, M, Taliercio, C, Tardocchi, M, Terranova, D, Ugoletti, M, Valisa, M, Vianello, N, Zaniol, B, Carraro L., Zuin M., Abate D., Agostinetti P., Agostini M., Aprile D., Barbisan M., Belpane A., Berton G., Bonotto M., Brombin M., Cavazzana R., Cinnirella L., Ciufo S., Croci G., Cordaro L., D'Isa F., Dal Bello S., Dal Molin A., De Masi G., Emma G., Fadone M., Fassina A., Fiorucci D., Franz P., Grando L., Guiotto F., La Matina M., Marchiori G., Marconato N., Mario I., Marrelli L., Milazzo R., Molisani S., Moresco M., Muraro A., Perelli Cippo E., Peruzzo S., Porcu P., Pomaro N., Puiatti M. E., Putignano O., Rigamonti D., Rigoni Garola A., Rizzolo A., Ruffini F., Scarin P., Spagnolo S., Spolaore M., Taliercio C., Tardocchi M., Terranova D., Ugoletti M., Valisa M., Vianello N., Zaniol B., Carraro, L, Zuin, M, Abate, D, Agostinetti, P, Agostini, M, Aprile, D, Barbisan, M, Belpane, A, Berton, G, Bonotto, M, Brombin, M, Cavazzana, R, Cinnirella, L, Ciufo, S, Croci, G, Cordaro, L, D'Isa, F, Dal Bello, S, Dal Molin, A, De Masi, G, Emma, G, Fadone, M, Fassina, A, Fiorucci, D, Franz, P, Grando, L, Guiotto, F, La Matina, M, Marchiori, G, Marconato, N, Mario, I, Marrelli, L, Milazzo, R, Molisani, S, Moresco, M, Muraro, A, Perelli Cippo, E, Peruzzo, S, Porcu, P, Pomaro, N, Puiatti, M, Putignano, O, Rigamonti, D, Rigoni Garola, A, Rizzolo, A, Ruffini, F, Scarin, P, Spagnolo, S, Spolaore, M, Taliercio, C, Tardocchi, M, Terranova, D, Ugoletti, M, Valisa, M, Vianello, N, Zaniol, B, Carraro L., Zuin M., Abate D., Agostinetti P., Agostini M., Aprile D., Barbisan M., Belpane A., Berton G., Bonotto M., Brombin M., Cavazzana R., Cinnirella L., Ciufo S., Croci G., Cordaro L., D'Isa F., Dal Bello S., Dal Molin A., De Masi G., Emma G., Fadone M., Fassina A., Fiorucci D., Franz P., Grando L., Guiotto F., La Matina M., Marchiori G., Marconato N., Mario I., Marrelli L., Milazzo R., Molisani S., Moresco M., Muraro A., Perelli Cippo E., Peruzzo S., Porcu P., Pomaro N., Puiatti M. E., Putignano O., Rigamonti D., Rigoni Garola A., Rizzolo A., Ruffini F., Scarin P., Spagnolo S., Spolaore M., Taliercio C., Tardocchi M., Terranova D., Ugoletti M., Valisa M., Vianello N., and Zaniol B.

Abstract

The RFX-mod2 device, the upgraded version of the previous RFX-mod with a modified magnetic boundary, is presently under realization and will start to be operated in 2025. Significant upgrades of the diagnostic capabilities have been proposed and are under development. These include a largely increased number of in-vessel magnetic and electrostatic sensors, a new fast reciprocating manipulator for the exploration of the edge plasma in a wide range of experimental conditions, the improved Thomson scattering and soft x-ray diagnostics system for a detailed determination of the behavior of the electron temperature profile, new dedicated systems for the space and time resolved analysis of x-ray spectra and neutron rate, a reflectometric diagnostic for real-time determination of plasma position, two diagnostics devoted to the imaging of light impurities and influxes behavior along with arrays of halo current sensors. These diagnostic upgrades will be accompanied by a significant effort to improve the control of the electron density and of the impurity influxes by means of proper treatment of plasma facing components with in-vessel fixed electrodes distributed over the first wall. The described advancements will allow a deeper understanding of physics phenomena in the wide variety of magnetic configurations, including the tokamak, the reversed-field pinch and the Ultra-low q, which can be produced in RFX-mod2 thanks to its flexibility and unique MHD control capabilities.

Published
2024

42. Ambulatori multidisciplinari

Author

Lupi, E, Carugno, A, Cavazzana, I, Ceruti, P, Chiara Gerardi, M, Benedetti, S, Elide Lupi, Andrea Carugno, Ilaria Cavazzana, Paolo Ceruti, Maria Chiara Gerardi, Sara Benedetti, Lupi, E, Carugno, A, Cavazzana, I, Ceruti, P, Chiara Gerardi, M, Benedetti, S, Elide Lupi, Andrea Carugno, Ilaria Cavazzana, Paolo Ceruti, Maria Chiara Gerardi, and Sara Benedetti

Published
2024

43. Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy

Author

Sobrino, Steicy, Magnani, Alessandra, Semeraro, Michaela, Martignetti, Loredana, Cortal, Akira, Denis, Adeline, Couzin, Chloé, Picard, Capucine, Bustamante, Jacinta, Magrin, Elisa, Joseph, Laure, Roudaut, Cécile, Gabrion, Aurélie, Soheili, Tayebeh, Cordier, Corinne, Lortholary, Olivier, Lefrere, François, Rieux-Laucat, Frédéric, Casanova, Jean-Laurent, Bodard, Sylvain, Boddaert, Nathalie, Thrasher, Adrian J., Touzot, Fabien, Taque, Sophie, Suarez, Felipe, Marcais, Ambroise, Guilloux, Agathe, Lagresle-Peyrou, Chantal, Galy, Anne, Rausell, Antonio, Blanche, Stephane, Cavazzana, Marina, and Six, Emmanuelle

Published
2023
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44. Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT

Author

Schuetz, C., Gerke, J., Ege, M., Walter, J., Kusters, M., Worth, A., Kanakry, J. A., Dimitrova, D., Wolska-Kuśnierz, B., Chen, K., Unal, E., Karakukcu, M., Pashchenko, O., Leiding, J., Kawai, T., Amrolia, P. J., Berghuis, D., Buechner, J., Buchbinder, D., Cowan, M. J., Gennery, A. R., Güngör, T., Heimall, J., Miano, M., Meyts, I., Morris, E. C., Rivière, J., Sharapova, S. O., Shaw, P. J., Slatter, M., Honig, M., Veys, P., Fischer, A., Cavazzana, M., Moshous, D., Schulz, A., Albert, M. H., Puck, J. M., Lankester, A. C., Notarangelo, L. D., and Neven, B.

Published
2023
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45. Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression

Author

Panagiotis Antoniou, Giulia Hardouin, Pierre Martinucci, Giacomo Frati, Tristan Felix, Anne Chalumeau, Letizia Fontana, Jeanne Martin, Cecile Masson, Megane Brusson, Giulia Maule, Marion Rosello, Carine Giovannangeli, Vincent Abramowski, Jean-Pierre de Villartay, Jean-Paul Concordet, Filippo Del Bene, Wassim El Nemer, Mario Amendola, Marina Cavazzana, Anna Cereseto, Oriana Romano, and Annarita Miccio

Subjects
Science
Abstract

Antoniou and colleagues used base editing to generate a variety of mutations inducing γ-globin and rescue the β-hemoglobinopathy phenotype. This strategy was safe and effective in long-term repopulating hematopoietic stem/progenitor cells.

Published
2022
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46. Autoantibody status according to multiparametric assay accurately estimates connective tissue disease classification and identifies clinically relevant disease clusters

Author

Micaela Fredi, Nicola Bizzaro, Margherita Zen, Chiara Baldini, Ilaria Cavazzana, Roberto Giacomelli, Valeria Riccieri, Marco Fornaro, Franco Franceschini, Roberto Gerli, Anna Ghirardello, Paola Migliorini, Maurizio Benucci, Maria Infantino, Mariangela Manfredi, Elena Bartoloni, Antonella Fioravanti, Amelia Rigon, Silvia Piantoni, Onelia Bistoni, Francesca Bellisai, Carlo Perricone, Giacomo Cafaro, Danilo Villalta, Stefania Masneri, Paola Parronchi, Boaz Palterer, Stefania Del Rosso, Fabiana Topini, Manuela Sebastiano, Emirena Garrafa, Sara Cheleschi, Maria-Romana Bacarelli, Marilina Tampoia, Daniele Cammelli, Luisa Arcarese, Patrizia Rovere Querini, and Valentina Canti

Subjects
Medicine
Abstract

Objective Assessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential clinical manifestations. The purpose of this study was to evaluate the ability of multiparametric assay to correctly classify patients with multiple CTDs and healthy controls (HC), independent of clinical features, and to evaluate whether serological status could identify clusters of patients with similar clinical features.Methods Patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SjS), undifferentiated connective tissue disease (UCTD), idiopathic inflammatory myopathies (IIM) and HC were enrolled. Serum was tested for 29 autoantibodies. An XGBoost model, exclusively based on autoantibody titres was built and classification accuracy was evaluated. A hierarchical clustering model was subsequently developed and clinical/laboratory features compared among clusters.Results 908 subjects were enrolled. The classification model showed a mean accuracy of 60.84±4.05% and a mean area under the receiver operator characteristic curve of 88.99±2.50%, with significant discrepancies among groups. Cluster analysis identified four clusters (CL). CL1 included patients with typical features of SLE. CL2 included most patients with SjS, along with some SLE and UCTD patients with SjS-like features. CL4 included anti-Jo1 patients only. CL3 was the largest and most heterogeneous, including all the remaining subjects, overall characterised by low titre or lower-prevalence autoantibodies.Conclusion Extended multiparametric autoantibody assay allowed an accurate classification of CTD patients, independently of clinical features. Clustering according to autoantibody titres is able to identify clusters of CTD subjects with similar clinical features, independently of their final diagnosis.

Published
2023
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49. P1257: SMART101 DONOR T-LYMPHOID PROGENITORS TO ACCELERATE IMMUNE RECONSTITUTION POST-HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTATION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE: SI101-02 PHASE I/II

Author

Fabio Ciceri, Régis Peffault de Latour, Raynier Devillier, Patrizia Chiusolo, Aurelie Bauquet, Laura Simons, Pierre Heimendinger, Pierre Gaudeaux, Olivier Negre, Tayebeh-Shabi Soheili, Juliette Paillet, Isabelle Andre, Sebastien Oster, Marina Cavazzana, and Frederic Lehmann

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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50. P1403: SI101-01 PHASE I/II STUDY EVALUATING SAFETY AND EFFICACY OF ALLOGENEIC SMART101 T-LYMPHOID PROGENITOR INJECTION TO ACCELERATE IMMUNE RECONSTITUTION AFTER T-CELL DEPLETED ALLOGENEIC HSCT

Author

Jaap Jan Boelens, Muhammad Umair Mushtaq, Joseph Mcguirk, Aurelie Bauquet, Laura Simons, Pierre Heimendinger, Pierre Gaudeaux, Isabelle Andre, Juliette Paillet, Olivier Negre, Tayebeh-Shabi Soheili, Sebastien Oster, Marcel R.M. van den Brink, Frederic Lehmann, Marina Cavazzana, and Miguel-Angel Perales

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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