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1. Proteomics reveals specific biological changes induced by the normothermic machine perfusion of donor kidneys with a significant up-regulation of Latexin

Author

Zaza, G, Neri, F, Bruschi, M, Granata, S, Petretto, A, Bartolucci, M, di Bella, C, Candiano, G, Stallone, G, Gesualdo, L, Furian, L, Zaza, G, Neri, F, Bruschi, M, Granata, S, Petretto, A, Bartolucci, M, di Bella, C, Candiano, G, Stallone, G, Gesualdo, L, and Furian, L

Abstract

Renal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35–37 °C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, its biological effects on marginal kidneys are unclear. We therefore used mass spectrometry to determine the proteomic profile of kidney tissue and urine from eight organs reconditioned for 120 min using a Kidney Assist device. Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine samples were collected at T0 (urine produced in the first 15 min after the beginning of normothermic reperfusion), T30, T60 and T120. Multiple algorithms, support vector machine learning and partial least squares discriminant analysis were used to select the most discriminative proteins during NMP. Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 during NMP. Machine learning algorithms identified the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1 and F9) in the kidney and urine after NMP. Latexin (LXN), an endogenous carboxypeptidase inhibitor, resulted the most-upregulated protein at T120, and this result was confirmed by ELISA. In addition, functional analysis revealed that the most strongly upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins represented the complement system and coagulation cascade. Our proteomic analysis demonstrated that even brief periods of NMP induce remarkable metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic.

Published
2023

2. The ELIMED transport and dosimetry beamline for laser-driven ion beams

Author

Romano, F., Schillaci, F., Cirrone, G.A.P., Cuttone, G., Scuderi, V., Allegra, L., Amato, A., Amico, A., Candiano, G., De Luca, G., Gallo, G., Giordanengo, S., Guarachi, L. Fanola, Korn, G., Larosa, G., Leanza, R., Manna, R., Marchese, V., Marchetto, F., Margarone, D., Milluzzo, G., Petringa, G., Pipek, J., Pulvirenti, S., Rizzo, D., Sacchi, R., Salamone, S., Sedita, M., and Vignati, A.

Published
2016
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4. Evidence for charge-based mimicry in anti dsDNA antibody generation

Author

Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, Ghiggeri, G, Bruschi, Maurizio, Angeletti, Andrea, Kajana, Xhuliana, Moroni, Gabriella, Sinico, Renato Alberto, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe Alvise, Esposito, Pasquale, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Verrina, Enrico, Franceschini, Franco, Ravelli, Angelo, Prunotto, Marco, Meroni, Pier Luigi, Ghiggeri, Gian Marco, Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, Ghiggeri, G, Bruschi, Maurizio, Angeletti, Andrea, Kajana, Xhuliana, Moroni, Gabriella, Sinico, Renato Alberto, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe Alvise, Esposito, Pasquale, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Verrina, Enrico, Franceschini, Franco, Ravelli, Angelo, Prunotto, Marco, Meroni, Pier Luigi, and Ghiggeri, Gian Marco

Abstract

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation.

Published
2022

5. Towards a proton imaging system

Author

Civinini, C., Brianzi, M., Bruzzi, M., Bucciolini, M., Candiano, G., Capineri, L., Cirrone, G.A.P., Cuttone, G., Lo Presti, D., Marrazzo, L., Mazzaglia, E., Menichelli, D., Pieri, S., Randazzo, N., Sipala, V., Stancampiano, C., Talamonti, C., Tesi, M., and Valentini, S.

Published
2010
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6. Neutrophil Extracellular Traps (NETs) profiles in patients with incident SLE and lupus nephritis

Author

Bruschi, M, Bonanni, A, Petretto, A, Vaglio, A, Pratesi, F, Santucci, L, Migliorini, P, Bertelli, R, Galetti, M, Belletti, S, Cavagna, L, Moroni, G, Franceschini, F, Fredi, M, Pazzola, G, Allegri, L, Sinico, Ra, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, Ga, Ramoino, P, Bianchini, P, Puppo, F, Pupo, F, Negrini, S, Mattana, F, Emmi, G, Garibotto, G, Santoro, D, Scolari, F, Ravelli, A, Tincani, A, Cravedi, P, Volpi, S, Candiano, G, Ghiggeri, Gm, Bruschi, M, Bonanni, A, Petretto, A, Vaglio, A, Pratesi, F, Santucci, L, Migliorini, P, Bertelli, R, Galetti, M, Belletti, S, Cavagna, L, Moroni, G, Franceschini, F, Fredi, M, Pazzola, G, Allegri, L, Sinico, R, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Ramoino, P, Bianchini, P, Puppo, F, Pupo, F, Negrini, S, Mattana, F, Emmi, G, Garibotto, G, Santoro, D, Scolari, F, Ravelli, A, Tincani, A, Cravedi, P, Volpi, S, Candiano, G, and Ghiggeri, G

Subjects
lupus nephritis, Systemic Lupus Erythematosus (SLE), Neutrophil Extracellular Traps (NETs)
Abstract

Objective. Neutrophil extracellular traps (NET) expose modified antigens for autoantibodies in vasculitis. Little is known about levels and removal pathways of NET in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). We determined circulating levels and defined NET removal in large subsets of patients with incident SLE (iSLE), some of whom had new-onset nephritis. Methods. Serum levels of NET (ELISA), DNase1/DNase1L3 (ELISA), and DNase activity (functional assay) were determined in 216 patients with iSLE [103 had incident LN (iLN)], in 50 patients with other primary glomerulonephritis, and in healthy controls. Ex vivo NET production by neutrophils purified from a random selection of patients was quantified as elastase/DNA release and by immunofluorescence techniques. Results. Serum NET levels were very high in iSLE/iLN compared to all groups of controls and correlated with anti-dsDNA, C3-C4, and proteinuria; iLN had the highest levels. DNase activity was decreased in iLN compared to SLE (20% had one-half DNase activity) despite similar serum levels of DNase1/DNase1L3. In these cases, pretreatment of serum with protein A restored DNase efficiency; 1 patient was homozygous for a c.289_290delAC variant of DNASE1L3. Ex vivo NET production by neutrophils purified from LN, SLE, and normal controls was similar in all cases. Conclusion. Patients with iLN have increased circulating NET and reduced DNase activity, the latter being explained by the presence of inhibitory substances in circulation and/or by rare DNase1L3 mutations. Accumulation of NET derives from a multifactorial mechanism, and is associated and may contribute to disease severity in SLE, in particular to renal lesions. (Clinical trial registration: The Zeus study was registered at ClinicalTrials.gov, study number NCT02403115).

Published
2020

9. Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study

Author

Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, Ghiggeri, Gian Marco, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

Objectives: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Published
2021

10. Second wave antibodies in autoimmune renal diseases: The case of lupus nephritis

Author

Angeletti, A, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Ravelli, A, Ghiggeri, G, Angeletti, Andrea, Bruschi, Maurizio, Moroni, Gabriela, Sinico, Renato, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Ravelli, Angelo, Ghiggeri, Gian Marco, Angeletti, A, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Ravelli, A, Ghiggeri, G, Angeletti, Andrea, Bruschi, Maurizio, Moroni, Gabriela, Sinico, Renato, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

Clinical Trial registry name and registration number: Zeus study, NCT02403115

Published
2021

11. Neutrophil Extracellular Traps in the Autoimmunity Context

Author

Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Trezzi, B, Emmi, G, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Manfredi, Angelo, Ramirez, Giuseppe A., Esposito, Pasquale, Negrini, Simone, Trezzi, Barbara, Emmi, Giacomo, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, Ghiggeri, Gian Marco, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Trezzi, B, Emmi, G, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Manfredi, Angelo, Ramirez, Giuseppe A., Esposito, Pasquale, Negrini, Simone, Trezzi, Barbara, Emmi, Giacomo, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. NETs are composed of either DNA or nucleosome proteins and hundreds of cytoplasm proteins, a part of which undergo post-translational modification during the steps leading to NETs. There is a thin balance between the production and the removal of circulating NETs from blood where digestion of DNA by circulating DNases 1 and IL3 has a critical role. A delay in NET removal may have consequences for autoimmunity. Recent studies have shown that circulating NET levels are increased in systemic lupus erythematosus (SLE) for a functional block of NET removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations. In SLE, the persistence in circulation of NETs signifies elevated concentrations of either free DNA/nucleosome components and oxidized proteins that, in some cases, are recognized as non-self and presented to B-cells by Toll-like receptor 9 (TLR9). In this way, it is activated as an immunologic response, leading to the formation of IgG2 auto-antibody. Monitoring serum NET levels represents a potential new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NET formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE. Clinical Trial Registration Number: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Published
2021

12. Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis

Author

Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Volpi, S, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela&nbsp, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello&nbsp, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Mosca, Marta, Tincani, Angela&nbsp, Candiano, Giovanni, Prunotto, Marco, Volpi, Stefano, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, Ghiggeri, Gian Marco, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Volpi, S, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela&nbsp, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello&nbsp, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Mosca, Marta, Tincani, Angela&nbsp, Candiano, Giovanni, Prunotto, Marco, Volpi, Stefano, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

Objectives: Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods: A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. Results: The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion: Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration: The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

Published
2021

14. Serum IgG2 antibody multi composition in systemic lupus erythematosus and in lupus nephritis

Author

Bruschi, M, Moroni, G, Sinico, Ra, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, Ga, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, and Ghiggeri, Gm.

Published
2020

15. The Italian project for a proton imaging device

Author

Cirrone, G.A.P., Candiano, G., Cuttone, G., Lo Nigro, S., Lo Presti, D., Randazzo, N., Sipala, V., Russo, M., Aiello, S., Bruzzi, M., Menichelli, D., Scaringella, M., Miglio, S., Bucciolini, M., Talamonti, C., and Pallotta, S.

Published
2007
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26. 314. A multi-centre study to evaluate physical acceptance reference values, tolerances and action levels for a new PET/CT scanner

Author

Sardina, D., primary, Politi, G., additional, Abbate, B., additional, Gallias, K.K., additional, Caputo, V., additional, Brogna, A., additional, Candiano, G., additional, Piraneo, S., additional, De Vincolis, R., additional, Rabito, A., additional, Pedalino, A., additional, Occhipinti, A., additional, and Di Rosa, F., additional

Published
2018
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33. Monte Carlo application based on GEANT4 toolkit to simulate a laser-plasma electron beam line for radiobiological studies

Author

Lamia, D, Russo, G, Casarino, C, Gagliano, L, Candiano, G, Labate, L, Baffigi, F, Fulgentini, L, Giulietti, A, Koester, P, Palla, D, Gizzi, L, Gilardi, M, Lamia D., Russo G., Casarino C., Gagliano L., Candiano G. C., Labate L., Baffigi F., Fulgentini L., Giulietti A., Koester P., Palla D., Gizzi L. A., Gilardi M. C., Lamia, D, Russo, G, Casarino, C, Gagliano, L, Candiano, G, Labate, L, Baffigi, F, Fulgentini, L, Giulietti, A, Koester, P, Palla, D, Gizzi, L, Gilardi, M, Lamia D., Russo G., Casarino C., Gagliano L., Candiano G. C., Labate L., Baffigi F., Fulgentini L., Giulietti A., Koester P., Palla D., Gizzi L. A., and Gilardi M. C.

Abstract

We report on the development of a Monte Carlo application, based on the GEANT4 toolkit, for the characterization and optimization of electron beams for clinical applications produced by a laser-driven plasma source. The GEANT4 application is conceived so as to represent in the most general way the physical and geometrical features of a typical laser-driven accelerator. It is designed to provide standard dosimetric figures such as percentage dose depth curves, two-dimensional dose distributions and 3D dose profiles at different positions both inside and outside the interaction chamber. The application was validated by comparing its predictions to experimental measurements carried out on a real laser-driven accelerator. The work is aimed at optimizing the source, by using this novel application, for radiobiological studies and, in perspective, for medical applications.

Published
2015

35. Alanine/ESR dosimetry for electron Intra-Operative RadioTherapy: output factor measurements and Monte Carlo-GEANT4 simulations for IORT mobile dedicate accelerator

Author

LONGO, Anna, MARRALE, Maurizio, RUSSO, G, CASARINO, C, CANDIANO, G, GALLO, Salvatore, CARLINO, Antonio, BRAI, Maria, LONGO, A, MARRALE, M, RUSSO, G, CASARINO, C, CANDIANO, G, GALLO, S, CARLINO, A, and BRAI, M

Subjects
Output Factors, IORT, Settore FIS/01 - Fisica Sperimentale, Settore MED/36 - Diagnostica Per Immagini E Radioterapia, GEANT4, Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin), IEORT, ESR
Abstract

Intra-operative radiation therapy (IORT) is a treatment modality where a single high dose of radiation is delivered directly to the tumor bed or to the exposed tumor during the surgical intervention, while avoiding surrounding dose-limiting structures. Mobile electron linear accelerators dedicated to IORT have been manufactured which have promoted a local large diffusion of this radiotherapy modality. For breast irradiation, a single fraction of 21 Gy delivered on the target volume during the surgical procedure is equivalent to the total dosage (60 Gy) usually delivered during 30 external fractionated radiotherapy at 2Gy/fraction. Alternatively, a single dose of 10 Gy can be administered as Intra-Operative Boost to the tumor bed, followed by hypo-fractionated or conventional external beam whole breast radiotherapy. This work reports a comparison between the response of alanine and Markus ionization chamber carried out for measurements of the output factors (OF) of electron beams produced by a linear accelerator used for IORT. Output factors (OF) for conventional high-energy electron beams are normally measured using ionization chamber according to international dosimetry protocols. However, the electron beams used in IORT have characteristics of dose per pulse, energy spectrum and angular distribution quite different from beams usually used in external radiotherapy, so the direct application of international dosimetry protocols may introduce additional uncertainties in dosimetric determinations. The high dose per pulse could lead to an inaccuracy in dose measurements with ionization chamber, due to overestimation of ks recombination factor. Furthermore, the electron fields obtained with IORT-dedicated applicators have a wider energy spectrum and a wider angular distribution than the conventional fields, due to the presence of electrons scattered by the applicator’s wall. For this reason, a dosimetric system should be characterized by a minimum dependence from the beam energy and from angle of incidence of electrons. This become particularly critical for small and bevelled applicators. All of these reasons lead to investigate the use of detectors different from the ionization chamber for measuring the OFs. Furthermore, the complete characterization of the radiation field is achieved also by the use of Monte Carlo Geant4 simulations which allows to obtain detailed information on dose distributions. We compared the output factors obtained by means of alanine dosimeters and Markus ionization chamber. The results are characterized by a good agreement of response of alanine pellets and Markus ionization chamber and Monte Carlo results (within about 3%) for both flat and bevelled applicators.

Published
2015

36. Investigation of applicability of alanine pellets and films for dosimetry of proton clinical beams

Author

PANZECA, Salvatore, BRAI, Maria, CANDIANO, G, CIRRONE, G, COLLURA, Giorgio, CUTTONE, G, GALLO, Salvatore, LAROSA, G, LEANZA, L, LONGO, Anna, ROMANO, F, SCUDERI, V, MARRALE, Maurizio, PANZECA, S, BRAI, M, CANDIANO, G, CIRRONE, G, COLLURA, G, CUTTONE, G, GALLO, S, LAROSA, G, LEANZA, L, LONGO, A, ROMANO, F, SCUDERI, V, and MARRALE, M

Subjects
Laser Driven, ESR, Alanine, ELIMED, Proton, Settore FIS/01 - Fisica Sperimentale, Settore FIS/04 - Fisica Nucleare E Subnucleare, Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Abstract

Laser-driven proton has recently gained a great interest as an alternative to conventional and more expensive acceleration techniques. These ion beams have desirable qualities such as small source size, high luminosity and small emittance to be used in different physics fields. This is very promising specially for the future perspective of a new concept of hadrontherapy based on laser-based devices could be developed, replacing traditional accelerating machines. ELIMED (Medical Applications at Extreme Light Infrastructure) is a task-force originally born by an idea of ELI-Beams (Prague) and INFN-LNS (Italian Institute for Nuclear Physics of Catania) researchers. ELIMED main goal is to perform proof-of-principle experiments aimed to demonstrate that laser-accelerated high-energy proton beams (up to 70 MeV in the first phase) can be potentially used for the specific case of ocular proton therapy. In this work we report the investigation of the dosimetric features of alanine pellets exposed to protons produced by means of the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) proton therapy facility. This analysis is preliminary for the application of the alanine dosimeters in laser-driven proton beams. ESR spectrometry with alanine is now widely recognized as the most accurate method of transfer dosimetry in the industrial (kGy) dose range. It is well established for calibrating industrial radiation sources against national standards (NIST, IAEA, NPL) and for comparisons between national laboratories. The accuracy of the method is generally very high, largely due to the low sensitivity of the alanine response to irradiation variables (energy, dose rate, temperature, etc.), and the ability of ESR spectrometers to measure dosimeter signals very precisely. As a matter of fact, the main requirements for a suitable system such as: linear response to dose, sensitivity, tissue equivalence, absence of energy dependence, absence of fading, small dimensions, ruggedness, and nondestructive readout, to a large extent are met by the alanine/ESR dosimetry. Here we analyzed the performances of two different alanine/ESR systems (3 mm pellets and 0.1 mm films) irradiated with therapy proton beams (62 MeV). The LET dependence of the response was obtained from the analysis of pellet irradiated with a modulated beam. The energy dependence of the response was derived from the analysis of film stacks irradiated with pristine beams. Use of thin films allowed for a high resolution sampling of the proton slowing down mechanisms. Alanine measurements are compared with Markus parallel plate ionization chamber and are aided by Monte Carlo calculations for medical physics using GEANT4 code

Published
2015

38. A new Thomson Spectrometer for high energy laser-driven beams diagnostic

Author

Cirrone, G, Tramontan, A, Candiano, G, Carpinelli, M, Cavallaro, S, Cutroneo, M, Cuttone, G, De Martinis, C, Giove, D, Krasa, J, Korn, G, Maggiore, M, Margarone, D, Pisciotta, P, Prokupek, J, Romano, F, Schillaci, F, Scuderi, V, Torrisi, L, Velyhan, A, Cirrone G. A. P., Tramontan A., Candiano G., CARPINELLI, Massimo, Cavallaro S., Cutroneo M., Cuttone G., De Martinis C., Giove D., Krasa J., Korn G., Maggiore M., Margarone D., Pisciotta P., Prokupek J., Romano F., Schillaci F., Scuderi V., Torrisi L., Velyhan A., Cirrone, G, Tramontan, A, Candiano, G, Carpinelli, M, Cavallaro, S, Cutroneo, M, Cuttone, G, De Martinis, C, Giove, D, Krasa, J, Korn, G, Maggiore, M, Margarone, D, Pisciotta, P, Prokupek, J, Romano, F, Schillaci, F, Scuderi, V, Torrisi, L, Velyhan, A, Cirrone G. A. P., Tramontan A., Candiano G., CARPINELLI, Massimo, Cavallaro S., Cutroneo M., Cuttone G., De Martinis C., Giove D., Krasa J., Korn G., Maggiore M., Margarone D., Pisciotta P., Prokupek J., Romano F., Schillaci F., Scuderi V., Torrisi L., and Velyhan A.

Abstract

Thomson Spectrometers (TPs) are widely used for beam diagnostic as they provide simultaneous information on charge over mass ratio, energy and momentum of detected ions. A new TP design has been realized at INFN-LNS within the LILIA (Laser Induced Light Ion Acceleration) and ELIMED (MEDical application at ELI-Beamlines) projects. This paper reports on the construction details of the TP and on its experimental tests performed at PALS laboratory in Prague, with the ASTERIX IV laser system. Reported data are obtained with polyethylene and polyvinyl alcohol solid targets, they have been compared with data obtained from other detectors. Consistency among results confirms the correct functioning of the new TP. The main features, characterizing the design, are a wide acceptance of the deflection sector and a tunability of the, partially overlapping, magnetic and electric fields that allow to resolve ions with energy up to about 40 MeV for protons.

Published
2014

39. Medical research and multidisciplinary applications with laser-accelerated beams: The ELIMED netwotk at ELI-Beamlines

Author

Tramontana, A, Anzalone, A, Candiano, G, Carpinelli, M, Cirrone, G, Cuttone, G, Korn, G, Licciardello, T, Maggiore, M, Manti, L, Margarone, D, Musumarra, A, Perozziello, F, Pisciotta, P, Raffaele, L, Romano, F, Stancampiano, C, Schillaci, F, Scuderi, V, Torrisi, L, Tudiscob, S, Tramontana A., Anzalone A., Candiano G., CARPINELLI, Massimo, Cirrone G. A. P., Cuttone G., Korn G., Licciardello T., Maggiore M., Manti L., Margarone D., Musumarra A., Perozziello F., Pisciotta P., Raffaele L., Romano F., Romano F. P., Stancampiano C., Schillaci F., Scuderi V., Torrisi L., Tudiscob S., Tramontana, A, Anzalone, A, Candiano, G, Carpinelli, M, Cirrone, G, Cuttone, G, Korn, G, Licciardello, T, Maggiore, M, Manti, L, Margarone, D, Musumarra, A, Perozziello, F, Pisciotta, P, Raffaele, L, Romano, F, Stancampiano, C, Schillaci, F, Scuderi, V, Torrisi, L, Tudiscob, S, Tramontana A., Anzalone A., Candiano G., CARPINELLI, Massimo, Cirrone G. A. P., Cuttone G., Korn G., Licciardello T., Maggiore M., Manti L., Margarone D., Musumarra A., Perozziello F., Pisciotta P., Raffaele L., Romano F., Romano F. P., Stancampiano C., Schillaci F., Scuderi V., Torrisi L., and Tudiscob S.

Abstract

Laser accelerated proton beams represent nowadays an attractive alternative to the conventional ones and they have been proposed in different research fields. In particular, the interest has been focused in the possibility of replacing conventional accelerating machines with laser-based accelerators in order to develop a new concept of hadrontherapy facilities, which could result more compact and less expensive. With this background the ELIMED (ELIMED: ELI-Beamlines MEDical applications) research project has been launched by LNS-INFN researchers (Laboratori Nazionali del Sud-Istituto Nazionale di Fisica Nucleare, Catania, IT) and ASCR-FZU researchers (Academy of Sciences of the Czech Republic-Fyzikální ústar, Prague, Cz), within the pan-European ELI-Beamlines facility framework. Its main purposes are the demonstration of future applications in hadrontherapy of optically accelerated protons and the realization of a laser-accelerated ion transport beamline for multidisciplinary applications. Several challenges, starting from laser-target interaction and beam transport development, up to dosimetric and radiobiological issues, need to be overcome in order to reach the final goals. The design and the realization of a preliminary beam handling and dosimetric system and of an advanced spectrometer for high energy (multi-MeV) laser-accelerated ion beams will be shortly presented in this work.

Published
2014

41. Dosimetria tramite Risonanza Elettronica di Spin (ESR) in RadioTerapia IntraOperatoria (IORT): misure di Output Factors e simulazioni Monte Carlo-GEANT4

Author

Gallo, S., Marrale, M., Longo, A., Russo, G., Casarino, C., Candiano, G., and Brai, M.

Subjects
Settore FIS/01 - Fisica Sperimentale, IORT, ESR, EPR, MC-Geant4, Alanina, Dosimetria, elettroni, Settore MED/36 - Diagnostica Per Immagini E Radioterapia, Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Published
2016

42. The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells

Author

Manti, L., primary, Perozziello, F.M., additional, Borghesi, M., additional, Candiano, G., additional, Chaudhary, P., additional, Cirrone, G.A.P., additional, Doria, D., additional, Gwynne, D., additional, Leanza, R., additional, Prise, K. M., additional, Romagnani, L., additional, Romano, F., additional, Scuderi, V., additional, and Tramontana, A., additional

Published
2017
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43. Status of the ELIMED multidisciplinary and medical beam-line at ELI-Beamlines

Author

Romano, F, primary, Cirrone, G A P, additional, Cuttone, G, additional, Schillaci, F, additional, Scuderi, V, additional, Amico, A, additional, Candiano, G, additional, Giordanengo, S, additional, Guarachi, L F, additional, Korn, G, additional, Larosa, G, additional, Leanza, R, additional, Manna, R, additional, Marchese, V, additional, Marchetto, F, additional, Margarone, D, additional, Milluzzo, G, additional, Petringa, G, additional, Pipek, J, additional, Sacchi, R, additional, and Vignati, A, additional

Published
2017
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44. MRgFUS Uterine Fibroids treatments in Sicily: Preliminary Results and comparison of a Semi-Automatic and manual contouring

Author

MIDIRI, Massimo, MILITELLO, Carmelo, VITABILE, Salvatore, GENOVA, Claudio, GANGUZZA, Francesca, GERACI, Laura, GAGLIARDO, Cesare, Tardino, S., Candiano, G., Russo, G., Vicari, G., Gilardi, M., Midiri, M., Militello, C., Vitabile, S., Genova, C., Ganguzza, F., Tardino, S., Candiano, G., Russo, G., Vicari, G., Geraci, L., Gagliardo, C., and Gilardi, M.

Subjects
Settore ING-INF/05 - Sistemi Di Elaborazione Delle Informazioni, MRgFUS, uterine fibroids, segmentation, Settore MED/36 - Diagnostica Per Immagini E Radioterapia
Abstract

Background: Traditional surgery for uterine fibroids treatments (e.g. myomectomy, hysterectomy) offers very invasive therapeutic approaches, which not always preserve reproductive potential of the woman. MRgFUS (MR guided Focused UltraSound) is a new and non-invasive technique for uterine fibroids treatment, not requiring hospitalization and recovery time [1]. On June 2011 and July 2012 the first treatments were started at HSR-Giglio Hospital in Cefalù and at University Hospital (DIBIMEF) in Palermo. An initial assessment of MRgFUS treatment was made by computing the thermally-ablated volume of uterine fibroid. This volume was evaluated considering the NPV (Non Perfused Volume) on a post-treatment MR dataset acquired with contrast medium. Nowadays, the used approach is a time-expensive and operator-dependent manual segmentation procedure. In this paper, the preliminary results of the two Sicilian facilities are showed and a semi- automatic segmentation approach is proposed, based on multi-seed region-growing technique, to calculate the NPV. The realized approach gives a quantitative evaluation in the post-treatment phase. Materials and Methods: The MRgFUS procedures, regarding women affected by single/multiple uterine fibroid, were performed using the ExAblate 2000 and 2100 (InSightec, Haifa, Israel), which is fully integrated with a 1.5 Tesla MR Scanner (GE Medical System, Milwaukee, WI). For NPV manual and semi-automatic evaluation we have used the sagittal or coronal images acquired after the treatment with a gadolinium-based contrast medium (FSPGR+FS+C protocol). The proposed semi-automatic approach in based on multi-seed region-growing, where it is possible to individualize the processing steps: • pre-processing filtering; • region-growing segmentation; • post-processing filtering; • NPV computation. Results: Among all 23 performed treatments, 69.57% have obtained a NPV, manually evaluated, bigger than 60%, successful treatment threshold, and the 65.22% > 70% and 47.83% > 80%. The evaluation of our segmentation approach was performed by calculating Jaccard and Dice similarity indexes and specificity and sensitivity values. In order to obtain the above indexes, the results of the proposed region-growing approach were compared with the manual segmentation. Preliminary segmentation tests obtained the following results: • Jaccard Index: 87.83%; • Dice Index: 94.12%; • Sensitivity: 91.59%; • Specificity: 89.72%. Conclusion: The MRgFUS provides an important new non-invasive and effective treatment for uterine fibroids. The proposed multi-seed region-growing segmentation approach allows to estimate the NPV in a semi-automatic and operator-independent way. Obtained segmentation indexes show the effectiveness of the implemented technique.

Published
2013

45. Stable incorporation of Alpha-smooth muscle actin into stress fibers is dependent on specific tropomyosin isoforms

Author

Prunotto M., Bruschi M., Gunning P., Gabbiani G., Weibel F., Ghiggeri G.M., Petretto A., Scaloni A., Bonello T., Schevzov G., Alieva I., Bochaton-Piallat M.-L., Candiano G., Dugina V., and Chaponnier C.

Subjects
Myofibroblast, Actin isoforms, Proteomic, TGF?
Abstract

Alpha-Smooth Muscle Actin (Alpha-SMA), a widely characterized cytoskeletal protein, represents the hallmark of myofibroblast differentiation. Transforming growth factor Beta 1 (TGFBeta1) stimulates Alpha-SMA expression and incorporation into stress fibers, thus providing an increased myofibroblast contractile force that participates in tissue remodeling. We have addressed the molecular mechanism by which Alpha-SMA is stably incorporated into stress fibers in human myofibroblasts following exposure to TGF?1. The unique N-terminal sequence AcEEED, which is critical for Alpha-SMA incorporation into stress fibers, was used to screen for AcEEED binding proteins. Tropomyosins were identified as candidate binding proteins. We find that after TGF?1 treatment elevated levels of the Tpm1.6/7 isoforms, and to a lesser extent Tpm2.1, precede the increase in ?-SMA. RNA interference experiments demonstrate that ?-SMA fails to stably incorporate into stress fibers of TGF?1 treated fibroblasts depleted of Tpm1.6/7, but not other tropomyosins. This does not appear to be due to exclusive interactions between Alpha-SMA and just the Tpm1.6/7 isoforms. We propose that an additional AcEEED binding factor may be required to generate Alpha-SMA filaments containing just Tpm1.6/7 which result in stable incorporation of the resulting filaments into stress fibers.

Published
2015

46. A transport beamline solution to control optically accelerated proton beams

Author

Schillaci, F., Amato, A., Ando, L., Attili, L., Borghesi, M., Candiano, G., Cirrone, G. A. P., Luigi Cosentino, Costa, M., Cuttone, G., Luca, G., Doria, D., Gallo, G., Larosa, G., Leanza, R., Korn, G., Manna, R., Maggiore, M., Marchese, V., Margarone, D., Maugeri, A., Milluzzo, G., Musumarra, A., Pandola, L., Petringa, G., Pulvirenti, S., Rifuggiato, D., Rizzo, D., Romano, F., Salamone, S., Sedita, M., Seminara, A., Scuderi, V., Tramontana, A., Trovato, B., and Viglianisi, C.

Subjects
Atomic and Molecular Physics, and Optics
Abstract

Laser-target interaction represents a very promising field for several potential applications,from the nuclear physics to the radiobiology. However optically accelerated particle beams arecharacterized by some extreme features, not suitable for many applications. Therefore, beyondthe improvements at the laser-target interaction level, many researchers are spending their effortsfor the development of specific beam transport devices in order to obtain controlled andreproducible output beams.In this background, the ELIMED (ELI-Beamlines MEDical applications)project was born. Within 2017, a dedicated transport beam-line coupled with dosimetricsystems, named ELIMED, will be installed at the Extreme Light Infrastructure Beamlines(ELI-Beamlines) facility in Prague (CZ),as a part of the ELIMAIA (ELI Multidisciplinary Applicationsof laserâA ¸SIon Acceleration) beamline

Published
2015

49. Do retinal rod outer segment disks carry out oxidative phosphorylation?

Author

Panfoli, I., Pepe, I. M., Morelli, A., Tacchetti, C., Bachi, A., Candiano, G., Diaspro, A., Bianchini, P., Silvia Ravera, Calzia, D., Calzia, D, Ravera, S, Bianchini, P, Diaspro, A, Candiano, G, Bachi, A, Tacchetti, Carlo, Morelli, A, Pepe, Im, Panfoli, I., D., Calzia, S., Ravera, P., Bianchini, A., Diaspro, G., Candiano, A., Bachi, A., Morelli, I. M., Pepe, and I., Panfoli

Published
2009

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