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1. IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience

Author

Elisabetta Setola, S. Benini, A. Righi, G. Gamberi, E. Carretta, C. Ferrari, S. Avnet, E. Palmerini, G. Magagnoli, M. Gambarotti, P. L. Lollini, M. Cesari, S. Cocchi, A. Paioli, A. Longhi, K. Scotlandi, M. A. Laginestra, D. M. Donati, N. Baldini, and T. Ibrahim

Subjects
Chondrosarcoma, IDH mutation, Prognostic factors, cancer metabolism, Sarcoma, Bone sarcoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. Methods 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. Results IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10–57) for IDHmut vs. 57% (95%CI: 30–77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1–65) IDHmut vs. 16% (95%CI: 0.7–52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. Conclusions This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

Published
2023
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2. Does the Time of Onset of Urinary Symptoms Affect Microablative Fractional CO2 Laser Efficacy in Postmenopausal Women?

Author

Ruffolo, A.F. Casiraghi, A. Marotta, E. Degliuomini, R. Parma, M. Athanasiou, S. Benini, V. Candiani, M. Salvatore, S.

Abstract

Background and Objective: To evaluate the safety and efficacy of transvaginal fractional microablative CO2 laser therapy (MLT) on urinary symptoms in postmenopausal women with genitourinary syndrome of menopause (GSM) in relation to the timing of their onset; if prior to or after menopause. Secondary, the efficacy of MLT on vulvovaginal atrophy (VVA)-related symptoms. Study Design/Materials and Methods: This is a retrospective analysis of prospectively collected data. Postmenopausal women affected by at least one urinary symptom (urinary frequency, urgency incontinence, stress urinary incontinence) and VVA symptom each (dryness, dyspareunia, itching, burning) were enrolled. Our population was divided into two groups in relation to the onset of urinary symptoms, prior to or after menopause. Women were treated with three CO2 MLT laser sessions, administered at a 4-week interval. For urinary symptoms evaluation, we used the following disease-specific questionnaires previously validated in Italy: the Urogenital Distress Inventory score (UDI-6) and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). For each single VVA symptom, we assessed patient's severity perception with a 10-point visual analog scale. Time points of the study were at entry (T0) and at 16 weeks since the first treatment (T1). Collected data were analyzed with the Pearson χ 2 test for categorical variables and the Wilcoxon rank-sum test (for non-normally distributed data), and statistical significance was defined with a P-value 0.05). Secondary, all VVA symptoms showed a statistically significant improvement (P < 0.05) at 16 weeks from baseline; no differences were registered between groups. No adverse events were recorded. Conclusion: This study confirms the safety and efficacy of CO2 MLT for GSM symptoms. When urinary symptoms are considered, it seems that MLT might have a higher efficacy when symptoms started after menopause, in particular when they are part of the OAB syndrome. Lasers Surg. Med. © 2021 Wiley Periodicals LLC. © 2021 Wiley Periodicals LLC

Published
2021

4. Primary malignant myoepithelioma of the distal femur

Author

Giovanni Pignatti, Franco Bertoni, Licciana Zanella, S. Benini, Marco Alberghini, Patrizia Bacchini, and Gianandrea Pasquinelli

Subjects
Microbiology (medical), Pathology, medicine.medical_specialty, Myoepithelioma, business.industry, Myoepithelial cell, General Medicine, Anatomy, Extraskeletal Myxoid Chondrosarcoma, Pathology and Forensic Medicine, Stroma, Eosinophilic, Malignant Myoepithelioma, Immunology and Allergy, Medicine, Immunohistochemistry, Differential diagnosis, business
Abstract

A 55-year-old male presented with a 1-month history of localized pain caused by an osteolytic and destructive lesion in the right distal femur. Histologically, the tumour consisted of spindle cells intermingled with epithelioid eosinophilic cells arranged in small cords embedded in a hyalinized-to-chondromyxoid stroma. Electron microscopy and immunohistochemistry showed features of myoepithelial differentiation. RT-PCR failed to demonstrate chimeric transcripts of extraskeletal myxoid chondrosarcoma. The final diagnosis was primary malignant myoepithelioma of bone. The patient is alive with lung metastases 13 months after surgery. Primary malignant myoepithelioma of bone is an exceptionally rare neoplasm that should be considered in the differential diagnosis with the more aggressive myxoid spindle cell sarcomas.

Published
2007

5. Urease

Author

S. Benini, MUSIANI, FRANCESCO, CIURLI, STEFANO LUCIANO, S. Benini, F. Musiani, and S. Ciurli

Subjects
ENZYME, UREASE, NICKEL
Abstract

Urease is a nickel-dependent enzyme that catalyzes the reaction of water with urea. The reaction initially produces ammonia and carbamate, which then spontaneously decomposes to yield another molecule of ammonia and hydrogen carbonate. The structure and function of ureases are described.

Published
2013

6. Insulin-like growth factor binding protein 3 as an anti-cancer molecule in Ewing's sarcoma

Author

S. Benini, M. C. Manara, P. Cohen, Y. Oh, ZUNTINI, MONIA, NICOLETTI, GIORDANO, NANNI, PATRIZIA, PICCI, PIERO, SCOTLANDI, KATIA, S. Benini, M. Zuntini, M.C. Manara, P. Cohen, G. Nicoletti, P. Nanni, Y Oh, P. Picci, and K. Scotlandi

Abstract

The IGF/IGF-IR system plays a major role in the pathogenesis and progression of Ewing’s sarcoma. In this paper we evaluated whether the insulin-like growth factor binding protein-3 (IGFBP-3), a molecule with growth-inhibitory and pro-apoptotic activities, may be exploited for therapeutic applications in the treatment of Ewing’s sarcoma (EWS). Expression of IGFBP-3 was analyzed in a panel of EWS cell lines and clinical samples. Parameters related to malignancy (growth in anchorage-independent conditions, migration, invasion and angiogenesis properties) were studied to establish the potential in vitro anticancer effects of exogenous IGFBP-3. The activity of the molecule against metastasis was analysed by taking advantage of selected clones in which IGFBP-3 endogenous production was induced by gene transfection. We observed a generally low expression of IGFBP-3 either in a panel of EWS cell lines or clinical samples. Exogenous IGFBP-3 remarkably inhibits EWS growth both in monolayer and anchorage-independent conditions and significantly reduces cell motility. Forced expression of IGFBP-3 in TC-71 EWS cells confirms the growth and migratory effects observed with the exogenous protein, decreases the production or activity of the matrixmetalloprotease MMP- 9 and vascular endothelial factor (VEGF)-A and abrogates EWS metastasis ability. IGFBP-3 acts mainly through IGF-dependent mechanisms and the protein may therefore represent an alternative strategy to inhibit IGF-IR functions. The data indicates IGFBP-3 as a molecule of therapeutic potential in EWS.

Published
2006

8. Crystals of cytochrome c-553 from Bacillus pasteurii show diffraction to 0.97 A resolution

Author

S, Benini, S, Ciurli, W R, Rypniewski, and K S, Wilson

Subjects
Bacillus, Cytochrome c Group, Crystallography, X-Ray
Abstract

We report here the purification and characterization of a c-type cytochrome present in the soluble fraction of the gram-positive, alkaliphilic, and highly ureolytic soil bacterium Bacillus pasteurii. The cytochrome is acidic (pI = 3.3), has a molecular mass of 9.5 kDa, and appears to dimerize in 150 mM ionic strength solution. The electronic spectrum is typical of a low-spin hexa-coordinated heme iron. Crystals of the protein in the oxidized state were grown by vapor diffusion at pH 5, by using 3.2 M ammonium sulfate as precipitant. Diffraction data at ultrahigh resolution (0.97 A) and completeness (99.9%) have been collected under cryogenic conditions, by using synchrotron radiation. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with cell constants a = 37.14, b = 39.42, c = 44.02 A, and one protein monomer per asymmetric unit. Attempts to solve the crystal structure by ab initio methods are in progress.

Published
1997

9. Immunoscintigraphy of adenocarcinomas by means of 111In-labelled F(ab')2 fragments of anti-CEA monoclonal antibody F023C5

Author

G. A. Scassellati, D. Turci, Giovanni Paganelli, A. G. Siccardi, S. Benini, M. G. Bartoli, Giuseppe Viale, L. Callegaro, G. Deleide, and P. Riva

Subjects
Pathology, medicine.medical_specialty, Lung Neoplasms, medicine.drug_class, Breast Neoplasms, Adenocarcinoma, Monoclonal antibody, Immunoscintigraphy, Metastatic carcinoma, Lesion, Immunoglobulin Fab Fragments, Carcinoembryonic antigen, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Radionuclide Imaging, Gastrointestinal Neoplasms, biology, business.industry, Indium Radioisotopes, Antibodies, Monoclonal, General Medicine, medicine.disease, Carcinoembryonic Antigen, Toxicity, biology.protein, Immunohistochemistry, medicine.symptom, business
Abstract

F(ab')2 fragments of F023C5, an anti-CEA monoclonal antibody, were conjugated to diethylenetriamine pentaacetic acid (DTPA) and converted into a ready to use reagent for instant 111In-labelling. The resulting 111In radiopharmaceutical (2-3 mCi/0.5 mg of F(ab')2 fragments) was administered intravenously and tested for its ability to image (at 48-72 h after administration) 31 primary and 85 metastatic carcinoma lesions in 70 adenocarcinoma patients (26 gastrointestinal, 18 breast and 26 lung tumor patients) whose serum CEA was elevated in 43 cases and normal in the other 27. The results were as follows: no adverse reactions or evidence of toxicity were observed in any of the patients. positive immunoscintigraphy results were obtained in 78% CEA-seropositive and in 64% seronegative patients. the fraction of documented lesions which was imaged was 69% in CEA-seropositive patients and 39% in seronegative patients. several 'unexpected' radiolocalizations were imaged; 30/34 were confirmed as (previously occult) tumour lesions in follow-up studies. In 6 patients, the immunoscintigraphic demonstration of previously occult lesions contributed to the early detection of tumour recurrences. the major limitation of the method is the non-specific radioactivity accumulation in the liver, which prevents the detection of liver metastases. in CEA-seropositive patients the fraction of imaged extra-hepatic tumour lesions is over 80%. the major cause of negative immunoscintigraphy results is lack of CEA in the tumour lesion, as demonstrated by immunohistochemistry of surgically removed tumours.

Published
1988

13. [Retropneumoperitoneum]

Author

C, SECCO, S, BENINI, and A, VITTONE

Subjects
Retropneumoperitoneum, Pneumoperitoneum, Abdomen, Humans, Insufflation, Pneumoperitoneum, Artificial, Injections, Intraperitoneal
Published
1951

15. [Studies on duodenopancreatectomy]

Author

G B, SOARDI and S, BENINI

Subjects
Pancreatic Neoplasms, Duodenal Neoplasms, Duodenum, Neoplasms, Humans, Pancreaticoduodenectomy
Published
1951

17. Antibody-guided diagnosis: An Italian experience on CEA-expressing tumours

Author

G. Moscatelli, A. G. Siccardi, G. Paganelli, S. Benini, and P. Riva

Subjects
Cancer Research, medicine.medical_specialty, Pathology, Lung Neoplasms, medicine.drug_class, Breast Neoplasms, Monoclonal antibody, Gastroenterology, Immunoscintigraphy, Breast cancer, Neoplasms, Internal medicine, medicine, Humans, Radionuclide Imaging, Lung cancer, Lung, Gastrointestinal Neoplasms, biology, business.industry, Antibodies, Monoclonal, medicine.disease, Carcinoembryonic Antigen, Clinical trial, medicine.anatomical_structure, Oncology, biology.protein, Differential diagnosis, Antibody, business
Abstract

Within the Italian CNR Biomedical Technology programmes a large multicentre clinical trial on CEA-expressing carcinomas has been carried out. F(ab')2 fragments of anti-CEA monoclonal antibody (MAb) FO23C5, radiolabelled with either 131I or 111In, were supplied to 10 different Italian nuclear medicine departments. Over 500 patients with gastrointestinal, lung, breast, and other carcinomas have been investigated. The results obtained in our nuclear medicine department are reported here. In GI cancer group, the 131I compound showed better results except in liver metastases detected only in 28/57 patients. In the lung cancer group, very satisfactory results were achieved in primary tumours and local or systemic recurrences: 111In tracer was preferentially used. In the breast cancer group immunoscintigraphy proved to be helpful in differential diagnosis of neoplastic and benign bone lesions. Significant improvements of diagnostic sensitivity were achieved in GI cancer patients by means of i.p. administration. Finally, 12 patients with advanced disease were given different 131I radioiodinated MAbs (100 mCi average dose). Administration route was either i.v. (3 cases) or i.p. (9 cases). Clinical and instrumental evidence of complete (1) or partial (7) response was observed in 8 patients.

18. Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

Author

Aloisi, Gaetano, Marengoni, Alessandra, Morandi, Alessandro, Zucchelli, Alberto, Cherubini, Antonio, Mossello, Enrico, Mario, Bo, Di Santo Simona, Mazzone, Andrea, Trabucchi, Marco, Cappa, Stefano, Fimognari, Filippo, Antonelli Incalzi Raffaele, Gareri, Pietro, Perticone, Francesco, Campanini, Mauro, Montorsi, Marco, Latronico, Nicola, Zambon, Antonella, Bellelli, Giuseppe, Rispoli, Vincenzo, Malara, Alba, Spadea, Fausto, Di Cello Serena, Ceravolo, Francesco, Fabiano, Francesco, Chiaradia, Giuseppe, Gabriele, Amedeo, Lenino, Peluso, Andrea, Taristano, Settembrini, Vincenzo, Capomolla, Domenico, Citrino, Antonella, Scriva, Antonietta, Bruno, Irene, Secchi, Roberto, De Martino Eugenio, Muccinelli, Roberto, Lupi, Gerardo, Paonessa, Patrizio, Fabbri, Andrea, Passuti Maria Teresa, Castellari, Sofia, Andrea, Po, Gaggioli, Guido, Varesi, Massimo, Moneti, Paolo, Capurso, Sebastiano, Latini, Vincenzo, Ghidotti, Stefano, Riccardelli, Francesco, Macchi, Maurizio, Rigo, Rosaria, Claudio, Pascale, Bosio, Angelo, Cerrato, Flavio, Bardelli, Benedetta, Boffelli, Stefano, Cassinadri, Angela, Franzoni, Simone, Spazzini, Elena, Andretto, Daniela, Tonini, Gabriele, Andreani, Laura, Coralli, Mirco, Balotta, Antonio, Cancelliere, Roberto, Ballardini, Giorgio, Simoncelli, Margherita, Mancini, Annarita, Strazzacapa, Mara, Fabio, Stefano, De Filippi Francesco, Giudice, Chiara, Dentizzi, Cosimo, Azzini, Margherita, Cazzadori, Marco, Mastroeni, Valeria, Bertassello, Paolo, Santana, Helena, Benati, Claudia, Nesta, Elisa, Tobaldini, Chiara, Guerini, Fabio, Tambara, Elena, Mombelloni, Paolo, Fontanini, Fulvio, Lassa, Gabriella, Lassa, Pizzorni, Crosio, Oliverio, Martina, Del, Grosso, Luciano, Luca, Giavedoni, Cristina, Bidoli, Giuliano, Mazzei, Bruno, Corsonello, Andrea, Fusco, Sergio, Vena, Silvio, De Vuono Tommaso, Maiuri, Giorgio, Fimognari Filippo Luca, Arone, Andrea, Sgro, Giovanni, Nicolazzo, Rossella, Castegnaro, Eugenio, De Rosa Salvatore, Sechi Bazzano Rossella, Benvenuti, Enrico, Del Lungo Ilaria, Giardini, Sante, Giulietti, Chiara, Di Bari Mauro, Barghini, Eleonora, Paoli, Martina, Fiordelli, Irene, Barucci, Riccardo, Sgrilli, Federica, Bertoletti, Erik, D'Amico, Ferdinando, Caronzolo, Francesco, Grippa, Alessandro, Lombardo, Giuseppina, Pipicella, Tiziana, Saitta, Antonino, Corica, Francesco, Cucinotta, Valeria, Giaritta, Prestipino, Larosa, Daniela, Cucinotta, Domenico, Basile, Giorgio, March, Albert, Nitti Maria Teresa, Felici, Alessandro, Pavan, Silvia, Piazzani, Fabrizio, Lunelli, Alessandra, Dimori, Sergio, Margotta, Alessandro, Soglia, Tiziano, Postacchini, Demetrio, Brunelli, Roberto, Santini, Silvia, Francavilla, Monia, Macchiati, Ilenia, Sorvillo, Francesca, Giuli, Cinzia, Mecocci, Patrizia, Longo, Annalisa, Addesi, Desiree, Rosa Paola Cerra, Bencardino, Giuseppe, Falbo, Tania, Grillo, Nadia, Filice, Marco, Mirella, Filippo, Fanto, Fausto, Isaia, Gianluca, Pezzilli, Stella, Bergamo, Daniele, Furno, Elisabetta, Rrodhe, Sokol, Lucarini, Simonetta, Dijk, Babette, Dall'Acqua, Francesca, Cappelletto, Francesco, Calvani, Donatella, Becheri, Dimitri, Mottino, Giuseppe, Mitidieri, Costanza, Antonio, Vito, Bartalucci, Francesca, Magherini, Lorenza, Malin, Novella, Boni, Franca, Gambardella Paoli Martina Lucia, Valente, Carlo, Bracali, Ilaria, Bracali, Foschini, Alice, Porrino, Paola, Ceci, Giacomo, Bottignole, Giuliana, Tibaldi, Michela, Coppo, Eleonora, Ettore, Evaristo, Camellini, Cinzia, Servello, Adriana, Grassi, Alessandro, Rozzini, Renzo, Tironi, Sara, Grassi Maria Grazia, Troisi, Elio, Caltagirone, Carlo, Franchini, Flaminia, Ratto, Federica, Pavoni, Beatrice, Toniolo, Sofia, Gabutto, Anna, Quazzo, Loredana, Rosatello, Annalisa, Suraci, Domenico, Tagliabue, Benedetta, Perrone, Chiara, Ferrara, Lucia, Castagna, Alberto, Tremolada Maria Luisa, Castoldi, Giuseppe, Barbero, Stefano, Oltramonti, Davide, Piano, Simonetta, Serviddio, Gaetano, Lo Buglio Aurelio, Gurrera, Tiziana, Merlo, Valeria, Rovai, Carla, Cotroneo Antonino Maria, Carlucci, Rosaria, Abbaldo, Anna, Monzani, Fabio, Qasem Ahmad Amedeo, Bini, Giacomo, Tafuto, Silvia, Galli, Giovanni, Bruni Amalia Cecilia, Mancuso, Giovanna, Mancuso, Gerardo, De Luca Giuseppe Massimiliano, Calipari Daniela., Bernardini, Bruno, Corsini, Carla, Ciccarelli, Michele, Dal Farra Sara, Dal, Farra, Cagnin, Annachiara, Fragiacomo, Federica, Pompanin, Sara, Amodio, Piero, Cagnin, Marco, Zurlo, Amedeo, Guerra, Gianluca, Pala, Marco, Menozzi, Luca, Delli Gatti Chiara, Magon, Stefania, Manfredini, Roberto, De Giorgi Alfredo, Fabbian, Fabio, Tiseo, Ruana, Misurati, Elisa, Boari, Benedetta, Molino, Christian, Gallerani, Massimo, Di Francesco Vincenzo, Faccioli, Silvia, Pellizzari, Luca, Fontana, Giorgia, Barbagallo, Giuseppe, Lunardelli Maria Lia, Martini, Emilio, Ferrari, Eleonora, Macchiarulo, Maria, Corneli, Maria, Bacci, Monica, Battaglia, Giuseppe, Anastasio, Luigi, Lo Storto Mario Sostene, Seresin, Chiara, Simonato, Matteo, Loreggian, Michele, Cestonaro, Fausta, Durando, Mario, Latella, Raffaele, Mazzoleni, Marta, Russo, Giuseppe, Ponte, Martino, Valchera, Alessandro, Salustri, Giuseppe, Petritola, Donatella, Costa, Alfredo, Sinforiani, Elena, Cotta Matteo Ramusino, Pizio Renato Nicola, Cester, Alberto, Formilan, Marino, Bonometto, Pietro, Carbone, Pasqualina, Cazzaniga, Ilaria, Appollonio, Ildebrando, Cereda, Diletta, Stabile, Andrea, Xhani, Rubjona, Acampora, Roberto, Tremolizzo, Lucio, Pieruzzi, Federico, Ciaccio, Antonio, Pontecorvi, Valerio, Burti, Cesare, Mokini, Zhirajr, Vitale, Giovanni, Amigoni, Maria, Sparacino, Mariaelena, Bottacchi, Edo, Bucciantini, Elisabetta, Di Giovanni Marco, Franchi, Fabrizio, Lucchetti, Lucio, Mariani, Claudio, Grande, Giulia, Rapazzini, Piero, Mauri, Marco, Romanelli, Giuseppe, Nicosia, Franco, Margola, Alessio, Bonardelli, Stefano, Porcella, Laura, Portolani, Nazario, Concoreggi, Carlo, Grassini, Chiara, Salvi, Andrea, Bianchetti, Luca, Spagnoli, Francesca, Apuzzo, Roberto, Fontanella, Ceraso, Anna, Castelli, Francesco, Fugazza, Luciano, Guerrini, Chiara, De Paduanis Giovanna, Iallonardo, Lucia, Palumbo, Pasquale, Zuliani, Giovanni, Ortolani, Beatrice, Capatti, Eleonora, Soavi, Cecilia, Bianchi, Lara, Francesconi, Daniela, Miselli, Agata, Brombo, Gloria, Romagnoli, Tommaso, Pazzaglini, Chiara, Miselli Maria Agata, Dall'Agata, Marco, Suardi, Teresa, Zaccarini, Cinzia, Riva, Manuela, Mirra, Gianluca, Muti, Ettore, Bottura, Renato, Moretti, Gianpaolo, Secreto, Piero, Bisio, Erika, Cecchettani, Marco, Naldi, Tamara, Pallavicino, Alessandra, Pugliese, Michela, Iozzo Rosaria Cosima, Grassi, Guido, Bombelli, Michele, Delloro, Raffaella, Quarti Trevano Fosca, Giussani Carlo Giorgio, Paterno, Giovanni, Contro, Ernesto, Mannironi, Antonio, Giorli, Elisa, Oberti, Sara, Fierro, Brigida, Piccoli, Tommaso, Giacalone, Fabio, Mandas, Antonella, Serchisu, Luca, Costaggiu, Diego, Pinna, Elisa, Orru, Francesca, Mannai, Martina, Cordioli, Zeno, Pelizzari, Luca, Turcato, Emanuela, Arduini, Pietro, Cacace, Carlo, Chiloiro, Roberta, Cimino, Rosella, Ruberto, Carmen, Ruotolo, Giovanni, Greco, Laura, Dal Santo Pierluigi, Andriolli, Antonino, Burattin, Giuseppe, Rossi, Laura, Andreolli, Antonino, Cervati, Giovanna, Catalano, Giuseppe, Tezza, Fabiana, Pizzardini, Maddalena, Stievano, Laura, Crippa, Patrizia, Aloisio, Paola, Di Monda Tiziana, Malighetti, Alessandro, Galbassini, Gloria, Ivaldi, Claudio, Russo Anna Maria, Bennati, Ettore, Pino, Elisabetta, Zavarise, Gianmaria, Pesci, Alberto, Suigo, Giulia, Faverio, Paola, Gori, Andrea, Perego Sabrina Perego, Zanasi, Massimo, Moniello, Giovanni, Rostagno, Carlo, Cartei, Alessandro, Polidori, Gianluca, Ungar, Andrea, Melis Maria Ramona, Martellini, Eleonora, Torrini, Monica, Giordano, Antonella, Leone, Giovanna, Migliorini, Marta, Caramelli, Francesca, Battiston, Bruno, Berardino, Maurizio, Cavallo, Simona, Masse, Alessandro, Santoro, Anna, Lombardi, Bruna, D'Ippolito, Pierpaolo, Furini, Angela, Villani, Daniele, Raimondi, Clara, Guarneri, Massimo, Paolucci, Stefano, Bassi, Andrea, Coiro, Paola, De Angelis Domenico, Morone, Giovanni, Venturiero, Vincenzo, Palleschi, Lorenzo, Raganato, Paolo, Di Niro Giuseppina, Casini Anna Rosa, Bove, Loredana, Imoscopi, Alessandra, Isaia, Giancarlo, Tibaldi, Vittoria, Calvi, Elisa, Clementi, Carlotta, Zanocchi, Mauro, Agosta, Luca, Criasia, Antonio, Spertino, Elena, Nortarelli, Antonella, Provenzano, Giuseppe, Principato, Pietro, Rizzo, Anita, Cellura, Eleonora, Mari, Daniela, Romano Federica Ylenia, Rosini, Francesca, Mansi, Marta, Rossi, Silvia, Riccardelli, Alex, Inzaghi, Lorenzo, Bonini, Giulia, Rossi, Paolo, Potena, Alfredo, Lichii, Mihaela, Candiani, Tiziana, Grimaldi, William, Bertani, Emiliano, Porta, Alessandra, Calogero, Pietro, Pinto, Daniela, Bernardi, Roberto, Nicolino, Francesco, Galetti, Caterina, Gianstefani, Alice, Corvalli, Giulia, Mulazzani, Lorenzo, Odetti, Patrizio, Monacelli, Fiammetta, Prefumo, Matteo, Canepa, Marta, Minaglia, Cecilia, Paolisso, Giuseppe, Rizzo Maria Rosaria, Prestano, Raffaele, Dalise Anna Maria, Barra, Davide, Dal Bosco Livio, Asprinio, Vincenzo, Dallape, Luciana, Maina, Paola, Perina, Elisa, Bartoli Rossi Isaura, Pluderi, Alice, Maina, Antonella, Pecoraro, Elisabetta, Sciarra, Michela, Prudente, Angela, Mete, Francesca, Ventura, Manuel, Cesari, Luisella, Pernigotti Luigi Maria, Santangelo, Tina, Benini, Lucia, Levato, Francesco, Mhiuta, Victor, Alius, Florin, Davidoaia, Diana, Giardini, Vittorio, Garancini, Mattia, Bellamoli, Claudio, Terranova, Luciano, Bozzini, Claudia, Tosoni, Paolo, Provoli, Emma, Cascone, Luisa, Dioli, Andrea, Ferrarin, Gianfranco, Bucci, Adelmo, Bua, Guido, Fenu, Sara, Bianchi, Giovanna, Casella, Silvia, Romano, Valentina, Poli, Maurizio, Mascherona, Ilenia, Belotti, Gloria, Cavaliere, Sabina, Cuni, Estella, Merciuc, Nina, Oberti, Rosella, Veneziani, Silvia, Capoferri, Emanuela, De Bernardi Elisabetta, Colombo, Katia, Bravi, Marco, Negrinotti, Nicoletta, D'Arcangelo, Paolo, Montenegro, Nicola, Montanari, Roberto, Lamanna, Pierpaolo, Gasperini, Beatrice, Montesi, Isabella, Diotallevi, Stefania, Altobelli, Gaia, Cacinaro, Filippo, Palama, Chiara, Di Emidio Chiara, Scarpini, Elio, Arighi, Andrea, Scrimieri, Antonia, Fumagalli, Giorgio, Basilico, Paola, Migone De Amicis Margherita, Mancarella, Marta, Maira, Diletta, Granata, Antonino, Ranalli, Claudia, Cammilli, Alessandra, Cavallini Maria Chiara, Tricca, Manola, Natella, Daniela, Gabbani, Luciano, Tesi, Francesca, Martella, Letizia, Imbrici, Rosalba, Pacchioni, Maurizio, Gianbattista, Guerrini, Scotuzzi Anna Maria, Sozzi, Ferdinando, Valenti, Luigi, Chiarello, Antonino, Monella, Monia, Pilotto, Alberto, Prete, Camilla, Senesi, Barbara, Meta Anna Cristina, Pendenza, Enrico, Pasqualetti, Giuseppe, Polini, Antonio, Tognini, Sara, Ballino, Elena, Dell'Aquila, Giuseppina, Gasparrini Pina Maria, Marotti, Elisabetta, Migale, Monica, Falsetti, Lorenzo, Salvi, Aldo, Toigo, Gabriele, Ceschia, Giuliano, Rosso, Alessia, Tongiorgi, Chiara, Scarpa, Cristina, De Dominicis Luigino, Pucci, Eugenio, Renzi, Sara, Cartechini, Elisabetta, Tomassini Pia Francesca, Del Gobbo Maurizio, Ugenti, Francesca, Romeo, Pasquale, Nardelli, Anna, Lauretani, Fulvio, Visioli, Sandra, Montanari, Ilaria, Ermini, Francesca, Giordano, Antonio, Pigato, Giorgio, Simeone, Emilio, Colameco, Franco, Cecamore, Antonella, Scurti, Rosa, Lupinetti Maria Cristina, Barbujani, Mario, Perazzi, Beatrice, Giampieri, Marina, Amoruso, Raffaele, Piccinini, Maristella, Ferrari, Camilla, Gambetti, Claudio, Sfrappini, Mario, Semeraro, Letizia, Striuli, Rinaldo, Mariani, Claudia, Pelliccioni, Giuseppe, Marinelli, Donatella, Fabi, Katia, Rossi, Tommaso, Pesallaccia, Martina, Sabbatini, Debora, Gobbi, Beatrice, Cerqua, Raffaella, Tagliani, Giancarla, Schlauser, Elena, Caser, Luciano, Caramello, Elisa, Sandigliano, Franca, Rosso, Giorgio, Bendini, Chiara, Davoli, Maria, Casella, Monica, Prampolini, Raffaella, Scevola, Moreno, Vitale, Enrico, Brugiolo, Roberto, Brugiolo, Fagherazzi, Carlo, Scarpa, Alberto, Zara, Daniela, Bertozzo, Giulia, Granziera, Serena, Barazzuol, Michele, Maugeri, Domenico, Sorace, Rosaria, Anzaldi, Massimiliano, De Gesu Roberto, Morrone, Giuseppe, Davolio, Federica, Fabbo, Andrea, Palmieri, Marina, Forti, Paola, Pirazzoli, Luca, Fabbri, Elisa, Terenzi, Laura, Bergolari, Federica, Wenter, Christian, Ruffini, Ingrid, Insam, Miriam, Abraham, Elisabeth, Kirchlechner, Christine, Lasco, Antonino, Arena Maria Grazia, Parise, Pasquale, Boccali, Andrea, Amici, Serena, Gambacorta, Maurizia, Ferrari, Alberto, Lasagni, Anna, Lovati, Roberto, Giovinazzo, Francesca, Kimak, Elzbieta, Zappa, Paolo, Medici, Francesco, Lo Castro Marika, Mauro, Flavia, De Luca Alessandro, Sancesario, Giuseppe, Martorana, Alessandro, Scaricamazza, Beatrice, Di Lorenzo Francesco, Liguori, Claudio, Vita, Natale, Giomi, Mirna, Forte, Floriana, Padovani, Alessandro, Rozzini, Luca, Caratozzolo, Salvatore, Cottino, Maria, Vitali, Silvia, Marelli, Eleonora, Tripi, Gabriele, Miceli, Salvatore, Urso, Giovanni, Grioni, Giuseppe, Vezzadini, Giuliana, Misaggi, Giulia, Forlani, Chiara, Avanzi, Stefano, Saulle, Serena, Casarini, Claudia, Viggiano, Marilena, Alberto, Luisa, Ghianda, Diego, Giordano, Alessandro, Iemolo, Francesco, Giordano, Antonello, Sanzaro, Enzo, D'Asta, Gabriele, Proietto, Maria, Carnemolla, Anna, Razza, Grazia, Spadaro, Daniela, Bertolotti, Marco, Mussi, Chiara, Neviani, Francesca, Chiesa, Roberto, Guerzoni, Valentina, Morselli, Linda, Venturelli, Francesca, Tarozzi, Adriano, Balestri, Francesca, Mannarino, Giulio, Bigolari, Michela, Natale, Alessia, Grassi, Simona, Bottaro, Cinzia, Stefanelli, Sara, Bovone, Ugo, Tortorolo, Umberto, Quadri, Roberto, Leone, Giuseppe, Ponzetto, Maria, Frasson, Paola, Annoni, Giorgio, Bruni, Adriana, Confalonieri, Roberto, Corsi, Maurizio, Moretti, Daniela, Teruzzi, Fabiola, Umidi, Simona, Mazzola, Paolo, Perego, Sabrina, Persico, Ilaria, Olivieri, Giulia, Bonfanti, Alessandra, Hajnalka, Szabo, Galeazzi, Marianna, Massariello, Francesca, Anzuini, Alessandra, Caffarra, Paolo, Barocco, Federica, Spallazzi, Marco, Ceda Gian Paolo, Morganti, Simonetta, Artoni, Andrea, Chioatto, Paolo, Bortolamei, Sandra, Soattin, Lucia, Beneamino, Borelli, Barilaro, Giuseppe, Bertazzoli, Marco, Rota, Elisabetta, Adobati, Annamaria, Zuccher, Paola, Dal Fabbro Angela, Lo Nigro Ambra, Franchetti, Lorena, Toniolo, Marika, Marcuzzo, Cinzia, Rollone, Marco, Guerriero, Fabio, Sgarlata, Carmelo, Anna, Santoro, Zatti, Giovanni, Piatti, Massimiliano, Graci, Jole, Benati, Giuseppe, Boschi, Federica, Biondi, Mario, Fiumi, Nicoletta, Erika, Tamburini, Locatelli Sergio Mario, Mauri, Sabrina, Beretta, Mauro, Margheritis, Laura, Desideri, Giovanbattista, Liberatore, Ester, Carucci Anna Cecilia, Bonino, Paolo, Caput, Margherita, Antonietti Maria Paola, Polistena, Giuseppe, De la Pierre Franz, Mari, Marcello, Massignani, Paola, Tombesi, Fabio, Selvaggio, Fabio, Verbo, Brunella, Bodoni, Paolo, Marchionni, Niccolo, Sabatini, Tony, Mussio, Eleonora, Magni, Eugenio, Bianchetti, Angelo, Crucitti, Andrea, Titoldini, Giulia, Cossu, Beatrice, Fascendini, Sara, Licini, Cristina, Tomasoni, Angela, Calderazzo, Massimo, Tropiano, Daniela, Lagana, Valentina, Melotti Rita Maria, Lilli, Albina, Buda, Simona, Adversi, Marco, Noro, Gabriele, Turco, Renato, Chiara, Ubezio M., Mantovani Anna Roberta, Viola Maria Cristina, Serrati, Carlo, Pretta, Stefano, Infante, Maria, Gentile, Simona, D'Ambrosio, Viviana, Mazzanti, Paolo, Brambilla, Cristina, Sportelli, Silvia, Platto, Caterina, Faraci, Bianca, Quattrocchi, Daniela, Pisu, Cristina, Sicuro, Francesca, Del Grosso Luciano Luca, Zagnoni, Piergiuseppe, Ghiglia, Stefania, Mosca, Massimiliano, Corazzin, Ileana, Deola, Mariangela, Biagini Carlo Adriano, Bencini, Francesca, Cantini, Claudia, Tonon, Elisabetta, Pierinelli, Silvia, Onofrj, Marco, Thomas, Astrid, Borbone, Filomena, Bonanni, Laura, Cacchio, Gabriella, Comi, Giancarlo, Magnani, Giuseppe, Santangelo, Roberto, Mazzeo, Salvatore, Caso, Francesca, Cecchetti, Giordano, Sant’Angelo, Roberto, Barbieri, Cristina, Giroldi, Liviana, Bandini, Fabio, Masina, Marco, Malservisi, Simona, Cicognani, Annalena, Ricca, Laura, Piccininni, Maristella, Tassinari, Tiziana, Brogi, Davide, Sugo, Annalisa, Filippi, Alessandra, Manfredi, Sonia, Vanni, Valerio, Usai carlo Andrea, Colombo, Enrico, Renna Vera Francesca, Sauchella, Assunta, Prete, Mauro, Bisagni, Pietro, Masini, Roberto, Carrabetta, Salvatore, Barone, Antonella, Razzano, Monica, Imperoli, Giuseppe, Bini, Angela, Serra, Francesco, D’Agostino, Valeria, Gianolla, Federico, Pietrangeli, Lucia, Velardi, Antonella, Di Cello Elisabetta, Rosati, Cristina, Casali, Nadia, Casali, Sessa, Maria, Abruzzi, Luciano, Costanzi, Chiara, Bini, Paolo, Pignata, Michele, Buonaugurio, Enrico, Vollery, Maria, Carrieri, Giovanni, Cioni, Giorgio, Toschi, Andrea, Metra, Marco, Ranieri, Piera, Ceccon, Anna, Magrin, Laura, Marin, Sara, Barbara, Sofia, Ghedini, Laura, Moroni, Matteo, Paragona, Marco, Pallotti Maria Caterina, Rota, Carla, Gottardi, Federica, Tomasoni, Clara, Cappuccio, Melania, Bonini, Giampaolo, Guerini, Stefano, Guerini, Valeria, Merlaj, Lucia, Tovaglieri, Maurizio, Antonio, Grillo, Francesca, Arenare, Mineo, Tonino, Kanah, David, Vianello, Giorgio, Vianello, Piero, Balducci, Ubaldo, Sidoti, Vincenzo, Montanari, Stefano, Murelli Flavio Teodolindo Busonera, Albanese, Paolo, Maselli, Monica, Bolzetta, Francesco, Fabris, Roberto, Durante-Mangoni, Emanuele, Testoni, Michela, Di Stefano Fabio, Seccia, Loredana, Sonzini, Valeria, Fabiano, Maria, Di Giorgio Annabella, De Cosmo Salvatore, Greco, Antonio, D’Onofrio, Grazia, Sancarlo, Daniele, Resta, Gianluca, Girardello, Renzo, Girardello, Minervini, Sergio, Boni, Morena, Vitali, Mariagrazia, Pizzoni, Marina, De Colle Paolo, Frattola, Alessandra, Orlandini, Francesco, La Regina Micaela, Padulo, Filomena, Margheriti, Cristina, Rolano, Dario, Moscatelli, Giancarla, Radaelli, Guido, Montini, Elena, Prete, Cosimo, Novello, Marileda, Bramuzzo, Igor, Bertin, Nicole, Rinaldo, Elena, Paolillo, Ciro, Riccardi, Angela, Benedetti, Claudia, Rizzi, Barbara, Montagna, Francesca, Cutaia, Chiara, Baca, Oliver, Colombo, Mauro, Procino, Giuseppe, Tarara, Rosaria, Dell’Acqua, Davide, Cislaghi, Stefania, Cairati, Marco, Porta, Massimo, Scaglione, Luca, De Feo Martina, Vertolli, Paola, Salvati, Lia, Cinotti, Sandro, De Santis Valentina, Biferi, Erminia, Cheli, Paola, Rebizzo, Romina, Salvatore, Minisola, Luciano, Colangelo, Abete, Pasquale, Liguori, Ilaria, Curcio, Francesca, Spassini, Guglielmo, Engheben, Marco, Rotunno, Sara, Rotunno, Arosio, Paola, Angelini, Claudio, Reggiani, Francesco, Cappelli, Alessandro, Marcheselli, Simona, Fratticci, Lara, Ranzani, Paola, Cesarini, Simonetta, Cerini, Antonella, Gallucci, Fernando, Serra, Emanuela, Sola, Mariolina, Delitala, Alessandro, Pes, Chiara, Lobianco, Giulia, Giani, Alessandro, Famularo, Simone, Sandini, Marta, Pinotti, Enrico, Gianotti, Luca, Battuello, Antonella, Pintore, Giulia, Rossi, Andrea, Rubele, Sofia, Sant, Selena, Vignati, Marco, Clerici, Danila, Rosa, Fabio, Bandirali Maria Pia, Cattaneo, Nicoletta, Boffi, Laura, Avalli, Leonello, Scanziani, Margherita, De Notaris Stefania, Del Santo Pierluigi, Del, Santo, Catalano, Felice, Fogli, Danilo, Di Bella Giovanna, Landi, Francesco, Salini, Sara, Brunetti Maria Angela, Cappa, Giorgetta, Galvagno, Giovanni, Cena, Paola, Bruno, Gerardo, Raspo, Silvio, Semeraro, Pedrotti, Sabrina, Palmieri Vincenzo Ostilio, Palasciano, Giuseppe, Belfiore, Anna, Portincasa, Piero, Sabbà, Carlo, Solfrizzi, Vincenzo, D’Introno, Alessia, Valiani, Vincenzo, Bologna, Carolina, Ciarambino, Tiziana, Magnani, Turelli, Paola, Pazzaglia, Ugo, Rodella, Federica, Piana, Giacomo, Castellano, Maurizio, Garelli, Anna, Garelli, Casella, Elisa, Campana, Federica, Coschigliano Maria Antonietta, Marinangeli, Luigi, Lorico, Fabio, Bazzano, Salvatore, Menculini, Giuseppe, Gelosa, Giorgio, Viviana Ambrogio Teresa, Piras, Valentina, Ciricugno, Andrea, Bollari, Alessandra, Coen, Daniele, Magliola, Renata, Milanesio, Deborah, Muzzulini Carlo Lorenzo, Fogliacco, Paolo, Marinella, Turla, Cotelli Maria Sofia, Bianchi, Marta, Siano, Pietro, Capo, Giuseppe, Napoletano, Rosa, Politi, Cecilia, Mancini, Concetta, Del Buono Corrado, De Bartolomeo Giuseppe, Martinelli, Addolorata, Cefalogli, Carmen, Cozzi, Roberto, Virtuani Angelo Giovanni, Moschettini, Gianfilippo, Mastroianni, Franco, Roglia, Daniela, D'Amico, Gabriella, Palella, Mirella, Endrizzi, Cristina, Trotta, Lucia, Zanetti, Orazio, Terazzi, Emanuela, Sacchetti, Marta, Fleetwood, Thomas, Tondo, Giacomo, Di Fazio Ignazio, Bruni, Andrea, Orsitto, Giuseppe, Fabbro, Emanuela, D’Imporzano, Elena, Casanova, Anna, Bertolio, Serena, Nervo, Silvestri, Roberto, Semproni, Elena, Pintus, Manuela, Aloe, Francesca, Tagliaccica, Angelo., Aloisi G., Marengoni A., Morandi A., Zucchelli A., Cherubini A., Mossello E., Bo M., Di Santo S.G., Mazzone A., Trabucchi M., Cappa S., Fimognari F.L., Incalzi R.A., Gareri P., Perticone F., Campanini M., Montorsi M., Latronico N., Zambon A., Bellelli G., Rispoli V., Malara A., Spadea F., Di Cello S., Ceravolo F., Fabiano F., Chiaradia G., Gabriele A., Lenino P., Andrea T., Settembrini V., Capomolla D., Citrino A., Scriva A., Bruno I., Secchi R., De Martino E., Muccinelli R., Villa Del Sole R.S.A., Lupi G., Paonessa P., Fabbri A., Passuti M.T., Castellari S., Po A., Gaggioli G., Varesi M., Moneti P., Capurso S., Latini V., Ghidotti S., Riccardelli F., Macchi M., Rigo R., Claudio P., Angelo B., Flavio C., Benedetta B., Boffelli S., Cassinadri A., Franzoni S., Spazzini E., Andretto D., Tonini G., Andreani L., Coralli M., Balotta A., Cancelliere R., Ballardini G., Simoncelli M., Mancini A., Strazzacapa M., Fabio S., De Filippi F., Giudice C., Dentizzi C., Azzini M., Cazzadori M., Mastroeni V., Bertassello P., Benati H.S.C., Nesta E., Tobaldini C., Guerini F., Elena T., Mombelloni P., Fontanini F., Gabriella L., Pizzorni C., Oliverio M., Del Grosso L.L., Giavedoni C., Bidoli G., Mazzei B., Corsonello A., Fusco S., Vena S., De Vuono T., Maiuri G., Luca F.F., Andrea A., Giovanni S., Rossella N., Castegnaro E., De Rosa S., Benvenuti E., Del Lungo I., Giardini S., Giulietti C., Mauro D.B., Eleonora B., Martina P., Irene F., Riccardo B., Federica S., Bertoletti E., D'Amico F., Caronzolo F., Grippa A., Lombardo G., Pipicella T., Antonino S., Francesco C., Valeria P.G., Daniela L., Domenico C., Giorgio B., March A., Nitti M.T., Felici A., Pavan S., Piazzani F., Lunelli A., Dimori S., Margotta A., Soglia T., Postacchini D., Brunelli R., Santini S., Francavilla M., Macchiati I., Sorvillo F., Giuli C., Mecocci P., Longo A., Addesi D., Rosa P.C., Bencardino G., Falbo T., Grillo N., Marco F., Mirella F., Fanto F., Isaia G., Pezzilli S., Bergamo D., Furno E., Rrodhe S., Lucarini S., Dijk B., Dall'Acqua F., Calvani D., Becheri D., Giuseppe M., Costanza M., Vito A., Francesca B., Magherini L., Novella M., Franca B., Gambardella P.M.L., Valente C., Ospedale N., Ilaria B., Alice F., Porrino P., Ceci G., Giuliana B., Michela T., Eleonora C., Ettore E., Camellini C., Servello A., Grassi A., Rozzini R., Tironi S., Grassi M.G., Troisi E., Carlo C., Gabriella D.S.S., Flaminia F., Federica R., Beatrice P., Sofia T., Gabutto A., Quazzo L., Rosatello A., Suraci D., Tagliabue B., Perrone C., Ferrara L., Castagna A., Tremolada M.L., Giuseppe C., Stefano B., Davide O., Piano S., Serviddio G., Lo Buglio A., Gurrera T., Merlo V., Rovai C., Cotroneo A.M., Carlucci R., Abbaldo A., Monzani F., Qasem A.A., Bini G., Tafuto S., Galli G., Bruni A.C., Mancuso G., Calipari D., Bernardini B., Corsini C., Michele C., Sara D.F., Cagnin A., Fragiacomo F., Pompanin S., Piero A., Marco C., Zurlo A., Guerra G., Pala M., Menozzi L., Delli Gatti C., Magon S., Roberto M., Alfredo D.G., Fabio F., Ruana T., Elisa M., Christian M., Marco P., Massimo G., Di Francesco V., Faccioli S., Pellizzari L., Giorgia F., Barbagallo G., Lunardelli M.L., Martini E., Ferrari E., Macchiarulo M., Corneli M., Bacci M., Battaglia G., Anastasio L., Lo Storto M.S., Seresin C., Simonato M., Loreggian M., Cestonaro F., Durando M., Latella R., Mazzoleni M., Russo G., Ponte M., Valchera A., Salustri G., Petritola D., Costa A., Sinforiani E., Cotta M.R., Pizio R.N., Cester A., Formilan M., Pietro B., Carbone P., Cazzaniga I., Appollonio I., Cereda D., Stabile A., Xhani R., Acampora R., Tremolizzo L., Federico P., Antonio C., Valerio P., Cesare B., Zhirajr M., Giovanni V., Maria A., Mariaelena S., Bottacchi E., Bucciantini E., Di Giovanni M., Franchi F., Lucchetti L., Mariani C., Grande G., Rapazzini P., Marco M., Romanelli G., Franco N., Alessio M., Nicola L., Laura P., Nazario P., Chiara G., Soccorso P., Andrea S., Luca B., Francesca S., Roberto A., Anna C., Infettive M., Fugazza L., Guerrini C., De Paduanis G., Iallonardo L., Palumbo P., Zuliani G., Ortolani B., Capatti E., Soavi C., Bianchi L., Francesconi D., Miselli A., Gloria B., Tommaso R., Chiara P., Agata M.M., Dall'Agata M., Luca M., Gianluca G., Suardi T., Zaccarini C., Manuela R., Mirra G., Muti E., Bottura R., Gianpaolo M., Secreto P., Bisio E., Cecchettani M., Naldi T., Pallavicino A., Pugliese M., Iozzo R.C., Grassi G., Michele B., Dell'Oro R., Fosca Q.T., Giorgio G.C., Giovanni P., Ernesto C., Mannironi A., Giorli E., Oberti S., Fierro B., Piccoli T., Giacalone F., Mandas A., Serchisu L., Costaggiu D., Pinna E., Orru F., Mannai M., Cordioli Z., Pelizzari L., Turcato E., Arduini P., Cacace C., Chiloiro R., Cimino R., Ruberto C., Giovanni R., Pietro G., Laura G., Alberto C., Carmen R., Dal Santo P., Andriolli A., Burattin G., Rossi L., Antonino C.G.A., Tezza F., Maddalena P., Laura S., Crippa P., Aloisio P., Di Monda T., Malighetti A., Galbassini G., Ivaldi C., Russo A.M., Bennati E., Pino E., Zavarise G., Pesci A., Suigo G., Faverio P., Andrea G., Sabrina P., Zanasi M., Moniello G., Rostagno C., Cartei A., Polidori G., Ungar A., Melis M.R., Martellini E., Enrico M., Monica T., Antonella G., Giovanna L., Migliorini M., Caramelli F., Battiston B., Berardino M., Cavallo S., Alessandro M., Anna S., Lombardi B., D'Ippolito P., Furini A., Villani D., Clara R., Guarneri M., Paolucci S., Bassi A., Coiro P., De Angelis D., Morone G., Venturiero V., Palleschi L., Raganato P., Di Niro G., Rosa C.A., Loredana B., Imoscopi A., Tibaldi V., Bottignole G.G., Calvi E., Clementi C., Zanocchi M., Agosta L., Criasia A., Spertino E., Nortarelli A., Provenzano G., Principato P., Rizzo A., Cellura E., Mari D., Romano F.Y., Rosini F., Mansi M., Rossi S., Riccardelli A., Inzaghi L., Bonini G., Rossi P., Potena A., Lichii M., Candiani T., Grimaldi W., Bertani E., Alessandra P., Calogero P., Pinto D., Bernardi R., Nicolino F., Galetti C., Gianstefani A., Giulia C., Lorenzo M., Odetti P., Monacelli F., Prefumo M., Fiammetta M., Canepa M., Minaglia C., Paolisso G., Rizzo M.R., Prestano R., Dalise A.M., Barra D., Dal Bosco L., Asprinio V., Dallape L., Perina E., Bartoli I.R., Pluderi A., Maina A., Pecoraro E., Sciarra M., Prudente A., Paola M., Francesca M., Manuel V., Luisella C., Maria P.L., Tina S., Benini L., Levato F., Mhiuta V., Alius F., Davidoaia D., Giardini V., Garancini M., Bellamoli C., Terranova L., Bozzini C., Tosoni P., Provoli E., Cascone L., Dioli A., Ferrarin G., Bucci A., Bua G., Fenu S., Bianchi G., Casella S., Romano V., Maurizio P., Mascherona I., Belotti G., Cavaliere S., Cuni E., Merciuc N., Oberti R., Veneziani S., Capoferri E., De Bernardi E., Colombo K., Bravi M., Nicoletta N., D'Arcangelo P., Montenegro N., Montanari R., Lamanna P., Gasperini B., Isabella M., Stefania D., Gaia A., Filippo C., Palama C., Di Emidio C., Scarpini E., Arighi A., Fumagalli G., Basilico P., De Amicis Margherita M., Marta M., Diletta M., Granata A., Ranalli C., Cammilli A., Cavallini M.C., Tricca M., Natella D., Gabbani L., Tesi F., Martella L., Imbrici R., Guerrini G., Scotuzzi A.M., Sozzi F., Valenti L., Chiarello A., Monia M., Pilotto A., Prete C., Senesi B., Meta A.C., Pendenza E., Pasqualetti G., Polini A., Tognini S., Ballino E., Dell'Aquila G., Gasparrini P.M., Marotti E., Migale M., Scrimieri A., Falsetti L., Salvi A., Toigo G., Ceschia G., Rosso A., Tongiorgi C., Scarpa C., De Dominicis L., Pucci E., Renzi S., Cartechini E., Tomassini P.F., Del Gobbo M., Ugenti F., Romeo P., Nardelli A., Lauretani F., Visioli S., Montanari I., Ermini F., Giordano A., Pigato G., Simeone E., Colameco F., Cecamore A., Scurti R., Lupinetti M.C., Barbujani M., Perazzi B., Giampieri M., Amoruso R., Piccinini M., Ferrari C., Gambetti C., Sfrappini M., Semeraro L., Striuli R., Pelliccioni G., Marinelli D., Fabi K., Rossi T., Pesallaccia M., Sabbatini D., Gobbi B., Cerqua R., Tagliani G., Schlauser E., Caser L., Caramello E., Sandigliano F., Rosso G., Ferrari A., Bendini C., Luisa D.M., Casella M., Prampolini R., Scevola M., Vitale E., Roberto B., Carlo F., Sergio F., Alberto S., Daniela Z., Giulia B., Serena G., Maugeri D., Sorace R., Anzaldi M., De Gesu R., Morrone G., Davolio F., Fabbo A., Palmieri M., Zoli M., Forti P., Pirazzoli L., Fabbri E., Terenzi L., Bergolari F., Wenter C., Ruffini I., Insam M., Abraham E., Kirchlechner C., Cucinotta D., Antonino L., Basile G., Grazia A.M., Parise P., Boccali A., Amici S., Gambacorta M., Lasagni A., Lovati R., Giovinazzo F., Kimak E., Zappa P., Medici F., Lo Castro M., Mauro F., De Luca A., Sancesario G., Martorana A., Scaricamazza B., Toniolo S., Di Lorenzo F., Liguori C., Lasco A., Vita N., Giomi M., Forte F., Padovani A., Rozzini L., Ceraso A., Salvatore C., Cottino M., Vitali S., Marelli E., Tripi G., Miceli S., Urso G., Grioni G., Vezzadini G., Misaggi G., Forlani C., Avanzi S., Serena S., Claudia C., Marilena V., Alberto L., Diego G., Alessandro G., Iemolo F., Sanzaro E., D'Asta G., Proietto M., Carnemolla A., Razza G., Spadaro D., Bertolotti M., Mussi C., Neviani F., Roberto C., Valentina G., Linda M., Francesca V., Tarozzi A., Balestri F., Mannarino G., Bigolari M., Natale A., Grassi S., Bottaro C., Stefanelli S., Bovone U., Tortorolo U., Quadri R., Leone G., Ponzetto M., Frasson P., Annoni G., Bruni A., Confalonieri R., Corsi M., Moretti D., Teruzzi F., Umidi S., Mazzola P., Perego S., Persico I., Olivieri G., Bonfanti A., Hajnalka S., Galeazzi M., Massariello F., Anzuini A., Caffarra P., Barocco F., Spallazzi M., Paolo C.G., Simonetta M., Chioatto P., Bortolamei S., Soattin L., Ruotolo G., Beneamino B., Giuseppe B., Bertazzoli M., Rota E., Adobati A., Scarpa A., Granziera S., Zuccher P., Dal Fabbro A., Zara D., Lo Nigro A., Franchetti L., Toniolo M., Marcuzzo C., Rollone M., Guerriero F., Sgarlata C., Masse A., Zatti G., Piatti M., Graci J., Benati G., Boschi F., Biondi M., Fiumi N., Erika T., Locatelli S.M., Mauri S., Beretta M., Margheritis L., Desideri G., Liberatore E., Carucci A.C., Bonino P., Caput M., Antonietti M.P., Polistena G., De La Pierre F., Mari M., Massignani P., Tombesi F., Selvaggio F., Verbo B., Bodoni P., Marchionni N., Sabatini T., Mussio E., Magni E., Bianchetti A., Crucitti A., Titoldini G., Cossu B., Fascendini S., Licini C., Tomasoni A., Calderazzo M., Daniela T., Valentina L., Melotti R.M., Lilli A., Buda S., Adversi M., Noro G., Turco R., Ubezio M.C., Mantovani A.R., Viola M.C., Serrati C., Pretta S., Infante M., Gentile S., D'Ambrosio V., Mazzanti P., Brambilla C., Sportelli S., Platto C., Faraci B., Quattrocchi D., Pernigotti L.M., Pisu C., Sicuro F., Zagnoni P., Ghiglia S., Mosca M., Corazzin I., Deola M., Di Agordo O., Biagini C.A., Bencini F., Cantini C., Tonon E., Pierinelli S., Onofrj M., Thomas A., Filomena B., Bonanni L., Gabriella C., Comi G., Magnani G., Santangelo R., Mazzeo S., Francesca C., Giordano C., Roberto S., Barbieri C., Giroldi L., Bandini F., Masina M., Malservisi S., Cicognani A., Ricca L., Piccininni M., Tassinari T., Brogi D., Sugo A., Alessandra F., Sonia M., Valerio V., Andrea U.C., Enrico C., Vera R.F., Assunta S., Gianmaria Z., Mauro P., Barone A., Razzano M., Giuseppe I., Angela B., Francesco S., D'Agostino V., Federico G., Lucia P., Antonella V., Di Cello E., Cristina C., Nadia C., Maria S., Luciano A., Chiara C., Bini P., Pignata M., Enrico B., Maria V., Giovanni C., Giorgio C., Piera R., Alberto Z., Ceccon A., Magrin L., Marin S., Barbara S., Matteo M., Caterina P.M., Carla R., Federica G., Clara T., Melania C., Giampaolo B., Stefano G., Valeria G., Lucia M., Giovambattista D., Ester L., Cecilia C.A., Maurizio T., Nadia B., Grillo A., Arenare F., Tonino M., David K., Giorgio V.P., Ubaldo B., Vincenzo S., Stefano M., Marino F., Flavio M.T.B., Paolo A., Monica M., Francesco B., Roberto F., Paolo B., Durante-Mangoni E., Testoni M., Di Stefano F., Loredana S., Daniela M., Valeria S., Fabiano M., Di Giorgio A., De Cosmo S., Greco A., D'Onofrio G., Daniele S., Gianluca R., Renzo G., Sergio M., Morena B., Vitali M., Marina P., De Colle P., Cristina S., Orlandini F., La Regina M., Desiree A., Mario B., Paola P., Padulo F., Cristina M., Dario R., Giancarla M., Guido R., Elena M., Marileda N., Igor B., Nicole B., Elena R., Paolillo C., Riccardi A., Claudia B., Barbara R., Silvia V., Oliver B., Mauro C., Eleonora M., Giuseppe P., Rosaria T., Maria C., Dell'Acqua D., Stefania C., Massimo P., Luca S., De Feo M., Paola V., Lia S., Sandro C., De Santis V., Erminia B., Paola C., Romina R., Minisola S., Luciano C., Pasquale A., Ilaria L., Guglielmo S., Marco E., Sara R., Paola A., Claudio A., Francesco R., Alessandro C., Simona M., Lara F., Paola R., Simonetta C., Antonella C., Generoso U., Fernando G., Giuliano C., Emanuela S., Mariolina S., Alessandro D., Giulia L., Famularo S., Sandini M., Pinotti E., Gianotti L., Antonella B., Giulia P., Sante G., Rossi A., Rubele S., Sant S., Marco V., Danila C., Fabio R., Bandirali M.P., Nicoletta C., Laura B., Paolo T., Luciano T., Leonello A., Margherita S., De Notaris S., Del Santo P., Laura R., Fabiana T., Giovanna C., Antonino A., Felice C., Danilo F., Di Bella G., Francesco L., Salini S., Angela B.M., Giorgetta C., Giovanni G., Gerardo B., Silvio R., Letizia S., Davide B., Rosaria R.M., Maria D.A., Raffaele P., Palmieri V.O., Palasciano G., Belfiore A., Portincasa P., Carlo S., D'Introno A., Valiani V., Carolina B., Tiziana C., Paola T., Ugo P., Giacomo P., Castellano M., Anna G., Elisa C., Federica C., Antonietta C.M., Luigi M., Fabio L., Salvatore B., Gelosa G., Viviana A.T., Piras V., Andrea C., Alessandra B., Coen D., Magliola R., Milanesio D., Muzzulini C.L., Paolo F., Marinella T., Sofia C.M., Marta B., Siano P., Capo G., Napoletano R., Cecilia P., Mancini C., Del Buono C., De Bartolomeo G., Addolorata M., Carmen C., Giovanni V.A., Moschettini G., Franco M., Mulli O.F., Daniela R., D'Amico G., Mirella P., Endrizzi C., Trotta L., Ciarambino T., Orazio Z., Emanuela T., Marta S., Thomas F., Giacomo T., Di Fazio I., Andrea B., Giuseppe O., Emanuela F., Serena A., D'Imporzano E., Serena B., Erika N., Elena S., Manuela P., Francesca A., Angelo T., Aloisi, G., Marengoni, A., Morandi, A., Zucchelli, A., Cherubini, A., Mossello, E., Bo, M., Di Santo, S.G., Mazzone, A., Trabucchi, M., Cappa, S., Fimognari, F.L., Incalzi, R.A., Gareri, P., Perticone, F., Campanini, M., Montorsi, M., Latronico, N., Zambon, A., Bellelli, G., Rispoli, V., Malara, A., Spadea, F., Di Cello, S., Ceravolo, F., Fabiano, F., Chiaradia, G., Gabriele, A., Lenino, P., Andrea, T., Settembrini, V., Capomolla, D., Citrino, A., Scriva, A., Bruno, I., Secchi, R., De Martino, E., Muccinelli, R., Villa Del Sole, R.S.A., Lupi, G., Paonessa, P., Fabbri, A., Passuti, M.T., Castellari, S., Po, A., Gaggioli, G., Varesi, M., Moneti, P., Capurso, S., Latini, V., Ghidotti, S., Riccardelli, F., Macchi, M., Rigo, R., Claudio, P., Angelo, B., Flavio, C., Benedetta, B., Boffelli, S., Cassinadri, A., Franzoni, S., Spazzini, E., Andretto, D., Tonini, G., Andreani, L., Coralli, M., Balotta, A., Cancelliere, R., Ballardini, G., Simoncelli, M., Mancini, A., Strazzacapa, M., Fabio, S., De Filippi, F., Giudice, C., Dentizzi, C., Azzini, M., Cazzadori, M., Mastroeni, V., Bertassello, P., Benati, H.S.C., Nesta, E., Tobaldini, C., Guerini, F., Elena, T., Mombelloni, P., Fontanini, F., Gabriella, L., Pizzorni, C., Oliverio, M., Del Grosso, L.L., Giavedoni, C., Bidoli, G., Mazzei, B., Corsonello, A., Fusco, S., Vena, S., De Vuono, T., Maiuri, G., Luca, F.F., Andrea, A., Giovanni, S., Rossella, N., Castegnaro, E., De Rosa, S., Benvenuti, E., Del Lungo, I., Giardini, S., Giulietti, C., Mauro, D.B., Eleonora, B., Martina, P., Irene, F., Riccardo, B., Federica, S., Bertoletti, E., D'Amico, F., Caronzolo, F., Grippa, A., Lombardo, G., Pipicella, T., Antonino, S., Francesco, C., Valeria, P.G., Daniela, L., Domenico, C., Giorgio, B., March, A., Nitti, M.T., Felici, A., Pavan, S., Piazzani, F., Lunelli, A., Dimori, S., Margotta, A., Soglia, T., Postacchini, D., Brunelli, R., Santini, S., Francavilla, M., Macchiati, I., Sorvillo, F., Giuli, C., Mecocci, P., Longo, A., Addesi, D., Rosa, P.C., Bencardino, G., Falbo, T., Grillo, N., Marco, F., Mirella, F., Fantò, F., Isaia, G., Pezzilli, S., Bergamo, D., Furno, E., Rrodhe, S., Lucarini, S., Dijk, B., Dall'Acqua, F., Calvani, D., Becheri, D., Giuseppe, M., Costanza, M., Vito, A., Francesca, B., Magherini, L., Novella, M., Franca, B., Gambardella, P.M.L., Valente, C., Ospedale, N., Ilaria, B., Alice, F., Porrino, P., Ceci, G., Giuliana, B., Michela, T., Eleonora, C., Ettore, E., Camellini, C., Servello, A., Grassi, A., Rozzini, R., Tironi, S., Grassi, M.G., Troisi, E., Carlo, C., Gabriella, D.S.S., Flaminia, F., Federica, R., Beatrice, P., Sofia, T., Gabutto, A., Quazzo, L., Rosatello, A., Suraci, D., Tagliabue, B., Perrone, C., Ferrara, L., Castagna, A., Tremolada, M.L., Giuseppe, C., Stefano, B., Davide, O., Piano, S., Serviddio, G., Lo Buglio, A., Gurrera, T., Merlo, V., Rovai, C., Cotroneo, A.M., Carlucci, R., Abbaldo, A., Monzani, F., Qasem, A.A., Bini, G., Tafuto, S., Galli, G., Bruni, A.C., Mancuso, G., Mancuso, G., Calipari, D., Bernardini, B., Corsini, C., Michele, C., Sara, D.F., Cagnin, A., Fragiacomo, F., Pompanin, S., Piero, A., Marco, C., Zurlo, A., Guerra, G., Pala, M., Menozzi, L., Delli Gatti, C., Magon, S., Roberto, M., Alfredo, D.G., Fabio, F., Ruana, T., Elisa, M., Benedetta, B., Christian, M., Marco, P., Massimo, G., Di Francesco, V., Faccioli, S., Pellizzari, L., Giorgia, F., Barbagallo, G., Lunardelli, M.L., Martini, E., Ferrari, E., Macchiarulo, M., Corneli, M., Bacci, M., Battaglia, G., Anastasio, L., Lo Storto, M.S., Seresin, C., Simonato, M., Loreggian, M., Cestonaro, F., Durando, M., Latella, R., Mazzoleni, M., Russo, G., Ponte, M., Valchera, A., Salustri, G., Petritola, D., Costa, A., Sinforiani, E., Cotta, M.R., Piano, S., Pizio, R.N., Cester, A., Formilan, M., Pietro, B., Carbone, P., Cazzaniga, I., Appollonio, I., Cereda, D., Stabile, A., Xhani, R., Acampora, R., Tremolizzo, L., Federico, P., Antonio, C., Valerio, P., Cesare, B., Zhirajr, M., Giovanni, V., Maria, A., Mariaelena, S., Bottacchi, E., Bucciantini, E., Di Giovanni, M., Franchi, F., Lucchetti, L., Mariani, C., Grande, G., Rapazzini, P., Marco, M., Romanelli, G., Franco, N., Alessio, M., Stefano, B., Nicola, L., Laura, P., Nazario, P., Carlo, C., Chiara, G., Soccorso, P., Andrea, S., Luca, B., Francesca, S., Roberto, A., Marco, F., Anna, C., Francesco, C., Infettive, M., Fugazza, L., Guerrini, C., De Paduanis, G., Iallonardo, L., Palumbo, P., Zuliani, G., Ortolani, B., Capatti, E., Soavi, C., Bianchi, L., Francesconi, D., Miselli, A., Gloria, B., Tommaso, R., Chiara, P., Agata, M.M., Dall'Agata, M., Luca, M., Gianluca, G., Suardi, T., Zaccarini, C., Manuela, R., Mirra, G., Muti, E., Bottura, R., Gianpaolo, M., Secreto, P., Bisio, E., Cecchettani, M., Naldi, T., Pallavicino, A., Pugliese, M., Iozzo, R.C., Grassi, G., Michele, B., Dell'Oro, R., Fosca, Q.T., Giorgio, G.C., Giovanni, P., Ernesto, C., Mannironi, A., Giorli, E., Oberti, S., Fierro, B., Piccoli, T., Giacalone, F., Mandas, A., Serchisu, L., Costaggiu, D., Pinna, E., Orrù, F., Mannai, M., Cordioli, Z., Pelizzari, L., Turcato, E., Arduini, P., Cacace, C., Chiloiro, R., Cimino, R., Ruberto, C., Giovanni, R., Pietro, G., Laura, G., Alberto, C., Carmen, R., Dal Santo, P., Andriolli, A., Burattin, G., Rossi, L., Antonino, C.G.A., Giuseppe, C., Tezza, F., Maddalena, P., Laura, S., Crippa, P., Aloisio, P., Di Monda, T., Malighetti, A., Galbassini, G., Ivaldi, C., Russo, A.M., Bennati, E., Pino, E., Zavarise, G., Pesci, A., Suigo, G., Faverio, P., Andrea, G., Sabrina, P., Zanasi, M., Moniello, G., Rostagno, C., Cartei, A., Polidori, G., Ungar, A., Melis, M.R., Martellini, E., Enrico, M., Monica, T., Antonella, G., Giovanna, L., Migliorini, M., Caramelli, F., Battiston, B., Berardino, M., Cavallo, S., Alessandro, M., Anna, S., Lombardi, B., D'Ippolito, P., Furini, A., Villani, D., Clara, R., Guarneri, M., Paolucci, S., Bassi, A., Coiro, P., De Angelis, D., Morone, G., Venturiero, V., Palleschi, L., Raganato, P., Di Niro, G., Rosa, C.A., Loredana, B., Imoscopi, A., Isaia, G., Tibaldi, V., Bottignole, G.G., Calvi, E., Clementi, C., Zanocchi, M., Agosta, L., Criasia, A., Spertino, E., Nortarelli, A., Provenzano, G., Principato, P., Rizzo, A., Cellura, E., Mari, D., Romano, F.Y., Rosini, F., Mansi, M., Rossi, S., Riccardelli, A., Inzaghi, L., Bonini, G., Rossi, P., Potena, A., Lichii, M., Candiani, T., Grimaldi, W., Bertani, E., Alessandra, P., Calogero, P., Pinto, D., Bernardi, R., Nicolino, F., Galetti, C., Gianstefani, A., Giulia, C., Lorenzo, M., Odetti, P., Monacelli, F., Prefumo, M., Fiammetta, M., Canepa, M., Minaglia, C., Paolisso, G., Rizzo, M.R., Prestano, R., Dalise, A.M., Barra, D., Dal Bosco, L., Asprinio, V., Dallape, L., Perina, E., Bartoli, I.R., Pluderi, A., Maina, A., Pecoraro, E., Sciarra, M., Prudente, A., Paola, M., Francesca, M., Manuel, V., Luisella, C., Maria, P.L., Tina, S., Benini, L., Levato, F., Mhiuta, V., Alius, F., Davidoaia, D., Giardini, V., Garancini, M., Bellamoli, C., Terranova, L., Bozzini, C., Tosoni, P., Provoli, E., Cascone, L., Dioli, A., Ferrarin, G., Bucci, A., Bua, G., Fenu, S., Bianchi, G., Casella, S., Romano, V., Maurizio, P., Mascherona, I., Belotti, G., Cavaliere, S., Cuni, E., Merciuc, N., Oberti, R., Veneziani, S., Capoferri, E., De Bernardi, E., Colombo, K., Bravi, M., Nicoletta, N., D'Arcangelo, P., Montenegro, N., Galli, G., Montanari, R., Lamanna, P., Gasperini, B., Isabella, M., Stefania, D., Gaia, A., Filippo, C., Palamà, C., Di Emidio, C., Scarpini, E., Arighi, A., Fumagalli, G., Basilico, P., De Amicis Margherita, M., Marta, M., Diletta, M., Granata, A., Ranalli, C., Cammilli, A., Cavallini, M.C., Tricca, M., Natella, D., Gabbani, L., Tesi, F., Martella, L., Imbrici, R., Guerrini, G., Scotuzzi, A.M., Sozzi, F., Valenti, L., Chiarello, A., Monia, M., Pilotto, A., Prete, C., Senesi, B., Meta, A.C., Pendenza, E., Pasqualetti, G., Polini, A., Tognini, S., Ballino, E., Dell'Aquila, G., Gasparrini, P.M., Marotti, E., Migale, M., Scrimieri A., Falsetti, L., Salvi A., Toigo, G., Ceschia, G., Rosso, A., Tongiorgi, C., Scarpa, C., Maurizio, P., De Dominicis, L., Pucci, E., Renzi, S., Cartechini, E., Tomassini, P.F., Del Gobbo, M., Ugenti, F., Romeo, P., Nardelli, A., Lauretani, F., Visioli, S., Montanari, I., Ermini, F., Giordano, A., Pigato, G., Simeone, E., Colameco, F., Cecamore, A., Scurti, R., Lupinetti, M.C., Barbujani, M., Perazzi, B., Giampieri, M., Amoruso, R., Piccinini, M., Ferrari, C., Gambetti, C., Sfrappini, M., Semeraro, L., Striuli, R., Mariani, C., Pelliccioni, G., Marinelli, D., Fabi, K., Rossi, T., Pesallaccia, M., Sabbatini, D., Gobbi, B., Cerqua, R., Tagliani, G., Schlauser, E., Caser, L., Caramello, E., Sandigliano, F., Rosso, G., Ferrari, A., Bendini, C., Luisa, D.M., Casella, M., Prampolini, R., Scevola, M., Vitale, E., Roberto, B., Carlo, F., Sergio, F., Alberto, S., Daniela, Z., Giulia, B., Serena, G., Michele, B., Maugeri, D., Sorace, R., Anzaldi, M., De Gesu, R., Morrone, G., Davolio, F., Fabbo, A., Palmieri, M., Barbagallo, G., Zoli, M., Forti, P., Pirazzoli, L., Fabbri, E., Terenzi, L., Bergolari, F., Wenter, C., Ruffini, I., Insam, M., Abraham, E., Kirchlechner, C., Cucinotta, D., Antonino, L., Basile, G., Grazia, A.M., Parise, P., Boccali, A., Amici, S., Gambacorta, M., Lasagni, A., Lovati, R., Giovinazzo, F., Kimak, E., Zappa, P., Medici, F., Lo Castro, M., Mauro, F., De Luca, A., Sancesario, G., Martorana, A., Scaricamazza, B., Toniolo, S., Di Lorenzo, F., Liguori, C., Lasco, A., Vita, N., Giomi, M., Forte, F., Padovani, A., Rozzini, L., Ceraso, A., Salvatore, C., Cottino, M., Vitali, S., Marelli, E., Tripi, G., Miceli, S., Urso, G., Grioni, G., Vezzadini, G., Misaggi, G., Forlani, C., Avanzi, S., Serena, S., Claudia, C., Marilena, V., Alberto, L., Diego, G., Alessandro, G., Iemolo, F., Giordano, A., Sanzaro, E., D'Asta, G., Proietto, M., Carnemolla, A., Razza, G., Spadaro, D., Bertolotti, M., Mussi, C., Neviani, F., Roberto, C., Valentina, G., Linda, M., Francesca, V., Tarozzi, A., Balestri, F., Mannarino, G., Bigolari, M., Natale, A., Grassi, S., Bottaro, C., Stefanelli, S., Bovone, U., Tortorolo, U., Quadri, R., Leone, G., Ponzetto, M., Frasson, P., Annoni, G., Bruni, A., Confalonieri, R., Corsi, M., Moretti, D., Teruzzi, F., Umidi, S., Mazzola, P., Perego, S., Persico, I., Olivieri, G., Bonfanti, A., Hajnalka, S., Galeazzi, M., Massariello, F., Anzuini, A., Caffarra, P., Barocco, F., Spallazzi, M., Paolo, C.G., Simonetta, M., Andrea, A., Chioatto, P., Bortolamei, S., Soattin, L., Ruotolo, G., Beneamino, B., Giuseppe, B., Bertazzoli, M., Rota, E., Adobati, A., Scarpa, A., Granziera, S., Zuccher, P., Dal Fabbro, A., Zara, D., Lo Nigro, A., Franchetti, L., Toniolo, M., Marcuzzo, C., Piano, S., Rollone, M., Guerriero, F., Sgarlata, C., Massè, A., Zatti, G., Piatti, M., Graci, J., Benati, G., Boschi, F., Biondi, M., Fiumi, N., Erika, T., Locatelli, S.M., Mauri, S., Beretta, M., Margheritis, L., Desideri, G., Liberatore, E., Carucci, A.C., Bonino, P., Caput, M., Antonietti, M.P., Polistena, G., De La Pierre, F., Mari, M., Massignani, P., Tombesi, F., Selvaggio, F., Verbo, B., Bodoni, P., Marchionni, N., Sabatini, T., Mussio, E., Magni, E., Bianchetti, A., Crucitti, A., Titoldini, G., Cossu, B., Fascendini, S., Licini, C., Tomasoni, A., Calderazzo, M., Daniela, T., Valentina, L., Prampolini, R., Melotti, R.M., Lilli, A., Buda, S., Adversi, M., Noro, G., Turco, R., Ubezio, M.C., Mantovani, A.R., Viola, M.C., Serrati, C., Pretta, S., Infante, M., Gentile, S., D'Ambrosio, V., Mazzanti, P., Brambilla, C., Sportelli, S., Platto, C., Faraci, B., Quattrocchi, D., Pernigotti, L.M., Pisu, C., Sicuro, F., Del Grosso, L.L., Zagnoni, P., Ghiglia, S., Mosca, M., Corazzin, I., Deola, M., Di Agordo, O., Biagini, C.A., Bencini, F., Cantini, C., Tonon, E., Pierinelli, S., Onofrj, M., Thomas, A., Filomena, B., Bonanni, L., Gabriella, C., Comi, G., Magnani, G., Santangelo, R., Mazzeo, S., Giuseppe, M., Francesca, C., Giordano, C., Roberto, S., Barbieri, C., Giroldi, L., Bandini, F., Masina, M., Malservisi, S., Cicognani, A., Ricca, L., Ricca, L., Piccininni, M., Tassinari, T., Brogi, D., Sugo, A., Alessandra, F., Sonia, M., Valerio, V., Andrea, U.C., Enrico, C., Vera, R.F., Assunta, S., Gianmaria, Z., Mauro, P., Pietro, B., Roberto, M., Salvatore, C., Barone, A., Razzano, M., Giuseppe, I., Angela, B., Francesco, S., D'Agostino, V., Federico, G., Lucia, P., Antonella, V., Di Cello, E., Cristina, C., Nadia, C., Maria, S., Luciano, A., Chiara, C., Bini, P., Pignata, M., Enrico, B., Maria, V., Giovanni, C., Giorgio, C., Andrea, T., Marco, M., Piera, R., Alberto, Z., Ceccon, A., Magrin, L., Marin, S., Barbara, S., Marco, M., Laura, G., Matteo, M., Marco, P., Caterina, P.M., Carla, R., Federica, G., Clara, T., Melania, C., Giampaolo, B., Stefano, G., Valeria, G., Lucia, M., Giovambattista, D., Ester, L., Cecilia, C.A., Maurizio, T., Vera, R.F., Nadia, B., Grillo, A., Arenare, F., Tonino, M., David, K., Giorgio, V.P., Ubaldo, B., Vincenzo, S., Stefano, M., Marino, F., Flavio, M.T.B., Paolo, A., Monica, M., Francesco, B., Roberto, F., Paolo, B., Durante-Mangoni, E., Testoni, M., Di Stefano, F., Loredana, S., Daniela, M., Valeria, S., Fabiano, M., Di Giorgio, A., De Cosmo, S., Greco, A., D'Onofrio, G., Daniele, S., Gianluca, R., Renzo, G., Sergio, M., Morena, B., Vitali, M., Marina, P., De Colle, P., Cristina, S., Alessandra, F., Orlandini, F., La Regina, M., Desirée, A., Mirella, F., Mario, B., Paola, P., Padulo, F., Cristina, M., Dario, R., Giancarla, M., Guido, R., Elena, M., Prete, C., Marileda, N., Igor, B., Nicole, B., Elena, R., Paolillo, C., Riccardi, A., Claudia, B., Barbara, R., Francesca, M., Silvia, V., Chiara, C., Oliver, B., Mauro, C., Eleonora, M., Giuseppe, P., Rosaria, T., Maria, C., Dell'Acqua, D., Stefania, C., Marco, C., Massimo, P., Luca, S., De Feo, M., Paola, V., Lia, S., Sandro, C., De Santis, V., Erminia, B., Paola, C., Romina, R., Minisola, S., Luciano, C., Pasquale, A., Ilaria, L., Francesca, C., Guglielmo, S., Marco, E., Sara, R., Paola, A., Claudio, A., Francesco, R., Alessandro, C., Simona, M., Lara, F., Paola, R., Simonetta, C., Antonella, C., Generoso, U., Fernando, G., Giuliano, C., Emanuela, S., Mariolina, S., Alessandro, D., Chiara, P., Giulia, L., Alessandro, G., Famularo, S., Sandini, M., Pinotti, E., Gianotti, L., Antonella, B., Giulia, P., Sante, G., Rossi, A., Rubele, S., Sant, S., Marco, V., Danila, C., Fabio, R., Bandirali, M.P., Nicoletta, C., Laura, B., Paolo, T., Luciano, T., Leonello, A., Margherita, S., De Notaris, S., Del Santo, P., Laura, R., Fabiana, T., Giovanna, C., Antonino, A., Felice, C., Giuseppe, B., Danilo, F., Di Bella, G., Francesco, L., Salini, S., Angela, B.M., Giorgetta, C., Giovanni, G., Paola, C., Gerardo, B., Silvio, R., Letizia, S., Sabrina, P., Davide, B., Rosaria, R.M., Maria, D.A., Raffaele, P., Palmieri, V.O., Palasciano, G., Belfiore, A., Portincasa, P., Carlo, S., Vincenzo, S., D'Introno, A., Valiani, V., Carolina, B., Tiziana, C., Giordano, C., Paola, T., Ugo, P., Federica, R., Giacomo, P., Castellano, M., Anna, G., Elisa, C., Federica, C., Antonietta, C.M., Luigi, M., Fabio, L., Salvatore, B., Giuseppe, M., Gelosa, G., Viviana, A.T., Piras, V., Andrea, C., Alessandra, B., Coen, D., Magliola, R., Milanesio, D., Muzzulini, C.L., Paolo, F., Marinella, T., Sofia, C.M., Marta, B., Siano, P., Capo, G., Napoletano, R., Cecilia, P., Mancini, C., Del Buono, C., De Bartolomeo, G., Addolorata, M., Carmen, C., Roberto, C., Giovanni, V.A., Moschettini, G., Franco M., Mulli, O.F., Daniela, R., D'Amico, G., Mirella, P., Endrizzi, C., Trotta, L., Ciarambino, T., Orazio, Z., Emanuela, T., Marta, S., Thomas, F., Giacomo, T., Di Fazio, I., Andrea, B., Giuseppe, O., Emanuela, F., Serena, A., D'Imporzano, E., Anna, C., Serena, B., Erika, N., Roberto, S., Elena, S., Manuela, P., Francesca, A., Angelo, T., Aloisi, G, Marengoni, A, Morandi, A, Zucchelli, A, Cherubini, A, Mossello, E, Bo, M, Di Santo, S, Mazzone, A, Trabucchi, M, Cappa, S, Fimognari, F, Incalzi, R, Gareri, P, Perticone, F, Campanini, M, Montorsi, M, Latronico, N, Zambon, A, Bellelli, G, and Faverio, P

Subjects
Male, diagnosis, medications, 0302 clinical medicine, prevention, Aged, 80 and over, Delirium, Drug Prescriptions, Female, Hospital Departments, Humans, Prevalence, Polypharmacy, Prescription Drugs, 80 and over, Medicine, LS4_4, 030212 general & internal medicine, Acute hospital, media_common, Confounding, elderly patients, hip fracture, hospitalized patients, prediction rule, risk factor, dementia, events, medications, prevention, diagnosis, risk-factor, risk factor, hip fracture, Psychiatry and Mental Health, medicine.symptom, events, Drug, medicine.medical_specialty, hospitalized-patients, media_common.quotation_subject, MEDLINE, Socio-culturale, elderly-patients, elderly patients, behavioral disciplines and activities, 03 medical and health sciences, Internal medicine, mental disorders, Dementia, Medical prescription, prediction rule, Aged, business.industry, hospitalized patients, medicine.disease, nervous system diseases, dementia, business, 030217 neurology & neurosurgery
Abstract

Objective This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P = .009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.

Published
2019

19. Chemistry of Ni2+ in Urease: Sensing, Trafficking, and Catalysis

Author

Barbara Zambelli, Francesco Musiani, Stefano Benini, Stefano Ciurli, B. Zambelli, F. Musiani, S. Benini, and S. Ciurli

Subjects
inorganic chemicals, Transcription, Genetic, Metal ions in aqueous solution, NICKEL, Bacillus, GTPase, NICKEL REGULATION, GTP Phosphohydrolases, Enzyme catalysis, Enzyme activator, Bacterial Proteins, UREASE, Catalytic Domain, Binding site, metal trafficking, Ions, Metal ion homeostasis, chemistry.chemical_classification, Binding Sites, Helicobacter pylori, biology, Chemistry, Active site, Enterobacter aerogenes, General Medicine, General Chemistry, Phosphate-Binding Proteins, Canavalia, Enzyme, Biochemistry, Biocatalysis, biology.protein, Carrier Proteins
Abstract

Transition metals are both essential to enzymatic catalysis and limited in environmental availability. These two biological facts have together driven organisms to evolve mechanisms for selective metal ion sensing and utilization. Changes in metal ion concentrations are perceived by metal-dependent transcription factors and transduced into appropriate cellular responses, which regulate the machineries of competitive metal ion homeostasis and metallo-enzyme activation. The intrinsic toxicity of the majority of metal ions further creates a need for regulated intracellular trafficking, which is carried out by specific chaperones. The Ni(2+)-dependent urease enzymatic system serves as a paradigm for studying the strategies that cells use to handle an essential, yet toxic, metal ion. Although the discovery of urease as the first biological system for which nickel is essential for activity dates to 1975, the rationale for Ni(2+) selection, as well as the cascade of events involving metal-dependent gene regulation and protein-protein interactions leading to enzyme activation, have yet to be fully unraveled. The past 14 years since the Account by Hausinger and co-workers (Karplus, P. A.; Pearson, M. A.; Hausinger, R. P. Acc. Chem. Res. 1997, 30, 330-337) have witnessed impressive achievements in the understanding of the biological chemistry of Ni(2+) in the urease system. In our Account, we discuss more recent advances in the comprehension of the specific role of Ni(2+) in the catalysis and the interplay between Ni(2+) and other metal ions, such as Zn(2+) and Fe(2+), in the metal-dependent enzyme activity. Our discussion focuses on work carried out in our laboratory. In particular, the structural features of the enzyme bound to inhibitors, substrate analogues, and transition state or intermediate analogues have shed light on the catalytic mechanism. Structural and functional information has been correlated to understand the Ni(2+) sensing effected by NikR, a nickel-dependent transcription factor. The urease activation process, involving insertion of Ni(2+) into the urease active site, has been in part dissected and analyzed through the investigation of the molecular properties of the accessory proteins UreD, UreF, and UreG. The intracellular trafficking of Ni(2+) has been rationalized through a deeper understanding of the structural and metal-binding properties of the metallo-chaperone UreE. All the while, a number of key general concepts have been revealed and developed. These include an understanding of (i) the overall ancillary role of Zn(2+) in nickel metabolism, (ii) the intrinsically disordered nature of the GTPase responsible for coupling the energy consumption to the carbon dioxide requirement for the urease activation process, and (iii) the role of the accessory proteins regulating this GTPase activity.

Published
2011

20. Holo-Ni2+ Helicobacter pylori NikR contains four square-planar nickel-binding sites at physiological pH

Author

Stefano Benini, Michele Cianci, Stefano Ciurli, S. Benini, M. Cianci, and S. Ciurli

Subjects
Models, Molecular, Binding Sites, biology, Nickel binding, Chemistry, NICHEL, HELICOBACTER PYLORI, Crystal structure, Helicobacter pylori, Hydrogen-Ion Concentration, biology.organism_classification, Crystallography, X-Ray, Protein Structure, Tertiary, Inorganic Chemistry, Crystallography, Bacterial Proteins, Transcription (biology), Nickel, Transcription factor, NIKR, Histidine
Abstract

The crystal structure of Helicobacter pylori holo-NikR, a Ni(2+)-dependent transcription factor, determined at pH 7.3, shows four square-planar nickel-binding sites, involving one cysteinate and three histidine ligands. This observation reconciles previous inconsistencies among calorimetric data, structural information at non-physiological pH, and computational studies.

Published
2011

21. High resolution crystal structure of Rubrivivax gelatinosus cytochrome c'

Author

Wojciech Rypniewski, Stefano Ciurli, Keith S. Wilson, Stefano Benini, S. Benini, W.R. Rypniewski, K.S. Wilson, and S. Ciurli

Subjects
Models, Molecular, biology, Cytochrome, Cytochromes c', Chemistry, Cytochrome c, Betaproteobacteria, Crystal structure, Hydrogen-Ion Concentration, Crystallography, X-Ray, Biochemistry, Electron transport chain, Inorganic Chemistry, Metal, Crystallography, Electron transfer, visual_art, X-ray crystallography, visual_art.visual_art_medium, biology.protein, Histidine
Abstract

The structure of the cytochrome c' from the purple non-sulfur phototrophic bacterium Rubrivivax gelatinosus was determined using two crystals grown independently at pH 6.3 and pH 8. The resolution attained for the two structures (1.29 A and 1.50 A for the crystals at high and low pH, respectively) is the highest to date for this class of proteins. The two structures were compared in detail in an attempt to investigate the influence of pH on the geometry of the haem and of the coordination environment of the Fe(III) ion. However, while the results suggest some small propensity for the movement of the metal atom out of the plane of the haem ring upon pH increase, the accuracy of the measurements at these two pH below the pK of the axial histidine is not sufficient to provide hard evidence of a shift in the iron position and associated changes.

Published
2007

22. Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing's sarcoma

Author

Ghislaine Bernard, Pier Luigi Lollini, Stefania Benini, Katia Scotlandi, Giordano Nicoletti, Piero Picci, Antonio Curti, Stefania Perdichizzi, Maria Cristina Manara, Alain Bernard, Patrizia Nanni, K. Scotlandi, S. Perdichizzi, G. Bernard, G. Nicoletti, P. Nanni, P.-L. Lollini, A. Curti, M. C. Manara, S. Benini, A. Bernard, and P. Picci

Subjects
Cancer Research, medicine.drug_class, CD99, Sarcoma, Ewing, 12E7 Antigen, Monoclonal antibody, Antigen, Antigens, CD, Cell Line, Tumor, medicine, Humans, Doxorubicin, Antibiotics, Antineoplastic, biology, Ewing's sarcoma, Bone metastasis, Antibodies, Monoclonal, medicine.disease, Hematopoietic Stem Cells, medicine.anatomical_structure, Oncology, biology.protein, Cancer research, Drug Therapy, Combination, Bone marrow, Antibody, Cell Adhesion Molecules, medicine.drug
Abstract

CD99 is a 32 kDa surface glycoprotein that is involved in the migration of leukocytes, cell–cell adhesion and apoptosis of T cells and Ewing’s sarcoma (ES) cells, two cell types with a high level of CD99 expression. Engagement of the molecule induces a rapid death signal that appears to be related to the level of expression of this antigen. The rapid apoptosis induced by agonistic anti-CD99 monoclonal antibodies is of clinical interest in ES, a tumour for which no new drugs have been described as clearly effective in the last 10 years. In this study, we show that an anti-CD99 monoclonal antibody can be used to advantage in association with doxorubicin. Striking effectiveness was observed against local tumours and metastases. No remarkably toxic effects of anti-CD99 monoclonal antibody were found in bone marrow against blood precursors. These results provide the necessary rationale and support for a novel modality of therapeutic intervention, which may have application in the care of patients with ES.

Published
2005

23. Conventional Spinal Chordomas: Investigation of SMARCB1/INI1 Protein Expression, Genetic Alterations in SMARCB1 Gene, and Clinicopathological Features in 89 Patients.

Author

Maioli M, Cocchi S, Gambarotti M, Benini S, Magagnoli G, Gamberi G, Griffoni C, Gasbarrini A, Ghermandi R, Noli LE, Alcherigi C, Ferrari C, Bianchi G, Asioli S, Pignotti E, and Righi A

Abstract

The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical-thoracic-lumbar tumor location ( p = 0.033) and inadequate surgical margins ( p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins., Competing Interests: The authors declare no conflicts of interest.

Published
2024
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24. SynthOutdoor : A synthetic dataset for 3D outdoor light estimation.

Author

Zanardelli M, Moghaddam MG, Leonardi R, Benini S, and Adami N

Abstract

In this work, we present a novel dataset, SynthOutdoor , comprising 39,086 high-resolution images, aimed at addressing the data scarcity in the field of 3D light direction estimation under the assumption of distant lighting. SynthOutdoor was generated using our software (which is also publicly available), that in turn is based on the Unity3D engine. Our dataset provides a set of images rendered from a given input scene, with the camera moving across a predefined path within the scene. This dataset captures a wide variety of lighting conditions through the implementation of a solar cycle. The dataset's ground truth is composed of the following elements: the 3D light direction and color intensity of the sun; the color intensity of the ambient light; the instance segmentation masks of each object and the surface normals map, in which each pixel is assigned with the 3D surface normal in that point (encoded as 3 color channels). By providing not only the light direction and intensity, but also the geometric and semantic information of the rendered images, our dataset can be used not only for light estimation, but also for more general tasks such as 3D geometry and shading estimation from 2D images., (© 2024 The Authors.)

Published
2024
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25. Fighting the scanner effect in brain MRI segmentation with a progressive level-of-detail network trained on multi-site data.

Author

Svanera M, Savardi M, Signoroni A, Benini S, and Muckli L

Subjects
Humans, Child, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Brain diagnostic imaging, Algorithms, Artifacts, Magnetic Resonance Imaging, Neuroimaging
Abstract

Many clinical and research studies of the human brain require accurate structural MRI segmentation. While traditional atlas-based methods can be applied to volumes from any acquisition site, recent deep learning algorithms ensure high accuracy only when tested on data from the same sites exploited in training (i.e., internal data). Performance degradation experienced on external data (i.e., unseen volumes from unseen sites) is due to the inter-site variability in intensity distributions, and to unique artefacts caused by different MR scanner models and acquisition parameters. To mitigate this site-dependency, often referred to as the scanner effect, we propose LOD-Brain, a 3D convolutional neural network with progressive levels-of-detail (LOD), able to segment brain data from any site. Coarser network levels are responsible for learning a robust anatomical prior helpful in identifying brain structures and their locations, while finer levels refine the model to handle site-specific intensity distributions and anatomical variations. We ensure robustness across sites by training the model on an unprecedentedly rich dataset aggregating data from open repositories: almost 27,000 T1w volumes from around 160 acquisition sites, at 1.5 - 3T, from a population spanning from 8 to 90 years old. Extensive tests demonstrate that LOD-Brain produces state-of-the-art results, with no significant difference in performance between internal and external sites, and robust to challenging anatomical variations. Its portability paves the way for large-scale applications across different healthcare institutions, patient populations, and imaging technology manufacturers. Code, model, and demo are available on the project website., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lars Muckli reports financial support was provided by EU Horizon 2020 Framework Programme for Research and Innovation., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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26. The utility of FISH analysis in the diagnosis of BCOR-rearranged sarcomas.

Author

Cocchi S, Gambarotti M, Gamberi G, Magagnoli G, Maioli M, Stevanin M, Samperi F, Righi A, and Benini S

Subjects
Humans, Repressor Proteins genetics, Retrospective Studies, In Situ Hybridization, Fluorescence, Reproducibility of Results, Biomarkers, Tumor genetics, Biomarkers, Tumor analysis, DNA-Binding Proteins genetics, Transcription Factors genetics, Proto-Oncogene Proteins genetics, Sarcoma diagnosis, Sarcoma genetics, Sarcoma pathology, Soft Tissue Neoplasms diagnosis, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms pathology
Abstract

Background: A BCL6 corepressor (BCOR) gene alteration is a genetic signature of rare subsets of sarcomas. The identification of this alteration has recently contributed to the definition of new entities in the current WHO (2020) classification of soft tissue and bone tumours. We retrospectively examined cases of BCOR-rearranged sarcoma (BRS) to assess the reliability of the BCOR FISH analysis using an IVD (in vitro diagnostic) probe., Methods: We investigated and compared the molecular diagnostic strategies and features by collecting 17 data from patients with a BCOR gene rearrangement detected using quantitative-Reverse Transcription-Polymerase Chain Reaction (qRTPCR), Next-Generation Sequencing (NGS) and Fluorescence in situ hybridization (FISH)., Results: We describe fourteen BCOR::CCNB3 sarcomas, one spindle cell sarcoma with a novel BCOR::MAML1 fusion, one spindle cell sarcoma with a novel BCOR::AHR fusion, and one ossifying fibromyxoid tumour with a BCOR::ZC3H7B fusion. FISH analysis of all, except one, BCOR::CCNB3 sarcoma, showed a FISH break-apart pattern with mild signal separation. The MAML1::BCOR sarcoma showed large-space split signals, while in the two patients with AHR::BCOR and ZC3H7B::BCOR fusions, no BCOR rearrangement was observed using FISH., Conclusions: Our study indicates that BCOR FISH analysis using an IVD probe, may be useful to detect the presence of a BCOR rearrangement, including both translocations and inversions; however, negative results, in some cases, can occur., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Published
2024
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27. 3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.

Author

Poonsiri T, Dell'Accantera D, Loconte V, Casnati A, Cervoni L, Arcovito A, Benini S, Ferrari A, Cipolloni M, Cacioni E, De Franco F, Giacchè N, Rinaldo S, Folli C, Sansone F, Berni R, and Cianci M

Subjects
Tolcapone, Autonomic Pathways, Prealbumin, Benzophenones
Abstract

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson's disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis., Competing Interests: The authors Nicola Giacch&egrave;, Marco Cipolloni, Elisa Cacioni, and Francesca De Franco are employees of TES Pharma.

Published
2023
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28. Determination and Kinetic Characterization of a New Potential Inhibitor for AmsI Protein Tyrosine Phosphatase from the Apple Pathogen Erwinia amylovora .

Author

Albani S, Polsinelli I, Mazzei L, Musiani F, and Benini S

Subjects
Virulence, Protein Tyrosine Phosphatases genetics, Protein Tyrosine Phosphatases metabolism, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents metabolism, Plant Diseases microbiology, Polysaccharides, Bacterial metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism, Erwinia amylovora, Malus metabolism, Erwinia genetics, Erwinia metabolism
Abstract

Erwinia amylovora is a Gram-negative bacterium, responsible for the fire blight disease in Rosaceae plants. Its virulence is correlated with the production of an exopolysaccharide (EPS) called amylovoran, which protects the bacterium from the surrounding environment and helps its diffusion inside the host. Amylovoran biosynthesis relies on the expression of twelve genes clustered in the ams operon. One of these genes, amsI , encodes for a Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) called Ea AmsI, which plays a key role in the regulation of the EPS production pathway. For this reason, Ea AmsI was chosen in this work as a target for the development of new antibacterial agents against E. amylovora . To achieve this aim, a set of programs (DOCK6, OpenEye FRED) was selected to perform a virtual screening using a database of ca. 700 molecules. The six best-scoring compounds identified were tested in in vitro assays. A complete inhibition kinetic characterization carried out on the most promising molecule (n-Heptyl β-D-glucopyranoside, N7G) showed an inhibition constant of 7.8 ± 0.6 µM. This study represents an initial step towards the development of new Ea AmsI inhibitors able to act as antibacterial agents against E. amylovora infections.

Published
2023
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29. Fusion transcriptome profiling defines the monoclonal origin of multifocal epithelioid haemangioma of bone.

Author

Errani C, De Benedictis I, Righi A, Valenti B, Del Savio E, Baldazzi D, Benini S, Sbaraglia M, Vega Jimenez B, Vanel D, Donati DM, Dei Tos AP, and Maestro R

Subjects
Humans, Retrospective Studies, Bone and Bones pathology, Biopsy, Hemangioma, Bone Neoplasms genetics, Bone Neoplasms pathology
Abstract

Aims: Epithelioid haemangioma (EH) of bone remains a highly controversial entity. Indeed, the WHO classifies EHs of soft tissues as benign tumours, whereas bone EHs are considered intermediate-locally aggressive tumours due to common multifocal presentation and local destructive growth. To gain insights into the clinical behaviour and biology of EH of bone we retrospectively analysed 42 patients treated in a single institution from 1978 to 2021., Methods and Results: Multifocal presentation was detected in 17 of 42 patients (40%) primarily as synchronous lesions. Patients were treated with curettage (57%), resection (29%) or biopsy, followed by radiotherapy or embolisation (14%). Follow-up (minimum 24 months) was available for 38 patients, with only five local recurrences (13%) and no death of disease. To clarify whether the synchronous bone lesions in multifocal EH represent multicentric disease or clonal dissemination, four cases were profiled by RNA-sequencing. Separate lesions from the same patient, which showed a similar transcriptional profile, expressed the same fusion transcript (involving FOS or FOSB) with identical gene breakpoints., Conclusions: These results indicate that, in EH of bone, multifocal lesions are clonally related and therefore represent the spread of a same neoplastic clone rather than simultaneous independent tumours. This finding is in apparent contradiction with the benign clinical course of the disease, and suggests that tumour dissemination in bone EH probably reflects a phenomenon of passive spreading, with tumour cells colonising distal sites while maintaining their benign biological nature., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Published
2023
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30. NTRK rearranged sarcoma of the bone. Role for larotrectinib in the neoadjuvant setting of an ultra-rare tumor: a case report.

Author

Palmerini E, Frega G, Gambarotti M, Frisoni T, Cesari M, Bazzocchi A, Miceli M, Donati DM, Fanti S, Nanni C, Benini S, Longhi A, Paioli A, Marrari A, Hakim R, Righi A, and Ibrahim T

Abstract

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene-fusion targeted molecules revolutionized the paradigm of treatment of a limited subgroup of cancers of various histologies. Entrectinib and larotrectinib obtained unprecedented response rates in patients with cancer harboring NTRK rearrangements. This evidence recently led to the agnostic approval of these drugs, and evidence (confirmation) of their activity in a broader disease setting is emerging. Here, we report the case of a patient affected by EML4-NTRK3 rearranged undifferentiated spindle cell bone sarcoma treated with larotrectinib, and we argue (discuss about) the incidence and clinical presentation of NTRK gene-fusion positive bone sarcomas, the potential use of upfront treatment with NTRK inhibitors in neoadjuvant setting, and the role of a multidisciplinary tumor board. Despite the rarity of these rearrangements in patients with primitive bone sarcomas, the therapy with NTRK inhibitors represents a highly effective strategy to be pursued in selected cases even in neoadjuvant settings. The management of these very rare cancers should always be discussed in a multidisciplinary board of reference centers., Competing Interests: EP has served on advisory boards for Daiichy Sankyo, Deciphera Pharmaceuticals, Eusa Pharma, and SynOx Therapeutics outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Palmerini, Frega, Gambarotti, Frisoni, Cesari, Bazzocchi, Miceli, Donati, Fanti, Nanni, Benini, Longhi, Paioli, Marrari, Hakim, Righi and Ibrahim.)

Published
2023
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31. CineScale2: a dataset of cinematic camera features in movies.

Author

Savardi M, Kovács AB, Signoroni A, and Benini S

Abstract

The position and orientation of the camera in relation to the subject(s) in a movie scene, namely camera "level" and camera "angle" , are essential features in the film-making process due to their influence on the viewer's perception of the scene. We provide a database containing camera feature annotations on camera angle and camera level, for about 25,000 image frames. Frames are sampled from a wide range of movies, freely available images, and shots from cinematographic websites, and are annotated on the following five categories - Overhead, High, Neutral, Low, and Dutch - for what concerns camera angle, and on six different classes of camera level: Aerial, Eye, Shoulder, Hip, Knee, and Ground level. This dataset is an extension of the Cinescale dataset [1], which contains movie frames and related annotations regarding shot scale. The CineScale2 database enables AI-driven interpretation of shot scale data and opens to a large set of research activities related to the automatic visual analysis of cinematic material, such as movie stylistic analysis, video recommendation, and media psychology. To these purposes, we also provide the model and the code for building a Convolutional Neural Network (CNN) architecture for automated camera feature recognition. All the material is provided on the the project website; video frames can be also provided upon requests to authors, for research purposes under fair use., (© 2023 The Authors. Published by Elsevier Inc.)

Published
2023
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32. IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

Author

Setola E, Benini S, Righi A, Gamberi G, Carretta E, Ferrari C, Avnet S, Palmerini E, Magagnoli G, Gambarotti M, Lollini PL, Cesari M, Cocchi S, Paioli A, Longhi A, Scotlandi K, Laginestra MA, Donati DM, Baldini N, and Ibrahim T

Subjects
Humans, Isocitrate Dehydrogenase genetics, Mutation, Exons, Chondrosarcoma genetics, Bone Neoplasms genetics
Abstract

Background: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients., Methods: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed., Results: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt., Conclusions: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Published
2023
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33. Burden and resources in caregivers of people with multiple sclerosis: A qualitative study.

Author

Benini S, Pellegrini E, Descovich C, and Lugaresi A

Subjects
Humans, Quality of Life, Stress, Psychological psychology, Family psychology, Qualitative Research, Caregivers psychology, Multiple Sclerosis
Abstract

Background: Caregivers of people with Multiple Sclerosis are required to provide ongoing assistance especially during the advanced stages of the disease. They have to manage interventions and assume responsibilities which significantly impact both their personal quality of life and family's dynamics., Objective: A qualitative phenomenological study was carried out to understand the experience of burden in caregivers and their resources to manage it. The study also explores how healthcare services involved in the Multiple Sclerosis Clinical Pathway respond to the needs of well-being of patients and family members., Methods: 17 caregivers were involved in focus groups and in semi-structured individual interviews., Results: Fatigue is experienced by all respondents and it starts when physical disabilities increase or when people become aware of them. Many caregivers declare that they refer to intrinsic (love towards their relatives, patience and dedication) or extrinsic (family members, hobbies) resources to cope with the burden of assistance. Patient associations and the Multiple Sclerosis Clinical Pathway play a significant role in supporting caregivers., Conclusions: Fatigue, loneliness, and isolation are experienced by caregivers and strongly affect their quality of life and health status. The study highlights caregivers' need to reconcile working times with care times, to give more space to self-care and to have moments to share their experiences with someone else. These needs should be at the core of health policies in order to avoid physical and emotional breakdowns which could lead to the rupture of the relational balance on which home care is based., Competing Interests: SB, EP and CD have declared that no competing interests exist. AL has the following competing interests: has served as a Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Roche, Sanofi/ Genzyme and Teva Advisory Board Member. She received congress and travel/accommodation expense compensations or speaker honoraria from Alexion, Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institutions received research grants from Novartis and Sanofi/Genzyme., (Copyright: © 2023 Benini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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34. Osteogenic sarcomas of the hands: A case series with emphasis in its peculiarities and literature review.

Author

de la Guardia V, O'Meally AA, Gambarotti M, Spinnato P, Frisoni T, Cocchi S, Magagnoli G, Ibrahim T, Benini S, Pacheco M, and Righi A

Subjects
Animals, Mice, Prognosis, Immunohistochemistry, Bone Neoplasms pathology, Osteosarcoma pathology
Abstract

Aim: To present our experience on osteosarcomas of the hands and review the existing literature pertaining osteosarcomas in this extremely rare location., Methods: and results: Seven cases of osteosarcomas of the hands were reviewed, and a literature search of all primary osteosarcomas of the hands was performed. All tumors occurred in adults (mean age, 41 years) and were located mainly around the metacarpophalangeal joints. All patients presented with localized long-lasting pain as main symptom. The mean size at diagnosis was 33 mm. Three tumors were low-grade central osteosarcomas, 1 low-grade central chondroblastoma-like osteosarcoma and 3 high-grade osteosarcomas. All tumors were positive for mouse double-minute 2 homolog (MDM2) immunohistochemistry. Three cases yielded results with fluorescence in-situ amplification for MDM2 (12q15)/CEP12. At last follow-up, one patient with a high-grade osteosarcoma was dead of disease. The literature review revealed similar demographic and site distribution of osteosarcomas within the hands than our series and an unusually high proportion of low-grade central and parosteal osteosarcomas when compared to the proportion of these infrequent neoplasms in the whole skeleton., Conclusions: osteosarcomas of hands present in older individuals compared to the population affected by conventional osteosarcomas of all sites. Importantly from a diagnostic, therapeutic and prognostic points of view, around 40% of osteosarcomas of the hands are low-grade osteosarcomas of the central or parosteal types., Competing Interests: Conflict of interest Authors declare no present or potential conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Published
2023
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35. The Efficacy of Molecular Analysis in the Diagnosis of Bone and Soft Tissue Sarcoma: A 15-Year Mono-Institutional Study.

Author

Benini S, Gamberi G, Cocchi S, Magagnoli G, Fortunato AR, Sciulli E, Righi A, and Gambarotti M

Subjects
Humans, Biomarkers, Tumor genetics, Formaldehyde, Paraffin Embedding, Reverse Transcriptase Polymerase Chain Reaction, Sarcoma diagnosis, Sarcoma genetics, Sarcoma pathology
Abstract

The histological diagnosis of sarcoma can be difficult as it sometimes requires the combination of morphological and immunophenotypic analyses with molecular tests. A total of 2705 tissue samples of sarcoma consecutively collected from 2006 until 2020 that had undergone molecular analysis were assessed to evaluate their diagnostic utility compared with histological assessments. A total of 3051 molecular analyses were performed, including 1484 gene fusions tested by c/qRT-PCR, 992 gene rearrangements analysed by FISH, 433 analyses of the gene status of MDM2, 126 mutational analyses and 16 NGS analysis. Of the samples analysed, 68% were from formalin-fixed, paraffin-embedded tissue and 32% were from frozen tissue. C/qRT-PCR and FISH analyses were conclusive on formalin-fixed, paraffin-embedded tissue in 74% and 76% of samples, respectively, but the combination of the two methods gave us conclusive results in 96% and 89% of frozen and formalin-fixed, paraffin-embedded tissues, respectively. We demonstrate the utility of c/qRT-PCR and FISH for sarcoma diagnosis and that each has advantages in specific contexts. We conclude that it is possible to accurately predict the sarcoma subtype using a panel of different subtype-specific FISH probes and c/qRT-PCR assays, thereby greatly facilitating the differential diagnosis of these tumours.

Published
2022
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36. The Flavone Cirsiliol from Salvia x jamensis Binds the F 1 Moiety of ATP Synthase, Modulating Free Radical Production.

Author

Carlini L, Tancreda G, Iobbi V, Caicci F, Bruno S, Esposito A, Calzia D, Benini S, Bisio A, Manni L, Schito A, Traverso CE, Ravera S, and Panfoli I

Subjects
Adenosine Triphosphate metabolism, Animals, Antioxidants, Free Radicals, Hydrogen Peroxide, Mammals metabolism, Molecular Docking Simulation, Reactive Oxygen Species, Flavones pharmacology, Salvia metabolism
Abstract

Several studies have shown that mammalian retinal rod outer segments (OS) are peculiar structures devoid of mitochondria, characterized by ectopic expression of the molecular machinery for oxidative phosphorylation. Such ectopic aerobic metabolism would provide the chemical energy for the phototransduction taking place in the OS. Natural polyphenols include a large variety of molecules having pleiotropic effects, ranging from anti-inflammatory to antioxidant and others. Our goal in the present study was to investigate the potential of the flavonoid cirsiliol, a trihydroxy-6,7-dimethoxyflavone extracted from Salvia x jamensis , in modulating reactive oxygen species production by the ectopic oxidative phosphorylation taking place in the OS. Our molecular docking analysis identified cirsiliol binding sites inside the F1 moiety of the nanomotor F 1 F o -ATP synthase. The experimental approach was based on luminometry, spectrophotometry and cytofluorimetry to evaluate ATP synthesis, respiratory chain complex activity and H 2 O 2 production, respectively. The results showed significant dose-dependent inhibition of ATP production by cirsiliol. Moreover, cirsiliol was effective in reducing the free radical production by the OS exposed to ambient light. We report a considerable protective effect of cirsiliol on the structural stability of rod OS, suggesting it may be considered a promising compound against oxidative stress.

Published
2022
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37. Erwinia tasmaniensis levansucrase shows enantiomer selection for (S)-1,2,4-butanetriol.

Author

Polsinelli I, Salomone-Stagni M, and Benini S

Subjects
Butanols, Crystallography, X-Ray, Erwinia, Gram-Positive Bacteria, Hexosyltransferases, Anti-Bacterial Agents, Gram-Negative Bacteria
Abstract

Levansucrases are biotechnologically interesting fructosyltransferases due to their potential use in the enzymatic or chemo-enzymatic synthesis of glycosides of non-natural substrates relevant to pharmaceutical applications. The structure of Erwinia tasmaniensis levansucrase in complex with (S)-1,2,4-butanetriol and its biochemical characterization suggests the possible application of short aliphatic moieties containing polyols with defined stereocentres in fructosylation biotechnology. The structural information revealed that (S)-1,2,4-butanetriol mimics the natural substrate. The preference of the protein towards a specific 1,2,4-butanetriol enantiomer was assessed using microscale thermophoresis binding assays. Furthermore, the results obtained and the structural comparison of levansucrases and inulosucrases suggest that the fructose binding modes could differ in fructosyltransferases from Gram-positive and Gram-negative bacteria., (open access.)

Published
2022
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38. Periosteal chondrosarcoma: A case series in a referral center with survivorship analysis.

Author

Pacheco M, Barra L, Gambarotti M, Magagnoli G, Sbaraglia M, Asioli S, Cocchi S, Carretta E, Frisoni T, Benini S, Dei Tos AP, and Righi A

Subjects
Adult, Female, Humans, Male, Neoplasm Recurrence, Local pathology, Referral and Consultation, Retrospective Studies, Survivorship, Bone Neoplasms genetics, Bone Neoplasms pathology, Bone Neoplasms surgery, Chondrosarcoma genetics, Chondrosarcoma pathology, Chondrosarcoma surgery
Abstract

Background: Periosteal chondrosarcomas are among the rarest types of chondrosarcomas dealt with in few small series of cases. In this study, we aimed to present our experience with this chondrosarcoma, seek for prognostic factors for OS and DFS and survey the status of IDH1 and IDH2., Results: 55 periosteal chondrosarcomas were retrospectively identified. Median age was 37 years, there was a male predominance (62%). The great majority of cases involved the metaphysis of long bones of the extremities. The median size of the tumors was 7.5 cm. Thirty patients underwent to subtotal surgical resection, 22 to tangential resection and the remaining 3 to amputation. The margins, reported in 54 cases, were wide/radical in 38 patients (70.4%), marginal in 9 (16.7%) and intralesional in 7 (12.9%). Histologically, 23 (42%) were grade 1; 27 (49%), grade 2; 3 (5%), grade 3 and 2 (4%) were dedifferentiated. A third of cases in which mutational analysis was feasible harbored heterozygous mutations in codon 132 of IDH1. Fifty-four cases were included for follow-up (median, 137 months). Four patients had local recurrences and six patients developed metastasis to the lungs. All patients that developed metastasis died of disease, two died of unrelated causes and 46 were alive without disease. OS and DFS was not found to be statistically associated with clinical and pathological parameters considered., Conclusions: periosteal chondrosarcomas exhibit a low-grade behavior that can be adequately treated with marginal excisions. Clinical and morphologic parameters do not seem to predict their outcome., Competing Interests: Declaration of competing interest All authors affirm that we have no actual or potential conflicts of interest, including any financial, personal, or other relationships with other people or organizations., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Published
2022
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39. Primary malignant peripheral nerve sheath tumors of bone: a clinicopathologic reappraisal of 8 cases.

Author

Gambarotti M, Righi A, Sbaraglia M, Cocchi S, Benini S, Magagnoli G, Frisoni T, Palmerini E, Picci P, and Dei Tos AP

Subjects
Humans, Nerve Sheath Neoplasms pathology, Neurofibrosarcoma, Sarcoma, Soft Tissue Neoplasms pathology
Abstract

Primary spindle cell and pleomorphic sarcomas of bone represent an exceedingly rare group of mesenchymal malignancies that include soft tissue histotypes, as malignant peripheral nerve sheath tumor. Outside the head and neck region, only 36 cases of primary malignant peripheral nerve sheath tumor of bone have been described. We retrieved from our archives eight cases of primary malignant peripheral nerve sheath tumor of bone arising outside the head and neck region, describing their clinical, radiological, and morphologic features. Our series, in which all but one patient died of diseases after a median of seven months, confirms that primary malignant peripheral nerve sheath tumors of bone are aggressive tumors. Pathologists should be aware of this rare histotype. More aggressive and active adjuvant treatments should be investigated., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Published
2022
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40. CIC rearranged sarcomas: A single institution experience of the potential pitfalls in interpreting CIC FISH results.

Author

Cocchi S, Gamberi G, Magagnoli G, Maioli M, Righi A, Frisoni T, Gambarotti M, and Benini S

Subjects
Adolescent, Adult, Aged, Biomarkers, Tumor genetics, Child, Female, Humans, In Situ Hybridization, Fluorescence methods, In Situ Hybridization, Fluorescence statistics & numerical data, Liposarcoma, Myxoid pathology, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Real-Time Polymerase Chain Reaction methods, Real-Time Polymerase Chain Reaction statistics & numerical data, Transcription Factors analysis, Transcription Factors genetics, In Situ Hybridization, Fluorescence standards, Liposarcoma, Myxoid diagnostic imaging, Liposarcoma, Myxoid genetics, Oncogene Proteins, Fusion analysis
Abstract

Aim: The aim of this study was to establish how reliable FISH CIC analysis using an IVD (in vitro diagnostic) commercial probe is., Methods and Results: A series of 19 CIC-DUX4 sarcomas were evaluated. The samples presenting CIC-DUX4 fusion transcript detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Sanger sequencing and/or Next Generation Sequencing were selected for Fluorescent in Situ Hybridization (FISH) CIC analysis with CIC break-apart IVD probe and compared to molecular analysis. CIC FISH analysis showed 26% of false negatives., Conclusion: Our results indicate that, in the setting of CIC-DUX4 fusion positive small round cell sarcomas, CIC FISH using IVD commercial probe may lead to false-negative results. This novel study evaluates the diagnostic use of a commercial IVD CIC probe for FISH., (Copyright © 2022. Published by Elsevier GmbH.)

Published
2022
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41. Primary synovial sarcoma of bone: a retrospective analysis of 25 patients.

Author

Righi A, Gambarotti M, Benini S, Gibertoni D, Asioli S, Magagnoli G, Gamberi G, Sbaraglia M, Cocchi S, Staals E, Palmerini E, and Dei Tos AP

Subjects
Adolescent, Adult, Aged, Bone Neoplasms pathology, Child, Female, Humans, Immunohistochemistry, Male, Middle Aged, Retrospective Studies, Sarcoma, Synovial pathology, Young Adult, Antibodies analysis, Bone Neoplasms diagnosis, Oncogene Proteins, Fusion immunology, Sarcoma, Synovial diagnosis
Abstract

Aims: To evaluate the diagnostic accuracy of SSX and SSX::SS18 antibodies in decalcified surgical specimens and outcome of synovial sarcomas (SS) of bone., Methods and Results: Twenty-five cases were classified as bone SS (prevalence 0.32% among malignant primary bone sarcoma). Median age was 34 years (range = 9-79). Twenty-four of 25 patients presented with non-metastatic tumours, one with lung metastases. The majority of tumours involved the long bones of extremities with metaphyseal origin. Mean size of the tumour was 7.1 cm. Twenty cases (80%) were monophasic and five (20%) were biphasic. SS18::SSX fusion-specific antibody had 92% sensitivity and 99% specificity for primary bone SS, whereas SSX C-terminus antibody had 100% sensitivity and 94% specificity. Fluorescence in-situ hybridisation (FISH) analysis was feasible in nine (36%) cases and detected SS18 rearrangement in all nine cases. All patients underwent surgical removal of their primary tumour, with adequate margins in 18 (72%) patients. Chemotherapy with metothrexate, cisplatin, doxorubicin and ifosfamide was used in the seven patients. Two patients with inadequate surgical margins received radiotherapy. With a median follow-up of 80 months (range = 6-428), 5- and 10-year overall survival (OS) was 66.6% and 47.9%, respectively, and 5 and 10 years' disease-free survival (DFS) was 36.8% [95% confidence interval (CI) = 18.0-55.7%] and 32.2% (95% CI = 14.6-51.2%), respectively. A significant improvement in 10 years' DFS in patients undergoing chemotherapy compared with patients who did not was observed (P = 0.039)., Conclusions: Our series highlights the utility of SS18::SSX fusion-specific and SSX C-terminus antibodies to support the diagnosis of SS. Adjustment chemotherapy was associated with improved prognosis in this series., (© 2021 John Wiley & Sons Ltd.)

Published
2022
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42. CEREBRUM-7T: Fast and Fully Volumetric Brain Segmentation of 7 Tesla MR Volumes.

Author

Svanera M, Benini S, Bontempi D, and Muckli L

Subjects
Humans, Brain anatomy & histology, Brain diagnostic imaging, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods, Neural Networks, Computer, Neuroimaging methods
Abstract

Ultra-high-field magnetic resonance imaging (MRI) enables sub-millimetre resolution imaging of the human brain, allowing the study of functional circuits of cortical layers at the meso-scale. An essential step in many functional and structural neuroimaging studies is segmentation, the operation of partitioning the MR images in anatomical structures. Despite recent efforts in brain imaging analysis, the literature lacks in accurate and fast methods for segmenting 7-tesla (7T) brain MRI. We here present CEREBRUM-7T, an optimised end-to-end convolutional neural network, which allows fully automatic segmentation of a whole 7T T1 w MRI brain volume at once, without partitioning the volume, pre-processing, nor aligning it to an atlas. The trained model is able to produce accurate multi-structure segmentation masks on six different classes plus background in only a few seconds. The experimental part, a combination of objective numerical evaluations and subjective analysis, confirms that the proposed solution outperforms the training labels it was trained on and is suitable for neuroimaging studies, such as layer functional MRI studies. Taking advantage of a fine-tuning operation on a reduced set of volumes, we also show how it is possible to effectively apply CEREBRUM-7T to different sites data. Furthermore, we release the code, 7T data, and other materials, including the training labels and the Turing test., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2021
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43. Artificial Intelligence in hair research: A proof-of-concept study on evaluating hair assembly features.

Author

Daniels G, Tamburic S, Benini S, Randall J, Sanderson T, and Savardi M

Subjects
Algorithms, Humans, Proof of Concept Study, Artificial Intelligence, Hair chemistry
Abstract

Objective: The first objective of this study was to apply computer vision and machine learning techniques to quantify the effects of haircare treatments on hair assembly and to identify correctly whether unknown tresses were treated or not. The second objective was to explore and compare the performance of human assessment with that obtained from artificial intelligence (AI) algorithms., Methods: Machine learning was applied to a data set of hair tress images (virgin and bleached), both untreated and treated with a shampoo and conditioner set, aimed at increasing hair volume whilst improving alignment and reducing the flyway of the hair. The automatic quantification of the following hair image features was conducted: local and global hair volumes and hair alignment. These features were assessed at three time points: t 0 (no treatment), t 1 (two treatments) and t 2 (three treatments). Classifier tests were applied to test the accuracy of the machine learning. A sensory test (paired comparison of t 0 vs t 2 ) and an online front image-based survey (paired comparison of t 0 vs t 1 , t 1 vs t 2 , t 0 vs t 2 ) were conducted to compare human assessment with that of the algorithms., Results: The automatic image analysis identified changes to hair volume and alignment which enabled the successful application of the classification tests, especially when the hair images were grouped into untreated and treated groups. The human assessment of hair presented in pairs confirmed the automatic image analysis. The image assessment for both virgin hair and bleached only partially agreed with the analysis of the subset of images used in the online survey. One hypothesis is that treatments changed somewhat the shape of the hair tress, with the effect being more pronounced in bleached hair. This made human assessment of flat images more challenging than when viewed directly in 3D. Overall, the bleached hair exhibited effects of higher magnitude than the virgin hair., Conclusions: This study illustrated the capacity of artificial intelligence for hair image detection and classification, and for image analysis of hair assembly features following treatments. The human assessment partially confirmed the image analysis and highlighted the challenges imposed by the presentation mode., (© 2021 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Published
2021
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44. BS-Net: Learning COVID-19 pneumonia severity on a large chest X-ray dataset.

Author

Signoroni A, Savardi M, Benini S, Adami N, Leonardi R, Gibellini P, Vaccher F, Ravanelli M, Borghesi A, Maroldi R, and Farina D

Subjects
Humans, SARS-CoV-2, X-Rays, COVID-19 diagnostic imaging, Deep Learning, Radiography, Thoracic
Abstract

In this work we design an end-to-end deep learning architecture for predicting, on Chest X-rays images (CXR), a multi-regional score conveying the degree of lung compromise in COVID-19 patients. Such semi-quantitative scoring system, namely Brixia score, is applied in serial monitoring of such patients, showing significant prognostic value, in one of the hospitals that experienced one of the highest pandemic peaks in Italy. To solve such a challenging visual task, we adopt a weakly supervised learning strategy structured to handle different tasks (segmentation, spatial alignment, and score estimation) trained with a "from-the-part-to-the-whole" procedure involving different datasets. In particular, we exploit a clinical dataset of almost 5,000 CXR annotated images collected in the same hospital. Our BS-Net demonstrates self-attentive behavior and a high degree of accuracy in all processing stages. Through inter-rater agreement tests and a gold standard comparison, we show that our solution outperforms single human annotators in rating accuracy and consistency, thus supporting the possibility of using this tool in contexts of computer-assisted monitoring. Highly resolved (super-pixel level) explainability maps are also generated, with an original technique, to visually help the understanding of the network activity on the lung areas. We also consider other scores proposed in literature and provide a comparison with a recently proposed non-specific approach. We eventually test the performance robustness of our model on an assorted public COVID-19 dataset, for which we also provide Brixia score annotations, observing good direct generalization and fine-tuning capabilities that highlight the portability of BS-Net in other clinical settings. The CXR dataset along with the source code and the trained model are publicly released for research purposes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Published
2021
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45. Primary sclerosing epithelioid fibrosarcoma of the spine: a single-institution experience.

Author

Righi A, Pacheco M, Pipola V, Gambarotti M, Benini S, Sbaraglia M, Frisoni T, Boriani S, Dei Tos AP, and Gasbarrini A

Subjects
Adult, Diagnosis, Differential, Female, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Mucin-4 genetics, RNA-Binding Protein EWS genetics, RNA-Binding Protein FUS genetics, Soft Tissue Neoplasms diagnosis, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms pathology, Spine pathology, Epithelioid Cells pathology, Fibrosarcoma diagnosis, Fibrosarcoma genetics, Fibrosarcoma pathology
Abstract

Aims: To present our experience on spinal sclerosing epithelioid fibrosarcoma (SEF) and review the existing literature pertaining to SEF of the spine., Methods and Results: Six cases of spinal SEF were reviewed, and a literature search of all primary SEFs of the spine was performed. All tumours occurred in adults (median age, 41 years) and were located all along the spine, the lumbar vertebrae being the most commonly involved. All patients presented with pain that they had experienced for months. The mean tumour size at diagnosis was 52 mm. Five tumours showed a spectrum of microscopic features consistent with pure SEF, and one showed a hybrid morphology with areas of low-grade fibromyxoid sarcoma. All were diffusely and strongly positive for mucin 4. Two cases were initially misdiagnosed as epithelioid haemangioendothelioma and aggressive chondroblastoma. Fluorescence in-situ hybridisation showed rearrangements of either FUS or EWSR1 in four cases. Reverse transcription polymerase chain reaction showed the presence of FUS-CREB3L1 and EWSR1-CREB3L1 fusion transcripts in two cases and one case, respectively. Of five patients with follow-up data available, two developed one or more local recurrences and three patients had metastatic disease. Distant metastases were mainly to other osseous locations, followed by lungs and lymph nodes. At last follow-up, three patients had died of disease and one was alive with multiple metastases., Conclusions: SEF is an aggressive sarcoma that can involve the spine. It is important to recognise the spine as the primary location of SEF, in order to avoid misdiagnosis as more common primary spinal neoplasms, which can impact on therapeutic approaches., (© 2021 John Wiley & Sons Ltd.)

Published
2021
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46. Giant Cell Tumor of Bone in Patients under 16 Years Old: A Single-Institution Case Series.

Author

Ambrosi F, Righi A, Benini S, Magagnoli G, Chiaramonte I, Manfrini M, Gasbarrini A, Frisoni T, and Gambarotti M

Abstract

Background: Giant cell tumor of bone is a locally aggressive, rarely metastasizing tumor that accounts for about 5% of bone tumors and generally occurs in patients between 20 and 45 years old. A driver mutation in the histone 3.3 (H3.3) gene H3F3A has been identified in as many as 96% of giant cell tumors of bone. The immunohistochemical expression of H3F3A H3.3 G34 expression was found in 97.8% of cases. In the present study, we describe our series of cases of giant cell tumor of bone in pediatric patients <16 years old., Methods: All cases of giant cell tumor of bone in pediatric patients <16 years old treated in our institute between 1982 and 2018 were reviewed. Immunohistochemistry and/or molecular analysis for H3F3A gene mutations was performed to confirm the diagnosis. A group of aneurysmal bone cysts in patients <16 years old was used as a control group., Results: Fifteen cases were retrieved. A pronounced female predominance (93%) was observed. A pure metaphyseal central location occurs in 2 skeletally immature patients., Conclusions: Giant cell tumor of bone should be distinguished from its mimickers due to differences in prognosis and treatment. Immunohistochemical and molecular detection of H3F3A gene mutation represents a reliable diagnostic tool.

Published
2021
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47. Lipoblastoma-like tumor of the spermatic cord: case report and review of the literature.

Author

Gambarotti M, Erdogan KE, Righi A, Benini S, Raspollini MR, Rose AD, Magagnoli G, Sbaraglia M, and Dei Tos AP

Subjects
Adolescent, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Genital Neoplasms, Male chemistry, Genital Neoplasms, Male genetics, Genital Neoplasms, Male surgery, Humans, Immunohistochemistry, Lipoblastoma chemistry, Lipoblastoma genetics, Lipoblastoma surgery, Male, Molecular Diagnostic Techniques, Spermatic Cord chemistry, Spermatic Cord surgery, Genital Neoplasms, Male pathology, Lipoblastoma pathology, Spermatic Cord pathology
Abstract

Lipoblastoma-like tumor is a very rare mesenchymal tumor believed to be restricted to female patients and only recently reported in the spermatic cord of a male patient. We describe herein an additional case of lipoblastoma-like tumor occurring in the spermatic cord, describing its histopathological, immunohistochemical, and molecular features.

Published
2021
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48. CineScale: A dataset of cinematic shot scale in movies.

Author

Savardi M, Kovács AB, Signoroni A, and Benini S

Abstract

We provide a database containing shot scale annotations (i.e., the apparent distance of the camera from the subject of a filmed scene) for more than 792,000 image frames. Frames belong to 124 full movies from the entire filmographies by 6 important directors: Martin Scorsese, Jean-Luc Godard, Béla Tarr, Federico Fellini, Michelangelo Antonioni, and Ingmar Bergman. Each frame, extracted from videos at 1 frame per second, is annotated on the following scale categories: Extreme Close Up (ECU), Close Up (CU), Medium Close Up (MCU), Medium Shot (MS), Medium Long Shot (MLS), Long Shot (LS), Extreme Long Shot (ELS), Foreground Shot (FS), and Insert Shots (IS). Two independent coders annotated all frames from the 124 movies, whilst a third one checked their coding and made decisions in cases of disagreement. The CineScale database enables AI-driven interpretation of shot scale data and opens to a large set of research activities related to the automatic visual analysis of cinematic material, such as the automatic recognition of the director's style, or the unfolding of the relationship between shot scale and the viewers' emotional experience. To these purposes, we also provide the model and the code for building a Convolutional Neural Network (CNN) architecture for automated shot scale recognition. All this material is provided through the project website, where video frames can also be requested to authors, for research purposes under fair use., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2021 The Author(s).)

Published
2021
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49. Association of Clinicopathological Features With Outcome in Chondrosarcomas of the Head and Neck.

Author

Asioli S, Ruengwanichayakun P, Zoli M, Guaraldi F, Sollini G, Greco P, Facco C, Gibertoni D, Jiménez BV, Benini S, Turri-Zanoni M, Pasquini E, Mazzatenta D, Foschini MP, and Righi A

Subjects
Adolescent, Adult, Aged, Chondrosarcoma genetics, Chondrosarcoma surgery, Female, Head and Neck Neoplasms genetics, Head and Neck Neoplasms surgery, Humans, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Mutation, Retrospective Studies, Treatment Outcome, Young Adult, Chondrosarcoma diagnosis, Head and Neck Neoplasms diagnosis
Abstract

Objective: The aim of this study is to assess the association between clinical and radiological features as well as of isocitrate dehydrogenase 1 and 2 ( IDH 1,2) mutations with outcome in head and neck chondrosarcomas., Study Design: Retrospective study., Setting: Tertiary referral center., Methods: Clinical, histological, and molecular data of patients with head and neck chondrosarcomas treated by surgery were collected., Results: Forty-six patients were included. The mean age at diagnosis was 56 years (range, 17-78). The tumor originated from the skull base (52.2%), facial bones (28.2%), or laryngotracheal area (19.6%). At last follow-up (median 52.5 months), 38 patients were alive, 30 of which were disease free, whereas 8 had died, 4 of disease progression and 4 of other causes. Fourteen (30.4%) had local recurrence and 2 (4.3%) had lung metastasis. All cases were negative for cytokeratin AE1/AE3, brachyury, and IDH1 at immunohistochemistry, while Sanger sequencing identified IDH1/2 point mutations, typically IDH1 R132C, in 9 (37.5%) tumors arising from the skull base. Margin infiltration on the surgical specimen negatively affected the outcome, whereas no correlation was identified with IDH mutation status., Conclusions: An adequate margin positively affects survival. IDH mutation status does not affect patient outcome.

Published
2021
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50. The structural and functional characterization of Malus domestica double bond reductase MdDBR provides insights towards the identification of its substrates.

Author

Caliandro R, Polsinelli I, Demitri N, Musiani F, Martens S, and Benini S

Subjects
Amino Acid Sequence, Apoproteins genetics, Apoproteins metabolism, Arabidopsis chemistry, Arabidopsis enzymology, Binding Sites, Butanones metabolism, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression, Genetic Vectors chemistry, Genetic Vectors metabolism, Kinetics, Malus enzymology, Models, Molecular, NADP metabolism, Oxidoreductases genetics, Oxidoreductases metabolism, Plant Proteins genetics, Plant Proteins metabolism, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Rubus chemistry, Rubus enzymology, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Thermodynamics, Nicotiana chemistry, Nicotiana enzymology, Apoproteins chemistry, Butanones chemistry, Malus chemistry, NADP chemistry, Oxidoreductases chemistry, Plant Proteins chemistry
Abstract

In this study we describe the crystal structures of the apoform, the binary and the ternary complexes of a double bond reductase from Malus domestica L. (MdDBR) and explore a range of potential substrates. The overall fold of MdDBR is similar to that of the medium chain reductase/dehydrogenase/zinc-dependent alcohol dehydrogenase-like family. Structural comparison of MdDBR with Arabidopsis thaliana DBR (AtDBR), Nicotiana tabacum DBR (NtDBR) and Rubus idaeus DBR (RiDBR) allowed the identification of key amino acids involved in cofactor and ligands binding and shed light on how these residues may guide the orientation of the substrates. The enzyme kinetic for the substrate trans-4-phenylbuten-2-one has been analyzed, and MdDBR activity towards a variety of substrates was tested. This enzyme has been reported to be involved in the phenylpropanoid pathway where it would catalyze the NADPH-dependent reduction of the α, β-unsaturated double bond of carbonyl metabolites. Our study provides new data towards the identification of MdDBR natural substrate and the biosynthetic pathway where it belongs. Furthermore, the originally proposed involvement in dihydrochalcone biosynthesis in apple must be questioned., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published
2021
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