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2. Digital transition in pathology lab: a survey from the Lombardy region

Author

Belloni, E, Bonoldi, E, Bovo, G, Buoro, S, Cerati, M, Cribiú, F, Dainese, E, Del Gobbo, A, Facchetti, M, Gianatti, A, Gianelli, U, Giunta, P, L'Imperio, V, Milione, M, Nebuloni, M, Pagni, F, Paulli, M, Piga, A, Pasotti, F, Belloni, Elisa, Bonoldi, Emanuela, Bovo, Giorgio, Buoro, Sabrina, Cerati, Michele, Cribiú, Fulvia Milena, Dainese, Emanuele, Del Gobbo, Alessandro, Facchetti, Mattia, Gianatti, Andrea, Gianelli, Umberto, Giunta, Paolo, L'Imperio, Vincenzo, Milione, Massimo, Nebuloni, Manuela, Pagni, Fabio, Paulli, Marco, Piga, Antonella, Pasotti, Fabio, Belloni, E, Bonoldi, E, Bovo, G, Buoro, S, Cerati, M, Cribiú, F, Dainese, E, Del Gobbo, A, Facchetti, M, Gianatti, A, Gianelli, U, Giunta, P, L'Imperio, V, Milione, M, Nebuloni, M, Pagni, F, Paulli, M, Piga, A, Pasotti, F, Belloni, Elisa, Bonoldi, Emanuela, Bovo, Giorgio, Buoro, Sabrina, Cerati, Michele, Cribiú, Fulvia Milena, Dainese, Emanuele, Del Gobbo, Alessandro, Facchetti, Mattia, Gianatti, Andrea, Gianelli, Umberto, Giunta, Paolo, L'Imperio, Vincenzo, Milione, Massimo, Nebuloni, Manuela, Pagni, Fabio, Paulli, Marco, Piga, Antonella, and Pasotti, Fabio

Abstract

Objective: Digital pathology is an opportunity to revise the routine and old artisanal workflow, moving to standard operating procedures, quality control and reproducibility. Here the results of a survey promoted by the Coordinamento della Medicina di Laboratorio (CRC Med Lab) of the Lombardy region in Italy are reported to shed light on the current situation of digital adoption in the country. Methods: The survey composed of 58 questions was sent to 60 pathology laboratories. The results were collected and most significant answers were reported and discussed. Results: Answers were received from 57 (95%) laboratories, a minority organized in spoke-hub networks (16%) with a centralized processing phase (11%). Hybrid manual/computer-assisted traceability was prevalent (36%), with QR/barcode labeling starting within the pathology lab (23%). Different laboratory information systems (LIS) were employed, mostly with alert functions and/or multimedial file attachments (56% and 46%, respectively). The majority opted for a semi-automated tracking management (44, 77%) and 18 centers (32%) were partly digitizing the routine (3⁄4 scanning < 25% of slides). Whole slide images were retained for 3.7 years in average; in-house blocks/slides archiving was still preferred (30, 53%), with 1838 (±1551) and 1798 (±1950) days (5 years) internal permanence for blocks and slides that are stored in out-source (mean turnaround time for return on-demand 3.7±2.1, range 1-10 days). Conclusions: The advantages of digital pathology must be balanced against the challenges faced in the structural revision of the pathology workflow. This regional scouting can represent the foundation to build an efficient and connected digital pathology system in the territory.

Published
2024

3. Pathology Laboratory Archives: Conservation Quality of Nucleic Acids and Proteins for NSCLC Molecular Testing

Author

Eccher, A, Seminati, D, L’Imperio, V, Casati, G, Pilla, D, Malapelle, U, Piga, I, Bindi, G, Marando, A, Bonoldi, E, Dainese, E, Riefolo, M, D’Errico, A, Costantini, M, Lugli, A, Grassi, S, Scarpa, A, Dei Tos, A, Pagni, F, Eccher, Albino, Seminati, Davide, L’Imperio, Vincenzo, Casati, Gabriele, Pilla, Daniela, Malapelle, Umberto, Piga, Isabella, Bindi, Greta, Marando, Alessandro, Bonoldi, Emanuela, Dainese, Emanuele, Riefolo, Mattia, D’Errico, Antonia, Costantini, Matteo, Lugli, Alberto, Grassi, Stefano, Scarpa, Aldo, Dei Tos, Angelo Paolo, Pagni, Fabio, Eccher, A, Seminati, D, L’Imperio, V, Casati, G, Pilla, D, Malapelle, U, Piga, I, Bindi, G, Marando, A, Bonoldi, E, Dainese, E, Riefolo, M, D’Errico, A, Costantini, M, Lugli, A, Grassi, S, Scarpa, A, Dei Tos, A, Pagni, F, Eccher, Albino, Seminati, Davide, L’Imperio, Vincenzo, Casati, Gabriele, Pilla, Daniela, Malapelle, Umberto, Piga, Isabella, Bindi, Greta, Marando, Alessandro, Bonoldi, Emanuela, Dainese, Emanuele, Riefolo, Mattia, D’Errico, Antonia, Costantini, Matteo, Lugli, Alberto, Grassi, Stefano, Scarpa, Aldo, Dei Tos, Angelo Paolo, and Pagni, Fabio

Abstract

In the molecular era, proper archival conditions within pathology laboratories are crucial, especially for formalin-fixed paraffin-embedded (FFPE) tissue specimens retrieved years after the original diagnosis. Indeed, improper preservation can impact the integrity of nucleic acids and protein antigens. This study evaluates the quality status of stored FFPE blocks using multilevel omics approaches. FFPE blocks from 45 Non-Small Cell Lung Carcinoma (NSCLC) cases were analyzed. The blocks were collected from six different pathology archives across Italy with distinct environmental characteristics. Nucleic acids’ quantity and quality, as well as protein antigens, were assessed using various techniques, including MALDI-MSI. RNA was quantitatively higher, but more fragmented, compared to DNA. DNA quantity and quality were suitable for molecular analyses in 94.4% and 62.3% of samples, respectively. RNA quantity was adequate across all samples, but it was optimal only in 22.3% of cases. DNA quality started to deteriorate after 6–8 years, whereas RNA quality diminished only after 10 years of storage. These data might suggest a particular DNA susceptibility to FFPE blocks conservation. Immunohistochemical intensity decreased significantly after 6–8 years of storage, and MALDI-MSI analysis revealed that younger tissue blocks contained more unique proteomic signals than the older ones. This study emphasizes the importance of proper FFPE archiving conditions for molecular analyses. Governance should prioritize attention to pathology archives to ensure quality preservation and optimize predictive testing. By elucidating the nuances of FFPE block storage, this research paves the way for enhanced molecular diagnostics and therapeutic insights regarding oncology and beyond.

Published
2024

4. IRIDE White Book, An Interdisciplinary Research Infrastructure based on Dual Electron linacs&lasers

Author

Alesini, D., Alessandroni, M., Anania, M. P., Andreas, S., Angelone, M., Arcovito, A., Arnesano, F., Artioli, M., Avaldi, L., Babusci, D., Bacci, A., Balerna, A., Bartalucci, S., Bedogni, R., Bellaveglia, M., Bencivenga, F., Benfatto, M., Biedron, S., Bocci, V., Bolognesi, M., Bolognesi, P., Boni, R., Bonifacio, R., Boscolo, M., Boscherini, F., Bossi, F., Broggi, F., Buonomo, B., Calo', V., Catone, D., Capogni, M., Capone, M., Castellano, M., Castoldi, A., Catani, L., Cavoto, G., Cherubini, N., Chirico, G., Cestelli-Guidi, M., Chiadroni, E., Chiarella, V., Cianchi, A., Cianci, M., Cimino, R., Ciocci, F., Clozza, A., Collini, M., Colo', G., Compagno, A., Contini, G., Coreno, M., Cucini, R., Curceanu, C., Dabagov, S., Dainese, E., Davoli, I., Dattoli, G., De Caro, L., De Felice, P., Della Longa, S., Monache, G. Delle, De Spirito, M., Di Cicco, A., Di Donato, C., Di Gioacchino, D., Di Giovenale, D., Di Palma, E., Di Pirro, G., Dodaro, A., Doria, A., Dosselli, U., Drago, A., Escribano, R., Esposito, A., Faccini, R., Ferrari, A., Ferrario, M., Filabozzi, A., Filippetto, D., Fiori, F., Frasciello, O., Fulgentini, L., Gallerano, G. P., Gallo, A., Gambaccini, M., Gatti, C., Gatti, G., Gauzzi, P., Ghigo, A., Ghiringhelli, G., Giannessi, L., Giardina, G., Giannini, C., Giorgianni, F., Giovenale, E., Gizzi, L., Guaraldo, C., Guazzoni, C., Gunnella, R., Hatada, K., Ivashyn, S., Jegerlehner, F., Keeffe, P. O., Kluge, W., Kupsc, A., Iannone, M., Labate, L., Sandri, P. Levi, Lombardi, V., Londrillo, P., Loreti, S., Losacco, M., Lupi, S., Macchi, A., Magazu', S., Mandaglio, G., Marcelli, A., Margutti, G., Mariani, C., Mariani, P., Marzo, G., Masciovecchio, C., Masjuan, P., Mattioli, M., Mazzitelli, G., Merenkov, N. P., Michelato, P., Migliardo, F., Migliorati, M., Milardi, C., Milotti, E., Milton, S., Minicozzi, V., Mobilio, S., Morante, S., Moricciani, D., Mostacci, A., Muccifora, V., Murtas, F., Musumeci, P., Nguyen, F., Orecchini, A., Organtini, G., Ottaviani, P. L., Pace, E., Paci, M., Pagani, C., Pagnutti, S., Palmieri, V., Palumbo, L., Panaccione, G. C., Papadopoulos, C. F., Papi, M., Passera, M., Pasquini, L., Pedio, M., Perrone, A., Petralia, A., Petrillo, C., Petrillo, V., Pillon, M., Pierini, P., Pietropaolo, A., Polosa, A. D., Pompili, R., Portoles, J., Prosperi, T., Quaresima, C., Quintieri, L., Rau, J. V., Reconditi, M., Ricci, A., Ricci, R., Ricciardi, G., Ripiccini, E., Romeo, S., Ronsivalle, C., Rosato, N., Rosenzweig, J. B., Rossi, G., Rossi, A. A., Rossi, A. R., Rossi, F., Russo, D., Sabatucci, A., Sabia, E., Sacchetti, F., Salducco, S., Sannibale, F., Sarri, G., Scopigno, T., Serafini, L., Sertore, D., Shekhovtsova, O., Spassovsky, I., Spadaro, T., Spataro, B., Spinozzi, F., Stecchi, A., Stellato, F., Surrenti, V., Tenore, A., Torre, A., Trentadue, L., Turchini, S., Vaccarezza, C., Vacchi, A., Valente, P., Venanzoni, G., Vescovi, S., Villa, F., Zanotti, G., Zema, N., and Zobov, M.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment, Physics - Accelerator Physics
Abstract

This report describes the scientific aims and potentials as well as the preliminary technical design of IRIDE, an innovative tool for multi-disciplinary investigations in a wide field of scientific, technological and industrial applications. IRIDE will be a high intensity 'particle factory', based on a combination of a high duty cycle radio-frequency superconducting electron linac and of high energy lasers. Conceived to provide unique research possibilities for particle physics, for condensed matter physics, chemistry and material science, for structural biology and industrial applications, IRIDE will open completely new research possibilities and advance our knowledge in many branches of science and technology. IRIDE will contribute to open new avenues of discoveries and to address most important riddles: What does matter consist of? What is the structure of proteins that have a fundamental role in life processes? What can we learn from protein structure to improve the treatment of diseases and to design more efficient drugs? But also how does an electronic chip behave under the effect of radiations? How can the heat flow in a large heat exchanger be optimized? The scientific potential of IRIDE is far reaching and justifies the construction of such a large facility in Italy in synergy with the national research institutes and companies and in the framework of the European and international research. It will impact also on R&D work for ILC, FEL, and will be complementarity to other large scale accelerator projects. IRIDE is also intended to be realized in subsequent stages of development depending on the assigned priorities., Comment: 270 pages

Published
2013

5. IRIDE: Interdisciplinary research infrastructure based on dual electron linacs and lasers

Author

Ferrario, M, Alesini, D, Alessandroni, M, Anania, MP, Andreas, S, Angelone, M, Arcovito, A, Arnesano, F, Artioli, M, Avaldi, L, Babusci, D, Bacci, A, Balerna, A, Bartalucci, S, Bedogni, R, Bellaveglia, M, Bencivenga, F, Benfatto, M, Biedron, S, Bocci, V, Bolognesi, M, Bolognesi, P, Boni, R, Bonifacio, R, Boscherini, F, Boscolo, M, Bossi, F, Broggi, F, Buonomo, B, Calo, V, Catone, D, Capogni, M, Capone, M, Cassou, K, Castellano, M, Castoldi, A, Catani, L, Cavoto, G, Cherubini, N, Chirico, G, Cestelli-Guidi, M, Chiadroni, E, Chiarella, V, Cianchi, A, Cianci, M, Cimino, R, Ciocci, F, Clozza, A, Collini, M, Colo, G, Compagno, A, Contini, G, Coreno, M, Cucini, R, Curceanu, C, Curciarello, F, Dabagov, S, Dainese, E, Davoli, I, Dattoli, G, De Caro, L, De Felice, P, De Leo, V, Dell Agnello, S, Della Longa, S, Delle Monache, G, De Spirito, M, Di Cicco, A, Di Donato, C, Di Gioacchino, D, Di Giovenale, D, Di Palma, E, Di Pirro, G, Dodaro, A, Doria, A, Dosselli, U, Drago, A, Dupraz, K, Escribano, R, Esposito, A, Faccini, R, Ferrari, A, Filabozzi, A, Filippetto, D, Fiori, F, Frasciello, O, Fulgentini, L, Gallerano, GP, Gallo, A, Gambaccini, M, Gatti, C, Gatti, G, Gauzzi, P, Ghigo, A, Ghiringhelli, G, Giannessi, L, Giardina, G, Giannini, C, Giorgianni, F, and Giovenale, E

Subjects
SC Linac, FEL, Particle physics, Neutron source, Compton source, Advanced accelerators concepts, physics.ins-det, hep-ex, physics.acc-ph, Nuclear & Particles Physics, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Other Physical Sciences, Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics
Abstract

This paper describes the scientific aims and potentials as well as the preliminary technical design of IRIDE, an innovative tool for multi-disciplinary investigations in a wide field of scientific, technological and industrial applications. IRIDE will be a high intensity "particles factory", based on a combination of high duty cycle radio-frequency superconducting electron linacs and of high energy lasers. Conceived to provide unique research possibilities for particle physics, for condensed matter physics, chemistry and material science, for structural biology and industrial applications, IRIDE will open completely new research possibilities and advance our knowledge in many branches of science and technology. IRIDE is also supposed to be realized in subsequent stages of development depending on the assigned priorities. © 2013 Elsevier B.V.

Published
2014

6. LISA: Mars and the limits of life

Author

Galletta, G., D'Alessandro, M., Bertoloni, G., Fanti, G., Dainese, E., Pelizzo, M., Ferri, F., Pavarin, D., Bettanini, C., Bianchini, G., and Debei, S.

Subjects
Astrophysics
Abstract

We describe the results of the first tests made on LISA, a simulator of planetary environments designed and built in Padua, dedicated to the study of the limit of bacterial life on the planet Mars. Tests on the cryogenic circuit, on the UV illumination and on bacterial coltures at room temperature that shall be used as references are described., Comment: 4 pages, 3 figures. Mem. SAIt, in press

Published
2007

7. The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

Author

Di Sabatino, A, Battista, N, Biancheri, P, Rapino, C, Rovedatti, L, Astarita, G, Vanoli, A, Dainese, E, Guerci, M, Piomelli, D, Pender, SLF, MacDonald, TT, Maccarrone, M, and Corazza, GR

Subjects
Digestive Diseases, Autoimmune Disease, Crohn's Disease, Cannabinoid Research, Inflammatory Bowel Disease, Oral and gastrointestinal, Animals, Arachidonic Acids, Cannabinoid Receptor Modulators, Cytokines, Humans, Inflammatory Bowel Diseases, Intestinal Mucosa, Intestines, Mice, Myofibroblasts, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, STAT4 Transcription Factor, T-Box Domain Proteins, Biological Sciences, Medical and Health Sciences, Immunology
Abstract

Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.

Published
2011

12. Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey

Author

Fusco, N, Ivanova, M, Frascarelli, C, Criscitiello, C, Cerbelli, B, Pignataro, M, Pernazza, A, Sajjadi, E, Venetis, K, Cursano, G, Pagni, F, Di Bella, C, Accardo, M, Amato, M, Amico, P, Bartoli, C, Bogina, G, Bortesi, L, Boldorini, R, Bruno, S, Cabibi, D, Caruana, P, Dainese, E, De Camilli, E, Dell'Anna, V, Duda, L, Emmanuele, C, Fanelli, G, Fernandes, B, Ferrara, G, Gnetti, L, Gurrera, A, Leone, G, Lucci, R, Mancini, C, Marangi, G, Mastropasqua, M, Nibid, L, Orrù, S, Pastena, M, Peresi, M, Perracchio, L, Santoro, A, Vezzosi, V, Zambelli, C, Zuccalà, V, Rizzo, A, Costarelli, L, Pietribiasi, F, Santinelli, A, Scatena, C, Curigliano, G, Guerini-Rocco, E, Martini, M, Graziano, P, Castellano, I, D'Amati, G, Fusco, Nicola, Ivanova, Mariia, Frascarelli, Chiara, Criscitiello, Carmen, Cerbelli, Bruna, Pignataro, Maria Gemma, Pernazza, Angelina, Sajjadi, Elham, Venetis, Konstantinos, Cursano, Giulia, Pagni, Fabio, Di Bella, Camillo, Accardo, Marina, Amato, Michelina, Amico, Paolo, Bartoli, Caterina, Bogina, Giuseppe, Bortesi, Laura, Boldorini, Renzo, Bruno, Sara, Cabibi, Daniela, Caruana, Pietro, Dainese, Emanuele, De Camilli, Elisa, Dell'Anna, Vladimiro, Duda, Loren, Emmanuele, Carmela, Fanelli, Giuseppe Nicolò, Fernandes, Bethania, Ferrara, Gerardo, Gnetti, Letizia, Gurrera, Alessandra, Leone, Giorgia, Lucci, Raffaella, Mancini, Cristina, Marangi, Grazia, Mastropasqua, Mauro G, Nibid, Lorenzo, Orrù, Sandra, Pastena, Maria, Peresi, Monica, Perracchio, Letizia, Santoro, Angela, Vezzosi, Vania, Zambelli, Claudia, Zuccalà, Valeria, Rizzo, Antonio, Costarelli, Leopoldo, Pietribiasi, Francesca, Santinelli, Alfredo, Scatena, Cristian, Curigliano, Giuseppe, Guerini-Rocco, Elena, Martini, Maurizio, Graziano, Paolo, Castellano, Isabella, d'Amati, Giulia, Fusco, N, Ivanova, M, Frascarelli, C, Criscitiello, C, Cerbelli, B, Pignataro, M, Pernazza, A, Sajjadi, E, Venetis, K, Cursano, G, Pagni, F, Di Bella, C, Accardo, M, Amato, M, Amico, P, Bartoli, C, Bogina, G, Bortesi, L, Boldorini, R, Bruno, S, Cabibi, D, Caruana, P, Dainese, E, De Camilli, E, Dell'Anna, V, Duda, L, Emmanuele, C, Fanelli, G, Fernandes, B, Ferrara, G, Gnetti, L, Gurrera, A, Leone, G, Lucci, R, Mancini, C, Marangi, G, Mastropasqua, M, Nibid, L, Orrù, S, Pastena, M, Peresi, M, Perracchio, L, Santoro, A, Vezzosi, V, Zambelli, C, Zuccalà, V, Rizzo, A, Costarelli, L, Pietribiasi, F, Santinelli, A, Scatena, C, Curigliano, G, Guerini-Rocco, E, Martini, M, Graziano, P, Castellano, I, D'Amati, G, Fusco, Nicola, Ivanova, Mariia, Frascarelli, Chiara, Criscitiello, Carmen, Cerbelli, Bruna, Pignataro, Maria Gemma, Pernazza, Angelina, Sajjadi, Elham, Venetis, Konstantinos, Cursano, Giulia, Pagni, Fabio, Di Bella, Camillo, Accardo, Marina, Amato, Michelina, Amico, Paolo, Bartoli, Caterina, Bogina, Giuseppe, Bortesi, Laura, Boldorini, Renzo, Bruno, Sara, Cabibi, Daniela, Caruana, Pietro, Dainese, Emanuele, De Camilli, Elisa, Dell'Anna, Vladimiro, Duda, Loren, Emmanuele, Carmela, Fanelli, Giuseppe Nicolò, Fernandes, Bethania, Ferrara, Gerardo, Gnetti, Letizia, Gurrera, Alessandra, Leone, Giorgia, Lucci, Raffaella, Mancini, Cristina, Marangi, Grazia, Mastropasqua, Mauro G, Nibid, Lorenzo, Orrù, Sandra, Pastena, Maria, Peresi, Monica, Perracchio, Letizia, Santoro, Angela, Vezzosi, Vania, Zambelli, Claudia, Zuccalà, Valeria, Rizzo, Antonio, Costarelli, Leopoldo, Pietribiasi, Francesca, Santinelli, Alfredo, Scatena, Cristian, Curigliano, Giuseppe, Guerini-Rocco, Elena, Martini, Maurizio, Graziano, Paolo, Castellano, Isabella, and d'Amati, Giulia

Abstract

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.

Published
2023

13. Small Bowel Intussusception Due to Rare Cardiac Intimal Sarcoma Metastasis: A Case Report

Author

Chiarelli, M, Zago, M, Tagliabue, F, Burati, M, Riva, C, Vanzati, A, Dainese, E, Gabrielli, F, Guttadauro, A, De Simone, M, Cioffi, U, Chiarelli M., Zago M., Tagliabue F., Burati M., Riva C., Vanzati A., Dainese E., Gabrielli F., Guttadauro A., De Simone M., Cioffi U., Chiarelli, M, Zago, M, Tagliabue, F, Burati, M, Riva, C, Vanzati, A, Dainese, E, Gabrielli, F, Guttadauro, A, De Simone, M, Cioffi, U, Chiarelli M., Zago M., Tagliabue F., Burati M., Riva C., Vanzati A., Dainese E., Gabrielli F., Guttadauro A., De Simone M., and Cioffi U.

Abstract

Background: Intimal sarcomas are rare malignant mesenchymal tumors arising from the heart and large blood vessels. Their intraluminal growth leads to vascular obstructive symptoms and peripheral neoplastic embolization. Direct infiltration of the lungs or metastases to the pulmonary system, occur in 40% of cases and extrathoracic spread is frequent, also in presentation. Intussusception is an unusual event in adults, accounting for <5% of bowel obstructions. In most cases it is caused by a malignancy and requires surgical resection. Case Presentation: We describe a rare case of a 50-year-old man suffering of bowel obstruction due to intussusception sustained by a small bowel metastasis of a primary cardiac intimal sarcoma. One year and a half before the onset of abdominal symptoms, a grade II intimal sarcoma was removed from his left atrium and consequently he followed a chemotherapy protocol. Four months later a CT scan revealed local recurrence. Eighteen months after heart surgery he referred to the ER with abdominal pain. CT scan showed an ileal intussusception and the patient was scheduled for surgery. A tract of 10 cm ileus was removed containing an intramural polypoid solid mass. Histological analyses revealed a grade II intimal sarcoma consistent with his first diagnosis. Conclusion: Primary heart tumors are late found and often partially resected, therefore metastatic pathways are to be expected. Adult small bowel intussusception is a rare event and caused by a malignancy in one third of cases. Therefore, our recommendation is to always resect the tract involved in order to perform a proper diagnosis.

Published
2021

15. PD-L1 Testing and Squamous Cell Carcinoma of the Head and Neck: A Multicenter Study on the Diagnostic Reproducibility of Different Protocols

Author

Crosta, S, Boldorini, R, Bono, F, Brambilla, V, Dainese, E, Fusco, N, Gianatti, A, L'Imperio, V, Morbini, P, Pagni, F, Crosta, Simona, Boldorini, Renzo, Bono, Francesca, Brambilla, Virginia, Dainese, Emanuele, Fusco, Nicola, Gianatti, Andrea, L'Imperio, Vincenzo, Morbini, Patrizia, Pagni, Fabio, Crosta, S, Boldorini, R, Bono, F, Brambilla, V, Dainese, E, Fusco, N, Gianatti, A, L'Imperio, V, Morbini, P, Pagni, F, Crosta, Simona, Boldorini, Renzo, Bono, Francesca, Brambilla, Virginia, Dainese, Emanuele, Fusco, Nicola, Gianatti, Andrea, L'Imperio, Vincenzo, Morbini, Patrizia, and Pagni, Fabio

Abstract

Immune checkpoint inhibitors for blocking the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are now available for squamous cell carcinoma of the head and neck (HNSCC) in relapsing and/or metastatic settings. In this work, we compared the resulting combined positive score (CPS) of PD-L1 using alternative methods adopted in routine clinical practice and determined the level of diagnostic agreement and inter-observer reliability in this setting. The study applied 5 different protocols on 40 tissue microarrays from HNSCC. The error rate of the individual protocols ranged from a minimum of 7% to a maximum of 21%, the sensitivity from 79% to 96%, and the specificity from 50% to 100%. In the intermediate group (1 ≤ CPS < 20), the majority of errors consisted of an underestimation of PD-L1 expression. In strong expressors, 5 out of 14 samples (36%) were correctly evaluated by all the protocols, but no protocol was able to correctly identify all the "strong expressors". The overall inter-observer agreement in PD-L1 CPS reached 87%. The inter-observer reliability was moderate, with an ICC of 0.774 (95% CI (0.651; 0.871)). In conclusion, our study showed moderate interobserver reliability among different protocols. In order to improve the performances, adequate specific training to evaluate PD-L1 by CPS in the HNSCC setting should be coordinated.

Published
2021

19. Acral cutaneous lesions in the time of COVID‐19

Author

Recalcati, S., primary, Barbagallo, T., additional, Frasin, L.A., additional, Prestinari, F., additional, Cogliardi, A., additional, Provero, M.C., additional, Dainese, E., additional, Vanzati, A., additional, and Fantini, F., additional

Published
2020
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25. Towards zero energy hospital buildings: a polyclinic building as case study

Author

Dainese, E., Walker, Shalika, Maassen, Wim, Zeiler, Wim, Dainese, E., Walker, Shalika, Maassen, Wim, and Zeiler, Wim

Abstract

The need for (nearly) Zero Energy Buildings (nZEBs) becomes increasingly important due to climate change and increasing energy prices. Considering that, on average the existing hospitals use 3.5 times more energy than the nZEB requirement, reaching zero energy a very challenging task. However, monitoring hospitals’ energy flows together with a holistic view on building functions and occupancy can contribute to achieving potential energy savings, which is lacking in the current hospital buildings. Therefore, in this study, the energy saving potentials of a polyclinic building of a hospital in the Netherlands was investigated through a holistic inspection of the building and its occupancy. The analysis is performed in order to investigate the building characteristics, energy supply and demand. It was found that the number of people present was considerably lower than the full capacity, with 30% average occupancy in the medical facilities and 70% for the administrative areas. The air supply of the current ventilation system was found to be constant irrespective of the number of people present in these rooms. Furthermore, a discrepancy of 30- 50% was found between designed and installed lighting systems. The analysis of the polyclinic showed possible energy-saving measures with controlled ventilation rates and lighting according to the occupancy.

Published
2019

27. Amine oxidase from Euphorbia characias: Kinetic and structural characterization

Author

Pintus, F, Sabatucci, A, Maccarrone, M, Dainese, E, and Medda, R

Subjects
Euphorbia characias, Kinetics, Molecular Structure, latex, Euphorbia, small-angle X-ray scattering, 2,4,5-trihydroxyphenyl alanine quinone, copper amine oxidases, human vascular adhesion protein-1, Amine Oxidase (Copper-Containing), 5-trihydroxyphenyl alanine quinone
Abstract

This minireview focuses on a plant copper/2,4,5-trihydroxyphenyl alanine quinone amine oxidase isolated from the latex of the shrub Euphorbia characias (ELAO). This enzyme has been investigated in terms of both molecular structure and kinetic mechanism. The characterization of this enzyme allowed us to identify specific amino acids and domains that play a key role in modulating substrate access into the active site not only for ELAO but also for other plant and mammalian amine oxidases. As mammalian amine oxidases are implicated in several physiological and pathological conditions, the deep structural characterization of their active site accession mechanisms could be the starting point for the development of enzyme modulators with high therapeutic potential. Thus, this paper gives structural/functional insights that open new perspectives in the research about the whole amine oxidase family.

Published
2017

28. In silico mapping of allosteric ligand binding sites in type-1 cannabinoid receptor

Author

Sabatucci, A, Tortolani, D, Dainese, E, and Maccarrone, M

Subjects
Allosteric modulators, CB1 binding, in silico mapping, Molecular Docking Simulation, Binding Sites, Receptor, Cannabinoid, CB1, Humans, Computer Simulation, Ligands, Hydrophobic and Hydrophilic Interactions, Allosteric Site
Abstract

The recent resolution of the crystal structure of type-1 cannabinoid receptor (CB

Published
2017

30. Molecular dynamics study on the Apo- and Holo-forms of 5-lipoxygenase

Author

Torras, J, Maccarrone, M, Dainese, E, Universitat Politècnica de Catalunya. Departament d'Enginyeria Química, and Universitat Politècnica de Catalunya. IMEM - Innovació, Modelització i Enginyeria en (BIO) Materials

Subjects
Enzyme flexibility, Enginyeria química [Àrees temàtiques de la UPC], 5-LOX, Dinàmica molecular, Molecular dynamics
Abstract

Lipoxygenases (LOXs) are nonheme iron-containing enzymes catalyzing the dioxygenation of polyunsaturated fatty acids. LOX catalytic activity depends on the presence of iron in the active site and the iron removal is also able to affect the membrane binding properties of the enzyme. Leukotrienes biosynthesis is initiated by the action of 5-LOX at the level of nuclear membrane and the mechanism of enzyme-membrane interaction is thought to involve structural flexibility and conformational changes at the level of the protein tertiary structure. In this study, we have analyzed by molecular dynamics simulations the conformational changes induced by iron removal in 5-LOX. The data indicate that the degree of enzyme flexibility is related to the presence of iron into the active site that is able to stabilize the protein increasing its rigidity. These findings provide further evidence that the conformation and the functional activity of LOXs is tuned by the presence of iron at the active site, suggesting new approaches for the design of enzyme inhibitors.

Published
2017
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31. Localization of Viral Antigens and Brain Ultrastructural Findings in Striped Dolphins (Stenella coeruleoalba) with ‘Brain-Only’ Dolphin morbillivirus Infection

Author

Di Guardo, G., primary, Giacominelli-Stuffler, R., additional, Baffoni, M., additional, Pietroluongo, G., additional, Di Francesco, C.E., additional, Dufrusine, B., additional, Dainese, E., additional, Cocumelli, C., additional, Eleni, C., additional, Lucà, R., additional, Roperto, F.P., additional, Roperto, S., additional, Casalone, C., additional, Di Francesco, G., additional, Leonardi, L., additional, Centelleghe, C., additional, and Mazzariol, S., additional

Published
2017
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49. IRIDE : Interdisciplinary research infrastructure based on dual electron linacs and lasers

Author

Ferrario, M., Alesini, D., Alessandroni, M., Anania, M. P., Andreas, S., Angelone, M., Arcovito, A., Arnesano, F., Artioli, M., Avaldi, L., Babusci, D., Bacci, A., Balerna, A., Bartalucci, S., Bedogni, R., Bellaveglia, M., Bencivenga, F., Benfatto, M., Biedron, S., Bocci, V., Bolognesi, M., Bolognesi, P., Boni, R., Bonifacio, R., Boscherini, F., Boscolo, M., Bossi, F., Broggi, F., Buonomo, B., Calo, V., Catone, D., Capogni, M., Capone, M., Cassou, K., Castellano, M., Castoldi, A., Catani, L., Cavoto, G., Cherubini, N., Chirico, G., Cestelli-Guidi, M., Chiadroni, E., Chiarella, V., Cianchi, A., Cianci, M., Cimino, R., Ciocci, F., Clozza, A., Collini, M., Colo, G., Compagno, A., Contini, G., Coreno, M., Cucini, R., Curceanu, C., Curciarello, F., Dabagov, S., Dainese, E., Davoli, I., Dattoli, G., De Caro, L., De Felice, P., De Leo, V., Agnello, S. Dell, Della Longa, S., Delle Monache, G., De Spirito, M., Di Cicco, A., Di Donato, C., Di Gioacchino, D., Di Giovenale, D., Di Palma, E., Di Pirro, G., Dodaro, A., Doria, A., Dosselli, U., Drago, A., Dupraz, K., Escribano, R., Esposito, A., Faccini, R., Ferrari, A., Filabozzi, A., Filippetto, D., Fiori, F., Frasciello, O., Fulgentini, L., Gallerano, G. P., Gallo, A., Gambaccini, M., Gatti, C., Gatti, G., Gauzzi, P., Ghigo, A., Ghiringhelli, G., Giannessi, L., Giardina, G., Giannini, C., Giorgianni, F., Giovenale, E., Giulietti, D., Gizzi, L., Guaraldo, C., Guazzoni, C., Gunnella, R., Hatada, K., Iannone, M., Ivashyn, S., Jegerlehner, F., Keeffe, P. O., Kluge, W., Kupsc, Andrzej, Labate, L., Sandri, P. Levi, Lombardi, V., Londrillo, P., Loreti, S., Lorusso, A., Losacco, M., Lukin, A., Lupi, S., Macchi, A., Magazu, S., Mandaglio, G., Marcelli, A., Margutti, G., Mariani, C., Mariani, P., Marzo, G., Masciovecchio, C., Masjuan, P., Mattioli, M., Mazzitelli, G., Merenkov, N. P., Michelato, P., Migliardo, F., Migliorati, M., Milardi, C., Milotti, E., Milton, S., Minicozzi, V., Mobilio, S., Morante, S., Moricciani, D., Mostacci, A., Muccifora, V., Murtas, F., Musumeci, P., Nguyen, F., Orecchini, A., Organtini, G., Ottaviani, P. L., Pace, C., Pace, E., Paci, M., Pagani, C., Pagnutti, S., Palmieri, V., Palumbo, L., Panaccione, G. C., Papadopoulos, C. F., Papi, M., Passera, M., Pasquini, L., Pedio, M., Perrone, A., Petralia, A., Petrarca, M., Petrillo, C., Petrillo, V., Pierini, P., Pietropaolo, A., Pillon, M., Polosa, A. D., Pompili, R., Portoles, J., Prosperi, T., Quaresima, C., Quintieri, L., Rau, J. V., Reconditi, M., Ricci, A., Ricci, R., Ricciardi, G., Ricco, G., Ripani, M., Ripiccini, E., Romeo, S., Ronsivalle, C., Rosato, N., Rosenzweig, J. B., Rossi, A. A., Rossi, A. R., Rossi, F., Rossi, G., Russo, D., Sabatucci, A., Sabia, E., Sacchetti, F., Salducco, S., Sannibale, F., Sarri, G., Scopigno, T., Sekutowicz, J., Serafini, L., Sertore, D., Shekhovtsova, O., Spassovsky, I., Spadaro, T., Spataro, B., Spinozzi, F., Stecchi, A., Stellato, F., Surrenti, V., Tenore, A., Torre, A., Trentadue, L., Turchini, S., Vaccarezza, C., Vacchi, A., Valente, P., Venanzoni, G., Vescovi, S., Villa, F., Zanotti, G., Zema, N., Zobov, M., Zomer, F., Ferrario, M., Alesini, D., Alessandroni, M., Anania, M. P., Andreas, S., Angelone, M., Arcovito, A., Arnesano, F., Artioli, M., Avaldi, L., Babusci, D., Bacci, A., Balerna, A., Bartalucci, S., Bedogni, R., Bellaveglia, M., Bencivenga, F., Benfatto, M., Biedron, S., Bocci, V., Bolognesi, M., Bolognesi, P., Boni, R., Bonifacio, R., Boscherini, F., Boscolo, M., Bossi, F., Broggi, F., Buonomo, B., Calo, V., Catone, D., Capogni, M., Capone, M., Cassou, K., Castellano, M., Castoldi, A., Catani, L., Cavoto, G., Cherubini, N., Chirico, G., Cestelli-Guidi, M., Chiadroni, E., Chiarella, V., Cianchi, A., Cianci, M., Cimino, R., Ciocci, F., Clozza, A., Collini, M., Colo, G., Compagno, A., Contini, G., Coreno, M., Cucini, R., Curceanu, C., Curciarello, F., Dabagov, S., Dainese, E., Davoli, I., Dattoli, G., De Caro, L., De Felice, P., De Leo, V., Agnello, S. Dell, Della Longa, S., Delle Monache, G., De Spirito, M., Di Cicco, A., Di Donato, C., Di Gioacchino, D., Di Giovenale, D., Di Palma, E., Di Pirro, G., Dodaro, A., Doria, A., Dosselli, U., Drago, A., Dupraz, K., Escribano, R., Esposito, A., Faccini, R., Ferrari, A., Filabozzi, A., Filippetto, D., Fiori, F., Frasciello, O., Fulgentini, L., Gallerano, G. P., Gallo, A., Gambaccini, M., Gatti, C., Gatti, G., Gauzzi, P., Ghigo, A., Ghiringhelli, G., Giannessi, L., Giardina, G., Giannini, C., Giorgianni, F., Giovenale, E., Giulietti, D., Gizzi, L., Guaraldo, C., Guazzoni, C., Gunnella, R., Hatada, K., Iannone, M., Ivashyn, S., Jegerlehner, F., Keeffe, P. O., Kluge, W., Kupsc, Andrzej, Labate, L., Sandri, P. Levi, Lombardi, V., Londrillo, P., Loreti, S., Lorusso, A., Losacco, M., Lukin, A., Lupi, S., Macchi, A., Magazu, S., Mandaglio, G., Marcelli, A., Margutti, G., Mariani, C., Mariani, P., Marzo, G., Masciovecchio, C., Masjuan, P., Mattioli, M., Mazzitelli, G., Merenkov, N. P., Michelato, P., Migliardo, F., Migliorati, M., Milardi, C., Milotti, E., Milton, S., Minicozzi, V., Mobilio, S., Morante, S., Moricciani, D., Mostacci, A., Muccifora, V., Murtas, F., Musumeci, P., Nguyen, F., Orecchini, A., Organtini, G., Ottaviani, P. L., Pace, C., Pace, E., Paci, M., Pagani, C., Pagnutti, S., Palmieri, V., Palumbo, L., Panaccione, G. C., Papadopoulos, C. F., Papi, M., Passera, M., Pasquini, L., Pedio, M., Perrone, A., Petralia, A., Petrarca, M., Petrillo, C., Petrillo, V., Pierini, P., Pietropaolo, A., Pillon, M., Polosa, A. D., Pompili, R., Portoles, J., Prosperi, T., Quaresima, C., Quintieri, L., Rau, J. V., Reconditi, M., Ricci, A., Ricci, R., Ricciardi, G., Ricco, G., Ripani, M., Ripiccini, E., Romeo, S., Ronsivalle, C., Rosato, N., Rosenzweig, J. B., Rossi, A. A., Rossi, A. R., Rossi, F., Rossi, G., Russo, D., Sabatucci, A., Sabia, E., Sacchetti, F., Salducco, S., Sannibale, F., Sarri, G., Scopigno, T., Sekutowicz, J., Serafini, L., Sertore, D., Shekhovtsova, O., Spassovsky, I., Spadaro, T., Spataro, B., Spinozzi, F., Stecchi, A., Stellato, F., Surrenti, V., Tenore, A., Torre, A., Trentadue, L., Turchini, S., Vaccarezza, C., Vacchi, A., Valente, P., Venanzoni, G., Vescovi, S., Villa, F., Zanotti, G., Zema, N., Zobov, M., and Zomer, F.

Abstract

This paper describes the scientific aims and potentials as well as the preliminary technical design of RUDE, an innovative tool for multi-disciplinary investigations in a wide field of scientific, technological and industrial applications. IRIDE will be a high intensity "particles factory", based on a combination of high duty cycle radio-frequency superconducting electron linacs and of high energy lasers. Conceived to provide unique research possibilities for particle physics, for condensed matter physics, chemistry and material science, for structural biology and industrial applications, IRIDE will open completely new research possibilities and advance our knowledge in many branches of science and technology. [RIDE is also supposed to be realized in subsequent stages of development depending on the assigned priorities.

Published
2014
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50. Homologous prime boosting based on intranasal delivery of non-pathogenic invasive Escherichia coli expressing MPT64, decreases Mycobacterium tuberculosis dissemination

Author

Sali, Michela, Dainese, E, Morandi, M, Zumbo, A, Rocca, S, Goussard, S, Palù, G, Grillot Courvalin, C, Delogu, Giovanni, Manganelli, R., Sali, Michela (ORCID:0000-0003-3609-2990), Delogu, Giovanni (ORCID:0000-0003-0182-8267), Sali, Michela, Dainese, E, Morandi, M, Zumbo, A, Rocca, S, Goussard, S, Palù, G, Grillot Courvalin, C, Delogu, Giovanni, Manganelli, R., Sali, Michela (ORCID:0000-0003-3609-2990), and Delogu, Giovanni (ORCID:0000-0003-0182-8267)

Abstract

Protein-subunit vaccines as boosting strategies against tuberculosis (TB) infection are currently in the pipeline of TB vaccine research. Their main limitation is represented by their poor immunogenicity, which makes it necessary to couple protein-subunits with adjuvant molecules. In this study, we employed replication-deficient invasive Escherichia coli strains to deliver Mycobacterium tuberculosis proteins to the cytoplasm of non-phagocytic eukaryotic cells using various priming and prime-boosting vaccination protocols. Our results demonstrate that intranasal administration of invasive E. coli expressing the M. tuberculosis protective antigen MPT64 to mice primed with a recombinant BCG strain over-expressing MPT64 on its surface, decrease bacterial burden in mice spleens. Our data suggest that replication-deficient invasive E. coli may represent a suitable platform for BCG/rBCG priming followed by homologous-boosting immunization strategies.

Published
2014

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