762 results on '"Maiello P"'
Search Results
2. Fishing in the gene-pool: implementing trawl-associated eDNA metaprobe for large scale monitoring of fish assemblages
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Maiello, Giulia, Bellodi, Andrea, Cariani, Alessia, Carpentieri, Paolo, Carugati, Laura, Cicala, Davide, Ferrari, Alice, Follesa, Cristina, Ligas, Alessandro, Sartor, Paolo, Sbrana, Alice, Shum, Peter, Stefani, Matteo, Talarico, Lorenzo, Mariani, Stefano, and Russo, Tommaso
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- 2024
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3. Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial
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Martinelli, Erika, Ciardiello, Davide, Martini, Giulia, Napolitano, Stefania, Del Tufo, Sara, D’Ambrosio, Luca, De Chiara, Marco, Famiglietti, Vincenzo, Nacca, Valeria, Cardone, Claudia, Avallone, Antonio, Cremolini, Chiara, Pietrantonio, Filippo, Maiello, Evaristo, Granata, Vincenza, Troiani, Teresa, Cappabianca, Salvatore, Ciardiello, Fortunato, Nardone, Valerio, and Reginelli, Alfonso
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- 2024
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4. The Data Analysis of BULLKID: A Monolithic Array of Particle Absorbers Sensed by KIDs
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Delicato, D., Ahmad, A., Bandiera, L., Calvo, M., Cappelli, M., Castello, G. Del, Roccagiovine, M. Del Gallo, Giammei, M., Guidi, V., Maiello, D., Pettinacci, V., Romagnoni, M., Tamisari, M., Cruciani, A., Mazzolari, A., Monfardini, A., and Vignati, M.
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- 2024
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5. Low-energy spectrum of the BULLKID detector array operated on surface
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Delicato, D., Ahmad, A., Bandiera, L., Calvo, M., Cappelli, M., Del Castello, G., Roccagiovine, M. del Gallo, Giammei, M., Guidi, V., Maiello, D., Pettinacci, V., Romagnoni, M., Tamisari, M., Cruciani, A., Mazzolari, A., Monfardini, A., and Vignati, M.
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High Energy Physics - Experiment ,Physics - Instrumentation and Detectors - Abstract
We present the first continuous operation in a surface lab of BULLKID, a detector for searches of light Dark Matter and precision measurements of the coherent and elastic neutrino-nucleus scattering. The detector consists of an array of 60 cubic silicon particle absorbers of 0.34 g each, sensed by cryogenic kinetic inductance detectors. The data presented focusses on one of the central elements of the array and on its surrounding elements used as veto. The energy spectrum resulting from an exposure of 39 hours to ambient backgrounds, obtained without radiation shields, is flat at the level of $(2.0\pm0.1\,{\rm stat.}\pm0.2\,{\rm syst.})\times10^6$ counts / keV kg days down to the energy threshold of $160\pm13$ eV. The data analysis demonstrates the unique capability of rejecting backgrounds generated from interactions in other sites of the array, stemming from the segmented and monolithic structure of the detector.
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- 2023
- Full Text
- View/download PDF
6. Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
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Ünal, Pelin, Lu, Ye, Bueno-de-Mesquita, Bas, van Eijck, Casper H. J., Talar-Wojnarowska, Renata, Szentesi, Andrea, Gazouli, Maria, Kreivenaite, Edita, Tavano, Francesca, Małecka-Wojciesko, Ewa, Erőss, Bálint, Oliverius, Martin, Bunduc, Stefania, Nóbrega Aoki, Mateus, Vodickova, Ludmila, Boggi, Ugo, Giaccherini, Matteo, Kondrackiene, Jurate, Chammas, Roger, Palmieri, Orazio, Theodoropoulos, George E., Bijlsma, Maarten F., Basso, Daniela, Mohelnikova-Duchonova, Beatrice, Soucek, Pavel, Izbicki, Jakob R., Kiudelis, Vytautas, Vanella, Giuseppe, Arcidiacono, Paolo Giorgio, Włodarczyk, Barbara, Hackert, Thilo, Schöttker, Ben, Uzunoglu, Faik G., Bambi, Franco, Goetz, Mara, Hlavac, Viktor, Brenner, Hermann, Perri, Francesco, Carrara, Silvia, Landi, Stefano, Hegyi, Péter, Dijk, Frederike, Maiello, Evaristo, Capretti, Giovanni, Testoni, Sabrina Gloria Giulia, Petrone, Maria Chiara, Stocker, Hannah, Ermini, Stefano, Archibugi, Livia, Gentiluomo, Manuel, Cavestro, Giulia Martina, Pezzilli, Raffaele, Di Franco, Gregorio, Milanetto, Anna Caterina, Sperti, Cosimo, Neoptolemos, John P., Morelli, Luca, Vokacova, Klara, Pasquali, Claudio, Lawlor, Rita T., Bazzocchi, Francesca, Kupcinskas, Juozas, Capurso, Gabriele, Campa, Daniele, and Canzian, Federico
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- 2024
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7. Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
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Ascierto, Paolo A., Casula, Milena, Bulgarelli, Jenny, Pisano, Marina, Piccinini, Claudia, Piccin, Luisa, Cossu, Antonio, Mandalà, Mario, Ferrucci, Pier Francesco, Guidoboni, Massimo, Rutkowski, Piotr, Ferraresi, Virginia, Arance, Ana, Guida, Michele, Maiello, Evaristo, Gogas, Helen, Richtig, Erika, Fierro, Maria Teresa, Lebbe, Celeste, Helgadottir, Hildur, Queirolo, Paola, Spagnolo, Francesco, Tucci, Marco, Del Vecchio, Michele, Cao, Maria Gonzales, Minisini, Alessandro Marco, De Placido, Sabino, Sanmamed, Miguel F., Mallardo, Domenico, Paone, Miriam, Vitale, Maria Grazia, Melero, Ignacio, Grimaldi, Antonio M., Giannarelli, Diana, Dummer, Reinhard, Sileni, Vanna Chiarion, and Palmieri, Giuseppe
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- 2024
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8. Mechanical power is associated with cardiac output and pulmonary blood flow in an experimental acute respiratory distress syndrome in pigs
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Yingying Zhang, Jakob Wittenstein, Anja Braune, Raphael Theilen, Lorenzo Maiello, Giulia Benzi, Thomas Bluth, Thomas Kiss, Xi Ran, Thea Koch, Patricia R. M. Rocco, Marcus J. Schultz, Jörg Kotzerke, Marcelo Gama De Abreu, Robert Huhle, and Martin Scharffenberg
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ARDS ,cardiac output ,mechanical power ,pulmonary blood flow ,ventilator-induced lung injury ,68Gallium ,Physiology ,QP1-981 - Abstract
BackgroundDespite being essential in patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) may cause lung injury and hemodynamic instability. Mechanical power (MP) may describe the net injurious effects of MV, but whether it reflects the hemodynamic effects of MV is currently unclear. We hypothesized that MP is also associated with cardiac output (CO) and pulmonary blood flow (PBF).Methods24 anesthetized pigs with experimental acute lung injury were ventilated for 18 h according to one of three strategies: 1) Open lung approach (OLA), 2) ARDS Network high-PEEP/FIO2 strategy (HighPEEP), or 3) low-PEEP/FIO2 strategy (LowPEEP). Total MP was assessed as the sum of energy dissipated to overcome airway resistance and energy temporarily stored in the elastic lung tissue per minute. The distribution of pulmonary perfusion was determined by positron emission tomography. Regional PBF and MP, assessed in three iso-gravitational regions of interest (ROI) with equal lung mass (ventral, middle, and dorsal ROI), were compared between groups.ResultsMP was higher in the LowPEEP than in the OLA group, while CO did not differ between groups. After 18 h, regional PBF did not differ between groups. During LowPEEP, regional MP was higher in the ventral ROI compared to OLA and HighPEEP groups (2.5 ± 0.3 vs. 1.4 ± 0.4 and 1.6 ± 0.3 J/min, respectively, P < 0.001 each), and higher in the middle ROI compared to the OLA group (2.5 ± 0.4 vs. 1.6 ± 0.5 J/min, P = 0.04). MP in the dorsal ROI did not differ between groups (1.4 ± 0.9 vs. 1.4 ± 0.5 vs. 1.3 ± 0.8 J/min, P = 0.916). Total MP was independently associated with CO [0.34 (0.09, 0.59), P = 0.020]. Regional MP was positively associated with PBF irrespective of the regions [0.52 (0.14, 0.76), P = 0.01; 0.49 (0.10, 0.74), P = 0.016; 0.64 (0.32, 0.83), P = 0.001 for ventral, middle, and dorsal ROI, respectively]. Subgroup analysis revealed a significant association of MP and CO only in the OLA group as well as a significant association between MP with regional PBF only in the HighPEEP group.ConclusionIn this model of acute lung injury in pigs ventilated with either open lung approach, high, or low PEEP tables recommended by the ARDS network, MP correlated positively with CO and regional PBF, whereby these clinically relevant lung-protective ventilation strategies influenced the associations.
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- 2024
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9. Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis
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Maiorano, Brigida Anna, De Giorgi, Ugo, Verzoni, Elena, Maiello, Evaristo, Procopio, Giuseppe, Conteduca, Vincenza, and Di Maio, Massimo
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- 2024
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10. Intravenous Bacille Calmette–Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis
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Larson, Erica C., Ellis-Connell, Amy L., Rodgers, Mark A., Gubernat, Abigail K., Gleim, Janelle L., Moriarty, Ryan V., Balgeman, Alexis J., Ameel, Cassaundra L., Jauro, Solomon, Tomko, Jaime A., Kracinovsky, Kara B., Maiello, Pauline, Borish, H. Jake, White, Alexander G., Klein, Edwin, Bucsan, Allison N., Darrah, Patricia A., Seder, Robert A., Roederer, Mario, Lin, Philana Ling, Flynn, JoAnne L., O’Connor, Shelby L., and Scanga, Charles A.
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- 2023
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11. Low-energy spectrum of the BULLKID detector array operated on surface
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D. Delicato, A. Ahmad, L. Bandiera, M. Calvo, M. Cappelli, G. Del Castello, M. del Gallo Roccagiovine, M. Giammei, V. Guidi, D. Maiello, V. Pettinacci, M. Romagnoni, M. Tamisari, A. Cruciani, A. Mazzolari, A. Monfardini, and M. Vignati
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Astrophysics ,QB460-466 ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract We present the first continuous operation in a surface lab of BULLKID, a detector for searches of light Dark Matter and precision measurements of the coherent and elastic neutrino-nucleus scattering. The detector consists of an array of 60 cubic silicon particle absorbers of 0.34 g each, sensed by cryogenic kinetic inductance detectors. The data presented focusses on one of the central elements of the array and on its surrounding elements used as veto. The energy spectrum resulting from an exposure of 39 h to ambient backgrounds, obtained without radiation shields, is flat at the level of $$(2.0\pm 0.1\,\mathrm{stat.}\pm 0.2\,\mathrm{syst.})\times 10^6$$ ( 2.0 ± 0.1 stat . ± 0.2 syst . ) × 10 6 counts/keV kg days down to the energy threshold of $$160\pm 13$$ 160 ± 13 eV. The data analysis demonstrates the unique capability of rejecting backgrounds generated from interactions in other sites of the array, stemming from the segmented and monolithic structure of the detector.
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- 2024
- Full Text
- View/download PDF
12. Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
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Pelin Ünal, Ye Lu, Bas Bueno-de-Mesquita, Casper H. J. van Eijck, Renata Talar-Wojnarowska, Andrea Szentesi, Maria Gazouli, Edita Kreivenaite, Francesca Tavano, Ewa Małecka-Wojciesko, Bálint Erőss, Martin Oliverius, Stefania Bunduc, Mateus Nóbrega Aoki, Ludmila Vodickova, Ugo Boggi, Matteo Giaccherini, Jurate Kondrackiene, Roger Chammas, Orazio Palmieri, George E. Theodoropoulos, Maarten F. Bijlsma, Daniela Basso, Beatrice Mohelnikova-Duchonova, Pavel Soucek, Jakob R. Izbicki, Vytautas Kiudelis, Giuseppe Vanella, Paolo Giorgio Arcidiacono, Barbara Włodarczyk, Thilo Hackert, Ben Schöttker, Faik G. Uzunoglu, Franco Bambi, Mara Goetz, Viktor Hlavac, Hermann Brenner, Francesco Perri, Silvia Carrara, Stefano Landi, Péter Hegyi, Frederike Dijk, Evaristo Maiello, Giovanni Capretti, Sabrina Gloria Giulia Testoni, Maria Chiara Petrone, Hannah Stocker, Stefano Ermini, Livia Archibugi, Manuel Gentiluomo, Giulia Martina Cavestro, Raffaele Pezzilli, Gregorio Di Franco, Anna Caterina Milanetto, Cosimo Sperti, John P. Neoptolemos, Luca Morelli, Klara Vokacova, Claudio Pasquali, Rita T. Lawlor, Francesca Bazzocchi, Juozas Kupcinskas, Gabriele Capurso, Daniele Campa, and Federico Canzian
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Association study ,Enhancer ,Pancreatic cancer ,Single nucleotide polymorphism ,Transcription factor binding site ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
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- 2024
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13. A powerful machine learning approach to identify interactions of differentially abundant gut microbial subsets in patients with metastatic and non-metastatic pancreatic cancer
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Annacandida Villani, Andrea Fontana, Concetta Panebianco, Carmelapia Ferro, Massimiliano Copetti, Radmila Pavlovic, Denise Drago, Carla Fiorentini, Fulvia Terracciano, Francesca Bazzocchi, Giuseppe Canistro, Federica Pisati, Evaristo Maiello, Tiziana Pia Latiano, Francesco Perri, and Valerio Pazienza
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Microbiota ,machine learning ,pancreatic cancer ,metastasis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Pancreatic cancer has a dismal prognosis, as it is often diagnosed at stage IV of the disease and is characterized by metastatic spread. Gut microbiota and its metabolites have been suggested to influence the metastatic spread by modulating the host immune system or by promoting angiogenesis. To date, the gut microbial profiles of metastatic and non-metastatic patients need to be explored. Taking advantage of the 16S metagenomic sequencing and the PEnalized LOgistic Regression Analysis (PELORA) we identified clusters of bacteria with differential abundances between metastatic and non-metastatic patients. An overall increase in Gram-negative bacteria in metastatic patients compared to non-metastatic ones was identified using this method. Furthermore, to gain more insight into how gut microbes can predict metastases, a machine learning approach (iterative Random Forest) was performed. Iterative Random Forest analysis revealed which microorganisms were characterized by a different level of relative abundance between metastatic and non-metastatic patients and established a functional relationship between the relative abundance and the probability of having metastases. At the species level, the following bacteria were found to have the highest discriminatory power: Anaerostipes hadrus, Coprobacter secundus, Clostridium sp. 619, Roseburia inulinivorans, Porphyromonas and Odoribacter at the genus level, and Rhodospirillaceae, Clostridiaceae and Peptococcaceae at the family level. Finally, these data were intertwined with those from a metabolomics analysis on fecal samples of patients with or without metastasis to better understand the role of gut microbiota in the metastatic process. Artificial intelligence has been applied in different areas of the medical field. Translating its application in the field of gut microbiota analysis may help fully exploit the potential information contained in such a large amount of data aiming to open up new supportive areas of intervention in the management of cancer.
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- 2024
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14. Low-energy spectrum of the BULLKID detector array operated on surface
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Delicato, D., Ahmad, A., Bandiera, L., Calvo, M., Cappelli, M., Del Castello, G., del Gallo Roccagiovine, M., Giammei, M., Guidi, V., Maiello, D., Pettinacci, V., Romagnoni, M., Tamisari, M., Cruciani, A., Mazzolari, A., Monfardini, A., and Vignati, M.
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- 2024
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15. Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial
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Laura Orlando, Evaristo Maiello, Michele Orditura, Anna Diana, Giuliano Antoniol, Maria Grazia Morritti, Michele Aieta, Mariangela Ciccarese, Salvatore Pisconti, Roberto Bordonaro, Antonio Russo, Antonio Febbraro, Paola Schiavone, Annamaria Quaranta, Chiara Caliolo, Dario Loparco, Margherita Cinefra, Giuseppe Colucci, and Saverio Cinieri
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Metronomic chemotherapy ,Her2 negative advanced breast cancer ,Anthracyclines ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC. Methods: Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity. Results: From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A). Conclusions: First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.
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- 2024
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16. Effects of Gypsum Application at Different Levels of Nutrient Solution Electrical Conductivity on Yield, Quality and Antioxidant Activity of Soilless Strawberry Grown in Cocopeat
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Otilia C. MURARIU, Alessio V. TALLARITA, Vasile STOLERU, Eugenio COZZOLINO, Massimo MIRABELLA, Silvia Brindusa HAMBURDA, Pasquale LOMBARDI, Antonio CUCINIELLO, Roberto MAIELLO, Vincenzo CENVINZO, and Gianluca CARUSO
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Fragaria x ananassa Duch ,soilless ,firmness ,dry matter ,soluble solids ,colour ,Food processing and manufacture ,TP368-456 - Abstract
Research on strawberry (Fragaria x ananassa Duch.) was carried out in greenhouse in 2022-2023, arranging a 4 x 2 factorial experiment, consisting of four levels of electrical conductivity of the nutrient solutions (1.2, 1.7, 2.2, and 2.7 dS m-1) and application of gypsum (without application – control and application). The plants were grown in coconut fibre substrate from late October to early June. The 2.2 dS m-1 ECsol resulted in the highest yield, whereas the highest values of dry matter and soluble solids were recorded under 2.7 dS m-1 ECsol. Gypsum application resulted in the increase of dry matter, soluble solids, firmness and colour components. The 2.2 and 2.7 dS m-1 ECsol led to the highest levels of hydrophilic and lipophilic antioxidant activities as well as polyphenols and vitamin C. From the research carried out on strawberry grown in coconut fibre, it arose that the 2.2 dS m-1 EC of the nutrient solution showed the best effect on yield, but it did not generally differ from 2.7 dS m-1 regarding the quality of the 'fruits'. Gypsum treatment represents an effective strategy to improve some important qualitative characteristics of strawberry 'fruits', under the perspective of sustainable management of crop systems.
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- 2024
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17. Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma
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Brigida Anna Maiorano, Giovanni Schinzari, Carmine Carbone, Geny Piro, Ernesto Rossi, Massimo Di Maio, Annamaria Di Giacomo, and Evaristo Maiello
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urothelial carcinoma ,avelumab ,cytokines ,NLR ,biomarkers ,prognostic ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundAvelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Cytokines represent circulating mediators of the complex interaction between cancer, the immune system, and inflammation. Inflammation, a hallmark of cancer, can be expressed by circulating factors. In different tumor subtypes, peripheral blood biomarkers, such as circulating cytokines, and systemic inflammatory indexes, have been addressed as potential prognostic factors for immune checkpoint inhibitors. However, their role in mUC still needs to be determined.MethodsBetween February 2021 and April 2023, we prospectively collected plasma cytokines and inflammation indexes in 28 patients with mUC before starting avelumab as first-line maintenance. The primary endpoint was the relationship between baseline cytokines and inflammatory indexes with the clinical benefit (CB), defined as the number of Responders. Secondary endpoints included the correlation of baseline cytokines and inflammatory indexes with progression-free survival (PFS), overall survival (OS), and the number and grade of immune-related adverse events.ResultsHigh pre-treatment levels of interferon (IFN)-γ and interleukin (IL)-2, and low levels of IL-6, IL-8, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic-inflammation index (SII) were associated with clinical benefit and longer survival. In the multivariate analysis, low IL-8, NLR, and SII levels maintained a positive prognostic value for OS.ConclusionOur data suggest that, in mUC patients receiving avelumab, pre-treatment levels of plasma cytokines and inflammatory indexes may serve as potential prognostic biomarkers for response and efficacy. In particular, patients with signs of pre-therapeutic inflammation showed a significantly lower response and survival to avelumab. On the contrary, low systemic inflammation and high levels of cytokines characterized responders and longer survivors.
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- 2024
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18. Author Correction: Intravenous Bacille Calmette–Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis
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Larson, Erica C., Ellis-Connell, Amy L., Rodgers, Mark A., Gubernat, Abigail K., Gleim, Janelle L., Moriarty, Ryan V., Balgeman, Alexis J., Ameel, Cassaundra L., Jauro, Solomon, Tomko, Jaime A., Kracinovsky, Kara B., Maiello, Pauline, Borish, H. Jake, White, Alexander G., Klein, Edwin, Bucsan, Allison N., Darrah, Patricia A., Seder, Robert A., Roederer, Mario, Lin, Philana Ling, Flynn, JoAnne L., O’Connor, Shelby L., and Scanga, Charles A.
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- 2024
- Full Text
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19. Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
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Paolo A. Ascierto, Milena Casula, Jenny Bulgarelli, Marina Pisano, Claudia Piccinini, Luisa Piccin, Antonio Cossu, Mario Mandalà, Pier Francesco Ferrucci, Massimo Guidoboni, Piotr Rutkowski, Virginia Ferraresi, Ana Arance, Michele Guida, Evaristo Maiello, Helen Gogas, Erika Richtig, Maria Teresa Fierro, Celeste Lebbe, Hildur Helgadottir, Paola Queirolo, Francesco Spagnolo, Marco Tucci, Michele Del Vecchio, Maria Gonzales Cao, Alessandro Marco Minisini, Sabino De Placido, Miguel F. Sanmamed, Domenico Mallardo, Miriam Paone, Maria Grazia Vitale, Ignacio Melero, Antonio M. Grimaldi, Diana Giannarelli, Reinhard Dummer, Vanna Chiarion Sileni, and Giuseppe Palmieri
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Science - Abstract
Abstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.
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- 2024
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20. Biostimulant Effects of Algae Species, Arbuscular Mycorrhizal Fungi, and Their Combinations on Yield and Quality of Yellow Tomato Landrace Under Different Crop Cycles
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Soumaya Abidi, Alessio Vincenzo Tallarita, Eugenio Cozzolino, Vasile Stoleru, Otilia Cristina Murariu, Amina Abidi, Roberto Maiello, Vincenzo Cenvinzo, Pasquale Lombardi, Antonio Cuciniello, Lamia Hamrouni, Gianluca Caruso, and Rafik Balti
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sustainable agriculture ,local variety ,biostimulants ,brown algae extracts ,arbuscular mycorrhizal fungi (AMF) ,fruit colour ,Plant culture ,SB1-1110 - Abstract
Recent agricultural research has prioritized the development of environmentally friendly management strategies to ensure food security, among which the application of biostimulants such as brown algae extracts, arbuscular mycorrhizal fungi (AMF), and their combination are included. The experimental protocol was based on the factorial combination of two planting times (4 May and 1 June) and seven biostimulant treatments (three brown algae species, Cystoseria tamariscifolia—C.t.; Fucus vesiculosus—F.v.; Padina pavonica—P.p.; arbuscular mycorrhizal fungi—AMF; C.t. + AMF; F.v. + AMF; P.p. + AMF) plus an untreated control. The earlier transplant resulted in a higher yield, due to the higher number of fruits per plant, and a higher plant fresh and dry biomass. The treatments with P.p. and F.v. extracts and the combination P.p. + AMF led to the highest yields (56.7 t ha−1), mainly due to the highest fruit number per plant. The earlier planting time led to higher values of dry residue, soluble solids, firmness, and colour component ‘a’. The highest values of fruit dry residue were recorded under the F.v. and P.p. extracts, and the combinations F.v. + AMF and P.p. + AMF, the highest soluble solid content with P.p. treatment, and firmness under P.p. + AMF. The highest levels of ‘L’ and ‘a’ fruit colour components were obtained under the P.p. extract treatment, of ‘b’ upon the application of P.p. and F.v. extract, and AMF + P.p. and AMF + F.v. The later planting time led to significantly higher values of the antioxidant parameters, as did the application of the P.p. extract and P.p. + AMF. CAT activity was more intense corresponding to the later tomato crop cycle, P.p. extract, and AMF + P.p. Overall, our study highlights the potential of biostimulants, particularly brown algae extracts and their combination with AMF, to improve tomato yield, antioxidant properties, and biochemical activities.
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- 2024
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21. Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians
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Piccardi, Margherita, Gentiluomo, Manuel, Bertoncini, Stefania, Pezzilli, Raffaele, Erőss, Bálint, Bunduc, Stefania, Uzunoglu, Faik G., Talar-Wojnarowska, Renata, Vanagas, Tomas, Sperti, Cosimo, Oliverius, Martin, Aoki, Mateus Nóbrega, Ermini, Stefano, Hussein, Tamás, Boggi, Ugo, Jamroziak, Krzysztof, Maiello, Evaristo, Morelli, Luca, Vodickova, Ludmila, Di Franco, Gregorio, Landi, Stefano, Szentesi, Andrea, Lovecek, Martin, Puzzono, Marta, Tavano, Francesca, van Laarhoven, Hanneke W. M., Zerbi, Alessandro, Mohelnikova-Duchonova, Beatrice, Stocker, Hannah, Costello, Eithne, Capurso, Gabriele, Ginocchi, Laura, Lawlor, Rita T., Vanella, Giuseppe, Bazzocchi, Francesca, Izbicki, Jakob R., Latiano, Anna, Bueno-de-Mesquita, Bas, Ponz de Leon Pisani, Ruggero, Schöttker, Ben, Soucek, Pavel, Hegyi, Péter, Gazouli, Maria, Hackert, Thilo, Kupcinskas, Juozas, Poskiene, Lina, Tacelli, Matteo, Roth, Susanne, Carrara, Silvia, Perri, Francesco, Hlavac, Viktor, Theodoropoulos, George E., Busch, Olivier R., Mambrini, Andrea, van Eijck, Casper H. J., Arcidiacono, Paolo, Scarpa, Aldo, Pasquali, Claudio, Basso, Daniela, Lucchesi, Maurizio, Milanetto, Anna Caterina, Neoptolemos, John P., Cavestro, Giulia Martina, Janciauskas, Dainius, Chen, Xuechen, Chammas, Roger, Goetz, Mara, Brenner, Hermann, Archibugi, Livia, Dannemann, Michael, Canzian, Federico, Tofanelli, Sergio, and Campa, Daniele
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- 2023
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22. Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes
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Oliviero, Barbara, Dei Cas, Michele, Zulueta, Aida, Maiello, Roberta, Villa, Alessandro, Martinelli, Carla, Del Favero, Elena, Falleni, Monica, Montavoci, Linda, Varchetta, Stefania, Mele, Dalila, Donadon, Matteo, Soldani, Cristiana, Franceschini, Barbara, Maestri, Marcello, Piccolo, Gaetano, Barabino, Matteo, Bianchi, Paolo Pietro, Banales, Jesus M., Mantovani, Stefania, Mondelli, Mario U., and Caretti, Anna
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- 2023
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23. Evaluation of inherited germline mutations in cancer susceptibility genes among pancreatic cancer patients: a single-center study
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Tavano, Francesca, Gioffreda, Domenica, Fontana, Andrea, Palmieri, Orazio, Gentile, Annamaria, Latiano, Tiziana, Latiano, Anna, Latiano, Tiziana Pia, Scaramuzzi, Matteo, Maiello, Evaristo, Bazzocchi, Francesca, and Perri, Francesco
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- 2023
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24. Corrigendum: Spatial analysis of demersal food webs through integration of eDNA metabarcoding with fishing activities
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Davide Cicala, Giulia Maiello, Fabio Fiorentino, Germana Garofalo, Daniela Massi, Alice Sbrana, Stefano Mariani, Simone D’Alessandro, Matteo Stefani, Lucie Perrodin, and Tommaso Russo
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Food Webs Analysis (FWA) ,environmental DNA (eDNA) ,marine communities ,abiotic factors ,fishing pressure ,Mediterranean Sea ,Science ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Published
- 2024
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25. Harmonization of tumor mutation burden testing with comprehensive genomic profiling assays: an IQN Path initiative
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Nicola Normanno, Paolo Chiodini, Riziero Esposito Abate, Raffaella Pasquale, Alessandra Sacco, Vittorio Simeon, Monica Rosaria Maiello, and Daniela Frezzetti
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Although conflicting results emerged from different studies, the tumor mutational burden (TMB) appears as one of most reliable biomarkers of sensitivity to immune checkpoint inhibitors. Several laboratories are reporting TMB values when performing comprehensive genomic profiling (CGP) without providing a clinical interpretation, due to the lack of validated cut-off values. The International Quality Network for Pathology launched an initiative to harmonize TMB testing with CGP assay and favor the clinical implementation of this biomarker.Methods TMB evaluation was performed with three commercially available CGP panels, TruSight Oncology 500 (TSO500), Oncomine Comprehensive Plus Assay (OCA) and QIAseq Multimodal Panel (QIA), versus the reference assay FoundationOne CDx (F1CDx). Archived clinical samples derived from 60 patients with non-small cell lung cancer were used for TMB assessment. Adjusted cut-off values for each panel were calculated.Results Testing was successful for 91.7%, 100%, 96.7% and 100% of cases using F1CDx, TSO500, OCA and QIA, respectively. The matrix comparison analysis, between the F1CDx and CGP assays, showed a linear correlation for all three panels, with a higher correlation between F1CDx and TSO500 (rho=0.88) than in the other two comparisons (rho=0.77 for QIA; 0.72 for OCA). The TSO500 showed the best area under the curve (AUC, value 0.96), with a statistically significant difference when compared with the AUC of OCA (0.83, p value=0.01) and QIA (0.88, p value=0.028). The Youden Index calculation allowed us to extrapolate TMB cut-offs of the different panels corresponding to the 10 mutations/megabase (muts/Mb) cut-off of F1CDx: 10.19, 10.4 and 12.37 muts/Mb for TSO500, OCA and QIA, respectively. Using these values, we calculated the relative accuracy measures for the three panels. TSO500 showed 86% specificity and 96% sensitivity, while OCA and QIA had lower yet similar values of specificity and sensitivity (73% and 88%, respectively).Conclusion This study estimated TMB cut-off values for commercially available CGP panels. The results showed a good performance of all panels on clinical samples and the calculated cut-offs support better accuracy measures for TSO500. The validated cut-off values can drive clinical interpretation of TMB testing in clinical research and clinical practice.
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- 2024
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26. TV Series: A Form of Adaptation to The Contemporary Media Condition
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Angela Maiello
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postcinema ,transmedia storytelling ,tv series ,Fine Arts ,Aesthetics ,BH1-301 - Abstract
The article connects the forms of contemporary TV series with the narrative and participatory logics of contemporary media. In particular, the author proposes to consider the wide diffusion and popularity of TV series as a form of response and adaptation to the contemporary media condition. The article proposes an analysis of the ways in which the human instinct for storytelling finds form in contemporary participatory media practices. This reflection is situated within the broader debate on post-cinema and the ways in which new technologies have transformed cinema and audiovisual products. This theoretical perspective is related to the well-known twentieth-century philosophical reflection on the status of narration. TV series, therefore, are a response to the “call for concordance” (Ricœur) that is nowadays more evident than ever. Yet there seems to be a sort of paradox here, that characterises the TV series aesthetic experience: in the process of accomplishing this concordance, by creating solid and unitary world, TV series adapt that transmedia aesthetic (Jenkins) of fragmentation that is typical of contemporary media logic. At the end the author discusses some examples.
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- 2023
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27. Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians
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Margherita Piccardi, Manuel Gentiluomo, Stefania Bertoncini, Raffaele Pezzilli, Bálint Erőss, Stefania Bunduc, Faik G. Uzunoglu, Renata Talar-Wojnarowska, Tomas Vanagas, Cosimo Sperti, Martin Oliverius, Mateus Nóbrega Aoki, Stefano Ermini, Tamás Hussein, Ugo Boggi, Krzysztof Jamroziak, Evaristo Maiello, Luca Morelli, Ludmila Vodickova, Gregorio Di Franco, Stefano Landi, Andrea Szentesi, Martin Lovecek, Marta Puzzono, Francesca Tavano, Hanneke W. M. van Laarhoven, Alessandro Zerbi, Beatrice Mohelnikova-Duchonova, Hannah Stocker, Eithne Costello, Gabriele Capurso, Laura Ginocchi, Rita T. Lawlor, Giuseppe Vanella, Francesca Bazzocchi, Jakob R. Izbicki, Anna Latiano, Bas Bueno-de-Mesquita, Ruggero Ponz de Leon Pisani, Ben Schöttker, Pavel Soucek, Péter Hegyi, Maria Gazouli, Thilo Hackert, Juozas Kupcinskas, Lina Poskiene, Matteo Tacelli, Susanne Roth, Silvia Carrara, Francesco Perri, Viktor Hlavac, George E. Theodoropoulos, Olivier R. Busch, Andrea Mambrini, Casper H. J. van Eijck, Paolo Arcidiacono, Aldo Scarpa, Claudio Pasquali, Daniela Basso, Maurizio Lucchesi, Anna Caterina Milanetto, John P. Neoptolemos, Giulia Martina Cavestro, Dainius Janciauskas, Xuechen Chen, Roger Chammas, Mara Goetz, Hermann Brenner, Livia Archibugi, Michael Dannemann, Federico Canzian, Sergio Tofanelli, and Daniele Campa
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Neandertal ,Pancreatic cancer ,Association study ,Introgression ,Eurasians ,Admixture ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.
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- 2023
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28. Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP)
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Galli, Elena, Fortina, Anna Belloni, Ricci, Giampaolo, Maiello, Nunzia, Neri, Iria, Baldo, Ermanno, Berti, Irene, Bonamonte, Domenico, Capra, Lucetta, Carboni, Elena, Carello, Rossella, Caroppo, Francesca, Cavagni, Giovanni, Chinellato, Iolanda, Cipriani, Francesca, Comberiati, Pasquale, Diociaiuti, Andrea, Di Lernia, Vito, Duse, Marzia, Filippeschi, Cesare, Giannetti, Arianna, Giovannini, Mattia, Licari, Amelia, Marseglia, Gian Luigi, Pace, Manuela, Patrizi, Annalisa, Pajno, Giovanni Battista, Peroni, Diego, Villani, Alberto, and Eichenfield, Lawrence
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Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Pediatric Research Initiative ,Good Health and Well Being ,Adolescent ,Child ,Dermatitis ,Atopic ,Dermatology ,Humans ,Hyperplasia ,Pediatricians ,Pediatrics ,Atopic Dermatitis ,Childhood ,Position Paper ,Management ,Topical Therapies ,New Drugs ,Paediatrics and Reproductive Medicine ,Paediatrics - Abstract
Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.
- Published
- 2022
29. Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)
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Degiuli, Maurizio, Ortenzi, Monica, Tomatis, Mariano, Puca, Lucia, Cianflocca, Desiree, Rega, Daniela, Maroli, Annalisa, Elmore, Ugo, Pecchini, Francesca, Milone, Marco, La Mendola, Roberta, Soligo, Erica, Deidda, Simona, Spoletini, Domenico, Cassini, Diletta, Aprile, Alessandra, Mineccia, Michela, Nikaj, Herald, Marchegiani, Francesco, Maiello, Fabio, Bombardini, Cristina, Zuolo, Michele, Carlucci, Michele, Ferraro, Luca, Falato, Armando, Biondi, Alberto, Persiani, Roberto, Marsanich, Patrizia, Fusario, Daniele, Solaini, Leonardo, Pollesel, Sara, Rizzo, Gianluca, Coco, Claudio, Di Leo, Alberto, Cavaliere, Davide, Roviello, Franco, Muratore, Andrea, D’Ugo, Domenico, Bianco, Francesco, Bianchi, Paolo Pietro, De Nardi, Paola, Rigamonti, Marco, Anania, Gabriele, Belluco, Claudio, Polastri, Roberto, Pucciarelli, Salvatore, Gentilli, Sergio, Ferrero, Alessandro, Scabini, Stefano, Baldazzi, Gianandrea, Carlini, Massimo, Restivo, Angelo, Testa, Silvio, Parini, Dario, De Palma, Giovanni Domenico, Piccoli, Micaela, Rosati, Riccardo, Spinelli, Antonino, Delrio, Paolo, Borghi, Felice, Guerrieri, Marco, and Reddavid, Rossella
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- 2023
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30. Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes
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Barbara Oliviero, Michele Dei Cas, Aida Zulueta, Roberta Maiello, Alessandro Villa, Carla Martinelli, Elena Del Favero, Monica Falleni, Linda Montavoci, Stefania Varchetta, Dalila Mele, Matteo Donadon, Cristiana Soldani, Barbara Franceschini, Marcello Maestri, Gaetano Piccolo, Matteo Barabino, Paolo Pietro Bianchi, Jesus M. Banales, Stefania Mantovani, Mario U. Mondelli, and Anna Caretti
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Medicine ,Science - Abstract
Abstract Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.
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- 2023
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31. Net gain: Low‐cost, trawl‐associated eDNA samplers upscale ecological assessment of marine demersal communities
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Giulia Maiello, Lorenzo Talarico, Chris Brodie, Paolo Carpentieri, Alice Sbrana, Peter Shum, Stefano Mariani, and Tommaso Russo
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environmental DNA ,environmental impacts ,fished communities ,marine biodiversity ,trawl fishery ,Tyrrhenian Sea ,Environmental sciences ,GE1-350 ,Microbial ecology ,QR100-130 - Abstract
Abstract Marine biodiversity stewardship requires costly and time‐consuming capture‐based monitoring techniques, which limit our understanding of the distribution and status of marine populations. Here, we reconstruct catch and demersal community composition in a set of 24 fishing sites in the central Tyrrhenian Sea by gathering environmental DNA (eDNA) aboard commercial bottom‐trawl fishing vessels. We collected genetic material from two sources: the water draining from the net after the end of hauling operations (“slush”), and custom‐made rolls of gauze tied to a hollow perforated sphere placed inside the fishing net (“metaprobe”). Species inventories were generated using a combination of fish‐specific (Tele02 12S) and universal metazoan (COI) molecular markers. DNA metabarcoding data recovered over 90% of the caught taxa and accurately reconstructed the overall structure of the assemblages of the examined sites, reflecting expected differences linked to major drivers of community structure in Mediterranean demersal ecosystems, such as depth, distance from the coast, and fishing effort. eDNA also returned a “biodiversity bonus” mostly consisting of pelagic species not catchable by bottom trawl but present in the surrounding environment. Overall, the “metaprobe” gauzes showed a greater biodiversity detection power as compared to “slush” water, both qualitatively and quantitatively, strengthening the idea that these low‐cost sampling devices can play a major role in upscaling the gathering of data on both catch composition and the broader ecological characteristics of marine communities sustaining trawling activities. This approach has the potential to drastically expand the reach of ecological monitoring, whereby fishing vessels operating across the oceans may serve as opportunistic scientific platforms to increase the strength and granularity of marine biodiversity data.
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- 2024
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32. Spatial analysis of demersal food webs through integration of eDNA metabarcoding with fishing activities
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Davide Cicala, Giulia Maiello, Fabio Fiorentino, Germana Garofalo, Daniela Massi, Alice Sbrana, Stefano Mariani, Simone D’Alessandro, Matteo Stefani, Lucie Perrodin, and Tommaso Russo
- Subjects
Food Webs Analysis (FWA) ,environmental DNA (eDNA) ,marine communities ,abiotic factors ,fishing pressure ,Mediterranean Sea ,Science ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Abstract
The evaluation of the status of marine communities, and especially the monitoring of those heavily exploited by fisheries, is a key, challenging task in marine sciences. Fishing activities are a major source of disruption to marine food webs, both directly, by selectively removing components at specific trophic levels (TL), and indirectly, by altering habitats and production cycles. Food web analysis can be very useful in the context of an Ecosystem Approach to Fisheries, but food web reconstructions demand large and expensive data sets, which are typically available only for a small fraction of marine ecosystems. Recently, new technologies have been developed to easily, quickly and cost-effectively collect environmental DNA (eDNA) during fishing activities. By generating large, multi-marker metabarcoding data from eDNA samples obtained from commercial trawlers, it is possible to produce exhaustive taxonomic inventories for the exploited ecosystems, which are suitable for food-web reconstructions. Here, we integrate and re-analyse the data of a recent study in which the α diversity was investigated using the eDNA opportunistically collected during fishing operations. Indeed, we collect highly resolved information on species feeding relationships to reconstruct the food webs at different sites in the Strait of Sicily (Mediterranean Sea) from eDNA and catch data. After observing that the trophic networks obtained from eDNA metabarcoding data are more consistent with the available knowledge, a set of food web indicators (species richness, number of links, direct connectance and generality) is computed and analysed to unravel differences in food webs structure through different areas (spatial variations). Species richness, number of links and generality (positively) and direct connectance (negatively) are correlated with increasing distance from the coast and fishing effort intensity. The combined effects of environmental gradients and fishing effort on food web structure at different study sites are then examined and modelled. Taken together, these findings indicate the suitability of eDNA metabarcoding to assist and food web analysis, obtain several food web-related ecological indicators, and tease out the effect of fishing intensity from the environmental gradients of marine ecosystems.
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- 2024
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33. Cetuximab as third‐line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild‐type circulating tumor DNA: Individual patient data pooled analysis of CRICKET and CAVE trials
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G. Martini, D. Ciardiello, V. Famiglietti, D. Rossini, C. Antoniotti, T. Troiani, S. Napolitano, L. Esposito, T. P. Latiano, E. Maiello, M. Del Re, S. Lonardi, G. Aprile, D. Santini, G. Masi, A. Avallone, N. Normanno, F. Pietrantonio, C. Pinto, F. Ciardiello, C. Cremolini, and E. Martinelli
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cetuximab ,immunotherapy ,metastatic colorectal cancer ,rechallenge ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The rechallenge strategy is based on the concept that a subset of patients with RAS wild‐type (WT) metastatic colorectal cancer (mCRC) could still benefit of epidermal growth factor receptor (EGFR) inhibition, after progression to an anti‐EGFR based‐therapy. We performed a pooled analysis of two‐phase II prospective trials to determine the role of rechallenge in third‐line mCRC patients with RAS/BRAF WT baseline circulating tumor DNA (ctDNA). Individual data of 33 and 13 patients from CAVE and CRICKET trials that received as third‐line therapy cetuximab rechallenge were collected. Overall survival (OS), Progression‐free survival (PFS), Overall response rate (ORR), Stable disease (SD) >6 months were calculated. Adverse events were reported. For the whole 46 patient population, median PFS (mPFS) was 3.9 months (95% Confidence Interval, CI 3.0–4.9) with median OS (mOS) of 16.9 months (95% CI 11.7–22.1). For CRICKET patients, mPFS was 3.9 months (95% CI 1.7–6.2); mOS was 13.1 months (95% CI 7.3–18.9) with OS rates at 12, 18, and 24 months of 62%, 23%, and 0%, respectively. For CAVE patients, mPFS was 4.1 months (95% CI 3.0–5.2); mOS was 18.6 months (95% CI 11.7–25.4) with OS rates at 12, 18, 24 months of 61%, 52%, 21%, respectively. Skin rash was more frequently reported in CAVE trial (87.9% vs. 30.8%; p = 0.001), whereas a increased incidence of hematological toxicities was observed in CRICKET trial (53.8%% vs. 12.1%; p = 0.003). Third‐line cetuximab rechallenge in combination with either irinotecan or avelumab in RAS/BRAF WT ctDNA mCRC patients represents a promising therapy.
- Published
- 2023
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34. Correction to: Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis
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Maiorano, Brigida Anna, De Giorgi, Ugo, Verzoni, Elena, Maiello, Evaristo, Procopio, Giuseppe, Conteduca, Vincenza, and Di Maio, Massimo
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- 2024
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35. The Impact of Inadequate Exposure to Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors on the Development of Resistance in Non-Small-Cell Lung Cancer Cells
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Daniela Frezzetti, Vincenza Caridi, Laura Marra, Rosa Camerlingo, Amelia D’Alessio, Francesco Russo, Serena Dotolo, Anna Maria Rachiglio, Riziero Esposito Abate, Marianna Gallo, Monica Rosaria Maiello, Alessandro Morabito, Nicola Normanno, and Antonella De Luca
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non-small-cell lung cancer ,EGFR mutations ,resistance ,EGFR–tyrosine kinase inhibitors ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients treated with EGFR–tyrosine kinase inhibitors (TKIs) inevitably develop resistance through several biological mechanisms. However, little is known on the molecular mechanisms underlying acquired resistance to suboptimal EGFR-TKI doses, due to pharmacodynamics leading to inadequate drug exposure. To evaluate the effects of suboptimal EGFR-TKI exposure on resistance in NSCLC, we obtained HCC827 and PC9 cell lines resistant to suboptimal fixed and intermittent doses of gefitinib and compared them to cells exposed to higher doses of the drug. We analyzed the differences in terms of EGFR signaling activation and the expression of epithelial–mesenchymal transition (EMT) markers, whole transcriptomes byRNA sequencing, and cell motility. We observed that the exposure to low doses of gefitinib more frequently induced a partial EMT associated with an induced migratory ability, and an enhanced transcription of cancer stem cell markers, particularly in the HCC827 gefitinib-resistant cells. Finally, the HCC827 gefitinib-resistant cells showed increased secretion of the EMT inducer transforming growth factor (TGF)-β1, whose inhibition was able to partially restore gefitinib sensitivity. These data provide evidence that different levels of exposure to EGFR-TKIs in tumor masses might promote different mechanisms of acquired resistance.
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- 2024
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36. Familial Dilated Cardiomyopathy: A Novel MED9 Short Isoform Identification
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Monica Franzese, Mario Zanfardino, Andrea Soricelli, Annapaola Coppola, Ciro Maiello, Marco Salvatore, Concetta Schiano, and Claudio Napoli
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RNA sequencing ,heart failure ,dilated cardiomyopathy ,precision medicine ,atherosclerosis ,mediator complex ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Familial dilated cardiomyopathy (DCM) is among the leading indications for heart transplantation. DCM alters the transcriptomic profile. The alteration or activation/silencing of physiologically operating transcripts may explain the onset and progression of this pathological state. The mediator complex (MED) plays a fundamental role in the transcription process. The aim of this study is to investigate the MED subunits, which are altered in DCM, to identify target crossroads genes. RNA sequencing allowed us to identify specific MED subunits that are altered during familial DCM, transforming into human myocardial samples. N = 13 MED subunits were upregulated and n = 7 downregulated. MED9 alone was significantly reduced in patients compared to healthy subjects (HS) (FC = −1.257; p < 0.05). Interestingly, we found a short MED9 isoform (MED9s) (ENSG00000141026.6), which was upregulated when compared to the full-transcript isoform (MED9f). Motif identification analysis yielded several significant matches (p < 0.05), such as GATA4, which is downregulated in CHD. Moreover, although the protein–protein interaction network showed FOG2/ZFPM2, FOS and ID2 proteins to be the key interacting partners of GATA4, only FOG2/ZFPM2 overexpression showed an interaction score of “high confidence” ≥ 0.84. A significant change in the MED was observed during HF. For the first time, the MED9 subunit was significantly reduced between familial DCM and HS (p < 0.05), showing an increased MED9s isoform in DCM patients with respect to its full-length transcript. MED9 and GATA4 shared the same sequence motif and were involved in a network with FOG2/ZFPM2, FOS, and ID2, proteins already implicated in cardiac development.
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- 2024
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37. Prevalence and determinants of permanent atrial fibrillation in post-menopausal hypertensive women
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Maria Maiello, Annagrazia Cecere, Marco Matteo Ciccone, and Pasquale Palmiero
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Atrial fibrillation ,postmenopausal women ,hypertension ,obesity ,left atrial ,Medicine - Abstract
Objective. We studied the prevalence and major predisposing factors of permanent atrial fibrillation (PAF) in a population of hypertensive post-menopausal (HPMW) women. Materials and Methods. We enrolled 125 consecutive HPMW with PAF, 125 HPMW in sinus rhythm were the control group (CG). Women with valvular heart disease, coronary artery disease, WPW syndrome, left ventricular (LV) ejection fraction
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- 2023
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38. Enfortumab vedotin in metastatic urothelial carcinoma: the solution EVentually?
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Brigida Anna Maiorano, Martina Catalano, Evaristo Maiello, and Giandomenico Roviello
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enfortumab vedotin ,ADC ,antibody-drug conjugate ,nectin-4 ,urothelial carcinoma ,bladder cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Metastatic urothelial carcinoma (mUC) is an aggressive malignancy with a dismal prognosis. Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of an antibody targeting Nectin-4. This protein is highly expressed in UC cells. After binding, monomethyl auristatin E is released into cells, causing UC cell death. EV has been approved as a single agent for pre-treated mUC, with interesting improvements in response rate and survival in a setting with limited treatment options. More recently, EV approval occurred in cisplatin-ineligible naïve mUC patients in combination with pembrolizumab. Our review aims to summarize the pharmacological properties, clinical studies, and future developments of EV in mUC.
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- 2023
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39. Evaluation of inherited germline mutations in cancer susceptibility genes among pancreatic cancer patients: a single-center study
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Francesca Tavano, Domenica Gioffreda, Andrea Fontana, Orazio Palmieri, Annamaria Gentile, Tiziana Latiano, Anna Latiano, Tiziana Pia Latiano, Matteo Scaramuzzi, Evaristo Maiello, Francesca Bazzocchi, and Francesco Perri
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Pancreatic cancer ,Genetic testing ,Next Generation Sequencing ,Germline variants ,Prevalence ,Cancer family history ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Germline mutations in cancer susceptibility genes were identified in pancreatic cancer (PanC) patients with a sporadic disease and in those unselected for family cancer history. Methods With the aim to determine the prevalence of germline predisposition genes mutations in PanC, and to evaluate whether they were associated with the presence of PanC, we profiled a custom AmpliSeq panel of 27 cancer susceptibility genes in 47 PanC patients and 51 control subjects by using the Ion Torrent PGM system. Results Multigene panel testing identified a total of 31 variants in 27 PanC (57.4%), including variants with pathogenic/likely pathogenic effect, those of uncertain significance, and variants whose clinical significance remains currently undefined. Five patients carried more than one variant in the same gene or in different genes. Eight patients (17.0%) had at least one pathogenic/likely pathogenic variant in four main genes: CFTR (10.6%), BRCA2 (8.5%), ATM and CHEK2 (2.1%). Pathogenic/likely pathogenic mutation were identified in patients with positive PanC family history (20%) or in patients without first-degree relatives affected by PanC (13.6%). All the BRCA2 mutation carriers were unselected PanC patients. The presence of mutations in BRCA2 was significantly associated with an increased occurrence of PanC and with positive family history for endometrial cancer (p = 0.018). Conclusions This study confirmed the potential remarkable contribution of BRCA2 in assessing the presence of PanC. Overall our findings supported the recommendation of offering the germline testing to all the PanC patients with the intent to reduce the number of underdiagnosed carriers of mutations in predisposition genes, and not to preclude their relatives from the opportunity to benefit from surveillance programs.
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- 2023
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40. LIFE BEYOND LONG-TERM CANCER SURVIVORS: CONCERNS AND UPDATES
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Paolo Tralongo, Vittorio Mattioli, Roberto Bordonaro, Franco DI Raimondo, Francesco Ferraù, Giordano Beretta, Concetta Biondo, Livio Blasi, Riccardo Bottino, Carlo Carnaghi, Simona Carnio, Amanda Casirati, Luigi Cavanna, Roberta De Angelis, Francesco de Lorenzo, Andrea Di Cataldo, Massimo Di Maio, Davide Dondi, Fabio Efficacie, Fabio Fichera, Guido Gini, Stefano Giordani, Riccardo Haupt, Elisabetta Iannelli, Gabriella Insolia, Mario Lazzaro, Lavinia Lo Curzio, Evaristo Maiello, Sandro Barni, Carmelo Nicolosi, Domenico Priolo, Elena Puzzo, Stefania Rapisardi, Daniela Respini, Giuseppe Saglio, Daniela Sambataro, Nicola Silvestris, Rosalia Maria Sorce, Alfredo Spartà, Chiara Barone, Laura Valvo, Maria Vasile, Stefano Vitello, and Monica Zerilli
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life beyond cancer ,cancer rehabilitation ,long-term surveillance ,social issues ,financial issues ,insurance issues ,childhood cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
During the Conference on Cancer Long-term Survivors, held in Siracusa (Italy) on September 16, 2022, Oncologists, General Practitioners, Epidemiologists, Hematologists, Pediatric Oncologists, Nurses, Industry Medical Affairs and Patients' Advocates came together to discuss the clinical implications of the condition beyond acute cancer. The debate was based both on the current literature on this topic, and on the opinion of all participants. Specifically, numerous issues were discussed in the round tables, but focused mainly on the following topics: - REASONS FOR SUCCESS IN IMPROVING SURVIVAL RATES - REHABILITATION - LONG-TERM SURVEILLANCE - PEDIATRIC AND YOUNG ADULT ISSUES - SOCIAL, FINANCIAL AND INSURANCE ISSUES This Opinion Paper aims to stimulate a suitable support to the growing population of people cancer disease free or with long-term or late effects. The development of new models can promote actions towards the elimination of obstacles and difficulties in cancer survivorship care.
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- 2023
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41. Insulin-like growth factor-1 (IGF-1) as predictor of cardiovascular mortality in heart failure patients: data from the T.O.S.CA. registry
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De Giorgi, Alfredo, Marra, Alberto Maria, Iacoviello, Massimo, Triggiani, Vincenzo, Rengo, Giuseppe, Cacciatore, Francesco, Maiello, Ciro, Limongelli, Giuseppe, Masarone, Daniele, Perticone, Francesco, Filardi, Pasquale Perrone, Paolillo, Stefania, Mancini, Antonio, Volterrani, Maurizio, Vriz, Olga, Castello, Roberto, Passantino, Andrea, Campo, Michela, Modesti, Pietro Amedeo, Salzano, Andrea, D’Assante, Roberta, Arcopinto, Michele, Raparelli, Valeria, Fabbian, Fabio, Sciacqua, Angela, Colao, Annamaria, Suzuki, Toru, Bossone, Eduardo, and Cittadini, Antonio
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- 2022
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42. Big Data in cardiac surgery: real world and perspectives
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Andrea Montisci, Vittorio Palmieri, Maria Teresa Vietri, Silvia Sala, Ciro Maiello, Francesco Donatelli, and Claudio Napoli
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Big Data ,Cardiac surgery ,Artificial intelligence ,Machine learning ,Coronary revascularization ,Valvular heart diseases ,Surgery ,RD1-811 ,Anesthesiology ,RD78.3-87.3 - Abstract
Abstract Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed to recognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.
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- 2022
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43. Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts
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Raffaele Marfella, Nunzia D’Onofrio, Gelsomina Mansueto, Vincenzo Grimaldi, Maria Consiglia Trotta, Celestino Sardu, Ferdinando Carlo Sasso, Lucia Scisciola, Cristiano Amarelli, Salvatore Esposito, Michele D’Amico, Paolo Golino, Marisa De Feo, Giuseppe Signoriello, Pasquale Paolisso, Emanuele Gallinoro, Marc Vanderheyden, Ciro Maiello, Maria Luisa Balestrieri, Emanuele Barbato, Claudio Napoli, and Giuseppe Paolisso
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Heart transplantation ,Diabetes ,HbA1c ,Diabetic cardiomyopathy ,RAS-inhibition therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control. Objectives We investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1–9, Ang 1–7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts. Methods We evaluated 197 first HTX recipients (107 non-T2DM, 90 T2DM). All patients were treated with angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) at hospital discharge. Patients underwent clinical evaluation (metabolic status, echocardiography, coronary CT-angiography, and endomyocardial biopsies). Biopsies were used to evaluate ACE2, GlycACE2, Ang 1–9, Ang 1–7, MasR, NAFT, and fibrosis. Results GlycACE2 was higher in T2DM compared tonon-T2DM cardiomyocytes. Moreover, reduced expressions of Ang 1–9, Ang 1–7, and MasR were observed, suggesting impaired effects of RAS-inhibition in diabetic hearts. Accordingly, biopsies from T2DM recipients showed higher fibrosis than those from non-T2DM recipients. Notably, the expression of GlycACE2 in heart biopsies was strongly dependent on glycemic control, as reflected by the correlation between mean plasma HbA1c, evaluated quarterly during the 12-month follow-up, and GlycACE2 expression. Conclusion Poor glycemic control, favoring GlycACE2, may attenuate the cardioprotective effects of RAS-inhibition. However, the achievement of tight glycemic control normalizes the anti-remodeling effects of RAS-inhibition. Trial registration: https://clinicaltrials.gov/ NCT03546062.
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- 2022
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44. Association between metabolic syndrome, hypertension, and chronic depression: a postmenopausal women prevention study
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Pasquale Palmiero, Maria Maiello, Francesca Amati, Marco Matteo Ciccone, and Timir Paul
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Postmenopausal women ,metabolic syndrome ,hypertension ,depression ,cardiomyopathy ,Medicine - Abstract
Background. Chronic depression (CD) is common among postmenopausal women and is associated with an increased risk of cardiovascular disease (CVD). The diagnosis of CD is a challenging problem in clinical practice which is vastly underdiagnosed. CD detection in postmenopausal women with metabolic syndrome (MetS) or hypertension is necessary for CVD prevention. Our study aims to assess the prevalence of CD in postmenopausal women and the relationship between CD and MetS or hypertension. Results. The rate of CD was significantly higher among postmenopausal women with MetS compared with the control group [18% versus 8%; Odds ratio (OR) 2.2, P
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- 2023
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45. Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational studyResearch in context
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Melissa Bersanelli, Elena Verzoni, Alessio Cortellini, Raffaele Giusti, Lorenzo Calvetti, Paola Ermacora, Marilena Di Napoli, Annamaria Catino, Valentina Guadalupi, Giorgia Guaitoli, Vieri Scotti, Francesca Mazzoni, Antonello Veccia, Pamela Francesca Guglielmini, Fabiana Perrone, Marco Maruzzo, Ernesto Rossi, Chiara Casadei, Vincenzo Montesarchio, Francesco Grossi, Mimma Rizzo, Maria Grazia Travagliato Liboria, Manlio Mencoboni, Fable Zustovich, Lucia Fratino, Caterina Accettura, Saverio Cinieri, Andrea Camerini, Mariella Sorarù, Paolo Andrea Zucali, Serena Ricciardi, Antonio Russo, Giorgia Negrini, Maria Chiara Banzi, Gaetano Lacidogna, Giuseppe Fornarini, Letizia Laera, Claudia Mucciarini, Matteo Santoni, Claudia Mosillo, Andrea Bonetti, Lucia Longo, Donata Sartori, Editta Baldini, Michele Guida, Mauro Iannopollo, Roberto Bordonaro, Maria Francesca Morelli, Pierosandro Tagliaferri, Massimiliano Spada, Anna Ceribelli, Rosa Rita Silva, Franco Nolè, Giordano Beretta, Petros Giovanis, Daniele Santini, Stefano Luzi Fedeli, Oriana Nanni, Evaristo Maiello, Roberto Labianca, Carmine Pinto, Alberto Clemente, Michele Tognetto, Ugo De Giorgi, Sandro Pignata, Massimo Di Maio, Sebastiano Buti, and Diana Giannarelli
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Influenza-like illness ,Influenza vaccination ,Flu vaccine ,Immune checkpoint inhibitors ,Cancer patients ,ICI ,Medicine (General) ,R5-920 - Abstract
Summary: Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5–34.6) in vaccinated vs. 20.9 months (16.6–25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4–14.6) vs. 9.6 months (CI 7.9–11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62–0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11–1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.
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- 2023
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46. Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens.
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Maral Budak, Joseph M Cicchese, Pauline Maiello, H Jacob Borish, Alexander G White, Harris B Chishti, Jaime Tomko, L James Frye, Daniel Fillmore, Kara Kracinovsky, Jennifer Sakal, Charles A Scanga, Philana Ling Lin, Véronique Dartois, Jennifer J Linderman, JoAnne L Flynn, and Denise E Kirschner
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Biology (General) ,QH301-705.5 - Abstract
Tuberculosis (TB) continues to be one of the deadliest infectious diseases in the world, causing ~1.5 million deaths every year. The World Health Organization initiated an End TB Strategy that aims to reduce TB-related deaths in 2035 by 95%. Recent research goals have focused on discovering more effective and more patient-friendly antibiotic drug regimens to increase patient compliance and decrease emergence of resistant TB. Moxifloxacin is one promising antibiotic that may improve the current standard regimen by shortening treatment time. Clinical trials and in vivo mouse studies suggest that regimens containing moxifloxacin have better bactericidal activity. However, testing every possible combination regimen with moxifloxacin either in vivo or clinically is not feasible due to experimental and clinical limitations. To identify better regimens more systematically, we simulated pharmacokinetics/pharmacodynamics of various regimens (with and without moxifloxacin) to evaluate efficacies, and then compared our predictions to both clinical trials and nonhuman primate studies performed herein. We used GranSim, our well-established hybrid agent-based model that simulates granuloma formation and antibiotic treatment, for this task. In addition, we established a multiple-objective optimization pipeline using GranSim to discover optimized regimens based on treatment objectives of interest, i.e., minimizing total drug dosage and lowering time needed to sterilize granulomas. Our approach can efficiently test many regimens and successfully identify optimal regimens to inform pre-clinical studies or clinical trials and ultimately accelerate the TB regimen discovery process.
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- 2023
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47. Mycobacterium tuberculosis-Specific CD4 T Cells Expressing Transcription Factors T-Bet or RORγT Associate with Bacterial Control in Granulomas
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Nicole L. Grant, Kristen Kelly, Pauline Maiello, Helena Abbott, Shelby O’Connor, Philana Ling Lin, Charles A. Scanga, and JoAnne L. Flynn
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MHC class II tetramer ,Mycobacterium tuberculosis ,T cell ,granuloma ,lung infection ,macaque ,Microbiology ,QR1-502 - Abstract
ABSTRACT Despite the extensive research on CD4 T cells within the context of Mycobacterium tuberculosis (Mtb) infections, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate the identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, namely, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, thereby providing data for the synthesis of MHC class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments, postinfection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+ cells had increased frequencies of the activation marker CD69 as well as the transcription factors T-bet and RORγT, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+ cells was positively correlated with the granuloma bacterial burden, the frequency of RORγT or T-bet within tetramer+ cells was inversely correlated with the granuloma bacterial burden, thereby highlighting the importance of having activated, polarized, Mtb-specific cells for the control of Mtb in lung granulomas. IMPORTANCE Tuberculosis, caused by the bacterial pathogen Mycobacterium tuberculosis, kills 1.5 million people each year, despite the existence of effective drugs and a vaccine that is given to infants in most countries. Clearly, we need better vaccines against this disease. However, our understanding of the immune responses that are necessary to prevent tuberculosis is incomplete. This study seeks to understand the functions of T cells that are specific for M. tuberculosis at the site of the disease in the lungs. For this, we developed specialized tools called MHC class II tetramers to identify those T cells that can recognize M. tuberculosis and applied the tools to the study of this infection in nonhuman primate models that mimic human tuberculosis. We demonstrate that M. tuberculosis-specific T cells in lung lesions are associated with control of the bacteria only when those T cells are expressing certain functions, thereby highlighting the importance of combining the identification of specific T cells with functional analyses. Thus, we surmise that these functions of specific T cells are critical to the control of infection and should be considered as a part of the development of vaccines against tuberculosis.
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- 2023
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48. Thoracic ultrasound combined with low-dose computed tomography may represent useful screening strategy in highly exposed population in the industrial city of Taranto (Italy)
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Carla Maria Irene Quarato, Elisa Dama, Michele Maggi, Beatrice Feragalli, Cristina Borelli, Anna Del Colle, Marco Taurchini, Evaristo Maiello, Salvatore De Cosmo, Donato Lacedonia, Maria Pia Foschino Barbaro, Giovanna Elisiana Carpagnano, Giulia Scioscia, Paolo Graziano, Rosalinda Termine, Elisabettamaria Frongillo, Sonia Santamaria, Mariapia Venuti, Maria Arcangela Grimaldi, Stefano Notarangelo, Annarita Saponara, Massimiliano Copetti, Tommaso Colangelo, Roberto Cuttano, Dimitrios Macrodimitris, Francesco Mazzarelli, Michela Talia, Antonio Mirijello, Luca Pazienza, Rita Perna, Anna Simeone, Doriana Vergara, Antonio Varriale, Massimo Carella, Fabrizio Bianchi, and Marco Sperandeo
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transthoracic ultrasound ,high-resolution computed tomography ,lung cancer ,interstitial lung abnormalities ,screening protocol ,environmental exposure ,Medicine (General) ,R5-920 - Abstract
ObjectivesWe validated a screening protocol in which thoracic ultrasound (TUS) acts as a first-line complementary imaging technique in selecting patients which may deserve a second-line low-dose high resolution computed tomography (HRCT) scan among a population of asymptomatic high-risk subjects for interstitial lung abnormalities (ILA) and lung cancer. Due to heavy environmental pollution burden, the district Tamburi of Taranto has been chosen as “case study” for this purpose.MethodsFrom July 2018 to October 2020, 677 patients aged between 45 and 65 year and who had been living in the Tamburi district of Taranto for at least 10 years were included in the study. After demographic, clinical and risk factor exposition data were collected, each participant underwent a complete TUS examination. These subjects were then asked to know if they agreed to perform a second-level examination by low-dose HRCT scan.ResultsOn a total of 167 subjects (24.7%) who agreed to undergo a second-level HRCT, 85 patients (50.9%) actually showed pleuro-pulmonary abnormalities. Interstitial abnormalities were detected in a total of 36 patients on HRCT scan. In particular, 34 participants presented subpleural ILAs, that were classified in the fibrotic subtype in 7 cases. The remaining 2 patients showed non-subpleural interstitial abnormalities. Subpleural nodules were observed in 46 patients. TUS showed an overall diagnostic accuracy of 88.6% in detecting pleuro-pulmonary abnormalities in comparison with HRCT scan, with a sensitivity of 95.3%, a specificity of 81.7%, a positive predictive value of 84.4% and a negative predictive value of 94.4%. The matched evaluation of specific pulmonary abnormalities on HRTC scan (i.e., interstitial abnormalities or pulmonary nodules) with determinate sonographic findings revealed a reduction in both TUS sensibility and specificity. Focusing TUS evaluation on the assessment of interstitial abnormalities, a thickened pleural line showed a sensitivity of 63.9% and a specificity of 69.5%, hypoechoic striae showed a sensitivity of 38.9% and a specificity of 90.1% and subpleural nodules showed a sensitivity of 58.3% and a specificity of 77.1%. Regarding to the assessment of subpleural nodules, TUS showed a sensitivity of 60.9% and a specificity of 81.0%. However, the combined employment of TUS examination and HRCT scans allowed to identify 34 patients with early subpleural ILA and to detect three suspicious pulmonary nodules (of which two were intraparenchymal and one was a large subpleural mass), which revealed to be lung cancers on further investigations.ConclusionA first-line TUS examination might aid the identification of subjects highly exposed to environmental pollution, who could benefit of a second-line low-dose HRCT scan to find early interstitial lung diseases as well as lung cancer.Protocol registration codePLEURO-SCREENING-V1.0_15 Feb, 17.
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- 2023
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49. Commiato
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Rosa Maiello
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Associazione italiana biblioteche ,bibliotecari ,professione ,Bibliography. Library science. Information resources - Published
- 2023
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50. Correction: Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)
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Degiuli, Maurizio, Ortenzi, Monica, Tomatis, Mariano, Puca, Lucia, Cianflocca, Desiree, Rega, Daniela, Maroli, Annalisa, Elmore, Ugo, Pecchini, Francesca, Milone, Marco, La Mendola, Roberta, Soligo, Erica, Deidda, Simona, Spoletini, Domenico, Cassini, Diletta, Aprile, Alessandra, Mineccia, Michela, Nikaj, Herald, Marchegiani, Francesco, Maiello, Fabio, Bombardini, Cristina, Zuolo, Michele, Carlucci, Michele, Ferraro, Luca, Falato, Armando, Biondi, Alberto, Persiani, Roberto, Marsanich, Patrizia, Fusario, Daniele, Solaini, Leonardo, Pollesel, Sara, Rizzo, Gianluca, Coco, Claudio, Di Leo, Alberto, Cavaliere, Davide, Roviello, Franco, Muratore, Andrea, D’Ugo, Domenico, Bianco, Francesco, Bianchi, Paolo Pietro, De Nardi, Paola, Rigamonti, Marco, Anania, Gabriele, Belluco, Claudio, Polastri, Roberto, Pucciarelli, Salvatore, Gentilli, Sergio, Ferrero, Alessandro, Scabini, Stefano, Baldazzi, Gianandrea, Carlini, Massimo, Restivo, Angelo, Testa, Silvio, Parini, Dario, De Palma, Giovanni Domenico, Piccoli, Micaela, Rosati, Riccardo, Spinelli, Antonino, Delrio, Paolo, Borghi, Felice, Guerrieri, Marco, and Reddavid, Rossella
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- 2023
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