A cento anni dalla Grande Guerra. Vol. 3

The volumes on the Great War that are here published are the result of a series of seminars held at the Department of Political and Social Sciences of the University of Florence between 2014 and 2015. Starting from the occasion of the centennial, the authors wanted to take stock of some specific aspects of the studies related to the First World War. To this purpose, historians, military analysts, political scientists and sociologists have questioned the meaning of the fracture that marks the beginning of the twentieth century and, consequently, the basic aspects of the new policy of the “short century”, from both an Italian and European perspective

La coopération aéronautique franco-italienne. Une relation déséquilibrée

Introduction Les relations franco-italiennes dans le domaine aéronautique au cours de la Grande Guerre furent particulièrement étroites et il n’aurait pas pu en aller autrement compte tenu non seulement du rôle pionnier de la France dans ce secteur, mais aussi de la place de la technologie et des capitaux français dans le développement de l’industrie d’armement italienne avant la guerre. Quand l’Italie intervint dans le conflit en mai 1915, les liens se resserrèrent encore et s’étendirent aux..

Bibliometria e scienze del libro: internazionalizzazione e vitalit\ue0 degli studi italiani

The vitality of a scientific field is usually attested by the fallout that research and publications have on the community of scholars who practice it and, therefore, on the development of the discipline itself and of its methodologies. The degree of “health” of a field of study, as well as its ability to get out of its niche of scholars and to see its validity recognised, is assessed by analysing whether and to what extent the works are read, commented on, cited by scholars from other geographical contexts and / or other scientific branches. The volume presents a research focused on the analysis of the level of internationalisation and vitality of Italian studies in the disciplines related to the study of books and documents, conducted through a series of parallel bibliometric investigations (query of citation databases, searches in Google scholar, application alternative metrics, library catalog analysis).La vitalit\ue0 di un settore scientifico \ue8 normalmente attestata dalla ricaduta che le ricerche e le pubblicazioni hanno sulla comunit\ue0 degli studiosi che la praticano e, quindi, sullo sviluppo della disciplina stessa e delle sue metodologie. Il grado di ‘salute’ di un campo di studio, nonch\ue9 la sua capacit\ue0 di uscire fuori dalla propria nicchia di studiosi e di vedere riconosciuta la propria validit\ue0, si valuta, infatti, analizzando se e in quale misura i lavori vengano letti, commentati, citati da studiosi di altri contesti geografici e/o di altri rami scientifici. Nel volume viene descritta una ricerca incentrata sull’analisi del livello di internazionalizzazione e di vitalit\ue0 degli studi italiani nelle discipline del libro e del documento, condotta attraverso una serie di indagini parallele di tipo bibliometrico (interrogazione dei database citazionali, ricerche in Google scholar, applicazione di metriche alternative, library catalog analysis)

A Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) for ovarian cancer

Abstract Background Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC). Methods pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence. pAXLxCD3ε mediated T-cell infiltration, activation and proliferation were assessed by immunofluorescence microscopy and by flow cytometry. Activity of pAXLxCD3ε was also investigated in combination with poly-ADP ribose polymerase inhibitors (PARPi). In vivo antitumor activity of pAXLxCD3ε was evaluated in immunocompromised (NSG) mice bearing intraperitoneal or subcutaneous EOC xenografts and immunologically reconstituted with human peripheral blood mononuclear cells (PBMC). Results pAXLxCD3ε induced dose-dependent cytotoxicity by activation of T lymphocytes against EOC cells, regardless of their histologic origin. The addition of PARPi to cell cultures enhanced pAXLxCD3ε cytotoxicity. Importantly, in vivo, pAXLxCD3ε was highly effective against EOC xenografts in two different NSG mouse models, by inhibiting the growth of tumor cells in ascites and subcutaneous xenografts. This effect translated into a significantly prolonged survival of treated animals. Conclusion pAXLxCD3ε is an active therapeutics against EOC cells providing a rational for its development as a novel agent in this still incurable disease. The preclinical validation of a first-in-class agent opens the way to the development of a new 14Fn3-based scaffold platform for the generation of innovative immune therapeutics against cancer

TERRA G-quadruplex stabilization as a new therapeutic strategy for multiple myeloma

BackgroundMultiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability, and telomere dysfunction is an important cause of acquired genomic alterations. Telomeric repeat-containing RNA (TERRA) transcripts are long non-coding RNAs involved in telomere stability through the interaction with shelterin complex. Dysregulation of TERRAs has been reported across several cancer types. We recently identified a small molecule, hit 17, which stabilizes the secondary structure of TERRA. In this study, we investigated in vitro and in vivo anti-MM activities of hit 17.MethodsAnti-proliferative activity of hit 17 was evaluated in different MM cell lines by cell proliferation assay, and the apoptotic process was analyzed by flow cytometry. Gene and protein expressions were detected by RT-qPCR and western blotting, respectively. Microarray analysis was used to analyze the transcriptome profile. The effect of hit 17 on telomeric structure was evaluated by chromatin immunoprecipitation. Further evaluation in vivo was proceeded upon NCI-H929 and AMO-1 xenograft models.ResultsTERRA G4 stabilization induced in vitro dissociation of telomeric repeat-binding factor 2 (TRF2) from telomeres leading to the activation of ATM-dependent DNA damage response, cell cycle arrest, proliferation block, and apoptotic death in MM cell lines. In addition, up-regulation of TERRA transcription was observed upon DNA damage and TRF2 loss. Transcriptome analysis followed by gene set enrichment analysis (GSEA) confirmed the involvement of the above-mentioned processes and other pathways such as E2F, MYC, oxidative phosphorylation, and DNA repair genes as early events following hit 17-induced TERRA stabilization. Moreover, hit 17 exerted anti-tumor activity against MM xenograft models.ConclusionOur findings provide evidence that targeting TERRA by hit 17 could represent a promising strategy for a novel therapeutic approach to MM

Emile Driant/Capitaine Danrit. La warfiction francese tra revanche ed orientalismo

Emile Driant/Capitaine Danrit. La warfiction francese tra revanche ed orientalism

ERAS program adherence-institutionalization, major morbidity and anastomotic leakage after elective colorectal surgery: the iCral2 multicenter prospective study

Background Enhanced recovery after surgery (ERAS) programs influence morbidity rates and length of stay after colorectal surgery (CRS), and may also impact major complications and anastomotic leakage rates. A prospective multicenter observational study to investigate the interactions between ERAS program adherence and early outcomes after elective CRS was carried out. Methods Prospective enrolment of patients submitted to elective CRS with anastomosis in 18 months. Adherence to 21 items of ERAS program was measured upon explicit criteria in every case. After univariate analysis, independent predictors of primary endpoints [major morbidity (MM) and anastomotic leakage (AL) rates] were identified through logistic regression analyses including all significant variables, presenting odds ratios (OR). Results Institutional ERAS protocol was declared by 27 out of 38 (71.0%) participating centers. Median overall adherence to ERAS program items was 71.4%. Among 3830 patients included in the study, MM and AL rates were 4.7% and 4.2%, respectively. MM rates were independently influenced by intra- and/or postoperative blood transfusions (OR 7.79, 95% CI 5.46-11.10; p < 0.0001) and standard anesthesia protocol (OR 0.68, 95% CI 0.48-0.96; p = 0.028). AL rates were independently influenced by male gender (OR 1.48, 95% CI 1.06-2.07; p = 0.021), intra- and/or postoperative blood transfusions (OR 4.29, 95% CI 2.93-6.50; p < 0.0001) and non-standard resections (OR 1.49, 95% CI 1.01-2.22; p = 0.049). Conclusions This study disclosed wide room for improvement in compliance to several ERAS program items. It failed to detect any significant association between institutionalization and/or adherence rates to ERAS program with primary endpoints. These outcomes were independently influenced by gender, intra- and postoperative blood transfusions, non-standard resections, and standard anesthesia protocol

Delayed colorectal cancer care during covid-19 pandemic (decor-19). Global perspective from an international survey

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care