Flow-volume curve analysis for predicting recurrence after endoscopic dilation of airway stenosis

The flow-volume curve is a simple test for diagnosing upper airway obstruction. We evaluated its use to predict recurrence in patients undergoing endoscopic dilation for treatment of benign upper airway stenosis

Specific ADAM10 inhibitors localize in exosome-like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells

Shedding of ADAM10 substrates, like TNFa, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms of these molecules and ADAM10 can be carried and spread in the microenvironment by exosomes released by tumor cells. We reported new ADAM10 inhibitors able to prevent MICA shedding in Hodgkin lymphoma (HL), leading to recognition of HL cells by cytotoxic lymphocytes. In this paper, we show that the mature bioactive form of ADAM10 is released in exosome-like vesicles (ExoV) by HL cells and lymph node mesenchymal stromal cells (MSC). We demonstrate that ADAM10 inhibitors are released in ExoV by MSC or HL cells, endocytosed by bystander cells and localized in the endolysosomal compartment in HL MSC. ExoV released by HL cells can enhance MICA shedding by MSC, while ExoV from MSC induce TNFa or CD30 shedding by HL cells. Of note, ADAM10 sheddase activity carried by ExoV is prevented with the ADAM10 inhibitors LT4 and CAM29, pretreating either the ExoVproducing or the ExoV-receiving cells. In particular, both inhibitors reduce CD30 shedding maintaining the anti-tumor effects of the ADC Brentuximab-Vedotin or the anti-CD30 Iratumumab on HL cells. Thus, spreading of ADAM10 activity due to ExoV can result in the release of cytokines, like TNFa,a lymphoma growth factor, or soluble molecules, like sMICA or sCD30, that potentially interfere with host immune surveillance or immunotherapy. ADAM10 blockers can interfere with this process, allowing the development of anti-lymphoma immune response and/or efficient ADC-based or human antibody-based immunotherapy

Human Gut-Associated Natural Killer Cells in Health and Disease

It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals and virus infections. The functions of NK cells in the gut are much more complex. Gut NK cells are not precisely organized in lymphoid aggregates but rather scattered in the epithelium or in the stroma, where they come in contact with a multitude of antigens derived from commensal or pathogenic microorganisms in addition to components of microbiota. Furthermore, NK cells in the bowel interact with several cell types, including epithelial cells, fibroblasts, macrophages, dendritic cells, and T lymphocytes, and contribute to the maintenance of immune homeostasis and development of efficient immune responses. NK cells have a key role in the response to intestinal bacterial infections, primarily through production of IFNγ, which can stimulate recruitment of additional NK cells from peripheral blood leading to amplification of the anti-bacterial immune response. Additionally, NK cells can have a role in the pathogenesis of gut autoimmune inflammatory bowel diseases (IBDs), such as Crohn's Disease and Ulcerative Colitis. These diseases are considered relevant to the generation of gastrointestinal malignancies. Indeed, the role of gut-associated NK cells in the immune response to bowel cancers is known. Thus, in the gut immune system, NK cells play a dual role, participating in both physiological and pathogenic processes. In this review, we will analyze the known functions of NK cells in the gut mucosa both in health and disease, focusing on the cross-talk among bowel microenvironment, epithelial barrier integrity, microbiota, and NK cells

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study)

Background Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58–85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). Conclusions The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Evaluating Asynchronous Message Boards to Support Cross-Cultural Communities of High-School Students

Can online forums effectively support collaboration, discussion, and cultural exchange among high-school students from different countries? We present results from the analysis of a set of asynchronous message boards within Learning@Europe, a project where students meet in real time in shared 3D virtual environments, and keep in touch through online forums. Between March 2005 and December 2006 about 5000 students and 250 teachers from 17 European countries took part in Learning@Europe, posting on a total of 194 forums. Focusing on a detailed analysis of the first L@E implementation (involving about 1000 students and 50 teachers from 6 European countries), we show how forums can support more or less effectively collaboration and discussion tools, what challenges must be faced, and how the tool’s evaluation must take into account the components and set of goals of the entire learning experience

E-Learning e accessibilità per il patrimonio culturale, E- Learning and Accessibility for Cultural Heritage

L’articolo descrive i risultati di due progetti innovativi nell’ambito dei Beni Culturali condotti da HOC (http://hoc.elet.polimi.it) il laboratorio multidisciplinare del dipartimento di Elettronica e Informazione del Politecnico di Milano: SEE (e-learning avanzato) e WED (accessibilità al Web per utenti non vedenti). Il progetto SEE (Shrine Educational Experience; www.seequmran.it), risultato di cooperazione tra il Politecnico e il Museo di Israele di Gerusalemme, può essere definito come un’esperienza educativa sul tema dei rotoli del Mar Morto e argomenti correlati. Studenti di classi diverse si incontrano in un mondo 3D condiviso in Internet per discutere, imparare e giocare in uno scambio interculturale coinvolgente, che crea legami di reciproca comprensione tra culture diverse. Il progetto WED riguarda invece l’accessibilità al Web per utenti non vedenti. L’assunto di base è che l’interazione tra un essere umano e una macchina possa essere paragonata a una sorta di dialogo, studiando le cui caratteristiche in paragone a quelle dei dialoghi naturali, è possibile sviluppare linee guida per un design che sposti l’interazione dal canale visivo a quello orale.The paper describes the results of two innovative projects, in the field of Cultural Heritage, carried on by HOC (http://hoc.elet.polimi.it) the multidisciplinary Laboratory of the Politecnico di Milano Department of Electronics and Information: SEE (advanced e-learning) and WED (accessibility to the web for blind users). SEE (Shrine Educational Experience; www.seequmran.it) project, the result of cooperation between Politecnico and the Israel Museum of Jerusalem, provides an educational experience concerning the Dead Sea Scrolls and related issues. Students of different classes meet in a 3D world, shared over the Internet, to discuss, learn and play together in an engaging intercultural exchange, creating bonds and understanding between different cultures. WED addresses the issue of accessibility to the Web for visually impaired users. The assumption is that the interaction between a human being and a machine can be compared to a sort of dialogue:studying its features and comparing them with efficient natural dialogues, it is possible to develop design guidelines in order to switch the interaction from the visual to the oral channel