The tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells

Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin)-dependent manner. Tim-3 participates in galectin-9 secretion and is also released in a free soluble form. Galectin-9 impairs the anti-cancer activity of cytotoxic lymphoid cells including natural killer (NK) cells. Soluble Tim-3 prevents secretion of interleukin-2 (IL-2) required for the activation of cytotoxic lymphoid cells. These results were validated in ex vivo experiments using primary samples from AML patients. This pathway provides reliable targets for both highly specific diagnosis and immune therapy of AML

Results Obtained with FBK Pixel Sensor Prototypes for the HL-LHC Tracker Upgrade of the CMS Experiment

The High Luminosity Phase of the CERN Large Hadron Collider (HL-LHC) will require an extensive upgrade of the CMS Inner Tracking system based on high radiation tolerant silicon pixel sensors capable of withstanding fluences up to $\mathrm{23 \times 10^{15} n_{eq}/cm^{2}}$ (1MeV equivalent neutrons). Thin planar and 3D pixel sensors have been recently selected by CMS to be installed in the upgraded pixel tracker. Thanks to their structure, the 3D pixel sensors have some advantages with respect to planar ones, and are presently more suitable candidates for the innermost layer of the tracker. In this presentation results obtained with FBK planar and FBK 3D sensors readout by prototype read-out chip RD53A will be shown. Both sensor types have 25x100 $\mathrm{\mu m^{2}}$ pitch and 150 $\mathrm{\mu m}$ thickness, and they were manufactured in collaboration with INFN. The sensors readout by the chip were irradiated to several fluences up to the one foreseen for HL-LHC. The analysis of collected data shows very high hit detection efficiency and good spatial resolution as measured after irradiation

Machine Learning techniques in breast cancer prognosis prediction: A primary evaluation.

More than 750 000 women in Italy are surviving a diagnosis of breast cancer. A large body of literature tells us which characteristics impact the most on their prognosis. However, the prediction of each disease course and then the establishment of a therapeutic plan and follow-up tailored to the patient is still very complicated. In order to address this issue, a multidisciplinary approach has become widely accepted, while the Multigene Signature Panels and the Nottingham Prognostic Index are still discussed options. The current technological resources permit to gather many data for each patient. Machine Learning (ML) allows us to draw on these data, to discover their mutual relations and to esteem the prognosis for the new instances. This study provides a primary evaluation of the application of ML to predict breast cancer prognosis. We analyzed 1021 patients who underwent surgery for breast cancer in our Institute and we included 610 of them. Three outcomes were chosen: cancer recurrence (both loco-regional and systemic) and death from the disease within 32 months. We developed two types of ML models for every outcome (Artificial Neural Network and Support Vector Machine). Each ML algorithm was tested in accuracy (=95.29%-96.86%), sensitivity (=0.35-0.64), specificity (=0.97-0.99), and AUC (=0.804-0.916). These models might become an additional resource to evaluate the prognosis of breast cancer patients in our daily clinical practice. Before that, we should increase their sensitivity, according to literature, by considering a wider population sample with a longer period of follow-up. However, specificity, accuracy, minimal additional costs, and reproducibility are already encouraging

DNA damage response and repair genes in advanced bone and soft tissue sarcomas: An 8-gene signature as a candidate predictive biomarker of response to trabectedin and olaparib combination

Advanced and unresectable bone and soft tissue sarcomas (BSTS) still represent an unmet medical need. We demonstrated that the alkylating agent trabectedin and the PARP1-inhibitor olaparib display antitumor activity in BSTS preclinical models. Moreover, in a phase Ib clinical trial (NCT02398058), feasibility, tolerability and encouraging results have been observed and the treatment combination is currently under study in a phase II trial (NCT03838744)

Progresses in the pulse shape identification with silicon detectors within the FAZIA Collaboration

In the last few years the FAZIA [1] collaboration has been investigating the properties of silicon detectors - in particular the crystal orientation and resistivity non-uniformity - in order to better pin down the detector characteristics that influence their performances for particle identification using Delta E-E and Pulse Shape Analysis (PSA) techniques. In this paper we present the first particle identification results obtained with detectors selected for good resistivity uniformity and using a "non-channeled" configuration. A new digital electronics was also designed for the R&D phase of FAZIA and was tested under beam for the first time. A quantitative procedure to measure the observed performances is applied in order to quantify the particle identification thresholds. Particle identification thresholds of similar to 2.5 AMeV for Z similar to 3-10 have been reached with the studied reaction

Impact of mitral regurgitation on the outcome of patients treated with CRT-D: data from the InSync ICD Italian Registry.

Background: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical-echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT-D]). Methods and Results: A total of 659 HF patients underwent successful implantation of CRT-D and were enrolled in a multicenter prospective registry (median follow-up of 15 months). Following baseline echocardiographic evaluation, patients were stratified into two groups according to the severity of MR: 232 patients with more than mild MR (Group MR+: grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR (Group MR−). On 6- and 12-month echocardiographic evaluation, MR was seen to have improved in the vast majority of MR+ patients, while it remained unchanged in most MR− patients. On 12-month follow-up evaluation, a comparable response to CRT was observed in the two groups, in terms of the extent of left ventricular reverse remodeling and combined clinical and echocardiographic response. During long-term follow-up, event-free survival did not differ between MR+ and MR− patients, even when subpopulations of patients with ischemic heart disease and with dilated cardiomyopathy were analyzed separately. On multivariate analysis, the only independent predictor of death from any cause was the lack of β-blocker use. Conclusions: This observational analysis supports the use of CRT-D in HF patients with clinically significant MR; MR had no major influence on patient outcom

Effects of pre‐operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or >= 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Measurement of inclusive and differential cross sections for single top quark production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceMeasurements of the inclusive and normalised differential cross sections are presented for the production of single top quarks in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13 TeV. The data used were recorded with the CMS detector at the LHC during 2016–2018, and correspond to an integrated luminosity of 138 fb$^{−1}$. Events containing one electron and one muon in the final state are analysed. For the inclusive measurement, a multivariate discriminant, exploiting the kinematic properties of the events is used to separate the signal from the dominant $\textrm{t}\overline{\textrm{t}}$ background. A cross section of $79.2\pm 0.9{\left(\textrm{stat}\right)}_{-8.0}^{+7.7}\left(\textrm{syst}\right)\pm 1.2\left(\textrm{lumi}\right)$ pb is obtained, consistent with the predictions of the standard model. For the differential measurements, a fiducial region is defined according to the detector acceptance, and the requirement of exactly one jet coming from the fragmentation of a bottom quark. The resulting distributions are unfolded to particle level and agree with the predictions at next-to-leading order in perturbative quantum chromodynamics.[graphic not available: see fulltext