Low plasma PD-L1 levels, early tumor onset and absence of peritoneal carcinomatosis improve prognosis of women with advanced high-grade serous ovarian cancer

BackgroundThe most common subtype of ovarian cancer (OC) showing immunogenic potential is represented by the high-grade serous ovarian cancer (HGSOC), which is characterized by the presence of tumor-infiltrating immune cells able to modulate immune response. Because several studies showed a close correlation between OC patient's clinical outcome and expression of programmed cell death protein-1 or its ligand (PD-1/PD-L1), the aim of our study was to investigate if plasma levels of immunomodulatory proteins may predict prognosis of advanced HGSOC women.Patients and methodsThrough specific ELISA tests, we analyzed plasma concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in one hundred patients affected by advanced HGSOC, before surgery and therapy. The Kaplan-Meier method was used to generate the survival curves, while univariate and multivariate analysis were performed using Cox proportional hazard regression models.ResultsFor each analyzed circulating biomarker, advanced HGSOC women were discriminated based on long (>= 30 months) versus short progression-free survival (PFS < 30 months). The concentration cut-offs, obtained by receiver operating characteristic (ROC) analysis, allowed to observe that poor clinical outcome and median PFS ranging between 6 and 16 months were associated with higher baseline levels of PD-L1 (> 0.42 ng/mL), PD-1 (> 2.48 ng/mL), BTN3A1 (> 4.75 ng/mL), pan-BTN3As (> 13.06 ng/mL), BTN2A1 (> 5.59 ng/mL) and BTLA (> 2.78 ng/mL). Furthermore, a lower median PFS was associated with peritoneal carcinomatosis, age at diagnosis > 60 years or Body Mass Index (BMI) > 25. A multivariate analysis also suggested that plasma concentrations of PD-L1 <= 0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p = 0.002), age at diagnosis <= 60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p = 0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p = 0.003) were significant prognostic marker for a longer PFS in advanced HGSOC patients.ConclusionsThe identification of high-risk HGSOC women could be improved through determination of the plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels

The design and validation of the R1 personal humanoid

In recent years the robotics field has witnessed an interesting new trend. Several companies started the production of service robots whose aim is to cooperate with humans. The robots developed so far are either rather expensive or unsuitable for manipulation tasks. This article presents the result of a project which wishes to demonstrate the feasibility of an affordable humanoid robot. R1 is able to navigate, and interact with the environment (grasping and carrying objects, operating switches, opening doors etc). The robot is also equipped with a speaker, microphones and it mounts a display in the head to support interaction using natural channels like speech or (simulated) eye movements. The final cost of the robot is expected to range around that of a family car, possibly, when produced in large quantities, even significantly lower. This goal was tackled along three synergistic directions: use of polymeric materials, light-weight design and implementation of novel actuation solutions. These lines, as well as the robot with its main features, are described hereafter

The Muon Portal Double Tracker for the Inspection of Travelling Containers

The Muon Portal Project has as its goal the design and construction of a real-size working detector prototype in scale 1:1, to inspect the content of travelling containers by means of the secondary cosmic-ray muon radiation and to recognize high-Z hidden materials (i.e. U, Pu). The tomographic image is obtained by reconstructing the input and output trajectories of each muon when it crosses the container and, consequently, the scattering angle, making use of two trackers placed above and below the container. The scan is performed without adding any external radiation, in a reasonable time (few minutes) and with a good spatial and angular resolution. The detector consists of 8 planes each segmented in 6 identical modules. Each module is made of scintillating strips with two WaveLength Shifting fibers (WLS) inside, coupled to Silicon photomultipliers. The customized read-out electronics employs programmable boards. Thanks to a smart read-out system, the number of output channels is reduced by a factor 10. The signals from the front-end modules are sent to the read-out boards, in order to convert analog signals to digital ones, by comparison with a threshold. The data are pre-analyzed and stored into a data acquisition PC. After an intense measurement and simulation campaign to carefully characterize the detector components, the first detection modules ( 1 ×3 m2) have been already built. In this paper the detector architecture, particularly focusing on the used electronics and the main preliminary results will be presented. <P /

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Interaction Potential for a System of N Charged Particles Near a Spherical Interface

International audienceBy integration of the electrostatic energy density of the system, we provide analytical expressions of the potential for a system of N charged particles in the presence of a surface which separates two continuous media, conductor, dielectric or vacuum. Such situations correspond, for example, to a number of electrons inside a spherical cavity of a conductor or interacting with a dielectric sphere. Bound states are analyzed for different values of the sphere radius

3d stereo estimation and fully automated learning of eye-hand coordination in humanoid robots

This paper deals with the problem of 3D stereo estimation and eye-hand calibration in humanoid robots. We first show how to implement a complete 3D stereo vision pipeline, enabling online and real-time eye calibration. We then introduce a new formulation for the problem of eye-hand coordination. We developed a fully automated procedure that does not require human supervision. The end-effector of the humanoid robot is automatically detected in the stereo images, providing large amounts of training data for learning the vision-to-kinematics mapping. We report exhaustive experiments using different machine learning techniques; we show that a mixture of linear transformations can achieve the highest accuracy in the shortest amount of time, while guaranteeing real-time performance. We demonstrate the application of the proposed system in two typical robotic scenarios: (1) object grasping and tool use; (2) 3D scene reconstruction. The platform of choice is the iCub humanoid robot

The iCub platform: a tool for studying intrinsically motivated learning

Instrinsically motivated robots are machines designed to operate for long periods of time, performing tasks for which they have not been programmed for. These robots make extensive use of explorative, often unstructured actions in search for opportunities to learn and to extract information from the environment. Research in this eld faces challenges that need advances not only on the algorithms but also on the experimental platforms. The iCub is a humanoid platform that was designed to support research in cognitive systems. We review in this paper the chief characteristics of the iCub robot, devoting particular attention to those aspects that makes the platform particularly suitable to the study of intrinsically motivated learning. We provide details on the software architecture, the mechanical design and the sensory system. We report examples of experiments and software modules to show how the robot can be programmed to obtain complex behaviors involving the interaction with the environment. The goal of this paper is to illustrate the potential impact of the iCub on the scientic community at large, but, in particular on the eld of instrinsically motivated learning

SF3B1 modulators affect key genes in metastasis and drug influx: a new approach to fight pancreatic cancer chemoresistance

Aim: Because mutations of splicing factor 3B subunit-1 (SF3B1) have been identified in 4% of pancreatic ductal adenocarcinoma (PDAC) patients, we investigated the activity of new potential inhibitors of SF3B1 in combination with gemcitabine, one of the standard drugs, in PDAC cell lines.Methods: One imidazo[2,1-b][1,3,4]thiadiazole derivative (IS1) and three indole derivatives (IS2, IS3 and IS4), selected by virtual screening from an in-house library, were evaluated by the sulforhodamine-B and wound healing assay for their cytotoxic and antimigratory activity in the PDAC cells SUIT-2, Hs766t and Panc05.04, the latter harbouring the SF3B1 mutations. The effects on the splicing pattern of proto-oncogene recepteur d’origine nantais (RON) and the gemcitabine transporter human equilibrative nucleoside transporter-1 (hENT1) were assessed by PCR, while the ability to reduce tumour volume was tested in spheroids of primary PDAC cells.Results: The potential SF3B1 modulators inhibited PDAC cell proliferation and prompted induction of cell death. All compounds showed an interesting anti-migratory ability, associated with splicing RON/ΔRON shift in SUIT-2 cells after 24 h exposure. Moreover, IS1 and IS4 potentiated the sensitivity to gemcitabine in both conventional 2D monolayer and 3D spheroid cultures, and these results might be explained by the statistically significant increase in hENT1 expression (P &lt; 0.05 vs. untreated control cells), potentially reversing PDAC chemoresistance.Conclusion: These results support further studies on new SF3B1 inhibitors and the role of RON/hENT1 modulation to develop effective drug combinations against PDAC