Rheumatoid factor: a novel determiner in cancer history

The possible interplay between autoimmunity and cancer is a topic that still needs to be deeply explored. Rheumatoid factors are autoantibodies that are able to bind the constant regions (Fc) of immunoglobulins class G (IgGs). In physiological conditions, their production is a transient event aimed at contributing to the elimination of pathogens as well as limiting a redundant immune response by facilitating the clearance of antibodies and immune complexes. Their production can become persistent in case of different chronic infections or diseases, being for instance a fundamental marker for the diagnosis and prognosis of rheumatoid arthritis. Their presence is also associated with aging. Some studies highlighted how elevated levels of rheumatoid factors (RFs) in the blood of patients are correlated with an increased cancer risk, tumor recurrence, and load and with a reduced response to anti-tumor immunotherapies. In line with their physiological roles, RFs showed in different works the ability to impair in vitro anti-cancer immune responses and effector functions, suggesting their potential immunosuppressive activity in the context of tumor immunity. Thus, the aim of this review is to investigate the emerging role of RFs as determiners of cancer faith

CD137+ T-cells: protagonists of the immunotherapy revolution

The CD137 receptor is expressed by activated antigen-specific T-cells. CD137+ T-cells were identified inside TILs and PBMCs of different tumor types and have proven to be the naturally occurring antitumor effector cells, capable of expressing a wide variability in terms of TCR specificity against both shared and neoantigenic tumor-derived peptides. The aim of this review is thus summarizing and highlighting their role as drivers of patients’ immune responses in anticancer therapies as well as their potential role in future and current strategies of immunotherapy. The CD137 receptor (4-1BB, TNF RSF9) is an activation induced molecule expressed by antigen-specific T-cells. The engagement with its ligand, CD137L, is capable of increasing Tcell survival, proliferation, and cytokine production. This allowed to identify the CD137+ T-cells as the real tumor-specific activated T-cell population. In fact, these cells express various TCRs that are specific for a wide range of tumor-derived peptides, both shared and neoantigenic ones. Moreover, their prevalence in sites close to the tumor and their unicity in killing cancer cells both in vitro and in vivo, raised particular interest in studying their potential role in different strategies of immunotherapy. They indeed showed to be a reliable marker able to predict patient’s outcome to immune-based therapies as well as monitor their response. In addition, the possibility of isolating and expanding this population, turned promising in order to generate effector antitumor T-cells in the context of adoptive T-cell therapies. CD137-targeting monoclonal antibodies have already shown their antitumor efficacy in cancer patients and a number of clinical trials are thus ongoing to test their possible introduction in different combination approaches of immunotherapy. Finally, the intracellular domain of the CD137 receptor was introduced in the anti-CD19 CAR-T cells that were approved by FDA for the treatment of pediatric B-cell leukemia and refractory B-cell lymphoma

new methodologies for the documentation of fortifiedarchitecture in the state of ruins

Fortresses and castles are important symbols of social and cultural identity providing tangible evidence of cultural unity in Europe. They are items for which it is always difficult to outline a credible prospect of reuse, their old raison d'être- namely the military, political and economic purposes for which they were built- having been lost. In recent years a Research Unit of the University of Bologna composed of architects from different disciplines has conducted a series of studies on fortified heritage in the Emilia Romagna region (and not only) often characterized by buildings in ruins. The purpose of this study is mainly to document a legacy, which has already been studied in depth by historians, and previously lacked reliable architectural surveys for the definition of a credible as well as sustainable conservation project. Our contribution will focus on different techniques and methods used for the survey of these architectures, the characteristics of which- in the past- have made an effective survey of these buildings difficult, if not impossible. The survey of a ruin requires, much more than the evaluation of an intact building, reading skills and an interpretation of architectural spaces to better manage the stages of documentation and data processing. Through a series of case studies of fortified buildings in ruins, we intend to describe the reasons that guided the choice of the methods and tools used and to highlight the potentials and the limits of these choices in financial terms

Myeloid cells in glioblastoma microenvironment

Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells are the most predominant contributors to the GBM microenvironment; these cells are critical regulators of immune and therapeutic responses to GBM. Here, we will review the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, myeloid-derived suppressor cells, dendritic cells, and neutrophils. Epigenetic, metabolic, and phenotypic peculiarities of microglia and bone marrow-derived macrophages will also be assessed. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in GBM patients

Architectures and Key Technical Challenges for 5G Systems Incorporating Satellites

Satellite Communication systems are a promising solution to extend and complement terrestrial networks in unserved or under-served areas. This aspect is reflected by recent commercial and standardisation endeavours. In particular, 3GPP recently initiated a Study Item for New Radio-based, i.e., 5G, Non-Terrestrial Networks aimed at deploying satellite systems either as a stand-alone solution or as an integration to terrestrial networks in mobile broadband and machine-type communication scenarios. However, typical satellite channel impairments, as large path losses, delays, and Doppler shifts, pose severe challenges to the realisation of a satellite-based NR network. In this paper, based on the architecture options currently being discussed in the standardisation fora, we discuss and assess the impact of the satellite channel characteristics on the physical and Medium Access Control layers, both in terms of transmitted waveforms and procedures for enhanced Mobile BroadBand (eMBB) and NarrowBand-Internet of Things (NB-IoT) applications. The proposed analysis shows that the main technical challenges are related to the PHY/MAC procedures, in particular Random Access (RA), Timing Advance (TA), and Hybrid Automatic Repeat reQuest (HARQ) and, depending on the considered service and architecture, different solutions are proposed.Comment: Submitted to Transactions on Vehicular Technologies, April 201

Pandemic recession, helicopter money and central banking: Venice, 1630

This paper analyses the monetary policy that the Most Serene Republic of Venice implemented in the years of calamities using a modern equivalent of helicopter money, precisely an extraordinary money issuing, coupled with capital losses for the issuer. We consider the 1629 famine and the 1630-1631 plague as a negative macroeconomic shock that the incumbent government addressed using fiscal monetization. Consolidating the balance sheets of the Mint and of the Giro Bank, and having heterogenous citizens - inequality matters - we show that the Republic implemented what was, in effect, helicopter money driven by political economy reasons, in order to avoid popular riots

Long-term effects of functional appliances in treated versus untreated patients with Class II malocclusion: A systematic review and meta-analysis

Objective To assess the cephalometric skeletal and soft-tissue of functional appliances in treated versus untreated Class II subjects in the long-term (primarily at the end of growth, secondarily at least 3 years after retention). Search methods Unrestricted electronic search of 24 databases and additional manual searches up to March 2018. Selection criteria Randomised and non-randomised controlled trials reporting on cephalometric skeletal and soft-tissue measurements of Class II patients (aged 16 years or under) treated with functional appliances, worn alone or in combination with multi-bracket therapy, compared to untreated Class II subjects. Data collection and analysis Mean differences (MDs) and 95% confidence intervals (95% CIs) were calculated with the random-effects model. Data were analysed at 2 primary time points (above 18 years of age, at the end of growth according to the Cervical Vertebral Maturation method) and a secondary time point (at least 3 years after retention). The risk of bias and quality of evidence were assessed according to the ROBINS tool and GRADE system, respectively. Results Eight non-randomised studies published in 12 papers were included. Functional appliances produced a significant improvement of the maxillo-mandibular relationship, at almost all time points (Wits appraisal at the end of growth, MD -3.52 mm, 95% CI -5.11 to -1.93, P < 0.0001). The greatest increase in mandibular length was recorded in patients aged 18 years and above (Co-Gn, MD 3.20 mm, 95% CI 1.32 to 5.08, P = 0.0009), although the improvement of the mandibular projection was negligible or not significant. The quality of evidence was \u2018very low\u2019 for most of the outcomes at both primary time points. Conclusions Functional appliances may be effective in correcting skeletal Class II malocclusion in the long-term, however the quality of the evidence was very low and the clinical significance was limited