Acute Lymphoblastic Leukemia Immunotherapy Treatment: Now, Next, and Beyond

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody–drug conjugates, chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients

A Methodology to Characterize Power Control Systems for Limiting Exposure to Electromagnetic Fields Generated by Massive MIMO Antennas

The fifth-generation (5G) New Radio (NR) cellular network has been launched recently. The assignment of new spectrum bands and the widespread use of Massive MIMO (MaMIMO) and beamforming techniques for better radio coverage are two major features of the new architecture. They imply both opportunities and challenges, one of the most daring one among the latter ones is the research for methods to assess human exposure to electromagnetic fields radiated by the base stations. The long-term time-varying behavior and spatial multiplexing feature of the MaMIMO antennas, along with the radio resource utilization and adoption of Time-Division Duplexing (TDD), requires that the assessment of exposure to electromagnetic fields radiated by 5G systems is based on a statistical approach that relies on the space and time distribution of the radiated power. That, in turn, is determined through simulations based on the actual maximum transmitted power - defined as the 95 th percentile of the empirical distribution obtained from historical data of radiated power - rather than on the nominal one. To ensure that exposure limits are never exceeded, a monitoring and control system (usually referred to as Power Lock (PL)) that limits the transmitted power can be used. In this paper we propose a methodology, independent from the specific technical solution implemented by the manufacturer, to characterize such control systems and determine their capability to limit the average power transmitted over a given time interval to a value that keeps the corresponding average exposure to electromagnetic fields below a specified value. Experimental results show the effectiveness of the methodology and that it can also be used to identify when the PL interacts with the higher levels of the MaMIMO system architecture

A Theoretical and Experimental Investigation on the Measurement of the Electromagnetic Field Level Radiated by 5G Base Stations

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A New Paradigm in 5G Maximum Power Extrapolation for Human Exposure Assessment: Forcing gNB Traffic Toward the Measurement Equipment

5G base stations usually use different beams to transmit broadcast and user data. Moreover the broadcast beam is always “on air”, whilst the traffic beam is not. This represents a problem in Maximum Power Extrapolation (MPE) procedures for exposure assessment. In fact, currently adopted measurement approaches are based on the mere observation of phenomena. Recently, a different approach for MPE has been proposed by Adda et al., 2020, forcing the traffic toward the measuring position by means of a dedicated User Equipment (UE). Consequently, the measurer loses the “passive” role assumed in the approach usually adopted, and acquires an active role forcing the system under test to assume the most suitable configuration. The use of beam-forcing UEs opens new exciting possibilities, since it makes it possible to take advantage of the UE-specific signals for the estimation for the MPE procedure. The aim of this paper is to explore the potential offered by UE-specific data structures within the MPE considering a real case regarding data acquired on a currently operative 5G base station

Methodology Based on Vector and Scalar Measurement of Traffic Channel Power Levels to Assess Maximum Exposure to Electromagnetic Radiation Generated by 5G NR Systems

Maximum-Power Extrapolation (MPE) for mobile telecommunication sources follows an established paradigm based on the identification and measurement of a channel that acts as a power reference. Prior to the 5G era, the role of reference channel has been played by always-on broadcast signals since they had the great advantage of being always transmitted at the maximum power level allowed for a generic signal channel. However, the beamforming implemented by 5G sources obliges us to rethink this approach. In fact, with beamforming the 5G source can transmit data traffic streams through a beam characterized by a much higher gain than the broadcast one. This implies that the detected power for traffic beams could be much higher than the corresponding power of broadcast beams. In this paper, a novel approach for 5G MPE procedure is presented, where the direct measurement of the received power of a traffic beam is used to assess the maximum exposure generated by a 5G system. An innovative specific experimental setup is also proposed, with the use of a User Equipment (UE) with the aim of forcing the traffic beam toward the measurement positions. In this way, it is possible to directly measure the power of each Resource Element (RE) transmitted by the traffic beam. As opposed to other MPE proposals for 5G, the discussed technique does not require any correction of the measured data since it relies only on the traffic beam pointing toward the measurement position, simplifying the overall MPE procedure and thus reducing the uncertainty of the MPE estimated field strength

Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked toCD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell–mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy