Search Results (13)

Background: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1–3 prior treatments. Methods: Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: After a median follow-up time of 12.9 months (range, 1–77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to a range of pathological outcomes, including metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation and progression remain incompletely understood. Oxidative stress and lipid peroxidation are pivotal in the “multiple parallel hit model”, contributing to hepatic cell death and tissue damage. Gut microbiota plays a substantial role in modulating hepatic oxidative stress through multiple pathways: impairing the intestinal barrier, which results in bacterial translocation and chronic hepatic inflammation; modifying bile acid structure, which impacts signaling cascades involved in lipidic metabolism; influencing hepatocytes’ ferroptosis, a form of programmed cell death; regulating trimethylamine N-oxide (TMAO) metabolism; and activating platelet function, both recently identified as pathogenetic factors in MASH progression. Moreover, various exogenous factors impact gut microbiota and its involvement in MASLD-related oxidative stress, such as air pollution, physical activity, cigarette smoke, alcohol, and dietary patterns. This manuscript aims to provide a state-of-the-art overview focused on the intricate interplay between gut microbiota, lipid peroxidation, and MASLD pathogenesis, offering insights into potential strategies to prevent disease progression and its associated complications. Full article

A simple sensor for the quantitation of tryptophan (Trp) has been developed using a glassy carbon electrode (GCE) modified with electro-synthesized carbon dots functionalized with glycine (Gly@CDs). The surface functionalization with an amino acid led to the formation of large clusters of nanostructures. To our knowledge, this is the first study in which a Gly@CDs clusters modified GCE is used for the analysis of Trp. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) are the techniques used to study Trp electrochemical behavior in an alkaline solution using such an electrode. A linear concentration range was found for Trp from 5 × 10⁻⁶ to 5 × 10⁻³ mol L⁻¹ with a detection limit (LOD) of 5 × 10⁻⁶ mol L⁻¹. The reproducibility and repeatability data were satisfactory in terms of RSD%. Moreover, the stability during the time of the modified electrode was considered, evidencing interesting results. The described sensor was used for the determination of Trp in herbal tea and a dietary supplement, and the results were compared with those obtained with HPLC-ESI-MS in the Selected Ion Recording (SIR) mode as an independent method. The electrochemical sensor presents significant advantages in terms of low cost, portability, ease of handling and not requiring skilled personnel. Full article

Natural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) through protease-mediated cleavage or in an extracellular vesicle (EV) is a mode to control their cell surface expression and a mechanism used by cancer cells to evade NKG2D-mediated immunosurveillance. EVs are emerging as important players in mediating cell-to-cell communication due to their ability to transfer biological material to acceptor cells. Herein, we investigated the spreading of NKG2DLs of both MIC and ULBP molecules through the EV-mediated cross-dressing on multiple myeloma (MM) cells. We focused our attention on two MICA allelic variants, namely MICA*008 and MICA*019, representing the prototype of short and long MICA alleles, respectively, and on ULBP-1, ULBP-2, and ULBP-3. Our findings demonstrate that both ULBP and MICA ligands can be acquired from tumor cells through EVs enhancing NK cell recognition and killing. Moreover, besides MICA, EVs expressing ULBP-1 but not ULBP-2 and 3 were detected in bone marrow aspirates derived from a cohort of MM patients. Our findings shed light on the role of EV-associated MICA allelic variants and ULBP molecules in the modulation of NKG2D-mediated NK cell immunosurveillance in the tumor microenvironment. Moreover, the EV-mediated transfer of NKG2DLs could suggest novel therapeutic approaches based on the usage of engineered nanoparticles aimed at increasing cancer cell immunogenicity. Full article

The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence. Full article

In this study, we deposit a Ge-rich Ge–Sb–Te alloy by physical vapor deposition (PVD) in the amorphous phase on silicon substrates. We study in-situ, by X-ray and ultraviolet photoemission spectroscopies (XPS and UPS), the electronic properties and carefully ascertain the alloy composition to be GST 29 20 28. Subsequently, Raman spectroscopy is employed to corroborate the results from the photoemission study. X-ray diffraction is used upon annealing to study the crystallization of such an alloy and identify the effects of phase separation and segregation of crystalline Ge with the formation of grains along the [111] direction, as expected for such Ge-rich Ge–Sb–Te alloys. In addition, we report on the electrical characterization of single memory cells containing the Ge-rich Ge–Sb–Te alloy, including I-V characteristic curves, programming curves, and SET and RESET operation performance, as well as upon annealing temperature. A fair alignment of the electrical parameters with the current state-of-the-art of conventional (GeTe)_n-(Sb₂Te₃)_m alloys, deposited by PVD, is found, but with enhanced thermal stability, which allows for data retention up to 230 °C. Full article

In March 2019, the World Health Organization (WHO) recognized the COVID-19 pandemic as a global issue. To reduce the spread of this disease, health safety pathways were implemented worldwide. These extraordinary measures changed people’s lifestyles, e.g., by being forced to isolate, and in many cases, to work remotely from home. Low back pain (LBP), the most common cause of disability worldwide, is often a symptom of COVID-19. Moreover, it is often associated with different lifestyle features (type of job, physical activity, body weight). Therefore, the purpose of this systematic review and meta-analysis was to estimate the effect of the COVID-19 lockdown on LBP intensity and prevalence compared with LBP rates before the pandemic. A systematic search was performed on Scopus, PubMed, and Cochrane Central. Overall, eight studies with 2365 patients were included in the analysis. We used the Joanna Briggs Institute (JBI) critical appraisal tool to evaluate the risk of bias: six studies (75%) were at moderate risk of bias and two studies (25%) were at low risk of bias. These studies showed an increase in both the prevalence and intensity of LBP during the COVID-19 lockdown. Full article

The search for a novel technology able to detect and reconstruct nuclear and electron recoil events with the energy of a few $\mathrm{keV}$ has become more and more important now that large regions of high-mass dark matter (DM) candidates have been excluded. Moreover, a detector sensitive to incoming particle direction will be crucial in the case of DM discovery to open the possibility of studying its properties. Gaseous time projection chambers (TPC) with optical readout are very promising detectors combining the detailed event information provided by the TPC technique with the high sensitivity and granularity of latest-generation scientific light sensors. The CYGNO experiment (a CYGNus module with Optical readout) aims to exploit the optical readout approach of multiple-GEM structures in large volume TPCs for the study of rare events as interactions of low-mass DM or solar neutrinos. The combined use of high-granularity sCMOS cameras and fast light sensors allows the reconstruction of the 3D direction of the tracks, offering good energy resolution and very high sensitivity in the few keV energy range, together with a very good particle identification useful for distinguishing nuclear recoils from electronic recoils. This experiment is part of the CYGNUS proto-collaboration, which aims at constructing a network of underground observatories for directional DM search. A one cubic meter demonstrator is expected to be built in 2022/23 aiming at a larger scale apparatus (30 m${}^3$–100 m${}^3$) at a later stage. Full article

Chronic low back pain (CLBP) is the most common cause of disability worldwide, affecting about 12% to 30% of the adult population. Psychological factors play an important role in the experience of pain, and may be predictive of pain persistence, disability, and long-term sick leave. The aim of this meta-analysis was to identify and to describe the most common psychological approaches used to treat patients who suffer from CLBP. A systematic search was performed on PubMed/MEDLINE and Cochrane Central. Overall, 16 studies with a total of 1058 patients were included in the analysis. Our results suggest that cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) interventions are both associated with an improvement in terms of pain intensity and quality of life when singularly compared to usual care. Disability also improved in both groups when compared to usual care. Significant differences in fear-avoidance beliefs were noted in the CBT group compared to usual care. Therefore, psychological factors are related to and influence CLBP. It is crucial to develop curative approaches that take these variables into account. Our findings suggest that CBT and MBSR modify pain-related outcomes and that they could be implemented in clinical practice. Full article

The CYGNO project aims at developing a high resolution Time Projection Chamber with optical readout for directional dark matter searches and solar neutrino spectroscopy. Peculiar CYGNO’s features are the 3D tracking capability provided by the combination of photomultipliers and scientific CMOS camera signals, combined with a helium-fluorine-based gas mixture at atmospheric pressure amplified by gas electron multipliers structures. In this paper, the performances achieved with CYGNO prototypes and the prospects for the upcoming underground installation at Laboratori Nazionali del Gran Sasso of a 50-L detector in fall 2021 will be discussed, together with the plans for a 1-m${}^3$ experiment. The synergy with the ERC consolidator, grant project INITIUM, aimed at realising negative ion drift operation within the CYGNO 3D optical approach, will be further illustrated. Full article

The AB refers to the performance impairment that occurs when visual selective attention is overloaded through the very rapid succession of two targets (T1 and T2) among distractors by using the rapid serial visual presentation task (RSVP). Under these conditions, performance is typically impaired when T2 is presented within 200–500 ms from T1 (AB). Based on neuroimaging studies suggesting a role of top-down attention and working memory brain hubs in the AB, here we potentiated via anodal or sham tDCS the activity of the right DLPFC (F4) and of the right PPC (P4) during an AB task. The findings showed that anodal tDCS over the F4 and over P4 had similar effects on the AB. Importantly, potentiating the activity of the right frontoparietal network via anodal tDCS only benefitted poor performers, reducing the AB, whereas in good performers it accentuated the AB. The contribution of the present findings is twofold: it shows both top-down and bottom-up contributions of the right frontoparietal network in the AB, and it indicates that there is an optimal level of excitability of this network, resulting from the individual level of activation and the intensity of current stimulation. Full article

Masonry towers are part of a valuable architectural heritage characterizing the landscape of many historical areas. These towers are vulnerable structures that are prone to earthquake damage. Hence, the design of effective seismic upgrading interventions is an important task for preserving such architectural forms for future generations. In view of that, the objective of this study is to contribute a possible addition to the portfolio of available approaches for seismic upgrading of masonry towers. This goal was pursued by exploring an innovative structural solution that does not alter the external appearance of the tower and its static scheme under gravity loads, yet is able to increase its capacity to withstand seismic actions through added damping. Specifically, the proposed solution consists of a steel structure internal to the masonry tower that incorporates fluid viscous dampers. In order to evaluate its potentialities, a real case study was taken as a testbed structure, historic analysis as well as geometric and architectural surveys were undertaken, an initial design for the upgrading was made, and numerical simulations were performed. The obtained results, although preliminary, highlight the potentialities of the proposed structural solution for the seismic upgrading of masonry towers and might open the way to future developments and applications. Full article