Background: Emerging evidence has highlighted the importance of extracellular vesicle (EV)-based biomarkers of resistance to immunotherapy with checkpoint inhibitors in metastatic melanoma. Considering the tumor-promoting implications of urokinase-type plasminogen activator receptor (uPAR) signaling, this study aimed to assess uPAR expression in the plasma-derived EVs of patients with metastatic melanoma to determine its potential correlation with clinical outcomes. Methods: Blood samples from 71 patients with metastatic melanoma were collected before initiating immunotherapy. Tumor-derived and immune cell-derived EVs were isolated and analyzed to assess the relative percentage of uPAR⁺ EVs. The associations between uPAR and clinical outcomes, sex, BRAF status, baseline lactate dehydrogenase levels and number of metastatic sites were assessed. Results: Responders had a significantly lower percentage of tumor-derived, dendritic cell (DC)-derived and CD8⁺ T cell-derived uPAR +EVs at baseline than non-responders. The Kaplan-Meier survival curves for the uPAR⁺EV quartiles indicated that higher levels of melanoma-derived uPAR⁺ EVs were strongly correlated with poorer progression-free survival (p<0.0001) and overall survival (p<0.0001). We also found a statistically significant correlation between lower levels of uPAR⁺ EVs from both CD8⁺ T cells and DCs and better survival. Conclusions: Our results indicate that higher levels of tumor-derived, DC-derived and CD8⁺ T cell-derived uPAR⁺ EVs in non-responders may represent a new biomarker of innate resistance to immunotherapy with checkpoint inhibitors. Moreover, uPAR⁺ EVs represent a new potential target for future therapeutic approaches.

Antibody physisorption at a solid interface is a very interesting phenomenon that has important effects on applications such as the development of novel biomaterials and the rational design and fabrication of high-performance biosensors. The strategy selected to immobilize biorecognition elements can determine the performance level of a device and one of the simplest approaches is physical adsorption, which is cost-effective, fast, and compatible with printing techniques as well as with green-chemistry processes. Despite its huge advantages, physisorption is very seldom adopted, as there is an ingrained belief that it does not lead to high performance because of its lack of uniformity and long-term stability, which, however, have never been systematically investigated, particularly for bilayers of capture antibodies. Herein, the homogeneity and stability of an antibody layer against SARS-CoV-2-Spike1 (S1) protein physisorbed onto a gold surface have been investigated by means of multi-parametric surface plasmon resonance (MP-SPR). A surface coverage density of capture antibodies as high as (1.50 ± 0.06) × 10¹² molecules per cm⁻² is measured, corresponding to a thickness of 12 ± 1 nm. This value is compatible with a single monolayer of homogeneously deposited antibodies. The effect of the ionic strength (i_s) of the antibody solution in controlling physisorption of the protein was thoroughly investigated, demonstrating an enhancement in surface coverage at lower ionic strength. An atomic force microscopy (AFM) investigation shows a globular structure attributed to i_s-related aggregations of antibodies. The long-term stability over two weeks of the physisorbed proteins was also assessed. High-performance sensing was proven by evaluating figures of merit, such as the limit of detection (2 nM) and the selectivity ratio between a negative control and the sensing experiment (0.04), which is the best reported performance for an SPR S1 protein assay. These figures of merit outmatch those measured with more sophisticated biofunctionalization procedures involving chemical bonding of the capture antibodies to the gold surface. The present study opens up interesting new pathways toward the achievement of a cost-effective and scalable biofunctionalization protocol, which could guarantee the prolonged stability of the biolayer and easy handling of the biosensing system.

The study of visuomotor adaptation (VMA) capabilities has been encompassed in various experimental protocols aimed at investigating human motor control strategies and/or cognitive functions. VMA-oriented frameworks can have clinical applications, primarily in the investigation and assessment of neuromotor impairments caused by conditions such as Parkinson’s disease or post-stroke, which affect the lives of tens of thousands of people worldwide. Therefore, they can enhance the understanding of the specific mechanisms of such neuromotor disorders, thus being a potential biomarker for recovery, with the aim of being integrated with conventional rehabilitative programs. Virtual Reality (VR) can be entailed in a framework targeting VMA since it allows the development of visual perturbations in a more customizable and realistic way. Moreover, as has been demonstrated in previous works, a serious game (SG) can further increase engagement thanks to the use of full-body embodied avatars. Most studies implementing VMA frameworks have focused on upper limb tasks and have utilized a cursor as visual feedback for the user. Hence, there is a paucity in the literature about VMA-oriented frameworks targeting locomotion tasks. In this article, the authors present the design, development, and testing of an SG-based framework that addresses VMA in a locomotion activity by controlling a full-body moving avatar in a custom VR environment. This workflow includes a set of metrics to quantitatively assess the participants’ performance. Thirteen healthy children were recruited to evaluate the framework. Several quantitative comparisons and analyses were run to validate the different types of introduced visuomotor perturbations and to evaluate the ability of the proposed metrics to describe the difficulty caused by such perturbations. During the experimental sessions, it emerged that the system is safe, easy to use, and practical in a clinical setting. Despite the limited sample size, which represents the main limitation of the study and can be compensated for with future recruitment, the authors claim the potential of this framework as a useful instrument for quantitatively assessing either motor or cognitive impairments. The proposed feature-based approach gives several objective parameters as additional biomarkers that can integrate the conventional clinical scores. Future studies might investigate the relation between the proposed biomarkers and the clinical scores for specific disorders such as Parkinson’s disease and cerebral palsy.

While a substantial amount of research activity has been conducted in fields related to organic photonics and electronics, including the development of devices such as organic field-effect transistors, organic photovoltaics, and organic light-emitting diodes for applications encompassing organic thermoelectrics, organic batteries, excitonic organic materials for photochemical and optoelectronic applications, and organic thermoelectrics, this perspective review will primarily concentrate on the emerging and rapidly expanding domain of organic bioelectronics and neuromorphics. Here we present the most recent research findings on organic transistors capable of sensing biological biomarkers down at the single-molecule level (i.e., oncoproteins, genomes, etc.) for the early diagnosis of pathological states and to mimic biological synapses, paving the way to neuromorphic applications that surpass the limitations of the traditional von Neumann computing architecture. Both organic bioelectronics and neuromorphics exhibit several challenges but will revolutionize human life, considering the development of artificial synapses to counteract neurodegenerative disorders and the development of ultrasensitive biosensors for the early diagnosis of cancer to prevent its development. Moreover, organic bioelectronics for sensing applications have also triggered the development of several wearable, flexible and stretchable biodevices for continuous biomarker monitoring.

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.

Biosensors are versatile in many applications, but their adoption as reliable point-of-care tests is hindered by challenges in systematic optimization. Experimental design provides a solution by guiding their effective development and refinement.