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The early identification of microvascular changes in patients with Coronavirus Disease 2019 (COVID-19) may offer an important clinical opportunity. This study aimed to define a method, based on deep learning approaches, for the identification of COVID-19 patients from the analysis of the raw PPG signal, acquired with a pulse oximeter. To develop the method, we acquired the PPG signal of 93 COVID-19 patients and 90 healthy control subjects using a finger pulse oximeter. To select the good quality portions of the signal, we developed a template-matching method that excludes samples corrupted by noise or motion artefacts. These samples were subsequently used to develop a custom convolutional neural network model. The model accepts PPG signal segments as input and performs a binary classification between COVID-19 and control samples. The proposed model showed good performance in identifying COVID-19 patients, achieving 83.86% accuracy and 84.30% sensitivity (hold-out validation) on test data. The obtained results indicate that photoplethysmography may be a useful tool for microcirculation assessment and early recognition of SARS-CoV-2-induced microvascular changes. In addition, such a noninvasive and low-cost method is well suited for the development of a user-friendly system, potentially applicable even in resource-limited healthcare settings.

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a late-onset autoinflammatory disorder caused by somatic mutations in the gene. It is characterized by systemic inflammation, a wide spectrum of rheumatologic features, including chondritis and inflammatory arthritis, dermatologic manifestations (e.g. neutrophilic dermatosis or vasculitis-like lesions), and hematologic abnormalities like macrocytic anemia and myelodysplastic syndrome. Due to its heterogeneity, diagnosis is frequently delayed. Early recognition of hallmark inflammatory symptoms, particularly by rheumatologists, is critical for timely diagnosis and management. We conducted a retrospective analysis of 37 patients over the age of 50. Next-Generation Sequencing (Illumina HiSeq2500) was employed to assess mutations. Clinical, genetic, and demographic data were extracted from electronic medical records. Twenty patients [100% male; median age 73 years (IQR 67-77)] were confirmed to carry somatic mutations. All patients exhibited constitutional symptoms (100%) and at least one rheumatologic manifestation, including chondritis (75%), arthralgia or arthromyalgia (50%), arthritis (30%), osteopenia or osteoporosis (15%), myalgia or myositis (10%), and tenosynovitis (5%). Dermatologic and hematologic abnormalities frequently co-occurred. Infectious complications were observed in 80% of patients and were a major contributor to overall morbidity. This study underscores the need for a phenotype-driven diagnostic approach to facilitate earlier identification of VEXAS syndrome. Our findings suggest that current estimates of prevalence in rheumatology settings may significantly underestimate the true disease burden. Improved awareness and interdisciplinary collaboration, particularly among rheumatologists, hematologists, and dermatologists, are essential to enhance recognition, diagnosis, and comprehensive care for individuals affected by this complex syndrome.

Metabolic rate is commonly thought to scale with body mass to the 3/4 power as a result of universal body design constraints. However, recent comparative work has shown that the metabolic-scaling slope may vary significantly among species and higher taxa, apparently in response to different lifestyles and ecological conditions, though the precise mechanisms involved are not well understood. To better understand these underappreciated ecological effects and their causes, it is important to control for extraneous phylogenetic and environmental influences. We demonstrate how this may be done by comparing the ontogenetic scaling of resting metabolic rate among populations of the same species (the amphipod Gammarus minus ) in mid-Appalachian freshwater springs with similar, relatively constant environmental conditions, except for the varying presence of the predatory fish Cottus cognatus . We found that populations of G. minus exhibit significantly lower metabolic-scaling slopes (0.54-0.62) in three freshwater springs with C. cognatus than in two springs without these fish (0.76-0.77). We tested multiple hypothetical causes for these population differences. Our results best supported the hypothesis that metabolic scaling was influenced by the effects of size-selective predation on the ontogeny of growth, a metabolically expensive process. The body size scaling of growth is significantly less steep in the populations inhabiting springs with vs. without fish, thus paralleling the interpopulation differences in metabolic scaling. Prematurational growth of G. minus is as high or higher in the fish springs, whereas postmaturational growth is significantly lower, often approaching zero. Similarly, the amphipods in the fish springs tend to have higher metabolic rates at small sizes, but lower metabolic rates at large sizes, compared to those in the fishless springs. Our results do not support other hypothetical causes of the interpopulation variation in metabolic scaling, including differential scaling of cell size or low-metabolism body components (fat and mineralized exoskeleton), or possible effects of other environmental factors associated with the presence of fish. However, fish-induced population differences in adult behavioral activity may influence metabolic scaling in G. minus , a possibility under current study. We conclude that ecological factors may significantly influence metabolic scaling, contrary to common belief.

B cells participate in immune surveillance in human circulation and tissues, including tumors such as melanoma. By contrast, the role of humoral responses in cutaneous immunity is underappreciated. We report circulating skin-homing CD22+CLA+B cells in healthy volunteers and melanoma patients (n = 73) and CD22+ cells in melanoma and normal skin samples (n = 189). Normal and malignant skin featured mature IgG and CD22 mRNA, alongside mRNA for the transiently-expressed enzyme Activation-induced cytidine Deaminase (AID). Gene expression analyses of publically-available data (n = 234 GEO, n = 384 TCGA) confirmed heightened humoral responses (CD20, CD22, AID) in melanoma. Analyses of 51 melanoma-associated and 29 normal skin-derived IgG sequence repertoires revealed lower IgG1/IgG total representation compared with antibodies from circulating B cells. Consistent with AID, comparable somatic hypermutation frequencies and class-switching indicated affinity-matured antibodies in normal and malignant skin. A melanoma-associated antibody subset featured shorter complementarity-determining (CDR3) regions relative to those from circulating B cells. Clonal amplification in melanoma-associated antibodies and homology modeling indicated differential potential antigen recognition profiles between normal skin and melanoma sequences, suggesting distinct antibody repertoires. Evidence for IgG-expressing B cells, class switching and antibody maturation in normal and malignant skin and clonally-expanded antibodies in melanoma, support the involvement of mature B cells in cutaneous immunity.

Augmented and mixed reality in the medical field is becoming increasingly important. The creation and visualization of digital models similar to reality could be a great help to increase the user experience during augmented or mixed reality activities like surgical planning and educational, training and testing phases of medical students. This study introduces a technique for enhancing a 3D digital model reconstructed from cone-beam computed tomography images with its real coloured texture using an Intel D435 RGBD camera. This method is based on iteratively projecting the two models onto a 2D plane, identifying their contours and then minimizing the distance between them. Finally, the coloured digital models were displayed in mixed reality through a Microsoft HoloLens 2 and an application to interact with them using hand gestures was developed. The registration error between the two 3D models evaluated using 30,000 random points indicates values of: 1.1 ± 1.3 mm on the x-axis, 0.7 ± 0.8 mm on the y-axis, and 0.9 ± 1.2 mm on the z-axis. This result was achieved in three iterations, starting from an average registration error on the three axes of 1.4 mm to reach 0.9 mm. The heatmap created to visualize the spatial distribution of the error shows how it is uniformly distributed over the surface of the pointcloud obtained with the RGBD camera, except for some areas of the nose and ears where the registration error tends to increase. The obtained results indicate that the proposed methodology seems effective. In addition, since the used RGBD camera is inexpensive, future approaches based on the simultaneous use of multiple cameras could further improve the results. Finally, the augmented reality visualization of the obtained result is innovative and could provide support in all those cases where the visualization of three-dimensional medical models is necessary.

Inflammation mechanisms play a critical role in muscle homeostasis, and in Muscular Dystrophies (MDs), the myofiber damage triggers chronic inflammation which significantly controls the disease progression. Immunomodulatory strategies able to target inflammatory pathways and mitigate the immune-mediated damage in MDs may provide new therapeutic options. Owing to its capacity of influencing the immune response and enhancing tissue repair, stem cells’ secretome has been proposed as an adjunct or standalone treatment for MDs. In this review study, we discuss the challenging points related to the inflammation condition characterizing MD pathology and provide a concise summary of the literature supporting the potential of perinatal stem cells in targeting and modulating the MD inflammation.

Purpose – The purpose of this paper is to explore the impact of different cultural typologies (i.e. innovative, competitive, bureaucratic and community) on employees’ knowledge-sharing processes within multinational corporations (MNCs) by taking a subsidiary perspective. It particularly applies the competing values framework to the study of individuals’ orientations toward sharing knowledge with others while also investigating the influence of top management support on such orientations. Design/methodology/approach – To test the proposed hypotheses, in this paper, survey data of 389 employees from six Italian subsidiaries are empirically analyzed by running hierarchical regressions on the two dimensions of knowledge-sharing processes, i.e. knowledge donating and knowledge collecting. Findings – The results show that the four types of organizational culture differently affect the knowledge-sharing sub-processes and confirm the importance of a strong top management support to facilitate interpersonal relationships. Research limitations/implications – Despite the cross-sectional nature of the data and the limitations arising from the subsidiaries’ position in the country, the findings suggest managers to pay great attention to the positive side of bureaucracy by emphasizing the need for order and efficiency while, at the same time, providing employees with a constant and encouraging support toward knowledge-sharing activities. Originality/value – The paper adds empirical evidence to the limited existing research on knowledge-sharing sub-processes of knowledge donating and collecting, extends the understanding of how different organizational cultures affect such processes, and contributes to the literature on MNCs’ knowledge-based activities by adopting a subsidiary perspective.

Basophils are involved in manifestations of hypersensitivity, however, the current understanding of their propensity for activation and their prognostic value in cancer patients remains unclear. As in healthy and atopic individuals, basophil populations were identified in blood from ovarian cancer patients (n = 53) with diverse tumor histologies and treatment histories. Ex vivo basophil activation was measured by CD63 expression using the basophil activation test (BAT). Irrespective of prior treatment, basophils could be activated by stimulation with IgE- (anti-FcεRI and anti-IgE) and non-IgE (fMLP) mediated triggers. Basophil activation was detected by ex vivo exposure to paclitaxel, but not to other anti-cancer therapies, in agreement with a clinical history of systemic hypersensitivity reactions to paclitaxel. Protein and gene expression analyses support the presence of basophils (CCR3, CD123, FcεRI) and activated basophils (CD63, CD203c, tryptase) in ovarian tumors. Greater numbers of circulating basophils, cells with greater capacity for ex vivo stimulation (n = 35), and gene signatures indicating the presence of activated basophils in tumors (n = 439) were each associated with improved survival in ovarian cancer. Circulating basophils in cancer patients respond to IgE- and non-IgE-mediated signals and could help identify hypersensitivity to therapeutic agents. Activated circulating and tumor-infiltrating basophils may be potential biomarkers in oncology.

BackgroundCancer immunotherapy with monoclonal antibodies and chimeric antigen receptor (CAR) T cell therapies can benefit from selection of new targets with high levels of tumor specificity and from early assessments of efficacy and safety to derisk potential therapies.MethodsEmploying mass spectrometry, bioinformatics, immuno-mass spectrometry and CRISPR/Cas9 we identified the target of the tumor-specific SF-25 antibody. We engineered IgE and CAR T cell immunotherapies derived from the SF-25 clone and evaluated potential for cancer therapy.ResultsWe identified the target of the SF-25 clone as the tumor-associated antigen SLC3A2, a cell surface protein with key roles in cancer metabolism. We generated IgE monoclonal antibody, and CAR T cell immunotherapies each recognizing SLC3A2. In concordance with preclinical and, more recently, clinical findings with the first-in-class IgE antibody MOv18 (recognizing the tumor-associated antigen Folate Receptor alpha), SF-25 IgE potentiated Fc-mediated effector functions against cancer cells in vitro and restricted human tumor xenograft growth in mice engrafted with human effector cells. The antibody did not trigger basophil activation in cancer patient blood ex vivo, suggesting failure to induce type I hypersensitivity, and supporting safe therapeutic administration. SLC3A2-specific CAR T cells demonstrated cytotoxicity against tumor cells, stimulated interferon-γ and interleukin-2 production in vitro. In vivo SLC3A2-specific CAR T cells significantly increased overall survival and reduced growth of subcutaneous PC3-LN3-luciferase xenografts. No weight loss, manifestations of cytokine release syndrome or graft-versus-host disease, were detected.ConclusionsThese findings identify efficacious and potentially safe tumor-targeting of SLC3A2 with novel immune-activating antibody and genetically modified cell therapies.

Purpose Building on the attitude–behavior relationship model, this study aims to contribute to customer orientation literature by suggesting that service employees’ commitment (i.e. personal attitude) affects their customer orientation via the effect of their participation in knowledge sharing with colleagues (i.e. employees’ behavior). Design/methodology/approach The empirical analysis has been developed around survey data, collected from 165 service workers of Italian museums. The hypotheses are tested through the SPSS PROCESS macro plugin. Findings Drawing on the importance of human capital to tourism organizations, this study illustrates that affective commitment has a positive and significant influence on employees’ customer orientation, and that this relationship is fully mediated by knowledge-sharing behaviors. Practical implications As attitudes are more stable than behaviors, the findings suggest that managers of tourism organizations implement appropriate selection and recruitment techniques, together with adequate involvement and empowerment activities, to identify and support individuals whose attitudes fit the organizational goals. Originality/value Acknowledging the contribution that workers can give to service organizations’ success, this paper enriches the understanding of the mechanisms that underlie the relationship between employees’ attitudes and their orientation toward the customer. Building on the cognitive dissonance theory, it adds to extant research on the individual antecedents of employees’ customer orientation by shedding light on the attitude–behavior relationship in tourism organizations.