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The transport sector worldwide relies heavily on oil products, and private cars account for the largest share of passenger mobility in several countries. Public transport could represent an interesting alternative under many perspectives, including a decrease in traffic, pollutants, and climate emissions. However, for public transport to succeed, it should be attractive for final users, representing a viable alternative to private mobility. In this work, we analyse the spatial distribution of public transport service provision within two metropolitan cities, considering the three key dimensions of mobility, competitiveness, and accessibility of public transport. The results show that private car performs better than public transport in all scopes considered, and that performance indicators are highly variable among city areas, indicating inequalities in social and environmental sustainability in urban systems. The outcomes of the analysis provide interesting insights for policy makers and researchers that deal with similar topics, and can also be extended to other cities and countries.

IntroductionExtracellular vesicles (EVs) can be released by any cell and are crucial for cell-to-cell communications. EVs have been characterized in patients with solid and hematological tumors, where they play an important role in tumor progression and metastasis. EVs may express different surface proteins derived from the parental cells, including immunomodulatory molecules, such as HLA-G and PDL1.MethodsWe isolated EV from bone marrow (BM) samples of patients with Neuroblastoma (NB) and healthy controls and we analyzed the expression of CD56, GD2 and immune checkpoints on EV by flow cytometry. Next, we analyzed the function of T cells in vitro in the presence or absence of NB patients' BM-derived EV, in terms of proliferation and cytokine production. Finally, we analyzed the correlation between the expression of immune checkpoints on EV and the clinical outcome of patients.ResultsWe found a higher expression of CD56 on EVs derived from BM of patients with NB than in those from healthy donors (HD). However, CD56 expression was not dependent on BM infiltration of NB cells. Moreover, the analysis of GD2 expression revealed that only a small fraction of EVs was released by infiltrating NB cells, whereas the majority may derive from BM-resident cells. BM-derived EVs from NB patients display a higher expression of HLA-G and PD-L1 than those derived from HD. Nonetheless, such EVs are able to modulate T cell immune responses. We measured a robust response, in vitro, towards a common bacterial antigen, including the release of GM-CSF and proinflammatory cytokines, like IFN-a and IL-6, from mononuclear cells. Some of these immunomodulatory features are dependent on the expression of HLA-G and PD-L1, whereas others may rely on other mechanism(s). Finally, a high expression of CD56, HLA-G and PD-L1 on BM-derived EVs may represent a good prognostic factor.ConclusionsWe described the presence of HLA-G and PDL1-bearing EVs in the BM of NB patients, which may represent a mechanism performed by resident BM cells to counteract the inflammation occurring in the BM microenvironment of NB patients.

BackgroundShared biological factors may play a role in both the cognitive deficits and the increased prevalence of metabolic syndrome observed in individuals with Schizophrenia (SCZ). These factors could entail disturbances in tryptophan (Trp) to both melatonin (MLT) and kynurenine (Kyn) metabolic pathways, as well as inflammation and alterations in the gut microbiome composition.MethodsThe present research project aims to investigate this hypothesis by recruiting 170 SCZ patients from two different recruitment sites, assessing their cognitive functions and screening for the presence of metabolic syndrome. Additionally, we plan to assess the impact of a 3-month cognitive remediation therapy on 30 of these patients. We will analyze clinical data alongside serum biomarkers and gene expression related to the Trp- to MLT and Kyn metabolic pathways, markers of inflammatory and composition of the gut microbiome. The association between Trp-MLT-Kyn levels, expression levels of selected genes, inflammatory markers and clinical phenotypes will be analyses in the context of general linear models.DiscussionThis project has the potential to identify some typical SCZ symptomatic clusters that will be more stringently associated with variations in the Trp-MLT-Kyn/inflammatory system and with a better response to cognitive remediation therapy. Moreover, in a future perspective, it may highlight a group of patients who may benefit from a pharmacological treatment aiming at reinstating the physiological Trp to MLT and Kyn system. Therefore, it has the potential to move research toward a personalized approach for SCZ management.

Abstract The security of data communications is one of the crucial challenges that our society is facing today. Quantum Key Distribution (QKD) is one of the most prominent methods for guaranteeing ultimate security based on the laws of quantum physics. In this work, the results obtained during the Italian Industry 4.0 Quantum Testbed (II4QuTe) project are reported where the authors realised a QKD testbed securely connecting the Competence Industry Manufacturing 4.0 (CIM4.0) located in Torino and a TIM edge node located 10 km away from the testbed. The edge node accommodates the server providing computation capabilities for managing the real‐time data generated by the machines within the CIM4.0 digital factory pilot line, thus gracefully integrating QKD with the MEC (Multi‐access Edge Computing) paradigm. The experiment was conducted for more than 69 h, establishing an average key generation rate of 5.125 keys/s (AES‐256 keys) and demonstrating the stability of the entire end‐to‐end encryption system.

Honey, a natural food with a rich history, is produced by honeybees and other species of bees from nectar, other plant fluids, and honeydew of sap-sucking insects. During foraging, these bees may be exposed to plant protection products (PPPs), metals, and metalloids, potentially leading to residues in honey and hive products that could have a negative impact on human safety. Recognizing the lack of an appropriate methodology for pesticide contamination of honey and other hive products, this research aims to support the need for studies on residues in pollen and bee products for human consumption to establish safe maximum residue levels (MRLs) for consumers. A UHPLC-MS/MS residues method and a modified QuEChERS extraction were applied to simultaneously determine 237 pesticide residues in honey and pollen. The study in North Sardinia analyzed honey and pollen samples from six areas for pesticide residues and verified 27 heavy metals and metalloid residues using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The data obtained showed residues at levels close to the LOQ of the method, cycloate in a few samples of pollen, and dichlorvos, zoxamide, cycloate, and chlorantraniliprole in honey samples. All samples showed the absence of heavy metal contamination. Overall, no risk to human health was identified. The results of this study confirm that honey and pollen may be a good bioindicator of environmental contamination of a wide area surrounding honeybee hives.

Artichoke (Cynara cardunculus L.) is an herbaceous perennial plant from the Mediterranean Basin, cultivated as a poly-annual crop in different countries. Artichoke produces a considerable amount of waste at the end of the harvesting season in the field (5.2 tons/ha/year, DW) and from the industrial processing of fresh-cut products during the harvesting time (800 tons/year). The qualitative and quantitative phenolic profile and inulin content of artichoke samples from the field and industrial processing waste have been investigated after green extraction. The best operative conditions were achieved using the dried biomass extracted with water at 80 °C for 120 min and a matrix-to-solvent ratio of 1:30. The data obtained showed that the concentration of total polyphenols in fresh artichokes followed this order: stems > heads > leaves > outer bracts. Chlorogenic acid and 3,4 di-O-caffeoylquinic acid were the most concentrated caffeoylquinic derivates, whereas luteolin 7-O-malonyglucoside, luteolin 7-O-glucoside and 7-O-rutinoside were the most abundant flavonoids. The artichoke by-products showed high polyphenolic and inulin values, thus representing an important source of health-promoting biomolecules for application in pharmaceutical and cosmeceutical fields. According to the principles of circular economy, the work scheme proposed in this article, the use of waste and its processing into useful products such as nutraceutical supplies could provide a practical and economic opportunity for companies and farmers involved in the cultivation and industrial processing of artichokes.

The recent observation of possible granular superconductivity in highly oriented pyrolytic graphite (HOPG) has attracted significant research interest. Here we report a novel investigation on the structural-properties of exfoliated-HOPG. We investigated two types of exfoliation methods, involving either a full (method-1) or partial (method-2) contact between adhesive tape and the main HOPG. Structural characterization was obtained by employing X-ray diffraction (XRD), Raman spectroscopy and electron microscopy (SEM). In particular, Raman point and mapping spectroscopy revealed significant structural-transitions from ABA (Bernal) to ABC (rhombohedral) stacking (stacking-faults), in those samples obtained with the method-2. Interestingly, strained regions exhibiting structural-deformations with a ridge-like morphology were reproducibly identified. The acquired Raman-spectra revealed a local enhancement of the D and D’ bands-intensity together with contributions arising from Electronic Raman Scattering (ERS) across the band-gap of rhombohedral-graphite, at middle (∼1870 cm−1) and high (∼ 2680 cm−1) frequency. HRTEM of the samples produced with the method-2 allowed also for the identification of local-coexistence of ripplocation-like defects with moiré superlattices, an indicator of non-uniform c-axis configuration.

The winemaking process generates an annual global production of about 10 million tons of waste consisting of stalks, skin, and seeds. The possible reutilization of wine pomace is strictly linked to its chemical composition. In this preliminary study, three different Sardinian white grapes (Malvasia, Vermentino and Nasco) grown in the same area were evaluated through a whole wine production chain. To reduce environmental impact, all the grapes were treated following the integrated production practice (IPP) strategies. The adopted agronomic methods and the main physico-chemical parameters of the fresh fruits and musts were evaluated. A fully qualitative and quantitative characterization of the phenolic fraction of the pomace extracts was performed by HPLC-DAD after a post-winemaking process. Water and ethanol were utilized as green solvents in the extraction process. Additionally, the entire pomace post-winemaking process was carried out within the winery facilities to reduce energy loss and road transportation. The findings demonstrated that large amounts of beneficial polyphenols are present in pomace extracts, and that the type of grape used, agronomic practices, and winemaking method all influence the quantity and quality of the extracts. The polyphenol concentrations in the Vermentino (28,391.5 ± 7.0 mg/kg) and Malvasia pomace (11,316.3 ± 6.5 mg/kg) were found to be the highest and lowest, respectively.

This study aims to analyse a single-centre cohort series of patients who underwent parotidectomy for primary malignant parotid tumours. A retrospective chart review of 64 consecutive patients treated from November 2010 to March 2022 was performed. Outcomes were analysed by Kaplan-Meier curves. Sixty-four patients with a primary parotid malignancy were included in the study, with one bilateral case in this cohort. Patients were classified as stage I–II in 39 cases and stage III–IV in 26 cases. The five-year overall survival (OS), disease-specific survival (DSS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 78.4%, 89%, 92.5%, and 87.1%, respectively. Univariate analysis showed that high-risk histology, stage IV disease, lymphovascular invasion, perineural invasion, node metastasis, skin involvement, facial nerve involvement, and positive or close margins were risk factors associated with poorer outcomes. At present, the best evidence suggests that radical surgery should be the standard approach, and adjuvant therapy, in terms of radiotherapy/chemoradiotherapy, is recommended in patients with risk factors.

Mental health of undergraduate students is receiving more attention because of the increase in the prevalence and intensity of psychological distress. Our aim is to verify the effectiveness of a cognitive behavioural counselling service in reducing psychological distress and improving academic self-efficacy in a sample of 124 students (57% above the clinical cut-off) using a pre-post assessment design. Data show a significant reduction of distress and symptoms scores among students who completed the intervention and half of them had a reliable change. Preliminary data also show a significant improvement in academic self-efficacy. University counselling services represent common first-line services for students and are effective in treating psychological distress in a wide range of clinical and sub-clinical situations.

Introduction B7-H3 is a potential target for pediatric cancers, including neuroblastoma (NB). Vobramitamab duocarmazine (also referred to as MGC018 and herein referred to as vobra duo) is an investigational duocarmycin-based antibody-drug conjugate (ADC) directed against the B7-H3 antigen. It is composed of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody chemically conjugated through a cleavable valine-citrulline linker to a duocarmycin-hydroxybenzamide azaindole (vc-seco-DUBA). Vobra duo has shown preliminary clinical activity in B7-H3-expressing tumors.Methods B7-H3 expression was evaluated by flow-cytometry in a panel of human NB cell lines. Cytotoxicity was evaluated in monolayer and in multicellular tumor spheroid (MCTS) models by the water-soluble tetrazolium salt,MTS, proliferation assay and Cell Titer Glo 3D cell viability assay, respectively. Apoptotic cell death was investigated by annexin V staining. Orthotopic, pseudometastatic, and resected mouse NB models were developed to mimic disease conditions related to primary tumor growth, metastases, and circulating tumor cells with minimal residual disease, respectively.Results All human NB cell lines expressed cell surface B7-H3 in a unimodal fashion. Vobra duo was cytotoxic in a dose-dependent and time-dependent manner against all cell lines (IC50 range 5.1–53.9 ng/mL) and NB MCTS (IC50 range 17.8–364 ng/mL). Vobra duo was inactive against a murine NB cell line (NX-S2) that did not express human B7-H3; however, NX-S2 cells were killed in the presence of vobra duo when co-cultured with human B7-H3-expressing cells, demonstrating bystander activity. In orthotopic and pseudometastatic mouse models, weekly intravenous treatments with 1 mg/kg vobra duo for 3 weeks delayed tumor growth compared with animals treated with an irrelevant (anti-CD20) duocarmycin-ADC. Vobra duo treatment for 4 weeks further increased survival in both orthotopic and resected NB models. Vobra duo compared favorably to TOpotecan-TEMozolomide (TOTEM), the standard-of-care therapy for NB relapsed disease, with tumor relapse delayed or arrested by two or three repeated 4-week vobra duo treatments, respectively. Further increased survival was observed in mice treated with vobra duo in combination with TOTEM. Vobra duo treatment was not associated with body weight loss, hematological toxicity, or clinical chemistry abnormalities.Conclusion Vobra duo exerts relevant antitumor activity in preclinical B7-H3-expressing NB models and represents a potential candidate for clinical translation.

BackgroundThe development of standardized treatments for idiopathic sudden sensorineural hearing loss (ISSNHL) is hampered by uncertainty over the etiology of this disorder. Systemic steroids are historically the primary therapy, with variable hearing outcomes. Over the last two decades, intratympanic steroids (ITS) and hyperbaric oxygen therapy (HBOT) have been proposed as salvage treatments in case of failure of systemic steroids. The present study aims to evaluate the effectiveness of these salvage treatments in addition to systemic steroids.MethodsWe performed a retrospective study on 75 consecutive patients with a diagnosis of ISSNHL who were admitted to the Department of Otorhinolaryngology of our hospital between December 2018 and December 2022. All patients received primary treatment with systemic steroids. In case of slight or no hearing recovery within the 5th day from the beginning of the therapy (T1), a salvage treatment with ITS or HBOT was proposed. Patients were divided into three groups according to the therapy received: systemic steroids (group A), systemic steroids + HBOT (group B), and systemic steroids + ITS (group C). Pure-tone average at 500, 1000, 2000, and 3000 Hz and the mean gain were evaluated at T1 and 3 months after the beginning of the salvage treatment (T2). The hearing recovery was assessed according to the Siegel's criteria.ResultsSixty-two patients (31 men and 31 women, mean age 56 years) with failure of the primary treatment were definitively enrolled in the study: 34 (54.8%) in group A, 16 (25.8%) in group B, and 12 (19.4%) in group C. The ratio of patients responding to therapy was higher in group A (29.4%) than in groups B (18.75%) and C (16.7%). We did not find any statistically significant difference between groups in terms of mean hearing gain at T2 (17.4 ± 15.4 dB in group A vs. 18.6 ± 21.1 dB in group B and 15.7 ± 14.2 dB in group C, p = 0.9).ConclusionIn our experience, ITS or HBOT associated with systemic steroids, as salvage treatment, did not show significant improvement in hearing outcomes. The evolution of ISSNHL, regardless of the treatment, remains unpredictable.

Recent studies identified pregnancy as a high-risk condition for the development of maternal-fetal complications in the case of the SARS-CoV-2 infection. Therefore, the scientific community is now considering pregnant women a “fragile” category that should be vaccinated with high priority. The number of pregnant women undergoing hospitalization since summer 2021, including Intensive Care Unit admission, is growing, as well as the risk of preterm birth. Evidence from both animals and humans suggest that, similarly to other vaccines routinely administered in pregnancy, COVID-19 vaccines are not crossing the placenta, do not increase the risk of miscarriage, preterm birth, stillbirth, the birth of small gestational age neonates, as well as the risk of congenital abnormalities. To date, the World Health Organization and scientific literature are promoting and encouraging the vaccination of all pregnant and lactating women. The aim of our narrative review is to present the available literature regarding this issue with the aim to provide appropriate answers to the most frequent requests, doubts, and fears that have led many expecting and lactating women not to become vaccinated during this pandemic period.

Honey, a natural food with a rich history, is produced by honeybees and other species of bees from nectar, other plant fluids, and honeydew of sap-sucking insects. During foraging, these bees may be exposed to plant protection products (PPPs), metals, and metalloids, potentially leading to residues in honey and hive products that could have a negative impact on human safety. Recognizing the lack of an appropriate methodology for pesticide contamination of honey and other hive products, this research aims to support the need for studies on residues in pollen and bee products for human consumption to establish safe maximum residue levels (MRLs) for consumers. A UHPLC-MS/MS residues method and a modified QuEChERS extraction were applied to simultaneously determine 237 pesticide residues in honey and pollen. The study in North Sardinia analyzed honey and pollen samples from six areas for pesticide residues and verified 27 heavy metals and metalloid residues using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The data obtained showed residues at levels close to the LOQ of the method, cycloate in a few samples of pollen, and dichlorvos, zoxamide, cycloate, and chlorantraniliprole in honey samples. All samples showed the absence of heavy metal contamination. Overall, no risk to human health was identified. The results of this study confirm that honey and pollen may be a good bioindicator of environmental contamination of a wide area surrounding honeybee hives. [ABSTRACT FROM AUTHOR]

Background: Shared biological factors may play a role in both the cognitive deficits and the increased prevalence of metabolic syndrome observed in individuals with Schizophrenia (SCZ). These factors could entail disturbances in tryptophan (Trp) to both melatonin (MLT) and kynurenine (Kyn) metabolic pathways, as well as inflammation and alterations in the gut microbiome composition. Methods: The present research project aims to investigate this hypothesis by recruiting 170 SCZ patients from two different recruitment sites, assessing their cognitive functions and screening for the presence of metabolic syndrome. Additionally, we plan to assess the impact of a 3-month cognitive remediation therapy on 30 of these patients. We will analyze clinical data alongside serum biomarkers and gene expression related to the Trp- to MLT and Kyn metabolic pathways, markers of inflammatory and composition of the gut microbiome. The association between Trp-MLT-Kyn levels, expression levels of selected genes, inflammatory markers and clinical phenotypes will be analyses in the context of general linear models. Discussion: This project has the potential to identify some typical SCZ symptomatic clusters that will be more stringently associated with variations in the Trp-MLT-Kyn/inflammatory system and with a better response to cognitive remediation therapy. Moreover, in a future perspective, it may highlight a group of patients who may benefit from a pharmacological treatment aiming at reinstating the physiological Trp to MLT and Kyn system. Therefore, it has the potential to move research toward a personalized approach for SCZ management. [ABSTRACT FROM AUTHOR]

Introduction: Extracellular vesicles (EVs) can be released by any cell and are crucial for cell-to-cell communications. EVs have been characterized in patients with solid and hematological tumors, where they play an important role in tumor progression and metastasis. EVs may express different surface proteins derived from the parental cells, including immunomodulatory molecules, such as HLA-G and PDL1. Methods: We isolated EV from bone marrow (BM) samples of patients with Neuroblastoma (NB) and healthy controls and we analyzed the expression of CD56, GD2 and immune checkpoints on EV by flow cytometry. Next, we analyzed the function of T cells in vitro in the presence or absence of NB patients' BM-derived EV, in terms of proliferation and cytokine production. Finally, we analyzed the correlation between the expression of immune checkpoints on EV and the clinical outcome of patients. Results: We found a higher expression of CD56 on EVs derived from BM of patients with NB than in those from healthy donors (HD). However, CD56 expression was not dependent on BM infiltration of NB cells. Moreover, the analysis of GD2 expression revealed that only a small fraction of EVs was released by infiltrating NB cells, whereas the majority may derive from BM-resident cells. BM-derived EVs from NB patients display a higher expression of HLA-G and PD-L1 than those derived from HD. Nonetheless, such EVs are able to modulate T cell immune responses. We measured a robust response, in vitro, towards a common bacterial antigen, including the release of GM-CSF and proinflammatory cytokines, like IFN-a and IL-6, from mononuclear cells. Some of these immunomodulatory features are dependent on the expression of HLA-G and PD-L1, whereas others may rely on other mechanism(s). Finally, a high expression of CD56, HLA-G and PD-L1 on BM-derived EVs may represent a good prognostic factor. Conclusions: We described the presence of HLA-G and PDL1-bearing EVs in the BM of NB patients, which may represent a mechanism performed by resident BM cells to counteract the inflammation occurring in the BM microenvironment of NB patients. [ABSTRACT FROM AUTHOR]