The DOF (DNA binding with one finger) family of plant-specific transcription factors (TF) was first identified in maize in 1995. Since then, DOF proteins have been shown to be present in the whole plant kingdom including the unicellular alga Chlamydomonas reinhardtii. The DOF TF family is characterised by a highly conserved DNA binding domain (DOF domain), consisting of a CX2C-X21-CX2C motif which is able to form a zinc finger structure. Early in the study of DOF proteins it became clear their relevance for seed biology. Indeed, the Prolamine Binding Factor (PBF), one of the first DOF proteins characterised, controls the endosperm-specific expression of the zein genes in maize. Subsequently, several DOF proteins from both monocots and dicots have been shown to be primarily involved in seed development, dormancy and germination, as well as in seedling development and other light-mediated processes. In the last two decades the molecular network underlying these processes have been outlined, and the main molecular players and their interactions have been identified. In this review, we will focus on the DOF TFs involved in these molecular networs, and on their interaction with other proteins.

The transition from a dormant to a germinating seed represents a crucial developmental switch in the life cycle of a plant. Subsequent transition from a germinating seed to an autotrophic organism also requires a robust and multi-layered control. Seed germination and seedling growth are multistep processes, involving both internal and external signals, which lead to a fine-tuning control network.

This paper provides a comprehensive overview of the potential applications of dual energy CT (DECT) in improving image quality and diagnostic capabilities of CT arthrography (CTA) in clinical practice. The paper covers the use of virtual non contrast (VNC) images, in which the injected contrast medium is reduced from the articular cavity, in order to better analyze 2D and 3D images of the bone. Moreover , virtual monoenergetic imaging (VMI) applications and their potential use for the reduction of metal artifacts and improving image contrast are reviewed. The role of virtual non calcium (VNCa) in detecting bone marrow edema surrounding the imaged joint will be discussed. Furthermore , the role of iodine map to enhance the contrast between soft tissues, optimizing the visualization of contrast material, and to distinguish contrast material from calcifications is described. Finally, a case series including different joints is provided to underline the additional advantages of high spatial resolution dual energy CT reconstructed images.

A visual study of spiral galaxies from a subset of spiral galaxies in the Dark Energy Survey Data Release 2 finds that a significant number show long tails of baryonic matter, often much longer than the apparent diameter of the galaxy. Examples from less than 10% of the candidates are shown here and their possible origin is discussed. The tails were only seen connected to spiral galaxies; no examples of tails connected to elliptical galaxies or to artifacts were found. In many examples the tail is associated with what appears to be a colliding galaxy, but in many others there is no sign of one. An intriguing possibility is that in the latter cases the tails are produced by an encounter with an unseen object, either a massive black hole or a compact galaxy with mostly dark matter.

Recent analyses of cosmic microwave background (CMB) maps have been interpreted as demonstrating that the Universe was born without an initial rotation. However, these analyses are based on unrealistic models and do not contain essential ingredients such as quantum effects, the strong, weak and gravitational interactions between the components, their intrinsic spins and magnetic moments, as well as primordial black holes. If the Universe was born spinning these effects would distribute the initial spin angular momentum among its components long before the CMB forms at recombination. A primordial spin would now appear as a nonzero total angular momentum of its components along the direction of the original spin, and a primordial large-scale rotation would no longer be apparent. The existence of a special axis or direction would break a fundamental symmetry assumed in general relativity, cosmic isotropy, and a net angular momentum implies a cosmic parity violation.

The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterwards spread on land. In particular, seed size had a pivotal role as for evolutionary success and agronomic trait, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated as for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size, and how developmental processes are influenced by them. Besides, new insights on the genetic-molecular control of this adaptive trait are presented.

Few studies have examined the pros and cons of integrated TB and HIV service delivery in public healthcare facilities, and even fewer have proposed conceptual models for improved integration. This study intends to fill that vacuum by outlining the development of a facility-based paradigm for integrating TB, HIV and patients services. The design of the proposed model were in stages that involved the evaluation of existing TB-HIV integration model and synthesis of both quantitative and qualitative data from the study sites which were selected public healthcare facilities at both rural and peri-urban settings in Oliver Reginald (O.R) Tambo District Municipality in Eastern Cape, South Africa. Secondary data on 2009-2013 TB-HIV clinical outcomes were obtained from multiple sources for quantitative analysis. Qualitative data involved focus group discussions among patient and heath care staff, which was thematically analysed. The development of a possibly better model and validation of this model show that the district's health system was reinforced by the model's guiding principles, which placed a strong emphasis on inputs, processes, outcomes, and integration effects.The model is adaptable to different healthcare delivery systems but will require support from healthcare stakeholders and professionals to be successful.

Dynamic virtual testing by Hardware in the Loop (HIL) real time simulation systems is common to minimize physical tests to validate and verify control algorithms, logics and software, under normal and emergency conditions. The accurate but costly HIL models setup activities could have an extended use to simulate faulty conditions that are seldom observable in the real system, yet they must be detected in advance and recognized. Data driven diagnostic methods have reached a mature development, in various sectors, proving effective in early detecting slowly varying deviations from nominal patterns of signals, even without a priori knowledge of their nature and behavior. These methods rely on vast amount of data logged from real systems that are ever and ever richer of monitoring telemetries that are worth being exploited. However, due to the usually reliable and safe systems being managed, it is often difficult to collect enough data on anomalous situations to validate fault detection and isolation and limit false positives. HIL model-based simulations allow generating and observing operational domains or transients rarely observed in real operations. This allows identifying the signals that are most correlated to faults and that could be selected to setup data-based diagnostic models of parts or subsystems, which are more suitable than the whole HIL model for online diagnostics, as well as to identify the features and trends that are most symptomatic of anomalous conditions.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles which may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlighted that mitochondrial dysfunction due to loss of mitochondrial flexibility, may arise before overt NAFLD and since the early stages of liver injury. Mitochondrial failure not only promotes hepatocellular damage, but also release signals (mito-DAMPs) which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by remodeling of glucidic-lipidic metabolism combined to reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research purposes and for development of potential preventive or curative strategies.

Autonomous aircraft are the key enablers of future urban services, such as postal and transportation systems. Digital Twins (DT) are promising cutting-edge technologies that can transform the future transport ecosystem into an autonomous and resilient system. However, since DT is a data-driven solution based on AI, proper data management is essential in implementing DT as a Service (DTaaS). One of the challenges in DT development is the availability of real-life data, particularly for training algorithms and verifying the functionality of DT. The current article focuses on data augmentation through synthetic data generation. This approach can facilitate the development of DT in case the developers do not have enough data to train the Machine Learning (ML) algorithm. The current twinning approach provides a prospective ideal state of the engine used for proactive monitoring of the engine’s health as an anomaly detection service. In line with the track of Unmanned Aircraft Vehicles (UAV) for Urban Air Mobility in Smart Cities applications, this paper focuses specifically on the common Hybrid turbo-shaft in drones/helicopters. However, there is a significant gap in real-life similar synthetic data generation in the UAV domain literature. Therefore, Rolling Linear Regression and Kalman Filter algorithms were implemented on noise-added data, which simulate the data measured from the engine in a real-life operational lifecycle. For both thermal and hybrid models, the corresponding DT model has shown high efficiency in noise filtration and a certain amount of predictions with a lower error rate on all engine parameters, except the engine torque.

Socio-ecologic, socio-economic, and socio-technical transitions are opportunities that require fundamental changes in the system. These will encounter matters associated with security, service adoption by end-users, infrastructure and availability. The purpose of this study is to examine and overcome the risks to take advantage of opportunities through the novel Risky-Opportunity Analysis Method (ROAM). A novel quantitative method is designed to determine when, after making some changes, the risks become acceptable so that the opportunity does not deviate from the objectives. The approach provided a quantitative evaluation of the possible changes in parallel with digitization, towards providing a green Service Supply Chain (SSC). The result of ROAM shows that the most cost-effective change to increase the resilience of the system is a solution (SMS) which is different from that identified by a TOPSIS multi-criteria method. Real-word decisions in change management should tackle the complexity of systems and uncertainty of events during and after transition through a careful analysis of the alternatives. A case-study was carried out to evaluate the alternatives of an ancillary service in the Payment Service Providers (PSP). The comparison of the ROAM results with the traditional TOPSIS of the case-study unveils the priority of the ROAM in practice when the alternatives are Risky-Opportunities. The existing risk assessment tools do not take advantage of risky opportunities. To this aim, the current article introduces the term Risky-Opportunity, and two indexes Stress and Strain of the alternatives that are designed to be employed in the new quantitative ROAM approach.

We study the work fluctuations in ergotropic heat engines, namely two-strokes quantum Otto engines where the work stroke is designed to extract the ergotropy (the maximum amount of work by a cyclic unitary evolution) from a couple of quantum systems at canonical equilibrium at two different temperatures, whereas the heat stroke thermalizes back the systems to their respective reservoirs. We provide an exaustive study for the case of two qutrits whose energy levels are equally spaced at two different frequencies by deriving the complete work statistics. By varying the values of temperatures and frequencies, only three kinds of optimal unitary strokes are found: the swap operator U1, an idle swap U2 (where one of the qutrits is regarded as an effective qubit), and a non trivial permutation of energy eigenstates U3, which indeed corresponds to the composition of the two previous unitaries, namely U3 = U2U1. While U1 and U2 are Hermitian (and hence involutions), U3 is not. This point has an impact on the thermodynamic uncertainty relations (TURs) which bound the signal-to-noise ratio of the extracted work in terms of the entropy production. In fact, we show that all TURs derived from a strong detailed fluctuation theorem are violated by the transformation U3.

The last decade was characterized by the reduction of hospital beds throughout Europe. When facing Covid pandemic, this has been an issue of major importance as hospitals were seriously overloaded with an unexpected growth in demand. The dichotomy formed by the scarcity of beds and the need for acute care was handled by the Bed Management (BM) function. This study explores how BM was able to help the solidness of the healthcare system, managing hospital beds at best and recruiting others in different set-tings as intermediate care, in a large Local Health Authority (LHA) in central Italy. Ad-ministrative data show how the provision of appropriate care was achieved recruiting approximately 500 beds belonging to private healthcare facilities affiliated with the re-gional healthcare system and exercising at best the BM function. The ability of the system to absorb the extra demand caused by Covid was made possible using intermediate care beds, which allowed to stretch the logistic boundaries of the hospitals, and by the promptness of Bed Management in converting beds in Covid beds and reconverting them and timely managing internal patient logistic, thus creating space according to the healthcare demand.

This study uses a wind turbine case study to showcase an architecture for implementing a distributed digital twin in which all important aspects of a predictive maintenance solution in a DT use a fog computing paradigm, and the typical predictive maintenance DT is improved to offer better asset utilization and management through real time condition monitoring, predictive analytics, and health management of selected components of Wind turbines in a wind farm.. Digital twin (DT) is a technology that sits at the intersection of Internet of Things, Cloud Computing and Software Engineering to provide a suitable tool for replicating physical objects in the digital space. This can facilitate the implementation of asset management in manufacturing systems through predictive maintenance solutions leveraged by Machine Learning (ML). With DTs, a solution architecture can easily use data and software to implement asset management solutions such as Condition Monitoring and Predictive Maintenance using acquired sensor data from physical objects and computing capabilities in the digital space. While DT offers a good solution, it is an emerging technology that could be improved with better standards, architectural framework, and implementation methodologies. Researchers in both academia and industry have showcased DT implementations with different levels of success. However, DTs remain limited in standards and architectures that offer efficient predictive maintenance solutions with real time sensor data, and intelligent DT capabilities. An appropriate feedback mechanism is also needed to improve asset management operations.

Considering tumors from an evolucionary perspective, successive tumor cells undergo turnover in response to stressful conditions which pressures tumor cells to adapt to a new environment. Tumor cells uses parts of themselves to communicate and share biological information, known as extracellular vesicles (EV) secretion to promote their survival and “survive to each and every metabolic cost”. Tumor microenvironment (TME) is a miscellaneous of cells, factors, extracellular matrix proteins and EVs. EVs include smalls (<160nm, exosomes) and larger (100-1,000nm, microvesicles) lipid bilayer enclosed packages of biomolecules that are shed by tumors to TME. Tumor-derived extracellular vesicles transfer adaptative stress signaling to recipient cells, reprograming these cells. Heat Shock Proteins (HSP) are more prominent stress response regulators found in exosomes. HSP-loaded exosomes actively reprogram tumor and TME cells to acquire mechanisms that contribute to tumor progression and therapy resistance. The intercellular communication mediated by HSP-loaded EVs favors the escape of tumor cells from, endoplasmic reticulum (ER) stress, hypoxia, apoptosis and anti-cancer therapies. Extracellular HSPs activate and deactivate immune response, induce cell differentiation, changes vascular homeostasis, and help to augment the pre-metastatic niche formation. Here we will explore the EV mechanism of HSP transmission among TME cells and the relevance of these intercellular communications for resistance to therapies in cancer.

This paper deals with the formulation of a Cobot kinematic model by developing both the direct and inverse kinematics and choosing the noa transformation matrix for defining the end-effector position and orientation with respect to the base frame. These algorithms have been validated via software in Matlab environment and by means of suitable experimental tests, which have been carried out by using a UR5e Cobot. Moreover, a specific industrial application regarding the robotized assembling of a multi-cylinder IC engine, has been designed in terms of layout and corresponding automatic cycle that is intended as a sequence of the robot elementary actions. In particular, the proposed robotized cell is composed by the UR5e Cobot along with its controller and a suitable electropneumatic circuit that includes a PLC with its user interface, which are both governed by means of a specific electronic board and a switch control box. The IC engine in scale of 1:5 and specific parts of the end-effector, which takes the role of vacuum gripper and torque limiting screwdriver, have been designed and manufactured by using a 3D printer.

Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

The important sampling parameters of a headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) procedure, extraction temperature, extraction time and sample volume were optimized to quantify 23 important impact odorants in reduced alcohol red and white wines. A three-factor design of Box-Behnken experiments was used to determine optimized sampling conditions for each analyte, and a global optimized condition at every ethanol concentration of interest determined using a desirability function that accounts for a low signal response for compounds. Shiraz and Chardonnay wines were dealcoholized from 13.7 and 12.2% v/v ethanol respectively, to 8 and 5% v/v, using a commercially available membrane-based technology. A sample set of the reduced alcohol wines were also reconstituted to their natural ethanol level to evaluate the effect of ethanol content reduction on volatile composition. The three-factor Box-Behnken experiment ensured an accurate determination of the headspace concentration of each compound at each ethanol concentration, allowing comparisons between wines at varying ethanol levels to be made. Overall, the results showed that the main effect of extraction temperature was considered the most critical factor when studying the equilibrium of reduced alcohol wine impact odorants. The impact of ethanol reduction upon the concentration of volatile compounds clearly resulted in losses of impact odorants from the wines. The concentration of most analytes decreased with dealcoholization compared to that of the natural samples. Significant differences were also found between the reconstituted volatile composition and 5% v/v reduced alcohol wines, revealing that the dealcoholization effect is the result of a combination between the type of dealcoholization treatment and reduction in wine ethanol content.

Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator ok NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

The global process of urbanization, and the modification of social interaction determined by the pandemic crisis poses the issue of the place of vulnerable users, and in particular children, within the contemporary city. This research aims to elaborate a theoretical and methodological framework, based on the concepts of affordance and capability, for analyzing the potential of public spaces to enable and support children’s independent activities. This potential, or meaningful usefulness, is expressed by the Index of Meaningful Usefulness of public Urban Spaces (IUIS). The latter is calculated via the tool ‘Opportunities for Children in Urban Spaces’ (OCUS). This methodology is applied to the analysis of significant public spaces within the historic center of the city of Iglesias in Sardinia, Italy. The results reveal adequate usefulness of the selected spaces, while underlining criticalities related to intrinsic spatial and physical attributes. The application to the case study confirms the validity of the theoretical and methodological framework embodied in the OCUS tool for supporting urban design and planning by orienting place-shaping processes towards the acknowledgement of children’s needs.

The COVID-19 pandemic has had a profound impact on the mental health, adjustment, and psychological well-being of young adults. Despite extensive research conducted in this area, eudaimonic well-being, one specific form of psychological well-being focusing on self-knowledge and self-realization within existential challenges, has received comparatively less attention. The current study aimed to investigate the potential linkages between two key psychological factors, psychological inflexibility and fear of death, with eudaimonic well-being among young adults in the context of the Covid-19 pandemic. One year after the outbreak, 317 young Italian adults (18-34 yrs.) participated in an online survey, including measures of psychological inflexibility (AAQ-II), fear of death (CL-FODS), and eudaimonic well-being (PWB). Results showed that psychological inflexibility was negatively associated with all the dimensions of Ryff’s model of eudaimonic well-being, while fear of death of others was found to be associated with three of these dimensions (autonomy, environmental mastery, and self-acceptance). Results also indicated a mediation role of psychological inflexibility in the association between fear of death and eudaimonic well-being. These findings expand our knowledge of the potential factors that may influence eudaimonic well-being and provide insights for clinical work with young adults challenged by uncertain times.

Terpenoids are toxic compounds produced by plants as a defense strategy against insect herbivores. We tested the effect of Origanum vulgare terpenoids on the generalist herbivore Spodoptera littoralis and the response of the plant to herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene expression (qPCR) was evaluated on selected plant genes involved in both terpene biosynthesis. The insect detoxification response to terpenes was evaluated by monitoring antioxidant enzymes activity and expression of insect genes involved in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression was modulated by S. littoralis feeding. The herbivore-induced increased level of terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by decreasing larval survival and growth rate. The assimilation by S. littoralis of more than 50% of ingested terpenes correlated with the possible toxic effects of O. vulgare terpenoids. In choice test experiments, carvacrol and γ-terpinene mediated the larval feeding preferences, wherease the prolonged feeding on O. vulgare terpenoids (particularly on γ-terpinene) exerted relevant antinutritional effects on larvae. S. littoralis was found to react to O. vulgare terpenoids by increasing its antioxidant enzymes activities and gene expression, although this was not sufficient to sustain the toxicity of O. vulgare terpenoids.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

Health related quality of life’s (HRQoL) different domains of functioning can serve as a good prognosticator of later life’s outcomes for children and adolescents. Understanding associated factors is crucial for promoting better health and life satisfaction. This study aimed to investigate the impact of socio-economic status (SES), physical activity (PA) and cardio-fitness on the Health-Related Quality of Life (HRQoL) in 224 Italian early adolescents attending secondary school in the Emilia-Romagna region located in northern Italy. The present cross-sectional study included measures of SES, demographic factors, cardio-fitness measures and self-reported PA levels. In a multivariate model, younger students and females reported higher HRQoL (β=-0.139, P<.05, 95% CI: -0.254 – -0.023 and β=0.142, P<.05, 95% CI: 0.011 – 0.273 respectively). Having both parents employed and having higher familiar educational status resulted in higher HRQoL. Greater engagement in routine PA was positively associated with HRQoL (β=0.429, P<.001, 95% CI: 0.304 – 0.554). Endurance (speed) was positively associated with HRQoL (β=0.221, P<.01, 95% CI: 0.087 – 0.355) and students with longer times on the shuttle run reported less HRQoL (β=-0.207, P<.01, 95% CI: -0.337 – -0.077). Findings reinforced the importance of promoting regular PA among students and addressing SES disparities to improve HRQoL. The study suggests a focus on expanding research measures and evaluating targeted PA interventions for a more comprehensive understanding of children’s well-being. These findings highlight the crucial roles of demographic, PA and cardio-fitness measures in child’s HRQoL, thus providing relevant information for stakeholders who work in the education, public health, and health policy sectors.

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body's defence systems going beyond the well-established associations with defence system delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

This study assesses the impact of nurse-originated changes in central venous catheter (CVC) management on the incidence of central line-associated bloodstream infections (CLABSI) and catheter-related bloodstream infections (CRBSI). It is a single-center retrospective cohort study conducted at an urban, tertiary referral, and academic center serving pediatric patients. The study cohort comprised 236 patients and 323 CVCs seen between 2012 and 2022. CLABSI and CRBSI were defined according to the Centers for Disease Control and Prevention definitions. Oncology nurse leaders developed CVC-specific educational modules for CLABSI prevention. All relevant information during the CVC maintenance period was noted in the patient's CVC logbook. 24 (7%) cases of confirmed CLABSI were identified. The incidence of CVC-related infections was 0.32 cases per 1000 catheter days. The incidence decreased by 40% between the first and second three-year study period. Documented exit-site infection was reported in 32 (10%) cases. The correlation between exit-site infection and CLABSI was found in 9 (28%) cases. Our CVC-related infection rates are significantly lower than the incidence reported by the Italian Association of Pediatric Hematology and Oncology, which settles at 3-5 cases per 1000 catheter days. Our data confirm the effectiveness of local CVC management guidelines in preventing CVC-related infectious complications.

Background: Patients with allergic rhinitis (AR) have bothersome symptoms that may assess using the visual analog scale (VAS). Asthma frequently is associated with AR. The present study investigated the role of VAS in children with newly-diagnosed AR. Methods: Parameters were VAS for nasal and asthma symptoms, and doctor’s perception of these diseases, medication use, and asthma comorbidity. Results: 67% of AR children had asthma. Severity of perceived nasal symptoms was associated with more intense asthma symptoms and doctor’s perception of disease severity (p<0.001 and p=0.02, re-spectively. Conclusions: Allergic rhinitis frequently is associated with asthma in child-hood. Symptom perception assessment using VAS is a simple tool for assessing their intensity. Moreover, the severity of nasal symptoms is associated with asthma symptom severity. Therefore, asthma should be carefully considered in AR children and require appropriate symptom perception assessment.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Socio-demographic factors are responsible of health inequalities also in vaccination. The aim of this study was to evaluate their role at population level through a population-based study performed on the whole population entitled to receive COVID-19 vaccines in Umbria Region, Italy, and registered to the Regional Healthcare Service as of February 28th, 2021. Socio-demographic characteristics and vaccination status in terms of uptake at least one dose of any available vaccine, completion of the primary vaccination cycle and uptake of the booster doses as of February 28th, 2022 were col-lected from the Umbria regional database. The percentage of eligible population who did not initiate the COVID-19 vaccination, complete the full vaccination cycle and get the booster dose was 11.8%, 1.2% and 21.5% respectively. A younger age, being a not-Italian citizen, and not holding an ex-emption for chronic disease/disability and a GP/FP were associated to all the endpoints. Females, as compared to males, were more likely to not initiate the vaccination but less likely to not receive the booster dose. On the contrary, results on the deprivation index were not conclusive. The findings, beyond confirming current knowledge at population level, provide new inputs for better tailoring vaccination campaigns.

Auricular keloids pose significant aesthetic and functional challenges, and traditional treatments often fall short in ad-dressing these. Our study presents an innovative combined approach of ablative CO2 and dye laser therapy for improved keloid management. This treatment protocol was applied to 15 patients with auricular keloids after an initial multispec-tral analysis to assess keloid composition. The laser sequence was tailored per patient based on this analysis. Evalua-tions using the Vancouver Scar Scale and Patient and Observer Scar Assessment Scale were carried out at baseline and at 3-week intervals post-treatment. The results showed a significant reduction in these scores at the final follow-up (p<0.05), suggesting improvements in keloid color, texture, and pliability, with minimal adverse events. Additionally, no recur-rence of keloids was observed. Our findings indicate that this novel methodology of multispectral analysis followed by tailored laser therapy may offer a safe and effective solution for auricular keloids, promising enhanced keloid treatment and prevention of recurrence. However, further investigations, including randomized controlled trials, are needed to confirm and optimize this treatment protocol.

Indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2, originated from gene duplication before vertebrate diver-gence. While IDO1 has a well-defined role in immune regulation, the biological role of IDO2 remains unclear. Discovered in 2007, IDO2 is located near the IDO1 gene. Because of their high sequence similarity, IDO2 was initially thought to be a tryptophan (Trp)-degrading enzyme like IDO1. Differently from what expected, IDO2 displays extremely low catalytic activity toward Trp. Nevertheless, many studies, often contradictory, tried to demonstrate that IDO2 modulates immune responses by catabolizing Trp into kynurenine, a hypothesis un-convincing and, let’s say, linked to the first life of IDO2. Here, we review its “new life”, the one in which IDO2 has a functional role beyond Trp metabolism. The IDO2’s evolutionary persistence across species, despite be-ing almost inactive as an enzyme, suggests it has some relevant biological importance. IDO2 expression in human normal cells is poor, but significant in various cancers, with two prevalent SNPs. Overall, the com-parison of IDO2 to IDO1 as a Trp-degrading enzyme may have led to misunderstandings about IDO2’s true physiological and pathological roles. New insights suggest that IDO2 might function more as a signaling molecule, particularly in cancer contexts, and further studies could reveal its potential as a target for cancer therapy.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Flavonoids are polyphenolic phytochemical compounds found in many plants, fruits, vegetables, and leaves. They have a multitude of medicinal applications due to their anti-inflammatory, anti-oxidative, anti-viral, and anti-carcinogenic properties. Furthermore, they also have neuroprotective and cardioprotective effects. Their biological properties depend on the chemical structure of flavonoids, their mechanism of action, and their bioavailability. The flavonoid’s beneficial effects have been proven for a variety of diseases. In the last few years, it is demonstrated that flavonoids’ effects are mediated by inhibiting the NF-κB (Nuclear Factor-κB) pathway. In this review, we have summarized the effects of some flavonoids on the most common diseases such as cancer, cardiovascular, and neurodegenerative human diseases. In particular, here we collected all recent studies describing plant-derived flavonoids’ protective and prevention role, by specifically focusing their action on the NF-κB signaling pathway.

The suppression of natural spaces due to the urban sprawl and increase of the built and agricultural environments has impacted the water resources quality, especially in areas with high population density, as the metropolitan regions. Considering the advance in Brazilian environmental legal framework, the present study aims to verify whether land use has still significantly affected water quality, through a case study in the Stones River watershed, a peri-urban river basin at a metropolitan region, Brazil. Analysis of physical-chemical indicators, collected at several sample points with different land-use (urban areas, commercial forestry, riparian forestry, mixed vegetation, pasture, and sugar cane plantation) at different seasons of the year (dry and rainy) were carried out. As a result, it was verified some statistically significant spatiotemporal effects on the of water quality caused associated to the land-use. In conclusion, in spite of the advances in the Brazilian law, land-use has still significantly affected the water quality, demanding public policies and decisions, so that effective compliance with legal guidelines is ensured.

Despite the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitor-urinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a high sensibility to immune checkpoint inhibitors, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitors receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.

When we are asleep we lose the ability to promptly respond to external stimuli and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways, we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to which extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

Cooperation is widely recognized to be challenging for the well-balanced development of human societies. The emergence of cooperation in populations has been largely studied in the context of the Prisoner's Dilemma game, where temptation to defect and fear to be betrayed by others often activate defective strategies. In this paper we analyze the decision making mechanisms fostering cooperation in the two-strategy Stag-Hunt and Chicken games, which include the mixed strategy Nash equilibrium, describing partially cooperative behavior. We find the conditions for which cooperation is asymptotically stable in both full and partial cases, and we show that the partially cooperative steady state is also globally stable in the simplex. Furthermore, we show that the last can be more rewarding than the first, thus making the mixed strategy effective, although people cooperate at a lower level with respect to the maximum allowed, as it is reasonably expected in real situations. Our findings highlight the importance of Stag-Hunt and Chicken games in understanding the emergence of cooperation in social networks.

The impact of controlled breathing on cognitive and affective processing has been recognized since ancient times, giving rise to multiple practices aimed at achieving different psychophysical states, mostly related to mental clarity and focus, stress reduction and relaxation. Previous scientific research explored the effects of unilateral nostril breathing (UNB) over brain activity, emotional and cognitive functions. Most evidence concluded for a contralateral effect, but many other controversial results make it difficult to come to an unambiguous interpretation. In the present study, we invited a pilot sample of 20 participants to take part in an 8-days breathing training, assigned either to the right nostril (URNB) or the left nostril breathing condition (ULNB). Then, each day, we assessed participants’ well-being indices with mood and mind-wandering scales. Results revealed that, after the daily practice, both groups reported improved well-being perception. However, the effect was specifically related to the nostril involved. URNB produced more benefits in terms of stress reduction and relaxation, while ULNB significantly reduced mind-wandering occurrences, increasingly over time. Our results are only partially in agreement with previous evidence, indicating the need for a more complex interpretive model that considers multiple brain networks and integrates central and peripheral nervous systems.

This contribution illustrates the training evaluation system developed within the Master’s Program in Family and Community Mediation at Università Cattolica del Sacro Cuore in Milan. This is an interim evaluation, which focuses on the training process and which considers fundamental the collaboration with the subjects of the training. The peculiarity of this work concerns the possibility of inserting research within the training process, following a logic of mutual enrichment both in terms of content and learning. The contribution illustrates in detail the outcome and the process evaluation system, defining the perspective, the objectives, and the methodology of implementation. In particular, the outcome evaluation focuses on the distal and proximal outcomes of the training, while the process analysis focuses on the dynamics within the group of participants. Although further evaluations involving different training groups and other training processes are needed, this training evaluation system allows to shed light on both the topic and the context in which training is delivered. The integration between different points of view and several levels of analysis allows the researchers to deepen the individual path of each participant as well as to have feedbacks on the progress of the training group as a whole.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune response. One-hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min-max) of age was 9.0 (1–18) for children and 42.5 (20–61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman’s correlation was 0.56 (p&lt;0.001). Sal-IgG and ser-IgG levels were correlated with age, but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4kAU/L) to 4.0% (3.77kAU/L). Linearity of the assay missed in 4/6 samples. No significant intra-subject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG have a good agreement with ser-IgG. Non-invasive saliva collection represents an alternative method for antibody measurement, especially in children.

This paper deals with the design and kinematic analysis of a novel mechanism for the elbow joint of an upper-limb exoskeleton, with the aim of helping operators, in terms of effort and physical resistance, in carrying out heavy operations. In particular, the proposed eight-bar el-bow joint exoskeleton mechanism consists of a motorized Watt I six-bar linkage and a suitable RP dyad, which connects mechanically the external parts of the human arm with the corre-sponding forearm by hook and loop velcro and thus, helping their closing relative motion for lifting objects during repetitive and heavy operations. This relative motion is not a pure rotation and thus, the upper part of the exoskeleton is fastened to the arm, while the lower part is not rigidly connected to the forearm, but through a prismatic pair which allows both rotation and sliding along the forearm axis. Instead, the human arm is sketched by means of a crossed four-bar linkage, which coupler link is considered as attached to the glyph of the prismatic pair, that is fastened to the forearm. Therefore, the kinematic analysis of the whole ten-bar mecha-nism, which is obtained by joining the Watt I six-bar linkage and the RP dyad to the crossed four-bar linkage, is formulated to investigate the main kinematic performance and for design purposes. The proposed algorithm has given several numerical and graphical results. Finally, a double-parallelogram linkage, as particular case of the Watt I six-bar linkage, was considered in combination with the RP dyad and the crossed four-bar linkage, by giving a first mechanical de-sign and a 3D printed prototype.

The aims of this study were: (1) to analyze the level of agreement of a sample of Italian people with the rights of people with physical and psychical disabilities (PwPHDs and PwPSYDs) to have satisfying sexuality, to marry, to adopt a child; (2) to inquire if PwPSYDs were subject to less recognition than PwPHDs; (3) to verify if socio-demographic characteristics, such as age, sex, education, occupation, geographical origin, relational status, sexual orientation, and religiosity, associated with being against these sexual and parenting rights (SPRs). An online anonymous questionnaire inquired the level of agreement or disagreement with statements regarding the SPRs of PwPHDs and PwPSYDs. 973 participants, aged 18 – 84 years (71.1% females) were considered for analyses; At least 7 out of 10 participants declared in favor of the SPRs of PwPHDs, while the SPRs of PwPSYDs were always subjected to higher underrecognition. Religiosity almost invariably associated to being against the SPRs of PwDs. Being male, of higher age and lower education also associated with lower recognition. A better identification of the less tolerant respondents and of the less recognized categories may allow for specific strategies for promoting the recognition of the SPRs for PwDs.

Metabolic dysfunction associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that T3 regulate hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of T3 contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of T3 dysfunction in the progression of MAFLD in an animal model. Method-ology: Male/adult Sprague Dawley rats (n=20) were allocated to a control group (standard di-et–2.93kcal/g) and diet group (CDHF–4.3kcal/g). Euthanasia took place in the 28th week. D3 ac-tivity and expression, UCP2 and D1 expression, REDOX status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an in-crease in D3 activity/expression (P<0.001) related to increased TBARS and carbonyls and GSH reduction in the MAFLD group (P<0.05). There was a T3-dependent decrease in UCP2 expression (P=0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (P < 0.001). Surprisingly, in and environment with lower T3 levels we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydro-genase (GDH) enzymes activity (P<0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability, and hepatic mitochondrial capacity. The Krebs cycle en-zymes were altered as well as reticulum stress. Taken together, these results shed new light on the role of T3 metabolism in MAFLD and new treatment opportunities.

The stochastic modelling of chemical physical processes is essentially based on a coarse-grained formulation of fluctuations, usually described by means of Wiener processes. By taking the paradigmatic example of chemical reaction kinetics, we propose a simple representation of microscopic stochastic dynamics grounded on the use of distributional derivatives of counting processes that account for elementary reactive events. This approach is consistent with the statistical analysis based on the Chemical Master Equation, and provides the formal setting for the existing algorithmic approaches (Gillespie algorithm). Some practical advantages of this formulation are addressed, and several other examples are discussed in connection with cluster formation, velocity fluctuations in liquid systems, and quantum transitions (radiative interactions) at the molecular level.

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

Background & Objective. Perinatal hypoxia acutely triggers the release of cytokines and chemokines from neurons, astrocytes and microglia. In response to hypoxia-ischemia resting/ramified microglia proliferate and undergo activation, with the production of proinflammatory molecules. The brain damage extension seems to be related with both the severity of hypoxia and the balance between pro and anti-inflammatory host response. Methods: In this preliminary study we compared in 10 neonates with hypoxic ischemic encephalopathy (HIE), during therapeutic hypothermia (TH), plasmatic cytokines and other inflammatory molecules levels: monocytic chemotactic-protein-1 (CCL2/MCP-1), CXCL8, glial fibrillary acidic protein (GFAP), Interferon gamma (IFN y), Interleukin 10 (IL-10), IL-18, IL-6, CCL3, ENOLASE2, Colony Stimulating Factor(GM-CSF), IL-1b, IL-12p70, IL-33, Tumor Necrosis Factor alpha(TNF), collected at four different time points during TH (24 hours, 25-48 hours, 49-72 hours) , and after the rewarming (7-10 days from birth). Five of enrolled babies had pathological brain MRI (“cases”) and 5 had a normal examination (“controls”). Cytokines were measured by Magnetic Luminex Assay (Luminex SV 013-17 (14), instrument Biorad Bio-Plex 100 s.n. LX 10005039304). MRI images were classified according to the Barkovich score. Results: Mean levels of all cytokines and molecules at time T1 were not significantly different in the two groups of patients. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. After rewarming, some molecules showed an upward trend. At T4, levels tended to be close again (with the exception of IL-6, IL10 and IL18). Infants with worse MRI showed plasmatic GFAP levels higher than those with normal MRI, while their IL-18 was lower. Mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both the groups of neonates. Conclusion. In children with worse brain MRI we found high levels of GFAP and of IL-10 at T4, considered respectively an early biomarker of brain damage and a predictor of adverse outcome, according to the literature, and a trend towards low IL-18 levels. We found the greatest, although not significant, difference between molecules levels in cases and controls at time points T2 and T3, during TH. With the rewarming some molecules showed an upward trend. We cannot exclude that the small sample size may prevent significance in the differences from being achieved.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, currently predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.

In this work, dry and hydrothermal carbonization (DC and HTC) of RDF pellets were conducted to evaluate the physical, chemical, and fuel properties of the produced chars. In the dry carbonization tests, biomass sawdust was incorporated in different proportions on the samples to minimize agglomeration caused by the melting of the plastic fraction. The experiments were carried out in a temperature of 400°C (DC) and 250-300°C (HTC), in a residence time of 30 minutes. The respective chars and hydrochars were characterized according to their mass yield, apparent density, proximate, elemental, and mineral composition, chlorine content, high heating value, thermogravimetric profile, and surface functional groups. The results showed that dry carbonization of RDF pellets with biomass incorporation, followed by a washing step, resulted in the production of chars with improved properties such as higher fixed carbon and HHV (25-26 MJ/kg) and lower ash and chlorine content. Additionally, the HTC experiments demonstrated that hydrochars showed improved properties without the need for biomass addition and washing, however, with no significant difference in the HHV (20-21 MJ/kg). Therefore, DC of RDF pellets with 10% biomass incorporation seems to be a promising option to overcome the constraints of RDF utilization as an alternative fuel.

In this study, we conducted a comprehensive analysis of the spatial distribution of soil organic carbon stock (SOC stock) and the associated uncertainties in two soil layers (0–10 cm and 0–30 cm; SOC stock 10 and SOC stock 30 respectively), in Valchiavenna, an alpine valley located in northern Italy . We employed the digital soil mapping (DSM) approach within different machine learning models, including multivariate adaptive regression splines (MARS), random forest (RF), support vector regression (SVR), and elastic net (ENET). Our dataset comprised soil data from 110 profiles, with SOC stock calculations for all sampling points based on bulk density (BD), whether measured or estimated, considering the presence of rock fragments. As environmental covariates for our research we utilized environmental variables, in particular geomorphometric parameters derived from a digital elevation model (with a 20 m pixel resolution), land cover data, and climat-ic maps. To evaluate the effectiveness of our models, we evaluated their capacity to predict SOC stock 10 and SOC stock 30 using the coefficient of determination (R2). The results for the SOC stock 10 were as follows: MARS 0.39, ENET 0.41, RF 0.69, and SVR 0.50. For the SOC stock 30, the corresponding R2 values were: MARS 0.45, ENET 0.48, RF 0.65, and SVR 0.62. Additionally, we calculated the Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) for further assessment. To map the spatial distribution of SOC stock and address uncertainties in both soil layers, we chose the RF model, due to its better performance, as indicated by the highest R2 and the lowest RMSE and MAE. The resulting SOC stock maps using the RF model demonstrated an accuracy of RMSE = 1.35 kg.m-2 for the SOC stock 10 and RMSE= 3.36 kg.m-2 for the SOC stock 30. To further evaluate and illustrate the precision of our soil maps, we conducted an uncertainty assessment and mapping by analyzing the standard deviation (SD) from 50 iterations of the best-performing RF model. This analysis effectively highlighted the high accuracy achieved in our soil maps. The maps of uncertainty demonstrated that the RF model better predicts the SOC stock 10 compared to the SOC stock 30.

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

New digital interventions have shown potential in managing asthma and improving patients' quality of life compared with conventional interventions. Our objective was to conduct an exhaustive survey of the application of digital health technologies in evaluating, treating, and self-managing psychological and psychopathological elements linked to asthma. We analyzed a compendium of research papers and systematic reviews pertaining to asthma, encompassing themes such as outdoor air pollution, early life wheezing disorders, atopic dermatitis, digital strategies for asthma self-management, psychiatric conditions and asthma, familial impacts on pediatric asthma, and the utilization of mobile health apps for managing asthma. We scrutinized eight chosen studies to evaluate the capacity of digital health technologies to enhance the man-agement and treatment outcomes of psychological factors related to asthma. The studies under review indicate that eHealth interventions, mixed reality instruments, mHealth technolo-gy-augmented nurse-led interventions, and smartphone apps incorporating Bluetooth-enabled sensors for asthma inhalers can markedly enhance self-management of symptoms, quality of life, and mental health outcomes, particularly in children and adolescents with asthma. Nonetheless, additional research is required to ascertain their efficacy and practicability across diverse populations and environments. Customized interventions that cater to the unique needs and preferences of asthma patients and associated psychological elements are vital to ensure the persistent and equitable adoption of these technologies. We underscore the significance of addressing psychological elements in the management and treatment of asthma and advocate for ongoing research and development in this domain.

Background: Interstitial lung disease (ILD) is a frequent complication in systemic sclerosis (SSc). So, an increased awareness of this complication is a real need in the clinical setting, because it may affect the prognosis of patients. In particular, an accurate strategy is desirable in order to detect ILD in its stages. So, we investigate the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to determine its potential in disease progression. Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and respiratory function tests (RFT) were performed. An expert rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. After the baseline assessment, the patients were followed every 3 months for 12 months. Results: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6% respectively. A good inter-observer reliability was observed (k = 0.72). In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitoring the disease progression.

Starting from the analysis of the lack of positivity of the Cattaneo heat equation, the article addresses the thermodynamic relevance of the positivity constraint in irreversible thermodynamics, than is at least as important as the entropic constraints. The fulfillment of this condition in hyperbolic models leads to the parametrization of the concentration fields with respect to internal variables associated with the microscopic dynamics. Using Brownian motion theory as a landmarking example for deriving macroscopic transport equations from the equations of motion at the particle/molecular level, we discuss two typical problems involving hydrodynamic interactions at microscale: surface chemical reactions at a solid interface of a diffusing reactant, and mass-balance equations in a complex viscoelastic fluid, in which the physics of the interaction leads either to the overcome the parabolic diffusion model or to consider the parametrization of the concentration with respect to the degrees of freedom associated with the relaxation dynamics of the solvent fluid.

Background: Acute intermittent porphyria (AIP) is caused by haploinsufficiency of porphobilin-ogen deaminase (PBGD) enzymatic activity. Acute attacks occur in response to fasting and altera-tions in glucose metabolism, insulin resistance and mitochondrial turnover may be involved in AIP pathophysiology. Therefore, we investigated the metabolic pathways in PBGD-silenced hepatocytes and assessed the efficacy of an insulin-mimic, the α-lipoic acid (α-LA) as a potential therapeutic strategy. Methods: HepG2 cells were transfected with a siRNA targeting PBGD (siPBGD). Cells were cul-tured with low glucose concentration to mimic fasting and exposed to α-LA alone or with glu-cose. Results: At baseline, siPBGD cells showed lower expression of genes involved in glycolysis and mitochondrial dynamics along with reduced total ATP levels. Fasting further unbalanced gly-colysis by inducing ATP shortage in siPBGD cells and activated DRP1, which mediates mito-chondrial separation. Consistently, siPBGD cells in fasted state showed the lowest protein levels of Complex IV which belong to the oxidative phosphorylation (OXPHOS) machinery. α-LA up-regulated glycolysis and prompted ATP synthesis and triglyceride secretion, thus possibly providing energy fuels to siPBGD cells by improving glucose utilization. Finally, siPBGD exposed to α-LA plus glucose raised mitochondrial dynamics, OXPHOS activity and energy production. Conclusions: α-LA-based therapy may ameliorate glucose metabolism and mitochondrial dys-functions in siPBGD hepatocytes. Keywords: AIP, PBGD, glucose metabolism, mitobiogenesis, α-lipoic acid

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

The aim of the present study is to investigate themes related to visitors’ perceptions of captive wildlife in particular, attitudes towards non-human primates (henceforth, primates). This research took place in free-roaming, multi-species primate sanctuary, Monkeyland (South Africa), where 400 visitors were interviewed using an anonymous survey both before and after attending a guided tour. The answers were divided into different categories, in order to standardize the motivations behind tourists’ choices. The results of the survey demonstrated that most visitors agree that a primate would not be a good companion animal. Visitors’ desire to touch primates was found to be positively correlated with desire for companion primates and inversely associated with visitor age. In response to: “would you like to touch a monkey?”, the majority of tourists who expressed this desire seemed aware that such interactions are not appropriate, with concern for animal welfare and human health. Of the various primate species present in the sanctuary, visitors preferred the ring-tailed lemur (Lemur catta) and, generally speaking, expressed appreciation for primates’ “cuteness”. Our results indicate a general awareness by the visitors on the importance of animal welfare in the human interactions with captive wildlife, in agreement with the “hands-off” policy of Monkeyland primate sanctuary. We discuss the findings from a general to zooanthropological point of view, proposing some reflections on the attitudes of visitors toward non-human primates.

In the twenty-first century– an era of increasing domestic and international tourism- there are boundless opportunities to encounter wild animals both in their home countries and ex situ in zoological facilities around the world. Tourism activity– especially at accredited zoos and sanctuaries –plays a crucial role in the conservation of wild animal populations, and influences the welfare of individuals within involved species. Unfortunately, not all zoos and sanctuaries prioritize the conservation and welfare of their animals, such as those who promote irresponsible and mutually-harmful visitor-animal encounters for economic profit. While the relationship between visitors and animals at zoological facilities has shifted over time to match evolving morals and sentiments towards animals, there is still a storied tendency of visitors preferring close encounters with charismatic wild species. Since the 1970s, researchers’ attention has increasingly focused on assessing the influence of the visitor effect, which refers to the impact that viewing, touching, feeding, holding, and riding captive wildlife has on the animals. Many wildlife attractions promote such encounters, despite research suggesting that close interactions with visitors can cause stress and harm to involved species. Such activities are further promoted through the “selfie tourism” phenomenon, in which visitors capture images of themselves in too-close proximity to wild animals to be shared on social media. In this commentary, we consider the challenge of “selfie tourism”, and how it can promote unethical relationships between humans and wildlife and lead to deleterious implications for the animals’ conservation and welfare.

Fire is a significant threat to human life and civil infrastructures. Builders and architects are hankering for safer and sustainable alternatives of concrete that do not compromise with their design intent or fire safety requirements. The aim of the present work is to improve the residual compressive performance of concrete in the post-fire exposure, by incorporating by-products from urban residues. Based on sustainability and circular economy motivations, the attention is focused on rubber tire fly ash, aged brick powder, and plastic (PET) bottle residuals used as partial sand replacement. The selected by-products from urban residues are used for the preparation of Cement-Based Composites (CBCs) in two different proportions (10 % and 15 %). The thermal CBC behaviour is thus investigated under realistic fire scenarios (i.e., Direct Flame (DF) for 1 hour (1h)), by following the ISO 834 standard provisions, but necessarily resulting in non-uniform thermal exposure for the cubic specimens. The actual thermal exposure is further explored with a Finite Element (FE) model, giving evidence of thermal boundaries effects. The post-fire residual compressive strength of heated concrete and CBC samples is hence experimentally derived, and compared to unheated specimens in ambient conditions. From the experimental study, the enhanced post-fire performance of CBCs with PET bottle residual is generally found superior to other CBCs or concrete. The structure-property relation is also established, with the support of Scanning Electron Microscopy (SEM) micrographs. Based on existing empirical models of literature for the prediction of the compressive or residual compressive strength of standard concrete, newly developed empirical relations for both concrete and CBCs are assessed.

Social media has become a powerful tool for spreading information and awareness campaigns on environmental issues, especially as they pertain to the conservation of wild animals. It is a double-edged sword, however, since it also facilitates the legal and illegal trade of wild animal species as well as the propagation of ‘wild animal selfies.’ This review presents some key literature to date which concerns the impact of social media on public perceptions of animals (such as through ‘viral’ videos), changing trends in animal encounters at wildlife tourism destinations, and the wildlife trade as it is facilitated by social media. Finally, avenues for future research are suggested with urgency, since the impact of social media on the welfare and conservation of wild animal species is most likely underestimated yet bears serious consequences.

Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer Disease will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed focussing on Alzheimer Disease pathogenesis.

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer associated to asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and the Epithelial Mesenchymal Transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos related primary oxidative damage is counteracted in the lung by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet fully understood. Moreover, asbestos exposure has been associated to induced EMT event, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in a possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells: as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Take as a whole, these results show, for the first time, a crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, so improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

This study aims to investigate a friction stir welded joint between steel and aluminum alloy. Friction stir welding is nowadays one of the most interesting joining technique due to the possibility to connect materials and thicknesses that are difficult or impossible to weld with traditional techniques. The main advantage is that Materials are not affected by thermal cycle problems during solidification and cooling and the absence of fumes and pollution during the process favors the quality of the welded joint. The life of metal joints could be greatly reduced in a corrosive environment, since the less noble material will tend to increase its corrosion rate while the nobler one will reduce its electrochemical dissolution. Accelerated ageing tests (i.e. salt fog test) are used to estimate the lifetime of metal joints in highly aggressive environments. The aim of the present work is to evaluate the durability at long ageing time in salt spray test (according to ASTM B117) of carbon steel/aluminum alloy joints, obtained by FSW. In this first part, mechanical tests results are reported. A deep metallographic and chemical investigation are going to be reported in the part 2.

Friction Stir Welding is a suitable solid-state joining technology to connect dissimilar materials. To produce an effective joint, it requires a phase of optimization which leads to the definition of process parameters such as pin geometry, tool rotational speed, rotation direction, welding speed, thickness of the sheets or tool tilt angle. The aim of this review is to present a complete and detailed frame of the main process parameters and their effect on the final performance of a friction stir welded joint in terms of mechanical properties and microstructure. Particularly, the attention was focused on the connection between different aluminum alloys. Moreover, the experimental results were correlated to the development and the applications of tools, which can effectively use in the design of the manufacturing process, such as finite element analyses, artificial neural networks, statistical studies. The review wants to be also a point of reference to identify the best combinations of process parameters based on the dissimilar aluminum to be joined.

Smartphones have become an integral part of our everyday lives and keep us busy while doing other primary activities such as driving, cycling or walking in traffic. The problem of digital distraction among drivers has been largely addressed, and interest is growing also on vulnerable road users as well: In fact, high percentages of pedestrians and cyclists are accustomed to checking their devices while moving in traffic. This research links to the presented theme and aims to investigate the extent to which digital distraction in the form of social media app checking influences pedestrian behavior. The focus of the study is specifically on signalized intersections. An outdoor, eye-tracking experiment was conducted on a specific route consisting of various elements typical of urban areas. Participants were asked to walk the predefined route twice, en-countering three signalized intersections: the first time they were asked to walk with their smartphone in hand, the second time without. The recordings of each participant's route were then analyzed, examining reaction time, crossing time and speed, fixations, and gaze paths. The results show a clear impact of digital devices on pedestrians' attention by increasing their reaction and crossing times and decreasing crossing speeds. In addition, the analysis of fixations found that 82.54% of the time was devoted to the smartphone, while interest in other street ele-ments decreased from 16.64% to 4.03%.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p&lt;0.001, Duncan’s new multiple range test) and their total duration (p&lt;0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p&lt;0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.

Green Tea Catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human Prostate Cancer (PCa) chemoprevention.In the last decades many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets including, cell surface receptors, lipid rafts and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentration that cannot be achieved in vivo.Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs bioavailability through still poor understood mechanisms. Recent efforts to develop delivery systems that increase GTCs overall bioavailability, by mean of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.

Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.

Facade elements are known to represent a building component with multiple performance parameters to satisfy. Among others, “advanced facades” take advantage of hybrid solutions, like the assemblage of laminated materials. In addition to enhanced mechanical properties that are typical of optimally composed hybrid structural components, these systems are energy-efficient, durable, and offer lightening comfort and optimal thermal performance. This is the case of the structural solution developed in joint research efforts of the University of Zagreb and the University of Ljubljana, within the Croatian Science Foundation VETROLIGNUM project. The design concept involves the mechanical interaction of timber and glass load-bearing members, without sealing or bonded glass-to-timber surfaces. Laminated glass infilled timber frames are recognized as a new generation of structural members with relevant load-carrying capacity (and especially the enhancement of earthquake resistance of framed systems), but also energy-efficient and cost-effective solutions.

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle >10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage III IV or higher cases. Conclusions: Early diagnosis and treatment before age 45, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management.

Nuclear magnetic resonance (NMR) is a technique used for many years by chemists for elucidation of molecular structure. Technological progress over the years has enabled this technique, making it easier to use. Thus, the LF-NMR (low-field NMR) was introduced as side technique, characterized by low man-agement costs and shorter analysis time than its main counterpart. The application of 1H LF-NMR for the quantification of ethyl alcohol in different alcoholic matrices is herein described, comparing results ob-tained with this technique with those determined by a reference gascromatographic method.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

This paper aims at providing a multisource data analysis, including direct data collection, focussed on daily average distances covered with motorised mobility. Its results can be used as a basis for policies involving a shift towards new propulsions, electric motors or hybrid electric vehicles (HEV) for road vehicles. A number of variables influence the propensity of drivers to acquire or use electric traction, even the option of plug-in hybrid electric vehicles (PHEV). This paper addresses one of such variable: the compliancy of electric traction regarding both hybrid plug-in solutions and full-electric vehicles, in addition to the autonomy of batteries (range), with the daily travels by road vehicles, mainly by automobiles. We want to understand whether the constraints leading towards a greater independence from crude oil rather than constraints concerning emissions, mainly in urban contexts, might be compliant with the habitual daily trips of drivers. We also want to understand if these daily trips have varied much during recent years and the consequences they may have on operational costs of plug-in automobiles. We are well aware that the average distances do not represent the actual daily runs of vehicles; yet similar distributions of daily distances for different case studies indicate that a high percentage of trips respond to certain features. After introducing a general overview of road-motorised mobility in Italy, the paper compares data from other studies to provide an indication of average daily driving distances. This reveals how different recent analyses converge on a limited range of average road distances covered daily by Italians, which is compliant with ranges allowed by electric batteries, provided that their low energy density in comparison with that of oil-derived fuels do not imply a significant increase in vehicle mass. Subsequently, average distances in some EU Countries are taken from the literature, and the results are also compared with U.S. data. The study extends the analysis of trends on the use of automobiles and road-vehicles to the international context by also addressing average daily distances covered for freight transport in some EU Countries, thereby providing a further basis for comparison and for understanding whether the daily motorised mobility can be considered as a stable phenomenon. Finally, an analysis is provided of the economic operational advantages from using plug-in vehicles. The main aim of this paper is thereafter to investigate the average daily motorised mobility of single vehicles – so not an aggregated motorised mobility as collected by some statistics – by using private motorised vehicles in Italy, with related trends; thereafter, to compare these data with those obtained from other countries, making use of both existing research studies and directly collected data; the final aim is to understand both the compliance of daily activities based on the use of automobiles with the autonomy of batteries (range) and to calculate some economic outcomes.

During the SARS-CoV-2 vaccination campaign, people with CF (pwCF) were considered a clinically vulnerable population. However, data on immunogenicity of anti-SARS-CoV-2 vaccines in pwCF are lacking. We conducted a prospective study enrolling all patients aged >12 and followed-up in our CF centre, who received two doses of the BNT162b2 vaccine in March-­­­October 2021. They underwent a blood sample for quantification of antibodies to the SARS-CoV-2 spike protein receptor binding domain immediately before receiving the first dose and after 3 and 6 months from the second dose. We enrolled 143 patients (median age: 21 years, range: 13-38); of whom 16 had a previous infection. Median antibody titer (interquartile range) after 3 months from vaccination was 1288 U/mL (730-2115) and decreased to 918 U/mL (534-1488) after 6 months (P<0.0001). Median values were higher among previously infected patients as compared to those naïve to SARS-CoV-2 (9107 vs 1229 U/mL at 3 months and 4810 vs 829 U/mL at 6 months, P<0.0001) with no significant differences in the rate of decline over time (P=0.135). All pwCF mounted an antibody response after two-doses of BNT162b2 vaccine that waned at 6 months from vaccination. Age ≥30 years and use of inhaled corticosteroids were associated with a lower humoral response.

Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

HPV51 belongs to group I high-risk HPV (hrHPV) genotypes with a high prevalence of infection in numerous epidemiological studies, although its occurrence varies across geographical regions. To better understand the presence of variants and genetic variation of HPV51, this study aimed to perform a phylogenetic analysis of the E6, E7 and L1 regions to detect the hrHPV variants circulating in women referred to colposcopy in two different Italian regions (Lombardy and Sardinia). Cervical samples were tested using Anyplex™ II HPV HR Detection. HPV51 positive samples were further analysed using previously described PCR protocols to obtain sequences of E6, E7 and L1. A positivity rate for HPV51 of 7.4% (26/351) and 13.6% (11/81) was found in Lombardy and Sardinia, respectively. The majority (34 out of 35) of the analyzed sequences clustered into the A lineage and only one sequence was grouped into B lineage. L1 capsid gene showed the presence of different mutations but none under positive selective pressure. Three nucleotide polymorphisms T6311G, A6312T and G6313A related to the two aminoacidic mutations V264G and G265S were found among all analysed sequences. This study contributes to implement data regarding the molecular epidemiology of HPV but additional analysis on a larger number of sequences is necessary to better understand the role of HPV variants in cervical lesions development.

Comprehensive understanding of tree characteristics and conditions holds paramount importance for the precise management of hazelnut orchards. It facilitates the determination of tree vigor, pruning requirements, phytosanitary interventions, and plant water consumption. The primary objective of this study was to explore, for the first time on a fruit tree with a bushy structure and across trees of four Italian distinct hazelnut cultivars, the efficacy of multispectral and thermal UAV (Unmanned Aerial Vehicle) technologies in assessing canopy attributes, vegetative growth, and predicting abiotic stresses. These technologies serve as tools for precision agriculture, enabling the computation of various indices such as the Normalized Difference Vegetation Index (NDVI) and crop water stress index (CWSI). The study of water content is of particular importance at this time, especially considering the increasing water stress levels in Europe as well as globally. While Red Green Blue (RGB) and thermal imagery collectively demonstrated superior performance in model reconstruction, the multispectral UAV remained more adept at characterizing size traits of hazelnut plants. Thermal images alone proved inadequate for accurately reconstructing hazelnut biometric characteristics. Furthermore, all indices were found to be cultivar-specific, underscoring the importance of conducting studies across different cultivars. The utilization of two UAVs, namely multispectral and thermal, facilitated the examination of the relationship between NDVI and CWSI across tree species.

Myofascial pain is the most common cause of chronic pain in the masticatory region and can be assessed through clinical analysis and muscle palpation. Generally, it appears with headache and orofacial pain associated with sensitive points (trigger points) due to the excessive contraction of the masticatory muscle fibres. The study aims to evaluate how a correct treatment of myofascial pain can improve the life quality of the affected patients. In this case series, 300 patients with myofascial pain were divided into two groups: 150 with intra- and extra-articular disorder and 150 with the only extra-articular disorder. Each group included 75 males and 75 females. All the patients were treated with gnathological therapy through passive aligners and biofeedback exercises for 4 months. They underwent pain assessment (through a visual analogue scale and muscular palpation test) before, during and after the treatment, and nuclear magnetic resonance of the temporomandibular joint before and after the gnathological treatment. The treatment considerably reduced the pain in all patients, without drugs, in 4 months, according to the visual analogue scales and the palpation test. The temporomandibular magnetic resonance in each patient was similar before and after the gnathological treatment. The improvement in pain did not depend on a change in the relationship between the articular condyle and the disc.

Activated sludge process is a well known method to treat municipal and industrial waste water. In this complex process, the oxygen concentration in the reactors plays a critical role in the plant efficiency. This paper proposes the use of a Long Short-Term Memory (LSTM) network to identify an input-output model suitable for the design of an oxygen concentration controller. The model is identified from easy-accessible measures collected from a real plant. This dataset covers almost a month. The performances achieved with the proposed LSTM model are compared with the ones obtained with a standard AutoRegressive model with eXogenous input (ARX). Both models catch the oscillation and the overall behaviour (ARX ρ=0.833 , LSTM ρ=0.921), but, while the ARX model fails in reaching the correct amplitude (FIT=41.20%), the LSTM presents satisfactory performance (FIT=60.56%).

Bootstrap resampling techinques, introduced by Efron and Rubin, can be presented in a general Bayesian framework, approximating the statistical distribution of a statistical functional φ(F), where F is a random distribution function. Efron’s and Rubin’s bootstrap procedures can be extended introducing an informative prior through the Proper Bayesian bootstrap. In this paper different bootstrap techniques are used and compared in predictive classification and regression models based on ensemble approaches, i.e. bagging models involving decision trees. Proper Bayesian bootstrap, proposed by Muliere and Secchi, is used to sample the posterior distribution over trees, introducing prior distributions on the covariates and the target variable. The results obtained are compared with respect to other competitive procedures employing different bootstrap techniques. The empirical analysis reports the results obtained on simulated and real data.

Electronic invoicing has become mandatory for Italian companies since January 2019. Invoices are structured in a predefined xml template where the information reported can be easily extracted and analyzed. The main aim of this paper is to exploit the information structured in electronic invoices to build an intelligent system which can facilitate accountants work. More precisely, this contribution shows how it is possible to automate part of the accounting process: all sent or received invoices of a company are classified into specific codes which represent the economic nature of the the financial transactions. In order to classify data contained in the invoices a machine learning multiclass classification problem is proposed using as input variables the information of the invoices to predict two different target variables, account codes and the VAT codes, which composes a general ledger entry. Different approaches are compared in terms of prediction accuracy. The best performance is achieved considering the hierarchical structure of the account codes.

The management of erectile dysfunction (ED) shows several grey zones, especially in terms of patient satisfaction and adherence to the treatment. The main and first-line treatment for ED is drug therapy, mainly phosphodiesterase-5 inhibitors (PDE-5is) but the adherence to the therapy is not optimal due to the low patient satisfaction reported in several cases. To address this issue, different administration routes and PDE-5is pharmacological formulations have been introduced in the pharmacological market. The pharmaceutical market has recently seen the introduction of a novel sildenafil oral suspension. This device offers access to all therapeutic regimens in one device, releasing 0.5 mL of suspension containing 12.5 mg of sildenafil with each pulse. This formulation enables tailored dosing based on clinical requirements and the demands of ED patients. Here, we aim to give a brief narrative review of the management of this new oral suspension in order to provide the readers with some suggestions to use in everyday clinical practice, on the basis of the recent evidence, by using an easy and rapid-to-consult questions and answers form. Also included are the conclusions of a board meeting of experienced andrologists regarding the most recent developments in this area.

Natural carotenoids are secondary metabolites that exhibit antioxidant, anti-inflammatory and anti-cancer properties. These types of compounds are in high demand by pharmaceutical, cosmetic, textile and food industries, leading to the search for new natural sources of carotenoids. In recent years, the production of carotenoids from bacteria has become of great interest for industrial applications. In addition to carotenoids with C40-skeletons, some bacteria have the ability to synthesize characteristic carotenoids with C30-skeletons. In this regard, a great variety of methodologies for the extraction and identification of bacterial carotenoids has been reported and this is the first review that condenses much of this information. To understand the diversity of these carotenoids, we present their biosynthetic origin in order to focus on the methodologies employed in their extraction and characterization. Special emphasis has been made on high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the analysis and identification of bacterial carotenoids. We end up this review showing their potential commercial use of bacterial carotenoids. This review is proposed as a guide for the identification of these metabolites, which are frequently reported in new bacteria strains.

Vulnerability is the big issue of the small inland urban centers exposed to the risk of depopulation. In the climate and in the context of an increasing seismic risk in the center-northern part of Italy, seismic vulnerability can become the determinant cause of the final abandonment of a small town. In some Italian regions, as well as Emilia Romagna, municipalities are implementing seismic vulnerability reduction policies based on the Emergency Limit Condition that has become a basic reference for ordinary land planning. This study proposes a valuation planning approach to the seismic vulnerability reduction carried out within the general planning framework concerning the Faentina Union, a group of five small towns located in the south-western part of the Province of Ravenna, Italy. The approach consists of three main stages: knowledge – the typological, constructive and technological description of the buildings specifically concerning their vulnerability degree; interpretation – the analyses aimed to outline a range of hypotheses about the damages in case of seism; planning – identifying the works intended to definitely reduce the vulnerability of the buildings. This stage includes a cost modelling tools aimed at outlining the trade-off between the extension and the intensity of the vulnerability reduction works, given the budget.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP) as cross-linking agents. The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied. All formulations showed excellent CUR trapping efficiency, exceeding 90%. In particular, the TPP-crosslinked macrobeads released 34 wt% of the charged CUR within minutes, while the remaining 66 wt% was released slowly due to the biodegradation of CS. The results indicate that the correct choice of gelling agent and its concentration leads to spherical particles capable of encapsulating CUR and releasing it in a wide range of kinetics depending on the specific application.

The unresolved territories are privileged places for the proliferation of degradation phenomena that affect the environment and human well-being. The impacts of their critical conditions go beyond the limits of the damaged urban fragments, involving the built environment, society, economy, culture and conditioning quality of life. This paper proposes a methodological approach to landscape design supported by an evaluation framework to orient strategic design planning with specific attention to unresolved territories consistent with circular economy perspective. The circular city principles are applied to spatial planning of landscape, by operationalising Ecosystem Services, Landscape Services, and Ecosystem Disservices, as interpretative categories for multi-dimensional regenerative strategies. Starting from the theoretical framework, the objective of the analysis is to implement an approach to the regenerative design of landscapes of waste, defined wastescapes. The industrial area of East Naples is the case study where an incremental evaluative approach has been defined to design scenarios to provide services and values, aimed to drive the conversion in a regenerativescape. A multi-criteria analysis through PROMETHEE-GAIA method has been implemented to compare the base case scenario with two incremental new scenarios and identify situated sustainable priorities.

The Covid-19 infodemic can be countered by scientific evidences, clear and consistent communication and improved health literacy of both individuals in need of information and those providing it. A rapid online survey was carried out to evaluate vaccine literacy (VL) skills in the general population and perceptions about candidate Covid-19 vaccines, as well as behavior and beliefs about current vaccinations. Observed VL levels were sufficiently high and consistent with previous observations - where comparable self-reported tools were administered face-to-face and paper-and-pencil - the mean functional score being =2.92, while the interactive-critical one was =3.27, on a maximum of 4. Perceptions regarding future Covid-19 vaccines, along with beliefs about vaccination, were mostly positive and significantly associated with functional and interactive-critical VL scales. Despite obvious limitations, the study confirms that rapid surveys via web are a suitable method to evaluate and trail attitudes during infectious disease outbreaks, and to assess health literacy skills about vaccination, which can be useful to adapt medical communication strategies, for a better understanding of the value of immunization.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related with a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide and it is estimated that is present in up to 25% of the world's population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthetized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allow the direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight about the mechanism and drugs action in NAFLD. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical disc. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using highly specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈ 0.39 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the lipid accumulation within the cells. Moreover, we discovered that at third day from lipids challenge, the hepatocytes increased the amount of albumin secreted. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation needed to unveil the biological significance of that cell behaviour.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.

Artificial intelligence (AI) tools, such as OpenAI's Chat Generative Pre-trained Transformer (ChatGPT), have great potential in various fields, such as healthcare, education, and industry. This review highlights the applications and challenges of the ChatGPT versions 3.5 and 4.0 in radiology. ChatGPT can process medical texts, analyze medical images, and generate reports and summaries for different audiences. ChatGPT can also answer patients' questions and translate complex medical information into a plain language. ChatGPT has shown impressive results in medical tests and quizzes, indicating its potential to enhance diagnostic accuracy and medical education. These models show promise for reducing diagnosis times and healthcare costs. However, ChatGPT also faces challenges and limitations, such as a lack of visual content, ethical and legal issues, data quality, and error detection. This review highlights the benefits and future directions of ChatGPT and artificial intelligence (AI) in radiology.