The purpose is to verify trends of scientific production from 2010 to 2020, considering the best universities of the United States, China, the European Union (EU) and private companies. The top 30 universities in 2020 in China, the EU, and the US and private companies were selected from the SCImago institutions ranking (SIR). The positions in 2020, 2015, 2010 in SIR and three sub-indicators were analyzed by means of non-parametric statistics, taking into consideration the effect of time and group on rankings. American and European Union universities have lost positions to Chinese universities and even more to private companies, which have improved. In 2020, private companies have surpassed all other groups considering Innovation as sub-indicator. The loss of leadership of European and partly American universities mainly concerns research linked to the production of patents. This can lead to future risks of monopoly that may elude public control and cause a possible loss of importance of research not linked to innovation.

Fused deposition modeling (FDM) is widely applied in various fields due to its affordability and ease of use. However, it faces challenges such as achieving high surface quality, precise dimensional tolerance and overcoming anisotropic mechanical properties. This paper analyzes and compare the machinability of 3D printed PLA, PETG and carbon fiber reinforced PETG focusing on surface roughness and burr formation. A design of experiments (DoE) with a full factorial design was used, considering three factors: rotation speed, feed rate and depth of cut. Each factor had different levels: rotational speed at 3000, 5500 and 8000 rpm; feed rate at 400, 600 and 800 mm/min; and depth of cut at 0.2, 0.4, 0.6, and 0.8 mm. Machinability was evaluated by roughness and burr height using a profilometer for all the materials under the same milling conditions. To evaluate the statistical significance of the influence of various processing parameters on surface roughness and burr formation in 3D printed components made of three different materials PLA, PETG and carbon fiber reinforced PETG, an analysis of variance (ANOVA) test was conducted. This analysis investigated whether variations in rotational speed, feed rate and depth of cut resulted in measurable and significant differences in machinability results. Results showed that milling parameters significantly affect roughness and burr formation, with optimal conditions for minimizing any misalignment highlighting the trade-offs in parameter selection. These results provide insights into the post-processing of FDM-printed materials with milling, indicating the need for a balanced approach to parameter selection based on application-specific requirements.

Predicting the popularity of posts on social networks has taken on significant importance in recent years, and several social media management tools now offer solutions to improve and optimize the quality of published content and to enhance the attractiveness of companies and organizations. Scientific research has recently moved in this direction, with the aim of exploiting advanced techniques such as machine learning, deep learning, natural language processing, etc., to support such tools. In light of the above, in this work we aim to address the challenge of predicting the popularity of a future post on Instagram, by defining the problem as a classification task and by proposing an original approach based on Gradient Boosting and feature engineering, which led us to promising experimental results. The proposed approach exploits big data technologies for scalability and efficiency and is general enough to be applied to other social media as well.

In recent years, drones have become increasingly prevalent in a wide range of applications, performing complex and critical tasks. To accomplish these tasks, drones cooperate by forming a Fly Ad-hoc Network (FANET) using specific routing protocols for communication. However, most of the routing protocols used in this type of network lack appropriate built-in security mechanisms, which creates numerous security challenges and concerns. To reduce the resulting security vulnerabilities and mitigate the impact of potential attacks, it is crucial to address these challenges before any deployment of FANETs. In this paper, we address two of the most harmful routing attacks - Sybil and Gray Hole and propose mitigating techniques to alleviate these attacks on FANET routing protocols. The proposed solution is secGPSR a secure version of the Greedy Perimeter Stateless Routing Protocol (GPSR). We validate the robustness of secGPSR through simulation using Omnet++ and present the results which show its effectiveness against Sybil and Gray Hole attacks.

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

Hydrogen is a promising energy carrier, exploitable to extract energy from fossil fuels, biomasses as well as intermittent renewable energy sources and its generation from fossil fuels with CO₂ separation at the source is one of the most promising pathway for fossil fuels utilization. This work is focused on a particular configuration, called Reformer and Membrane Module (RMM), which alternates stages of Steam Reforming (SR) reaction with H2 separation stages to overcome the thermodynamic limits of the conventional SR. The configuration has numerous advantages with respect to the more studied and tested membrane reactors and has been tested on a pilot scale during a pilot-scale research project. Although the numerous modelling works appeared in the literature, the design features of the material exchanger (in the so-called RMM architecture) of different geometrical configurations have not been developed and the mass transfer correlations, capable of providing design tools useful for such membrane modules, are not available. The purpose of this work is therefore to apply a physical-mathematical model of the mass transfer, in three different geometries, considering both concentration polarization and membrane permeation, in order to: i) simulate the cited experimental results, ii) estimate the scaling-up correlations for the “material exchange modules”; iii) identify the mass transfer limiting regime in relation to the gas mass flow rate.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

The increasing regulatory pressure to monitor and reduce GHG emissions and air pollutants requires cost-effective methods for their surveillance. The most common technique used for scientific investigations on gas concentration monitoring in barns are accurate but expensive and with a complex maintenance. This research study analysed the potential use of a low-cost portable measurement devices for the measurement of ammonia (NH3) and carbon dioxide (CO2) concentrations in an open dairy barn. A comparison between gas concentrations acquired at different heights from the floor by using portable devices and those acquired by a photoacoustic infrared multigas spectroscope (i.e., reference measurement) in the same sampling locations was carried out to determine the precision of the low-cost portable devices. The performance of low-cost portable devices was statistically analysed by the application of the one-way analysis of variance, correlation analysis and regression analysis. The results showed a significant difference between gas concentration values at various heights from the floor for both NH3 and CO2. The correlations between concentrations acquired by the low-cost portable device and the INNOVA were statistically significant (r=0.83; P<0.001) for gas concentrations monitored at 0.4 m from the floor. Compared with the reference measurement device, the low-cost devices were effective in the monitoring of NH3 concentrations at 0.40 m from the floor though it underestimated them in the barn at increasing of the height from the floor, whereas the device was not adequate for CO2 concentrations. In detail, the relative measurement error of the low-cost devices compared to INNOVA was reduced close to the floor during NH3 concentration measurements. Within these limitations, this device could be useful for monitoring NH3 concentration in the barn and to assess variation in NH3 concentrations mainly related to the animal occupied zone. Further efforts are needed in this field of research to identify low-cost device that could simplify emission estimation from open dairy barns.

In this work a new hydroelectric basin modelling approach is described and applied to the Pontecosi basin, Italy. Several types of data sources were used to learn the model: a number of weather stations, satellite observations, Reanalysis dataset and basin data. With the goal of predicting the water level of the basin, the model was composed by three cascade modules. Firstly, different spatial interpolation methods, such as Kriging, Radial Basis Function and Natural Neighbours, were compared and applied to interpolate the weather stations data nearby the basin area to infer the main environmental variables (air temperature, air humidity, precipitation and wind speed) in the basin area. Then, using these variables as inputs, a neural network was trained to predict the mean soil moisture concentration over the area, also to improve the low availability due to satellite orbits. Finally, a non-linear auto regressive exogenous input (NARX) model was trained to simulate the basin level with different prediction horizons, using the data from the previous modules and past basin data (water level, discharge flow rate, turbine flow rate). Accurate predictions of the basin water level were achieved within 1 to 6 hours ahead, with mean absolute errors (MAE) between 2cm and 10cm respectively.

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.

: Climate change necessitates urgent actions to mitigate carbon dioxide (CO2) emissions from fossil fuel-based energy generation. Among various strategies, the deployment of carbon capture and storage (CCS) solutions are critical for reducing emissions from point sources such as power plants and heavy industries. In this context, cryogenic carbon capture (CCC) via desublimation has emerged as a promising technology. While CCC offers high separation efficiency, minimal downstream compression work, and integration potential with existing industrial processes, challenges such as low operating temperatures and equipment costs persist. Ongoing research aims to address these hurdles in order to optimize the desublimation processes for widespread implementation. This review consolidates diverse literature works, providing insights into the strengths and limitations of CCC technology, including the latest pilot plant scale demonstrations. The transformative potential of CCC is first assessed on a theoretical basis, such as thermodynamic aspects and mass transfer phenomena. Then, recent advancements in the proposed process configurations are critically assessed and compared through key performance indicators. Furthermore, future research directions for this technology are clearly highlighted.

Background The acknowledgment of computed tomography (CT) defined diagnosis in high prevalence northern Italy may identify more patients with Coronavirus Disease-2019 (COVID 19) infection, than RT-PCR alone. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1st of February 2020 to 30th of April 2020, during the Covid-19 outbreak in Bergamo area. Therefore, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with diagnosis of COVID-19 infection: 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of COVID-19 infection is 22.9%, the mortality rate is 18.8%. Severe COVID-19 disease is associated with higher median age. We did not find any correlation between disease severity and sex, smoke or cardiovascular comorbidities. Remarkably, patients who were on treatment developed milder disease than cancer patients who were not on treatment. Conclusions The acceptance of CT-defined diagnosis in high prevalence area like Bergamo highlighted a larger number of COVID-19 oncological population than RT-PCR alone, in particular asymptomatic and mild symptomatic patients. We observed that actively treated patients had milder disease, according to previous studies that suggested a protective role of immunosuppression.

At the beginning of 2023 the Italian former prime minister, the former health minister and 17 others including the current president of Lombardy region, were placed under investigation on suspicion of aggravated culpable epidemic in connection with the government’s response at the start of the COVID-19 pandemic. The charges revolve around the failure by authorities to take adequate measures to prevent the spread of the virus in the Bergamo area, which experienced a significant excess of deaths during the initial outbreak. The aim of this paper is to analyse pandemic data of Italy and Lombardy region in the first 10 days of the pandemic, spanning from the 24th of February 2020 to the 4th of March 2020. The objective is to determine whether the use early warning indicators could have facilitated the identification of a critical increase in infections. This identification, in turn, would have enabled the timely formulation of strategies for pandemic containment, thereby reducing the number of deaths. In conclusion, to translate our findings into practical guidelines, we propose a low-cost early warning method for infectious respiratory diseases with asymptomatic carriers.

The medium-voltage DC (MVDC) technology has gained increasing interests in recent years. Power electronics devices dominate those grids. Accurate simulation of such a grid, with detailed models of switching semiconductors, can quickly became very time-consuming, according to the number of connected devices to be simulated. A simulation approach based on interactions on a continuous time model can be very interesting, especially for developing a system level control model of such a modern MVDC distribution grid. Aim of this paper is to present all the steps required for obtaining a continuous time modelling of a +/- 10 kV MVDC grid case study, including Solid State Transformer (SST) and Modular Multilevel Converter (MMC) based Active Front End (AFE). Additional aim of this paper is to supply an educational content about the use of the continuous time simulation approach, thanks to a detailed description of the various devices modelled into the presented MVDC grid. The results of a certain number of simulation scenarios are eventually presented.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

The present work was aimed at the chemical characterization and antimicrobial activity of some extracts of aerial parts (essential oils from leaves and inflorescences, and resins from inflorescences) of two legal hemp (Cannabis sativa) varieties, Tisza and Kompolti, grown in Sardinia. Chemical characterization was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antimicrobial activity of these extracts against a panel of microorganisms was also determined via minimum inhibitory concentration (M.I.C.) determination. While the results showed a minor or negligible antimicrobial activity of the extracts against Gram+ and Candida strains, a good antibacterial activity (especially of resins) was recorded against S. aureus; no substantial differences were detected between of the chemical compositions of the two Cannabis varieties.

Increasingly, there is a focus on utilising renewable energy resources in a bid to fulfil increasing energy requirements and mitigate the climate change impacts of fossil fuels. While most renewable resources are free, the technology used to usefully convert such resources is not and there is an increasing focus on improving the conversion economy and efficiency. To this end, advanced control technologies can have a significant impact and is already a relatively mature technology for wind turbines. Though hydroelectric plants can use simple regulation systems, significant benefits have been shown to accrue from the appropriate use of the same control methods designed for wind turbine plants. This represents the key point of the paper. In fact, to date, the application communities connected with wind and hydraulic energies have had little communication, resulting in little cross fertilisation of control ideas and experience, particularly from the more mature wind area to hydrodynamic systems. Therefore, this paper examines the models and the application of control technology across both domains, both from a comparative and contrasting point of view, with the aim of identifying commonalities in models and control objectives, as well as potential solutions. Key comparative reference points include the articulation of the exployed models, specification of control objectives, development of high--fidelity simulators, and development of solution concepts. Not least, in terms of realistic system requirements are the set of physical and constraints under which such renewable energy systems must operate, and the need to provide reliable and robust control solutions, which respect the often remote and relatively inaccessible location of many onshore and offshore deployments.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Social and behavioral rhythms (SBRs) are related to circadian rhythms well known as central points in the pathophysiology of bipolar disorders. The purpose is to verify in elderly people if having functional SBRs correlated with a positive perception of the quality of life (QoL) and health parameters and if there was an association between dysfunctionality of SBRs and Major Depressive Disorder (MDD). Sample: 141 people aged 65 years (58,9%Female). Each subject was submitted to SBRs Scale (in which higher scores show more dysfunctional SRB); SF-12 for QoL; PHQ-9 for depressive symptoms and underwent blood levels essays including cholesterol and triglyceride. The medical documented lifetime diagnosis including Major Depressive Disorder was taken into account. SBRs Scale score correlated inversely with SF-12 score (r=-0.360, p<0.0001) and positively with PHQ9 (r=0.396, p<0.0001). Lifetime MDD medical diagnosis was associated with a higher score at scale on social rhythms (24.811.9 vs 20.18.0, F=15.848, p<0.0001).The study highlighted, for the first time, that SBRs such as sleep, and nutrition have a role in well-being and that dysregulation of SBRs is related to MDD. Further longitudinal studies with a sufficient number of individuals will have to confirm these data and clarify causal links of the association between QoL and SBRs.

Advanced genomics, transcriptomics and epigenomics techniques are providing unprecedented insights into the understanding of the molecular underpinnings of the central nervous system, including the neuro-sensory cochlea of the inner ear. Here, we report for the first time a comprehensive and updated overview of the most advanced omics techniques for the study of nucleic acids, and their applications in cochlear research. We describe the available in vitro and in vivo models for hearing research, the principles of genomics, transcriptomics and epigenomics, alongside their most advanced technologies (like single cell omics and spatial omics), which allows to investigate the molecular events that occur at single cell resolution retaining the spatial information.

We generate numerically on a lattice an ensemble of stationary metrics, with spherical symmetry, which have Einstein action S_E « ħ. This is obtained through a Metropolis algorithm with weight exp(-β²S_E²) and β » ħ^-1. The squared action in the exponential allows to circumvene the problem of the non-positivity of S_E. The discretized metrics obtained exhibit a spontaneous polarization in regions of positive and negative scalar curvature. We compare this ensemble with a class of continuous metrics previously found, which satisfy the condition S_E=0 exactly, or in certain cases even the stronger condition R(x)=0 for any x. All these gravitational field configurations are of considerable interest in quantum gravity, because they represent possible vacuum fluctuations and are markedly different from Wheeler's ''spacetime foam''.

Contemporary cities are facing many challenges, from social and economic issues to the new risks related to the impacts of climate change. Focusing on energy consumptions, and the related GHG emissions, cities are considered not only the main global contributors but also the areas most exposed to risks, because of their density of population and economic activities. Implementing urban planning strategies with the purpose of increasing energy efficiency and resilience overall are, for all these reasons, considered a top priority. This paper investigates the innovative contents about energy-efficient and energy-resilient urban planning solutions that have started to be implemented in the cities of the Emilia-Romagna region. Two kinds of planning instruments are therefore analyzed: the voluntary Sustainable Energy and Climate Action Plans (SECAPs) and the mandatory General Urban Plans (GUPs), recently approved in several cities of Emilia-Romagna. A comparative analysis of three cities in the Emilia-Romagna region, Bologna, Modena and Ravenna, is proposed on the strategies of their newly local city plans and SECAPs with focus on energy management and planning. The aim is to assess whether the new structure of local city plans and the influence of SECAPs could be useful in implementing such urban energy resiliency solutions.

The interest on the use of renewable energy resources is increasing, especially towards wind and hydro powers, which should be efficiently converted into electric energy via suitable technology tools. To this aim, self--tuning control techniques represent viable strategies that can be employed for this purpose, due to the features of these nonlinear dynamic processes working over a wide range of operating conditions, driven by stochastic inputs, excitations and disturbances. Some of the considered methods were already verified on wind turbine systems, and important advantages may thus derive from the appropriate implementation of the same control schemes for hydroelectric plants. This represents the key point of the work, which provides some guidelines on the design and the application of these control strategies to these energy conversion systems. In fact, it seems that investigations related with both wind and hydraulic energies present a reduced number of common aspects, thus leading to little exchange and share of possible common points. This consideration is particularly valid with reference to the more established wind area when compared to hydroelectric systems. In this way, this work recalls the models of wind turbine and hydroelectric system, and investigates the application of different control solutions. The scope is to analyse common points in the control objectives and the achievable results from the application of different solutions. Another important point of this investigation regards the analysis of the exploited benchmark models, their control objectives, and the development of the control solutions. The working conditions of these energy conversion systems will be also taken into account in order to highlight the reliability and robustness characteristics of the developed control strategies, especially interesting for remote and relatively inaccessible location of many installations.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamin-ergic neurons responsible for unintended or uncontrollable movements. Mutations in leu-cine-rich repeat kinase 2 locus, contributes to genetic forms of PD. The fruit fly Drosophila mela-nogaster carrying this mutation (LRRK2-Dm), is an in vivo model of PD that develops motor impairment and stands for an eligible non mammalian paradigm to test novel therapeutic ap-proaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger. Pre-sents anti-inflammatory, antioxidant and neuroprotective properties making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1mM, for 14 and 21 days, in the LRRK2-Dm, with the aim to assess changes for rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-Bars). The shorter treat-ment with both molecules revealed efficacy at the higher dose improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-Bars failure was observed with the DHZ-DIM. Our data indicates that the DHZ-DIM exerts a more potent neuroprotective effect respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

The interest on the use of renewable energy resources is increasing, especially towards wind and hydro powers, which should be efficiently converted into electric energy via suitable technology tools. To this aim, data--driven control techniques represent viable strategies that can be employed for this purpose, due to the features of these nonlinear dynamic processes working over a wide range of operating conditions, driven by stochastic inputs, excitations and disturbances. Some of the considered methods, such as fuzzy and adaptive self--tuning controllers, were already verified on wind turbine systems, and similar advantages may thus derive from their appropriate implementation and application to hydroelectric plants. These issues represent the key features of the work, which provides some guidelines on the design and the application of these control strategies to these energy conversion systems. The working conditions of these systems will be also taken into account in order to highlight the reliability and robustness characteristics of the developed control strategies, especially interesting for remote and relatively inaccessible location of many installations.

In this paper we describe the potentialities of a tool for the visualization of experimental results directly on a three-dimensional model. The case study concerns the visualization of the results of a dynamic finite element analysis (FEA/FEM) applied to the calculation of seismic risk on works belonging to the Italian infrastructural heritage, specifically bridges, viaducts and overpasses. The project is based on finite element analysis performed on an exemplary set of 8 structures located on the Italian territory, performed by means of the open-source software framework OpenSees, according to the guidelines indicated in the Technical Standards for Construction NTC08. The application created for this project is classifiable as a webGIS, since all data are georeferenced and visualized on a map through an application executed through a browser. The graphical interface displays the interested works on the map of the Italian territory and allows to select them by mouse click. Following the selection, a 3D rendering of the model of the work and the surrounding terrain is shown, in which the results of the analysis are represented using color gradients directly on the three-dimensional model. The necessary tools are present for the selection of the type of result and for the animation in real time of the response of the work to the seismic action. The 3D representation is freely navigable by the user thanks to intuitive tools of panning, rotation and zoom through mouse and keyboard. The application takes advantage of HTML5, CSS and Javascript to show graphical features such as Cartesian diagrams of accelerograms used in modal analysis.

In this work we produced biochar by coffee waste and use it as filler in epoxy resin composite with the aim to increase their electrical properties. The biochar and biochar based composite electrical conductivity were studied in function of applied pressure and compared with carbon black and carbon black composite. The applied pressure has the aim to investigate the behaviour of filler in powder or dispersed in composite in function of compression. Results showed that even if the coffee biochar has less conductivity if compared with carbon black in powder form, it has better conductivity in composite if compared with carbon black. Composite mechanical properties were tested and they are generally improved respect to neat epoxy resin.

Human keratinocytes and melanoma can stick together to form clusters after eight days in co-culture. As in dynamic system concepts, one can consider cluster formation as the system attractor, cell seeding as the initial condition, and density change over time as a path within the basin of attraction. Herein, Cellular Automata, which is a class of Agent-Based Models, and Boolean Networks are discrete modeling methods used in population dynamics such that running the dynamics of cellular automata backward reveals an underlying network in terms of basin of attraction, also known as global dynamics. Thus, we hypothesize that one can estimate the local dynamic of an agent-based model from the basin of attraction of a boolean network. Here, we propose an approach to estimating these agent-based model rules, which consists of comparing the density states within each state transition and reaching a consensus among state transitions belonging to a basin of attraction of a boolean network. The objectives of this study are: (1) to infer a boolean network from the co-culture growth curve; (2) to estimate the rules of agent-based models; and (3) to implement spatial dynamics simulations. The binarization of the growth curve shows high population density after four days; the estimated agent-based model rules were compatible with cell proliferation and migration in agreement with literature, so we had to propose individual rules for survival and death. Spatial dynamics shows that (1) keratinocytes exhibit a higher density in neighborhoods where melanoma is present; (2) the chance of keratinocyte migration increases until the fourth day, then decreases, and the probability of survival increases substantially after four days; and (3) cells with low proliferation capacity die and free space for those with high ones. Our approach suggests that the attractor state of cell co-culture is induced mainly by an increase in keratinocyte migration and survival. Our approach has the potential to offer valuable clues about microenvironmental interactions or configurations that drive population dynamics.

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

In recent years, many studies have highlighted the consistent finding of amoxicillin in waters destined for wastewater treatment plants, in addition to superficial waters of rivers and lakes in both Europe and North America. In this paper, the amoxicillin degradation pathway was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants at three different pH values. The structures of 16 isolated degradation byproducts (DPs), one of which was isolated for the first time, were separated on a C-18 column via a gradient HPLC method. Then, combining mass spectrometry (MALDI-MS/TOF) and nuclear magnetic resonance, we compared commercial standards and justified a proposed formation mechanism beginning from the parent drug. Microbial growth inhibition bioassays with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were performed to determine the potential loss of antibacterial activity in isolated degradation byproducts. An increase of antibacterial activity in the DPs was observed compared to the parent compound.

The spread of high-performance personal computers, frequently equipped with powerful Graphic Processing Units (GPU), raised the interest on a set of techniques able to extract models of electromagnetic phenomena (and devices) directly from available examples of the desired behavior. Such approaches are collectively referred to as Machine Learning (ML). A typical representative ML approach is the so called “Neural Network” (NN). Using such data-driven models allows evaluating the output in a much shorter time when a theoretical model is available, or allows predicting the behavior of the systems and devices when no theoretical model is available. With reference to a simple yet representative benchmark electromagnetic problem, some of the possibilities and the pitfalls of the use of NN for the interpretation of measurements (inverse problem) or to obtain the required measurements (optimal design problem) are discussed. The investigated aspects include the choice of the NN model; the generation of the dataset(s); the selection of hyperparameters (hidden layers, training paradigm). Finally, the capabilities in the handling of ill-posed problems are critically revised.

This article argues that despite a citation review is a rarely used research tool, this can be very useful to assess the impact of new research topics, both from the future research direction and the bibliometric perspectives. An explorative study is presented around the research area marked as Industry 4.0 with the conference paper mentioned in the title of this citation review. Even though the given reference paper is relatively recent, there are already twenty-seven citations listed among three different scholar databases. These are Google Scholar, ResearchGate and Semantic Scholar. In light of this, the article provides a bibliometric confirmation and analysis for the progression of the line of research adopted by de Giorgio et al. in the exploration of non-traditional methods using virtual reality technology and human-robot collaboration for adaptive applications in Industry 4.0. Furthermore, it represents a model for the authors’ self-development and an example of an unconventional approach to scientific work that may help improve related bibliometric research and scholar database strategies to index new articles and topics in the future.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 hrs, with or without interleukin (IL)-1β (10 ng/mL). Viability was detected by MTT assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lym-phoma (BCL)2 expressions were analyzed by quantitative real time PCR. Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through NF-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting miRNA as possible mediators.

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

Soarinho Alkaline Intrusion, southeastern Brazil, makes part of the Serra do Mar Igneous Province, and it is composed of alkali feldspar syenite, alkali feldspar trachyte, quartz syenite, and mon-zonite. Geochemical and geochronological analysis of the Soarinho were compared with data from its neighbors Rio Bonito and Tanguá. Zircon U-Pb Laser Ablation ages show that Soarinho is youngest than Rio Bonito and Tanguá. Ages obtained from the monzonite (60 ± 2 Ma), alkali feldspar syenite (58 ± 2 Ma), and quartz syenite (58 ± 2 Ma) are indistinguishable within error. Petrographic and geochemical data show a clear contrast among Soarinho, Rio Bonito, Tanguá, and Lu-Hf isotopic data for the three alkaline intrusions (all negative), point to some similarities in their sources. The data suggest an enriched mantle source for Soarinho; however, an older con-tinental crust contribution cannot be discarded.

In this work, the nearest neighbor distances and Voronoi cell features of the Cu-Ag deposits were analyzed and fitted with Lognormal, Weibull, and Gamma distributions. The nearest neighbor distance distributions of the samples were compared with those of complete spatially random points, showing spatial inhomogenity due to the nucleation exclusion effect. The radial distribution function was calculated, showing both influences from the grain size and the nucleation exclusion effect. Voronoi cells were generated based on the shape of the grains. The size, occupancy, and coordination of the Voronoi cells were examined and fitted. The results show that despite the Cu-Ag deposits seem to be governed by instantaneous nucleation mode, the spatial distribution of the nuclei is more impacted by the nucleation exclusion effect than the Cu-only samples. This behavior is also justified by the grain size distribution generated with Voronoi cell size and occupancy distributions.

The circular economy (CE) has emerged as a viable alternative for tackling the problems caused by rising consumption, including solid waste (SW). The present study conducted a meta-analysis of research published between 2012 and 2022 on CE and solid waste management (SWM). A bibliometric analysis was used from the Web of Science (WoS) and Scopus databases. By studying the articles, we briefly discussed the connections between them and how one contributes to the evolution of the other. Some findings point to greater collaboration between Italy and Bolivia, followed by China and Malaysia. However, they move away from the traditional axes as the United States and Canada. In addition, it was found that the adoption of reuse and selective collection, in fact, allow the reduction of the volume of discarded materials. In this way, it was possible to conclude that a greater connection between CE and GRS makes it possible to optimize the useful life of landfills through the treatment of organic waste and recycling, to encourage waste picker cooperatives and selective collection programs, and to reduce the financial costs of the system as a whole, making it more durable and sustainable.

This study explores the innovative use of CO2 laser technology in frenuloplasty, a significant shift from traditional methods like scalpel surgery or electrocautery, towards a minimally invasive approach. The research involved 15 patients aged 25 to 50, undergoing frenuloplasty with a CO2 laser system equipped with a 7-inch defocused handpiece, set at 20Hz and 0.3W. This method diverges from conventional laser techniques, focusing on controlled laser passes combined with manual traction to elongate the fibrous tissue of the frenulum. The results demonstrated that the CO2 laser technique allowed for a precise and progressive modification of the frenulum, significantly reducing the risks of hemorrhage and secondary in-tention fibrosis. The healing process was notably expedited, with patients reporting satisfactory outcomes within a two-week period. Statistically significant improvements were observed in pa-tient-reported outcomes, as evidenced by the increases in the Short Form Health Survey (SF-12) scores, with the mean Physical Component Summary (PCS) score rising from 32.5 to 47.5 and the mean Mental Component Summary (MCS) score from 39.3 to 52.3 (p < 0.001 for both). The study concludes that CO2 laser frenuloplasty is an effective and safe technique, offering sub-stantial benefits in terms of reduced healing time and enhanced patient satisfaction. The signifi-cant improvements in SF-12 scores underscore the positive impact on patient quality of life, ad-vocating for the broader application of this technique in clinical practice. Further research is warranted to explore its potential in a wider clinical context.

Pediatric psychology action in the pediatric clinical-surgical high complexity unit has become increasingly necessary. It allows for the possibility of integrating complex pediatric clinical-surgical operations by reducing painful effects on the emotional world of children and adolescents. The pediatric psychologist in a pediatric unit continuously oversees children and adolescents (C/A) throughout the entire therapeutic process, extending activity to parents and healthcare personnel. In ill children and adolescents, physical pain and psychological suffering follow, with minimal temporary variations, the same clinical path with continuous changes which put a strain on the ability of children, adolescents, parents and healthcare staff to cope with stress.

Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.

Diabetes mellitus is acknowledged as a significant contributor to severe complications. The present work has explorated the potential role amentoflavone as an aldose reductase inhibitor through Docking Simulations. From these results this compound has shown excellent results with this enzyme with a high binding energy of -11 kcal/mol. If amentoflavone,a natural biflavonoid, proves effective in inhibiting aldose reductase, it could hold therapeutic promise for managing diabetic complications. However, it's crucial to emphasize that while computational studies offer valuable insights, experimental validation is essential to confirm the actual inhibitory effects and to establish the safety and efficacy of amentoflavone for this purpose. Further research and clinical studies are warranted to fully understand and harness the potential therapeutic benefits of amentoflavone in the context of diabetes.

In the last four years, the evolution and adoption of blockchain and, more generally, distributed ledger systems have shown the affirmation of many concepts and models with significant differences in system governance and suitable applications. This work aims to update the critical analysis of blockchain technologies carried out by our previous contribution to this journal, extending the focus to distributed ledger components and systems. Starting from the topical concept of decentralization, we introduce concepts and building blocks currently adopted in the available systems centering on their functional aspects and impact on possible applications. We present some conceptual framing tools helpful in the application context, and we will propose the concept of process authenticity, which we will discuss through two use cases: blockchain document dematerialization and e-voting.

A number of research projects and a rich literature have dealt with the theme of abandoned medieval villages in Sardinia since the end of the 60s of the last century. Some more or less precise catalogues and reviews of villages in limited territories have been published. Only recently, however, this subject is being addressed in an interdisciplinary manner, combining traditional historical research with the results of archaeological surveys and excavation campaigns, geo-archaeology, toponymy, paleoclimatology. This allows us to have a picture of the landscape and human settlement evolution with its historical changes, conditioned not only by institutional superstructures but also by human and natural traumatic events. Particular attention will be given to the sudden changes that occurred between the thirteenth and fourteenth centuries. To carry out this survey, it is possible to use some very powerful IT tools which, through the aggregation, organization, correlation and management of information, allow the geo-localization of abandoned villages as proven by the documentary evidence. Thus, on this documentation, existing and acquired in the future, is founded the construction of the related information system. The most easy and suitable tools for this purpose are the CMSs (Content Management Systems) which, in association with GIS (Geographic Information Systems) engines, allow spatial and contextual analysis of the settlements, as they were inserted in their territory. This type of tools aggregates different peculiarities of the object of study, supporting a multidisciplinary reading on the argument. The computerized tools, integrated as a system, offer the possibility to implement it, feeding it and correcting it continuously, basing on new acquisitions. In this study, we will examine a historical areal, for which we have a sufficient number of sources available: Sarrabus, Colostrai and Quirra, adding to the geographical visual information, the temporal visual evolution.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Cetacean Morbillivirus, the most relevant pathogen impacting the health and conservation of cetaceans worldwide, has shown in recent years an increased tendency to cross “interspecies barriers”, thereby giving rise to disease and mortality outbreaks in free-ranging dolphins and whales. The present article deals with the evolutionary “trajectories” of this viral pathogen, likely originating from Rinderpest Virus, along with its “journey” from land to sea (and viceversa), mimicking that of cetaceans' terrestrial ancestors.

Contemporary diagnostic practice in psychiatry relies on the tick-box approach of diagnostic manuals. In light of the obvious limitations of diagnostic systems, narrative formulations, whether in the form of biological, psychodynamic or behavioural cognitive ones, have been proposed. Their approach, which can be caricatured as one of drawing arrows, enriches our clinical tools and practice but in their explicitly theoretical orientation, as well as expanding the field of discovery, they also constrain it. In two previous papers I summarized the resulting limitations, with specific reference to the patient’s experience and proposed further enriching clinical perspicacity by attending to images and parataxis. The specific intent of attending to the patient’s experiences through a process that explicitly eschews narrativization, but allows clinical phenomena to “hang loose”, is to facilitate a process of clinical discovery and healing through practices of co-production between patient and clinician. In the present paper, I expand the range of phenomena that may assist in this co-production through adding attention to dreams to that of images and parataxis. In particular, I turn to the work of the Italian novelist Guido Morselli. Morselli agrues that the self is created through bundling experiences together through acts of “will” in order to establish our personal narrative. In doing so, however, the “will” forbids access to phenomena that do not fit the dominant narrative. Experience is therefore impoverished. Dream consciousness is a type of consciousness not harnessed by the constraints of narrativity. It allows a slipping of the narrative vigilance which bundles phenomena together to create a coherent narrative and thus offers a richer menu of potential experiences, including “bizarre” images that can serve to challenge our usual self-narrative and offer a new perspective on ourselves.

ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

The statistical bundle is the set of couples $(Q,W)$ of a probability density Q and a random variable W such that $\mathbb{E}$_Q [W] = 0. On a finite state space, we assume Q to be a probability density with respect to the uniform probability and give an affine atlas of charts such that the resulting manifold is a model for Information Geometry. Velocity and accelleration of a one-dimensional statistical model are computed in this set up. The Euler-Lagrange equations are derived from the Lagrange action integral. An example of Lagrangian using minus the entropy as potential energy is briefly discussed.

Bilateral recurrent nerve damage following total thyroidectomy in thyroid surgery represents severe complications. These complications have almost low incidence thanks also by using the Nerve Intraoperative Monitoring. The aim of this observational retrospective study is to evaluate the inception mode and the recovery time for different clinical laryngeal pictures that arise from this surgery. We enrolled 25 patients with bilateral vocal folds mobility deficit between October 2017 and October 2022, diagnosed in ENT Unit of University of Campania “L. Vanvitelli”, out of a total of 1417 patients undergoing total thyroidectomy. The 25 patients (23F,2M) aged from 24 to 78 years old (average age 51.7) presented a bilateral vocal folds motility deficit (occurring in about 0.1% of cases). All patients underwent 9 months diagnostic/therapeutic process, which started approximately 30 days after thyroid surgery. There are several outcomes of these complications with functional laryngeal defects being mainly related to respiratory and phonatory activities. These clinical manifestations evolve in different ways within a context of a wide range of possibilities, from spontaneous bilateral or monolateral recovery to functional or surgical restoration. This study allowed the acquisition of useful information about prognostic indications and an adequate therapeutic process, based on the specific clinical characteristics.

School-museum relations have gained considerable attention in the academic literature in recent decades. However, there still needs to be more research on their role in enhancing science education. This work reports the outcomes of the recovery, study, and valorization of the 18th-century geo-mineralogical collection belonging to the Collegio Nazareno, now housed at the Istituto San Giuseppe Calasanzio in Rome. The project consisted of four phases: 1) the securing of more than 1720 specimens; 2) their cataloging using the Italian national catalographic standards for the mineralogical and petrological heritage; 3) the establishment of new exhibit and storage areas; 4) the development of a self-instructive exhibition itinerary. The project, which was participated by the students enrolled in the fourth and fifth high school classes, revealed fascinating and unique specimens such as the ones collected by prominent Italian naturalists –e.g., Scipione Breislak (1750–1826) and Carlo Giuseppe Gismondi (1762–1824) – or those comprising the mineralogical collection donated by the Holy Roman Emperor Joseph II (1741–1740) to the Mineralogical Cabinet of the Collegio Nazareno in 1785. This work thus offers significant insights into the importance of natural history school museums as useful (and oft-forgotten) learning tools in science education.

Tourism may not sustainably support territories with limited natural resource stock as islands. The volume in visitor arrivals and the industry investments can increase the pressure even beyond sustainable levels. There is an evident and unresolved tension between these two great polarities, sustainability and economic growth driven by tourism. The aim for policymakers is to find an acceptable equilibrium between these two dimensions. This paper investigates the tourism evolution between 2007 and 2019 in 15 Mediterranean islands, comparing the tourism pressures through statistical indicators. The analysis will compare tourism demand and supply trends in these contexts. The performances will be evaluated to identify the Islands positioning between sustainability needs and tourism development opportunities considering post-covid-19 challenges.

Modified nucleobases are potentially useful building blocks when containing catalytically active functionalities and could be introduced in chiral tridimensional molecules such as nucleic acids, which creates the premises for the development of novel catalytic species. Herein we describe the synthesis of a novel β-C-nucleoside bearing a diol group at anomeric position, amenable as metal ligand or as organo-catalyst. The abasic ligand was successfully prepared and inserted into complementary DNA strand.

Evaluation of biliary strictures remains a challenge due to the low sensitivity of standard diagnostic work up, but the introduction of direct single-operator cholangioscopy (DSOC) changed this paradigm. Aim of our study was to evaluate diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS) and brush cytology in patients with indeterminate biliary stricture (IBS). We evaluated patients who underwent advanced diagnostic work up for IBS in our endoscopy unit from ‘01/2018 to ‘12/2022; all patients had at least one previous attempt to characterize the biliary stricture. Final diagnosis was based on surgical pathology and/or clinical and radiological follow-up of at least 12 months. A total of 57 patients with a mean age of 67.2 ± 10.0 years were included, with a mean follow up of 18.2 ± 18.1 months. IBS were mostly located in the distal common bile duct (45.6%) and final diagnosis was consistent with malignancy in 35 patients (61.4%). DSOC and IDUS showed a significantly higher accuracy (89.5% and 82.7% respectively) compared to standard cytology (61.5%, p <0.05). In our experience, DSOC visualization and IDUS both demonstrated an optimal diagnostic yield in the differentiation of IBS, with an acceptable safety profile both quantitatively and qualitatively.

Variance-driven decomposition based on the singular spectrum analysis of the European Project for Ice Coring in Antarctica (EPICA) dD, CO2 and CH4 records allowed a novel quantitative structural interpretation of all glacial/interglacial cycles and glacial terminations of the last 800 kyr. This bottom-up approach used the response components of EPICA stacked records to reconstruct the envelope of the thermal response through a physical interference model. The aim was to improve the understanding regarding the features of intensity, amplitude, and asymmetry of 73 marine isotope stages (MIS) and seven terminations. The Antarctic stack record can be described by a variance-weighted interference model of ten thermal waves of different origins (mid-term oscillation, orbitals and suborbitals) that stochastically interfere at a given time according to their relative differences in frequency, intensity, and polarity. Interglacial/glacial stages resulted from constructive interference and bipolar amplification of warming/cooling responses, respectively. The low intensity MISs (including 90% of substages) and the unbiased-dated terminations fell in the low interference regions where dominant destructive patterns minimise the thermal envelope. The positive skewness of the EPICA stack resulted from the constructive interference with a strong bias in the warming direction, especially after the Mid-Brunhes Event. Duration analysis of short eccentricity hemicycles exhibited an intrinsic unexpectedly prolonged mean cooling in the nominal solution (5.8 kyr) and its EPICA response as well (8.6 kyr), along with an interference-induced asymmetry (21.1 kyr). The overall effect resulted in the saw-tooth shape of glacial cycles which is heavily induced by interference and related to the intermediate feedback mechanisms controlled by short eccentricity.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

A brief overview of the past and present trajectories made by the A(H5N1) avian influenza virus among domestic birds, avian and mammalian wildlife species and humans is presented here, thereby taking into special account the 2.3.4.4b clade of the virus recently emerged in several geographic areas of the globe.

A Robust Optimization framework with original concepts and fundamentals also admitting a fusion of ideals from relative regret models and static robust optimization, containing conservatism concepts is disclosed. The algorithm uses a fine-tune strategy to tune the model so the robustness and a target ideality can be mutually achieved with a specified risk. The framework comprises original concepts, a mathematical approach and an algorithm. The statistical treatment of the data with the original concepts from the framework make it able to make short, middle or long-term decision-making setting. The framework has high tractability since the algorithm forces the creation of a setting that makes a robust optimization with the specified risk. The framework can be applied in linear and nonlinear mathematical models since that the objective function is monotonic in the domain of the active convex region. Several examples are solved to best understand the framework and all results demonstrated high tractability and performance. There is a wide range of applications. Along all the text, there is a profound discussion about its philosophy, objective, original concepts, fields of application, statistical and probabilistic fundamentals.

Background: Chronic post-surgical pain is a condition persisting at least three months after surgery. It is estimated that 25-60% of patients who underwent breast cancer removal surgery suffer from post-mastectomy pain syndrome and occurred anxiety, depression, sleep disturbance and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. Aim of this study was to evaluate the effects of physical activity on the intensity of pain, depression and anxiety in women underwent mastectomy for breast cancer removal. Methods: A prospective observational unicentric cohort study was performed. Patients were female underwent unilateral or bilateral mastectomy. Numerical Rating Scale (NRS), was used to assess pain intensity, Beck’s Depression Inventory (BDI) for depression and Generalized Anxiety Disorders-7 (GAD-7), for anxiety evaluation. Physical activity was assessed by International Physical activity questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All the evaluation was assessed 3 and 6 months after the surgery. Results: Adequate physical activity reduced intensity of pain, depression and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequate active women, showed a reduction of biomarkers of inflammation, cortisol, ACTH and an increase of BDNF. Conclusions: Our results suggest that physical activity can improve quality of life, reducing intensity of pain, inflammatory markers and it can be useful in the reduction of associated anxiety and depression.

The extensive collection of paper documents and books stored in the archives of universities worldwide is a hidden cultural heritage that is frequently inaccessible. To overcome this problem, the University of Genoa, Italy, seeks to collect, store, and digitize a wide variety of items, encompassing books, manuscripts, archival materials, and documents related to museum artifacts, which together form a cultural heritage of great importance and historical significance. To make such a cultural heritage accessible to both humans and machines, images and videos must be provided with alternate descriptions, metadata, and speech-to-text transcriptions while ancient texts, for which OCR techniques are often not effective, must be accompanied by word-for-word transcripts. This work presents the design of a transcription system for the “University Museum System” at the University of Genoa, Italy (SMA-UniGe), including user interface elements and users’ engagement techniques. The goal is to create an accessible digital heritage that can be enjoyed by all, facilitated by a community of digital volunteers who are eager to dedicate their time, have a great experience, socialize, and interact on the proposed transcription system. The system exploits gamification theory to transform the typically monotonous task of transcription into a captivating experience. This activity is in line with the so-called University third mission, i.e., the activity of public engagement that aims at generating knowledge outside the academic environment to the benefit of the social, cultural, and economic development.

Keywords: oligozoospermia; male infertility; epididymis; scrotal exploration; scrotal ultrasound; partial epididymal obstruction

The paper aims at presenting the results obtained in the development of a system allowing the detection and monitoring of forest fires and the continuous comparison of their intensity when several events occur simultaneously, as usually happens in the European Mediterranean countries during the summer season. The system, called SFIDE (Satellite FIre DEtection), exploits a geostationary satellite sensor (SEVIRI on board of MSG satellite series). The algorithm was developed several years ago in the framework of a project (SIGRI) funded by the Italian Space Agency (ASI). This algorithm has been completely reviewed in order to enhance its efficiency by reducing false alarms rate preserving a high sensitivity. Due to the very low spatial resolution of SEVIRI images (4x4 km² at Mediterranean latitude) the sensitivity of the algorithm should be very high to detect even small fires. The improvement of the algorithm has been obtained by: introducing the sun elevation angle in the computation of the preliminary thresholds to identify potential thermal anomalies (hot spots), introducing a contextual analysis in the detection of clouds and in the detection of night-time fires. The results of the algorithm have been validated in the Sardinia region by using ground true data provided by the regional Corpo Forestale e di Vigilanza Ambientale (CFVA). A significant reduction of the commission error (less than 10%) has been obtained with respect to the previous version of the algorithm and also with respect to fire-detection algorithms based on low earth orbit satellites.

(1) Background: Usually, the majority of patients suffering from vertigo and dizziness can be identified in four major categories: acute spontaneous vertigo, episodic (recurrent) vertigo, recurrent positional vertigo, chronic imbalance. Our purpose is to retrospectively evaluate the main causes of episodic vertigo and to find indications for a reliable clinical suspicion useful for a definitive diagnosis, comparing patients affected by different presenting symptomatology (acute vertigo, recurrent episodic vertigo, and imbalance) (2) Methods: we retrospectively evaluated the clinical records in a population of 249 consecutive patients observed for vertigo in our tertiary referral center in the period 1 January 2019 – 31 January 2020. On the basis of the reported clinical history, patients were divided into three groups: patients with first ever attack of vertigo, patients with recurrent vertigo and dizziness; patients with chronic imbalance. (3) Results: On the basis of the results of the instrumental examination, we arbitrary divided (for each type of symptoms) the patients in a group with a normal vestibular instrumental examination and a group of patients in which the clinical-instrumental evaluation showed some pathological results; a highly significant difference (p: 0.157) was found between recurrent and acute vertigo and between recurrent vertigo and imbalance. (4) Conclusions: patients with recurrent vertigo more frequently exhibit a negative otoneurological examination since they are often examined in the intercritical phase. A precise and in-depth research of the patient's clinical history is the key to suspect or make a diagnosis together with the search for some instrumental or clinical hallmark, especially in cases where the clinical picture does not fully meet the international diagnostic criteria.

The beautiful structures of single and multi-domain proteins are clearly ordered in some fashion but cannot be readily classified using group theory methods that are successfully used to describe periodic crystals. For this reason, protein structures are considered to be aperiodic, and may have evolved this way for functional purposes, especially in instances that require a combination of softness and rigidity within the same molecule. By analyzing the solved protein structures, we show that orientational symmetry is broken in the aperiodic arrangement of the secondary structural elements (SSEs), which we deduce by calculating the nematic order parameter, $P_2$. We find that the folded structures are nematic droplets with a broad distribution of $P_2$. We argue that non-zero values of $P_2$, leads to an arrangement of the SSEs that can resist mechanical forces, which is a requirement for allosteric proteins. Such proteins, which resist mechanical forces in some regions while being flexible in others, transmit signals from one region of the protein to another (action at a distance) in response to binding of ligands (oxygen, ATP or other small molecules).

Triangular resonators re-shaped with the Sierpinski geometry and U-shaped resonators have been designed, linking them with single-pole-double-through (SPDT) RF MEMS switches to provide frequency tuning for potential applications in the K-Band. Prototypes of band-stop narrowband filters working around 20 GHz and 26 GHz, interesting for RADAR and satellite communications, have been studied in coplanar waveguide (CPW) configuration, and the tuning was obtained by switching between two paths of the devices loaded with different resonators. As a result, dual-band operation or fine-tuning can be obtained depending on the choice of the resonator, acting as a building block. The studied filters belong to the more general group of devices inspired by the metamaterial design.

Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In the advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in the OC. Methods: We searched the PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were selected, of which 16 were phase I or II and 4 phase III trials. ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, atezolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab) were employed. No significant survival improvement was achieved; conversely, early terminations due to futility or toxicity were recorded. Combinations with chemotherapy, anti-VEGF, and, overall, PARP-inhibitors seem feasible and enhance the response rate and survival, notwithstanding a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of the OC might lead to an improved treatments selection and design of tailored trials.

Chitosan is a biopolymer derived from chitin. It is a non-toxic, biocompatible, bioactive, and biodegradable polymer. Due to its properties, chitosan has found applications in several and different fields such as agriculture, food industry, medicine, paper fabrication, textile industry, and water treatment. In addition to these properties, chitosan has a good film-forming ability which allows it to be widely used for the development of sensors and biosensors. This review is focused on the use of chitosan for the formulation of electrochemical chemosensors. It also aims to provide an overview of the advantages of using chitosan as an immobilization platform for biomolecules by highlighting its applications in electrochemical biosensors. Finally, applications of electro-chemical chitosan-based chemosensors and biosensors in food safety are illustrated

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.

The presence of heavy metals in industrial effluents has recently become a source of concern for human health and the environment. Efficient removal of metal ions and wastewater treatment is essential for protecting public health and the environment. In this study, we present an eco-friendly, green synthesis of reactive and fully dispersed zerovalent iron nanoparticles (nZVI) in carbon nanofibers via an electrospinning technique. In this novel study, green tea (GT) was used as environmentally friendly, polyvinyl alcohol (PVA) was used for the stabilization and reduction of nZVI, and tetraethyl orthosilicate (TEOS) was added to provide flexibility and to increase the specific surface area of the nZVI based nanofibers. GT contains polyphenols, which act as reducing agents, converting iron ions into nZVI and the particles can then serve as the building blocks for the carbon nanofibers. TEOS can also contribute to the stability of the nZVI by coating their surfaces with a silica layer. This silica layer helps prevent the oxidation of the nZVI, thereby reducing their catalytic activity. The nZVI-based composite (∼ 400 nm) / carbonized (∼ 200 nm) nanofibrous mats were fully characterized by scanning electron microscopy. The average size of the nZVI embedded in the composite and carbonized nanofibers can range from 50 nm to 100 nm. The x-ray diffraction (XRD) analysis of nZVI-based carbon nanofibers showed that there is no crystallinity and a single-phase cubic structure. Both energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FTIR) analysis also confirmed the formation of single-phase nZVI-based composite / carbonized nanofibers. The high intensity of the peaks in the FTIR spectrum indicates the formation of nZVI in the nanofibers structure. The electrospun nZVI-based carbon nanofibers have a higher surface area and better reactivity due to small particle size and large surface area-to-volume ratio. They can provide excellent water stability and dispersibility in water compared to bulk nZVI, which tend to agglomerate and settle quickly. Additionally, nanofiber morphology can enhance the mechanical strength and durability of the composite material. Due to low-cost synthesis and their high efficiency in removing pollutants, these nanofibers could be used as nano-filters for wastewater treatment.

Microstructured optical fibres (MOFs) are a new type of optical fibres that possess a wide range of optical properties and many advantages over common optical fibres. Those are provided by unique structures defined by a pattern of periodic or quasi-periodic arrangement of air holes that run through the fibre length. In recent years, MOFs have opened up new possibilities in the field of optics and photonics, enabling the development of advanced devices and novel optical systems for different applications. The key application areas of PCFs vary from telecommunications and high-power energy transmission to quantum optics and sensing. The stack-and-draw method is a standard manufacturing technique for MOFs, where a preform is first manually created and then drawn in a high-tech furnace into a fibre with the required final dimensions and position of the air holes. Since in the manufacturing process experimenters can control only a few parameters, mathematical models and numerical simulations of the drawing process are highly requested. They not only allow to deepen the understanding of physical phenomena occurring during the drawing process, but they also accurately predict the final cross-section shape and size of the fibre. In this manuscript, we assume thermal equilibrium between the furnace and the fibre and propose a functional form of the fibre temperature distribution. We utilise it with asymptotic mass, momentum, and evolution equations for free surfaces already available in the literature to describe the process of fibre drawing. By doing so, the complex heat exchange problem between the fibre and the furnace need not be solved. The numerical results of the whole asymptotic model overall agree well with experimental data available in the literature, both for the case of annular capillaries and for the case of holey fibres.

Coastal inundation is recently requiring a significant attention worldwide. The increasing frequency and intensity of extreme events (sea storms, tsunami waves) are highly stressing the coastal envi-ronments, e.g. endangering a large number of residential areas, ecosystems, tourist facilities, and also leading to potential environmental risks. Predicting such events and the generated coastal flooding is thus of paramount importance and can be reached by exploiting the potential of different tools, like remote sensors and numerical modeling. To this aim, a combination is possible between marine radars and wave-resolving propagation models. While instruments like X-band radars are able at precisely reconstructing both wave field and bathymetry within a coastal area that is some kilometers offshore, wave-resolving Boussinesq-type models can reproduce the wave propagation in the nearshore and the consequent coastal flooding. The present work illustrates the reconstruc-tion of coastal data (wave field and seabed depth) conducted using radar signals and a specifically suited data processing, named “Local Method”, and the use of such coastal data to run numerical simulations of wave propagation (using the FUNWAVE-TVD solver) aimed at reproducing coastal inundation over different scenarios. Such scenarios are built using two different European beaches, i.e. Senigallia (Italy) and Oostende (Belgium), and three different directional spreading values, to evaluate the performances in case of either long- or short-crested waves. The overall validation of the methodology, in terms of maximum inundation, shows good performances, especially in case of short-crested wind waves. Furthermore, the application on the Oostende beach demonstrates that the present methodology might work only using open-access tools, i.e. an easy investigation of the coastal inundation and a potential low-cost integration into early warning systems.

In this paper, we present an experimental procedure to enhance the dimensional accuracy of fabrication via Stereolithography (SLA) of features at the micro-scale. Using a custom benchmark part, deviations in feature dimensions (micro-pores diameters and depths) were detected and measured by confocal microscopy. Samples characterization and experimental observations allowed the identification of inaccuracy sources, mainly due to the laser beam scanning strategy and to the incomplete removal of uncured liquid resin in post-processing (i.e., IPA washing). As a technology baseline, the measured dimensional errors on pores diameters were up to -46%. A compensation method of the nominal laser spot diameter (85m) was defined and implemented resulting in relevant improvements in dimensional accuracy of 9.8% and 11.3% on full-open pores diameter and depth, respectively. Further investigation was performed on a customized test part to adjust the calibration procedure. The measurements revealed that the estimate of the laser beam spot size is 968m. Measurements on micro-pores having different sizes revealed that a constant compensation parameter (i.e., C=85, 96, 120m) is not fully effective at the micro-scale, where average errors still remain at -24%, -18.8%, and -16% for compensations equals to 85, 96 and 120m, respectively. A further experimental campaign allowed the identification of an effective nonlinear compensation law where the compensation parameter depends on the micro-feature size C= f (D). Results show a sharp improvement in dimensional accuracy on micro-pore fabrication, with errors consistently below +8.2%. The proposed compensation method can be extended for the fabrication of any micro-features without restrictions on the specific technology implementation. Concerning the inaccuracy introduced by the laser path, experimentation with a customized part allowed the optimization of the part orientation to reduce the errors and their differences along the X and Y machine axes.

Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

A number of decision support tools facilitating the use of Electric Vehicles (EVs) have been recently developed. Due to the EVs’ limited autonomy, routing and path planning are the main challenges treated in such tools. Specifically, determining at which Charging Stations (CSs) to stop, and how much the EV should charge at them is complex. This complexity is further compounded by the fact that charging times depend on the CS technology, the EV characteristics, and follow a nonlinear function. Considering these factors, we propose a path planning methodology for EVs with user preferences, where charging is performed at public CSs. To achieve this, we introduce the Electric Vehicle Shortest Path Problem with time windows and user preferences (EVSPPWP) and propose an efficient solution algorithm for it. Given an origin and a destination, the algorithm prioritizes CSs close to Points of Interest (POIs) that match user inputted preferences, and user-defined time windows are considered for activities such as lunch and spending the night at hotels. The algorithm produces flexible solutions by considering clusters of charging points (CPs) as separate CSs. Furthermore, the algorithm yields resilient paths by ensuring that recommended paths have a minimum number of CSs in their vicinity. The main contributions of our methodology are: modeling user-defined time windows, including user-defined weights for different POI categories, creating CSs based on clusters of CPs with sufficient proximity, using resilient paths, and proposing an efficient algorithm for solving the EVSPPWP. To facilitate the use of our methodology, the algorithm was integrated into a web interface. We illustrate the use of the web interface, giving usage examples and comparing different settings.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to investigate the comparison among pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were perfomred to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 x 109/ L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, an higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS ( p = 0.034) and OS ( p= 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as an independent and significant predictor of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

Human arteries show structural and functional peculiarities according to the nutrient and oxygen needs of a specific vascular district. This architectural heterogeneity is reflected in the pathological setting of cardiovascular diseases (CVDs). Indeed, the responsiveness to cardiovascular risk factors, the morphological and molecular patterns are discriminating factors among CVDs affecting different vascular beds. Micro-RNAs (miRNAs) are endogenous regulators of gene expression and fine tuners of vascular cell differentiation, thus these non-coding RNAs can modulate the arterial heterogeneity. The identification of a miRNA signature artery-specific would be promising in the therapy of CVDs, especially in frail elderly patients. In the present review we will provide a concise description of the arterial tree heterogeneity on structural and cellular basis, mainly in the pathological context. Secondly, we will address the miRNA potential as crucial mediators of arterial heterogeneity focusing on abdominal aorta and femoral artery, with the final goal of strengthening the search of more targeted therapies in CVDs and stratification approaches in frail elderly patients.

Electric Vehicles (EVs) are increasing the interdependence of transportation policies and the electricity market. EMMEV (Electricity Market Model with Electric Vehicles) is an experimental agent-based model that analyses how carbon reduction policy in transportation may increase number of Electric Vehicles and how does that would influence on the electricity price. Agents are ESCOs (Energy Service Providers) which can distribute fuels and their objective is to maximize their profit. In this paper, EMMEV is used to analyze the impacts of the LCFS (Low Carbon Fuel Standard), a performance-based policy instrument, on electricity prices and EV sales. The agents in EMMEV/regulated parties in LCFS should meet a certain CI (Carbon Intensity) target for their distributed fuel. In case, they cannot meet the target, they should buy credit to compensate for their shortfall and if they exceed, they can sell their excess. The results, considering the assumptions and limitations of the model, show that the banking strategy of the agents contributing in the LCFS might have negative impact on penetration of EVs, unless there is a regular Credit Clearance to trade credits. It is also shown that the electricity price as result of implementing the LCFS and increasing number of EVs has increased between 2–3 percent depending on banking strategy.

The COVID-19 pandemics has had an unprecedented global impact, and the COVID-19 mass vaccination campaign has been commonly regarded as crucial to overcome the pandemics. Since all-cause mortality is the best way to measure the consequences of a health intervention, the present study was devised to analyze the all-cause mortality data of the United Kingdom (UK), which are made publicly available broken down by vaccination status. Data from April 2021 to May 2023 were retrospectively collected and analyzed according to age groups and vaccination status and the Standardized Mortality Ratio (SMR) for all-cause mortality and for non-COVID-19 were calculated in comparison to the corresponding unvaccinated groups. Results show that, since an age group dependent date, the all-cause mortality SMRs were increasing in any of the age groups considered. Initially, the all-causes death SMRs were less than 1 for all age groups, but due to their growth, for the age groups 18-39, 80-89 and 90+ years by a certain date they exceeded the reference value. For the other age groups, as long as the trend is maintained, it is possible to predict the date in which the SMR would reach the value 1. Non-COVID-19 SMR values show a very similar trend. Their initial values much lower than 1 suggest the presence of significant biases in the ONS dataset which lead to an underestimation of the risks for those vaccinated, as it is not plausible that the vaccine protects from causes other than COVID-19. The finding that all-cause mortality SMRs in vaccinated in comparison to unvaccinated people increases over time requires careful examination to understand the underlying factors. Meanwhile, the other major countries should undertake a systematic collection of all-causes mortality broken down by vaccination status, and should be implemented a moratorium of the promotion of mass vaccination campaigns.

The paper deals with the Compound Inverse Rayleigh distribution, shown to constitute a proper model for the characterization of the probability distribution of extreme values of wind-speed, a topic which is gaining growing interest in the field of renewable generation assessment, both in view of wind power production evaluation and the wind-tower mechanical reliability and safety. The first part of the paper illustrates such model starting from its origin as a generalization of the Inverse Rayleigh model - already proven to be a valid model for extreme wind-speeds - by means of a continuous mixture generated by a Gamma distribution on the scale parameter, which gives rise to its name. Moreover, its validity to interpret different field data is illustrated, also by means of numerous numerical examples based upon real wind speed measurements. Then, a novel Bayes approach for the estimation of such extreme wind-speed model is proposed. The method relies upon the assessment of prior information in a practical way, that should be easily available to system engineers. In practice, the method allows to express one’s prior beliefs both in terms of parameters, as customary, and/or in terms of probabilities. The results of a large set of numerical simulations – using typical values of wind-speed parameters - are reported to illustrate the efficiency and the accuracy of the proposed method. The validity of the approach is also verified in terms of its robustness with respect to significant differences compared to the assumed prior information.

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.

The extensive use of rare earth elements (REEs) in a number of technologies is expected to impact on human health, including occupational REE exposures. A body of experimental evidence on REE-associated toxicity has been accumulated in recent decades. Unlike experimental studies, the consequences of REE exposures to human health have been subjected to relatively fewer investigations. Geographical studies have been conducted on residents in the Chinese REE mining districts, reporting on REE bioaccumulation, and associations between REE residential exposures and adverse health effects. A more limited series of studies has been focused on occupational REE exposures, such as movie operator (with occurrence of cerium aerosol) with the observation of pneumoconiosis and lung fibrosis. Similar effects have been reported in case reports for other workers, such as a lens grinder and a printer exposed to carbon-arc lamp emission. As for the occupations related to REE mining and processing, REE bioaccumulation in scalp hair and excess REE urine levels were reported. A study was devoted to workers employed in e-waste separation, showing alterations of several plasma markers. As for other REE occupational exposures, mention should be made of: a) mechanical workshops, with exposures to diesel exhaust microparticulate (containing nanoCeO₂ as a catalytic additive) and, b) production and manufacture of REE supermagnets for hybrid engines and wind turbines. Diesel exhaust microparticulate has been studied in animal models, leading to evidence of several pathological effects in animals exposed by respiratory or systemic routes. As for supermagnet production and manufacture, a body of literature is reviewed of experimental studies, and of human exposure studies showing several pathological effects of static magnetic fields, warranting further investigations.

This paper describes different variants of broadband and simple attenuator modules for beamforming applications, based on Radio Frequency Micro Electro-Mechanical Systems (RF-MEMS), framed within Coplanar Waveguide (CPW) structures. The modules proposed in the first part of this work differ in their actuation voltage, topology, and desired attenuation level. Fabricated samples of basic 1-bit attenuation modules, characterized by a moderate footprint of 690 x 1960 µm2 and aiming at attenuation levels of -2, -3 and -5 dB in the 24.25-27.5 GHz range, are presented in their variants featuring both low actuation voltages (5-7 V) as well as higher values (~ 45V), the latter ones ensuring larger mechanical restoring force (and robustness against stiction). Beyond the fabrication non-idealities that affected the described samples, the substantial agreement between simulations and measurement outcomes proved that the proposed designs could provide precise attenuation levels up to 40 GHz, ranging up to nearly -3 dB and -5 dB for the series and shunt variants, respectively. Moreover, they could be effective building blocks for future wideband and reconfigurable RF-MEMS attenuators. In fact, in the second part of this work, combinations of the discussed cells and other configurations meant for larger attenuation levels will be investigated.

Many metabolic processes at the molecular level support both viral attack strategies and human defenses during Covid-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021-2023) from PubMed reporting the discovery of hub-nodes specific for the liver during covid-19, identifying 142 hub-nodes. They are highly connected proteins from which to get deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to get by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein bio-synthesis. We used the SARS2-Human-Proteome Interaction Database (33,791 interactions), de-signed by us with BioGRID data to implement a reverse-engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins di-rectly involved in Covid, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary-topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs.

Abstract Precision medicine is essentially based on reliable and non-invasive biomarkers. Aim of this review has been to describe the newest biomarkers in the field of kidney transplantation and the kidney rejection, one of the commonest and severe complications. Standard of care tools to identify acute rejection are largely full of errors and of drawbacks. In recent years new and reliable biomarkers have been found. They are avoid of risks, non-invasive and able to detect rejection even in those frequent cases in which acute rejection are clinically asymptomatic and not otherwise identifiable. In recent years several biomarkers have been identified. Very recently have been found new relevant biomarkers able to diagnose rejection with high positive predictive value and low negative predictive value. These are the donor derived cell free DNA found in the recipient, the gene expression profile of the donor found in the recipient and the urinary cytokines that express modification in the graft tissue. The aim of this study has been to find the most recent findings in the literature on this topic and to describe the utility and possible limitation of such new biomarkers on kidney rejection.

Exoskeleton robots are a rising technology in industrial contexts to assist humans in onerous applications. Mechanical and control design solutions are intensively investigated to achieve a high performance human-robot collaboration (e.g., transparency, ergonomics, safety, etc.). However, the most of the investigated solutions involve high-cost hardware, complex design solutions and standard actuation. In the presented work, an industrial exoskeleton for lifting and transportation of heavy parts is proposed. A low-cost mechanical design solution is proposed, exploiting compliant actuation at the shoulder joint to increase safety and transparency in human-robot cooperation. A hierarchic model-based controller is then proposed (including the modeling of the compliant actuator) to actively assist the human while executing the task. An inner optimal controller is proposed for trajectory tracking, while an outer fuzzy logic controller is proposed to online deform the task trajectory on the basis of the human’s intention of motion. A gain scheduler is also designed to calculate the optimal control gains on the basis of the performed trajectory. Simulations have been performed in order to validate the performance of the proposed device, showing promising results. The prototype is under realization.

In this work a new method is proposed to tackle down the multiple objective optimization problem of the calculation of cation distribution in spinels structure, through the difference of intensity ratios between experimental and calculated intensities of cation sensitive Bragg planes, by introducing a new factor, Rabs, in Bertaut method. This factor is introduced as the sum of absolute R factors, and it is minimized by varying cation distribution. To test this method aluminate manganese spinel where synthesized though modified Pechini method and characterized though XRD. The results show to be in agreement with literature for the aluminum inversion in tetrahedral sites, which is near to the reported value of 10%. Also, it was noticed that the manganese atoms are present in octahedral sites with a mixed valence state of +2 and +3. Which might be an indicator that oxygen vacancies are present in the structure, so the vacancies value of oxygen is proposed considering the total charge of cations and thus proposing the value of 3.678 mol per formula unit of the spinel, thus having the next stoichiometry considering normalized Al and Mn, MnAl2O3.678. Finally, the last cation distribution proposed was [Mn0.867^(+2) Al0.129^(+3) ][Mn0.034^(+2) Mn0.098^(+3) Al1.871^(+3) ] O3.678 with a Rabs factor value of 0.6466, which considers the cation distribution and oxygen vacancies.

What is the function of cognition? On one influential account, cognition evolved to co-ordinate behaviour with environmental change or complexity (Godfrey-Smith 1996). Liberal interpretations of this view ascribe cognition to an extraordinarily broad set of biological systems – even bacteria, which modulate their activity in response to salient external cues, would seem to qualify as cognitive agents. However, equating cognition with adaptive flexibility per se glosses over important distinctions in the way biological organisms deal with environmental complexity. Drawing on contemporary advances in theoretical biology and computational neuroscience, we cash these distinctions out in terms of different kinds of generative models, and the representational and uncertainty-resolving capacities they afford. This analysis leads us to propose a formal criterion for delineating cognition from other, more pervasive forms of adaptive plasticity. On this view, biological cognition is rooted in a particular kind of functional organisation; namely, that which enables the agent to detach from the present and engage in counterfactual (active) inference.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

Semi-supervised consensus clustering is a promising strategy to compensate for the subjectivity of clustering and its sensitivity to design factors, with various techniques being recently proposed to integrate domain knowledge and multiple clustering partitions. In this article we present a new approach that makes double use of domain knowledge, namely to build the initial partitions as well as to combine them. In particular, we show how to model and integrate must-link and cannot-link constraints into the objective function of a generic consensus clustering (??) framework that maximizes the similarity between the consensus partition and the input partitions, which have, in turn, been enriched with the same constraints. In addition, borrowing from the theory of functional dependencies, the integrated framework exploits the notions of deductive closure and minimal cover to take full advantage of the logical implication between constraints. Using standard UCI benchmarks, we found that the resulting algorithm, termed ??? (double-Constrained Consensus Clustering), was more effective than plain ?? at combining base constrained partitions. We then argue that ??? is especially well-suited to profiling counterfeit e-commerce websites, because constraints can be acquired by leveraging specific domain features, and demonstrate its potential for detecting affiliate marketing programs. Taken together, our experiments suggest that ??? makes the process of clustering more robust and able to withstand changes in clustering algorithms, datasets, and features, with a remarkable improvement of average performance.

This article offers a theoretical framework to contextualise the concept of "Safety Culture" in the field of public safety and Disaster Risk Reduction (DRR), with the aim of supporting its understanding and measurement in our communities and finally attaining more disaster resilient societies. The work discusses the role of cultural dimensions in risk management and DRR and highlights the relevance of building knowledge and practices based on the consideration of culture and cultural variability in all phases of the risk management process. After an overview of the Safety Culture concept, including its origins, developments and applications, the text explores the transferability of this concept to the context of public safety. Then, based on the existing Safety Culture models, metrics and indicators from other sectors, the paper proposes an original definition of Safety Culture for the DRR context, shaped on a series of elements and dimensions specifically outlined for this context. Finally, the expected benefits of the application of Safety Culture concepts and techniques for further advances in DRR is discussed.

Here we report recent evidence of the presence of Eurasian otter (Lutra lutra) in the Mercure-Lao River valley, an area of great ecological interest situated in South Italy for which the last otter reports referred to spraints collected in 2002. This work contains information and a selection of photographs of otter footprints and spraints found from October 2005 to January 2019, and photographs of both a cub and an adult otter from the Mercure-Lao River area.

The purpose of this study is to improve the performance of walls under out-of-plane loads, particularly when subjected to the hammering action of the floors. The idea behind the paper is to provide the masonry walls with a device that behaves like a buttress, without having to build a traditional buttress. The solution presented here consists of a mechanical coupling between the three-dimensional net of steel ribbons of the CAM system and the CFRP strips. Since the steel ribbons of the CAM system have a pre-tension, the mechanical coupling allows the steel ribbons to establish a semi-rigid transverse link between the CFRP strips bonded on two opposite sides of a wall. Therefore, two vertical CFRP strips tied by the steel ribbons behave like the flanges of an I-beam and the flexural strength of the ideal I-beam counteracts the out-of-plane displacements of the wall. The experimental results showed that the combined technique inherits the strong points of both constituent techniques: the delamination load is comparable to that of the specimens reinforced with the CFRP strips and the overall behavior is ductile as for the specimens reinforced with the CAM system. They also allowed us to design a more performing combined technique.

The present paper deals with the retrofitting of unreinforced masonry (URM) buildings, subjected to in-plane shear and out of-plane loading when struck by an earthquake. After an introductive comparison between some of the latest punctual and continuous active retrofitting methods, the authors focused on the two most effective active continuous techniques, the CAM system and the Φ system, which also improve the box-type behavior of buildings. These two retrofitting systems allow us to increase both the static and dynamic load-bearing capacity of masonry buildings. Nevertheless, information on how they actually modify the stress field in static conditions is lacking and sometimes questionable, in the literature. Therefore, we performed a static analysis in the plane of Mohr/Coulomb, with the dual intent to clarify which of the two is preferable under static conditions and whether the models currently used to design the retrofitting systems are fully adequate.

The bivalve mollusc Pinna nobilis, endemic to the Mediterranean Sea, since 2016 is vanishing from the whole basin because of an infection by multiple pathogens that caused mass mortality events. In the Eastern Mediterranean some little populations seem to be resistant to the infection. These individuals could represent the only possibility for the species to recolonize now desert habitats. Thus, according to the recommendations of IUCN, the looking for living specimens of P. nobilis is a priority. As a result of a monitoring activity carried out in 2022-2024, along the Ionian cost of Apulia, in Southern Italy, the species has completely disappeared leaving only empty shells. Concurrent to the vanishing of P. nobilis, its congeneric P. rudis, resistant to the infection, seems to be taking advantage, becoming more common and colonizing habitats once exclusive of P. nobilis. In fact, from different areas of the Mediterranean, the sightings of P. rudis are increasing, together with the discovering of individuals exhibiting morphological traits that are a mixing between the two species. In some cases, these morphological features are not easy to detect, anyway the presence of these hybrids, resistant to the infection, is important for the conservation of the species.

Object segmentation is still considered a challenging problem in autonomous driving, particularly in consideration of real world conditions. Following this line of research, this paper approaches the problem of object segmentation using LiDAR-camera fusion and semi-supervised learning implemented in a fully-convolutional neural network. Our method is tested on real-world data acquired using our custom vehicle iseAuto shuttle. The data include all-weather scenarios, featuring night and rainy weather. In this work, it is shown that LiDAR-camera fusion with only a few annotated scenarios and semi-supervised learning, it is possible to achieve robust performance on real-world data in a multi-class object segmentation problem. The performance of our algorithm is measured in terms of intersection over union, precision, recall and area-under-the-curve average precision. Our network achieves 82% IoU in vehicle detection in day fair scenarios and 64% IoU in vehicle segmentation in night rain scenarios.

The paper deals with the modelization and optimization of an integrated multi-component energy system. On-off operation and presence-absence of components must be described by means of binary decision variables, besides equality and inequality constraints; furthermore, the synthesis and the operation of the energy system should be optimized at the same time. In this paper a hierarchical optimization strategy is used, adopting a genetic algorithm in the higher optimization level, to choose the main binary decision variables, whilst a MILP algorithm is used in the lower level, to choose the optimal operation of the system and to supply the merit function to the genetic algorithm. The method is then applied to a distributed generation system, which has to be designed for a set of users located in the center of a small town in the North-East of Italy. The results show the advantage of distributed cogeneration, when the optimal synthesis and operation of the whole system are adopted, and significant reduction in the computing time by using the proposed two-level optimization procedure.