Bio-separation of natural molecules as well as clinical compounds has been constantly developed in last decades. Several techniques are available but the majority of them presents drawbacks such us impossibility to be applied for industrial purposes. The main limitations for the scaling up are high costs and the fact that the devices work with microfluid dynamics. Nevertheless, magnetic bio-separation is considered the most prone to be used for large scale applications. Herein, we propose a simple magnetic separation method that is not based on microfluid dynamics, can work in a continuous- and high-flow rate and can be easily automated in order to be used for standard separation purposes. It is based on the use of an anisotropic flexible ferric magnetic strip, Teflon hoses and a pumping device. We show the modelling of the separation process along with an experimental test on iron oxide magnetic particles. The results showed that it is possible to remove, and separately collect, more than 92% of magnetic particles from a liquid solution of 100 ml in roughly 15 minutes.

Abstract: Nonalcoholic fatty liver disease, characterized by the lipid accumulation within hepatocytes exceeding 5% of liver weight, is strictly related to metabolic disorders and to obesity and diabetes and represents a health emergency worldwide. Being not available any standard therapy for NAFLD, a key role is ascribed to lifestyle intervention including phytonutrient intake to prevent NAFLD development and progression. We have used a rat model of NAFLD to evaluate the effect of dietary supplementation with red tomato and golden tomato, patented mix of fruit with different degrees of ripeness, particularly rich in naringenin and chlorogenic acid, after steatosis development. We have assessed the ef-fects on body weight, metabolic profile, and hepatic steatosis and a correlation between the amelioration of all the parameters and the liver gene expression was evidenced. We found that the genes mainly up regulated by tomatoes administration were HNF4, Lepr and GK, able to condition metabolic homeostasis. Our results suggest that there is a role for red and golden tomatoes, dietary intake as a nutraceutical approach of NAFLD prevention and therapy.

Despite being stored at 113 K and atmospheric pressure, LNG cold potential is not exploited to reduce green ships’ energy needs. An innovative system based on three Organic Ranking Cycles integrated into the regasification equipment is proposed to produce additional power and recover cooling energy from condensers. A first-law analysis identified ethylene and ethane as suitable working fluids for the first and the second ORC making available freshwater and ice. Propane, ammonia and propylene could be arbitrarily employed in the third ORC for air-conditioning. An environmental analysis that combines exergy efficiency, ecological indices and hazard aspects for marine environment and ship’s passengers, indicated propylene as safer and more environmentally friendly. The exergy analysis confirms more than 20% of the LNG potential can be recovered from every cycle to produce a net clean power of 76 kW, whereas 270 kW can be saved by recovering condensers' cooling power to satisfy some ship needs. Assuming the sailing mode, a limitation of 162 kg in LNG consumptions was determined, avoiding the emission of 1584 kg of CO2 per day. Marine thermal pollution is reduced by 3.5 times by recovering the working fluids' condensation heat for the LNG pre-heating.

Passive microwave measurements have been available on satellites dating back to the 1970s on research satellites flown by the National Aeronautics and Space Administration (NASA). Since then, several other sensors have been flown to retrieve hydrological products for both operational weather applications (e.g., the Special Sensor Microwave/Imager–SSM/I; the Advanced Microwave Sounding Unit–AMSU) and climate applications (e.g., the Advanced Microwave Scanning Radiometer–AMSR; the Tropical Rainfall Measurement Mission Microwave Imager–TMI; the Global Precipitation Mission Microwave Imager–GMI). Here the focus is on measurements from the AMSU-A, AMSU-B and Microwave Humidity Sounder (MHS). These sensors have been in operation since 1998 with the launch of NOAA-15, and are also on board NOAA-16, -17, -18, -19 and the MetOp-A and -B satellites. A data set called the “Hydrological Bundle” is a Climate Data Record (CDR) that utilizes brightness temperatures from Fundamental CDRs to generate Thematic CDRs (TCDR). The TCDR’s include: Total Precipitable Water (TPW), Cloud Liquid Water (CLW), Sea-Ice concentration (SIC), Land surface temperature (LST), Land surface emissivity (LSE) for 23, 31, 50 GHz, rain rate (RR), snow cover (SC), ice water path (IWP), and snow water equivalent (SWE). The TCDR’s are shown to be in general good agreement with similar products from other sources such as the Global Precipitation Climatology Project (GPCP) and the Modern-Era Retrospective Analysis for Research and Applications (MERRA-2). Because of the careful intercalibration of the FCDR’s, little bias is found among the different TCDR’s produced from individual NOAA and MetOp satellites, except for normal diurnal cycle differences.

The Active Distribution Networks (ADNs) are Multi-Input Multi-Output (MIMO) systems with coupled dynamics which cause interactions among the control loops of the Distributed Energy Resources (DERs). This undesired effect lead to performance degradation in the voltage control. To mitigate the effects of these unavoidable coupling, the present paper proposes a systematic design procedure based on the analysis of the interaction's sources. In details, each DER is equipped with a double loop PI to control the active and reactive powers output by the Voltage Source Converter (VSC) which connects the DER to the network's node. Furthermore, to guarantee Ancillary Services (ASs), the two loops are coupled by a simple mechanism of cooperation of the active power to voltage regulation realized by a filtered droop law. To achieve voltage regulation with reduced loop interactions, the PI parameters and the filter's pulse are designed according to a two sequential steps procedure based on the (Internal Model Control) IMC technique. Simulation studies are finally presented to demonstrate that the proposed design method achieves both reduction of the loop interaction and robust voltage control in presence of model parameter uncertainty in the MIMO model.

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on Electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. The study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation.

Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process. The benefits offered by the LIF experimental technique have been demonstrated and some frequent problems in its application analysed. The mixing time results for configurations with and without baffles for three types of impellers and four different rotational speeds have been presented. The false shorter mixing times in the non-baffled configurations have been observed and this phenomena explained by the existence of two segregated zones in the reactor and confirmed by additional experiments. The precise measurements in these cases have been shown as difficult using the LIF technique, particularly for higher rpms. The experimental data has been compared to the preliminary simulation results obtained from the Smoothed Particle Hydrodynamics method and the standard k-ε turbulence model with the modest success. The shortcomings of the SPH model have been recognized and the directions for the future work discussed.

Abstract: Rice is one of the most important food crops in sub-Saharan Africa. Climate change, variability, and economic globalization threaten to disrupt rice value chains across the subcontinent, undermining their important role in economic development, food security, and poverty reduction. This paper maps existing research on the vulnerability of rice value chains, synthesizes the evidence and the risks posed by climate change and economic globalization, and discusses agriculture and rural development policies and their relevance for the vulnerability of rice value chains in sub-Saharan Africa. Important avenues for future research are identified. These include the impacts of multiple, simultaneous pressures on rice value chains, the effects of climate change and variability on parts of the value chain other than production, and the forms and extent to which different development policies hinder or enhance the resilience of rice value chains in the face of climatic and other pressures.

Arthroplasty is commonly performed to treat advanced osteoarthritis or other degenerative joint conditions, but it can also be considered for young patients with severe joint damage that significantly limits their functionality and quality of life. Young patients are still at risk of aseptic mobilization and bone resorption due to the phenomenon of stress-shielding that causes an uneven distribution of tensions along the femoral contact surface prosthesis. This phenomenon can be limited by appropriately choosing the material of the prosthesis or by varying its stiffness, making sure that its mechanical behavior simulates that of the femur as much as possible. The aim of this study is to evaluate the mechanical behavior of a prosthesis optimized both in shape and material and in comparing the results with a standard titanium prosthesis. Methods: Through three-dimensional modeling and the use of software finite element method (FEM) such as ANSYS we simulate the mechanical behavior of traditional prosthesis and prosthesis optimized topologically respecting the ASTM F2996-13 standard Results: With topological optimization there is a stress reduction from 987 Mpa to 810 Mpa with a mass reduction of 30%. With the use of carbon fiber, it is possible to further reduce stress to 509 Mpa. Conclusions: The reduction of stress on the femoral stem allows an optimal distribution of the load on the cortical bone thus decreasing the problem of stress-shielding.

MzSTools is a plugin for QGIS developed by the Institute of Environmental Geology and Geoengineering of the National Research Council (CNR-IGAG). The plugin has been designed as a set of practical and easy-to-use tools to carry out seismic microzonation (SM) studies, by producing standard compliant geographic database and maps, thus making them accurate, homogeneous and uniform for all municipalities in Italy. A geodatabase based on SQLite/SpatiaLite Relational Database Management System (RDBMS) has been designed to collect and store data related to elements such as: geognostic surveys; bedrocks and cover terrains; superficial and buried geomorphological elements; tectonic-structural elements; elements of geological instability such as landslide zones, liquefaction zones and zones affected by active and capable faults; homogeneous microzones in seismic perspective, microzones characterized by a seismic amplification factor. MzSTools assembles in a single software environment a set of useful tools in a configurable QGIS project template, comprising layers, symbol libraries, cartographic styles and print layouts for the SM maps. The plugin is open source and hosted on the GitHub platform, and available via the official QGIS plugins repository (https://plugins.qgis.org/plugins/MzSTools/).

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

in the following article I analyze the trend of cultural and creative employment in the Italian regions between 2004 and 2022 through the use of ISTAT-BES data. After presenting a static analysis, I also present the results of the clustering analysis aimed at identifying groupings between Italian regions. Subsequently, an econometric model is proposed for estimating the value of cultural and creative employment in the Italian regions. Finally, I compare various machine learning models for predicting the value of cultural and creative employment. The results are critically discussed through an economic policy analysis.

Classically the walk in biped robotics was obtained controlling balance during the whole step, i.e. guaranteeing that the pressure point under the soles always stayed in the polygon of the supporting feet. However, this assumed that the feet were able to transfer torque to the ground during the whole gait cycle. In spite of the fact that the amount of transferrable torque in the feet-ground contact is limited, it is possible only during some phases of the step, and the overall process is energetically inefficient. On the other side, starting from the passive motion of the rimless wheel falling on an inclined surface, and ending to the inverted pendulum with a compass, balance in the whole was proven in spite of dynamical instability inside each step. Along this line results of Foot Placement Estimation (FPE) in 2-D and 3-D showed how energy efficient walk was possible, emulating the human walk with a free fall on the swing foot and energy restitution at the foot collision with the ground for the next step. This model assumes pointy feet, so without torque transfer to the ground. In the realm of FPE, in previous papers the present author adopted the 3-D inverted pendulum in polar coordinates (Spherical Inverted Pendulum - SIP) to introduce omnidirectional walks with arbitrarily changing characteristics. No torque control was used during the step, i.e the pendulum was always in free fall at each step, the only control actions were at the beginning of the next step. These actions are: the change of angular velocities at the start of a new step, with respect to those given after the collision (emulating the torque action in the brief double stance period), to recover for the losses, and the preparation of the position in the frontal and sagittal planes of the swing foot for the next collision. The present paper improves this paradigm, proposing a general model to account for all characteristics of the biped and of the gait, with adding a minimum of dynamical complexity with respect to the SIP. This model allows, not only to walk omnidirectionally on a flat surface, but also to go up and down staircases.

(1) Background: Considering highly selected patients with ductal carcinoma in situ (DCIS), active surveillance is a valid alternative to surgery. Our study is aimed at showing the reliability of post-biopsy complete lesion removal, documented by mammogram, as additional criterion to select these patients. (2) Methods: 2173 Vacuum Assisted Breast Biopsies (VABB) documented as DCIS have been reviewed. Surgery has been performed in all cases. We retrospectively collected the reports of post-VABB complete lesion removal and the histological results of the biopsy and surgery. We calculated the rate of upgrade of DCIS identified on VABB upon excision for patients with post-biopsy complete lesion removal and for those showing residual lesion. (3) Results: We observed 2173 cases of DCIS: 408 classified as low grade; 1262 as intermediate grade; 503 as high grade. The overall upgrading rate to invasive carcinoma was 15.2% (330/2173). The upgrade rate was significantly lower (8.2%) when considering patients showing mammographically documented complete removal of the lesion. (4) Conclusion: The absence of mammographically documented residual lesion following VABB is associated to a lower upgrading rate of DCIS to invasive carcinoma on surgical excision and should be considered when deciding the proper management DCIS diagnosis.

Sorption of pure CO2 and CH4 and CO2/CH4 binary gas mixtures in amorphous glassy Poly(2,6-dimethyl-1,4-phenylene) oxide (PPO) at 35°C up to 1000 Torr is investigated. Sorption experiments were carried out using an approach that combines barometry with FTIR spectroscopy in the transmission mode to quantify the sorption of pure and mixed gases in polymers. The pressure range is chosen to prevent any variation of the glassy polymer density. The solubility within the polymer of the CO2 present in the gaseous binary mixtures is practically coincident with the solubility of pure gaseous CO2, up to a total pressure of the gaseous mixtures equal to 1000 Torr and for CO2 mole fraction of ~0.5 mol mol-1 and ~0.3 mol mol-1. The Non-Equilibrium Thermodynamics for Glassy Polymers (NET-GP) modelling approach has been applied to the Non-Random Hydrogen Bonding (NRHB) lattice fluid model to fit the solubility data of pure gases. We have assumed here that no specific interactions are occurring between the matrix and the absorbed gas. The same thermodynamic approach has been then used to predict the solubility of CO2/CH4 mixed gases in PPO resulting in a deviation lower than 9.5% from the experimental results for CO2 solubility.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

A Digital Twin (DT) refers to a virtual representation or digital replica of a physical object, system, process, or entity. This concept involves creating a detailed, real-time digital counterpart that mimics the behavior, characteristics, and attributes of its physical counterpart. DTs have the potential to improve efficiency, reduce costs, and enhance decision-making by providing a detailed, real-time understanding of the physical systems they represent. While this technology is finding application in numerous fields, such as energy, healthcare, transportation, it appears to be a key component of the digital transformation of industries. In this paper, we present the research results achieved by IoTwins, a European research project aimed at investigating opportunities and issues of adopting DTs in the fields of industrial manufacturing and facility management. Particularly, we discuss a DT model and a reference architecture for use by the research community to implement a platform for the development and deployment of industrial DTs in the cloud continuum. Guided by the devised architectures’ principles, we implemented an open platform and a development methodology to help companies build DT-based industrial applications and deploy them in the so-called Edge/Cloud continuum. To prove the research value and the usability of the implemented platform, we discuss a simple yet practical development use case.

Background: Open AI developed ChatGPT, a language model based on the GPT architecture, designed for text-based communication. Trained on diverse internet texts, ChatGPT generates contextually appropriate responses using machine learning. It understands input through analysis and context interpretation, generating coherent and contextually relevant responses. Interaction is possible through messaging platforms. Materials and Methods: In November 2023, we utilized ChatGPT 3.5, the default version at that time, to answer questions from the Italian National Residency Program Admission Tests (SSMs) of 2021, 2022, and 2023. The questions cover clinical, diagnostic, analytical, therapeutic, and epidemiological scenarios, sometimes accompanied by images. The study compared ChatGPT's answers to the official corrections on the Italian Ministry of University and Research (MUR) website. The scoring method used for evaluation was 1 point for correct answers, 0 points for unanswered questions, and -0.25 points for incorrect answers, reflecting the SSM test scoring system. Results: In summary, ChatGPT was tested with a total of 420 questions, 140 for each test. It achieved an overall accuracy of 80.48%, providing correct answers for 338 questions and incorrect answers for 82 questions. When faced with questions containing both text and images, it answered 55% correctly and 45% incorrectly. The model's performance varied over time, with an 82.14% accuracy rate in 2021 and 2022 (115 correct out of 140) and a 77.14% accuracy rate in 2023 (108 correct out of 140). Applying thisscoring method to the SSM test, ChatGPT would have scored 105 points in 2021 and 2022, and 100 points in 2023. Conclusions: ChatGPT has exhibited above-average performance in the last three SSM tests, highlighting its robust capability to interpret clinical scenarios and offer precise diagnostic and therapeutic guidance. Despite this, some limitations persist, notably the software's inability to interpret non-textual information.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.

Background: Swimming and, specifically, front crawl, can be included among the "overhead" sports. Overhead sports are a risk factor for some problems of the musculoskeletal system, especially the shoulder. The aim of the study was assessing the incidence of shoulder and neck pain in a Masters Swimming Team and its correlation with the crawl stroke. Methods: It is an observational study through video-analysis of the stroke and a questionnaire. The participants are 61 athletes of a Master team, whose prevailing training stroke was the front crawl were selected for the present study. Their stroke was analyzed during training by a go-pro camera mounted on a sliding trolley on a track, evaluating with their trainer their technical defects. A questionnaire about frequency of shoulder and neck pain during the last five years was administered to all the participants at the study. Results: From the questionnaire, 45 and 55 out of 61 athletes had suffered from shoulder pain and cervical pain, respectively. Both types of pain were correlated with the weekly swimming volume. The swimmers with hyperflexion of the wrist and prolonged internal rotation in the pulling phase had shoulder problems. Those who suffered from current shoulder pain reduced the underwater time. The four swimmers with an excessive body roll during breathing and those who kept their heads extended, reported cervical pain. Conclusions: Shoulder and neck pain could be prevented with the correction of specific technical errors in crawl stroke.

Patients with Multiple Myeloma have an increased susceptibility to severe infections due to several various factors, especially the high tumor burden. The use of the anti-CD38 monoclonal antibodies-based therapies has changed the frequency and epidemiology of infections. We report herein the safety profile of the pivotal clinical trials conducted with anti-CD38 mAbs (daratumumab and isatuximab) and anti-SLAMF7 mAbs (elotuzumab) that led to the approval of regimens employed today in NDMM and RRMM patients.

BACKGROUND Relaxin (RLX), a hormone-like molecule with pleiotropic effects, has been found to reduce matrix deposition and mediate collagen degradation in animal models of chronic liver injuries and might be considered as an adjuvant therapeutic agent for progressive liver diseases. AIMS In the present study, we evaluated whether RLX affects the development of liver fibrosis in an experimental mouse model of NASH in C57BL6 male mice fed with a methionine-choline deficient diet (MCD). Methods Mice were treated per os as we intended to assess the enteric absorption and bioavailability of orally administered RLX (RLX purified from pig ovaries, IBSA SA, Lugano, Switzerland). Mice were fed the MCD diet for 6 weeks. After the initial 3 weeks, one group received drinking water supplemented with RLX (25 mcg/ml) whereas the other continued to receive regular water. A third group of mice fed a regular diet served as control. After 3 additional weeks mice were anesthetized and sacrificed. Results A significant, reduced expression of the pro-inflammatory cytokines TNF-α and of relevant markers of active fibrogenesis and extracellular matrix deposition, Col1A1 and α-SMA, was observed in mice treated with RLX vs controls. RLX also induced a significant decrease of TIMP1 and an increase of both MMP 2 and 9 when evaluated by zymographic analysis in liver extracts. Conclusions Although preliminary pharmacokinetics experiments showed barely detectable amounts of RLX in the blood of mice treated per os, these data support the absorption of orally administered RLX and confirm its potential therapeutic use in the management of liver fibrosis.

In this paper we overview all analytical engineering solutions for corrosion problems in pressure vessels delivered over the past 60 years. We briefly detail strengths and weaknesses of existing approaches, thus demonstrating the need for novel uniform corrosion analysis methods for both current and new applications. To complement the review, we also present a new analytical model allowing to estimate the lifetime of pressured elastic vessels with mechanically assisted corrosion. Both internal/external pressure and internal/external corrosion are captured and dissolution driven corrosion is also considered. The readily implemented method improves existing analytical approaches and is shown to be effective for thin and thick shells, as well as various loading and corrosion intensity and geometrical conditions.

Optimization of post polymerization processing of polyolefin elastomers (POE) is of considerable industrial interest. To this aim, experimental determination and theoretical interpretation of the thermodynamics and mass transport properties of POE-solvent mixtures is relevant. Sorption behaviour of n-hexane vapour in a commercial propylene-ethylene elastomer (V8880 VistamaxxTM from ExxonMobil) is addressed here, determining experimentally the sorption isotherms at temperatures ranging from 115 to 140 °C and pressure values of n-hexane vapour up to 1 atm. Sorption isotherms have been interpreted with the Non-Random-Hydrogen-Bonding Equation of State model retrieving, from data fitting, the value of the binary interaction parameter for the n-hexane/V8880 system. Both the case of temperature-independent and of temperature-dependent binary interaction parameter have been considered. Sorption kinetics was also investigated at different pressures and has been interpreted using a Fick’s model determining values of the mutual diffusivity as a function of temperature and of n-hexane/V8880 mixture composition. From these values, n-hexane intra-diffusion coefficient has been calculated interpreting its dependence on mixture concentration and temperature by a semi-empiric model based on free volume arguments.

In implantology, among the key choices, to obtain predictable results, it’s essential to establish, using CBCT, the bone site where to insert the implants; these sites must be identified on the mucosa and secondarily, during the surgical phase, on the cortical bone. Surgical templates are a valid aid especially in complex cases which require sev-eral implants. In cases of single implant, on the other hand, surgical guides are rarely used and the implant is inserted freehand and the identification of the implant site on the oral mucosa is more difficult; for this reason the clinician uses the teeth in the arch as a ref-erence. This experimental study is based on the use of a thermo-printed mask, con-taining radiopaque references which, worn by edentulous patients during the execu-tion of the CBCT, helps to evaluate the identification of the implant sites on the patient when surgical guides are not used and the free hand technique is adopted. This method is certainly reserved for experienced operators capable of identifying the correct angle of the implants with the freehand technique. The level of experience remains fundamental in the clinician's decision whether or not to use surgical guides; in fact, doctors with little experience should use surgical guides even in the simplest cases to reduce the risk of error.

In implantology, among the key choices, to obtain predictable results, it is essential to establish, on the basis of radiographic examinations, the bone site where to insert the implants; these selected locations must be identified first on the mucosa and then on the cortical bone. Surgical guides represent a valid aid especially in complex cases with more than 3 or 4 implants, whereas in single implant cases they are rarely used. This study evaluates the clinical precision with which the implant sites, on the patient's mucosa, are identified in surgical procedures planned without any templates. The verification of this precision is carried out through thermo-printed templates with radiopaque references which could however help the clinician to identify these sites in a simple, rapid and economical way.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

(1) Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this study is to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. (2) The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett's formula. (3) Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. 14% of the sample (23 patients) showed a prolongation of the QTc interval. 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone: in 90% of these patients, a normalization in the QTc length was established. (4) This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of a careful electrocardiographic monitoring in methadone-treated patients.

Graphs are largely used in computer science to model relations, or associations, among entities the compose complex systems. More recently, they found a broad field of application in bioinformatics and medical informatics supporting modelling, analysis of many systems. The applications span from representing interactions among molecules within cells, to model the functions of the brains. In order to support research, algorithms from graph theory that are able to extract knowledge from network should be coupled to efficient visualisation techniques. Although the importance of such topic, we retain that many challenges should be faced in the futures, such as automated pathway and network layout to better match biologists’ needs, the developing of a standard able to give more and better choices to represent nodes, edges finally, the developing of automated mechanism able to improve the network navigation methods that help users manage large and complex networks with the goal to improve the usability.

In the following article, we estimate the Renunciation of Healthcare Services-RHS in Italian regions in the context of the Environmental, Social and Governance-ESG model during the period 2004-2022. The data were acquired from the ISTAT-BES dataset. The data were analyzed using the following econometric techniques: Panel Data with Fixed Effects, Panel Data with Random Effects, Pooled Ordinary Least Squares-OLS, Weighted Least Square-WLS,. Results show that RHS tends to growth with the E-Component, is negatively associated to the S-Component, and positively associate with the G-Component within the ESG model. Furthermore, a clusterization with the unsupervised k-Means algorithm is presented and the results are discussed with a confrontation between optimal and suboptimal k values optimized with the Silhouette Coefficient. Finally, a confrontation among eight different machine-learning algorithms is performed to predict the future value of RHS. Outcomes show that the Simple Regression Tree is the best predictive algorithm and that the level of RHS is predicted to growth on average of 4.4% for the Italian regions. Results are critically discussed.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

As of today, 20 disease modifying drugs (DMD) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgement and experience of neurologists and the evaluation of therapeutic response can only be obtained by monitoring clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, the aim of this study is to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing-remitting courses. These patients were characterized on the basis of their age, sex, presence of oligoclonal bands, therapy and MRI lesion load at onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data we generated a few simulation scenarios for each patient, including those who matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which really occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Timely and accurate identification of change detection for areas depicted on nautical charts constitutes a key task for marine cartographic agencies in supporting maritime safety. Such a task is usually achieved through manual or semi-automated processes, based on best practices developed over the years requiring a substantial level of human commitment (i.e., to visually compare the chart with the new collected data or to analyze the result of intermediate products). This work describes an algorithm that aims to largely automate the change identification process as well as to reduce its subjective component. Through the selective derivation of a set of depth points from a nautical chart, a triangulated irregular network is created to apply a preliminary tilted-triangle test to all the input survey soundings. Given the complexity of a modern nautical chart, a set of feature-specific, point-in-polygon tests are then performed. As output, the algorithm provides danger-to-navigation candidates, chart discrepancies, and a subset of features that requires human evaluation. The algorithm has been successfully tested with real-world electronic navigational charts and survey datasets. In parallel to the research development, a prototype application implementing the algorithm was created and made publicly available.

Regeneration of peripheral nerves depends on the ability of axons to navigate through an altered extracellular environment. It has been suggested that Schwann cells facilitate this process through their secretion of neuropeptides and proteases. Using the RT4-D6P2T Schwann cell line (RT4), we have previously shown that RT4 cultures endogenously express the neuropeptide PACAP, and respond to exogenous stimulation by inducing the expression of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) through PAC1 receptor activation. In this study, based on recent findings showing that doxycycline and minocycline act as positive allosteric modulators (PAMs) of the PAC1 receptor, we tested if treatment with these tetracyclines could induce the expression and activity of tPA and uPA in RT4 cells. Using ELISA and zymographic analyses, we demonstrate that doxycycline and minocycline reliably induce the secretion and activity of both tPA and uPA, which is paralleled by an increased expression levels, as shown by immunocytochemistry and Western blots. These actions were mediated, at least in part, by the PAC1 receptor, as PACAP6-38 mitigated tetracycline-induced expression and activity of tPA and uPA. We conclude that doxycycline and minocycline can act as PAMs of the PAC1 receptor to promote proteolytic activity in RT4 cells.

(1) Background: The interplay between coronavirus disease 2019 (COVID-19) and laryngeal cancer represents a substantial challenge for both patients and healthcare. To garner information on recent mortality data for laryngeal cancer, including during the COVID-19 pandemic, we analyzed real-world data from the US Centers for Disease Control and Prevention (CDC). (2) Methods: We searched the CDC WONDER on-line database 2018-2022 using with the ICD-10 code for laryngeal cancer (C32; malignant neoplasm of larynx). We also performed a sub-analysis between genders, and across ten-year age groups. Data were analyzed with one-way analysis of variance (ANOVA) and Tukey post-hoc test. (3) Results: The trend of age-adjusted mortality ×100,000 did not change significantly between 2018-2022 (p=0.553). Males had higher age-adjusted mortality rates (M/F ratios between 4.6 and 5.0), but no significant variation was found in both genders (males: p=0.676; females: p=0.596). Although the mortality rate remained unchanged in people aged 35-84 years, the variation reached statistical significance in those aged 85 or older (p=0.004), displaying significant increase in 2021 compared to 2018 (p=0.006) and 2019 (p=0.039). (4) Conclusions: The impact of the COVID-19 pandemic on mortality for laryngeal cancer seemed to be relatively modest in the general US population. Nevertheless, closer attention must be paid to older people, in whom the unfavorable consequences of misdiagnosis or mistreating can be exacerbated.

Over the years, network analysis became a promising strategy to analyze complex system, i.e. systems composed by a large number of interacting elements. In particular, multilayer networks have emerged as a powerful framework for modelling and analysing complex systems with multiple types of interactions. Network analysis can be applied to pharmacogenomics to gain insights into the interactions between genes, drugs, and diseases. By integrating network analysis techniques with pharmacogenomic data, the goal consists to uncover complex relationships and identify key genes to use in pathway enrichment analysis to figure out biological pathways involved in drug response and adverse reactions. In this study, we model omics, diseases and drugs data together through the multilayer network representation. Then, we mined the multilayer network with a community detection algorithm by obtaining top communities. After that, we used the identified list of genes from the communities to perform pathway enrichment analysis (PEA) to figure out the biological function affected form the selected genes. The results show that the genes forming the top community have the multiple roles through different pathways.

The following article analyzes Italian companies with more than 10 employees that use online sales tools. The data used were acquired from the ISTAT-BES database. The article first presents a static analysis of the data aimed at framing the phenomenon in the context of Italian regional disparities. Subsequently, a clustering with k-Means algorithm is proposed by comparing the Silhouette coefficient and the Elbow method. The investigation of the innovative and technological determinants of the observed variable is carried out through the application of a panel econometric model. Finally, different machine learning algorithms for prediction are compared. The results are critically discussed with economic policy suggestions.

In the following article I analyze the determinants of regular internet users in the Italian regions. The data is analyzed both in terms of static analysis and also through the application of the k-Means algorithm optimized with the Elbow method. Subsequently, an econometric model is presented for estimating regular internet users in the Italian regions based on variables that reflect the state of technological innovation and digital culture. The results are analyzed and discussed in light of the implications that digitalisation has for triggering economic growth.

In the following article I take into consideration the role of knowledge workers in the Italian regions. The analysed data refers to the ISTAT-BES database. The metric analysis consists of an in-depth analysis of the trends of the regions and macro-regions, followed by clustering with the k-Means algorithm, the application of machine learning algorithms for prediction, and the presentation of an econometric model with panel methods date. The results are also critically discussed in light of the North-South divide and the economic policy implications.

(1) Background: Overall survival of the patients with renal cell carcinoma (RCC) depends mostly on extra-renal extension, documented by the invasion of the pelvicalyceal system, or the perinephric/renal sinus fat or the renal vein/its segmental intraparenchymal branches. Staging may be challenging because of the high inter-observer variability. We have introduced a more accurate procedure to detect the extra-renal extension and, to possibly evaluate the impact of such more laborious approach, we have compared the RCC pathological staging obtained following both standard and modified procedures; (2) Methods: We selected 54 consecutive cases of RCC diagnosed 18 months before and 54 consecutive cases diagnosed 18 months after the introduction of the new method of sampling. Clinico-pathological characteristics have been statistically analyzed; (3) Results: Most of the features analyzed were non statistically significative, except the extra-renal invasion. More precisely, the occurrence of retrograde venous invasion was higher in the cases grossly approached with the more accurate method; (4) Conclusions: Extra-renal extension to intraparenchymal renal vein branches may be underestimated, leading to an inappropriate under-staging. Using more accurate staging procedures, to disclose the occurrence of intra-renal veins tumoral thrombosis, helps to better define the pathological stage, allowing patients to benefit of better fitting treatments.

Forest fires are part of a set of natural disasters that have always affected regions of the world typically characterized by a tropical climate with long periods of drought. However, due to climate change in recent years, other regions of our planet have also been affected by this phenomenon, never seen before. One of them is certainly the Italian peninsula, and especially the regions of southern Italy. For this reason, the scientific community, as well as remote sensing one, is highly concerned in developing reliable techniques to provide useful support to the competent authorities. In particular, three specific tasks have been carried out in this work: (i) fire risk prevention, (ii) active fire detection, and (iii) post-fire area assessment. To accomplish these analyses, the capability of a set of spectral indices, derived from spaceborne remote sensing (RS) data, is assessed to monitor the forest fires. The spectral indices are obtained from Sentinel-2 multispectral images of the European Space Agency (ESA), which are free of charge and openly accessible. Moreover, the twin Sentinel-2 sensors allow to overcome some restrictions on time delivery and observation repeat time. The performance of the proposed analyses were assessed experimentally to monitor the forest fires occurred in two specific study areas during the summer of 2017: the volcano Vesuvius, near Naples, and the Lattari mountains, near Sorrento (both in Campania, Italy).

Keywords: olfactory rehabilitation; chronic pain; fMRI;

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

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

This work deals with a systematic review of literature data concerning the theme of the integrated approach to occupational health and safety management, with particular reference to the programming of assistance plans, which guide the company's organizational choices also by aiming at the principles of the Total Worker Health. In the current regulatory framework on this issue, the UNI ISO 45001: 2018 standard assumes particular relevance, which defines the dynamic approach to occupational health and safety management systems, paying particular attention to external contextual factors that may influence corporate organizational decisions. The adoption of these systems is not mandatory, but allows companies to fulfill their duties in terms of health and safety at work, through an organizational approach aimed at awareness, involvement and participation of all subjects of the company prevention system, overcoming the phase of the mere technological and prescriptive approach, towards a holistic vision of prevention, which places the person at the center of preventive actions. In this context, the role of institutional networks and socio-economic partnerships assumes particular importance, in the activation of territorial assistance interventions to support companies for the improvement of risk management levels. To this end, the importance of verifying the effectiveness of assistance interventions emerges from the scientific debate, through the use of indicators such as quantitative ones for measuring the performance of all phases of the intervention with particular attention to the effects in terms of improved solutions developed.

This paper provides an exhaustive narrative review of third-generation antipsychotics (TGAs), focusing on aripiprazole, cariprazine, brexpiprazole, and lurasidone for managing substance-induced psychosis. It includes a comprehensive literature review to evaluate the efficacy and tolerability of these medications. The paper emphasizes the distinct challenges in treating substance-induced psychosis, which is a psychiatric condition triggered by the misuse or withdrawal of various substances, leading to symptoms like hallucinations and delusions, and is distinct from primary psychotic disorders. It underscores the potential of TGAs in addressing both psychotic symptoms and substance-related issues, while highlighting the need for more research on long-term effects and advocating for an integrated approach combining pharmacological and psychological interventions

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.

The paper aims to investigate on the determinants of the capital structure of the Italian SMEs and it is based on a large panel of Italian manufacturing SMEs observed in the years 2001-2013. The analysis achieves a comparative investigation between the capital structure of the firms belonging in the Southern region, the so-called Italian Mezzogiorno that is the slow growing area of the country, and the firms of the Center-northern region of Italy, that is the more developed area of the country. Fixed effect panel techniques applied to the several standard leverage models allows to reaffirm some distinctive features showing differences of the financial behavior of regional firms.

The processed tomato is one of the major food products of Italy and characterized today many Italian Regions, in northern and southern Italy, even though the firms in the industry have had difficulties, in recent years, due to an increase in the cost of raw materials. Furthermore, tomato processing firms are often characterized by significant investment in fixed assets and working capital, with an consequent increase in equity and/or debt financing, with consequent increasing of the risk of bankruptcy, as happens to many firms in the sector in recent years. The aim of the research is than to analyze the risk of bankruptcy of tomato processing companies applying financial ratios. To achieve this goal, the research consider the annual data of a sample of 17 tomato processing firms operating in the Inter Regional Interprofessional Organization “OI Pomodoro da Industria Nord Italia”; firms’ data are divided into still-active (not-distressed) and failed (distressed) firms, with the aim of analyzing the differences between financial data and management practices of the two groups of firms to evaluate the sustainability of the business cycle. The company data suggest that larger firms, with adequate financial structure, have been able to withstand the tomato market crisis in recent years, where distressed firms are on average smaller and suffer from a higher recourse to debt capital with lower profit margins than not-distressed firms. The research could then be applied by entrepreneurs, managers, bankers and public operator to define good practices of management to be achieved and measured with financial ratios even in order reduce the risk of distress for firms operating in tomato sector.

This study seeks to interrogate the degree to which lecturers and students of higher institutions in Nigeria perceive the role of lecturers doubling as parents under the term lecturenting, i.e., a coinage used to refer to a person who performs the dual roles of lecturing and parenting students of higher institutions. The study is based on Professor Obiora Ike’s ideology of communication of values, normally applicable to traditionally homes only. The research used a quantitative survey of 266 undergraduates and 109 lecturers, totaling 375 respondents from two purposively selected higher institutions in Nigeria, namely: Edo state University Uzairue and Federal Polytechnic Auchi, both in Etsako West Local Government Area of Edo state, Nigeria. A questionnaire with a set of nine semi-structured questions was used to obtain data from the students during the school semesters between July 15 and August 31, 2022. The study was based on the value theory. Findings indicate that lecturers frequently engage in lecturenting which helped improve the academic performance of students but shows that students do not want lecturenting on their behavioral change. The study concludes that the more lecturers engage in Lecturenting, the more positive impact it will have on their students. It is recommended that lecturers should engage in the practice of lecturenting as it helps to improve student academic performance and that students should perceive lecturenting as positive as well as be favorably disposed to it and approach their lecturers for counselling frequently.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

This review article is aimed at exploring the possibility of developing an integrated approach in the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and – as much as possible – minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproduction techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted integrated approach is still highly challenging. This article aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. Then, we focus on the prospect for a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miR in the patient, thus allowing a relatively fast, non-invasive way to perform such testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory complexities arising from such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

We have studied the stochastic processes A and B concerning fade durations due to rain, by simulating attenuation time series A(t) (dB) in the zenith paths of GeoSurf satellite constellations, at sites located in different climatic regions, with the Synthetic Storm Technique. Process B gives the statistics of outages (occurrences), process A gives the statistics of outage duration (fraction of time), for the same rain attenuation threshold A(t)&gt;S. The two processes are not independent, therefore, we have studied the relationship between their probabilities and defined a uniformity index 0&lt;U(S)≤1. U(S) is useful for comparing real cases – fade durations fragmented in many different intervals, with changing S and site – and the limiting case of all fades lasting the same time. As S increases, U(S) increases, approaching 1 at very large thresholds. These results should guide the designers of future GeoSurf satellite constellations to consider the impact of A(t) on the diverse communications services. Process B (occurrences) impacts on non–real time services, such as data delivery, more disturbed by the number of outages rather than by their duration. Process A (fraction of time) impacts on real–time services such as television, video conference etc., more disturbed by the duration of the outage.

Welding between two or more pieces of metal is a widely used practice in various fields of medicine such as dentistry which also makes use of the support of dental laboratories where complex welding procedures are applied. The welding techniques available today are many and also very different from each other; they often require very different background knowledge, just as the results obtained may differ. Welds can be made at various stages of making a product that will be used on the patient; for example some welds are made directly by the manufacturer during the industrial processing phase. We then move on to the more common welding techniques carried out in dental laboratories and finally we also arrive at the intraoral welding carried out by the clinician inside the patient's oral cavity. This enormous variety of conditions in which those who practice welding can find themselves presupposes the application of the most appropriate technique; this review looks at the different methods and fields of application.

This work attempted to fabricate superhydrophobic fabric via simple immersion technique. Textile fabrics were coated with silica nanoparticles prepared from tetraethoxysilane (TEOS) to obtain sufficient roughness with hydrophobic surface chemistry. Then the coated fabrics were treated with polydimethylsiloxane (PDMS) and aminopropyltriethoxysilane (APTES) to reduce the surface energy. The effects of PDMS concentration on the surface morphology and superhydrophobicity of as-prepared fabric were investigated. The morphology and the composition of superhydrophobic fabric was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDS) and Fourier transform infrared (FTIR) spectroscopy. The results revealed the formation of spherical silica nanoparticles with average particle size of 250 nm throughout the fabric surface. The possible interactions between silica nanoparticles and APTES, as well as the fabrics were elucidated. Investigating the hydrophobicity of fabrics via water contact angle (WCA) measurement showed that the treated fabric exhibits excellent water repellency with a water contact angle as high as 151° and a very low water sliding angle. It also found that the treated fabric maintained most of its hydrophobicity against repeated washing. The comfort properties of the obtained superhydrophobic fabrics in term of air permeability and bending length did not reveal any significant changes.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Background: Many clinical conditions are affected by meteorological factors and climate changes. Psychiatric disorders are large contributors to the global disease burden, but the literature on the impact of climate changes on mental health is limited. The aim of this study is to investigate the correlation between rising temperatures and admissions for acute exacerbations of psychiatric disorders. Methods: Data were collected for summer months of years 2013 to 2022. Mean monthly tempera-tures were obtained from the meteorological station of the Department of Physics of the Universi-ty of Turin. Data on patients admitted to the acute psychiatric unit of San Luigi Gonzaga Univer-sity Hospital (Turin, Italy) were extracted from the hospital registry. Linear regression analyses were used to investigate the correlation between temperature and number of admissions. Results: A total of 1600 admissions to our psychiatric ward were recorded. Mean monthly temper-ature and monthly number of admissions were directly correlated (P = 0.0020). The correlation between temperature and admissions was significant for the subgroup of admissions due to Bipo-lar Disorders (BD) (P=0.0011), but not for Schizophrenia (P=0.6070) (SCZ) or Major Depressive Disorder (MDD) (P=0.0588). Conclusions: These results confirm the impact of meteorological factors on mental disorders, and in particular on the course of BD. This provides new insights into etiopathological mechanisms and can contribute to improved follow up and relapse prevention.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

The emergence of Digital Twin (DT) technology is creating unique opportunities for human so-ciety in terms of real-time data transfer from the physical environment to its digital replica. DT technology has two-way interaction capabilities that enable data exchange between physical and virtual environments, creating bidirectional data flows. Progress has been made in different in-dustry sectors, but the Architecture, Engineering, Construction, and Operation (AECO) sector still requires further development. Recent studies have shown the potential for DT-based platform implementation in the lifecycle management of buildings and infrastructure. This paper examines the development and implementation of DT technology in the construction sector, identifying key definitions, enablers and use cases, while comparing its use with other industries and evaluating benefits and future potential.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

In this work, two plasmonic structures with two different periodic nanostructures (nanodisk and nanostrip arrays) separated from the gold layer by an ultrathin dielectric Al2O3 layer are proposed, and their optical properties are simulated as 3-dimensional models using COMSOL Multiphysics software tool. The optical responses, such as the amplification of the electric field and the scattering, absorption and extinction cross sections of the two structures, are investigated and compared. The results show that both structures show strong field enhancement in their gap layer, and the structure with the periodic array of metal nanodisks shows stronger field enhancement and larger absorption, extinction, and scattering cross sections in its dipole resonance wavelength, which is defined as a bright plasmonic mode. In addition, some weaker resonant modes are observed for both structures and the reason for their generation is dis-cussed. The analysis of different possible modes in such structures is crucial for their application in various fields.

The theory of harmonic based function is discussed here within the framework of umbral operational methods. We derive a number of results based on elementary notions relying on the properties of Gaussian integrals.

Aims: To report on the clinico-pathological features of a series of 12 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Methods and methods: All mucoepidermoid carcinomas diagnosed in the period 1990-2012 were retrieved, the original histological preparations were reviewed to confirm the diagnosis, and from selected cases, showing exclusive intra-cystic neoplastic component, additional sections were cut at 3 subsequent 200m intervals and stained with Hematoxylin-Eosin, PAS and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Also, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of 5 years. The neosplasm were located in the hard palate (9 cases), the soft palate (2), the cheeck (2) and the retromolar trigone (1). In all instances histological examination was revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue and no solid areas or infiltrating tumour clusters were detected. Conservative surgical resection was performed in all cases and no recurrences or nodal metastases were observed during the follow up period. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumours. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic fashion and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues or metastasize.

The integral extraction via microwave-assisted hydrodiffusion and hydrodistillation of water-soluble bioproducts contained in the peel of Opuntia ficus-indica white and red cultivars harvested in Sicily, affords red and stable aqueous extracts mostly containing valued betanin, pectin and biophenols. Potentially useful as nutraceutical products, these aqueous extracts are a source of valued ingredients in high demand for a number of important food, cosmetic, beverage and nutraceutical applications.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

This study investigates the impact of experienced contact on prejudiced attitudes toward individuals with intellectual disabilities (ID), examining beliefs in a just world (BJW) and social dominance orientation (SDO) as potential serial mediators. Data were collected from 224 university students (M = 23.02, SD = 2.48). Path analysis modeling assessed the structural relationships between the study variables. The findings revealed that experienced contact was negatively and significantly associated with BJW and SDO. Additionally, BJW and SDO fully mediated the relationship between experienced contact and overt prejudice. These findings underscore the influence of individual differences on attitudes toward individuals with ID, establishing a crucial foundation for future research and the development of interventions aimed at reducing prejudice and discrimination.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematous, celiac disease and Sjögren syndrome, and lymphoma has been widely demonstrated by several epidemiologic studies. By a not yet entirely elucidated mechanism, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to persistent stimulation of both of B- and T-cells, and to the onset of different types of lymphoma in such patients. Specifically, patients affected by may develop lymphomas may years after the original diagnosis. Several epidemiologic, hematologic and histological factors may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly diffuse large B-cell and extranodal marginal zone lymphomas is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma and predictive factors still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57 y.o. patient. The diagnostic work-up, including radiograms, core needle biopsy and histological examination are discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

This article examines the evolution of bariatric surgery, with a focus on emerging technologies such as robotics and laparoscopy. In the case of gastric bypass, no significant differences have emerged between the two techniques in terms of hospitalization duration, weight loss, weight regain, or 30-day mortality. Robotic surgery, while requiring more time in the operating room, has been associated with lower rates of bleeding, mortality, transfusions, and infections. In revisional bariatric surgery, the robotic approach has shown fewer complications, shorter hospital stays, and a reduced need for conversion to open surgery. In the case of sleeve gastrectomy, robotic procedures have required more time and longer post-operative stays but have recorded lower rates of transfusions and bleeding compared to laparoscopy. However, robotic surgeries have proven to be more costly and potentially more complex in terms of post-operative complications. The review has also addressed the topic of the single anastomosis duodeno-ileal switch (SADIS), finding comparable results between robotic and laparoscopic techniques, although robotic procedures have required more time in the operating room. Robotic technology has proven to be safe and effective, albeit with slightly longer operating times in some cases.

Information and communication technologies play an increasingly important role in the process of acquiring knowledge from a territory and managing it at different scales. ICTs allow a rapid diffusion of data not only through institutional channels but also through social networks where the smart community share experiences and perceptions. In this sense, ICTs become strategic to support the promotion of sustainable tourism development of territories. An important tool to implement it, can be a circular smart dashboard, a decision support system in which the digital data are organized and processed to produce an information output, to be used, after the evaluation by the decision makers, as a new input for the system. The present paper deals with a wider research the authors are involved in, related to the reconversion and valorization of a former mining area towards slow tourism, as the Santa Barbara Walk (SBW), an ancient mining route in the Sulcis Iglesiente area (Sardinia, Italy) . In particular, we here focus on the design proposal of a dashboard, capable of organizing information concerning the main features of the walk, in order to facilitate a shared governance for an effective tourism promotion. The paper is based on a thorough recognition of the main characteristics of the Walk, both the material ones and the digital, immaterial ones. The SBW represents in fact a network connecting the main points of interest along the Walk. On the contrary, its digital network – consisting of intangible infrastructure and flows - is however fragmented in terms of policies and contents Also a state of disorganization in slow tourism promotion activities can be observed. The goal of this paper is to present and analysis of the area, and to propose an evaluation and planning tool as the design of a circular dashboard of the SBW.

Background: obese pre-diabetics have altered expression of cytokines, and sirtuin-1, that might influence myocardial function via microRNAs (miRs) expression. Objectives: to evaluate inflammatory/oxidative stress, miRs’ expression and cardiovascular function in obese pre-diabetics randomly assigned to metformin therapy vs. placebo vs. normo-glycemics at 12 months of follow-up. Materials and methods: eighty-three obese patients enrolled for abdominoplastic surgery, were divided in pre-diabetics (n 55), normo-glycemics (n 28), and assigned to hypocaloric diet. Pre-diabetics were randomly assigned to metformin (n 23) or to placebo (n 22) plus hypocaloric diet. Results: at enrollment, pre-diabetics obese vs. normo-glycemic presented higher values of glucose, insulin resistance (HOMA-IR), inflammatory/oxidative stress markers, miR-195 and miR-27, and lower values of sirtuin-1 (p<0.05). At 12 months of follow up, obese pre-diabetics with metformin vs. placebo experienced significant reduction of glucose values, HOMA-IR, and inflammatory/oxidative stress markers, with significant reduction of intima-media thickness (IMT), septum and posterior wall thickness, and left ventricle mass (LVM), (p <0.05). At 12 months of follow-up, obese pre-diabetics with placebo vs. normo-glycemics had higher values of inflammatory/oxidative stress markers, higher values of IMT, septum and posterior wall thickness, LVM, and myocardial performance index (MPI), (p<0.05). Obese pre-diabetics in metformin vs. placebo, and obese pre-diabetics with placebo vs. normoglycemics, had significant differences about IMT, MPI, and LVM (p<0.05). Obese pre-diabetics in metformin vs. placebo showed significant reduction of serum miR-195 and miR-27 (p<0.05). Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 ( p<0.05). Finally, we found inverse relation between IMT and insulin (R -0.351), HOMA-IR (R -0.340), miR-195 (R -0.355), miR-27 (R -0.181); between LVEF and Insulin (R -0.332), HOMA-IR (R -0.142), miR-195 (R -0.297) and miR-27 (R -0.163). We found inverse correlation between LVM and sirtuin-1 (R -0.272), Insulin (R -0.810), HOMA-IR (R-0.183), miR-195 (R -0.446) and miR-27 (R-0.433), and direct correlation with interleukin-6 (R 0.195). MPI inversely linked to miR-195 (R -0.260) and miR-27 (R -0.591). Conclusion: in obese pre-diabetics metformin therapy significantly reduces inflammation/oxidative stress, circulating miR-195 and miR-27, causing reduction of LVM, IMT and amelioration of cardiac performance.

Obturator herniæ are a quite rare type of abdominal hernia, accounting for less then 1% of all abdominal wall hernias and for 0.2-1.6% of patient with a small bowel obstruction. The obturator canal is the only portion of the obturator foramen that is not obliterated by the membrane of the same name and hosts the obturator neurovascular bundle; it is, for this reason, a locus minoris resistentiae, through which obturator hernias are formed, generally in elderly, multiparous women. Despite the fact that Computed Tomography offers the possibility of a quick, correct preoperative diagnosis, often signs and symptoms of obturator herniæ are quite unspecific; considering that, at the same time, patients with an obturator hernia are generally elderly, with concurrent conditions, this might cause delays in the diagnosis and treatment and produces the high postoperative mortality rates that obturator herniæ yield

Phagosomal escape and intracellular survival, often accompanied by Small Colony Variants (SCVs) formation, are typical features of infections caused by S. aureus. The survival in macro-phages favours S. aureus dissemination and complicates treatment. RAW 264.7 murine macro-phages infected with S. aureus USA300 and treated with erythromycin and 20mM carnosine, alone and in combination, were used as experimental model. SCVs were isolated from all treat-ment conditions, but only those undergoing the pressure of combined erythromycin and carnosine for 48 hours were stable for at least six passages on blood agar. Nucleic acid extraction was car-ried out for S. aureus USA300 wild-type and stable SCVs. Whole Genome Sequencing (WGS) was performed using Illumina DNA Prep and Illumina MiSeq, and quantitative reverse transcription PCR was performed. WGS analysis did not yield mutations pointing to differences between S. au-reus USA300 and stable SCVs, therefore the focus was shifted to evaluating gene expression vari-ations. Genes such as zur, mntR, uhpt, fur, sdrE were shown to be significantly up-regulated in SCVs compared to S. aureus USA300 wild-type, suggesting a global change that allows adapta-tion to intracellular persistence, including protection from inflammatory response and evasion of the immune system.

Plastic waste constitutes one of the most important sources of pollution worldwide. Despite the growing recycling trend, nowadays there are no effective technologies that can compensate for the continuous increase in plastic production. Polyesters and polyamides are one of the most produced single-use plastics, mainly used in manufacturing textiles and soft drinks bottles. Today, only a very low fraction of these polymers can be recycled. It can be done by exploiting two leading technologies: mechanical and chemical recycling. Mechanical recycling represents, nowadays, the most used industrial application. However, it can treat a very narrow range of waste materials due to the impossibility of removing dyes and the deterioration of mechanical properties due to the incompatibility of different plastic materials. Another critical limit of this recycling technology is the limited number of recycling loops that can be done due to the thermal degradation that occurs during the extrusion process. The second possibility is chemical recycling, which allows the depolymerization of the original product to recover the monomers directly. The main drawbacks are the long reaction times and the many solvents needed to achieve high-purity products. Therefore, chemical recycling is economically feasible, only for big companies that can produce the virgin polymer in situ. In this work, a new technology has been patented. This process is constituted of three main steps. The first one is the distillation-assisted cyclodepolymerization (DA-CDP), introduced as a modification of the CDP process. In this unit, cyclic oligomers together with high molecular weight compounds have been produced. Then, after polymer purification, it is possible to achieve the same molecular weight of the initial polymer in less than 30 minutes, exploiting the ring-opening polymerization (ROP) in the next step.

South Italy is characterised by a semi-arid climate with scarce rain and high evaporative demand, therefore the need to optimise water resources in this area is crucial, and climate change could worsen this condition. In citrus cultivation, which is one of the most important crops bred in Southern Italy, and more generally in Mediterranean regions, deficit irrigation strategies are im-plemented in order to cope with limited resource availability. On this basis, knowledge on how the territorial distribution of citrus would change in relation to these strategies constitutes valuable information for the stakeholders. Therefore, the objective of this study was to determine the prob-ability of presence of citrus in Sicily at changing of the percentage of water deficit application, in order to analyse change in the surface area and localisation of the crop. The methodology was based on the application of Species Distribution Models and Geographic Information Systems to the case study of the Province of Syracuse in Sicily. Different geostatistical and machine learning models were applied, based on 3-decades bioclimatic variables, DTM and irrigation; assessment of the outcomes was carried by using classification evaluation metrics. The analysis of the outcomes showed that uncorrelated predictor layers mainly included water input that affected most the probability of presence. Moreover, GIS analyses showed that deficit irrigation strategies would generate an overall reduction of cultivation surfaces in the territory and a decrease of citrus pres-ence in southern areas of the considered territory, where climate conditions are less favourable in terms of temperature and precipitations, thus providing useful information for decision support tools in agriculture and land use policy.

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

Total Hip Arthroplasty (THA) is a common surgical procedure used to treat hip osteoar-thritis and other joint conditions that cause pain and functional limitation. Traditionally, THA has been most performed in elderly patients, but in recent years there has been an in-crease in hip arthroplasties in young patients. Femoral prosthesis rupture is a rare but sig-nificant complication that can also occur in young patients undergoing total hip arthro-plasty (THA). Some of the factors that can contribute to femoral prosthesis ruptures include abnormal overload, defects in the design lack of geometric fit, type of materials used in the stem and femoral head connection. The aim of this study is to analyze the criticalities in the contact between the femoral head and the stem neck. In particular, the two types of con-tacts will be taken into consideration: proximal and distal and through the finite element method (FEA) the criticalities will be defined. The results show that in the proximal contact the voltages are higher than 500 Mpa. This is due to the fact that there are higher circum-ferential voltages. In addition, to prevent bacterial infiltration or debris from the outside, the distal connection is the recommended one.

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune-system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years of age is steadily increasing and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g. infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. SES can influence global health trajectory for an individual or a community, depending if SES is low or high. Sleep is sensitive to environmental stimuli, as well as living conditions. Plenty of studies linked sleep complaints with mood disorders, allostatic load or circadian disruption; but very few or none investigated deeply what happened earlier to sleep depending of SES. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. Even if recent evidence suggested that few of SES indicators like occupational status are linked with sleep disturbances, the relation between SES and health in general with sleep as an outcome or a mediator is not well documented. This scoping review synthetized studies which investigated physiological and psychological mechanisms resulting from a low SES and linked them with sleep disturbances as consequences or as mediators. This review also explore a possible role played by sleep in the relation between socioeconomic status and health inequalities.

The concepts of accessibility and urban walkability are the cornerstones of urban policies for the contemporary city, called upon to adopt sustainable development models in line with the objectives of the 2030 Agenda and the ambitious objectives of the 'European Green Deal'. These concepts are closely linked to the paradigm of a sustainable city (livable, healthy and inclusive), founded on a system of quality public spaces and on a network of services and infrastructures, both tangible and intangible, capable of strengthening or building new relationships: social, economic and environmental. It is therefore necessary to recognize potential opportunities for connection and permeability in consolidated urban environments, very often fragmented and characterized by enclaves. Within this framework, the city of Cagliari represents an interesting case study as it is characterized by the presence of a series of military complexes, real 'enclaves' which condition the proximity connections and, more generally, the walkability. In this sense, building on previous research and analysis of policies and projects aimed at reintroducing, even partially, this military asset into civilian life (Green Barracks Project - GBP - 2019), this study proposes and applies a methodology to improve urban accessibility in a flexible network logic, where 'walkability' can become not only a moment of possible "choice" but the basis for planning oriented to the '15 min city' model or, more generally, to the renewed, inclusive, safe, resilient and sustainable “City of proximity”.

The European corn borer (ECB) and in a lesser extent the western corn rootworm (Diabrotica virgifera virgifera LeConte) are a threat to maize in the Po Valley (Northern Italy), and its control can require insecticide applications. The results of a study to assess the effects of insecticide sprays on the beneficial insect Trichogramma brassicae (Hymenoptera Trichogrammatidae) and aphid predators are reported. A three-year research was carried out in two study areas, in Lombardy. In area 1, crop rotation was a common practice, while in area 2, maize monoculture was practiced. The ordinary trend of ECB egg masses attacked by T. brassicae was affected and parasitism rates were reduced as a result of exposure to insecticides (chlorpyriphos methyl, cypermethrin, alphacypermethrine, teflubenzuron). Repeated maize crop and insecticides spraying increased the aphid population abundance and negatively affected the aphid predator community, which mainly included ladybirds, hoverflies, bugs and lacewings. In sprayed fields, managed according to repeated crop protocols, the predator community was dominated by hoverflies, whereas ladybirds and Orius spp. prevailed in maize fields managed according to crop rotation protocols. Crop rotation protocols help to prevent ECB outbreaks; when threshold limit can be at risk, inundative release of T. brassicae or microbial control (i.e. use of preparation of Bacillus thuringiensis) can integrate natural biocontrol, a valuable alternative to chemical insecticides.

The dynamic response of a Bell-and-Bloom magnetometer to a parallel (to the bias field) time-dependent field is modelled beyond the commonly assumed quasi-static regime. The results unveil features that are related to the parametric nature of the considered system. It is shown that a for low-amplitude time-dependent field different operating conditions are possible and that, beside the commonly reported low-pass-filter behaviour, a band-pass response emerges. Moreover, we numerically show that for larger field amplitude the system, due to its parametric nature, has a kind of ``non-linear'' response.

A connection between the phenomenon of wafer bifurcation and that of spontaneous symmetry breaking (SSB) has been established. Indeed, by developing an analytical approximation of the elastic energy of a wafer coated with a thin layer (e.g. a metal), it is shown as the elastic potential energy, interpreted as a quantity contributing to the thermodynamic free energy, can be investigated within the framework of the Landau theory of the second order phase transitions. The elastic energy of a bifurcated wafer is a complex function of the stress and the curvatures in the two perpendicular directions. In this work, it is shown as a translation of the coordinate system of the curvatures allows to gain a potential which has a “Mexican hat” shape. This is a distinctive trait of the phenomenon of spontaneous symmetry breaking (SSB). Moreover, it is shown as the values of the coordinates at the minimum of the SSB potential agrees with those provided by the theory. Bifurcation is hence a phenomenon that can also be interpreted as a spontaneous symmetry breaking where the rotational symmetry of a disc shaped wafer is broken. It occurs because of a lowering of the wafer energy in the SSB broken symmetry configuration.

Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenge in the ophthalmological research field. Although this inherited retinal dystrophie is still incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidences about the cell therapies effectiveness, especially based on mesenchymal cells, in RP and focus on their therapeutic actions: limitation of both oxidative stress and apoptotic processes triggered by the disease, promoting cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP.

Background: Peripheral Ossifying Fibroma (POF) is a benign gingival tumor generally presenting as a slow-growing mass, usually not ulcerated, and without bleeding. Histopathological exam shows fibrous connective tissue with spots or extensive areas of intralesional calcifications, which can also be detectable on radiograms. Methods and case presentation: We present the case of a 4-year-old male with a retro-incisive swelling of the hard palate, associated with speaking and feeding difficulties. On CT scans, a small intralesional calcification was detected. After conscious sedation, the patient was subjected to diode laser excision (910 nm, 2W, CW, 300 m fiber) with-out post-operative complications. A review was conducted by searching the words “peripheral ossifying fibroma” AND “children” OR “infant” and including manuscripts of the last 15 years. Results: POF is an uncommon lesion of the oral mucosa and may sporadically affect the palatal mucosa in children. Considering its epidemiology and conventional clinical presentation as epu-lis, the pre-operative diagnosis may be relatively difficult. Risk factors could be represented by plaque, calculus, or trauma, all supporting a possible reactive pathogenesis, but a certain etiology is still missing. The main problem of POF is the recurrence rate, which is particularly high (8-20%), thus suggesting that a deep excision is recommended with full extension to the hard tis-sue of bone and to the adjacent periodontal ligament. Diode laser surgery may be recommended for such treatments, especially in pediatric patients, associated with intraoperative conscious se-dation. Data emerging from the relevant literature on POF management in children have been collected and discussed. Conclusions: The authors suggest the use of diode laser for the complete excision of POF, especially in less-compliant patients as children, with a low grade of comorbidi-ties and good outcomes, giving the surgeon a viable alternative to conventional surgery.

Liquid biopsy via isolation of circulating tumour cells (CTCs) represents a promising diagnostic tool capable of supplementing state-of-the-art for prostate cancer (PC) prognosis. Unfortunately, most of CTC technologies, such as AdnaTest or Cellsearch, critically rely on the Epithelial-Cell-Adhesion-Molecule (EpCAM) marker, limiting the possibility of detecting stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this tontext, dielectrophoresis (DEP) is an epCAM independent, label-free, enrichment system, separating rare cells simply on the basis of their specific electrical properties. As compared to other technollgies, DEP represents a superior technique in terms of running costs, cells yield and specificity, but due to its higher complexity, requires still further technical as well as clinical development. Interestingly, DEP can be improved by the use of microfluid, nanostructured materials and fluoroimaging in order to increase its potential applications. In the context of PC, the utility of DEP can be translated in its capacity to detect CTC in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotypes, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and early diagnosis.

Prostate Cancer (PCa) is still ranked as the first cancer in male population and evidences have suggested an alteration of glycemic and lipidic metabolism that are related to its progression and prognosis. Aim of the study is to investigate associations between enzymes’ expression, especially involved in the lipidic pathway, and PCa aggressiveness. We retrospectively analyzed data from 390 patients with PCa or benign prostatic hyperplasia (BPH) at the Department of Urology, University of Catania. Immunohistochemical slides were evaluated for the expression of proteins related to glucose and lipidic metabolism. A total of 286 were affected by PCa while 104 by BPH. We demonstrated that ATP-lyase (odds ratio [OR]: 1.71; p&lt;0.01), fatty acide sinthase (OR: 4.82; p&lt;0.01), carnitine palmitoyl transferase-1a (OR: 2.27; p&lt;0.05) were associated with androgen receptor (AR) expression. We found that steaoryl Co-A desaturase expression in PCa patients with total cholesterol ≥ 200 mg/dl was independently associated with ISUP ≥4 (OR: 4.22; p=0.049). We found that CPT-1a+ was associated with biochemical recurrence (hazard ratio: 1.94; p=0.03]). Our results support the evidences that the manipulation of lipidic metabolism could serve in the future to contrast PCa progression.

A sensory profile provides important information on the qualitative and quantitative properties of cheeses. Thus, tasters must be trained with reference standards that allow the calibration of the panel around shared sensory definitions. The ideal standard is simple to prepare, easily reproducible, discriminant and specific for the product evaluated. Therefore, commercial products and pure chemicals, which are currently implemented as reference standards, are not suitable. Furthermore, the lack of common practices in the dairy sectors has been widely highlighted. This study aimed to establish new and reproducible reference standards for the gustatory and olfactory descriptors of cheeses. Using casein, maize starch, powder skimmed milk and k-carrageenan, a tasteless and odourless product like a fresh cheese was produced. At this matrix, 20 odour and taste compounds have been added to obtain standards that have been evaluated by 60 tasters so as to define their recognisability and perceived intensity. These cheese standards are easy to reproduce, are stable and exhibited good recognisability. Overall, the reference standards proposed are suitable for the panel training and are a starting point for standardising practices and lexicon, thus enabling the comparability of sensory studies on cheese.

Lung cancer represents the most common form of cancer accounting for 1.8 million deaths globally in 2020.The 5-year relative survival rate for lung cancer is lower than many other leading cancer types. Over the last decade the treatment for advanced and metastatic non small cell lung cancer have dramatically improved due to the development of immune checkpoint inhibitors and the identification of targetable driver mutations. Recently, potentially effective inhibitors of a hitherto untargetable oncogenic driver mutation in NSCLC, Kirsten Rat Sarcoma (KRAS) have been developed. KRAS mutations are found in 20-25% of NSCLC and represent the most frequent mutation. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.

Renewable sources and electric distribution network can produce or make available a surplus of electric and thermal energies. The Intermediate Temperature Solid Oxide Electrolyzer (IT-SOE) fed by CO2-steam mixtures can store these electric and thermal energies producing CO-H2 mixtures with high conversion efficiency. Inside the IT-SOE, the CO2-steam mixtures are converted to CO-H2 mixtures and O2 through the cathode and anode electrochemical reactions and reverse water gas shift chemical reaction. In this article an IT-SOE stack fed by different types of steam mixtures was tested at different operating temperatures and the stack polarization and electric power curves were detected experimentally. At the highest hydrogen production operating temperature of the stack fed by steam mixtures, the experimental polarization and electric power curves of the stack fed by steam and CO2-steam mixtures were compared. A simulation model of the IT-SOE system (stack and furnace) fed by CO2-steam mixtures was formulated ad hoc and implemented in a Matlab environment and experimentally validated. At the highest hydrogen production stack operating temperature, the IT-SOE system thermal equilibrium current was evaluated through the simulation model. Moreover, the influence of this current on the IT-SOE system efficiency and the CO-H2 mixture degree of purity was highlighted.

Personalized medicine is an aspect of the P4 medicine (predictive, preventive, personalized and participatory) based precisely on the customization of all medical characters of each subject. In personalized medicine, the development of medical treatments and drugs is tailored to the individual characteristics and needs of each subject, according to the study of diseases at different scales from genotype to phenotype scale. To make concrete the goal of personalized medicine, it is necessary to employ high-throughput methodologies such as Next Generation Sequencing (NGS), Genome-Wide Association Studies (GWAS), Mass Spectrometry or Microarrays, that are able to investigate a single disease from a broader perspective. For example, by using genotyping microarrays (e.g. collections of Single Nucleotide Polymorphism - SNP) it is possible to uncover the reasons (i.e. mutation in genes) because a treatment works properly in some patients (for example absence of mutated genes), but it does not work (presence of mutated genes) in others. A side effect of high-throughput methodologies is the massive amount of data produced for each single experiment, that poses several challenges (e.g. high execution time and required memory) to bioinformatic software. Thus a main requirement of modern bioinformatic software is the use of good software engineering methods and efficient programming techniques, able to face those challenges, that include the use of parallel programming and efficient and compact data structures. Thus, to exploit all the potential of this massive amount of data in the short possible time (before that data becomes obsolete), the necessity to develop parallel software tools for efficient data collection and analysis arise. Moreover, due to the heterogeneity of the data produced by the different kinds of experimental platforms, it is necessary to automatize in a comprehensive software pipeline, the various steps that compose a bioinformatic analysis, such as: the preprocessing of raw data to remove noise or corrupted data; the annotation of data with external knowledge (e.g. Gene Ontology), and the integration of molecular data with clinical data. It should be noted that such steps are necessary to make statistical or data mining analysis more effective. This paper presents the design and the experimentation of a comprehensive software pipeline, named microPipe, for the preprocessing, annotation and analysis of microarray-based SNP genotyping data. A case study in pharmacogenomics is presented. The main advantages of using microPipe are: the reduction of errors that may happen when trying to make data compatible among different tools; the possibility to analyze in parallel huge datasets; the easy annotation and integration of data.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

Background: Over the past decades, efforts have been made to improve the nutritional well-being in people with cystic fibrosis (pwCF). Due to the correlation observed between nutritional indices and lung function, prevailing recommendations consistently advocate for BMI percentile goals at or above the 50th percentile in pwCF. Recent global trends show a notable increase in overweight and obese statuses among pwCF. This study aims to explore the nutritional status of Italian pwCF. Methods: Data from the Italian CF Patient’s Registry were analysed to assess the proportion of individuals categorized as underweight, target weight, overweight, and obese from 2010 to 2021. Patient-level comparison data from 2021 were also examined to identify potential determinants of overweight and obesity. Results: Analysis spanning 2010 to 2021 reveals a decrease of approximately 40% in underweight status among adults, while the proportion of malnourished patients 90, and lower prevalence of Pseudomonas aeruginosa colonization. Conclusions: Our study confirms the evolving nutritional status landscape among Italian adult pwCF, with a significant shift towards overweight and obesity over the past decade. These trends highlight the need for proactive measures within CF standards of care to adapt and address the changing needs of patients.

The emergence of new plant diseases is an increasingly important concern. Climate change is likely to be among the factors causing most of the emerging diseases endangering forest and tree heritage around the world. Such diseases may be caused by latent pathogens or microorganisms cryptically associated with plants. The shift from a non-pathogenic to a pathogenic stage may depend on physiological alterations of the host, environmental changes and/or stress factors. In some woods of the Salento peninsula (Apulia region, Italy) sudden declines of holm oak plants (Quercus ilex L.) have been observed since 2016. The morphological and molecular characterization of representative fungal isolates associated with canker and necrosis in declining plants indicated that these isolates belong to the Botryosphaeriaceae family, and the most frequent species were Diplodia corticola and Diplodia quercivora, followed by Neofusicoccum vitifusiforme. In artificially inoculated young holm oak plants, both D. corticola and D. quercivora species produced intense and severe subcortical and leaf margin necrosis. N. vitifusiforme, although less aggressive, induced the same symptoms. Our research in addition to confirm the involvement of D. corticola in olm oak decline, represents the first report of D. quercivora as a new pathogen on Quercus ilex in Italy. Furthermore, to the best of our knowledge, we also found N. vitifusiforme as a new pathogen on Q. ilex for the first time.

in this work formulations of "environmentally compatible" silicone-based antifouling synthesized in the laboratory and based on copper and silver on silica/titania oxides have been characterized, capable of replacing the non-ecological antifouling paints currently on the market. The texture properties and the morphological analysis of these powders with an antifouling action indicate that their activity is linked to the nanometric size of the particles and to the homogeneous dispersion of the metal on the substrate. The presence of two metal species on the same support limits the for-mation of nanometric species and therefore the formation of homogeneous compounds. The presence of the antifouling filler (specifically the one based on TiO2 and Ag) facilitates the achievement of a higher degree of cross-linking of the pure resin, and therefore a better compactness and completeness of the coating. This leads to a consequent better degree of adhesion to the tie-coat and therefore to the steel support used for the construction of the boats.

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.