Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

Curcumin, a major constituent of turmeric, has beneficial effects against several diseases. In cystic fibrosis (CF), this compound potentiates the activity of a number of cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Despite holding promise in the treatment of CF, the curcumin binding site in CFTR and the molecular mechanism of activation of this channel are still unknown. The results of the study, based on docking and molecular dynamics (MD) simulations, allow to propose that curcumin binds the closed ATP-free CFTR near the NBD1/ ICl1/ICl4 interface. The bound ligand, once approached by NBD2 during transient channel opening, lays at a multiple interdomain cross point. Thereafter, curcumin can bridge NBD1 and NBD2, and also ICL1/ICL4 and ICL2/ICL3 finally tightening the same interdomain interactions that normally uphold the active conformation in the wild type ATP-bound CFTR. The proposed binding site is compatible with biochemical observations made in previous CFTR-curcumin interaction studies. These findings provide the framework for the design of novel drugs that activate CFTR mutants characterized by defects in ATP binding and/or NBD dimerization, or even lacking NBD2.

We present a numerical study in which large-scale bulk simulations of self-assembled DNA constructs have been carried out with a realistic coarse-grained model. The investigation aims at obtaining a precise, albeit numerically demanding, estimate of the free energy for such systems. We then, in turn, use these accurate results to validate a recently proposed theoretical approach that builds on a liquid-state theory, the Wertheim theory, to compute the phase diagram of all-DNA fluids. This hybrid theoretical/numerical approach, based on the lowest order virial expansion and a nearest-neighbor DNA model, can provide, in an undemanding way, a thermodynamic description of DNA associating fluids that is in semi-quantitative agreement with experiments. We show that the predictions of such scheme are as accurate as the ones obtained with more sophisticated methods. We also demonstrate the flexibility of the approach by incorporating non-trivial additional contributions that go beyond the nearest-neighbor model to compute the DNA hybridization free energy.

In multi-objective optimization problems, the optimization target is to obtain a set of non-dominated solutions. Comparing solution sets is crucial in evaluating the performances of different optimization algorithms. The use of performance indicators is common in comparing those sets and, subsequently, optimization algorithms. A good solution set must be close to the Pareto-optimal front, well-distributed, maximally extended and fully filled. Therefore, an effective performance indicator must encompass these features as a whole and must be Pareto dominance compliant. Unfortunately, some of the known indicators often fail to properly reflect the quality of a solution set or cost a lot to compute. This paper demonstrates that the Degree of Approximation (DOA) quality indicator, is a weakly Pareto compliant unary indicator that gives a good estimation of the match between the approximated front and the Pareto-optimal front. Moreover, DOA computation is easy and fast.

DFT calculations on the photoisomerization reactions of pyridazine N-oxide derivatives are presented. The irradiation of 3,6-diphenylpyridazine N-oxide allowed to obtain the first excited singlet state that underwent to a ring opening reaction induced to the oxygen migration to the adjacent carbon atom, with the formation of a diazo derivative. This intermediate can give a ring closure reaction to give a pyrazole derivative, or, with a higher transition energy, it can lose nitrogen allowing the formation of 2,5-diphenylfuran. The irradiation of 3-phenylpyridazine N-oxide allowed the formation only of 2-phenylfuran. In this case, calculations allowed to explain this behavior. The first excited singlet state gave a photoisomerization reaction with the formation of the corresponding diazo intermediate. This intermediate could not be converted into the corresponding pyrazole derivative because it was converted into a N-formyl pyrazole never reported in literature. The only possible reaction is the loss of nitrogen and the formation of 2-phenylfuran.

Occupational accidents, despite continuous safety updates, are still a scourge in the occupational and forensic spheres, constituting, among other things, the subject of a large share of litigation. Demographic data can help to understand the areas where the application of health surveillance is lacking. This meta-analysis sets out to analyze data from studies on accidents at work, focusing on the correlation between the areas in which accidents occur and whether or not personal safety equipment is used, about the different regulations in force. For the selection of the data, a systematic review was carried out according to the PRISMA guidelines, with the primary objective of identifying the trend of occupational accidents in specific geographical areas, which differ in terms of the attention paid to preventive aspects. The data we highlighted showed, regarding the type of accident, substantial differences between low-income countries and industrialized countries (stratified according to the Human Development Index) and, an overall indifference as to whether or not individual safety devices were used, revealing that, despite the continuous normative evolution in the field of safety at work, even today, the investigative data on the actual application of the regulations, during accidents at work, is underestimated and little researched.

This review reports the available technologies for the flexible utilization of biomass towards negative CO₂ emissions and addresses the possibility to couple biogas production plants with the electrical grid converting excess electrical energy into storable chemical molecules. This changed mind-set towards biomass utilization can lead readily to the implementation of negative CO₂ emission along the entire bioenergy supply chain without limiting the potential for Power-to-X applications. First, the technologies for direct conversion of waste and wood into gaseous energy carriers are screened, to highlight the potential for the production of renewable fuels. Second, the processes for the removal of CO₂ from biogenic gas streams are analysed in terms of technological performance, cost and further potential for the CO₂ recovered. These technologies are the key to pre-combustion CO₂ capture and negative emissions. Third, the possibility of coupling biomass conversion and synthetic fuels production is explored, providing an overview on the technical maturity of the various energy storage processes. The flexible use of biomass can be an essential part of the future CO₂-free energy systems, as it can directly provide energy carriers all around the year and also large quantities of climate-neutral carbon for the production of synthetic fuels with renewable energy. In turn, when no additional renewable electricity is available, the CO₂ by-product from biofuel synthesis can be used for the negative emissions. This opens the way to an efficient strategy for the seasonal storage of electrical energy, realizing a carbon-neutral energy system coupled with the development of carbon-negative energy strategy.

Infrared (IR) thermography is a powerful tool to measure temperature with a high space and time resolution. A particular interesting application of this technology is in the field of catalysis, where new insights to highly dynamic surface reactions are possible. This paper presents guidelines for the development of a reactor cell that can aid in the efficient exploitation of infrared thermography for the investigation of catalytic and other surface reactions. Firstly, the necessary properties of the catalytic reactor are described. In fact, special equipment must be developed to ensure the realization of true operando conditions in the IR thermography experiments. Here, we provide the guidelines to assemble a chemical reactor with an IR transmitting window through which the reaction can be studied with the infrared camera. Secondly, we analyze the requirements towards the catalytic system to be directly observable by IR thermography. This includes the need for a catalyst that provides a sufficiently high heat production (or absorption) rate. We present selected examples of catalytic reactions that can be monitored by IR thermography and showing the potential of the technology in revealing transient and steady state chemical phenomena.

The implementation of the European Cohesion Policy aiming at fostering regions competitiveness, economic growth and creation of new jobs is documented over the period 2014–2020 in the publicly available Open Data Portal for the European Structural and Investment funds. On the base of this source, this paper aims at describing the process of data mining and visualization for information production on regional programmes performace in achieving effective expenditure of resouces.

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.

Considering the manufacturing of automotive components, there exists a dilemma around the substitution of traditional Cast Iron (CI) with lighter metals. Nowadays, aluminium alloys, being lighter compared to traditional materials, are considered as a more environmentally friendly solution. However, the energy required for the extraction of the primary materials and manufacturing of components is usually not taken into account in this debate. In this study, an extensive literature review has been performed to estimate the overall energy required for the manufacturing of an engine cylinder block using (a) cast iron and (b) aluminium alloys. Moreover, data from over 100 automotive companies, ranging from mining companies to consultancy firms, have been collected in order to support the soundness of this investigation. The environmental impact of the manufacturing of engine blocks made of these materials is presented with respect to the energy burden; the “cradle-to-grave approach” has been implemented to take into account the energy input of each stage of the component lifecycle starting from the resource extraction and reaching to the end-of-life processing stage. Our results indicate that although aluminium components contribute towards reduced fuel consumption during their use phase, the vehicle distance needed to be covered in order to compensate for the up-front energy consumption related to the primary material production and manufacturing phases is very high. Thus, the substitution of traditional materials with lightweight ones in the automotive industry should be very thoughtfully evaluated.

This article analyzes and compares the integration of two different maximum power point tracking (MPPT) control methods, which are tested under partial shading and fast ramp conditions. These MPPT methods are designed by Improved Particle Swarm Optimization (IPSO) and a combination technique between Neural Network and Perturb & Observe method (NN_P&O). These two methods are implemented and simulated for photovoltaic systems (PV), where various system responses, such as: voltage and power are obtained. The MPPT techniques were simulated using Matlab/Simulink environment. A comparison of the performance of IPSO and NN_P&O algorithms is carried out to confirm the best accomplishment of the two methods in terms of speed, accuracy and simplicity.

The increased availability of high resolution remote sensor data for precision agriculture 1 applications permits users to aquire deeper and more relevant knowledge about crops states that lead 2 inevitably to better decisions. The algorithm libraries being developed and evolved around these 3 applications rely on multi-spectral or hyper-spectral data acquired by using manned or unmanned 4 platforms. The current state of the art makes thorough use of vegetational indicies to guide the 5 operational management of agricultural land plots. One of the most challenging sub-problems is 6 to correctly identify and separate crop from soil. Thresholding techniques based on Normalized 7 Difference Vegetation Index (NDVI) or other such similar metrics have the advantage of being simple, 8 easy to read transformations of the data packed with useful information. Obvious difficulties arise 9 when crop/tree and soil have similar spectral responses as in case of grass filled areas in vineyards. 10 In this case grass and canopy are close in terms of NDVI values and thresholding techniques will 11 generally fail. Radiometric approaches could be integrated or replaced by a geometric approach that 12 is based on terrain data like Digital Surface Models (DSMs). These models are one of the ouputs 13 of orthorectification engines usually present in data acquired by using unmanned platforms. In 14 this paper we present two approaches based on DSM that are able to segment crop/tree from soil 15 while over gradient terrain. The DSM data are processed through a two dimensional data slicing or 16 reduction technique. Each slice is separately processed as a one dimensional time series to derive the 17 terrain and tree structures separately, here interpreted as object probability densities. In particular 18 the first approach is a Cartesian grid rasterization (CARSCAN) of the terrain and the second is its 19 immediate generalisation or radial grid rasterization of the DSM model (FANSCAN). The FANSCAN 20 recovers information from the original image at greater frequencies on the Fourier plane. These 21 approaches enable the identification of crop/tree from soil in case of slopes or hilly terrain without 22 any constraint on the displacement / direction of plant/tree row. The proposed algorithm uses pure 23 DSM information even if it is possible to fuse its output with other classifiers.

The art of dyeing textiles has a long history, as natural dyes have been used since prehis-toric times. With the development of synthetic dyes in the 19th century, the focus shifted from natural to synthetic dyes due to their superior properties. Recently, however, interest in natural dyes has increased again due to environmental and health concerns. Among industrial dyes, heterocyclic dyes, especially azo dyes, are of great importance due to their color brilliance and fastness. This review examines the synthesis, application and analysis of azo dyes, especially heterocyclic dyes. It deals with monoazo, diazo and polyazo dyes and highlights their structures, synthesis methods and fastness properties. In addition, the ecological impact of azo dyes and practical solutions for their synthesis and application are discussed.

In many industrial, automotive, and aerospace applications, electro-mechanical systems are subjected to random vibration excitations, and the most critical components are required to undergo qualification tests to verify their suitability. Measured field data are commonly considered as reference for the synthesis of random stationary signals used as shaker input excitations in laboratory tests. For the most popular procedures of random-control testing, the user sets the input profiles in terms of power spectral density (PSD) associated with randomized phases generated by the shaker controller to finally provide the physical motion. As a result, the overall probability distribution of the test signal tends toward Gaussian, whereas many real-life random excitations prove non-Gaussian due to distinctive bursts and peaks. The quantitative estimate of the number and amplitudes of peaks present in a certain signal is usually made through the statistical parameter known as kurtosis. The so-called kurtosis control methods presented in the literature are conceived to perform qualification tests with random and non-Gaussian vibration excitations. In this paper, two novel algorithms able to synthesize shaker input signals for random-control testing with prescribed PSD and kurtosis value are proposed, and the results of their application are comparatively discussed to assess their effectiveness and potentialities in different kinds of qualification testing, including accelerated fatigue-life tests.

It has been proposed that upregulation of the noradrenergic (NA) system through exposure to novelty might be one of the key components for building cognitive reserve and resilience to neurodegeneration. A personality trait that promotes greater interest in novel experiences is Openness to Experience (OE). Individuals who are high in OE exhibit strong curiosity towards novelty and are more likely to be exposed to novel stimuli throughout the lifespan.Performing voxel-based morphometry analyses, we examined whether OE in 135 healthy young adults was associated with Locus Coeruleus (LC) - the main core of the noradrenergic system. We also investigated whether LC mediates the relationship between OE and a key measure of reserve, I.Q. In comparison with other neuromodulators’ seeds (Dorsal and Median Raphe [DR-MR] -5-HT, Ventral Tegmental Area [VTA] -DA- and Nucleus Basalis of Meynert [NBM] -Ach-), results show that greater LC integrity was related to greater OE and IQ. Additionally, mediation analyses revealed that only LC mediated the relationship between OE and IQ. Furthermore, a Bayesian multiple regression was conducted to model the contribution of both isolated and combined neuromodulator seeds to OE trait express. This approach found that the LC + VTA could account for more variance in OE expression compared to the LC alone. Other weaker but significant associations were observed between DR and OE, between LC + NBM and Conscientiousness and between DR + NBM and Extraversion. These results are together suggestive that OE is primarily underpinned by monoaminergic functioning, and that the LC-NA system plays a central role mediating the interdependence between OE expression and cognition (IQ level). While offering further understanding of the neurobiology of human personality, these findings indicate a pivotal role of LC-NA system integrity in novelty seeking in daily life. This provides a psychobiological account for how OE expression may be beneficial for maintaining the noradrenergic system to facilitate cognitive reserve and resilience to neurodegenerative conditions.

Yogic and meditative traditions have long held that the fluctuations of the breath and the mind are intimately related. While respiratory modulation of cortical activity and attentional switching are established, the extent to which electrophysiological markers of attention exhibit synchronization with respiration is unknown. To this end, we examined 1) frontal midline theta-beta ratio, an indicator of attentional control state known to correlate with mind wandering episodes and functional connectivity of the executive control network; 2) pupil diameter (PD), a known proxy measure of locus coeruleus (LC) noradrenergic activity; and 3) respiration for evidence of phase synchronization and information transfer (multivariate Granger causality) during quiet restful breathing. Our results indicate that both TBR and PD are simultaneously synchronized with the breath, suggesting an underlying oscillation of an attentionally relevant electrophysiological index that is phase-locked to the respiratory cycle which could have the potential to bias the attentional system into switching states. We highlight the LC’s pivotal role as a coupling mechanism between respiration and TBR, and elaborate on its dual functions as both a chemosensitive respiratory nucleus and a pacemaker of the attentional system. We further suggest that an appreciation of the dynamics of this weakly coupled oscillatory system could help deepen our understanding of the traditional claim of a relationship between breathing and attention.

Shared public buildings have become centers of innovation, integrating advanced technologies to meet evolving societal needs. With a heightened emphasis on occupants’ health and well-being, these buildings serve as hubs for technological convergence, facilitating seamless connectivity and intelligent data analysis and management. Within this context, environmental monitoring emerges as a foundational element, pivotal to all aspects of building management. This article provides findings from the nationally funded RE-START project, which focuses on shared public buildings, with special regard to educational and medical facilities. The project explores enhanced indoor air quality monitoring, focusing in particular on CO2 concentration that is directly correlated with occupancy, as a fundamental element for developing health and safety protocols, energy efficiency strategies, integration of smart building technologies, and data-driven energy management. The intersection of environmental monitoring, energy efficiency, security, and IoT technologies in in indoor spaces are relevant. The outcomes of the study reveal the delicate nature of all the involved components, that need to be carefully developed in an integrated manner.

Mitochondrial dysfunction is relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the heart of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n=8) or placebo (n=8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and abundance of mtDNA4834 deletion), and mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. TFAM binding to mtDNA regions involved in replication and deletion generation was increased following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling was found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

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/).

Background and aim: Human Papillomavirus (HPV) is sexually transmitted, one of the three most common sexually transmitted infections (STIs) in both males and females, and the most common viral STI. A crucial public health strategy to protect people against HPV is through vaccination, which has shown its effectiveness in preventing HPV related diseases. Presently three types of vaccines are available (bivalent, quadrivalent, and nonavalent) and they all target at least the two most oncogenic virus genotypes (HPV 16, 18). In the past few years, the need to implement vaccination programmes that include all genders has been discussed in order to achieve herd immunity against HPV. To date, only a few countries have included young males in their vaccination programmes, so we aim through this review to provide an overview of the epidemiology of HPV and prevention strategies to prevent it, reporting the latest findings from the scientific literature.

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

The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. We present here an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species is studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species (HO₂^• and O₂^•− ), which are not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO₂^• and O₂^•− production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO₂^• and O₂^•− in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

Italian floriculture is facing structural changes. Possible options to maintain competitiveness of the involved companies include promotion of added values, from local productions to environmental sustainability. To quantify value and benefits of cleaner production processes and choices, a holistic view is necessary, and could be provided by life cycle assessment (LCA) methodology. Previous studies on ornamental products generally focused on data from one company or a small sample. The aim of this study was a gate-to-gate life cycle assessment of two ornamental species (Cyclamen persicum Mill. and Pelargonium ×hortorum Bailey) using data from a sample of 20 companies belonging to a floriculture district in Treviso, Veneto region. We also assessed the potential benefits for the environmental impact of the selected species of alternative management choices regarding plant protection and reuse of composted waste biomass. Life cycle impact assessment showed the higher impact scores for the zonal geranium, mainly as a consequence of greenhouse heating with fossil fuels. This factor, along with higher uniformity of production practices and technological level of equipment, translated in lower variability observed in comparison with cyclamen production, which shows a wider results range, in particular for eutrophication, acidification and human toxicity potentials. The application of integrated pest management had significant benefits in terms of impact reduction for acidification and human toxicity of cyclamen, while reduced use of mineral nutrients through compost amendment of growing media resulted in a reduced eutrophication potential. The achievable benefits for zonal geranium were not observable because of the dominant contribution of energy inputs.

In the context of sustainable development, integrating the work aspect into health promotion systems is essential, ensuring that employees maintain a healthy balance between their professional and personal lives, which respects and amplifies the potential of every individual. Lately, there has been a noticeable shift of medical professionals from the public to the private sector. This trend paints a bleak picture, highlighting the vulnerabilities of a system teetering on the brink of failure, with significant impacts on patient care. Among the myriad reasons behind this shift, burnout stands out prominently. Medical professionals face increasing pressures due to understaffing, limited organizational support, and insufficient resources, leading to feelings of cynicism, exhaustion, and detachment from their roles. Utilizing the Maslach et al. questionnaire, we assessed the risk of burnout among physicians in public hospitals to identify and underscore preventive measures and improvements, correlating our findings with key aspects of organizational empowerment. Our research indicates that enhancing interpersonal relationships and resources—both within teams and between the organization and its physicians—is crucial for the revival of the healthcare system. This approach aims at improving the delivery of healthcare services and offering appropriate recognition to healthcare professionals, aligning with the principles of sustainable employment.

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

This study aims at providing a systematic and critical review on the state-of-the-art of life cycle applications from the circular economy point of view. In particular, the main objective is to un-derstand how researchers adapt life cycle approaches for the measurement of the empirical cir-cular pathways of agri-food systems along the overall lifespan. To perform the literature review, PRISMA protocol was considered to conduct a review by qualitative synthesis. Specifically, an evaluation matrix has been set up to gather and synthesize research evidence, by classifying pa-pers according to several integrated criteria. The literature search was carried out employing scientific databases. Findings evidence that the most common circularity topics are about closed-loop production systems, i.e. nutrient recovery for agricultural purposes, production of renewable energy, valorization of residues and wastes as fertilizers, food waste, and agro-wastes recycling for agriculture. To evaluate the benefits/impacts of CE strategies, Life Cycle Assess-ment (LCA) proved to be the most common methodology applied by authors, as it can help to meet the main CE requirements slowing and closing resource loops.

Dicarbonyls are electrophiles able to generate the so-called advanced glycation end-products (AGEs). Human exposure occurs via ingestion (e.g., food), inhalation (e.g., electronic cigarettes) and dysregulation of endogenous metabolic pathways (e.g., glycolysis). Biological systems can prevent AGEs formation via enzymatic and nonenzymatic reactions. However, the continuous exposure to dicarbonyls may cause the depletion of endogenous substrates and the beginning of AGEs accumulation (i.e., carbonylation). Since this process has been associated with multiple disorders, several studies advocated the use of dicarbonyl binders as food preservatives or as drugs aimed at mitigating carbonylation damages. As reported for other toxicants (e.g., HNE, acrolein), the screening of selective and potent binders can be performed by measuring the residual amount of a selected dicarbonyl substrate, upon its incubation with candidate binders. Unfortunately, naturally occurring dicarbonyls are poorly responsive to many detectors (e.g., UV or MS). For this reason, most of the screening methods that have been reported to date relies on indirect quantification upon derivatization. However, this strategy can potentially lead to inaccurate results since the tested compounds can affect the derivatization yield. Therefore, we herein reported the use of benzylglyoxal (BGO) as a convenient, UV responsive, dicarboyl surrogate. By using BGO as a substrate, we setup an easy and cheap chromatographic assay for the direct measurement of the binding activity towards dicarbonyls, without derivatization. The method was qualified by assessing the binding ability of some known dicarbonyl binders, obtaining results consistent with literature.

In this work we identify combinations of technological activities that signal the presence local capabilities in a country to successfully export a product. We use country-level patent and trade data to generate a multi-layer network, and we apply maximization of entropy to generate synthetic data to effectively divide signal from noise. We show that in several sectors the signal far exceed the noise. Our exercise provides robust evidence of the presence of synergies between technologies to explain trade performances in specific markets. This can be highly useful for policy makers, to inform industrial and innovation policies.

This systematic literature review explores the burgeoning use of Artificial Intelligence (AI) in manufacturing systems, in line with the principles of Industry 4.0 and the growth of smart factories. In this landscape, AI is crucial in addressing the complexity and dynamism of contemporary manufacturing processes, including machine breakdowns, fluctuating orders and unpredictable job arrivals. This systematic literature review, conducted using the Scopus database and bibliometric tools, pursues two primary objectives. First, it identifies the prevailing trends in solving scheduling problems with AI and identifies the most commonly used AI techniques in the literature. Secondly, it analyses how authors have successfully employed AI to address production scheduling challenges in real-world industrial settings and assesses the benefits obtained by companies. The dynamic nature of manufacturing systems requires adaptive scheduling paradigms. AI, including Particle Swarm Optimization, Neural Networks, and Reinforcement Learning, is applied to optimize production processes, predict machine failures, and achieve substantial benefits. In real-world applications, these AI-driven solutions have led to reduced production costs, enhanced energy efficiency, and more efficient scheduling processes. AI is increasingly recognized as an essential tool in addressing the evolving challenges of modern manufacturing environments.

The assessment of seismic risk in urban areas with high seismicity is certainly one of the most important problems that territorial managers have to face. A reliable evaluation of this risk is the basis for the design of both specific seismic improvement interventions and emergency management plans. Unappropriate seismic risk assessments may provide misleading results and induce bad decisions with relevant economic and social impact.The seismic risk in urban areas is mainly linked to three factors, namely, “hazard”, “exposure” and “vulnerability”. Hazard measures the potential of an earthquake to produce harm; exposure evaluates the amount of population exposed to harm; vulnerability represents the proneness of considered buildings to suffer damages in case of an earthquake. Estimates of such factors may not always coincide with the perceived risk of the resident population. The propensity to implement structural seismic improvement interventions aimed at reducing the vulnerability of buildings depends significantly on the perceived risk.This paper investigates on the difference between objective and perceived risk and highlights some critical issues. The aim of this study is to calibrate opportune policies, which allow addressing the most appropriate seismic risk mitigation options with reference to current levels of perceived risk. We propose the introduction of a Seismic Policy Prevention index (SPPi). This methodology is applied to a case-study focused on a densely populated district of the city of Catania (Italy).

Motor intention is a high-level brain function related to planning for movement. Although studies have shown that motor intentions can be decoded from brain signals before movement execution, it was unclear whether intentions relating to mental imagery of movement could be decoded. Here, we investigated whether differences in spatial and temporal patterns of brain activation were elicited by intentions to perform different types of motor imagery and whether the patterns could be used by a multivariate pattern classifier to detect such differential intentions. The results showed that it is possible to decode intentions before the onset of different types of motor imagery from functional MR signals obtained from fronto-parietal brain regions, such as the premotor cortex and posterior parietal cortex, while controlling for eye movements and for muscular activity of the hands. These results highlight the critical role played by the aforementioned brain regions in covert motor intentions. Moreover, they have substantial implications for rehabilitating patients with motor disabilities.

This paper focuses on the characterization approach to evaluate the decay state of Pietra Serena of historic buildings in Florence (Italy). Pietra Serena is a Florentine sandstone largely used in the city especially during the Renaissance; it is a symbol of cultural heritage of Florence and constitutes a large part of the city center, which was named a World Heritage Site by UNESCO in 1982. Unfortunately, many environmental factors negatively affect the stone, increasing damage and the danger of falling material. Any detachment of stone fragments, in addition to constitute a loss in cultural heritage, can be dangerous for citizens and the many tourists that visit the city. The use of Non-Destructive Techniques (NDTs) as ultrasonic and Schmidt hammer tests can quantitatively define some mechanical properties and help to monitor the decay degree of building stone. In this study, the NDTs were combined with mineralogical, petrographical, chemical and physical analyses to investigate the stone materials, in order to correlate their features with the characteristics of the different artefacts in Pietra Serena. Correlations between the NDTs results and the compositional characteristics of the on-site stone were carried out; such discussion allows to identify zones of weakness and dangerous unstable elements.

In this paper a novel and flexible solution for fault prediction based on data collected from Supervisory Control and Data Acquisition (SCADA) system is presented. Generic fault/status prediction is offered by means of a data driven approach based on a self-organizing map (SOM)and the definition of an original Key Performance Indicator (KPI). The model has been assessed on a park of three photovoltaic (PV) plants with installed capacity up to 10 MW, and on more than sixty inverter modules of three different technology brands. The results indicate that the proposed method is effective in predicting incipient generic faults in average up to 7 days in advance with true positives rate up to 95%. The model is easily deployable for on-line monitoring of anomalies on new PV plants and technologies, requiring only the availability of historical SCADA data, fault taxonomy and inverter electrical datasheet.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardio-vascular magnetic resonance imaging can improve the risk for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhyth-mias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

: There has been an ever-increasing demand for energy from the past decades. Renewable energy technologies play a major role in satisfying the energy demand as well as in a decreased CO2 emissions. Solar and Wind energies are the major upcoming technologies in renewable energies. Decentralized power production is a system where the energy production and consumption are very close to each other. Microgrids can be decentralized or grid connected and they, with renewable energy sources, encounter a problem of storage as the power production from solar and wind is intermittent. This paper discusses the comparison between using batteries and pumped storage hydropower (PSH) as an energy storage system and the integration of wind and solar PV energy sources. HOMER software simulations are used to obtain optimized renewable energy integration in microgrid and to understand its economic analysis. Two scenarios are run with the model where one considers battery and the other considers PSH to obtain the economic and technical best results of these microgrids. The economic analysis showed a lower net present cost (NPC) and levelized cost of energy (LCOE) for the microgrid with PSH. The results show that microgrid with storage of PSH is economical with an NPC of 45.8 M€ and an LCOE of 0.379 €/kWh in comparison with batteries solution which has an NPC of 95.2M€ and an LCOE of 0.786 €/kWh. The role of storage is understood by differentiating the data into different seasons using Python for data analysis. Furthermore, sensitivity analysis is made by varying the capital cost multiplier of Solar PV and Wind Turbine to obtain optimal solutions.

The Infectious and Tropical Diseases Department of University of Brescia organized free rapid screening tests for HIV and HCV as part of the Fast Track City commitment. A cross-sectional study was conducted, consisting of an anonymous, multiple-choice questionnaire that was administered to individuals who underwent the screening or consultation. The study aimed to compare knowledge and attitudes towards HIV and HCV between age groups (18-40 vs. >40) and sexual orientations (heterosexual vs. LGBTQ+). Overall, 333 questionnaires were completed. Individuals over the age of 40 and those who identified as heterosexual had the lowest level of knowledge about HIV transmission (7.9% and 30% respectively), undetectable=untransmittable (19.7% and 39.4% respectively) and PrEP (9.2% and 18.2% respectively). They were also less willing to cohabit with people with HIV (PLHIV). Only 9.6% of the population demonstrated high levels of knowledge for both HIV and HCV. People over the age of 40 had the largest gaps in knowledge and would benefit the most from educational and prevention interventions.

Augmented Reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications is driving new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify the value and impact in the medical-scientific field especially in the improvement of diagnostic in complex fractures. Acetabulum fractures have always been a challenge among orthopedics, for volumetric complexity and low diagnostic reliability.Background/Objectives: The goal of this study is to determine whether these methods can improve the learning aspect and diagnostic accuracy of complex acetabulum fractures compared to gold standard CT (computed tomography). Methods: Orthopedic residents of our department have been selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum have been included in the study, obtaining : CT-scans, 3DP model, and AR model displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture according to methods. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: 20 residents (JUN=10, SEN=10) classified five fractures. Overall DAs were 26% (CT), 18% (3DP), and 29% (AR). AR-DA resulted to be superior to 3DP-DA (p=0,04). DA means (JUN vs SEN respectively) were :CT-DA was 20% vs 32% (p<0.05), 3DP-DA was 12% vs 24% (p=0.08), and AR-DA was 28% vs 30% (p=0,80). Overall RT was 61.2 sec (±24,6) for CT, 35.8 sec (±20,1) for 3DP, and 46,7 sec (±20,8) for AR. R was fairly poor between methods and groups. 3DPs resulted to have superior overall C (65%). Conclusions: AR resulted to have the same Overall DA as CT, independent from experience, 3DP has minor DA and R, but it resulted to be the most confident and fast method. Intra and interobserver R between methods remain very poor in residents.

Historically, Mangifera indica L. cultivations have been widely rooted in tropical areas of India, Africa, Asia and Central America. However, at least 20 years ago its spreading allowed the development of some cultivars, also in Sicily, the South of Italy, where the favorable subtropical climate and adapted soils represent the perfect field to create new sources of production for Sicilian agricultural supply chain. Currently, cultivations of Kensington Pride, Keitt, Klenn, Maya and Tommy Atkins varieties are active in Sicilian island and their products meet the requirements of local and European markets. Mango plants produce fleshy stone fruits rich in phytochemicals with an undisputed nutritional value for its high content of flavonoids, vitamins, micro- and macro-elements, vital for maintaining health. This review provides an overview of the antioxidant, anti-inflammatory and anticancer properties of Mango, a fruit that should be included in everyone’s diet for its multifaceted biochemical actions and nutraceutical potential.

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

This paper concerns about a stepwise modelling procedure for groundwater flow simulation in a complex carbonate, folded and faulted, multilayer aquifer, in the Apennine chain in Central Ita-ly, which constitutes a source of good quality water for human consumption. A perennial river acts as the main natural drain for groundwater while sustaining valuable water related ecosys-tems. The spatial distribution of recharge was estimated using the Thornthwaite-Mather method on 60 years of climate data. The system was conceptualized as three main aquifers separated by two locally discontinuous aquitards. Three numerical models were implemented by gradually adding complexity to the model grid: single layer (2D), three layers (Quasi-3D), and five layers (Fully-3D), using an equivalent porous medium approach, in order to find the best solution with a parsimonious model setting. To overcome dry-cell problems in the Fully-3D model, the New-ton-Raphson formulation for MODFLOW-2005 was invoked. Calibration results show that a Fully-3D model was required to match the observed distribution of aquifer outflow to the river baseflow. The numerical model demonstrated the major impact of folded and faulted geological structures on controlling the flow dynamics in terms of flow direction, water heads and spatial distribution of the outflows to the river and springs.

At present European buildings typically consume two to five times more energy than predicted at the design stage. An important cause of this performance gap is the discrepancies between the design specification and the As-Built condition. Such discrepancies are mainly due to the gaps in knowhow between design, production and construction professionals. Design is more and more contained into a virtual environment and loses touch with the physical production and construction sites. As the construction sector enters the Industry 4.0 era, Building Information Modelling (BIM) based Mixed Reality can intertwine virtual and real worlds to bridge the knowhow gaps.

Ovarian cancer is the deadliest gynecological malignancy of the reproductive organs in the United States. Cyclin-dependent kinase 1 (CDK1) is an important cell cycle regulatory protein that spe-cifically controls the G2/M phase transition of the cell cycle. RO-3306 is a selective, ATP-competitive, and cell-permeable CDK1 inhibitor that shows potent anti-tumor activity in multiple pre-clinical models. In this study, we investigated the effect of CDK1 expression on the prognosis of patients with ovarian cancer and the anti-tumorigenic effect of RO-3306 in both ovarian cancer cell lines and a genetically engineered mouse model of high-grade serous ovarian cancer (KpB model). In 147 patients with epithelial ovarian cancer, overexpression of CDK1 was significantly associated with poor prognosis, compared with a low expression group. RO-3306 significantly inhibited cellular proliferation, induced apoptosis, caused cellular stress, and reduced cell migration. Treatment of KpB mice with RO-3306 for four weeks showed a significant decrease in tumor weight under obese and lean conditions without obvious side effects. Overall, our results demonstrate that inhibition of CDK1 activity by RO-3306 effectively reduces cell proliferation and tumor growth, providing biological evidence for future clinical trials of CDK1 inhibitors in ovarian cancer

We present here a case of complex uterine anomaly – Obstructed HemiVagina with Ipsilateral Renal Agenesis (OHVIRA), also known as Herlyn-Werner-Wunderlich syndrome in a 13-year-old girl with the history of recurrent urinary tract infections (rUTI). In emergency room, trans-abdominal sonography revealed ovarian cyst and renal agenesis, without any suspicion of vaginal obstruction. This led to delay in the diagnosis of this uncommon anomaly. Finally, MRI findings confirmed the presence of OHVIRA syndrome. As the congenital anomalies of kidney and urinary tract (CAKUT) are in almost one third of cases associated with genital malformations, urologist should carefully search for patients with rUTI. The patient underwent simultaneous laparoscopy and vaginoscopy, what was in our opinion the most appropriate therapeutic decision. In this article we are also going to discuss the role of laparoscopy in the management of OHVIRA syndrome as well as other surgical techniques described in the literature.

The aim of this work is to propose two different and complementary sensors for the structural health monitoring of concrete beams. In particular, a diffused sensing element and a split ring resonator network are presented. The first sensor is able to detect the variation of the dielectric properties of the concrete along the whole beam length, for a diffuse monitoring both during the important concrete curing phase and also for the entire life cycle of the concrete beams. The resonators instead work punctually, in their surroundings, allowing an accurate evaluation of the permittivity both during the drying phase and after. This allows the continuous monitoring of any presence of water both inside the concrete beam and in points that can be critical, in the case of beams in dams, bridges or in any case subject to a strong presence of water which could lead to deterioration, or worse, cause serious accidents. Moreover, the punctual sensors are able to detect the presence of cracks in the structure and to localize them.

Aujeszky Disease Virus (ADV) is a double-stranded DNA virus with a lipoprotein envelope. The natural hosts of the infection are suidae, but the virus can infect many other mammals. The gold-standard method identified by the WOAH for the diagnosis of Aujeszky disease is ELISA method. The objective of this study was to compare the performance of meat juice and oral fluid matrices using a commercial ELISA kit designed for serum. A total of 80 blood and oral fluid samples were collected from four pig farms selected for this study. Diaphragm muscle samples of about 100 g and blood samples were collected from 213 animals at the abattoir. These biological matrices were collected from the same animals and tested using a competitive ELISA kit to detect antibodies against ADV. The relative accuracy of the meat juice compared to that of the serum was 96.7% (95% CI: 93.3%-98.7%), with 206 correct results out of 213. The relative accuracy of the oral fluid compared to that of the serum was 61.3% (95% CI: 49.7%-71.9%), with 58 correct results out of 80. Meat juice has a better combination of sensitivity and specificity than oral fluid. The usage of meat juice in routine diagnostic examinations could be achieved after further investigations to optimize the procedure.

Radiomics represents the science of extraction and analysis of a multitude of quantitative features from medical imaging, unrevealing quantitative potentiality of Radiologic images. This scientific review aims to provide radiologists a comprehensive understanding of radiomics, emphasizing its principles, applications, challenges, limits, and future prospects. Limits of standardization of actual scientific production are analyzed with the possible solutions proposed by some papers reported and commented. As the continuous evolution of medical images is ongoing, radiologists must be aware of new perspective to perform a central role in patients management.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

Dealing with and maintaining high-quality standards in the design and construction phases is challenging, especially for on-site construction. Issues like improper implementation of building components and poor communication can widen the gap between design specifications and actual conditions. To prevent this, particularly for energy-efficient buildings, it's vital to develop resilient, sustainable strategies. These should optimize resource use, minimize environmental impact, and enhance livability, contributing to carbon neutrality by 2050 and climate change mitigation. Traditional post-occupancy evaluations, which identify defects after construction, are impractical for addressing energy performance gaps. A new, real-time inspection approach is necessary throughout the construction process. This paper suggests an innovative guideline for prefabricated buildings, emphasizing digital 'self-instruction' and 'self-inspection'. These procedures ensure activities impacting quality adhere to specific instructions, drawings, and 3D models, incorporating relevant acceptance criteria to verify completion. This methodology, promoting alignment with planned energy-efficient features, is supported by BIM-based software and Augmented Reality (AR) tools, embodying Industry 4.0 principles. BIM and AR bridge the gap between virtual design and actual construction, improving stakeholder communication and enabling real-time monitoring and adjustments. This integration fosters accuracy and efficiency, key for energy-efficient and Nearly Zero-Energy Buildings, marking a shift towards a more precise, collaborative, and environmentally sensible construction industry.

Durum wheat is an important staple food used to obtain several products. At first the wheat is milled to obtain different products: bran, semolina and flour. These products are the base of several artifacts with varying properties both from a nutritional point of view and flavoring characteristics. It is known that most elements concentrate in the outer layers of the wheat seed (pericarp and aleurone) so that the content of the elements vary a lot in the ground products. The present study investigates the characterizing elements of the milled products and the effect of cultivation protocol applied. We measured, by ICP-OES, the concentration of 28 elements in the whole seed and in any grinding products; the results show that only few elements characterize each product. Few elements, but different for each product, permit to disclose the kind of agri-cultural method used: organic or conventional protocol. Five elements: B, Cd, Cu, K, Se, are the most important to distinguish between organic and conventional agriculture by PCA and PLS analysis; these elements also permit some differentiation of products.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

Building more energy efficient and sustainable urban areas that will both mitigate the effect of climate change and adapt for the future climate, requires the development new tools and methods that can help urban planners, architect and communities achieve this goal. In the current study, we designed a workflow that links different methodologies developed separately, to derive the energy consumption of a university school campus for the future. Three different scenarios for typical future years (2039, 2069, 2099) were run as well as a renovation scenario (Minergie-P). We analyse the impact of climate change on the heating and cooling demand of the buildings and determined the relevance of the accounting of the local climate in this particular context. The results from the simulations showed that in the future there will a constant decrease in the heating demand while for the cooling demand there will be a significant increase. It was further demonstrated that when the local climate was taken into account there was an even higher rise in the cooling demand but also that the proposed renovations were not sufficient to design resilient buildings. We then discuss the implication of this work on the simulation of building energy consumption at the neighbourhood scale and the impact of future local climate on energy system design. We finally give a few perspective regarding improved urban design and possible pathways for the future urban areas.

This publication aims to disseminate a step-by-step process that walks through the conceptualization and building of a low-cost (~ $150 monitoring device for airborne fine particulate matter (PM2.5), based on miniaturized sensors and components. Details on the implementation of the hardware and software are provided which facilitate the data acquisition, capture and analysis. The central components and their setup discussed in what follows include: the sensor device (called “P.ALP” – Ph.D. Air quality Low-cost Project), Arduino IDE (Integrated Development Environment) and R code (open-access software). A monitoring device for PM2.5, using low-cost sensors and technologies was successfully conceptualized, designed, and implemented. The P.ALP monitoring system was designed and developed to be a basic device, which can be further customized and implemented using the wide range of low-cost sensors available on the market.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Somatosensory tactile experience is a key aspect of our interaction with the environment. It is involved in object manipulation, in the planning and control of actions and, in its affective components, in the relationships with other individuals. It is also a foundational component of body awareness. An intriguing aspect of sensory perception in general and tactile perception in particular is the way in which stimulation comes to consciousness. Indeed, although being aware of something seems a rather self-evident and monolithic aspect of our mental states, sensory awareness may be in fact modulated by many different processes that impact on the mere stimulation of the skin, including the way in which we perceive our bodies as belonging to us. In this review, we first took into consideration the pathological conditions of absence of phenomenal experience of touch, in the presence of implicit processing, as initial models for understanding the neural bases of conscious tactile experience. Subsequently, we discussed cases of tactile illusions both in normal subjects and in brain-damaged patients which help to understand which high order processes impact tactile awareness. Finally, we discussed the observations reported in the review in light of some influential models of touch and body representation.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

The 2021/2022 influenza season was not characterised by a well-defined incidence peak. A high value of incidence was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets. The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N=940) in a population of central Italy during the 2021/2022 season. A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection. These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.

The therapeutic management of acquired thrombotic thrombocytopenic purpura (aTTP) has recently benefited from the introduction of caplacizumab, an agent directed to inhibition of platelet aggregation. This real-world analysis investigated the epidemiology, the demographic and clinical characteristics of aTTP patients in Italy before and after caplacizumab introduction in 2020. Hospitalized adults with aTTP were included using the administrative databases of healthcare entities covering 17 million residents. Epidemiological estimates of aTTP considered the 3-year period before and after caplacizumab introduction. After stratification by treatment or not with caplacizumab, aTTP patients were characterized for their demographic and clinical features. The annual incidence before and after 2020 was estimated in the range 4.3-5.8 cases/million and 3.6-4.6/million, respectively. From 2018 to 2022, 393 patients with aTTP were included, 42 of them treated with caplacizumab. Caplacizumab-treated patients were aged on average 46.8 years, 31% were males, and showed tendentially better clinical outcomes: no treated patients died at either 1 month or 3 months after caplacizumab treatment initiation, compared to 10.5% (1 month) and 11.1% (3 months) mortality among the untreated. Caplacizumab treatment was associated with a trend towards shorter hospital stays. These findings suggest that caplacizumab advent provided clinical and survival benefits for patients with aTTP.

Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a crucial role in monocyte survival and differentiation. Its overexpression is associated with aggressive tumor characterized by an immunosuppressive microenvironment and poor prognosis. CSF-1R ligands, IL-34 and M-CSF, are produced by many cells in the tumor microenvironment (TME), suggesting a key role for the receptor in the crosstalk between tumor, immune and stromal cells in the TME. Recently, CSF-1R expression was reported at the cell membrane of cancer cell from different solid tumors, capturing the interest of various research group interested in investigating the role of this receptor in non-myeloid cells. This review summarizes current data available on the expression and activity of CSF-1R in different tumor types. Notably, CSF-1R+ cancer cells have been shown to produce CSF-1R ligands, indicating that CSF-1R signaling is positively regulated in autocrine manner in cancer cells. Recent research demonstrated that CSF-1R signaling enhances cell transformation by supporting tumor cell proliferation, invasion, stemness and drug resistance. In addition, this review covers recent therapeutic strategies, including monoclonal antibodies and small molecule inhibitors, targeting the CSF-1R and designed to block the pro-oncogenic role of CSF-1R in cancer cell.

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) versus Deauville score (DS) in assessing chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (age 8-16 years) were enrolled at baseline, interim (after the 2nd or 3rd chemotherapy round), and post-therapy (upon completion of first-line chemotherapy) 18F-FDG PET-CT. Interim and post-therapy DS and ΔSUVmax% were compared as response predictors. Patients were classified as responders and non-responders based on 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively in predicting response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, with a 76.8% cutoff. Sensitivity, specificity (p<0.05) and NPV (p<0.01) were significantly higher using DS than ΔSUVmax%. In conclusion, DS can predict chemotherapy response better than ΔSUVmax% in pediatric HL patients.

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.

The RAINBOW Phase III study established the efficacy of the combination of paclitaxel and ramucirumab, a monoclonal antibody targeting VEGF receptor-2 (VEGF-R2), as second-line therapy. We retrospectively analyzed the data of patients treated with ramucirumab plus paclitaxel at our Institution to evaluate the impact of clinical heterogeneous figures on the efficacy and safety of this combination paclitaxel/ramucirumab in a real- life cohort of patients. After a median follow-up of 10.74 months, the median progression-free survival (PFS) was 5.8 months (95% CI: 3.04 - 5,63). Disease control rate (DCR) was 61% and the median duration of response (DOR) was 5.8 months. Median overall survival (OS) was 8.3 months. A trend toward better outcome was observed in HER2 positive patients. In multivariate analysis, nutritional status (p = 0.0001) and number of metastatic sites (p = 0.0266) resulted significantly related with longer PFS. Our analysis confirmed the efficacy and safety of the combination of ramucirumab with paclitaxel also in the real-life practice and the median PFS is significantly longer than that reported for Western population in previous studies. Subgroup analysis confirms the key-role of nutritional status as prognostic factor and suggests a possible interaction between EGF and angiogenesis pathways that deserves further investigations.

Background: The aim of this experimental work was to evaluate cheiloscopy potential: to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject, with a focus on assessing the method's limitations. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants. All the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, but the absence of a database greatly limits its use. Additionally, its use for sex identification does not seem to be reliable. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Background: The aim of this experimental work was to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants, all the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female and the presence of sex-linked features. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, and can be a valid tool in gender determination but the absence of a database greatly limits its use. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Enhancing soil fertility and maize productivity is crucial for sustainable agriculture. This study aimed to evaluate the effects of tillage practices, nitrogen management strategies, and acidified hydrochar on soil fertility and maize productivity. The experiment used a randomized complete block design with split-split plot arrangement and four replications. Main plots received shallow tillage and deep tillage. Sub-plots were treated with nitrogen (120 kg ha⁻¹) from farmyard manure and urea, including control, 33% FYM + 67% urea (MU), and 80% FYM + 20% urea (MF). Acidified hydrochar treatments H0 (no hydrochar) and H1 (with hydrochar, 2 t ha⁻¹) were applied to sub-sub plots. Deep tillage significantly increased plant height, biological yield, grain yield, ear length, grains ear-1, thousand grain weight, and nitrogen content compared to shallow tillage. MU and MF improved growth parameters and yield over the control. Hydrochar effects varied; H1 enhanced certain yield components but reduced plant height and soil properties compared to H0. Canonical discriminant analysis linked deep tillage and MU/MF nitrogen management with improved yield and soil characteristics. In conclusion, deep tillage combined with integrated nitrogen manage-ment enhances maize productivity and soil health. However, hydrochar application requires op-timization. These findings highlight the importance of selecting appropriate tillage and nitrogen strategies for sustainable maize production. These insights guide policymakers, agronomists, and agricultural extension services in adopting evidence-based strategies for sustainable agriculture, enhancing food production, and mitigating environmental impacts. Future research should in-vestigate long-term impacts across diverse environments to validate these results.

Aim: The aim of this study is to evaluate the possibility of discriminating between the two sexes through the simultaneous use of cheiloscopy and palatine rugoscopy. Materials and methods: 80 palate and lip impressions (40 male and 40 female) were analyzed. The palate impressions were acquired using both analogue and digital methods. The lip impres-sions were first acquired analogically and then scanned. The morphology of the palatine rugae in the palate impressions was analyzed, with the exclusion of segmental rugae. The lip prints were analyzed in sextants and the morphology of the lip wrinkles was evaluated. Results: Palatine rugoscopy shows that women have more curvy rugae than men and that men have more rugae on the left side than on the right. Cheiloscopy gave no statistically significant re-sults. Discussion: Palatine rugoscopy showed some differences between the sexes, however, these re-sults were not solid enough for reliable sex discrimination. Differences between the results of dif-ferent studies can be attributed to ethnic and methodological variations. Cheiloscopy, on the other hand, did not provide statistically significant results for sex discrimination. Conclusions: Given the scant results obtained from palatine rugoscopy and the lack of statisti-cally relevant results in cheiloscopy, together with a lack of concordance among the data found in literature, it is believed that it is not possible to discriminate between the two sexes by using the two methods contemporarily. Further research is needed.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Background: Interleukin (IL)-33 is a member of interleukin (IL)-1 family of cytokines which has been linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has direct effect on human gastric epithelial cells (GES-1) and on human gastric adenocarcinoma cell line (AGS) and gastric carcinoma cell line (NCI-N87), assessing its role in regulation of cell proliferation and cell cycle, apoptosis and necrosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Methods: cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assay, we also evaluated apoptosis by Caspase 3/8 Activity assay and Annexin V assays. Cell cycle were analyzed by means of Propidium Iodine assay and gene expression regulation was assessed by RT-PCR Profiling. Results: we found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell line, while it can stimulate proliferation and reduce apoptosis in normal epithelial cell line. These effects are also confirmed by the analysis of cell cycle gene expression which showed a reduced expression of proproliferative genes in cancer cells, in particular genes involved in G0/G1 and G2/M checkpoint. These results are confirmed by the gene expression analysis on surgical and bioptic specimens. Conclusions: the aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell type-dependent fashion.

There are scarce data regarding flu vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020-2021 campaign. It evaluated subjects’ adherence over the last 3 seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to vaccinate. The population was divided into two groups: fully adherent (all 3 campaigns, 117 patients) and non-fully adherent (1 or 2 campaigns, 102 patients). Adherence increased in non-fully adherent group in 2020-2021, but the pandemic did not affect the choice. Misbelieves emerged: influenza vaccine was considered protective SARS-CoV-2 (22.8% of total population); almost half of all patients thought influenza vaccine could improve their CD4+ cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p<0.05). A quarter of the non-fully adherent group would not have vaccinated in a location other than our clinic (24.5% vs 11.9% in fully adherent group, p<0.05). Conclusively, offering a secure and private space for vaccination seems to encourage vaccination; healthcare professionals should improve counselling to increase adherence and correct misbeliefs.

Currently, one of the main challenges is the mitigation of the effects of climate change on the agricultural sector. Conventional agriculture, with the intensive use of herbicides and pesticides to control weeds and pests, and the improper use of mineral fertilizers, contributes to climate change by causing increased greenhouse gases and groundwater pollution. Therefore, more innovative technologies must be used to overcome these problems. One possible solution is nanotechnology, which has the potential to revolutionize the conventional agricultural system. Active nanoparticles can be used both as a direct source of micronutrients and as a delivery platform for bioactive agrochemicals to improve crop growth, yield and quality. The use of nanoparticle formulations, including nanopesticides, nanoherbicides, nano-fertilizers and nano-emulsions, has been extensively studied to improve crop health and shelf life of agricultural products. Comprehensive knowledge of the interactions between plants and nanoparticles opens up new opportunities to improve cropping practices through the enhancement of properties such as disease resistance, crop yield, and nutrient use. The main objective of this review is to analyze the main effects of climate change on conventional agricultural practices, such as the use of pesticides, herbicides and fertilizers. It also focuses on how the introduction of nanoparticles into conventional practices can improve the efficiency of chemical pest control and crop nutrition. Finally, this review examines in depth the last 10 years (2014-2024) of scientific literature regarding the use of nanoparticles in agriculture to mitigate the effects of climate change.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.

Background Main treatment modality for spinal meningiomas (SM) is gross total resection (GTR). However, optimal timing of surgery, especially in cases with absent or mild neurological symptoms remains unclear. The aim of this study is to assess the impact of early-stage resection on neurological outcome, quality of life (QoL) and quality of care. The primary objective was a favorable neurological outcome (McCormick scale 1); Methods: We retrospectively analyzed data from patients operated on SM between 2011 and 2021. Patients with mild neurological symptoms preoperatively (McCormick scale 1 and 2) were compared to those with more severe neurological symptoms (McCormick scale 3-5). Disabilities and QoL were assessed according to validated questionnaires (SF36, ODI, NDI). Results: Age, spinal cord edema, thoracic localization, and spinal canal occupancy ratio were associated with more severe neurological symptoms (all p<.05). Patients presented with mild symptoms were associated with favorable neurological outcome (OR: 14.778 (95%CI 3.918-55.746, p<.001), which is associated with shorter hospitalization, better QoL and less disabilities (p<.05). Quality of care was comparable in both cohorts; Conclusions: Early surgical intervention of SM, before the development of severe neurological deficits, should be considered as it is associated with a favorable neurological outcome and quality of life.

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

Covid-19 disease is caused by SARS Cov-2 virus. Despite its high transmissibility, the CFR (Case Fatality Rate) of COVID-19 seems to be lower than the SARS (9,5%) and MERS (34,4%) ones⁹³ , but higher than the influenza one (0-1%)^94,95 . The disease is asymptomatic or paucisymptomatic in most of the patients, although in few cases it can be characterized by serious complications. The main causes of hospitalization in intensive care are represented by ALI (Acute Lung Injury), ARDS (Acute Respiratory Distress Syndrome), cardiovascular problems and coagulopathies (diffuse thrombosis, microthrombosis, embolisms, myocarditis, arrhytmias, heart failure, stroke)^96-98, acute nephropathy^99,100 and encephalopathies¹⁰¹. The virus presence in the vascular wall can cause endotheliitis, which triggers the process of diffuse coagulation that can lead to a worsening of the systemic inflammation. The exaggerated inflammatory response seems to be connected with the development of ARDS, MOF (Multiple Organ Failure) and coagulopathies^102-107.

The “red code” (RD) represents the highest levels of emergency in the emergency department (ED). The study retrospectively analyzed RDs in the Regina Margherita Children’s Hospital ED, a regional referral center in north Italy, between 1 July 2020 and 30 June 2023. The aim was to describe RD characteristics and to identify significant correlations between presenting complaints and clinical management. The study includes 934 RDs (0.9% of overall ED admissions); 64% were assigned based on the Pediatric Assessment Triangle alteration. Most patients, 86.5%, followed the medical pathway, while 13.5% were surgical cases. Admission complaints were respiratory (46.9%), neuropsychiatric (26.7%), traumatic (11.8%), cardiologic (9.3%), metabolic (3.8%), and surgical (1.5%). Seventy-six per cent of patients received vascular access, and intraosseous access was obtained in 2.2% of them. In one-third of RDs, an urgent critical care evaluation was necessary, and 19% of cases required admission to the intensive care unit. The overall mortality rate was 3.4% (0.4% in ED setting). The study identified six distinct diagnostic pathways, each associated with specific characteristics in clinical presentation, management, therapeutic interventions, and outcomes: this underscored the significance of a systematic approach in improving outcomes in pediatric RD management.

Traditionally, overnight fasting before elective surgery has been the routine in medical practice for risk reduction of pulmonary aspiration of gastric contents. Several original study and international societies recommend a 2‐h preoperative fast for clear fluids and a 6‐h fast for solids in most elective patients. We conducted a narrative review of the literature, searching electronic databases (Medline and CINAHL). We used PICO approach. The results of our review suggest that nutrition support in the perioperative period is very important to reduce length of hospital stay and reduced postoperative complication.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Background: During the stay in the neonatal intensive care unit, parents play a crucial role in the care of their infants. Recent studies reported a decrease in parental participation due to Coronavirus Disease (COVID-19) pandemic that determined restricted access policies in hospitals. The aim of this study is to describe the barriers to a good parents’ participation during the stay in the neonatal intensive care unit in the COVID-19 era. Methods: A quantitative observational study was carried out. Results: 270 parents participated in this study. Mothers’ participation in care seems to be higher as compared to fathers (p = 0.017). Parents who lived the birth of their first child reported a better level of participation in care when compared to those who lived the birth of their second born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infant if compared to parents of term newborns (p &lt; 0.001). Conclusions: Some more disadvantaged categories have reported lower scores: cultural and linguistic minorities, parents of multiple children and fathers. COVID-19 pandemic made several Family Centred Care activities not possible with a higher impact on those who benefited the most of these facilities. This study was prospectively registered by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on the 23/01/2024 with registration number CRRM;2023_12_07_01.

Nonsense mutations cause several genetic diseases such as Cystic fibrosis, Duchenne muscular dystrophy, β-thalassemia, and Shwachman-Diamond syndrome. These mutations induce the formation of a premature termination codon (PTC) inside the mRNA sequence that leads to the aberrant translation, resulting in the synthesis of truncated polypeptides. Nonsense suppression therapy mediated by translational readthrough-inducing drugs (TRIDs) is a promising approach to correct these genetic defects. TRIDs generate a ribosome miscoding of the PTC named “translational readthrough” and restore the synthesis of full-length and potentially functional protein. The new oxadiazole-core TRIDs NV848, NV914, and NV930 showed translational readthrough activity in nonsense-related in vitro systems. In this work, the possible off-target effect of NV molecules on natural termination codons (NTCs) was investigated. Two different in vitro approaches were used to assess if the NV molecules treatment induce NTCs readthrough: 1) A study of translational induced p53 molecular weight and functionality; 2) the evaluation of two housekeeping proteins (Cys-C and β2M) molecular weights. Our results showed that the treatment with NV848, NV914, or NV930 do not induce any translation alterations in both experimental systems. Data suggested that NV molecules have a specific action for the PTCs and an undetectable effect on the NTCs.

Scintillators play a key role in the detection chain of several applications which rely on the use of ionizing radiation, and it is often mandatory to extract and detect the generated scintillation light as efficiently as possible. In positron emission tomography (PET), for example, both energy resolution and coincidence resolving time, two of the key detection parameters, depend strongly on the total amount of light which reaches the photodetector surface as well as its spatial and temporal distribution. Typical inorganic scintillators do however feature a high index of refraction, which impacts light extraction efficiency in a negative way. Furthermore, several applications such as preclinical PET rely on pixelated scintillators with small pitch. In this case, applying reflectors on the crystal pixel surface, as done conventionally, can have a dramatic impact of the packing fraction and thus the overall system sensitivity. This paper presents a study on light extraction techniques, as well as combinations thereof, for two of the most used inorganic scintillators (LYSO and BGO). Novel approaches, employing distributed Bragg reflectors (DBRs), metal coatings, and a modified Photonic Crystal (PhC) structure, are described in detail and compared with commonly used techniques. The nanostructure of the PhC is surrounded by a hybrid organic/inorganic silica sol-gel buffer layer which ensures robustness while maintaining its performance unchanged. We observed in particular a maximum light gain of about 41% on light extraction and 21% on energy resolution for BGO, a scintillator which has gained interest in the recent past due to its prompt Cherenkov component and lower cost.

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

The remote monitoring of clinical parameters plays a fundamental role in different situations, like pandemic health emergencies and post-surgery conditions. In these situations, the patients might be impeded in their movements and it could be difficult to have a specific health monitoring. In recent years, technological advancements in smartphones have opened up new possibilities in this landscape. The present work aims to propose a new method for respiratory kinematics monitoring via smartphone sensors. In particular, a specific application was developed to register Inertial Movement Unit (IMU) sensors data from the smartphone for respiratory kinematics measurement and to guide the user through a specific acquisition session. The session was defined to allow for the monitoring of the respiratory movement in five prescribed positions. The application and the sequence were successfully tested on a given population of 77 healthy volunteers. The resulting accelerometers and gyroscope signals were processed to evaluate the significance of differences according to participants sex, vector components and smartphone positioning and, finally, to estimate the respiratory rate. The emerged statistical differences revealed the significance of information in the different acquisition positions.

The purpose of this Individually Randomized Group Treatment Trial was to compare an Acceptance and Commitment Therapy-based (ACT) group intervention and a Cog-nitive Behavioral Therapy-based (CBT) group intervention for weight loss maintenance in a sample of adult patients with obesity seeking treatment for weight loss. 155 over-weight adults (BMI: Kg/m2= 43.8[6.8]) attending a multidisciplinary rehabilitation program for weight loss were randomized into two conditions: ACT and CBT. Demo-graphical, physical, and clinical data were assessed at the beginning of the program (t0), at discharge (t1), and at 6-month follow-up (t2). The following measures were ad-ministered: The Acceptance and Action Questionnaire-II (AAQ-II) and the Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM). Generalized linear mixed models were performed to assess differences between groups. Moderation ef-fects for gender and eating disorders (ED) have been considered. From baseline to dis-charge no significant differences between interventions were found, with the only ex-ception of an improvement in the CORE-OM total score and in the CORE-OM subjective well-being subscale for those in the CBT condition. From discharge to follow-up ACT group participants showed significant results in terms of weight loss maintenance, CORE-OM total score, and CORE-OM and AAQ-II’s wellbeing, symptoms, and psy-chological problems subscales. Gender moderated the effects of time and intervention on the CORE-OM’ subscale reporting the risk for self-harm or harm others. The pres-ence of an eating disorder moderated the effect of time and intervention on the CORE-OM total score, on the CORE-Om’ symptoms and psychological problems sub-scales, and on the AAQ-II. Patients who received the ACT intervention were more likely to achieve a ≥5% weight loss from baseline to follow-up and to maintain the weight loss after discharge. The ACT intervention was thus effective in maintaining weight loss over time.

Esophageal cancer is an extremely deadly tumor that accounts for 5% of all cancer deaths. The two main subtypes of the disease are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To date, few studies analyse EAC for transcriptional signatures associated with diagnosis and/or prognosis, while most focus on the analysis of transcriptional profiles of ESCC. In this study, we used single-cell RNA sequencing (scRNA-seq) analysis of CD45+ cells enriched from Tumors and matched Non Tumor tissues from therapy naїve patients to identify all types of immune cells present in tumor immune infiltrate and its transcriptional profile. In addi-tion, we analysed the entire transcriptome in a cohort of 23 patients whose tissue biopsies were taken from Tumors and matched with Non Tumor tissue. The transcriptional signatures we obtained were then used to stratify a large cohort of TCGA EAC patients, demonstrating a strong association with their prognosis, as well as the ability to predict a patient's clinical outcome and better define the prognosis of EAC after surgery. In addition, these features may lead patients to effective therapies including immunotherapy approaches.

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this preliminary study, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for controls). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S individuals was defined by higher levels of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older individuals with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.

Background and Objectives Transpulmonary thermodilution has gained interest in recent years. It measures cardiac output (CO), stroke volume (SV), but also calculates global end diastolic indexed volume (GEDVI), and global ejection fraction (GEF). GEDVI is a static variable of cardiac preload. GEF provides information regarding cardiac function. GEF algorithm depends on SV and GEDVI. Therefore, in hypovolemic patients with decreased preload, SV or GEDVI could be decreased, and lead to altered GEF. The aim of our work was to evaluate whether impairment in GEDVI and SV may constitute a limitation for the interpretation of GEF in hypovolemic patients. A secondary objective was to determine factors independently associated with impaired GEF. Materials and Methods A retrospective study was conducted. Statistical analysis was performed by means of Mann Whitney and student t test. To determine correlation between GEF with SV, or GEF with GEDVI Pearson's coefficient was used. To determine factors independently associated with the presence of impaired GEF, binary logistic regression was performed. Results We included 113 patients with shock. Differences in mortality were detected in GEF (21[16-28] survivors versus 18 in non survivors[11-26]; p= 0.01). 38(34%) patients had hypovolemia. 44(39%) of them had depressed GEF values. Hypovolemic patients had lower GEF values than non-hypovolemic patients (16 [12-22] vs 20 [15-27]; p=0.01). Both SV and GEDVI had a statistically significant correlation with GEF (SV (Pearson's r 0.74; (p=0.00)) and GEDVI (Pearson's r -0.25; (p=0.00)). The only factors independently associated with low GEF were low SV and low GEDVI. Conclusion Hypovolemic patients frequently show low GEF values. We found correlation between SV and GEDVI with GEF. Low SV and low GEDVI were associated with low GEF. This could constitute a limitation in the interpretation of GEF and cardiac pump function. Hypovolemic patients could have low GEF without implying disorders in cardiac contractility.

.Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology. However the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-β-Gal in kidney biopsies obtained in a cohort [n=29] of incident patients who were followed up for 3 years as for standard of care. SA-β-Gal staining was approximately 4-fold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-β-Gal, but not proteinuria at the time of biopsy correlated with eGFR loss at follow-up; moreover, SA-β-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In summary, our study shows that SA-β-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD, and suggests that tubular SA-β-Gal is associated with accelerated loss of renal function.

An innovative wireless sensor network (WSN) based on Ultra-Wide Band (UWB) technology for 3D accurate superficial monitoring of ground deformations, as landslides and subsidence, is proposed. The system has been designed and developed as part of an European Life+ project, called Wi-GIM (Wireless Sensor Network for Ground Instability Monitoring). The details of the architecture, the localization via wireless technology and data processing protocols are described. The flexibility and accuracy achieved by the UWB two-way ranging technique is analysed and compared with the traditional systems, such as robotic total stations (RTSs), Ground-based Interferometric Synthetic Aperture Radar (GB-InSAR), highlighting the pros and cons of the UWB solution to detect the surface movements. An extensive field trial campaign allows the validation of the system and the analysis of its sensitivity to different factors (e.g., sensor nodes inter-visibility, effects of the temperature, etc.). The Wi-GIM system represents a promising solution for landslide monitoring and it can be adopted in conjunction with traditional systems or as an alternative in areas where the available resources are inadequate. The versatility, easy/fast deployment and cost-effectiveness, together with the good accuracy, make the Wi-GIM system a possible solution for municipalities that cannot afford expensive/complex systems to monitor potential landslides in their territory.

There are thousands of rare genetic diseases that could be treated with classical gene therapy strategies such as the addition of the defective gene via viral or non-viral delivery or by direct gene editing. However, several genetic defects are too complex for these approaches. These “genomic mutations” include aneuploidies, intra and inter chromosomal rearrangements, large deletions, or inversion and copy number variations. Chromosome Transplantation (CT) refers to the precise substitution of an endogenous chromosome with an exogenous one. By the addition of an exogenous chromosome and the concomitant elimination of the endogenous one, every genetic defect, irrespective of its nature, could be resolved. In the current review, we analyze the state of the art of this technique and discuss its possible application to human pathology. CT might not be limited to the treatment of human diseases. By working on sex chromosomes, we showed that female cells can be obtained from male cells, since chromosome-transplanted cells can lose either sex chromosome, giving rise to 46,XY or 46,XX diploid cells, a modification that could be exploited to obtain female gametes from male cells. Moreover, CT could be used in veterinary biology, since entire chromosomes containing an advantageous locus could be transferred to animals of zootechnical interest without altering their specific genetic background and the need for long and complex interbreeding. CT could also be useful to rescue extinct species if only male cells were available. Finally, the generation of “synthetic” cells could be achieved by repeated CT into a recipient cell. CT is an additional tool for genetic modification of mammalian cells.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Gold nanohole arrays are periodic metastructures gathering huge interest for biosensing applica-tions. The grating-like structure defines their plasmonic mode features and their angular disper-sion can be used to highlight efficiently their interaction with the fluorescence emission of a properly tuned fluorophore. Resorting to a properly tuned/engineered/optimised plasmonic na-nohole array and a commercial organic dye, we performed an accurate resolved angle-resolved optical characterization. The plasmonic fingerprints was consequently identified as a modification of the dye photoluminescence signal in terms of both spectral redistribution and enhancement. Interestingly, by analyzing the results, an advantageous measurement configuration can be iden-tified to better engineer a suitable platform for efficiency maximization in plasmon-enhanced flu-orescence-based applications. Therefore, the coupling mechanism with the plasmonic modes, and nanostructure properties can be carefully co-optimized.

We sought to compare native T1 mapping to conventional Late gadolinium enhancement (LGE) and T2-STIR techniques in a cohort of consecutive patients undergoing cardiac MRI (CMR).. CMR was performed in 323 patients, 206 males (64%), mean age 54±8 years and in 27 age- and sex- matched healthy controls. At T2-STIR images myocardial hyperintensity suggesting edema was found in 41 patients (27%). LGE images were positive in 206 patients (64%). T1 mapping was abnormal in 171 (49%). In 206 patients (64%) a matching between LGE and native T1 was found. T1 was abnormal in 32 out of 41 (78%) with edema at T2-STIR. Overall, LGE and/or T2-STIR were abnormal in 209 patients, whereas native T1 in 154(52%). Conventional techniques and T1 mapping were concordant in 208 patients (64%). In 39 patients T1 mapping was positive despite negative conventional techniques (12%). T1 mapping was able in conditions with diffuse myocardial damage as cardiac amyloidosis, scleroderma and Fabry disease (additive role in 42%). On contrast, T1 mapping was less effective in cardiac disease with regional distribution of myocardial damage as myocardial infarction, HCM, myocarditis. In conclusion, conventional LGE/T2-STIR and T1 mapping are complementary techniques and should be used together in every CMR examination.

After the influenza H1N1 pandemic of 2009, the seasonal A/Brisbane/59/2007 strain was replaced by the A/California/07/2009 strain for the influenza virus vaccine composition. After several seasons with no indications on the occurrence of antigenic drift, A/Michigan/45/2015 was chosen as the H1N1 vaccine strain for season 2017/2018. Since the immune response to influenza is shaped by the history of exposure to antigenically similar strains, the potential cross-protection between seasonal human influenza vaccine strains and the emerging pandemic strains was investigated. Human serum samples were tested by haemagglutination inhibition and single radial haemolysis assays against A/Brisbane/59/2007, A/California/07/2009, and A/Michigan/45/2015 strains. Strong cross-reactions between A/California/07/2009 and A/Michigan/45/2015 strains were observed in 2009/2010, most likely induced by the start of the 2009 pandemic, and the subsequent post-pandemic seasons from 2010/2011 onwards when A/California/07/2009 becomes the predominant strain. In 2014/2015 season, population immunity against A/California/07/2009 and A/Michigan/45/2015 strains increased again, associated with strong cross-reactions. While haemagglutination inhibition assay has a higher sensitivity for detection of new seasonal drift, the single radial haemolysis assay is an excellent tool to determine the presence of pre-existing immunity, allowing a potential prediction on the booster potential of influenza vaccines against newly emerging drifted strains.

Inflammatory Bowel Disease (IBD) is a chronic and progressive inflammatory disorder affecting the gastrointestinal tract (GT) caused by a wide range of genetic, microbial, and environmental factors. IBD is characterized by chronic inflammation, decreased gut microbial diversity and dysbiosis, with a lower amount of beneficial bacteria and a concomitant increase of pathogenic species. It is well known that dysbiosis is closely related to the induction of inflammation and oxidative stress, this last caused by an imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity that leads to cellular ROS accumulation. ROS are responsible for the intestinal epithelium oxidative damage and the increased intestinal permeability found in IBD patients and their reduction could represent a potential therapeutic strategy to limit the IBD progression and alleviate its symptom. Recent evidence highlighted that dietary polyphenols, natural antioxidants, are able to maintain redox equilibrium in the GT preventing gut dysbiosis, intestinal epithelium damage and radical inflammatory responses. Here, we suggest that the relatively new foodomics approaches, together with new technologies for promoting the antioxidative properties of dietary polyphenols, including novel delivery systems, chemical modifications and combination strategies, may provide critical insight to determine the clinical value of polyphenols for IBD therapy and a comprehensive perspective for implementing natural antioxidants as potential IBD candidate treatment.

: Introduction: Discovering compounds with antibacterial activity is crucial in the current fight against antibiotic-resistance. Material and Methods: We generate two QSAR model to design six new heteroaryl drug candidates; we assessed the antibacterial properties of the compounds against nine ATCC strains, the majority being part of the ESKAPE group, that include Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and also Salmonella enterica and Escherichia coli. We performed a synergic assay in which we combined PB4, a compound that we have previously tested in published studies, with GC-VI-70, one of the new compounds with the best cytotoxicity/MIC profile. We tested sub-MIC concentrations of PB4 with five antibiotics (linezolid, gentamycin, ampicillin, erythromycin, rifampin and imipenem) to examine the synergic effect on the ATCC strains. To evaluate compounds’ cytotoxicity, we performed a 24-hour and 48-hour 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Colorectal Adenocarcinoma (CaCo-2) cells. The antibiotics were tested, alone and in combination with PB4. Results: PB4 lowered the MIC measured for GC-VI-70 and for the various antibiotics employed in clinical use, and all the compounds presented in this study have cytotoxic activity against cells. Conclusions: These compounds show promising use in combination with antibiotics to improve their effectiveness at low concentrations, to prevent unwanted cytotoxic effects.

SARS-CoV-2 pandemic caused an increase in Intensive Care Unit (ICU) hospitalizations with rise in morbidity and mortality; nevertheless, there is still little evidence of pandemic impact on antibiotic resistance in ICU. Retrospective monocentric epidemiological study. All microorganisms isolated from all patients admitted to E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. Aim of the study was to describe and analyze the impact of SARS-CoV-2 pandemic on ICU microorganisms resistance patterns. 1,771 microorganisms identified, 221 (12.47%) had resistant pattern (Resistant Organisms; ROs) isolated from 1,679 patients during 12,030 hospitalization days. The majority of ROs were Gram-negative (79.66% 2018, 77.29% 2019, 61.83% 2020, 62.56% 2021, 60.75% 2022), but increase of Gram-positive microorganisms was observed (20.34% to 39.25% between 2018-2022). Prevalence of AR was: 19.44% 2018, 11.54% 2019, 38.04% 2020, 34.15% 2021, 39.29% 2022 for Gram-positives; 19.86%, 13.56%, 18.12%, 12.41%, 12.31% for Gram-negatives. Incidence of Ros showed COVID-related rise in 2020-2021, followed by a lowering trend since 2021, with new rise in 2022. Possible explanations are antibiotic overtreatment and drop of containing measures. Interesting finding is the cumulative lowering trend of carbapenem resistant K. pneumoniae and P. aeruginosa probably due to different patient features.

We statistically investigate the Coronavirus Disease 19 (hereinafter Covid-19) epidemics, which is particularly invasive in Italy. We show that the high apparent mortality (or Case Fatality Ratio, CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of infected cases. To give a more realistic estimate of the mortality of Covid-19, we use the most recent estimates of the IFR (Infection Fatality Ratio) of epidemic, based on the minimum observed CFR, and furthermore analyse data obtained from the ship Diamond Princess, a good representation of a ‘laboratory’ case-study from an isolated system in which all the people have been tested. From such analyses we derive more realistic estimates of the real extension of the infection, as well as more accurate indicators of how fast the infection propagates. We then point out from the various explanations proposed, the dominant factors causing such an abnormal seriousness of the disease in Italy. Finally, we use the deceased data, the only ones estimated to be reliable enough, to predict the total number of infected people and the interval of time when the infection in Italy could stop.