This study explores the integration of Artificial Intelligence (AI) and collaborative robotics in industrial surface finishing, focusing on feature detection on object reflective surfaces using neural networks in computationally constrained environments. Central to this investigation is the utilization of cameras considered as sensors that can capture detailed images of reflective surfaces. These images are then analyzed by a custom neural network, demonstrating the feasibility of feature detection with non-powerful computers. The public dataset for recognizing light reflection defects, available in the SPADD repository, supports this approach. Employing open-source tools like Darknet YOLOv3 and Yolo\_mark, this method proves particularly advantageous for small and medium-sized enterprises (SMEs) due to its low cost and maintenance requirements. This research highlights the challenges of AI and collaborative robotics in industrial applications, especially in adapting to varying conditions and the need for continuous training with new data coming from several sensors. Looking ahead, plans are in place to integrate this system with cobot-assisted polishing tasks, using cameras to enhance manufacturing efficiency and quality. This work contributes to the broader understanding of practical applications of AI in industrial automation, surface finishing processes, and the effective use of sensor technology.

This study examines the practicality and limitations of using a FANUC CRX-10 iA/l collaborative robot to assemble a product component, highlighting the trade-offs between increased roboisation and reduced manual intervention. Through a detailed case study in the i-Labs laboratory, critical factors affecting precision assembly such as station layout, tooling design and robot programming are discussed. The findings highlight the benefits of robots for non-stop operation, freeing up human operators for higher value tasks despite longer cycle times. In addition, the paper advocates further research into reliable gripping of small components, a current challenge for robotics. The work contributes to open science by sharing partial results and methods that could inform future problem solving in robotic assembly.

This paper presents a framework for the motion planning and control of redundant manipulators with the added task of collision avoidance. The algorithms that were previously studied and tested by the authors for planar cases are here extended to full mobility redundant manipulators operating in a three-dimensional workspace. The control strategy consists of a combination of off-line path planning algorithms with on-line motion control. The path planning algorithm is used to generate trajectories able to avoid fixed obstacles, detected before the robot starts to move; it is based on the potential fields method combined with a smoothing interpolation that exploits Bézier curves. The on-line motion control is designed to compensate for the motion of the obstacles and to avoid collisions along the kinematic chain of the manipulator; it is realized by means of a velocity control law based on the null space method for redundancy control. A term of the control law takes into account the speed of the obstacles as well as their position. In order to test the algorithms, a set of simulations are presented: the robot KUKA LBR iiwa is controlled in different cases, where fixed or dynamic obstacles interfere with its motion. Simulations are also used to estimate the required computational effort in order to verify the transferability to a real system.

In factory automation systems, hybrid wired/wireless networks are often deployed to connect devices of difficult reachability such as those mounted on mobile equipment. A widespread version of these networks makes use of Access Points (APs) to implement wireless extensions of Real--Time Ethernet (RTE) networks via the IEEE 802.11 Wireless LAN (WLAN). Unfortunately, APs may introduce random delays in packet forwarding, mainly related to the their internal behaviors (e.g. code processing times) that negatively impact on the whole performance of the automation systems. Consequently, the knowledge of these delays represent a crucial design information. This paper presents an original and effective method to measure the delays introduced by APs, exploiting a hybrid loop-back link and a simple set-up with moderate instrumentation requirements. The method, which requires an initial calibration by means of a reference AP, has been successfully tested on some commercial APs. As it will be shown, the proposed measurement procedure is general and, as such, can be profitably adopted in even different scenarios.

Background: To assess effectiveness, safety of computed tomography (CT)-guided cryoablation for treating adrenal metastases (AMs). Materials and Methods: This study involved 12 patients treated with 13 CT-guided cryoablation procedures for AMs between 2016 and 2020. Patients’ ineligible for surgery, with tumors ≤5 cm, and no significant health risks were included. The procedures, conducted by expert radiologists, included initial non-contrast CT scans to determine lesion morphology, followed by cryoablation with monitoring for complications. Post-treatment, patients underwent regular physical and laboratory checks, including hormonal analysis, and CT scans at specified intervals to assess the treatment's effectiveness and detect disease recurrence or progression. Results: In this study, 12 patients with AMs successfully underwent cryoablation, achieving a primary technical success rate of 91.7% and a secondary rate of 100% after a repeat procedure for one patient. All cryoablation sessions were completed without major complications, with ice ball formations extending 1 cm beyond tumor margins to ensure safety. Over an 8–24-month follow-up (average 16.3 months), six patients required further systemic therapy, with three developing extra-adrenal tumors. Local progression was noted in two patients (16.7%), one of whom underwent a repeat cryoablation. Systemic progression was observed in five patients, involving renal and NSCLC cancer recurrences and bone metastasis. The study reported five deaths due to tumor progression and heart failure, with an average overall survival duration of 32.4 ± 7.6 months.

The human microbiome is an extremely complex ecosystem considering the amount of bacterial species, their interactions, and its variability over time. Here we untangle the complexity of the human microbiome for the Irritable Bowel Syndrome (IBS) that is the most prevalent functional gastrointestinal disorder in human populations. Based on a novel information theoretic network inference model we detect species interaction networks that are functionally and structurally different for healthy and unhealthy individuals. Healthy networks are characterized by a neutral symmetrical pattern of species interactions and scale-free topology versus random unhealthy networks. We detect an inverse scaling relationship between species total outgoing information flow, meaningful of node interactivity, and relative species abundance (RSA). The top ten interacting species are also the least relatively abundant for the healthy microbiome and the most detrimental. These findings support the idea about the diminishing role of network hubs and hubs should be defined considering the total outgoing information flow rather than the node degree. Macroecologically, the healthy microbiome is characterized by the highest total species diversity growth rate, the lowest species turnover, and the smallest variability of RSA for all species. This result challenges current views that posit a universal association between healthy states and the highest absolute species diversity in ecosystems. Additionally, we show how the transitory microbiome is unstable and microbiome criticality is not at the phase transition between healthy and unhealthy states. We stress out the importance of considering interacting pairs versus single node dynamics when characterizing the microbiome and of ranking these pairs in terms of their dynamics. Interactions (i.e. species collective behavior) shape transition from healthy to unhealthy states.\\ The macroecological characterization of the microbiome is useful for diagnostic purposes and disease etiognosis, while species-specific analyses can detect species that are more beneficial leading to personalized design of pre- and pro-biotic treatments and microbiome engineering.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffer from poor generalization ability in presence of dataset shift. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black-box model (Random Forest), both studied with the aim to support clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

Having sustained, over the course of more than two decades, record-breaking natural catastrophe losses, American insurers and reinsurers are justifiably questioning the potential linkage between anthropogenic climate change and extreme weather. Here, we explore issues pertaining to this linkage, looking at both the likely short-term implications for the insurance industry, as well as potential longer-term impacts on financial performance and corporate resilience. We begin our discussion with an overview of the implications that climate change is likely to have on the industry, especially as it relates to how catastrophic risks are construed, assessed, and managed. We then present the rudiments of an econometric analysis that explores the financial resilience of the property/casualty (P/C) industry in the face of both natural and man-made catastrophes. In this analysis, we explore the profitability consequences of several illustrative scenarios involving large-scale losses from extreme weather—specifically, a sequence of storms like those striking the U.S. in 2004—and a scenario that explores the prospect of a Katrina-scale storm in combination with a mass terror attack on the scale of 9/11. At systemic levels of aggregation, our analysis suggests a high degree of macro-resilience for the insurance industry. Moreover, we find that insurer resilience is higher for larger impacts, considering both the speed of recovery, as well as the inverse of the area under the unaffected system profile. We conclude with a summary of our findings and a closing commentary that explores the potential implications of these results for P/C insurers moving forward.

Over the past several years there has been much debate with regards to the prognostic and clinical significance of pancreatic ductal adenocarcinoma (PDAC) with lymph nodes metastasis. The PDAC gene-expression knowledge and the biologic alterations underlying the lymph node involvement convey a clinical implication in dealing with the theranostic window.To this end, we provide an original bioinformatic dissection of the gene-expression differences of PDAC according to the nodal involvement from a large public available dataset. Comprehensive transcriptomic analysis from 143 RNA-seq patient’s derived samples indicated that WNT increased activation and a peculiar immune-microenvironment identify subjects with nodal involvement.In frame of this thinking, we validated the WNT pathway role in increasing the likelihood of lymphatic dissemination in vitro. Moreover, we demonstrated for the first time in a PDAC model the potential therapeutic window that XAV-939, a specific WNT pathway inhibitor, has in re-educating a tumour permissive immune system. Finally, we outline the potential implication on bystander molecular drivers exerted by WNT molecular inhibition, providing a picture of the proteomic oncogenic landscape changes elicited by XAV-939 on PDAC cells and their clinical implication. Our findings hold the promise to identify novel immune-based therapeutic strategies targeting WNT to enhance PDAC cytotoxicity and restore anti-PDAC immunity in nodes-positive disease.

We describe an interesting case report about a patient with hemophilia A with severe chronic elbow arthropathy who underwent multiple surgical because of his condition. We collected all the clinical and imaging findings, and we compared the decision-making flow chart and the surgery performed with the most recent indications, treatments and complications reported in the literature. The aim of this case report is to show how usually the hemophilic patient even if young usually comes to our attention from the beginning with complex and advance musculoskeletal disease. Elbow hemophilic arthropathy is a complex disease and the management in these patients could be more difficult than others because of the higher risk of complications rate after all surgical procedures, for this reason it’s very important to treat these patients in hub centers with expertise in well-coordinated multidisciplinary teams. The path from diagnosis to surgical treatment of hemophilic elbow arthropathy can be a risky one, as it happened in this case.

This paper reinterprets, differently from the existing literature, the relationship between law and economics not from the point of view of a lawyer-economist but rather from the point of view of an economist-mathematician, and it raises a methodological issue. To do so, some of the elements of the theory of sets are borrowed to argue that behavioral economics, its application to behavioral law and economics, and behavioral economists have generalized the pioneering work of Judge Calabresi, with reference to the famous books ‘Tragic Choices’ and ‘The Future of Law and Economics – Essays in Reform and Recollection’. Even if the usage of the theory of sets made in this paper is intuitive, some of its basics are reviewed in the appendix.

In this work, we experimentally investigate mass and heat transport phenomena in a modular device while converting a solution salinity difference into a temperature difference. Operations occur under fixed total ambient pressure and without mechanical moving parts, thus realizing a fully static conversion. Provided that a constant salinity gradient can be imposed, the proposed device is able to generate a steady cooling capacity. Here, we purposely operate with environmentally benign and easily accessible sodium chloride water solutions only. A numerical model is finally elaborated, validated and used to explore a wider range of possible device configurations and operating conditions.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

To maintain proteostasis, cells must integrate information and activities that supervise protein synthesis, protein folding, conformational stability, and also protein degradation. Extrinsic and intrinsic conditions can both impact on normal proteostasis, causing the appearance of proteotoxic stress. Initially, proteotoxic stress elicits adaptive responses aimed to restore proteostasis, allowing cells to survival the stress condition. However, if the proteostasis restoration fails, a permanent and sustained proteotoxic stress can be deleterious and cell death ensues. Many cancer cells convive with high levels of proteotoxic stress and this condition could be exploited in a therapeutic perspective. Understanding the cell death pathways engaged by proteotoxic stress is instrumental to better hijack the proliferative fate of cancer cells.

The details of abiogenesis to date remain a matter of debate and constitute a key mystery in science and philosophy. The prevailing scientific hypothesis implies an evolutionary process of increasing complexity on earth starting from (self-) replicating polymers. Defining the cut-off point where life begins is another moot point beyond the scope of this article. We will instead walk through the known evolutionary steps that lead from these first exceptional polymers to the vast network of living biomatter that spans our world today, focusing in particular on perception, from simple biological feedback mechanisms to the complexity that allows for abstract thought. We then will project from the well-known to the unknown to gain a glimpse on what the universe aims to accomplish with living matter, just to find that if the universe had ever planned to be comprehended, evolution still has a long way to go.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

Biosensors detect specific bio-analytes by generating a measurable signal from the interaction between the sensing element and the target molecule. Surface acoustic wave (SAW) biosensors offer unique advantages due to their high sensitivity, real-time response capability, and label-free detection. The typical SAW modes are the Rayleigh mode and the shear-horizontal mode. Both present pros and cons for biosensing applications and generally need different substrates and device geometries to be efficiently generated. This study investigates and characterizes ultra-high-frequency (UHF-) SAW resonator biosensors. It reveals the simultaneous presence of the two typical SAW modes, clearly separated in frequency, called slow and fast. The two modes are studied by numerical simulations and biosensing experiments with the glial-fibrillary-acidic-protein (GFAP) biomarker. The slow mode is generally more sensitive to changes in surface properties, such as temperature and mass changes, by a factor of about 1.4 with respect to the fast mode.

The biomass fraction of processed municipal and industrial wastes added to soil can maintain, and in some case improve, the soil’s organic fertility. One of the main constraints in the agricultural use of the sewage sludge is its content of heavy metals. In the long term, soil administration of sewage sludge in agriculture could result in a risk of environmental impact. The aim of this research was to evaluate the effects of medium-term fertilization with sewage sludge diversely processed on the soil’s organic carbon content and humification – mineralization soil’s processes and on the physical and mechanical properties of soil. Furthermore, the heavy metals accumulation in soil, in their total and available form, has been investigated. After eight years of administration to soil, the use of sewage sludge as an agricultural soil amendment has contributed to maintaining the soil’s organic fertility. An increase in concentrations of total Ni and Zn was detected in soil. For bioavailable form (DTPA-extractable) this trend was evidenced for all heavy metals analysed. However, the concentrations of total and available heavy metals in the soil did not exceed the legal threshold established by Italian law for unpolluted soils.

In this paper we derive a unified perspective for Optimal Transport (OT) theory and Mean Field Control (MFC) theory to analyse the learning process for Neural Networks algorithms in a high-dimensional framework. We consider Mean Field Neural Networks in the context of MFC theory, specifically the mean field formulation of OT theory that allows the development of highly efficient algorithms while providing a powerful tool in the context of explainable Artificial Intelligence.

In emergency situations, every second counts for an ambulance navigating through traffic. Efficient use of traffic light systems can play a crucial role in minimizing response time. This paper introduces a novel automated Real-Time Ambulance in an Emergency Detector (RTAIAED). The proposed system uses special Lookout Stations (LS) suitably positioned at a certain distance from each involved traffic light (TL), to obtain timely and safe transitions to green lights as the Ambulance in an Emergency (AIAE) approaches. The RTAIAED is particularly pertinent on one-way roads, addressing the challenge of regulating the sequence of traffic-lights-signals so as to minimize the time needed to safely grant the green signal to the AIAE. The proposed solution leverages a part-based model made of elementary detectors for video analysis, specifically realized with a customized YOLOv8 model, and for audio analysis, thanks to an additional neural network based on Mel Frequency Cepstral Coefficients (MFCCs). This way, the RTAIAED ensures the accurate and robust identification of an AIAE heading towards a traffic light in time to ensure a green light thanks to the strategic positioning of the LS detectors. Extensive experiments demonstrate the robustness of the approach and its reliable application in real-world scenarios thanks to its predictions in real-time, showcasing the ability to detect AIAEs even in challenging conditions such as noisy environments, nighttime, or adverse weather conditions, provided a suitable-quality camera is appropriately positioned. The proposed system can also find application in traffic flow management.

This paper investigates urban microclimate in relation to the typical major streets and mobility layout in Turin, i.e. boulevards with lateral minor roads, called “controviali”, an almost unique urban mobility layout. The aim is to examine the possibility of intervention in relation to the type and scope of mobility for microclimate mitigation and climate adaptation purposes. To this, this paper evaluates to which extent urban morphology and mobility features contribute to determining microclimatic conditions, to finally identify site-specific prioritised strategies to cope with its mitigation. This research is structured in two phases. The first phase is dedicated to urban-scale analysis of the streets with “controviali”, resulting in the creation of a database containing their properties and typology, to finally derive six clusters of boulevards. The second phase involves the selection of one representative case study per cluster and simulation of their microclimate conditions, performed by the software ENVI-met. The results are discussed in relation to the parameters proven in the prior literature review to have a major impact on the microclimate. The assessment of the results indicated which elements affect the climatic conditions the most, allowing for the proposal of different prioritised mitigation strategies in the conclusion.

Family doctors can have an active role in identifying significant population needs and solutions. During COVID-19 epidemic, patient home monitoring with pulse oximetry has been a key aspect of care of patients. However, pandemics bring shortage medical equipment such as pulse oximetry. Through the local maker community in a matter of days four “smart” pulsoximeters were created and built. Following Internet of Things principles, the pulsoximeters were programmed to transmit recorded data through Wi-Fi, in real time, directly to the doctors. Each protype pulsoximeter served a family doctor during the pandemic. Building instructions were shared in maker-oriented websites, potentially leading to additional small-scale productions.

This study compares the action of different handpieces (turbine, high-speed electric handpiece and piezoelectric device) on surface roughness of enamel and dentin when using diamond-coated working tips and burs of the same grit size. Experiment was conducted on 15 extracted first molars from patients aged 45 to 60 years. The occlusal portion was removed using a diamond-coated water wheel and then refined with a 120-130 μm grit bur in order to obtain a flat surface with an adequate exposition of the dentin core. Each surface was divided into three portions and every portion was finished with one of the three tested instruments. Rotary burs and piezoelectric tips had the same grit size (60 μm) and load on handpiece during preparation never exceeded 150 g. Surface roughness parameters (Ra, Rsk, Rku) were recorded with an optical profilometer and SEM analysis of treated surfaces and working tips was conducted. Ra and Rsk differed significantly between enamel and dentin only after using turbine (p=0.004 and p=0.007, respectively). No significant differences were observed in Ra, Rsk, and Rku between enamel and dentin when using high-speed electric handpiece or piezoelectric device. Turbine produced higher Ra and Rsk values on dentin than the other devices, while no significant differences were found between piezoelectric handpiece and high-speed electric contra-angle on both substrates. Summarizing, the findings of the present study demonstrated that turbine generated rougher surfaces on dentin compared to the other handpieces. Moreover, the turbine produced more asymmetrical surface profiles on both enamel and dentin. However, it should be considered that these differences in roughness (Ra) were within the range of 0.25-0.30 μm: it is still unclear if these variations, although statistically significant, will influence final clinical outcomes.

Starting from an original survey conducted in eight countries in 2021 (Canada, China, Germany, Italy, Russia, Spain, UK, and USA), this research explores the relationship between household food waste and dietary habits in a cross-country comparative perspective. 8,000 questionnaires were recorded from samples representative of adult population of each country through an online survey conducted between the 13th and the 24th of August. The questionnaires were built on the work of Waste Watcher International Observatory on Food and Sustainability, an international observatory of social, behavioral and lifestyles dynamics behind household food waste. Relationship between per capita self-reported amount of food waste (expressed in kilocalories) and self-declared dietary habits (Traditional, Healthy and Sustainable, Vegetarian, Smart, Confused) was estimated using multiple linear regression models. Results show that Smart diets are associated with higher values of food waste in Canada, Spain, UK and USA. Vegetarian diets are associated to lower food waste values in China, Germany, UK and USA but not in Italy, Russia and Spain. Since the share of population adopting a Smart diet is on average 2.7% of the sample, interventions for food waste reduction should focus on this specific type of consumers, often associated to larger amounts of food waste.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiological agent of the current pandemic worldwide. The pathological condition induced by this pathogen is known as COVID-19 disease. SARS-CoV-2 associated pandemic has been defined as a “public health emergency of international concern” by the International Health Regulation Emergency Committee of the World Health Organization. To date, considerable efforts are in progress to develop more advanced strategies against SARS-CoV-2. Despite the numerous scientific studies published, our knowledge regarding this pathogen is still incomplete, as this virus has been identified only recently. Therefore, scientific investigation of the SARS-CoV-2 has been possible only for a short period of time and effective management of the serious forms of this disease is still lacking. Considerable efforts are in progress worldwide with the purpose to develop more advanced strategies against this pathogen. In this review, we have analyzed the structural and the biological SARS-CoV-2 characteristics and those of other well-known RNA viruses, with the aim to identify possible similarities and analogies between all these pathogens, may be a very useful approach. These infectious agents have been widely studied since several years ago and, a large series of scientific reports are available in the literature regarding this topic. Therefore, focusing on the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Influenza viruses (IVs), we have collected their historical data, clinical manifestations, pathogenetic mechanisms and related infections. Taking advantage of the results of our research, we have assembled this narrative review, with the aim to get useful insights and lessons from HIV, HCV and IVs characteristics and, consequently, to transfer the obtained knowledge to the study of SARS-CoV-2 biology. There are well known differences between all these pathogens. In particular, they present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne pathogens, whereas HIV and HCV are bloodborne infectious agents. However, these viruses exhibit some potential common clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2. Accordingly, we have analysed and discussed the following points: 1) the biology, the pathogenesis and the clinical manifestations of SARS-CoV-2, HIV, HCV and IVs in mankind; 2) the onset and spreading of pandemics caused by respiratory viruses according to a perspective historical point of view; 3) the possible development of a persistent SARS-CoV-2 reservoir worldwide; 4) the possibility of SARS-CoV-2 reinfection/reactivation; 5) the possible involvement and impact of climatic factors in increasing the risk of SARS-CoV-2 spreading.

Background: The liver is involved in disseminated tuberculosis in more than 80% of the cases while primary liver involvement is rare, representing < 1% of all cases. Hepatic tuberculosis (TB) can be treated by conventional anti-TB therapy, however, diagnosing this disease still remains a challenge. The diagnosis might be particularly difficult in patients with a single liver lesion that could be misdiagnosed as a tumor or other focal liver lesions. While computed tomography and magnetic resonance imaging findings have been described, there is a paucity of literature on contrast-enhanced ultrasound (CEUS) features of hepatic TB. Case Summary: herein, we describe a case of a patient with tuberculous lymphadenopathy and chronic HCV-related liver disease who developed a single macronodular hepatic TB lesion. Due to the finding of a hepatocellular carcinoma (HCC) highly suggestive CEUS pattern, specifically a LR5 category according to the Liver Imaging Reporting and Data System (LI-RADS), and a good response to antitubercular therapy, a non-invasive diagnosis of HCC was made, and the patient underwent liver resection. We also review the published literature on imaging features of hepatic TB and discuss the diagnostic challenge represented by hepatic TB when occurs as a single focal liver lesion. Conclusions: this report shows for the first time that CEUS pattern of hepatic TB might be misinterpreted as HCC and specific imaging features are lacking. Personal history and epidemiological data are mandatory in interpreting CEUS findings of a focal liver lesion even when the imaging pattern is highly suggestive of HCC.

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

Wildfires have always been a part of the history of Mediterranean forests. However, forest regeneration after a wildfire is not certain. It depends on many factors, some of which may be influenced by land management activities. Failure of regeneration will cause a regime shift in the ecosystem, reducing the provision of ecosystem services and ultimately leading to desertification. How can we increase Mediterranean forests’ resilience to fire? To answer this question, we did a literature review, investigating chains of processes that allow forests to regenerate (which we label “regeneration mechanisms”), and assessed the impact of selected management practices documented in the WOCAT database on the regeneration mechanisms. We identified three distinct regeneration mechanisms that enable Mediterranean forests to recover, as well as the time frame before and after a fire in which they are at work, and factors that can hinder or support resilience. The three regeneration mechanisms enabling a forest to regenerate after a fire consist of regeneration (1) from a seed bank; (2) from resprouting individuals; and (3) from unburned plants that escaped the fire. Management practices were grouped into four categories: (1) fuel breaks, (2) fuel management, (3) afforestation, and (4) mulching. We assessed how and under what conditions land management modifies the ecosystem’s resilience. The results show that land management influences resilience by interacting with resilience mechanisms before and after the fire, and not just by modifying the fire regime. Our analysis demonstrates a need for adaptive – i.e. context- and time-specific – management strategies.

Small and micro hydropower represents an attractive solution for electricity generation, with low cost and low environmental impact. The pump-as-turbine (PAT) approach has promise in this application owing to its low purchase and maintenance costs. In this paper, a new method to predict the inverse characteristic of industrial centrifugal pumps is presented. This method is based on results of simulations performed with commercial three-dimensional CFD software. Model results have been first validated in pumping mode using data supplied by pump manufacturers. Then, results have been compared to experimental data for a pump running in reverse condition. Experimentation has been performed on a dedicated test bench installed in the Department of Civil Construction and Environmental Engineering of the University of Naples Federico II. Three different pumps, with different specific speeds, have been analyzed. Using the model results, the inverse characteristic and the best efficiency point have been evaluated. Finally, results of this methodology have been compared to prediction methods available in the literature.

In the last two decades, the continuous ever growing demand for energy has determined a significant development in the production of photovoltaic (PV) modules. Anyway, a critical and very important issue in the module design process is the adoption of suitable encapsulant materials and technologies for cell embedding. Therefore, adopted encapsulants have a significant impact on modules efficiency, stability and reliability, and to ensure the unchanged performance of PV modules in time, the encapsulant materials must be selected properly. The selection of encapsulant materials must maintain a good balance between the encapsulant performance in time and costs, related to materials production and technologies for cells embedding. However, the encapsulants must ensure excellent isolation of active photovoltaic elements by the environment, preserving accurately the PV cells against humidity, oxygen and accidental causes that may compromise the PV modules function. This review provides an overview of different encapsulant materials, their main advantages and disadvantages in adoption for PV production, and also in relation to used encapsulant technologies for cell embedding, additives and the interaction of these materials with other PV components.

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

Magneto-electrochemistry (MEC) is a unique paradigm in science, where electrochemical experiments are carried out as a function of an applied magnetic field, creating a new horizon of potential scientific and technological applications. Over the time, detailed understanding of this research domain was developed to identify and rationalize the possible effects exerted by a magnetic field on the various microscopic processes occurring in an electrochemical system, such as: electrolyte properties governed by charge-transfer process (electric conductivity, viscosity, and diffusivity), mass transfer, electrochemical kinetics and on the structure/quality of products formed either at the working electrode or in the electrochemical cell. Particularly, magnetic field controlled chiral architecture obtained from deposited metal, alloys and catalyst and their excellent enantio-recognition in experimental frame is highly appealing. Interestingly, Hall effect was also demonstrated in electrolytic medium via an impressive experimental technique which is being employed for further theoretical understanding in the field of magneto-electrochemical science. Later, a highly reproducible local temperature variation was observed in electrochemical electrolytes exposed to perpendicular magnetic and electric fields. However, until recent studies, none of the above mentioned reports considered the possibility of a spin-dependent related charge-transfer process. Recent experimental and theoretical studies reveal that electron’s transmission through chiral molecules is spin-selective and this effect has been referred to as chiral-induced spin-selectivity (CISS) effect. The CISS effect pave the way for the building up of a system characterized by a net magnetic moment exploiting the spin-filtering ability of chiral molecules. This interplay between chirality and magnetism may shed light on fundamental scientific aspects underlying the enantio-recognition and highly efficient electron-transfer that occurs in biological process.

The paper analyses how between 1956 and 2009 the agrarian metabolism of the Barcelona Metropolitan Region (BMR) has become less functional, losing circularity in biomass flows and in relationship to its landscape. We do so by adopting a Multi-EROI and flow-fund (MuSIASEM) analyses and its nexus with landscape functional structure. The study of agricultural flows of Final Produce, Biomass Reused and External Inputs is integrated with that of land use, livestock, power capacity and population changes between 1956 (at the beginning of the Green Revolution) and 2009 (fully industrialized agriculture). A multi-scale analysis is conducted at the landscape scale (seven districts within the Barcelona metropolitan region) as well as for the functions deployed, within an agroecosystem, by the mutual interactions between its funds (land-uses, livestock and farming population). A complex nexus between land, livestock, dietary patterns and energy needs is shown; we conclude that from the perspective of the circular bioeconomy the agrarian sector has gone worse hand in hand with the landscape functional structure. Therefore, a novel perspective in landscape agroecology is opened

SOX proteins are transcription factors which play a role in regulating the development of pro-genitor cells and tissue differentiation. Twenty members are known, clustered in eight groups named A to H, and sharing a common DNA-binding domain called the HMG (high-mobility-group) box. Eleven of the SOX genes have been associated with genetic disorders so far, covering a broad spectrum of developmental diseases. SOX4 is a single-exon gene and belongs to the SOXC group together with SOX11 and SOX12. SOX4 variants were recently described to cause a highly penetrant but heterogeneous disorder, with a phenotypic spectrum ranging from mild developmental delay and learning difficulties to intellectual disability with congenital anomalies. Nineteen pathogenic variants were reported to date, generally de novo, heterozygous, and inactivating, either stop-gain or missense, the latter ones primarily targeting the HMG domain. Further, a bi-allelic variant was reported in a single consanguineous family. Copy number variants, leading to whole gene deletion or duplication, are rare and not clearly associated with a neurodevelopmental disorder. Many open questions remain, regarding the definition of variants of unknown significance, a possible role of missense variants outside the HMG domain, genotype-phenotype correlation, the range of phenotypic spectrum and modifying factors, and treatment options.

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

The copper mining industry is increasingly using artificial intelligence methods to improve cop-per production processes. Recent studies reveal the use of algorithms such as Artificial Neural Network, Support Vector Machine, and Random Forest, among others, to develop models for predicting product quality. Other studies compare the predictive models developed with these machine learning algorithms in the mining industry, as a whole. However, not many copper mining studies published compare the results of machine learning techniques for copper recovery prediction. This study makes a detailed comparison between three models for predicting copper recovery by leaching, using four datasets resulting from mining operations in northern Chile. The algorithms used for developing the models were Random Forest, Support Vector Machine, and Artificial Neural Network. To validate these models, four indicators or values of merit were used: accuracy (acc), precision (p), recall (r), and Matthew’s correlation coefficient (mcc). This paper describes dataset preparation and the refinement of the threshold values used for the predictive variable most influential on the class (the copper recovery). Results show both a precision over 98.50% and also the model with the best behavior between the predicted and the real. Finally, the models obtained show the following mean values: acc=94.32, p=88.47, r=99.59, and mcc=2.31. These values are highly competitive as compared with those obtained in similar studies using other approaches in the context.

Specialized, reductionist, and linear approaches are applied in clinical research; they are based on linear logic and used towards therapeutic molecule-based targets. However, those approaches do not consider a systemic vision that describes the remote cause of the pathogenic activation. We propose new theoretical and practical methods for the next drug generation development. Self-organization, network structure, hierarchical organization, non-linearity, feedback circuits, reactions to information, and the view of drugs as information clarify the existing pharmacological methods. We suggest a perspective and hierarchical vision of the human organism based on six levels (mechanic and structural; metabolic; bodily dynamic; emotional, cognitive, spiritual). The therapy should restore the self-organization of every level using the “intelligent” modulation of the network responses. Multi-targeted drugs should act on the remote cause of the pathogenic cascade and be administered based on personal variability and networks. This approach may help the development of individualized, precise, and integrated medicine.

Plant trichomes are specialized unicellular structures that originate and project from above ground epidermal tissues on the surfaces of leaves, petals, stems, petioles, peduncles, and seed coats depending on species. Trichomes (also called ‘hairs’) play well-recognized roles in defense against insect herbivores, both as a physical barrier that obstructs herbivore movement and by mediating chemical defenses. By virtue of their physical properties (size, density), trichome hairs can directly operate to protect buds of plants from insect damage, reduce leaf temperature, increase light reflectance, prevent water loss, and decrease leaf abrasion. Great variety of trichomes and their accessibility makes them a useful model for studying the molecular processes of cell fate determination, cell cycle control and cellular morphogenesis. In leaves, the developmental control of the trichomatous complement has highlighted a regulatory network based on four fundamental elements: (i) genes that activate and/or modify the normal cell cycle of epidermal cells (i.e. endoreduplication cycles); (ii) transcription factors that create activator/repressor complexes with a central role in determining cell fate, initiation and differentiation of an epidermal cell in trichome; (iii) evidences that point out the interplay of the aforesaid complexes with various phytohormones; (iv) epigenetic mechanisms involved in trichome development. Here, we describe trichome development in leaves, commonly subjected to environmental injury, and where most genetic regulators have been characterized.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

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.

Coastal marine ecosystems worldwide, like Florida Bay, are increasingly affected by tide alteration and anthropogenic disturbances which affect water quality imbalance leading to algal blooms. Increased bloom persistence is a serious threat due to the long-lasting impact on processes like carbon cycle and services like species presence. However, exploring eco-environmental feedback patterns of algal blooms remains challenging and poorly investigated, also due to the paucity of data. Florida Bay, taken as an epitome, has long experienced algal blooms in its central and western regions, and in 2006 an unprecedented bloom occurred in the eastern habitats. We analyzed the occurrence of blooms from three perspectives: (1) the spatial spreading networks of chlorophyll-a (CHLa) that pinpoints source and unbalanced habitats; (2) the fluctuations of water quality factors pre- and post-bloom outbreaks to in assess environmental impacts of ecological dysbiosis and target prevention and control of algal of blooms; and (3) the biogeochemical-spreading network topological co-evolution to quantify ecosystemic stability and ecological shift likelihood in long-term. Here, we propose Transfer Entropy (TE) to quantify dynamical interactions between spatial areas and biogeochemical factors (ecosystem connectome) underpinning bloom emergence and spreading, as well as environmental effects; the Pareto principle is defined for identifying the salient eco-environmental interactions of CHLa. We quantified the spatial dynamics of algal blooms, and thus obtained areas in need for ecological monitoring and potential bloom control. Results show that algal blooms are increasingly persistent over space with long-term negative effects on water quality factor. A dichotomy is reported between spatial ecological corridors of spreading and biogeochemical networks as well as divergence from the optimal eco-organization: randomization of the former due to nutrients' overload and temperature increase leads to scale-free CHLa spreading and extreme outbreaks a posteriori. Subsequently this increases bloom persistence, turbidity and salinity with potentially strong ecological effects on highly biodiverse and vulnerable areas such as tidal flats and marshes. Algal blooms are important ecosystem regulators of nutrient cycles; however, beyond limit chlorophyll-a outbreaks cause aquatic species mortality due to their effect on water turbidity, nutrient balance (nitrogen and phosphorus in particular), salinity and temperature. Beyond compromising local environmental quality, socio-ecological services are also compromised at large scales, yet ecological assessment models like the one presented are in need of application in subtropical and tropical bays worldwide.

The utilization of Fiber Bragg Grating (FBG) sensors in innovative optical sensor networks has displayed remarkable potential in providing precise and dependable thermal measurements in hostile environments on Earth. Multi-Layer Insulation (MLI) blankets serve as critical components of spacecraft and are employed to regulate the temperature of sensitive components by reflecting or absorbing thermal radiation. To enable accurate and continuous monitoring of temperature along the length of the insulative barrier without compromising its flexibility and lightweight, FBG sensors can be embedded within the thermal blanket, thereby enabling distributed temperature sensing. This capability can aid in optimizing the thermal regulation of the spacecraft and ensuring the reliable and safe operation of vital components. Furthermore, FBG sensors offer several advantages over traditional temperature sensors, including high sensitivity, immunity to electromagnetic interference, and the ability to operate in harsh environments. These properties make FBG sensors an excellent option for thermal blankets in space applications, where precise temperature regulation is crucial for mission success. Nevertheless, the calibration of temperature sensors in vacuum conditions poses a significant challenge due to the lack of an appropriate calibration reference. Therefore, this paper aims to investigate innovative solutions for calibrating temperature sensors in vacuum conditions. The proposed solutions have the potential to enhance the accuracy and reliability of temperature measurements in space applications, which can enable engineers to develop more resilient and dependable spacecraft systems.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

Cytokines are a family of proteins which play a major role in the regulation of immune system, and enter the development of several diseases from rheumatoid arthritis to cancer and, more recently, COVID-19. Therefore, many efforts are currently being spent in therapy and diagnosis, producing inhibitory drugs, as well as biosensors for a rapid, poor invasive, and effective detection. In this regards, even more efficient cytokine receptors are under investigation. In this paper we analyze a set of receptors of cytokine IL-6, investigating their topological features by means of a theoretical approach. Our results suggest a topological indicator that may help in the identification of those receptors having the highest complementarity with the protein, a feature expected to ensure a stable binding. Furthermore, we propose and discuss the use of these receptors in an ideal experiment.

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

Nickel-based ethylene polymerization catalysts have unique features, being able to produce macromolecules with a variable content of branches, resulting in polymers ranging from semicrystalline plastics to elastomers to hyperbranched amorphous waxes and oils. In addition to Brookhart's α-diimine catalysts, iminopyridine Ni(II) complexes are among the most investigated systems. We report that Ni(II) complexes bearing aryliminopyridine ligands with bulky substituents both at the imino moiety and in the 6-position of pyridine afford either hyperbranched low molecular weight polyethylene oils or prevailingly linear crystalline polyethylenes or both depending on the ligand structure and the reaction conditions. The formation of multiple active species in situ is suggested by analysis of the post-polymerization catalyst residues, showing the partial reduction of the imino function. Some related arylaminopyridine Ni(II) complexes were also synthesized and tested, showing a peculiar behavior, i.e. the number of branches of the produced polyethylenes increases while ethylene pressure increases.

Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many dark aspects related to different patients profile, various associated risk factors and wide aetiologies. It comprises several pathophysiological pathways related to endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and high inflammatory response. Up to now, it has been described only for clinical appearance and most common associated risk factors without an effective characterization of biological processes responsible for cardiovascular deteriorations. Recent advances in laboratory and metabolomic researches showed that HFpEF appears strictly related to specific cells and molecular mechanisms dysregulation. Some biomarkers are capable to early identify these processes adding new insights into diagnosis and risk stratification. Additionally recent advances on intermediate metabolites reflecting provide relevant information on intrinsic cellular and energetic substrate alterations. The systematic combination of clinical imaging and laboratory data may lead to a precision medicine approach providing prognostic and therapeutic advantages. Current review reports traditional and emerging biomarkers recently investigated in HFpEF setting, and it purpose a new diagnostic approach based on integrative information achieved from risk factors burden, hemodynamic dysfunction and biomarkers signature partnership.

The high hydrophobicity of fullerenes and the resulting formation of aggregates in aqueous solutions hamper the possibility of their exploitation in many technological applications. Noncovalent bioconjugation of fullerenes with proteins is an emerging approach for their dispersion in aqueous media. Contrary to covalent functionalization, bioconjugation preserves the physicochemical properties of the carbon nanostructure. The unique photophysical and photochemical properties of fullerenes are then fully accessible for applications in nanomedicine, sensoristic, biocatalysis and materials science fields. However, proteins are not universal carriers. Their stability depends on the biological conditions for which they have evolved. Here we present two model systems based on pepsin and trypsin. These proteins have opposite net charge at physiological pH. They recognize and disperse C₆₀ in water. UV-Vis spectroscopy, zeta-potential and atomic force microscopy analysis demonstrates that the hybrids are well dispersed and stable in a wide range of pH’s and ionic strengths. A previously validated modelling approach identifies the protein-binding pocket involved in the interaction with C₆₀. Computational predictions, combined with experimental investigations, provide powerful tools to design tailor-made C₆₀@proteins bioconjugates for specific applications.

The compelling effects of climate change on forests may have been underestimated in the past few decades in practical forestry. Although the first attempts to draw attention to this complex problem appeared almost half a century ago, the debate has been conceptual rather than experimental and applicative. At first glance, the con-cerns were mainly related to sustainable forest management (SFM) issues, which obviously needed attention. Over time, the effects of climate change have been mainly considered in the context of the SFM; they started from various and somewhat different scales and goals. Over time, more research and awareness of the im-portance of SFM under the pressure of climate change have led to the development of a clearer field that can be defined as ‘adaptive forest management’ - to climate change. One of the characteristics of this discipline is to be featured by the absence of univocal methods and / or objectives to be pursued but to identify, verify, and adapt methods to the various climatic and forest types and conditions found in the field. Therefore, this work shows some phases of forest planning and management concepts and criteria over time and recalls some innovative and / or adaptive methods related to the approach to forest planning and management under climate change

Traditional high pressure mechanical compressors account for over half of the car station’s cost, have insufficient reliability and are not feasible for a large-scale fuel cell market. An alternative technology, employing a two-stage, hybrid system based on electrochemical and metal hydride compression technologies, represents an excellent alternative to conventional compressors. The high-pressure stage, operating at 100-875 bar, is based on a metal hydride thermal system. A techno-economic analysis of the metal hydride system is presented and discussed. A model of the metal hydride system was developed, integrating a lumped parameter mass and energy balance model with an economic model. A novel metal hydride heat exchanger configuration is also presented, based on mini-channel heat transfer systems, allowing for effective high-pressure compression. Several metal hydrides were analyzed and screened, demonstrating that one selected material, namely (Ti_0.97Zr_0.03)_1.1Cr_1.6Mn_0.4, is likely the best candidate material to be employed for high-pressure compressors under the specific conditions. System efficiency and costs were assessed based on the properties of currently available materials at industrial levels. Results show that the system can reach pressures on the order of 875 bar with thermal power provided at approximately 150 °C. The system cost is comparable with the current mechanical compressors and can be reduced in several ways as discussed in the paper.

In recent years, there has been a growing interest in utilizing natural antioxidants as alternatives to synthetic additives in food products. Apples and apple by-products have gained attention as a potential source of natural antioxidants due to their rich phenolic content. This review aims to provide a comprehensive overview of the antioxidant properties of apples and apple by-products, their extraction techniques as well as potential applications in food products because of their an-tioxidant or nutritional properties. The findings here reported highlights the proper utilization of apples and their by-products in food to reduce the detrimental effect on the environment and provide a positive impact on the economy.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

The idea of an extension of life for CubeSats is proposed to reduce space debris in a low-earth orbit. In this work, a gripper is designed for geometry-based grasping in berthing tasks. The grasping operation is outlined for square- and rectangle-profiled CubeSats. Equilibrium conditions are used to choose fingertips shape and parameters for grasping the CubeSat body. A design scheme is proposed to provide the required accuracy. A design concept is developed into a lab prototype by using low-cost 3D printing technique, and a mock-up grasping task that is representative of the berthing operation is evaluated with the lab prototype. Center-mass hanging setup for the prototype and grasped body is used to evaluate the impact of grasping, partially replicating the conditions in space by reducing the effect of gravity on the system.

This study examined the efficiency of a combined diagnostic approach in which bioamplification of Arizona 861 S1 citron was integrated with RT‒PCR to detect Citrus tristeza virus (CTV) and Hop Stunt Viroid (HSVd) in Citrus plants. The capacity of the combined method to diagnose mixed infections of CTV and HSVd, along with early single infections of both pathogens, was assessed by evaluating the incubation periods and differential detection capabilities between the combined and direct methods. The bioamplification method exhibited high sensitivity (100%) and specificity (100%) for CTV, enabling early detection even in patients with low-titer infections compared to direct RT‒PCR. However, for HSVd, the combined method achieved 50% sensitivity in early infections, highlighting the need for additional replicates to enhance diagnostic reliability. The relative concentrations of pathogens in mixed and simple infections were evaluated; the analysis revealed no significant differences, suggesting minimal interference between CTV and HSVd. This approach allows early detection of CTV but requires further refinement for HSVd diagnosis. These findings underscore the complementary roles of the cost-effectiveness of direct RT‒PCR and the sensitivity of the combined method in implementing effective disease control strategies in citrus crops.

The specialisation and intensification in agriculture have increased the productivity but have also led to the spread of monocultural systems, simplifying production and reducing genetic diversity. The purpose of this study was to propose crop diversification as a tool to increase biodiversity and achieve sustainable and resilient intensive agriculture, particularly in areas with water scarcity. In this paper, a combined Life Cycle Assessment (LCA) and Life Cycle Costing (LCC) was applied to evaluate the environmental and economic sustainability of a differentiated system of cultivation (pomegranate, almond and olive), according to modern intensive and superintensive cropping systems. Based upon the results obtained, it is deduced that pomegranate cultivation generated the highest environmental load, followed by almond and olive. From the financial analysis, it emerged that almond is the most profitable, followed by pomegranate and olive.

During summer 2016 in the District of Palermo, Italy, the rapid succession of four cases of invasive meningococcal disease among young adults, with one death, have had an extraordinary emphasis by Local and National mass media. The resultant “epidemic of panic” among general population overloaded vaccination Units of the Palermo District during following months. Strategies implemented by Sicilian and Local Public Health Authorities to counteract “meningitis fear” were: a) extension of active and free of charge anti-meningococcal tetravalent vaccination from age class 12–18 to 12–30 years old; b) implementation of vaccination units usual opening hours and rooms tailored for vaccine administration; c) development of informative institutional tools and timely communications throughout local mass media to reassure general population. In 2016, was observed an increase of anti-meningococcal coverage in Palermo District (+18% for 16th y.o. and + 14% for 18th y.o. cohorts) and at Regional Level (+11.2% and +13.5% respectively). Concurrent catch-up of other recommended vaccination for age (diphtheria-tetanus-pertussis-poliomyelitis and papillomavirus), resulted in further increase of doses administered. The fear for meningitis, managed by Sicilian Public Health Authorities, had positive reverberations in terms of prevention. In particular, informative strategies adopted sensibly contributed to get Sicilian young adults closer to vaccination issues.

The growing interest in environmental sustainability issues and, at the same time, the advantages offered by blockchain technology have strong connections between these two topics. This study explores the application of blockchain technology across various environmental domains, such as air quality, climate change impacts, and resource management. The research utilised a dual approach, combining a bibliometric analysis with VOSviewer and a topic analysis using BERT models to assess the discourse within both scientific literature extracted from Scopus and practical blockchain projects obtained from GitHub. The findings reveal that food security, energy, and sustainable agriculture are predominant topics in academic discussions, with a noticeable increase in focus from 2017 onwards. Practical projects are focused on transparent tracking and decentralised management. The overlap between academic and practical spheres is evident in the shared focus on energy and environmental management, demonstrating blockchain’s growing role in addressing global environmental challenges. The study underscores the importance of integrating theoretical research with practical implementations to harness blockchain’s full potential in promoting sustainable environmental practices.

A topic of growing interest in urban remote sensing is the automated extraction of geometrical building information for 3D city modeling. Roof geometry information is useful for applications such as urban planning, solar potential estimation and telecommunication installation planning, and wind flow simulations for pollutant diffusion analysis. Recent research has proven that the advance in remote sensing technologies and deep learning methods offer the prospects of deriving the roof structure information accurately and efficiently. In this study, we propose a Vectorized Roof Extractor- method based on Fully Convolutional Networks (FCNs) and advanced polygonization method to extract roof structure from aerial imagery and a normalized Digital Surface Models (nDSM) in a regularized vector format. The roof structure consists of building outlines, external edges of the building roof, inner rooflines, internal intersections of the main roof planes. The methodology is comprised of segmentation, vectorization and post-processing for outer rooflines, external edges of the building roof, and inner rooflines, and internal intersections of the main roof planes. For the comparison, we adapt the Frame field Learning (FFL) method originally designed to extract building polygons [1]. Our experiments are conducted on a custom data set derived for the city of Enschede, The Netherlands, using aerial imagery, nDSM and manually digitized training polygons. The results show that the proposed Vectorized Roof Extractor outperformed adapted FFL on PoLiS distance with values of 3.5 m and 1.2 m for outlines and inner rooflines, respectively. Furthermore, the model surpassed the adapted FFL on PoLiS-thresholded F-score for outlines and inner rooflines, with 0.31 and 0.57, respectively. The Vectorized Roof Extractor produced adequate visual results, with straighter walls and fewer missed inner roofline detections. It can predict buildings with common walls thanks to skeleton graph computation. To summarize, the proposed method is suitable for urban applications and has the potential to be improved further.

This study provides a unique procedure for validating and reconstructing temperature and precipitation data. Although developed from data in Middle Italy, the validation method is intended to be universal, subject to appropriate calibration according to the climate zones analysed. This~research is an attempt to create shared applicative procedures that are most of the time only theorized or included in some software without a clear definition of the methods. The purpose is to detect most types of errors according to the procedures for data validation prescribed by the World Meteorological Organization, defining practical operations for each of the five types of data controls: gross error checking, internal consistency check, tolerance test, temporal consistency, and~spatial consistency. Temperature and~precipitation data over the period 1931--2014 were investigated. The~outcomes of this process have led to the removal of 375 records (0.02%) of temperature data from 40 weather stations and 1286 records (1.67%) of precipitation data from 118 weather stations, and 171 data points reconstructed. In conclusion, this work contributes to the development of standardized methodologies to validate climate data and provides an innovative procedure to reconstruct missing data in the absence of reliable reference time series.

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

Background: The 2021 “Universal Definition of Heart Failure (HF)” Proposed the following left ventricle ejection (LVEF) phenotype classification: ≤40%; HF with intermediate LVEF: between 41-49% and HF with preserved LVEF: ≥50%. LVEF represents the percentage of left ventricular ejected volume in each cardiac cycle and Cut-points considered statistically normal are: ≥52% in men and ≥54% in women. The prevalence HFpEF is of 35-60% among the HF phenotypes, with a facing to increase rates in relation to HFrEF and is associated with mortality rates similar to those of HFrEF. The pathophysiology of HFpEF is based on vascular and metabolic dysfunction, therefore, there is less neurohumoral stimulation compared to HFrEF. Methodology: A systematic review was performed to report of information related to Sacubitril-valsartan and the treatment of HFrEF. Terms related to “treatment” and “brazil” were used in the databases PubMed (MEDLINE) and Scientific Electronic Library Online (SCIELO). Results: Clinical trials testing drugs that modulate the neurohumoral system in patients with HFpEF failed to demonstrate benefit in the combined endpoint of reduced mortality/hospitalization due to HF compared to placebo to date. Sacubitril-valsartan is a drug with a mechanism of action surrogate the pathophysiological concept of HFpEF, it is safe and decreased endpoints of natriuretic peptides and left atrial structure in a phase II clinical study. Conclusions: The PARAGON-HF trial demonstrated that sacubitril-valsartan reduced the primary endpoint of the study when assessed the pre-specified subgroup of LVEF≤57% and improved the secondary endpoints of performance status and renal function in the population.

The decarbonization of the built environment, both in new construction and renovation, is crucial to mitigate its relevant impact on climate change and achieve the Paris agreement goals. This study presents a systematic LCA-based methodology to assess the whole life carbon emissions of buildings, applied to a proposal for the regeneration of one of Milan’s disused railway yards. As an entry for the 2020 Reinventing Cities competition, Scalo Lambrate is a project for a mainly residential neighborhood with a public park. Strategies to reduce carbon emissions deriving both from the operational energy and construction and maintenance were evaluated and their effects compared to a reference scenario over a time horizon of 100 years. The results show that, while the opportunities to reduce carbon emissions during the use phase are somehow limited due to the already stringent performance requirements for new builds, the use of fast-growing biogenic materials for construction materials, even if mixed with more traditional ones, can provide a significant reduction of the global warming potential over the whole life cycle, with a reduction of 70% over the baseline. The remaining emissions can be offset with afforestation initiatives that, however, must be assessed against land use issues.

Adaptive Cruise Control (ACC) is useful in the most dangerous maneuvers such as braking and acceleration. This study assesses how ACC modifies traffic flows by analysing the differences be-tween manual and autonomous driving in connected and autonomous vehicles (CAVs). Using a platoon of 80 vehicles, tested in pairs on the road, it was possible to define the speed trends during braking and acceleration and the reaction times to the driving maneuvers (PRT, TH, TCC) with a kinematic data detector. The interactions between the CAV and the driver, have been studied in-novatively, i.e through gaze analysis. Situations of potential danger, characterized by the braking of the vehicle that precedes the car with the driver equipped with the eye tracker tool, have been recreated, considering the influence of the driver’s ACC experience. Results statistically confirmed that with the ACC switched on the reaction times are greater than manual driving (2.4/3.8 sec); this can lead to a reduction in road safety, further motivated by the rapid decrease in speed. The interpolation between automated and human data, finally, has allowed the detection of some criticalities of the system that are fundamental in order to reach the second level of automation.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

Multiple myeloma (MM) is a genetically heterogenous disease that includes a subgroup of 10-15% of patients facing dismal survival despite most intensive treatment. The aim of this review article is to provide an integrated clinical and biological overview on the high-risk MM discussing the novel therapeutic perspectives aimed to target the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug resistance can foster a better tailored clinical management of high-risk profile and refractoriness to therapy. Among the current clinical difficulties in MM, patient’s management manipulating the tumor niche represents a major challenge given the limited knowledge about the MM-milieu interaction. The angiogenesis and bystander infiltrate constitute pivotal mechanisms of mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy but variable and unpredictable responses in high-risk MM. Therefore, it would be worth to better select the population and the MM stage that could profit to a dual immune/vasculogenesis targeting. The comprehensive knowledge of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Despite significant improvements in the biology knowledge, MM is still a chronic and incurable neoplasia and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. Here, we corroborate previous biological findings providing a synthetic outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better personalize the patient-oriented clinical management.

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

In this study the effects of three different main preparatory tillage operations [ploughing at 0.4 m (P40) and 0.20 m (P20) depth and minimum tillage at 0.20 m depth (MT) each of them carried out at two different soil water contents (WC) [low, 58% (LH) and high, 80% (HH) of field capacity] were investigated. The results obtained in this research show high values of soil strength in term of Penetration resistance (CI) and shear strength (SS) particularly in deeper soil layers at lower water content. Fossil-fuel energy requirements both for P40 LH and P20 LH were 25 and 35% higher with respect to the HH treatments and tractor slip were very high (P40 LH = 32.4%) with respect to the P40 HH treatment (16%). Therefore soil water content had significantly influenced tractor performance during soil ploughing, particularly at 0.40 m depth while MT was not influenced at all. A significant correlation between grain yield and soil penetration resistance was found highlighting how soil strength may be good indicator of its productivity. Obtained results during these field tests allowed considering MT and P20 treatments more suitable for this type of soil in climate change scenarios.

Background: The use of barbed sutures for pharyngoplasty techniques is a new trend in sleep apnea surgery, but little is known about its short-term results depending on the different techniques. The objective of this study was to compare the surgical results in two different centers using barbed sutures in which the main difference was the loops performed in the soft palate. Methods: This is a retrospective study of patients with obstructive sleep apnea (OSA) operated in two centers. A statistical analysis comparing the ENT department of the Ospedale Morgagni-Pierantoni from Forlí with the ENT department of Dr. Peset University Hospital was performed. Results: The final sample size was 138 patients (70 from Forlí and 68 from Valencia). In both series, a significant improvement was observed in OSA patients with significant reductions in respiratory events not related to weight reduction. The mean delta Apnea-Hypopnea index was 13.36 (SD 21.3) in Forlí and 22.8 (SD 22.05) in Valencia (p<0.05). Forlí’s series had a higher proportion of multilevel surgeries than Valencia's and a lower proportion of tonsillar hypertrophy. Conclusion: The number of loops performed in the soft palate may improve the surgical results, nevertheless, this must be confirmed in prospective studies.

BACKGROUND: diabetic foot ulcers (DFU) represent the main cause of major amputations and hospitalizations in diabetic patients. Aim of this study was to assess safety and cost-efficacy of intramuscular injection of peripheral blood mononuclear cells (PBMNCs), in diabetic patients with no-option chronic limb-threatening ischemia (CLTI) and small artery disease (SAD). METHODS: a retrospective study was carried out on a series of types 2 diabetic patients with DFU grade Texas 3 and no-option CLTI and SAD. All patients had undergone at least a previous revascularization and were allocated in a surgery waiting-list for major amputation. The principal endpoint evaluated at 90 days was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoint were individual components of the primary endpoint, any serious and non-serious adverse events, direct costs at one year. RESULTS: the composite endpoint was achieved in 9 patients (60.0 %); one patient (6.7%) healed within 90 days and 26.7% and 46.7% showed TcPO2 ≥30 mmHg and a TcPO2 increase of at least 50% at 90 days, respectively. At 1-year, three (20.0%) patients underwent a major amputation (all diagnosed SAD grade III). One patient died after seven months, and seven patients (46.7%) healed. The overall median and mean cost per patient were 8,238±7,798€ and 4,426[3,798;8,262]€, respectively. CONCLUSIONS: the use of PBMNCs implants in no-option CLTI diabetic patients with SAD seems to be of help in reducing the risk of major amputation.

The vibrations of a Cartesian cutting machine caused by the pneumatic tool are studied with a sub-system approach. The cutting head is modeled as an equivalent robot arm which is able to mimic the measured resonances, The Cartesian structure is modeled according to the mode superposition approach. The full model is able to predict the variations in the response of the machine to tool excitation that are caused by the motion of the head along the rails of the Cartesian structure. Comparisons with experimental results are made. Finally, the mathematical model is used for assessing the effectiveness of a vibration absorber tuned to main resonance frequency of the cutting head.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

In our increasingly urbanized world, precise and up-to-date maps of human settlements are essential for sustainable urban development policies. The availability of open-access Sentinel-2 data from the Copernicus program presents an opportunity to create a comprehensive global map of human settlements, offering a detailed view of built areas on a large scale. This study estimates large-scale built-up fractions using encoder-decoder deep learning architectures like U-net, Res-U-net, and Attention-U-net in the large and complex urban area of Delhi, India. Openly available datasets like Open Street Map (OSM) and Microsoft building footprint datasets are used to derive built-up fractions at 10×10m resolution cells for over 34,000 km2. Our results show that Attention-U-net with the Huber loss function performs the best in different built-up densities (i.e., urban, semi-urban or rural) with an R2 score of 0.631, while Res-U-net and U-net obtained an R2 score of 0.623 and 0.612, respectively. The investigated networks significantly improve the accuracy over the latest Global Human Settlement Layer product (GHSL-S2), which uses a deep-CNN and reaches an R2 of 0.387 in our case study area. The result of this study yields a valuable spatial layer for examining the spatial distribution of human settlements across the entire spectrum from rural to urban areas.

Information and communication technologies (ICT) are increasingly permeating our daily life and we ever more commit our data to the cloud. Events like the COVID-19 pandemic put an exceptional burden upon ICT infrastructures. This involves increasing implementation and use of data centers, which increased energy use and environmental impact. The scope of this work is to take stock on data center impact, opportunities, and assessment. First, we estimate impact entity. Then, we review strategies for efficiency and energy conservation in data centers. Energy use pertain to power distribution, IT-equipment, and non-IT equipment (e.g. cooling): Existing and prospected strategies and initiatives in these sectors are identified. Among key elements are innovative cooling techniques, natural resources, automation, low-power electronics, and equipment with extended thermal limits. Research perspectives are identified and estimates of improvement opportunities are presented. Finally, we present an overview on existing metrics, regulatory framework, and bodies concerned.

The amount of outdoor particles that indoor environments receive depends on the particle infiltration factors (Fin), peculiar of each environment, and on the outdoor aerosol concentrations and size distributions. The respiratory doses received, while residing indoor, will change accordingly. This study aims to ascertain to what extent such doses are affected by the vertical distance from the traffic sources. Particle number size distributions have been simultaneously measured at street level and at about 20 m height in a street canyon in downtown Rome. The same Fin have been adopted to estimate indoor aerosol concentrations, due to the infiltration of outdoor particles and then the relevant daily respiratory doses. Aerosol concentrations at ground floor were more than double than at 20 m height and richer in ultrafine particles. Thus, although aerosol infiltration efficiency was on average higher at 20 m height than at ground floor, particles more abundantly infiltrated at ground level. On a daily basis, this involved a 2.5-fold higher dose at ground level than at 20 m height. At both levels, such doses were greater than those estimated over the period of activity of some indoor aerosol sources, therefore they represent an important contribution to the total daily dose.

Serelaxin (RLX), the recombinant form of human Relaxin-2 hormone, protects the heart from the ischemia/reperfusion (I/R)-induced damage due to its anti-inflammatory, anti-apoptotic and antioxidant properties. RLX exerts its actions by binding to its specific RXFP1 receptor whereby it regulates multiple cellular transduction pathways. In this in vitro study we offer first evidence for the involvement of AMP kinase/Sirtuin1 (AMPK/SIRT1) pathway in the protection afforded by RLX against H/R-induced damage in H9c2 cells. Treatment of the H/R-exposed cells with RLX (17 nmol L−1) enhanced SIRT1 expression and activity. Inhibition of SIRT1 signaling with EX527 (10 µmol L-1) reduced the beneficial effect of the hormone on mitochondrial efficiency and cell apoptosis. Moreover, RLX upregulated AMPK pathway, as shown by the increase in the expression of phospho-AMPK active protein. Finally, AMPK pathway inhibition by Compound C (10 and 20 μmol L−1) abrogated the increase in SIRT1 expression induced by RLX, thus suggesting the involvement of AMPK pathway in this effect of RLX. The results of this study strengthen the concept that RLX exerts its cardioprotective effects against H/R-induced injury by multiple pathways which also include AMPK/SIRT1.

The production of public goods is a necessary condition for the survival of the species but it comes at the expense of individual growth. In a prototype bacterial colony, we model the role of quorum sensing as a resource redistribution mechanism. Two types of bacterial colonies are analyzed, one made up of a single strain and one made up of two different strains. Based on a recent series of experimental data present in the literature, we analyze two types of strains with different extinction times: strains that consume available resources very quickly, therefore becoming extinct quickly, and strains that consume resources slowly and die due to aging. We show that the proposed quorum sensing model describes the main experimental result, namely that coexistence favors the survival of both strains. Furthermore, the production of public goods is maximized when both types of individuals have the maximum proliferation output. Finally, we highlight the role played by so-called dormant cells in the duration of survival time. These cells are of particular interest, because their ability to counteract different types of stress (e.g. the use of antibiotics) still constitutes a challenge.

Condition monitoring is today a crucial and unavoidable practice related to the use of widespread mechanical components as rolling element bearings. Despite the diffusion of new data-driven techniques to analyze vibrational signals and detect the state of health of the system, mathematical tools, deriving more or less directly from the Fourier transform and defined either on the time or the frequency domain or on a combination of them (i.e. signal-based techniques), remain still essential and irreplaceable in the light of the deep and detailed information they provide. In this paper the diagnostic efficacy of an ample spectrum of these methods is investigated, applying them to study faults occurrence in the first bearing dataset released by NASA IMS Center. Thanks to their analytical definition, which is formulated taking into consideration to some extent the mathematical nature of the signal, faults signatures can be clearly identified and their temporal development can be fully traced, confirming their ability as powerful means to constantly monitor the state of a system even in real-time applications.

The human immunodeficiency virus 1 (HIV-1) viral protease (PR) is one of the most studied viral enzymes, and approval of drugs targeting its catalytic activity opened the door to the develop-ment of highly active antiretroviral therapy (HAART). Despite the fact that its crucial role in viri-on maturation is well characterized, an increasing body of research is starting to focus on its abil-ity to cleave host cell proteins, based on recent advances in proteomics and genomics technologies. Such findings are apparently in contrast with the dogma of HIV-1 PR activity being restricted to the interior of nascent virions, and suggest catalytic activity within the host cell environment. Given the limited amount of PR present in the virion at the time of infection, it is tempting to specu-late that such events mainly occur during viral late gene expression, mediated by newly synthe-sized Gag-Pol polyprotein precursors, rather than at a very early stage of infection, before pro-viral integration. Among cellular targets of HIV-1 PR, three major clusters can be identified: pro-teins involved in viral and cellular translation, those controlling cell survival, and restriction fac-tors responsible for innate/intrinsic antiviral responses. Indeed, by cleaving host cell translation initiation factors HIV-1 PR can impair cap-dependent translation, thus promoting IRES-mediated translation of late viral transcripts and viral production, while by targeting several apoptotic fac-tors it modulates cell survival, thus promoting immune evasion and viral dissemination. Addi-tionally, HIV-1 PR counteracts restriction factors incorporated in the virion that would otherwise interfere with nascent virus vitality. Thus, HIV-1 PR appears to modulate host cell function at dif-ferent times and locations during its life cycle, to ensure efficient viral persistency and propaga-tion. This kind of PR-mediated host cell modulation is found in a plethora of different viruses and HIV-1 is no exception, and although we are far from having a complete picture, it is clear that the PR has a multifaceted role in interfering with host machineries to better suit viral replication, and is a field that needs to be explored further.

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile and non-destructive inference of transverse beam quality (emittance) using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded in to adaptive feedbacks and ML-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results based on simulation data and discuss progress towards implementation in regular operations.

Ambulatory heart rate (HR) monitors that acquire electrocardiogram (ECG) or/and photoplethysmographm (PPG) signals from the torso, wrists, or ears are notably less accurate in tasks associated with high levels of movement compared to clinical measurements. However, reliable estimation of HR can be obtained through data fusion from different sensors. These methods are especially suitable for multimodal hearable devices, where heart rate can be tracked from different modalities, including electrical ECG, optical PPG, and sounds (heart tones). Combined information from different modalities can compensate for single source limitations. In this paper, we evaluate the possible application of data fusion methods in hearables. We assess data fusion for heart rate estimation from simultaneous in-ear ECG and in-ear PPG, recorded on eight subjects while performing 5-minute sitting and walking tasks. Our findings show that data fusion methods provide a similar level of mean absolute error as the best single-source heart rate estimation but with much lower intra-subject variability, especially during walking activities. We conclude that data fusion methods provide more robust HR estimation than a single cardiovascular signal. These methods can enhance the performance of wearable devices, especially multimodal hearables, in heart rate tracking during physical activity.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

This work addresses the role of charge regulation (CR) and the associated fluctuations in the conformational and mechanical properties of weak polyelectrolytes. Due to CR, changes in the pH-value modifies the average macromolecular charge and conformational equilibria. A second effect is that, for a given average charge per site, fluctuations can alter the intensity of the interactions by means of correlation between binding sites. We investigate both effects by means of Monte Carlo simulations at constant pH-value, so that the charge is a fluctuating quantity. Once the average charge per site is available, we turn off the fluctuations by assigning the same average charge to every site. A constant charge MC simulation is then performed. We make use of a model which accounts for the main fundamental aspects of a linear flexible polyelectrolyte i.e. proton binding, angle internal rotation, bond stretching and bending. Steric excluded volume and differentiated treatment for short-range and long-range interactions are also included in the model. It can be regarded as a kind of "minimal'' model in the sense that contains a minimum number of parameters but still preserving the atomistic detail. It is shown that, if fluctuations are activated, gauche state bond probabilities increase, and the persistence length decreases, so that the polymer becomes more folded. Macromolecular stretching is also analyzed in presence of CR (the charge depends on the applied force) and without CR (the charge is fixed to the value at zero force). The analysis of the low force scaling behavior concludes that Pincus exponent becomes pH-dependent. Both with and without CR, a transition from 1/2 at high pH-values (phantom chain) to 3/5 to low pH-values (Pincus regime), is observed. Finally, the intermediate force stretching regime is investigated. It is found that CR induces a moderate influence in the force-extension curves and persistence length (which in this force regime becomes force-dependent). It is thus concluded that the effect of CR on the stretching curves is mainly due to changes in the average charge at zero force. It is also found that, for the cases studied, the effect of steric excluded volume is almost irrelevant compared to electrostatic interactions.

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

Qualtra, an innovative 10 MW geothermal power plant proposal, employs a closed-loop design to mitigate emissions, ensuring no direct release into the atmosphere. A thorough assessment utilizing energy and exergy analysis, Life Cycle Assessment (LCA), Exergo-economic and Exergo Environmental Analysis (EevA) was conducted. The LCA results, utilizing the ReCiPe 2016 midpoint methodology, encompass all the spectrum of environmental indicators provided. The technology implemented makes it possible to totally avoid direct atmospheric emissions from the Qualtra plant, so the environmental impact is mainly due to indirect emissions over the life cycle. The results obtained for the Global Warming Potential indicator is about 6.6 g CO2/kWh, notably lower compared to other conventional systems. Contribution analysis reveals that the construction phase dominates, accounting for over 90% of the impact in all LCA MidPoint categories. At the component level, a single score calculation incorporating normalization and weighting was executed. The resulting single score is then used into Exergo-Environmental Analysis (EEvA), highlighting the well system as the most impactful contributor, constituting approximately 45% of the total impact. Other substantial contributions to the environmental impact include the condenser (21%), the turbine (17%), and the HEGeo (14%). The Exergo-Economic analysis assesses cost distribution across major plant components, projecting an electricity cost of about 8.3 c€/kWh.

This study investigated the associations of imageability with fear reactivity. Imageability ratings of four word classes: positive and negative (i) emotional and (ii) propriosensitive, neutral and negative (iii) theoretical and (iv) neutral concrete filler, and fear reactivity scores – degree of fearfulness towards different situations (TF score) and total number of extreme fears and phobias (EF score), were obtained from 171 participants. Correlations between imageability, TF and EF scores were tested to analyze how word categories and their valence were associated with fear reactivity. Imageability ratings were submitted to recursive partitioning. Participants with high TF and EF scores had higher imageability for negative emotional and negative theoretical words. The correlations between imageability of negative emotional words and negative theoretical words for EF score were significant. Males showed stronger correlations for imageability of negative emotional words for EF and TF scores. High imageability for positive emotional words was associated with lower fear reactivity in females. These findings were discussed with regard to negative attentional bias theory of anxiety, influence on emotional systems, and gender-specific coping styles. This study provides insight into cognitive functions involved in mental imagery, semantic competence for mental imagery in relation to fear reactivity, and a potential psycholinguistic instrument assessing fear tendency.

Accurate channel estimation is of utmost importance for massive MIMO systems that allow providing significant improvements in spectral and energy efficiency. In this work, we investigate the spectral efficiency performance and present a channel estimator for multi-cell massive MIMO systems subjected to pilot-contamination. The proposed channel estimator performs well under moderate to aggressive pilot contamination scenarios without prior knowledge of the inter-cell large-scale channel coefficients and noise power. The estimator approximates the performance of a linear Minimum Mean Square Error (MMSE) as the number of antennas increases. Following, we derive a lower bound closed-form spectral efficiency of the Maximum Ratio Combining (MRC) detector in the proposed channel estimator. The simulation results highlight that the proposed estimator performance approaches the linear minimum mean square error (LMMSE) channel estimator asymptotically.

Advanced-Differential Interferometric SAR (A-DInSAR) has been used to monitor surface deformations in open pit mines and tailings dams. In this paper, ground deformations have been detected on the area of the tailings Dam-I at the Córrego do Feijão Mine (Brumadinho, Brazil) before its catastrophic failure occurred on 25 January 2019. Two techniques optimized for different scattering models, SBAS (Small BAseline Subset) and PSI (Persistent Scatterer Interferometry), were used to perform the analysis based on 26 Sentinel-1B images in IW mode, acquired on descending orbits from 03 March 2018 to 22 January 2019. A WorldDEM DSM product was used to remove the topographic phase component. The results provided by both techniques showed a synoptic and informative view of the deformation process affecting the study area, with a detection of persistent trend of deformations on the top, middle and bottom sectors of the dam face until its collapse, as well as the expected natural settlements on the tailings. It is worth noting the detection of an acceleration in the displacement time-series for a short period near the failure. The maximum accumulated displacements detected along the downstream slope face were -39 mm (SBAS) and -48 mm (PSI). It is reasonable to consider that Sentinel-1 would provide decision makers complementary motion information to the in-situ monitoring system for risk assessment and for a better understanding of on-going instability phenomena affecting the tailings dam.

For the agricultural sector to develop sustainably in the future, progress toward more environmentally friendly technologies and methods is crucial. It is necessary to increase output while reducing the demand for energy, agrochemicals, and water resources. Although greenhouses can be utilized successfully for this purpose, significant technical advancements are required, especially when it comes to heating, to lower the use of fossil fuels and boost energy efficiency. Infrared waves and microwaves, for instance, can warm plants without having to heat the entire greenhouse volume, which takes a significant amount of energy to compensate for heat loss to the outdoor environment. In this paper, through a thorough examination of the state of the art, a general overview of novel greenhouse heating systems based on radiation is reported. First, infrared heating of greenhouses is analyzed, then the strengths and weaknesses of microwave and dielectric heating are discussed, and finally the use of microwaves for soil sterilization is examined. All outcomes suggest these irradiation-based technologies can contribute significantly to an agriculture that is energetically sustainable.

In the last years, molecularly targeted agents and immune based treatments (ITs) have deeply changed the landscape of anti-cancer therapy. Indeed, ITs proved to be very effective in metastatic solid tumors, where outcomes were extremely poor with standard approaches. Such a scenario has been only partially reproduced in hematologic malignancies. In acute myeloid leukemia (AML), as innovative drugs are eagerly awaited in relapsed/refractory setting, different ITs have been explored, but the results are still unsatisfactory. In this work, we will discuss the most important clinical studies to date adopting ITs in AML, providing the bases to understand how this approach, although still in its infancy, may represent a promising therapeutic tool for the next future treatment of AML patients.

The traditionally dismal outcome of acute myeloid leukemia (AML) patients carrying the FMS-related tyrosine kinase 3 (FLT3) mutations has been mitigated by the recent introduction into the clinics of tyrosine kinase inhibitors (TKI) such as midostaurin and gilteritinib. The present work summarizes the clinical data that led to the use of gilteritinib in clinical practice. Gilteritinib is a 2nd generation TKI with deeper single-agent activity than 1st generation drugs against both FLT3-ITD and TKD mutations, in human studies. Moreover, the phase I/II dose-escalation, dose-expansion Chrysalis trial showed an acceptable safety profile of gilteritinib (diarrhea, elevated aspartate aminotransferase, febrile neutropenia, anemia, thrombocytopenia, sepsis, and pneumonia) and a 49% overall response rate (ORR) in 191 FLT3-mutated relapsed/refractory (R/R) AML patients. In 2019, the pivotal ADMIRAL trial showed that the median overall survival was significantly longer in patients treated with gilteritinib than among those receiving chemotherapy (9.3 vs 5.6 months, respectively) and the ORR to gilteritinib was 67.6%, outperforming the 25.8% for chemotherapy arm and leading to the license for its clinical use by the US Food and Drug Administration. Since then, several real-world experiences confirmed the positive results in the R/R AML setting. Finally, gilterinib based combinations currently under investigation with several compounds (venetoclax, azacitidine, conventional chemotherapy, etc.) and some practical tips (maintenance after allogeneic transplantation, interaction with antifungal drugs, extramedullary disease, and onset of resistance) will be analyzed in detail in the review.

This paper presents a novel theoretical and computational methodology for the generation of an onset turbulent field with prescribed properties in the numerical simulation of an arbitrary viscous flow. The methodology is based on the definition of a suitable distribution of volume force terms in the right–hand side of the Navier–Stokes equations. The distribution is represented by harmonic functions that are randomly variable in time and space. The intensity of the distribution is controlled by a simple PID strategy in order to obtain that the generated turbulent flow matches a prescribed turbulence intensity. A further condition is that a homogeneous isotropic flow is es- tablished downstream of the region where volume force terms are imposed. Although it is general, the proposed methodology is primarily intended for the computational modelling of hydrokinetic turbines in turbulent flows representative of tidal or riverine installations. A first numerical applica- tion is presented by considering the injection of homogeneous and isotropic turbulence with 16% intensity into a uniform unbounded flow. The analysis of statistical properties as auto-correlation, power spectral density, probability density functions, demonstrates that the generated flow tends to achieve satisfactory levels of stationarity and isotropy, whereas the simple control strategy used determines overestimated turbulent intensity levels.

The province of Macerata, Italy, is a topographically complex region which has been little studied in terms of its temperature and precipitation climatology. Temperature data from 81 weather stations and precipitation data from 55 rain gauges were obtained, and, following quality control procedures, were investigated on the basis of 3 standard periods: 1931-1960, 1961-1990 and 1991-2014. Spatial and temporal variations in precipitation and temperature were analysed on the basis of six topographic variable (altitude, distance from the sea, latitude, distance from the closest river, aspect, and distance from the crest line). Of these, the relationship with altitude showed the strongest correlation. Use of GIS software allowed investigation of the most accurate way to present interpolations of these data and assessment of the differences between the 3 investigated periods. The results of the analyses permit a thorough evaluation of climate change spatially over the last 60 years. Generally, the amount of precipitation is diminished while the temperature is increased across the whole study area, but with significant variations within it. Temperature increased by 2 to 3°C in the central part of the study area, while near the coast and in the mountains the change is between about 0 and 1°C, with small decreases focused in the Appennine and foothill belt (-1 to 0°C). For precipitation, the decrease is fairly uniform across the study area (between about 0-200 mm), but with some isolated areas of strong increase (200-300 mm) and only few parts of territory in which there is an increase of 0-200 mm, mainly in the southern part of the coast, to the south-west and inland immediately behind the coast. The monthly temperature trend is characterized by a constant growth, while for precipitation there is a strong decrease in the amount measured in January, February and October (between 25 and 35 mm on average).

MAD is the gold standard therapy for mild/moderate OSA and is a second-choice treatment in patients with severe OSA not responding to CPAP. The aim of this study was to analyze the upper airway characteristics of OSA patients and the morphological changes in the upper airway, inducted by four different types of mandibular advancement devices, using CBCT 3D imaging. Twenty-two patients were recruited after OSA diagnosis with polysomnography. Four different customized and titratable MAD were used and an initial CBCT scan was obtained for each patient. After 6 months to the end of the MAD titration phase, all the subjects showed an AHI of &lt; 5 or a decrease of 50% in AHI with MAD when compared with initial AHI and a second CBCT scan with MAD in situ was performed. An important improvement of the airway was observed (+33.76%) and a significant difference in the enlargement ratio between the posterior soft palate (+32.41%) and the posterior tongue (+36.96%) region was also found. The greatest increase in airway volume was achieved in patients treated with the MAD Forward and TAP (respectively +42.77% and + 41.63%). MAD therapy is effective to treat mild/severe OSA with increased upper airway volume. The design of the MAD can influence the effectiveness of the treatment.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

Background: This study aimed to evaluate survival rate, marginal bone levels, and full arch prosthetic success on short implants when placed in areas of severely resorbed and edentulous mandibles. Methods: This is a systematic review of all randomized controlled trials of at least 10 patients with a control group in which bone augmentations were performed that were published between January 2010 and February 2023. Only 3 relevant studies met the inclusion criteria. Results: It obtained demonstrate that short-term dental implant survival rates ranged from 94.2% to 97.4% with a 5-year follow-up and the prosthetic success rate varied by 62% during the same follow-up. The mean marginal bone level values ​​of the affected short implants ranged from 0.2 mm to 0.6 mm. Conclusions: The data obtained demonstrated that short dental implants positioned with criterion and precision as a full-arch fixed support are a valid therapeutic choice for the medium-long term rehabilitation of severe edentulous mandibular atrophy.

Cutaneous T-cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at a clinical and therapeutic level regarding the most well-known inflammatory mediators. An in-depth look has been given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression.From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major Interleukins known in inflammatory environments.Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL.In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

The hepatic sinusoids are lined by thin endothelium containing transcellular pores dubbed fenestra. These fenestrations are completely open channels connecting the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. The fenestrations are in the size range 0.05-0.35µm in diameter and cover between 5-15% of the sinusoidal endothelial surface area depending on their location along the sinusoids. Motivation/Research Question: So far, the narrowness of the sinusoids prevented the direct measurement of hemodynamic features such as sinusoidal pressure and flow velocity. A better understanding of these parameters might help in better understanding the physiology of the hepatic niche and possible implications in liver diseases. Few simulations of liver blood flow focus on the level of the individual sinusoid, fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium, and none have included i) a porosity gradient along the sinusoid wall modelled with through-all pores rather than a porus medium, ii) the presence of the Space of Disse, iii) lymphatic drainage. Model: Computed fluid dynamic (CFD) simulations performed using a numerical model with relevant anatomical characteristics (length, diameter, porous size and porosity). Boundary conditions included physiological/pathological values of inlet/outlet pressure and lymphatic outflow from the portal region of the SoD. Results: The pressure and flow velocity of the sinusoidal lumen was entirely dependent on the shape, i.e. constant versus divergent radius and not dependent on porosity in the sinusoidal wall. The velocity through the space of Disse (SoD) was affected by the addition of lymphatic drainage and increases in porosity in the pericentral area of the model. Variations in porosity also affected flow velocity through the fenestrations. Conclusions: The flow velocity in the SoD was modified by differences in porosity, while the flow velocity in the lumen of the sinusoids was unaffected, even by the absence of fenestrations. The overall shape of the vessel is the singular most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over the hepatocytes is the flow rate through the SoD, and is modestly affected by the distribution of porosity along the sinusoid, and by the addition of a lymphatic drainage, this parameter would be of interest for modelling blood exchange with the hepatic parenchyma, especially if accounting for zonation.

We propose a model for bacterial Quorum Sensing based on an auxiliary electrostatic-like interaction originating from a fictitious electrical charge that represents bacteria activity. A cooperative mechanism for charge/activity exchange is introduced to implement chemotaxis and replication. The bacteria system is thus represented by means of a complex resistor network where link resistances take into account the allowed activity-flow among individuals. By explicit spatial stochastic simulations, we show that the model exhibits different quasi-realistic behaviors from colony formation to biofilm aggregation. The electrical signal associated with Quorum Sensing is analyzed in space and time and provides useful information about the colony dynamics. In particular, we analyze the transition between the planktonic and the colony phases as the intensity of Quorum Sensing is varied.

Langevin simulations are conducted to investigate the Josephson escape statistics over a large set of parameter values for damping and temperature. The results are compared to both Kramers and Büttiker-Harris-Landauer (BHL) models, and good agreement is found with the Kramers model for high to moderate damping, while the BHL model provides further good agreement down to lower damping values. However, for extremely low damping, even the BHL model fails to reproduce the progression of the escape statistics. In order to explain this discrepancy we develop a new model, which shows that the bias sweep effectively cools the system below the thermodynamic value as the potential well broadens due to the increasing bias. A simple expression for the temperature is derived, and the model is validated against direct Langevin simulations for extremely low damping values.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.