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.

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.

Novel drugs profoundly changed the outcomes in CLL patients and traditional prognostic/predictive factors that were delineated in the era of chemo-immunotherapy need to be validated in the contest of these new targeted therapies. Currently, the most important prognostic genetic biomarkers are immunoglobulin heavy chain variable (IGHV) mutational status, genetic aberrations including del(17p)/TP53 abnormalities and the complex karyotype. In this review we discuss the prognostic/predictive role of these genetic markers in relation to novel treatments. Moreover, we present and discuss the new score systems that were elaborated and validated in the era of new drugs. Given the deeper responses obtained with small molecules, new prognostic/predictive markers, including measurable residual disease, and validated prognostic scores could possibly be incorporated into routine prognostic scores, to better identify “very-high” CLL patients, who will need more effective treatments.

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.

We study the deterministic dynamics of N point particles moving at constant speed in a 2D table made of two polygonal urns connected by an active rectangular channel, which applies a feedback-control on the particles, inverting the horizontal component of their velocities, when their number in the channel exceeds a fixed threshold. Such a bounce--back mechanism is non-dissipative: it preserves volumes in phase space. An additional passive channel closes the billiard table forming a circuit in which a stationary current may flow. Under specific constraints on the geometry and on the initial conditions, the large N limit allows nonequilibrium phase transitions between homogeneous and inhomogeneous phases. The role of ergodicity in making a probabilistic theory applicable is discussed both for rational and irrational urns. The theoretical predictions are compared with the numerical simulation results. Connections with the dynamics of feedback-controlled biological systems are highlighted.

Keywords: chronic lymphocytic leukemia; older patient, Bruton tyrosine kinase, BCL2, cost-effectiveness Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, pa-tient’s inclusion criteria were heterogeneous across trials designed for older patients and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events are required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies and registry analyses provided useful information on factors predicting for earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs and the overall expenditure for new drugs in CLL is projected to increase substantially posing an issue for sustainability. This being said, the choice of a finite duration treatment based on venetoclax containing regimens or treatment until progression with BTKi is today possible in high- income countries and the therapy choice drivers are represented by coexisting medical conditions rather than age, by patient expectations, logistics and sustainability.

An efficient, eco-compatible and very cheap method for the construction of triazoles via eliminative azide–olefin cycloaddition (EAOC) reaction has been developed by a catalytic system IL/FeCl3, offering an highly regioselective approach to structurally diverse 1,5-disubstituted 1,2,3-triazoles in up to 95% yield. This strategy features the reuse of catalytic system through simple operations. Mechanistic studies indicated that an asynchronous concerted dipolar cycloaddition-elimination process might be involved.

Process simulation represents an important tool for plant design and optimisation, either applied to well established or to newly developed processes. Suitable thermodynamic packages should be selected in order to properly describe the behaviour of reactors and unit operations and to precisely define phase equilibria. Moreover, a detailed and representative kinetic scheme should be available to predict correctly the dependence of the process on its main variables. This review points out some models and methods for kinetic analysis specifically applied to the simulation of catalytic processes, as a basis for process design and optimisation. Attention is paid also to microkinetic modelling and to the methods based on first principles, to elucidate mechanisms and calculate thermodynamic and kinetic parameters. Different case histories support the discussion. At first, we have selected two basic examples from the industrial chemistry practice, e.g. ammonia and methanol synthesis, which may be described through a relatively simple reaction pathway. Then, a more complex reaction network is deeply discussed to define the conversion of bioethanol into syngas/hydrogen or into building blocks, such as ethylene.

A simple procedure to obtain 1,5-disubstituted 1,2,3-triazoles, using the catalytic system erbium(III) trifluoromethanesulfonate, 1-methyl pyridinium trifluoromethanesulfonate and water is described. The reaction proceeds through an eliminative azide–olefin cycloaddition (EAOC) offering a highly regioselective approach and good yields (81–94%). The advantages of this method include simple operations of work-up and the ability of the catalytic system to be re-used five times without an evident loss in yield.

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.

BACKGROUND: Patients with diabetic foot ulcers (DFU) and chronic limb-threatening ischemia (CLTI are at higher risk for major amputations and mortality. The aim of this study was to assess the safety and cost-efficacy of intramuscular injection of autologous monocyte-rich PRP platelet-rich plasma Tropocells® PRP (Estar Medical, Holon, Israel) in diabetic patients with chronic limb-threatening ischemia (CLTI) in which revascularization was not feasible. METHODS: a retrospective study was carried out on a series of patients with type 2 diabetes, grade Texas 3C or D DFU, and CLTI. All patients had undergone at least a previous revascularization and were allocated to a surgery waiting list for major amputation. According to the data provided by the manufacturer (https://www.zuccatobiotech.it/index.php/prodotti/tropocells), the monocyte-rich PRP kit obtained a platelet-rich plasma with a high concentration of peripheral blood mononuclear cells (with a proportionately lower amount of lymphocytes), a low concentration of neutrophils and an almost complete depletion of red blood cells. All patients underwent a procedure of local infiltration of autologous mononuclear cells through multiple perilesional and intramuscular injections of 10 mL PBMNC suspensions (0.2–0.3 mL in boluses) performed below the knee along the relevant vascular axis (anterior tibial artery and posterior tibial artery) at intervals of 1–2 cm and to a mean depth of 1.5–2 cm, using a 21 G needle. The procedures were performed according to the instructions of the manufacturer and were repeated at least two times (maximum 3 times) at intervals of 30 days. The principal endpoint 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 endpoints were individual components of the primary endpoint, quality of life, any adverse events, and direct costs. All the endpoints were evaluated at 26 weeks. RESULTS: Out of 21 enrolled patients, 13 (61.9%) reached the primary endpoint, whereas three patients underwent a major amputation, and two patients died. The median TpCO2 was significantly increased, and pain was significantly reduced. The overall mean and median cost per patient were 9,255±7,328€ and 4,001 [2,991;7,565]€, respectively. CONCLUSIONS: the use of PBMNCs implants in patients with DFU and no-option CLTI seems to be efficacious in reducing the risk of major amputation and improve ulcer healing.

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.

Background: Fabry disease cardiomyopathy (FDCM) has manifested some resistance to enzyme replacement therapy (ERT) particularly in its advanced phase. Recently myocardial inflammation of autoimmune origin has been demonstrated in FDCM. Aims: Aim of the study is the assessment of circulating anti-globotriaosylceramide (GB3) antibody as biomarker of myocardial inflammation in FDCM. Its sensitivity was based on the evidence of overlapping myocarditis at left ventricular endomyocardial biopsy. Methods and Results: From January 1996 to December 2021, 85 patients received in our Department the histological diagnosis of FDCM and 48 (56.5%) of them had an overlapping myocardial inflammation with negative PCR for the common cardiotropic viruses, positive anti-heart and anti-myosin abs. The presence of anti-GB3 antibodies was evaluated with an Elisa assay (BioGeM scarl Medical Investigational Research, MIR - Ariano Irpino, Italy) in the FDCM patients and compared with controls of healthy individuals. Circulating levels of anti-GB3 autoantibodies were compared with the presence or absence of myocardial inflammation at histology and with the severity of FDCM. The assay results showed that 42 out of 48 FDCM subjects with myocarditis were positive for anti-Gb3 antibodies while 30 out of 37 FDCM patients without myocarditis had negative anti-GB3 antibodies, with a sensitivity of 87.5 % and a specificity of 83.5%. Conclusions: The present study suggests a potential positive role of antiGB3 antibodies as marker of overlapping cardiac inflammation in patients with FDCM.

Genomic selection (GS) is a predictive approach that was build up to increase the rate of genetic gain per unit of time in breeding programs. It has emerged as a valuable method for improving complex traits that are controlled by many genes with small effect. GS enables the prediction of breeding value of candidate genotypes for selection. In this work we address important issues related to GS and its implementation in tomato breeding context. Genomic constrains and critical parameters affecting the accuracy of prediction in such crop such as phenotyping, genotyping training population composition and size and statistical method should be carefully evaluated. Comparison of GS approaches for facilitating the selection of tomato superior genotypes during breeding program are also discussed. GS applied to tomato breeding has already shown to be feasible. We illustrated how GS can improve the rate of gain in elite lines selection, descendent and in backcross schemes. The GS schemes begin to be delineated and computer science can provide support for future selection strategies. A new breeding framework is beginning to emerge for optimizing tomato improvement procedures.

Laser in situ keratomileusis (LASIK) is the gold standard in the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap by a femtosecond laser, ablation of the underlying stromal bed by an excimer laser, and reposition of the flap. The corneal flap can be build in a 2-dimension (2D) fashion with tapered edges, or in a 3-dimension (3D) fashion, with angled sidecut. The latter reduces the risk of flap dislocation and infiltration of epithelial cells. This retrospective study compares with optical coherence tomography 3D and 2D flaps, and respective intra- and early post-operative complications. Four hundred consecutive eyes were included, 200 for each group. In the 3D group, the mean edge angle was 92°. The procedure was in average 5.2 seconds slower in the 3D group (p=0). Non visually significant flap folds were found in 13 eyes of the 2D group and in 7 eyes of the 3D group (p= 0.17). An intracorneal opaque bubble layer induced by laser photodisruption was more commonly observed in the 3D group (9 eyes vs. 2; p=0.03). In conclusion, the creation of a LASIK flap by a 3D-femtosecond laser cut was safe and effective.

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.

Cancer cells show an increased glutamine consumption. The glutaminase (GLS) enzyme controls a limiting step in the glutamine catabolism. Breast tumors, especially the triple negative subtype, have a high expression of GLS. Our recent study demonstrated that GLS activity and ammonia production are inhibited by Sirtuin 5 (SIRT5). We have developed MC3138, a selective SIRT5 activator. Treatment with MC3138 mimicked the deacetylation effect mediated by SIRT5 overexpression. Moreover, GLS activity is regulated by inorganic phosphate (Pi). Considering the interconnected role of GLS, SIRT5 and Pi for cancer growth, our hypothesis is that activation of SIRT5 and reduction of Pi could represent a valid anti-tumoral strategy. Treating cells with MC3138 and lanthanum acetate, a Pi chelator, decreased cell viability and clonogenicity. We also observed a modulation of LC3 and ULK1 with MC3138 and lanthanum acetate. Interestingly, inhibition of mitophagy marker BNIP3 was observed only in the presence of MC3138. Such autophagy and mitophagy modulation was accompanied by an increase of cytosolic and mitochondrial reactive oxygen species (ROS). In conclusion, our results show how SIRT5 activation and/or Pi binding can represent a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy leading to a deleterious accumulation of ROS.

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.

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

Cryptocurrencies have now become an emerging blockchain-based payment technology. Users’ identities on such networks are pseudo-anonymous in that all transactions made from an address are transparent and searchable by anyone; to preserve their privacy, users often use many different addresses. In recent years, some studies have been conducted regarding analyzing clusters of Bitcoin addresses that, according to certain heuristics, belong to the same entity. Such action allows law enforcement to have relevant information in cases where cryptocurrencies are used for illegal trafficking. Clustering methods based on a single heuristic do not allow the clustering of many addresses in a complete and accurate manner. This paper proposes Bitcoin Address Clustering based on multiple Heuristics (BACH), a tool that uses three different clustering heuristics to identify clusters of Bitcoin addresses, which are displayed through a three-dimensional graph. Based on the results, several analyses were conducted, including a comparison with Wallet Explorer, an address clustering tool similar to BACH. BACH, in addition to introducing the innovative feature of graphical visualization of the internal structure of clusters, is shown to improve address aggregation through the joint use of three heuristics for clustering.

Optical coherence tomography (OCT) can help in the diagnosis and treatment of infectious keratitis, but it has not been studied in cases occurring after corneal refractive surgery procedures such as femtosecond laser in situ keratomileusis (FS-LASIK) and keratorefractive lenticule extraction (KLEx). In these procedures a surgical interface is created, where infections usually start, thus determining a different OCT pattern compared to non-surgical infections, which instead begin in the corneal surface. A total of 4 cases of post-refractive surgery infectious keratitis are reported (2 after FS-LASIK and 2 after KLEx), in which the OCT identified an initial infiltrate in the interface, followed by interface inflammation. In 1 case after FS-LASIK, interface fluid accumulation occurred. In 1 case after KLEx, diffuse interface inflammation led to stromal reabsorption, later compensated by stromal reformation and epithelial hyperplasia, well documented by OCT.

Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However some critical issues related to ctDNA assays should be taken in consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC) qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of cfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs.

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.

Background: We aimed to explore microvascular changes evaluated with optical coherence tomography angiography (OCTA) in patients undergoing epiretinal membrane (ERM) pars-plana vitrectomy (PPV) combined with intravitreal Ozurdex implantation, compared with standard PPV. (2) Methods: Prospective interventional analysis on 25 eyes undergoing PPV+Ozurdex (Group A) and 25 eyes undergoing PPV alone. Best corrected visual acuity (BCVA) and OCTA parameters, such as vessel density (VD) of the superficial and deep capillary plexi (SCP and DCP) in the whole 6.4x6.4 mm and fovea area, were evaluated preoperatively and 3 months after surgery. (3) Results: Postoperative BCVA significantly improved in both groups. No cases of post-operative cystoid macular edema (CME) were reported in Group A vs. 2 eyes in Group B. In Group A we found a statistically significant increase of SCP’s VD in either the whole image (from 42.1±4.1 to 45.6±4.3 %, p=0.01) and the fovea image (from 38.5±7.5 to 41.7±4.2%, p=0.03). In Group B, we reported no significant variations in the SCP’s VDs. In the DCP, VD significantly increased only in the whole image in Group A. Stage 4 ERMs showed the greatest improvement in VD, especially in Group A. (4) Conclusions: In conclusion, intraoperative Ozurdex prompted a significant BCVA recover and limited the occurrence of postoperative CME compared to the standard procedure. Moreover, Ozurdex implant is associated with a better restoration of microvascular structure in either SCP and DCP.

The wide range of applications of nanoparticles (NPs) has increased the probability of environmental and occupational exposure. In a previous comparative study on cell line A549, we observed that oxidative stress caused by Co₃O₄ NPs affects the energetic homeostasis and the detoxification capacity, preventing autophagy induced by TiO₂ NPs. In this study, we have investigated the effects of NPs on the cell cycle.Cytofluorimetric analysis showed a slow-down of the cell cycle progression for both NPs, with increases in the percentage of resting cells in the G0/G1. These observations were confirmed by a reduced expression of all cyclins, especially of CCNE1 and CDK2, involved in the late stages of the G1 phase, coupled with a significant increase in the expression of p21 only for Co₃O₄ NP exposure. On the contrary, the effects of TiO₂ NPs were modest. Cell cycle related miRNA-34a, miRNA-126 and miRNA-1290 resulted increased at different early time-points (4-8h) but were down-expressed at 24h-48h only after TiO₂ NP exposure. Our results show that NPs have an antiproliferative effect and deregulate cell cycle on A549 cells. These effects should not be underestimated because regulation of cycle progression is crucial for cell survival and repair of genetic damage.

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.

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.

Climacteric fruits undergo a characteristic ripening process regulated by ethylene, a key plant hormone. Extending the shelf life of these fruits while preserving their postharvest quality poses a significant challenge for the food industry. This review provides a comprehensive overview of physiological and molecular strategies to delay ethylene-mediated ripening in climacteric fruits and their impact on shelf life, postharvest quality, sensory attributes, and volatile compounds. Additionally, it examines the role of ethylene in fruit ripening analysing various ethylene managing strategies including ethylene inhibitors, ethylene adsorbents and ethylene scavengers by catalytic oxidation The review concludes with future research directions including integrated strategies, environmental considerations and commercial applications for improving postharvest handling and fruit quality.

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.

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.

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.

Nanocrystalline silicon oxide (nc-SiOx:H) is a multipurpose material with its varied application in solar cells as a transparent front contact, intermediate reflector, back reflector layer and even tunnel layer for passivating contacts, owing to easy tailoring of its optical properties. In this work, we systematically investigate the influence of gas mixture (SiH4, CO2, PH3 and H2), RF power and process pressure on the optical, structural and passivation properties of thin n-type nc-SiOx:H films prepared in an industrial, high throughput, plasma-enhanced chemical vapor deposition (PECVD) reactor. We provide a detailed description of the n-type nc-SiOx:H material develop-ment using various characterization techniques (SEM, EDX, Raman spectroscopy, and spectro-scopic ellipsometry) with a focus on the relationship between the material properties and the pas-sivation they provide to n-type c-Si wafers characterized by their effective carrier lifetime (τeff). Further, we also outline the parameters to be kept in mind while developing different n-type nc-SiOx:H layers for different solar cell applications. We report a tunable optical gap (1.8 – 2.3 eV) for our n-type nc-SiOx:H films as well as excellent passivation properties with τeff up to 3.5 ms (iVoc ~ 715 mV) before annealing. Oxygen content plays an important role in determining the crystallinity and hence passivation quality of the deposited nanocrystalline silicon oxide films.

Seismic monitoring in areas where induced earthquakes could occur is a challenging topic for seismologists due to generally very low signal to noise ratio. Therefore, the seismological com-munity is devoting several efforts to the development of high-quality networks around the areas where fluid injection and storage and geothermal activities take place, also following the national induced seismicity monitoring guidelines. The use of advanced data-mining strategy, such as template matching filters, auto-similarity search and deep-learning approaches is recently further fostering such a monitoring enhancing the seismic catalogues and lowering the magnitude of completeness of these areas. In this framework, we carried out an experiment where a small-aperture seismic array was installed around the gas reservoir of Collalto, in North Italy. The continuous velocimetric data, acquired for 25 days, were analysed through the application of the optimized auto-similarity search technique FAST. The array was conceived as a cost-effective network, aimed at integrating, right above the gas storage site, the permanent high-resolution Collalto Seismic Network. The analysis allowed to detect micro-events down to magnitude Ml=-0.4 within a distance of ~15km from the array. Our results confirmed that the system based on the array installation and the FAST data-analysis might contribute to lower the magnitude of completeness around the site of about 0.7.

ZnO thin films with a thickness of 300 nm were deposited on Si and Al2O3 substrates using electron beam evaporation technique with the aim to be tested as low cost and low power consumption gas sensors for ozone (O3). To characterize the surface roughness and the grain size, which are the main parameters recognized to enhance gas sensitivity since they directly influence the effective sensing area, surface morphology and roughness analyses of the films were performed using scanning electron microscopy and atomic force microscopy, respectively. The crystalline structure and elemental composition were studied through Raman spectroscopy and X-ray photoelectron spectroscopy. Gas tests were conducted at room temperature and zero-bias voltage to assess the sensitivity and response as a function of time of the films to O3 pollutant. The results indicate that the films deposited on Al2O3 exhibit promising characteristics, such as high sensitivity and a very short response time (< 2 s) to the gas concentration. Additionally, it was observed that the films display pronounced degradation effects after a significant exposure to O3.

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.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

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.

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.

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.

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

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.

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.

Puberty identifies the transition from childhood to adulthood. It normally lasts from 3 to 5 years and begins from 9 years in males and 8 years in females, although with differences related to familiarity and geographical origin. Precocious puberty is the onset of signs of pubertal development before age 8 in girls and before age 9 in boys, it has an incidence of 1/5000–1/10.000 with an F:M ratio ranging from 3:1 to 20:1. Based on the mechanism that triggers puberty, precocious puberty can be classified as central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also known as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual characteristics, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analogs therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Among solar thermal collectors, the evacuated flat panel is emerging as a reference technology for operation at higher temperatures of up to 200 °C with an increased annual energy production owing to both direct and diffuse light capture. Accurate measurements of the optical properties of the selective absorbers used in such devices are key for a reliable estimation of the overall performance. These optical properties must be measured under high vacuum at high temperatures, conditions under which the panels are meant to operate. In this study, we accurately measured these properties using a calorimetric technique. The measurement procedure is based on a power balance equation for a flat sample suspended in a high-vacuum chamber with minimal thermal losses and is well adapted for this class of devices. Calorimetric measurements obtained under Sun and LED light revealed excellent reproducibility and good agreement with those obtained using traditional optical analysis at low temperatures in air. When extended up to the absorber stagnation temperature, which often exceeds 300 °C, the calorimetric measurements started to deviate from the optical measurements, indicating the importance of measuring under the operating conditions.

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.

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.

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.

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration which are based on the use of TCR alpha/beta depletion, CD45 RA depletion, T regulatory cells enrichment, NK cell-based immunotherapies and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

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.

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.

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: Covid-19 patients with any pre-existing cardio-vascular disease (CVD) are at highest risk for viral infection and for developing of severe disease. Pathophysiological mechanism is characterized by the viral link to Angioten-sin-Converting Enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and direct damage on myocardium, micro throm-bosis, and alterations of oxygen diffusion. Aim of the study is to analyze clinical course, treatment and outcome in patients (gender stratified) with pre-existing CVD. Methods: Out of the 1299 (700 M/599 F) patients admitted to Internal Medicine COVID Unit of “Castelli Hospital”, Lazio, Italy, from 01/01/2021 to 31/12/2021, 278 patients (167 M/111 F), mean age 76 (76 M/ 75 F) had previous CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. Results: Most common CVD pathologies were Hearth Failure (HF): 131 (72 M/59 F), Atrial Fibrillation (AF): 45 (25 M/20 F), Myocardial Infarction (MI): 26 (19 M/7 F) and associations among them. 100% of CVD COVID patients under-went Non-Invasive Ventilation (NIV) and were treated with more than 5 drugs. HF was linked with increased LOS (23 days) compared to AF (21 days), MI (18 days) and no CVD (16 days). Overall mean LOS was 16,5 days. 21,4% of total pa-tients had CVD. Conclusions: Timely identification and evaluation of patients with pre-existing CVD are fundamental for adequate treatment based on gender, severity and state of illness and for risk reduction. Keywords: polypharmacy, gender medicine; COVID 19; Sars CoV 2; cardiovas-cular disease.

This article addresses the problem of formation control of a quadrotor and one (or more) marine vehicles operating at the surface of the water with the end goal of encircling the boundary of a chemical spill, enabling such vehicles to carry and release chemical dispersants used during ocean cleanup missions to break-up oil molecules. Firstly, the mathematical models of the Medusa class of marine robots and quadrotor aircrafts are introduced, followed by the design of single vehicle motion controllers that allow these vehicles to follow a parameterized path individually using Lyapunov based techniques. At a second stage, a distributed controller using event triggered communications is introduced, enabling the vehicles to perform cooperative path following missions according to a pre-defined geometric formation. In the next step, a real time path planning algorithm is developed that makes use of a camera sensor, installed on-board the quadrotor. This sensor enables the detection in the image of which pixels encode parts of a chemical spill boundary and use them to generate and update in real time a set of smooth B-spline based paths for all the vehicles to follow cooperatively. The performance of the complete system is evaluated by resorting to 3-D simulation software, making it possible to simulate visually a chemical spill. Results from real water trials are also provided for parts of the system, where two Medusa vehicles are required to perform a static lawn-mowing path following mission cooperatively at the surface of the water.

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.

(1) Background: Grapes and their associated by-products (as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich egg with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A, and gallic acid were determined; (3) Results: In eggs laid by hens fed GP diet, Haugh units and yolk colour score were enhanced, and eggshell became thinner, but without affecting the breaking strength. No dietary effect was observed on vitamin contents in yolk. Higher gallic acid content was observed in yolk of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness and α- and γ-tocopherol concentration in yolks; (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound, but reduced shell thickness.

Brushless Synchronous Machines (BSM) are replacing conventional synchronous machines with static excitation in generation facilities due to the absence of sparking and lower maintenance. However, this excitation system makes challenging measuring electric parameters in the rotor. This fact highly difficult the detection of ground faults, which are the most common type of electrical fault in electric machines. In this paper, a ground fault detection method for BSM is proposed. It is based on an inductive AC/DC rotating current sensor installed in the shaft. In case of a ground fault in the rotating parts of the BSM, a fault current will flow through the rotor’s sensor, inducing voltage in its stator. Analyzing the frequency components of the induced voltage the detection of a ground fault in the rotating elements is possible. The ground faults detection method proposed covers the whole rotor and discern between DC and AC sides. To corroborate the detection method, experimental tests have been performed using a prototype of this sensor connected to laboratory synchronous machines achieving satisfactory results.

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.

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. We reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant Staphyloccus epidermidis (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring (TDM) as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by MR organism, especially in patients who need a long-term suppressive therapy.

While digitization can make the health industry faster and more efficient, there are many financial, social and organizational obstacles and barriers to its implementation. This article offers a systematic review of the main troubles detected from the literature review. Also there is a proposal of new kind of restrictions to pay attention. Finally, its offer an heterodox reading about the problem analyzed.

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.

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.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

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.

Aimed to obtain purple garlic varieties, 360 bolting bulbs from the Protected Geographical Indication (PGI) “Las Pedroñeras” were selected for their size, and the presence of abundant external scales. After a further selection, 243 out of the 360 bulbs were discarded due to undesired characteristics, as light purple color, high number of small cloves, cloves affected by Fusarium spp. and mites, among other. It was stablished that each bulb would give rise to a family. Thus, 117 families were planted under a random design during season 2021-2022. Either physiological, morphological and phenological traits were assessed for each family, and the affectations by pest and pathogens were also controlled. After the assessment of this trial, 103 out 117 families remained in the program, and were used for the establishment of a second trial the next season. Unlike the first trial, after the evaluations only 23 families remained in the program. There was observed a high variability for most of traits, with a great influence of families. The phenotypic behavior of families was significative influenced by environment, highlighting the need of their assessment under different environmental conditions. The high variability registered for the target sample, opens the possibility to select new garlic varieties from this PGI.

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).

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.

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

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.

Three autonomous communities have been the ones that, in the 2022-2023 season, anticipated the document approved by the Public Health Commission, recommending influenza vaccination for all children aged 6 to 59 months. The main objective of this work is to evaluate the attitude of healthcare professionals towards the first universal vaccination campaign in our region, as well as the acceptability of the vaccines used and the attitude towards the piloting of school vaccination. Cross-sectional, survey-based, descriptive study. All healthcare professionals involved in the campaign were invited to participate. The 91.9% of surveyed professionals thought that flu vaccination from 6 to 59 months was important or very important. 89.8% had previous experience regarding the intramuscular vaccine. The professionals valued the intranasal vaccine significantly more positively; however, there were no differences when asking for each of the vaccines without comparison. The inhaled vaccine was preferred by 97.5% for the following campaign. Piloted school vaccination showed 75% acceptance. The inhaled vaccine was preferred by most professionals and the piloted school vaccination was highly accepted, and independently associated to the importance of vaccination as considered by physicians, being a medical doctor, and participation in the pilot program.

The application of space robotic manipulators and heightened autonomy for ios represents a paramount pursuit for leading space agencies, given the substantial threat posed by space debris to operational satellites and forthcoming space endeavors. This work presents a guidance algorithm based on drl to solve for the space manipulator path-planning during the motion synchronization phase with the mission target. The goal is the trajectory generation and control of a spacecraft equipped with a 7-dof robotic manipulator, such that its end effector remains stationary with respect to the target point of capture. The ppo drl algorithm is used to optimize the manipulator’s guidance law, and the autonomous agent generates the desired joints rates of the robotic arm, which are then integrated and passed to a model-based feedback linearization controller. The agent is first trained to optimize its guidance policy and then tested extensively to validate the results against a simulated environment representing the motion synchronization scenario of an ios mission.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

Mineral profile of beef interests human health, but also animal performance and meat quality. This study analyzes the relationships of 20 minerals in beef (ICP-OES) with 3 animal performance and 13 meat quality traits analyzed on 182 samples of Longissimus thoracis. Animals’ breed and sex showed limited effects. The major sources of variation (farm/date of slaughter, individual animal within group and side/sample within animal) differed greatly from trait to trait. Mineral contents were correlated to animal performance and meat quality being significant 52 out of the 320 correlations at the farm/date level, and 101 out of the 320 at the individual animal level. Five latent factors explained 69% of mineral co-variation. The most important, “Mineral quantity” factor correlated with age at slaughter and with the meat color traits. Two latent factors (“Na+Fe+Cu” and “Fe+Mn”) correlated with performance and meat color traits. Two other (“K-B-Pb” and “Zn”) correlated with meat chemical composition and the latter also with carcass weight and daily gain, and meat color traits. Meat cooking losses correlated with “K-B-Pb”. Latent factor analysis appears be a useful means of disentangling the very complex relationships that the minerals in meat have with animal performance and meat quality traits.

Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. These fields of scientific action include promising applications i biomedical areas, in sensing, and in conductive and electrical phases. The sensible definition of supramolecular molecules is being set by investigators, who, because of the different sensitivities of their methods and observational timescales, may have different views as to what constitute these supramolecular structures. Besides, diverse polymers can be found to offer unique avenues for multifunctional systems with properties in medicine industrial applications. Aspects of this review provide different conceptual strategies to address molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. In this order of appreciations and ideas order, it is that this review report involves classic topics such as hydrogels that range from their relationship with drug delivery systems, to metallo-supramolecular materials, through applications in ophthalmic systems, in applications that require adhesiveness and electrically conductive hydrogels. This review also addresses systems that are largely based on hydrogel chemistry and the enormous opportunities to design very specific structures for applications that demand enormous specificity.

In this work, the analytical Lagrange-Kirchhoff model for the deformation for a taiko plate silicon is proposed. Under the conditions of validity of the linear theory of thin plates, the model is in agreement with the experimental data.

Powered lower limb exoskeletons (PLLE) have attracted much interest due to their potential applications. They provide assistance for persons with disabilities to accomplish activities of daily living (ADL), and more importantly assist them in achieving their rehabilitation goals. However, still there are unclear evidences on the quality and benefits that PLLEs can deliver to patients. This is due to limited usability and performance of current PLLEs, insufficient clinical use of PLLEs for different patients with high diversity in their disability type and impairment, and also the large gap between the technological state of the art and clinical expectations. In this study, we review and analyse various factors that can improve the effectiveness of PLLEs at yielding better assistance and rehabilitation training for patients with motor impairments. First, we define a set of criteria that characterize the majority of expectations for the rehabilitation and assistance domains and we use them for evaluating PLLEs depending on the context. Then, we include the effects of control strategies and combined approaches which include auxiliary devices such as Functional electrical stimulation and smart crutches applied to PLLEs with regard to the criteria we defined.

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.

In a Water-Cooled Lithium-Lead (WCLL) Breeding Blanket (BB), the heat generated by the plasma thermal radiation and nuclear reactions is removed mainly by two components; namely, the First Wall (FW) and the Breeding Zone (BZ). The FW faces the neutrons and charged particles fluxes generated by the fusion reactions and the thermal radiation coming from the plasma. The present work takes into account the FW cooling system inspired by the WCLL BB 2018 design of DEMO 2017 baseline. Unlike the baseline where a Pressurized-Water Reactor (PWR) setup is used for the coolant, various setup between the Boiling Water Reactor (BWR) and the High-Pressure (HP) BWR are studied in the present work operating in the Two-Phase Flow (TPF) regime. The 3D model of the FW in the WCLL BB 2018 design is simplified into a 1D model and a steady state analysis is carried out to optimize the mass flow rate of the water and the number of parallel channels at the BB cells at different poloidal locations of the reactor, which helps not only in reducing the used coolant but also in improving the Tritium Breeding Ratio (TBR). The present work takes into account forced convection in the liquid only region, the subcooled boiling region, and the saturated boiling region using suitable empirical or semi-empirical models from the literature. The results are validated against the existing results in the literature. In the end, related conclusions are made regarding the pros and cons of the studied operating conditions.

The increasing availability of longitudinal data (repeated numerical observations of same units at different times) requires the development of flexible techniques to automatically detect common errors in such data. Besides obvious and easily identifiable cases, such as missing or out-of-range data, large longitudinal dataset often present problems not easily traceable by the techniques used for generic datasets. In particular, elusive and baffling problems are i) inversion of one or more values from one unit to another; ii) anomalous jumps in the series of values, iii) errors in the timing of the values due to a recalculation operated by the data providers to compensate previous errors. This work proposes a statistical-mathematical approach based on a system of indicators that is able to capture the complexity of the described problems by working at the formal level, regardless of the specific meaning of the data. The proposed approach identifies suspect erroneous data and is applicable in a variety of contexts. We implement this approach in a relevant database of European Higher Education institutions (ETER) by analyzing Total academic staff, that is one of the most important variables, used in empirical analysis as proxy of size and also considered by policy makers at European level.

Eysenhardtia platycarpa (Fabaceae) is a medicinal plant used in México and it lacks biotechnological studies for its use. The aim of this work was to establish a cell suspension cultures (CSC) of E. platycarpa, determine the phytochemical profile, and evaluate its antifungal activity. Friable callus and CSC were established with 2 mg/L 1-naphthaleneacetic acid plus 0.1 mg/L kinetin. The highest total phenolics of CSC was 15.6 mg GAE/g dry weight and the total flavonoids content ranged from 56.2 to 104.1 µg QE/g dry weight. CG‒MS analysis showed that the dichloromethane extracts of CSC, sapwood and heartwood have a high amount of hexadecanoic acid (22.3 ‒ 35.3 %) and steroids (13.5 ‒ 14.7%). Heartwood and sapwood defatted hexane extracts have the highest amount of stigmasterol (≈ 23.4%) and β-sitosterol (≈ 43%), and leaf extracts presented β-amyrin (16.3%). Methanolic leaves extracts showed mostly sugars and some polyols, mainly D-pinitol (74.3%). Dichloromethane and fatty hexane extracts of CSC exhibited the percentages inhibition higher for Sclerotium cepivorum with 71.5 and 62.0%, respectively. The maximum inhibition for Rhizoctonia solani was with fatty hexane extracts of the sapwood (51.4%). Our study suggest that CSC extracts could be used as a possible complementary alternative to synthetic fungicides.

The larvae of some species of the subgenus Orthocladius s. str. (Diptera, Chironomidae) are here described for the first time with corrections and additions to the descriptions of adult males and pupal exuviae. The identification of larvae is generally not possible without association with their pupal exuviae and/or adult males, so the descriptions here are based only on reared material or on pupae with the associated larval exuviae. Usually, Chironomidae larvae can be separated on the basis of morphometric characters, and the most discriminant characters ones are: 1- the ratio between the width of median tooth of mentum (Dm) and the width of the first lateral tooth (Dl) = mental ratio (DmDl), 2- the ratio between the length of the first antennal segment (A1) and the combined length of segments 2-5 (A(2-5)2-5) = antennal ratio (AR). The shape of mandible, maxilla, and other body parts are almost identical in all the species considered in this study. The larva of Orthocladius (Symposiocladius) lignicola is very characteristic and can be separated by the shape of mentum and the larvae of all the known species of Symposiocladius are characterized by the presence of large Lauterborn organs on antennae and of tufts of setae on abdominal segments. The larvae of Orthocladius (Orthocladius) oblidens and Orthocladius (Orthocladius) rhyacobius can be distinguished from other species basing on their large Dm and to each other by AR. A principal component analysis was carried out using 5 characters: 1- Dm, 2- Dl, 3- length of A1, 4- width of A1 (A1W), 5- combined length of segments 2-5 (A2-5). The most discriminant characters were Dm and A1, confirming that DmDl and AR can be used to separate species at larval stage, but the large superposition of morphometric characters in different species confirms that association with pupal exuviae is in any case needed to identify larvae. In future perspective, the development of reference DNA barcodes from specimens identified by specialists is recommended since possibly the best tool for larvae identification, but association of barcodes with morphotypes is in any case fundamental.

Natural radioactivity of 238U, 232Th and 40K for liquid and solid samples collected from Sidi Salem dam (Tunisia) and Aïn Dalia dam (Algeria) were measured using TERRA detector of rays (gam-ma, beta, and alpha), Atomic adsorption and Gamma-ray spectrometry were used to analyze the levels of radionuclides and toxic heavy metals, respectively. Toxic heavy metals (Fe, Bb, Zn, Ni, Cu, Cr and Cd) and associated health risks in surface water and sediment of dams have been in-vestigated in this present study. The radioactivity mean rates in the water samples were 1.72±0.01, 0.068±0.01 and 94.6±1.04 Bql-1 for 238U, 232Th and 40K respectively (Tunisia dam) and were 1.9± 0.24, 0.09±0.01 and 131.43±1.03 Bql-1 for 238U, 232Th and 40K respectively (Algeria dam). The 238U, 232Th and 40K radioactivity mean concentration measured in the sediment samples were 2.67±0.01, 0.18±0.012 and 197.87±2.01 Bqkg-1 respectively (Tunisian dam) and were 4.34±0.05, 0.27±0.05 and 287.61±3.34 Bqkg-1 respectively (Algeria dam). The activity concentration of 40K was higher than that of 238U and 232Th for the water and sediment samples. The mean activity concen-trations follow the order 40K > 238U > 232Th. The cumulative impact can be a serious immediate radiological health burden on the ecosystem, environment and people's health in this study area and can be transposable to any other similar region. The good knowledge of monitoring quality and quantity for the transboundary water resources and the international collaborations are es-sential to safeguard human health (women’s breasts cancer, thyroid cancer, neurological im-pact…), and avoid the conflicts, especially during these climatic upheavals of drought.

The SARS-CoV-2 polybasic furin cleavage site is still a missing link. Remarkably, the two arginine residues of this protease recognition site are encoded by the CGG codon, which is rare in Betacoronavirus. However, the arginine pair is common at viral furin cleavage sites, but are not CGG-CGG encoded. The question is: Is this genetic footprint unique to the SARS-CoV-2? To address the issue, using Perl scripts, here I dissect in detail the NCBI Virus database in order to report the arginine dimers of the Betacoronavirus proteins. The main result reveals that a group of Middle East respiratory syndrome-related coronavirus (MERS-CoV) (isolates: camel/Nigeria/NVx/2016, host: Camelus dromedarius) also have the CGG-CGG arginine pair in the spike protein polybasic furin cleavage region. In addition, CGG-CGG encoded arginine pairs were found in the orf1ab polyprotein from HKU9 and HKU14 Betacoronavirus, as well as, in the nucleocapsid phosphoprotein from few SARS-CoV-2 isolates. To quantify the probability of finding the arginine CGG-CGG codon pair in Betacoronavirus, the likelihood ratio (LR) and a Markov model were defined. In conclusion, it is highly unlikely to find this genetic marker in betacoronaviruses wildlife, but they are there. Collectively, results shed light on recombination as origin of the virus CGG-CGG arginine pair in the S1/S2 cleavage site.

Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (¹⁰B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of ¹⁰B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of ¹⁰B in a specific tissue in real-time using noninvasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. Moreover, functional imaging technologies such as PET can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Anyway, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.

A therapy’s outcome is determined by a tumor’s response to treatment which, in turn, depends on multiple factors such as the severity of the disease and the strength of patient’s immune response. Gold standard cancer therapies are in most cases fragile when sought to break the ties to either tumor kill ratio or patient toxicity. Lately, research has shown that cancer therapy can be at most robust when handling adaptive drug resistance and immune escape patterns developed by evolving tumors. This is due to the stochastic and volatile nature of the interactions, at the tumor environment level, tissue vasculature, and immune landscape, induced by drugs. Herein, we explore the path towards antifragile therapy control, that generates treatment schemes that are not fragile but go beyond robustness. More precisely, we describe a first instantiation of a control-theoretic method to make therapy schemes cope with the systemic variability in the tumor–immune–drug interactions and gain more tumor kill with less patient toxicity. Considering the anti-symmetric interactions within a model of the tumor–immune–drug network, we introduce the antifragile control framework that demonstrates promising results in simulation. We evaluate our control strategy against state-of-the-art therapy schemes on various experiments and discuss the insights we gained on the potential that antifragile control could have in treatment design in clinical settings.

This work analyzes the visibility and scientific impact of publications related to agricultural value chains. The incidence of bibliometric indicators allows for the interpretation of bibliographic information generated worldwide. Objective: The objective of this research is to analyze the published literature and bibliometric indicators on agricultural value chains. The Web of Science database was used to extract value chains data. The study analyzed articles published between 2010 and 2020. The keywords used are "agricultural value chains'' and articles from journals or studies related to the subject were selected for bibliometric analysis and methodological review. In the search for the keyword, a total of 4208 results were extracted, of which 1,669 records were considered for analysis. The bibliometric analysis of the data reveals that Wageningen University (55) has the highest number of publications, followed by Chinese Acad Sci (26). The author Klerkx L (9) has the highest number of records, followed by Hellin J (7). With respect to the countries with the greatest contributions on the subject are: the People's Republic of China, Germany, Italy, France and the United States. The study contributes to the analysis of bibliometrics and provides a methodological review of published journal articles on agricultural value chains. This bibliographic study presents the history of research development in agricultural value chains.