Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

Myofascial pain is the most common cause of chronic pain in the masticatory region and can be assessed through clinical analysis and muscle palpation. Generally, it appears with headache and orofacial pain associated with sensitive points (trigger points) due to the excessive contraction of the masticatory muscle fibres. The study aims to evaluate how a correct treatment of myofascial pain can improve the life quality of the affected patients. In this case series, 300 patients with myofascial pain were divided into two groups: 150 with intra- and extra-articular disorder and 150 with the only extra-articular disorder. Each group included 75 males and 75 females. All the patients were treated with gnathological therapy through passive aligners and biofeedback exercises for 4 months. They underwent pain assessment (through a visual analogue scale and muscular palpation test) before, during and after the treatment, and nuclear magnetic resonance of the temporomandibular joint before and after the gnathological treatment. The treatment considerably reduced the pain in all patients, without drugs, in 4 months, according to the visual analogue scales and the palpation test. The temporomandibular magnetic resonance in each patient was similar before and after the gnathological treatment. The improvement in pain did not depend on a change in the relationship between the articular condyle and the disc.

This paper aims at providing a multisource data analysis, including direct data collection, focussed on daily average distances covered with motorised mobility. Its results can be used as a basis for policies involving a shift towards new propulsions, electric motors or hybrid electric vehicles (HEV) for road vehicles. A number of variables influence the propensity of drivers to acquire or use electric traction, even the option of plug-in hybrid electric vehicles (PHEV). This paper addresses one of such variable: the compliancy of electric traction regarding both hybrid plug-in solutions and full-electric vehicles, in addition to the autonomy of batteries (range), with the daily travels by road vehicles, mainly by automobiles. We want to understand whether the constraints leading towards a greater independence from crude oil rather than constraints concerning emissions, mainly in urban contexts, might be compliant with the habitual daily trips of drivers. We also want to understand if these daily trips have varied much during recent years and the consequences they may have on operational costs of plug-in automobiles. We are well aware that the average distances do not represent the actual daily runs of vehicles; yet similar distributions of daily distances for different case studies indicate that a high percentage of trips respond to certain features. After introducing a general overview of road-motorised mobility in Italy, the paper compares data from other studies to provide an indication of average daily driving distances. This reveals how different recent analyses converge on a limited range of average road distances covered daily by Italians, which is compliant with ranges allowed by electric batteries, provided that their low energy density in comparison with that of oil-derived fuels do not imply a significant increase in vehicle mass. Subsequently, average distances in some EU Countries are taken from the literature, and the results are also compared with U.S. data. The study extends the analysis of trends on the use of automobiles and road-vehicles to the international context by also addressing average daily distances covered for freight transport in some EU Countries, thereby providing a further basis for comparison and for understanding whether the daily motorised mobility can be considered as a stable phenomenon. Finally, an analysis is provided of the economic operational advantages from using plug-in vehicles. The main aim of this paper is thereafter to investigate the average daily motorised mobility of single vehicles – so not an aggregated motorised mobility as collected by some statistics – by using private motorised vehicles in Italy, with related trends; thereafter, to compare these data with those obtained from other countries, making use of both existing research studies and directly collected data; the final aim is to understand both the compliance of daily activities based on the use of automobiles with the autonomy of batteries (range) and to calculate some economic outcomes.

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

Residual dizziness after a liberating maneuver is often referred to by patients as a more disabling set of symptoms than the positional vertigo itself. This situation seems to involve more than half of subjects with labyrintholithiasis. The authors examine the hypothesis according to which residual dizziness involves subjects with labyrintholithiasis on the basis of otoconia.

Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related with a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide and it is estimated that is present in up to 25% of the world's population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthetized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allow the direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight about the mechanism and drugs action in NAFLD. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical disc. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using highly specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈ 0.39 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the lipid accumulation within the cells. Moreover, we discovered that at third day from lipids challenge, the hepatocytes increased the amount of albumin secreted. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation needed to unveil the biological significance of that cell behaviour.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.

In horses, quantitative assessment of gait parameters, as the use of inertial measurement units system (IMUs), might help in the decision-making process. However, it requires financial investment, is time-consuming, and lacks accuracy if displaced. An innovative Artificial Intelligence marker-less Motion Tracking System (AI-MTS) may overcome these limitations in the field. Our aim was to compare the level of agreement and accuracy between both systems and visual clinical assessment. Twenty horses underwent locomotion analysis by visual assessment, IMUs and AI- MTS systems, in the following conditions: straight hard (SH), straight soft (SS), left and right circle hard (LCH, RCH) and soft (LCS, RCS). A greater number of horses were considered sound by clinical examination, compared to those identified as symmetric by the two gait analysis systems. More limbs were considered asymmetric by the AI-MTS compared to IMUs, suggesting its greater sensitivity. The greatest agreement between the two systems was found for the difference between two minima in vertical head position in SH, while the lowest for the difference between two minima in vertical pelvis position in SS, reflecting the difficulties in assessing asymmetry of hindlimbs. Some degree of asymmetry may be clinically relevant, suggesting its regular use in training horses.

Dynamic virtual testing by Hardware in the Loop (HIL) real time simulation systems is common to minimize physical tests to validate and verify control algorithms, logics and software, under normal and emergency conditions. The accurate but costly HIL models setup activities could have an extended use to simulate faulty conditions that are seldom observable in the real system, yet they must be detected in advance and recognized. Data driven diagnostic methods have reached a mature development, in various sectors, proving effective in early detecting slowly varying deviations from nominal patterns of signals, even without a priori knowledge of their nature and behavior. These methods rely on vast amount of data logged from real systems that are ever and ever richer of monitoring telemetries that are worth being exploited. However, due to the usually reliable and safe systems being managed, it is often difficult to collect enough data on anomalous situations to validate fault detection and isolation and limit false positives. HIL model-based simulations allow generating and observing operational domains or transients rarely observed in real operations. This allows identifying the signals that are most correlated to faults and that could be selected to setup data-based diagnostic models of parts or subsystems, which are more suitable than the whole HIL model for online diagnostics, as well as to identify the features and trends that are most symptomatic of anomalous conditions.

Phytoestrogens are plant-derived bioactive compounds with estrogen-like properties. Their potential health benefits, especially in cancer prevention and treatment, have been a subject of considerable research in the past decade. Phytoestrogens exert their effects, at least in part, through interactions with estrogen receptors (ERs), mimicking or inhibiting the actions of natural estrogens. Recently, there has been growing interest in exploring the impact of phytoestrogens on osteosarcoma (OS), a type of bone malignancy that primarily affects children and young adults, and currently presenting limited treatment options. Considering the critical role of estrogen/ERs axis in bone development and growth, the modulation of ERs has emerged as a highly promising approach in the treatment of OS. This review provides an extensive overview of current literature on the effects of phytoestrogens on human OS models. It delves into the multiple mechanisms through which these molecules regulate the cell cycle, apoptosis and key pathways implicated in the growth and progression of OS, including ERs signaling. Moreover, potential interactions between phytoestrogens and conventional chemotherapy agents commonly used in OS treatment will be examined. Understanding the impact of these compounds in OS holds great promise for developing novel therapeutic approaches that can augment current OS treatment modalities.

The aim of the study is to evaluate the predictive factors of response to induction chemotherapy in patients with resectable NSCLC, treated at the unit of Thoracic Surgery of Siena University Hospital with radical surgery. From January 1, 2013 to December 31, 2020, 78 patients were recruited. We analyzed the outcomes in terms of 5-years OS based on the Estimated Regression Rate, N2 downstaging and age; two patients’ subgroups were created by age (Group A: age <66 years-old; Group B: age >66 years-old). No 5-year OS difference was observed based on age, while it was observed in patients with N2 downstaging (p=0.031). Bewtween patients with N2 downstaging, only patients in Group A had a significantly increased 5-year OS (p=0.019), while this was not observed in Group B (p=0-321); the same result was observed with the Estimated Regression Rate > 50% (Group A p=0.005; Group B p=0.391). The percentage of disease regression and the N2 down-staging after induction chemotherapy have great value on the survival, although this advantage seems to be observed mostly in younger patients. A multidisciplinary oncologic discussion of clinical cases could provide support in the careful selection of the ideal patients to undergo neoadjuvant treatment before radical surgery.

The study conducts a comparative life cycle assessment (LCA) analysis to assess the environmental impact of two different manufacturing processes used to produce transparent dental aligners. The former method consists of thermoforming a polymeric disc over 3D printed, customized models, while the second, more innovative approach involves the direct printing of aligners using additive manufacturing (AM), specifically applying digital light processing (DLP) technology. The analysis results highlight how adopting direct printing through AM brings significant advantages in terms of environmental sustainability, thanks to the substantial reduction in raw materials and electricity consumption. These drops translate into decreased potential environmental impacts across all impact categories considered within the EF 3.1 method. Furthermore, lowering the amount of raw materials needed in the direct printing process contributes to a notable decrease in the overall volume of waste generated, emphasising the environmental benefits of this innovative technique.

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, where it not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying the specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined osteoimmunology. Specifically, we have comprehensively elaborated on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis lead to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Cars are a highly inefficient mode of urban transport with significant negative impacts. Electric vehicles make it possible to eliminate direct CO2 emissions (though the total over a vehicle’s entire life cycle greatly offsets the advantages) but leave unchanged – or even aggravate – all the other negative effects on the quality of urban environments. Three visions for urban transport were presented: automobility, multimodality and accessibility. The first dominates North American cities, the second European one. The anomalies of these two visions have been examined. The automobility cities cannot manage the congestion and the attempts are self- defeating. The anomalies of multimodality city are related to the public space consumption for mobility and the impossibility to plan spatial proximity. The sustainable vision, that resolve the anomalies, is represented by the accessibility city in the Triple Access System (TAS) version which, however, still has a long way to go to be accepted and implemented.

The increasing demand for craft beer drives the search for novel ale yeast cultures from brew-ing-related wild environments. The focus of bioprospecting for craft cultures is to identify feral yeasts suitable to imprint unique sensorial attributes to the final product. Here, we integrated phylogenetic, genotypic, genetic, and metabolomic techniques to demonstrate that sour beer during aging in wooden barrel is a source of suitable craft ale yeast candidates. Differently from traditional lambic beer maturation phase, during aging of sour-matured production style beer, different biotypes of Saccharomyces cerevisiae dominated the cultivable in-house mycobiota, fol-lowed by Pichia membranifaciens, Brettanomyces bruxellensis, and Brettanomyces anomalus. In addi-tion, three putative S. cerevisiae x Saccharomyces uvarum hybrids were identified. S. cerevisiae feral strains sporulated, produced viable monosporic progenies, and have STA1 gene as well as the full-length promoter. During hopped wort fermentation four S. cerevisiae strains and the S. cere-visiae x S. uvarum hybrid WY213 overcame non-Saccharomyces strains in fermentative rate and ethanol production, except for P. membranifaciens WY122. This strain consumed maltose after a long lag phase, in contrast with the phenotypic profile descripted for the species. According to STA1+ genotype S. cerevisiae partially consumed dextrin, but no 4-vynil guaiacol was detected among VOCs, suggesting that these strains were phenolic off flavor-negative (POF-). In conclu-sion, the strains characterized here have relevant brewing properties and are exploitable as in-digenous craft beer starters.

Background: Anthropometric measurements play a crucial role in medico-legal practices. Actually, several scanning technologies are employed in post-mortem investigations for forensic anthropological measurements. This study aims to evaluate the precision, in-ter-rater reliability, and accuracy of a hand-held scanner in measuring various body parts. Methods: Three independent raters measured seven longitudinal distances using an iPad Pro equipped with a LiDAR sensor and specific software. These measurements were sta-tistically compared to manual measurements conducted by an operator using a laser level and a meterstick (considered the gold standard). Results: The Friedman’s test revealed minimal intra-rater variability in digital measurements. Inter-rater variability analysis yielded an ICC=1, signifying high agreement among the three independent raters. Addi-tionally, the accuracy of digital measurements displayed errors below 2%. Conclusions: Preliminary findings demonstrate that the pairing of LiDAR technology with the Polycam app showcases high precision, inter-rater agreement, and accuracy. Hand-held scanners show potential in forensic anthropology due to their simplicity, affordability, and porta-bility. However, further validation studies under real-world conditions are essential to es-tablish the reliability and effectiveness of handheld scanners in medico-legal settings.

Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection, however no clinical trial data are available and combined use of direct acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post-hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than linear shift of a drug effective concentration (IC50) at increasing concentrations of the companion drug, although the effect was prominent with DAA/DAA combinations but minimal or null with RDV/mAb combinations. These results support a cooperative effects of dual drug combinations in vitro, which should be further investigated in animal models before introduction into the clinic.

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

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.

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

Hypoxia-inducible factor (HIF)-1α represents the oxygen-sensitive subunit of HIF transcriptional factor, usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expression. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. We herein analyzed HIF-1α expression and localization in differentiating murine C2C12 myoblasts and SCs under normoxia and evaluated matrix metalloproteinase (MMP)-9 as a HIF-1α target, by biomolecular, biochemical, morphological and electrophysiological analyses. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression, differently from the more elongated and parallel-aligned cells, likely ready to fuse with each other, which show mainly a cytoplasmic localization of the factor. Multinucleated myotubes displayed both a nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. Short-interfering RNA silencing of HIF-1α and MMP-9 and MMP-9 pharmacological inhibition unraveled MMP-9 as HIF-1α downstream effector and HIF-1α/MMP-9 axis essential for the morpho-functional cell myogenic commitment.

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

Our work is regarding the analysis of land use changes, in the light of “saving soil” against the expansion due to unearned plus value of land: The loss of natural and agricultural surface in front of the expanding urban environment is a critical aspect of unsustainability of urban development, especially in the way it was carried out in the past decades. The measure of the physical transition of land use and characters from a more natural condition of land surface to a new artificial one, joint with a parallel analysis of the increase of land value due to such change is nowadays a major land-policy tool. The interplay of urban economics regulation with planning, reveals new key issues in urban governance and environmental preservation. In this paper it will be shown some experiment about the impact assessment of soil take, related with the seek of valorization of property inside the planning process. Our paper reports as well about the experimental activity carried out inside the MITO Lab of the Polytechnic of Bari, where reports about property values and environmental values have been produced, specially looking at the reality of the Apulia, a southern Italian Region, that is rich of farmlands and coastlines, often invaded by constructions with a severe loss of nature, landscape and ecosystems services.

Polar stratospheric clouds (PSCs) form in polar regions typically between 15 and 25 km, when the local temperature is sufficiently low. PSCs play an important role in the ozone chemistry and the dehydration and denitrification of the stratosphere. Lidars with a depolarization channel may be used to detect and classify different classes of PSCs. The main PSC classes are water ice, nitric acid trihydrate (NAT) and supercooled ternary solutions (STS), the latter being liquid droplets consisting of water, nitric acid and sulphuric acid. PSCs have been observed at the lidar observatory at Concordia Station from 2014 on. The harsh environmental conditions at Concordia during winter render successful lidar operation difficult. In order to facilitate the operation of the observatory several measures have been put in place to achieve an almost complete remote control of the system. PSC occurrence is strongly correlated with local temperatures and is affected by dynamics, as the PSC coverage during the observation season shows.

We study the work fluctuations in ergotropic heat engines, namely two-strokes quantum Otto engines where the work stroke is designed to extract the ergotropy (the maximum amount of work by a cyclic unitary evolution) from a couple of quantum systems at canonical equilibrium at two different temperatures, whereas the heat stroke thermalizes back the systems to their respective reservoirs. We provide an exaustive study for the case of two qutrits whose energy levels are equally spaced at two different frequencies by deriving the complete work statistics. By varying the values of temperatures and frequencies, only three kinds of optimal unitary strokes are found: the swap operator U1, an idle swap U2 (where one of the qutrits is regarded as an effective qubit), and a non trivial permutation of energy eigenstates U3, which indeed corresponds to the composition of the two previous unitaries, namely U3 = U2U1. While U1 and U2 are Hermitian (and hence involutions), U3 is not. This point has an impact on the thermodynamic uncertainty relations (TURs) which bound the signal-to-noise ratio of the extracted work in terms of the entropy production. In fact, we show that all TURs derived from a strong detailed fluctuation theorem are violated by the transformation U3.

In the Emergency Department (ED), pain is one of the symptoms that is most frequently reported, making it one of the most significant issues for the emergency physician, but is frequently under treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondary, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a systematic review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library and Controlled Trials Register finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. IN is simple to administer, non-invasive, rapid onset and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Analgesia needs to be tailored to each patient's features and type of pain: IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.

The last decade was characterized by the reduction of hospital beds throughout Europe. When facing Covid pandemic, this has been an issue of major importance as hospitals were seriously overloaded with an unexpected growth in demand. The dichotomy formed by the scarcity of beds and the need for acute care was handled by the Bed Management (BM) function. This study explores how BM was able to help the solidness of the healthcare system, managing hospital beds at best and recruiting others in different set-tings as intermediate care, in a large Local Health Authority (LHA) in central Italy. Ad-ministrative data show how the provision of appropriate care was achieved recruiting approximately 500 beds belonging to private healthcare facilities affiliated with the re-gional healthcare system and exercising at best the BM function. The ability of the system to absorb the extra demand caused by Covid was made possible using intermediate care beds, which allowed to stretch the logistic boundaries of the hospitals, and by the promptness of Bed Management in converting beds in Covid beds and reconverting them and timely managing internal patient logistic, thus creating space according to the healthcare demand.

Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients - obs-AMI and MINOCA - NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI, a larger LVEDV and a lower LVEF compared to normoglycemic ones. Conversely, MINOCA patients showed similar myocardial damage, irrespective of glycemia. Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. TILs has a strong prognostic role in triple negative breast cancer (TNBC). Little is known about his interaction with Androgen receptor (AR) and Forkhead box A1 (FOXA1). We analyzed the relationships between TIL levels, AR and FOXA1 expression and their clinical significance in TNBC patients. Further, we investigated their interaction with other biomarkers like programmed cell death ligand-1 (PD-L1), Breast Cancer Type 1 susceptibility protein (BRCA1), Poly [ADP-Ribose] Polymerase 1 (PARP1) and Na+/H+ Exchanger Regulatory Factor 1 (NHERF1). The expression of the proteins was evaluated by immunohistochemistry in 124 TNBC samples. TILs were performed adhering to International TILs Working Group 2014 criteria. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis. Multivariate analysis identified TILs as independent prognostic factor of disease free survival (DFS) (p=0.045). A Kaplan-Meyer analysis revealed that the patients with high TILs had a better DFS compared to patients with low TILs (p=0.037), and the phenotypes TILs-/AR+ and TILs-/FOXA1- had a worse DFS (p=0.032, p=0.001 respectively). AR was associated with FOXA1 expression (p=0.007), and the tumors FOXA1+ presented low levels of TILs (p=0.028). A poor DFS was observed for AR+/FOXA1+ tumors compared to other TNBCs (p=0.0117). Low TILs score was associated with poor patients’ survival, and TILs level in combination with AR or FOXA1 expression affected patient’s clinical outcome. In addition, AR+/FOXA1+ phenotype identified a specific subgroup of TNBC patients with poor prognosis. These data may suggest new ways of therapeutic intervention to support current treatments.

In the last two centuries, land use change (LUC) has been the most important direct changes driver for terrestrial ecosystems. To contrast the consequent ecosystems degradation, forward-looking spatial policies and target landscape and land-use planning processes, promoting a sustainable land use change, are needed. The present paper proposes a framework of action including different landscape planning and ecological approaches: from the spatial modelling to recognize the LUC and build different scenarios, to the ecosystem services (ESs) assessment to evaluate the possible environmental impacts. Three different scenarios were built: Trend, No-Tillage and Energy crops. The Sediment Delivery Ratio and Carbon Storage and Sequestration ESs were assessed and compared for each scenario. The aim of the paper is to support decision-makers and local communities into the landscape planning process. Results show that a regional development in line with past trend could lead to further land degradation. Instead, the two scenarios proposed in compliance with EU policies, could bring benefits only if related to moderate LUCs and respecting the naturally grass-vegetated land. From the local to global scale, a guided and shared LUC management allows implementing sustainable development, basing on a deep knowledge of physical-environmental but also social and economic issues.

Background Due to the COVID-19 pandemic, teledermoscopy has been increasingly used in the remote diagnosis of skin cancers. In a study conducted in 2020, we demonstrated a potential role of an inexpensive device (NurugoTM Derma) as a first triage to select the skin lesions that require a face-to-face consultation with dermatologists. Herein, we report the results of a novel study that aims to better investigate the performance of NurugoTM. Objectives i) verify whether the NurugoTM can be a communication tool between the General Practitioner (GP) and dermatologist in the first assessment of skin lesions; ii) analyze the degree of diagnostic-therapeutic agreement between dermatologists; iii) estimate the number of potentially serious diagnostic errors. Methods One hundred forty-four images of skin lesions were collected at the Dermatology Outpatient Clinic in Novara using a conventional dermatoscope (instrument F), the NurugoTM (instrument N), and the latter with the interposition of a laboratory slide (instrument V). The images were evaluated in-blind by four dermatologists, and each was asked to make a diagnosis and to specify a possible treatment. Results: Our data show that F gave higher agreement values for all dermatologists, concerning the real clinical diagnosis. Nevertheless, a medium/moderate agreement value was obtained also for N and V instruments and that can be considered encouraging and indicate that all examined tools can potentially be used for the first screening of skin lesions. The total amount of misclassified lesions was limited (especially with the V tool), with up to nine malignant lesions wrongly classified as benign. Conclusions NurugoTM, with adequate training, can be used to build a specific support network between GP and dermatologist or between dermatologists. Furthermore, its use could be extended to the diagnosis and follow-up of other skin diseases, especially for frail patients in emergencies such as the current pandemic context.

Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

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.

The global process of urbanization, and the modification of social interaction determined by the pandemic crisis poses the issue of the place of vulnerable users, and in particular children, within the contemporary city. This research aims to elaborate a theoretical and methodological framework, based on the concepts of affordance and capability, for analyzing the potential of public spaces to enable and support children’s independent activities. This potential, or meaningful usefulness, is expressed by the Index of Meaningful Usefulness of public Urban Spaces (IUIS). The latter is calculated via the tool ‘Opportunities for Children in Urban Spaces’ (OCUS). This methodology is applied to the analysis of significant public spaces within the historic center of the city of Iglesias in Sardinia, Italy. The results reveal adequate usefulness of the selected spaces, while underlining criticalities related to intrinsic spatial and physical attributes. The application to the case study confirms the validity of the theoretical and methodological framework embodied in the OCUS tool for supporting urban design and planning by orienting place-shaping processes towards the acknowledgement of children’s needs.

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

A new chiral Mn-salen catalyst, functionalized with a long aliphatic chain and a choline group, able to act as surfactant catalyst for green epoxidation in water, is here described. This catalyst was employed with a commercial surfactant (CTABr) leading to a nanoreactor for the enantioselective epoxidation of some selected alkenes in water, using NaClO as oxidant. This is the first example of nanoreactor for enantioselective epoxidation of non-functionalized alkenes in water.

Trauma is one of the most common causes of death or permanent disability in young people, so a timely diagnostic approach is crucial. In polytrauma patients, CEUS has been shown to be more sensitive than US for the detection of solid organ injuries, improving the identification and grading of traumatic abdominal lesions with levels of sensitivity and specificity similar to those seen with MDCT. CEUS is recommended for the diagnostic evaluation of hemodynamically stable patients with isolated blunt moderate-energy abdominal traumas and for the diagnostic follow-up of conservatively managed abdominal traumas. In this pictorial review we illustrate the advantages and disadvantages of CEUS and the procedure details with tips and tricks during investigation of blunt moderate-energy abdominal trauma as well as during follow-up in non-operative management.

Terpenoids are toxic compounds produced by plants as a defense strategy against insect herbivores. We tested the effect of Origanum vulgare terpenoids on the generalist herbivore Spodoptera littoralis and the response of the plant to herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene expression (qPCR) was evaluated on selected plant genes involved in both terpene biosynthesis. The insect detoxification response to terpenes was evaluated by monitoring antioxidant enzymes activity and expression of insect genes involved in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression was modulated by S. littoralis feeding. The herbivore-induced increased level of terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by decreasing larval survival and growth rate. The assimilation by S. littoralis of more than 50% of ingested terpenes correlated with the possible toxic effects of O. vulgare terpenoids. In choice test experiments, carvacrol and γ-terpinene mediated the larval feeding preferences, wherease the prolonged feeding on O. vulgare terpenoids (particularly on γ-terpinene) exerted relevant antinutritional effects on larvae. S. littoralis was found to react to O. vulgare terpenoids by increasing its antioxidant enzymes activities and gene expression, although this was not sufficient to sustain the toxicity of O. vulgare terpenoids.

The COVID-19 pandemic has had a profound impact on the mental health, adjustment, and psychological well-being of young adults. Despite extensive research conducted in this area, eudaimonic well-being, one specific form of psychological well-being focusing on self-knowledge and self-realization within existential challenges, has received comparatively less attention. The current study aimed to investigate the potential linkages between two key psychological factors, psychological inflexibility and fear of death, with eudaimonic well-being among young adults in the context of the Covid-19 pandemic. One year after the outbreak, 317 young Italian adults (18-34 yrs.) participated in an online survey, including measures of psychological inflexibility (AAQ-II), fear of death (CL-FODS), and eudaimonic well-being (PWB). Results showed that psychological inflexibility was negatively associated with all the dimensions of Ryff’s model of eudaimonic well-being, while fear of death of others was found to be associated with three of these dimensions (autonomy, environmental mastery, and self-acceptance). Results also indicated a mediation role of psychological inflexibility in the association between fear of death and eudaimonic well-being. These findings expand our knowledge of the potential factors that may influence eudaimonic well-being and provide insights for clinical work with young adults challenged by uncertain times.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

This paper aims to raise awareness on certain interoperability issues as we intend to shape industry 5.0 in order to enable a human-centric resilient society. We advocate that the need of sharing small and specific data will become more intensive as AI-based solutions will become more pervasive. Consequently, dataspaces should be carefully designed to address this need. We advance the conversation by presenting a case study from HR demonstrating how to predict the possibility of an employee experiencing attrition. Our experimental results show that we need more than 500 samples for developing a machine learning model to be sufficiently capable to generalize the problem. Consequently, our experimental results show the feasibility of the idea. However, in small and medium sized companies this approach cannot be implemented due to the limited number of samples. At the same time, we advocate that this obstacle may be overcome if multiple companies will join a shared dataspace, thus raising interoperability issues

A methodological similarity between Thomas Hobbes and Pëtr Kropotkin is the intention to spread a theoretical foundation to everyone, in the sense that they are willing to give to all the people a clear description of the reality and a subsequent political view. To do so, they use a scientific method, deductive (starting from empirical observations) in the case of Hobbes, inductive-deductive in the case of Kropotkin. Kropotkin underlines the educational value of the scientific method.In this work we want to highlight that, although they both start their argumentations from a materialist ontology, Hobbes and Kropotkin conjecture two completely different states of nature. Hobbes describes the state of nature through the two famous metaphors homo homini lupus (citing Plautus) and bellum omnium contra omnes, while Kropotkin introduced the theory of mutual aid. Both the theory of a state of war by Hobbes and the theory of mutual aid by Kropotkin have been revolutionary. Hobbes has been influenced by the scientific revolution initiated by Francis Bacon, one of his mentors, and Galileo Galilei, together with a criticism towards the ancient Greece philosophers, in particular Aristotle. Kropotkin has been influenced by the ground-breaking writings of Charles Darwin together with a very fruitful Russian scientific environment.We want to stress here that the disenchanted view of the human nature in Hobbes, a state of war due to the fact that everyone has rights on everything, helps him to legitimate sovereignty, while the positive view of human nature in Kropotkin, a spontaneous mutual aid among people in a community, helps him to legitimate anarchy. Therefore, the fascinating scientific methods of the two materialists Hobbes and Kropotkin to structure a solid political theory cannot neglect different views on human nature due to their historical contexts.

This paper illustrates an experimental activity for the closed-loop position control of an actuator made using shape memory alloy (SMA) wire. A solution with the self-sensing effect was implemented to miniaturize the systems, i.e., without external sensors. A proportional control algorithm was initially used, demonstrating the idea's feasibility: the wire can behave simultaneously as an actuator and sensor. An experimental investigation was subsequently conducted for the optimization of the developed actuator. As for the material, a Flexinol wire, Ni-Ti alloy, with a diameter of 0.150 mm and a length of 200 mm, was used. Preliminarily, a characterization of the SMA wire at constant and variable loads was carried out: the characteristics detected are elongation vs. electric current and elongation vs. electrical resistance. The control system is PC-based with a data acquisition card (DAQ). A drive board has been designed and built to read the wire's electrical resistance and power it by pulse width modulation (PWM). A notable result is that the actuator works with good precision and in dynamic conditions, even when it is called to support a load up to 65% different from that for which the electrical resistance-length correlation has previously been experimentally obtained, on which the control is based. This opens up the possibility of using the actuator in a counteracting configuration with a spring, which makes hardware implementation and control management simple.

(1) Background: Lifestyle changes, eventually associated with a nutraceutical, are recommended strategies for managing high-normal blood pressure (BP) patients with low-moderate cardiovascu-lar (CV) risk. Nitrates-enriched products (i.e., red beet extracts) may help reduce BP, exerting vas-oactive properties and enhancing adherence to lifestyle advice. Our study aimed to evaluate the effectiveness in clinical practice of generic written lifestyle advice and a beetroot-based nutraceu-tical prescription based on the 2018 ESC/ESH guidelines on 24-hour BP in a population with high-normal BP and low-moderate CV risk.; (2) Methods: A longitudinal observational study was con-ducted in two ESH hypertension excellence centres on 43 consecutive subjects with high-normal BP based on repeated office BP (OBP) measurements and a low-moderate CV risk. Twenty-four-hour ambulatory BP monitoring (ABPM) was carried out at baseline and three months after ge-neric written ESC/ESH advice for lifestyle changes associated with a nutraceutical containing 500 mg of dry beetroot extract; (3) Results: Mean age 50±11 years, 54% males, 58% overweight/obese, mean OBP 135±3/85±3 mmHg. At baseline, 24-hour BP, daytime BP and night-time BP were 127±7/80±6 mmHg, 131±8/83±6 mmHg and 118±8/70±5 mmHg, respectively, BP profiles compat-ible with hypertension status in some subjects. After a median follow-up of 98 (92-121) days, all BPs, except night-time diastolic BP, were significantly decreased: -3±6/-2±4 mmHg for 24-hour BP, -3.9±6.0/-3.0±4.0 mmHg for daytime BP and -3.3±7.4/-1.3±4.7 mmHg for night-time BP, respec-tively. No significant clinical changes in weight were detected. BP decreased independently of baseline BP level, gender, smoking status and BMI, while a more substantial decrease in BP was observed in older patients; (4) Conclusions: Our pilot study shows for the first time that written generic lifestyle advice based on ESC/ESH hypertension guidelines coupled with a beetroot-based nutraceutical may represent a valid initial non-pharmacological approach in subjects with high-normal BP and low-moderate CV risk even without personalized diet interventions.

The interplay between thrombosis and inflammation, known as thromboinflammation, is a significant pathway driving cardiovascular and autoimmune diseases, as well as COVID-19. Key modulators of this process have emerged as innate immune cells. Strategically positioned to promote thromboinflammation are neutrophils, the most predominant white blood cells in humans. Neutrophils can trigger an organized cell death pathway by releasing decondensed chromatin structures known as neutrophil extracellular traps. These structures are decorated with histones, cytoplasmic, and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects, which can accelerate disease progression. The activities of PAD4, which catalyses the citrullination of histones, and the neutrophil inflammasome are required for distinct steps leading to extracellular DNA release (NETosis). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. We will discuss how vascular blockages in thromboinflammation occur due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. It will also review the mechanisms whereby vaso-occlusive events in thrombo-inflammation depend on the interaction of neutrophil extracellular traps with von Willebrand factor and suggest the importance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and CVD.

The evaluation of the piezoelectric properties of ferroelectric ceramics generally has a high level of uncertainty, due to incomplete poling, porosity, domain wall clamping and other effects. In addition, the poling process is often difficult and dangerous, due to the risk of breaking or damaging the sample. A method is described for the evaluation of the potential intrinsic piezoelectric response that a ceramic would have after full poling, without poling it. The method relies on the fact that any material undergoes an elastic softening below the ferroelectric transition temperature, whose magnitude can be expressed in terms of the intrinsic piezoelectric and dielectric coefficients of the material. Such a softening is equivalent to an electromechanical coupling, averaged over all the components due to the unpoled state of the sample, and can be deduced from a single temperature scan of an elastic modulus of a ceramic sample, spanning the ferroelectric and paraelectric states. The strengths, limits and possible applications of the method are discussed.

Socio-demographic factors are responsible of health inequalities also in vaccination. The aim of this study was to evaluate their role at population level through a population-based study performed on the whole population entitled to receive COVID-19 vaccines in Umbria Region, Italy, and registered to the Regional Healthcare Service as of February 28th, 2021. Socio-demographic characteristics and vaccination status in terms of uptake at least one dose of any available vaccine, completion of the primary vaccination cycle and uptake of the booster doses as of February 28th, 2022 were col-lected from the Umbria regional database. The percentage of eligible population who did not initiate the COVID-19 vaccination, complete the full vaccination cycle and get the booster dose was 11.8%, 1.2% and 21.5% respectively. A younger age, being a not-Italian citizen, and not holding an ex-emption for chronic disease/disability and a GP/FP were associated to all the endpoints. Females, as compared to males, were more likely to not initiate the vaccination but less likely to not receive the booster dose. On the contrary, results on the deprivation index were not conclusive. The findings, beyond confirming current knowledge at population level, provide new inputs for better tailoring vaccination campaigns.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

The paper will analyze the pressures and vulnerabilities of the consolidated city from two perspectives: technical and social. Some design and pragmatic experiences conducted by the author in his teaching and research experience first at the Department of Urbanism of TUDelft in the Netherlands and currently at the PDTA Department of La Sapienza University of Rome will be introduced and analyzed. In the first research activity, whose case study is Rotterdam, all urban vulnerabilities related to climate change will be analyzed while in the second one, conducted in Viterbo, the vulnerability related to the hull of social inclusion, poor accessibility and psycho-social stress that plague our established cities will be treated. The two areas of study, different in size and spatial governance tools, are comparable because they allow deciphering the city's risks through lines of intervention that could serve as best practices and serve the urban planning disciplinary update also allowing to define a reflection on morphology and fabrics and on the shape of the city itself. Both teaching and research activities in which the author is involved allow the topic of urban vulnerability to be addressed with a broad exploratory scope that, in the final stage, hypothesizes design intervention on the neighborhood scale, identified as the most appropriate to provide plausible climate and social adaptation and mitigation responses.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, tumor distant recurrence remains a concern, prompting exploration of Total Neoadjuvant Therapy (TNT) as a comprehensive treatment strat-egy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Non-operative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving clinical complete response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for treatment response assessment. This review synthesizes current evidence on TNT, ICIs, NOM and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

Flavonoids are polyphenolic phytochemical compounds found in many plants, fruits, vegetables, and leaves. They have a multitude of medicinal applications due to their anti-inflammatory, anti-oxidative, anti-viral, and anti-carcinogenic properties. Furthermore, they also have neuroprotective and cardioprotective effects. Their biological properties depend on the chemical structure of flavonoids, their mechanism of action, and their bioavailability. The flavonoid’s beneficial effects have been proven for a variety of diseases. In the last few years, it is demonstrated that flavonoids’ effects are mediated by inhibiting the NF-κB (Nuclear Factor-κB) pathway. In this review, we have summarized the effects of some flavonoids on the most common diseases such as cancer, cardiovascular, and neurodegenerative human diseases. In particular, here we collected all recent studies describing plant-derived flavonoids’ protective and prevention role, by specifically focusing their action on the NF-κB signaling pathway.

When we are asleep we lose the ability to promptly respond to external stimuli and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways, we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to which extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

Cooperation is widely recognized to be challenging for the well-balanced development of human societies. The emergence of cooperation in populations has been largely studied in the context of the Prisoner's Dilemma game, where temptation to defect and fear to be betrayed by others often activate defective strategies. In this paper we analyze the decision making mechanisms fostering cooperation in the two-strategy Stag-Hunt and Chicken games, which include the mixed strategy Nash equilibrium, describing partially cooperative behavior. We find the conditions for which cooperation is asymptotically stable in both full and partial cases, and we show that the partially cooperative steady state is also globally stable in the simplex. Furthermore, we show that the last can be more rewarding than the first, thus making the mixed strategy effective, although people cooperate at a lower level with respect to the maximum allowed, as it is reasonably expected in real situations. Our findings highlight the importance of Stag-Hunt and Chicken games in understanding the emergence of cooperation in social networks.

Long Covid is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. The cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of Long Covid. Given the substantial lack of drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes which have been on the market for several years as adjuvant therapy of cerebral metabolic alterations resulting from neuroendocrine disorders, can be taken into consideration in an overall therapeutic strategy that aims to control the Long Covid associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their usefulness in Long Covid. Our initial clinical experience corroborates this rationale. Further research is imperative in order to obtain robust clinical evidence.

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

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.

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

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

Many historic buildings and monuments on the Salento Peninsula (Apulia, southern Italy) were built from locally quarried Miocene calcarenites belonging to the Pietra Leccese Formation (Late Burdigalian-early Messinian). The main facies consists of a homogeneous and porous biomicrite, pale yellow in color and fine- to medium-grained, very rich in planktonic Foraminifera and massive or thick-bedded in outcrop. Additionally, there are other facies among which Piromafo stands out for its aesthetic appearance, which is enhanced by its greenish-brown or greenish-grey colors. Its physical characteristics, in terms of thermal properties mainly due to the mineral content and fabric, make it a good refractory and insulation material. Piromafo occurs in the upper part of the Pietra Leccese Fm. and is repre-sented by a fine- to medium-grained glauconitic and phosphatic biomicrite with macrofossils, es-pecially Bivalves and Gastropods. Despite its important historical use as building and ornamental material, especially in the Roman and Baroque architecture, a research gap exists in the scientific literature describing the properties of the stone and their correlation. Therefore, the aim of this paper is to present a wide range of properties useful to explain the in-situ behavior and damage susceptibility of the stone in monu-ments and buildings, but also for selecting preservation treatments and strategies. Thus, an overall assessment of the main petrophysical and mechanical properties especially for restoration/conservation purposes was performed using both standard and unconventional tech-niques. Starting from rock fabric inspection, particular attention was given to the relationship be-tween pore-size distribution and, hydraulic and thermal properties of the material. Unconfined compressive strength, flexural strength and indirect tensile strength were also estimated.

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

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

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

This contribution illustrates the training evaluation system developed within the Master’s Program in Family and Community Mediation at Università Cattolica del Sacro Cuore in Milan. This is an interim evaluation, which focuses on the training process and which considers fundamental the collaboration with the subjects of the training. The peculiarity of this work concerns the possibility of inserting research within the training process, following a logic of mutual enrichment both in terms of content and learning. The contribution illustrates in detail the outcome and the process evaluation system, defining the perspective, the objectives, and the methodology of implementation. In particular, the outcome evaluation focuses on the distal and proximal outcomes of the training, while the process analysis focuses on the dynamics within the group of participants. Although further evaluations involving different training groups and other training processes are needed, this training evaluation system allows to shed light on both the topic and the context in which training is delivered. The integration between different points of view and several levels of analysis allows the researchers to deepen the individual path of each participant as well as to have feedbacks on the progress of the training group as a whole.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

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

The criteria of “Distinctness, Uniformity and Stability” as well as a high "overall quality index” are used to register the Italian modern varieties to the national register. Differently, local conservation varieties can be certified under different EU Directives having, as overall objective, the preservation of biodiversity and the containment of genetic erosion. In recent years, products derived from an-cient grains are perceived to be healthier and more sustainable by consumer, especially in Italy, with consequent higher market prices. Ancient tetraploid wheat varieties registered in the national reg-ister of conservation varieties are 28, 24 of which are Sicilian. They are supposed to have a wide genetic variability compared to modern ones, making them vulnerable of fraud because they are difficult to trace. It is therefore important to have tools able to discriminate the autochthonous Si-cilian varieties. This can be done by gluten proteins composition, which also gives information on the technological properties of derived products. Fifty-one accessions belonging to 22 ancient va-rieties of Sicilian tetraploid (mostly durum) wheat were analyzed. Although a wide intra-accession and intra-varietal variability was assessed, the gliadin pattern of bulks of seeds belonging to each variety was discriminatory. Moreover, differences in technological attitudes were found between landraces. This paves the way to use gluten protein patterns for traceability allowing local farmers and producers to valorize their products and assure consumers about the transparency of the entire supply chain.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

Sleep is a fundamental human need: sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms and pro-inflammatory responses. Sci-entific literature is finally starting to pay attention to the central role of sleep-wake rhythm alterations for patients health. Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. This study aims to understand the effects of sleep-wake rhythm alterations on health and quality of life on cancer patients treated with oxaliplatin. Study has been conducted through the creation and distribution of questionnaires to patients to inves-tigate the potential alteration of the sleep-wake quality. Evaluating the influence of the collected variables on sleep quality, only liver and biliary tract and pancreas tumor lo-calization, in males, and previous difficulty sleeping, and anxiety, worries and stress, in females, resulted statistically significant. The results obtained may serve as foundation for designing awareness campaigns and updating of patients, healthcare personnel and caregivers, to improve health and quality of patients life.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, at least in part, of exclusion. AOSD is generally mild, however a small percentage of patients can develop a fearsome as well potentially fatal complication, the macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with a cytokine storm production and monocyte/macrophage overactivation, and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. The Histiocyte Society, which is a nonprofit organization committed to improving the lives of patients with histiocytic disorders, currently suggests etoposide in combination with dexamethasone for the treatment of HLH/MAS, although a multidisciplinary collaboration using the resources and expertise of several specialists (e.g. rheumatologist, infectiologist, critical care medicine specialist) is always recommended. Hereby we propose the detailed description of the clinical case of a previously healthy young woman in which MAS was the dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge.

Cochlear implantation is the therapy used for patients with severe to profound sensorineural hearing loss. For the success of the surgery, it is important that each surgical step is performed with meticulous precision, starting from the correct patient’s position on the operating table. In elderly or obese patients, this can be difficult to achieve due to cervical rigidity. In these cases, the orthopedic position is an excellent choice to perform a mastoidectomy accurately, ensuring a safe procedure and avoiding unpleasant complications.

The stochastic modelling of chemical physical processes is essentially based on a coarse-grained formulation of fluctuations, usually described by means of Wiener processes. By taking the paradigmatic example of chemical reaction kinetics, we propose a simple representation of microscopic stochastic dynamics grounded on the use of distributional derivatives of counting processes that account for elementary reactive events. This approach is consistent with the statistical analysis based on the Chemical Master Equation, and provides the formal setting for the existing algorithmic approaches (Gillespie algorithm). Some practical advantages of this formulation are addressed, and several other examples are discussed in connection with cluster formation, velocity fluctuations in liquid systems, and quantum transitions (radiative interactions) at the molecular level.

This study presents a dynamic modeling approach to investigate the impact of saturation dynamics on HIV/AIDS transmission in the presence of vertical transmission and treatment strategies. The proposed model incorporates disease-free and endemic equilibria, with a focus on analyzing the basic reproduction number and conducting stability analysis. Results indicate that the disease-free equilibrium is locally asymptotically stable under certain conditions. The findings suggest that a combination of treatment interventions and awareness campaigns, along with other control measures, may play a crucial role in curbing the spread of the HIV/AIDS virus. This research contributes to understanding the complex dynamics of HIV/AIDS epidemics and highlights the importance of considering saturation effects in epidemic modeling.

Conservation Agriculture (CA) and the System of Rice Intensification (SRI) are both agroecologically-oriented production systems that support more productive, sustainable, and resource-conserving farming, with synergies arising from their respective assemblages of reinforcing agronomic methods. Application of CA principles enhances the growth, yield, and performance of the crops grown under the cropping system as well as the health and resilience of the whole ecosystem. SRI practices create more favorable conditions for the development of crop plants below- and above-ground, conditions that can be enhanced by CA management. SRI practices such as reduced plant density m-2 can elicit better phenotypic expression of the genetic potentials of crops grown with CA.. For these two agronomic systems to converge at field level, some of their respective practices for plant, soil, water, and nutrient management need to be modified or aligned. One such adaptation is to practice SRI in CA systems on permanent, no-till, mulch covered raised beds, with rainfall or irrigation water in the furrows between the beds furnishing and controlling water; and providing weed suppression and improved nutrient recycling. SRI rice cropping can benefit from the CA practices of no-tillage, soil mulch cover, and diversified cropping, both in paddies and on raised beds. Several examples have shown that this convergence of cropping systems is feasible for smallholding farmers as well as for larger-scale producers, and also that SRI practices within a CA system are amenable to considerable mechanization. This review article examines the compatibility between CA and SRI, considering examples of their being utilized in complementary ways. Further research and experimentation are needed to identify and assess appropriate practices for capitalizing upon their synergies.

Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune response. One-hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min-max) of age was 9.0 (1–18) for children and 42.5 (20–61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman’s correlation was 0.56 (p&lt;0.001). Sal-IgG and ser-IgG levels were correlated with age, but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4kAU/L) to 4.0% (3.77kAU/L). Linearity of the assay missed in 4/6 samples. No significant intra-subject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG have a good agreement with ser-IgG. Non-invasive saliva collection represents an alternative method for antibody measurement, especially in children.

The term Conjugated Linoleic Acid (CLA) refers generically to a class of positional and geometric conjugated dienoic isomers of linoleic acid. Among the isomers of linoleic acid cis9, trans11-CLA (c9, t11-CLA) and trans10, cis12-CLA (t10, c12-CLA) are found to be bio-logically active isomers, and they occur naturally in milk, dairy products and meat from ruminants. In addition, some vegetables and some sea-foods have also been reported to contain CLA. Although the CLA levels in these natural sources are insufficient to confer the essential health benefits, anti-carcinogenic or anti-cancer effects are of current interest. In the rumen, CLA is an intermediate of isomerization and the biohydrogenation process of linoleic acid to stearic acid conducted by ruminal microorganisms. In addition to rumen bacteria, some other bacteria, such as Propionibacterium, Bifidobacterium and some lactic acid bacteria (LAB) are also capable of producing CLA. In this regard, Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) has demon-strated the ability to produce CLA isomers from linoleic acid by multiple enzymatic activi-ties, including hydration, dehydration, and isomerization. L. plantarum is one of the most versatile species of LAB and the bacterium is widely used in the food industry as a micro-bial food culture. The studies reviewed in this article reveal how, in the production of some fermented foods, the use of appropriate strains of L. plantarum, as a starter or additional culture, can be considered a critical factor in the design of new CLA-enriched functional foods.

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

The aims of this study were: (1) to analyze the level of agreement of a sample of Italian people with the rights of people with physical and psychical disabilities (PwPHDs and PwPSYDs) to have satisfying sexuality, to marry, to adopt a child; (2) to inquire if PwPSYDs were subject to less recognition than PwPHDs; (3) to verify if socio-demographic characteristics, such as age, sex, education, occupation, geographical origin, relational status, sexual orientation, and religiosity, associated with being against these sexual and parenting rights (SPRs). An online anonymous questionnaire inquired the level of agreement or disagreement with statements regarding the SPRs of PwPHDs and PwPSYDs. 973 participants, aged 18 – 84 years (71.1% females) were considered for analyses; At least 7 out of 10 participants declared in favor of the SPRs of PwPHDs, while the SPRs of PwPSYDs were always subjected to higher underrecognition. Religiosity almost invariably associated to being against the SPRs of PwDs. Being male, of higher age and lower education also associated with lower recognition. A better identification of the less tolerant respondents and of the less recognized categories may allow for specific strategies for promoting the recognition of the SPRs for PwDs.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

Colorectal cancer is the third most diagnosed cancer in males and in females, representing 8% of estimated new cases and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9 – 12% are eligible for local treatments with radical intent, including surgical resection, SBRT and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Comprehensive understanding of tree characteristics and conditions holds paramount importance for the precise management of hazelnut orchards. It facilitates the determination of tree vigor, pruning requirements, phytosanitary interventions, and plant water consumption. The primary objective of this study was to explore, for the first time on a fruit tree with a bushy structure and across trees of four Italian distinct hazelnut cultivars, the efficacy of multispectral and thermal UAV (Unmanned Aerial Vehicle) technologies in assessing canopy attributes, vegetative growth, and predicting abiotic stresses. These technologies serve as tools for precision agriculture, enabling the computation of various indices such as the Normalized Difference Vegetation Index (NDVI) and crop water stress index (CWSI). The study of water content is of particular importance at this time, especially considering the increasing water stress levels in Europe as well as globally. While Red Green Blue (RGB) and thermal imagery collectively demonstrated superior performance in model reconstruction, the multispectral UAV remained more adept at characterizing size traits of hazelnut plants. Thermal images alone proved inadequate for accurately reconstructing hazelnut biometric characteristics. Furthermore, all indices were found to be cultivar-specific, underscoring the importance of conducting studies across different cultivars. The utilization of two UAVs, namely multispectral and thermal, facilitated the examination of the relationship between NDVI and CWSI across tree species.

Driven by the rapid uptake of battery electric vehicles, Li-ion power batteries are increasingly reused in stationary energy storage systems, and eventually recycled to recover all the valued components. Offering an updated global perspective, this study provides a circular economy insight on lithium-ion battery reuse and recycling.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Background: This study aims to set out key clinical features of different Motoric Cognitive Risk (MCR) subtypes based on individual quantitative measures of cognitive impairment and to compare their predictive power on survival over an 8-year observation time. Methods: We analyzed data from a population-based study of 1138 subjects aged 65 years and older in south Italy. These individuals were targeted and allocated to subtypes of the MCR phenotype according to the slowness criterion plus one other different cognitive domain for each characterized phenotype. Clinical evaluation and laboratory assays, along with a comprehensive battery of neuropsychological and physical tests, completed the sample investigation. Results: MCR prevalence was found to be 9.8% (N=112), 3.6% (N=41), 3.4% (N=39), and 1.8% (N=21) for the MCR, MCR-GlobalFunction, MCR-StructuredSCC, and MCR-SCC&amp;GlobalFunction, respectively. Univariate Cox survival analysis showed an association only of the MCR-GlobalFunction subtype with a significant, 1.5-fold increased risk of overall death as compared to the other counterparts (HR 2.53, 95%CI 1.28 to 4.99, P-value&lt;0.01) over an 8-year observation period, even after major adjustment (HR 2.02, 95%CI 1.02 to 4.02). Conclusions: MCR phenotypes assigned to the MMSE cognitive domain are more likely to have an increased risk of overall mortality, 1.5-fold higher than counterparts, over 8-year observation.

We describe a dataset that contains job description published on a popular online website in the information and technology sector. As the website focus mainly on United Kingdom based jobs, the data have a specific focus on this country. It contains 11.501 job vacancies and 13 related meta data information. The dataset is suitable for HR analysis using machine learning techniques such as natural language processing and neural networks.

Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.

Renal cell carcinoma (RCC) represents around 3% of all cancers, within which clear cell RCC (ccRCC) are the most common type (70–75%). The RCC disease regularly progresses asymptomatically and upon presentation is recurrently metastatic, so an early method of detection is necessary. The identification of one or more spe-cific biomarkers measurable in biofluids (i.e urine) by combined approaches could surely be appropriate for this kind of cancer, especially due to easy obtainability by non invasive method. OLR1 is a metabolic gene that encodes for the Lectin-like oxidized low-density lipoprotein re-ceptor-1 (LOX-1), implicated in inflammation, atherosclerosis, ROS and metabolic disor-der-associated carcinogenesis. Specifically, LOX-1 is clearly involved in tumor insurgence and progression of different human cancers. This work reports for the first time the presence of LOX-1 protein in ccRCC urine and its peculiar distribution in tumoral tissues. In parallel, urine samples headspace has been analyzed for the presence of the volatile compounds (VOCs) by SPME-GC/MS and gas sensor array. In particular, it was found by GC/MS analysis that 2-Cyclohexen-1-one,3-methyl-6-(1-methylethyl)- correlates with LOX-1 concentration in urine. Thus, the combined approach of VOCs analysis and protein quantification could led to promis-ing results in terms of diagnostic and prognostic potential for ccRCC tumor.

3D reality capturing has demonstrated increased efficiency and consistently accurate outcomes in architectural digitisation. Nevertheless, despite advancements in data collecting, 3D reality capturing still lacks full automation, especially in the post-processing and modelling phase. Artificial intelligence (AI) has been a significant focus, especially in computer vision, and tasks such as image classification and object recognition might be beneficial to the digitisation process and its subsequent utilisation. This article aims to examine the potential outcomes of integrating AI technology into the field of 3D reality-capturing, with a particular focus on its use in architectural scenarios. The main methods used for data collection are laser scanning (static or mobile) and photogrammetry. As a result, image data including RGB-D data (files containing both RGB colours and Depth information) and point clouds have become the most common raw datasets available for object mapping. The study comprehensively analyses the current use of 2D and 3D deep learning techniques in documentation tasks, particularly downstream applications. It also highlights the ongoing research efforts in developing real-time applications with the ultimate objective of achieving generalisation and improved accuracy.

The dataset reports a collection of earnings call transcripts, the related stock prices, and the related sector index. It contains a total of 188 transcripts, 11970 stock prices, and 1196 sector index values. Furthermore, all of these data originated in the period 2016-2020 and are related to the NASDAQ stock market. The data have been collected using Yahoo Finance and Thomson Reuters Eikon. Specifically, Yahoo Finance offered daily stock prices and traded volume. At the same time, Thomson Reuters Eikon has been used as source for the earnings call transcripts. The dataset can be used as a benchmark for the evaluation of several NLP techniques as well as machine learning algorithms for understanding their potential for financial applications. Moreover, it is also possible to expand the dataset by extending the period in which the data originated following a similar procedure.

Wild rocket plants were cultivated in a plastic greenhouse into two independent sectors, one for soil-bound (SbS) cultivation and another equipped for soilless (ScS) cultivation systems. In both SbS and ScS, the crop was subjected to treatments consisting in a high-compared to a low-input fertilization program (HF and LF treatment, respectively). Water use efficiency (WUE) and partial factor productivity (PFP) for nutrients (N, P, K, Ca and Mg for ScS, and N for SbS) were measured. Rocket leaves, separated for cultivation system and fertilization program, collected at different cuts during the growing cycle, were cold stored at 10 °C until 16 d. At each sampling day (at harvest and during the storage), sensory parameters, respiration rate, dry matter, colour, electrolyte leakage, antioxidant activity, total phenols, total chlorophyll and ammonia content were evaluated. In ScS, the PFP for all nutrients supplied as fertilizers showed a significant increase with the LF treatment, with values higher than 30 % for N, K and Ca. As for the postharvest performance, rocket leaves cultivated in ScS showed better qualitative traits than those cultivated in SbS, as suggested by the lower values of ammonia content and electrolyte leakage recorded at the end of storage in samples grown in ScS. Moreover, in ScS, data showed a lower membrane damage in LF than HF rocket leaves. Finally, regarding total chlorophyll content, even if no effect of treatments was recorded in SbS, rocket cultivated in ScS, showed a better retention of this parameter applying LF than HF treatment. In addition to this, a PLS model (R2 = 0.7) able to predict the cultivation system, using as variables total chlorophyll content no-destructively measured, was implemented.

In this paper, comprehensive datasets are presented to advance research on information security breaches. The datasets include data on disclosed information security breaches affecting S&P500 companies between 2020 and 2023, collected through manual search of the Internet. Overall, the datasets include 504 companies, with detailed information security breach and financial data available for 97 firms that experienced a disclosed information security breach. This document will describe the datasets in detail, explain the data collection procedure and shows the initial versions of the datasets.

This paper shows the results of applying high-resolution Unmanned Aircraft System (UAS) photogrammetric surveying on a large landslide. A real case study, where permanently installing GCPs could be complex, where natural shaped and formed land pose severe limitations in deploying ground targets with optimal geometric configuration. We analysed performances in terms of survey accuracy obtained by performing photogrammetric surveys through the Zenmuse P1 DJI optical camera and Phantom 4 Pro 2. In combination with DJI Matrice 300 UAS, the P1 camera allows direct georeferencing through GNSS observations in RTK mode. Photogrammetric surveys, performed through different georeferencing methods, have been compared. Several targets have been permanently installed on the ground over the maximum vegetation height to guarantee long-lasting reference over the years in the area, which is characterised by a diffuse short vegetation coverage. Multitemporal UAS surveys have been then compared using Digital Image Correlation (DIC) algorithms, and deformation maps have been produced. Afterwards, DIC results were compared with observations made by the GNSS ground-based permanent receivers resulting in a standard deviation of 0,077 m. Through results analysis, good accordance between ground-based GNSS observations and DIC analysis on the photogrammetric surveys have been identified for the same time span. To conclude, this type of landslide presents a moderate deformation speed; in such a case, effective deformations monitoring could be achieved using pseudo-direct georeferencing, which permitted a 0.24 m accuracy on the whole tested area.

At the entrance of some churches in Tuscany (Italy), the reproduction of an apparently undecipherable inscription can be found. At least from the 18^th century, this epigraphic puzzle has originated a debate on its interpretation. This study proposes a hypothesis based on the Latin alphabet used in texts contemporary to the churches where the inscription is reproduced and a possible interpretation of the message consistent with the official religious doctrine. The proposed deciphering is extended to the full text, including some signs that were previously considered as geometric forms or a specific elaboration of letters not attested in other contemporary documents.

In this study, we conducted a comprehensive analysis of the spatial distribution of soil organic carbon stock (SOC stock) and the associated uncertainties in two soil layers (0–10 cm and 0–30 cm; SOC stock 10 and SOC stock 30 respectively), in Valchiavenna, an alpine valley located in northern Italy . We employed the digital soil mapping (DSM) approach within different machine learning models, including multivariate adaptive regression splines (MARS), random forest (RF), support vector regression (SVR), and elastic net (ENET). Our dataset comprised soil data from 110 profiles, with SOC stock calculations for all sampling points based on bulk density (BD), whether measured or estimated, considering the presence of rock fragments. As environmental covariates for our research we utilized environmental variables, in particular geomorphometric parameters derived from a digital elevation model (with a 20 m pixel resolution), land cover data, and climat-ic maps. To evaluate the effectiveness of our models, we evaluated their capacity to predict SOC stock 10 and SOC stock 30 using the coefficient of determination (R2). The results for the SOC stock 10 were as follows: MARS 0.39, ENET 0.41, RF 0.69, and SVR 0.50. For the SOC stock 30, the corresponding R2 values were: MARS 0.45, ENET 0.48, RF 0.65, and SVR 0.62. Additionally, we calculated the Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) for further assessment. To map the spatial distribution of SOC stock and address uncertainties in both soil layers, we chose the RF model, due to its better performance, as indicated by the highest R2 and the lowest RMSE and MAE. The resulting SOC stock maps using the RF model demonstrated an accuracy of RMSE = 1.35 kg.m-2 for the SOC stock 10 and RMSE= 3.36 kg.m-2 for the SOC stock 30. To further evaluate and illustrate the precision of our soil maps, we conducted an uncertainty assessment and mapping by analyzing the standard deviation (SD) from 50 iterations of the best-performing RF model. This analysis effectively highlighted the high accuracy achieved in our soil maps. The maps of uncertainty demonstrated that the RF model better predicts the SOC stock 10 compared to the SOC stock 30.

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

The problem of real-time estimation of occupancy of buildings (number of people in various zones at every time instant) is relevant to a number of emerging applications that achieve high energy efficiency through feedback control. The measurement of CO2 concentration can be considered an important indicator that allows to define the occupation of closed and crowded spaces. Interesting cases can be school buildings and other buildings used in civil and residential (shopping centres, hospitals, etc.). This paper, starting from an experimental analysis in different classrooms of a University campus in real operating conditions, in different period of the year, proposes a possible correlation between CO2 concentration and the occupancy profile of the spaces. The acquired data are used to present some graphical correlations and to understand the most important variables or combination of them. Starting from an accurate analysis of the data, attempts are made to define a preliminary estimation method through the development of a mathematical models of occupancy dynamics in a building, which show interesting results.

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

In this paper we intend to present a dataset that contain a collection of tweets generated as reactions of the release of 50 different movies. The dataset can be used for gaining useful insights regarding the conversation that is generated around a particular movie. It is particularly suitable for conducting sentiment analysis and other NLP techniques. The dataset contains approximately 2.5 million tweets with their related meta data and cover 50 movies. For each movie, its IMDb rating is included. The movies are the 25 releases with the highest number of votes during 2020 and 2021. The collected tweets represent the reactions of the twitter community during the first week of the release date in US of that particular movie. The tweets per movie ranged from 1.000 to approximately 200.000 tweets with an average of 50.000 per release. We used The Internet Archive Wayback Machine in order to retrieve the IMDb movie rating after one week of the US release date. The tweets and related metadata have been collected using the Tweet Downloader tool.

Hydroxychloroquine, a known antiviral metabolite of chloroquine, is increasingly used along with antibiotic azithromycin for the treatment of COVID-19 infection. In about one month India, the world’s largest manufacturer, delivered hydroxychloroquine for treating COVID-19 to over 50 countries. The therapy is being used across the world both for patients staying at home at the early phase of symptoms, as well as for patients hospitalized. We summarize achievements as of late April 2020, review possible modes of action and suggest avenues for the quick scale-up of production of hydroxychloroquine.

Native infective endocarditis is a global phenomenon, defined by infection of a native heart valve and involving the endocardial surface. The causes and epidemiology of the disease have evolved in recent decades, with a doubling of the average patient age. A higher incidence was observed in patients with implanted cardiac devices that can result in right-sided infection of the tricuspid valve. The microbiology of the disease has also changed. Previously, staphylococci, which are most often associated with health-care contact and invasive procedures, were the most common cause of the disease. Nevertheless, this has now been superseded by streptococci. While innovative diagnostic and therapeutic strategies have emerged, mortality rates have not improved over the past year and remain at 30%, which is higher than for many cancer diagnoses. The lack of randomized trials and logistical constraints impede clinical management, and long-standing controversies such as the use of antibiotic prophylaxis persist. This state of the art review addresses clinical practice, controversies, and strategies to combat this potentially devastating disease.