Vibrational spectroscopies (FTIR, Raman) are exceptionally valuable tools for the identification and crystal-chemical study of fibrous minerals, and asbestos amphiboles in particular. Raman spectroscopy has been widely applied in toxicological studies and thus a large corpus of reference data on regulated species is found in the literature. However, FTIR spectroscopy has been mostly used in crystal-chemical studies and very few data are found on asbestos amphiboles. This paper is intended to fill this gap; we report new FTIR data collected on a suite of well-characterized samples of the five regulated amphibole species: anthophyllite, amosite and crocidolite, provided by the Union for International Cancer Control (UICC) Organization, and tremolite and actinolite, from two well-known occurrences. The data from these reference samples have been augmented by results from additional specimens to clarify some aspects of their spectroscopic features. We show that the FTIR spectra in both the OH-stretching region and in the lattice modes region can be effective for rapid identification of the asbestos type.

In order to reconstruct the origin and pathways of variola virus (VARV) dispersion, we analyzed 47 VARV isolates available in public databases and their SNPs. The mean substitution rate of the whole genomes was 9.41x10-6 (95%HPD:8.5-11.3x10-6) substitutions/site/year. The time of the tree root was estimated to be a mean 68 years (95%HPD:60.5–75.9). The phylogeographical analysis showed that the Far East and India were the most probable locations of the tree root and of the inner nodes, respectively, whereas for the outer nodes it corresponded to the sampling locations. The Bayesian Skyline plot showed that the effective number of infections started to grow exponentially in 1915-1920, peaked in the 1940s, and then decreased to zero. Our results suggests that the VARV major strains circulating between 1940s-1970s probably shared a common ancestor originated in the Far East; subsequently moved to India, which became the center of its dispersion to eastern and southern Africa, and then to central Africa and the Middle East, probably following the movements of people between south-eastern Asia and the other places with a common colonial history. These findings may help to explain the controversial reconstructions of the history of VARV obtained using long- and short- term calibrations.

The assessment of existing bridges constitutes a serious challenge for the researchers since their safety evaluation is a complex task due to several sources of uncertainty affecting the parameters identified in the knowledge process. In particular, a high level of uncertainties may arise in the case of prestressing systems requiring special investigation strategies and experimental technologies. The paper aims to investigate how the knowledge uncertainties influence the safety assessment of existing post-tensioned bridges. The semi-probabilistic approach is used, and uncertainties related to the knowledge process are described considering the number of tests, the confidence level assumed for the estimation of the problem parameters, and the measurement errors of in-situ tests. Results concerning a typical post-tensioned bridge are reported and the variability of the outcomes is discussed and compared with a reference case of “perfect knowledge”. The main results of the study confirm the general robustness of the semi-probabilistic Eurocodes safety format and provide an overview of dispersion due to different choices about the number of tests and confidence level. The measurement errors may lead to significant under-estimation of the computed structural capacity with respect to the reference one.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

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

The escalating demand for multifunctional and advanced materials for growing industries has turned scientific exploration to graphene-based hybrid filler polymer composites. The introduction of graphene with other fillers into polymer matrices results in astonishing properties and thus has gained significant attention in recent years. This study addresses the significance of graphene-based hybrid filler polymer composites in progressive materials science and engineering. The paper encloses some traditional and current preparation techniques employed in the fabrication of composites and a comprehensive review of successfully prepared graphene hybrid polymer composites with enhanced mechanical, thermal, and electrical properties reported in published research. The role of different factors, e.g., filler type, aspect ratios, filler-matrix compatibility, dispersion effects, homogeneity, filler orientation through polymer matrices, and curing conditions, are summarized. Finally, the applications in heavy industries, e.g., aerospace, electronics, energy storage, and automotive sectors were also analyzed. We hope this study will serve as a practical resource for new researchers and practitioners to understand and harness the full potential of these composites in various scientific and industrial fields.

This paper aims to contribute to refining the e-values for testing precise hypotheses, especially when dealing with nuisance parameters, leveraging the effectiveness of asymptotic expansions of the posterior. The proposed approach offers the advantage of bypassing the need for elicitation of priors and reference functions for the nuisance parameters and the multidimensional integration step. For this purpose, starting from a Laplace approximation, a posterior distribution for the parameter of interest only is considered and then a suitable objective matching prior is introduced, ensuring that the posterior mode aligns with an equivariant frequentist estimator. Consequently, both Highest Probability Density credible sets and the e-value remain invariant. Some targeted and challenging examples are discussed.

This work is aimed at showcasing one of the most engaging geoparks in Europe, the Gole della Breggia Geopark. By following its geotrail, the visitors can observe a great deal of features that encompass a wide variety of sedimentary, stratigraphic, tectonic and paleogeographic processes. Its contents are valorized by a comprehensive geotrail that encompasses 23 geostops, enriched with explanatory panels, which enable viewers to gain an overall picture of the complex processes that led to the present-day configuration of the outcrops encountered in the Geopark. We have selected five significative outcrops, which we have regarded as fully-fledged geosites, and which encompass the whole 170-million-year interval, from Early Jurassic to Late Miocene times, during which the rocks of the Geopark were deposited and deformed. We have performed an assessment of the five geosites, using the most common criteria that can be applied for geosite evaluation. The result of the assessment show that the most valuable geosite is the Lombardian Maiolica, highly representative of a pelagic limestone, which is rich in fossil contents, marked by integrity, scien-tific interest and has a major educational value. All geosites, thanks to a QR code added to each figure along the text, can be viewed as Virtual Geosites (VGs), integrated by 360° videos.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

The paper, through and extended literature review, based on bibliometrics and conceptual reasoning, analyzes the main models of coopetition, in order to verify the link between coopetition and innovation, getting to proposal that can be useful for further research.

We are currently witnessing a strong global transition towards new, more sustainable models of development and consumption. This transition is both activating and highlighting a series of discrepancies between the various actors in agri-food marketing systems, including the institutions that govern regulatory and trade aspects. These discrepancies highlight how, on a global level, the agri-marketing system is unable to provide adequate responses to the new principles of sustainability that are increasingly expected by civil society. This inability is often linked to the phenomena of opportunism, information asymmetries and lock-in effects (resulting from the slowness or inability of some sectors or actors to evolve technologically and culturally). The control of all these factors is often ineffective and often involves high transaction costs . These conditions lead the global market into an ongoing state of failure, creating structural holes, in which new forms of exchange are born, in response to the principles mentioned above. We identify these as nested markets: hybrid market forms that, thanks to new information technologies, create a new form of proximity that transcends the classical concept of physical proximity. This new proximity directly links producers and consumers in relationships based mainly on two substantial values: reciprocity and reputation. Both of these values significantly reduce transaction costs which today play an increasing role in determining the form and repetition of exchanges. This condition is difficult to interpret from classical and neo-classical economic theories. To do so it is necessary to use a multidisciplinary approach. In this article we combine neo-institutional theory and network analysis to interpret phenomena that are increasingly emerging in all areas of the world. Using these two theories, and case studies from Brasil, North America, China and Europe, we try to highlight how the market is not only the place where the price of products and of their quantities are formed. Market is a complex social spaces, where more-or-less stable relationships are formed, based on the values of reciprocity and reputation that determine behaviour and codes of conduct aimed at containing opportunism and encouraging sustainable, autonomous, forms of self-regulation. These relationships are also the driving forces that ensure the ongoing continuation of the exchanges and the diffusion and preservation of knowledge over time and space. These relationships represent the beating heart of nested markets and their dynamic ability to adapt to the continuous changes that occur in the socio-economic and environmental context in which they are rooted. In this way sustainability is built as an expression of the co-production between different actors (producers, consumers, institutions) and natural resources.

Rare diseases are characterized by a wide diversity of signs and symptoms and vary not only from disease to disease, but also from person to person, and living with a disease leads patients to peculiar experiences and treatments, without limits of time and space, as they extend to various environments and relationships of their lives. The objective of this study is the theoretical interaction between Value Co-creation (VC) and the Stakeholder Theory (ST) with the Shared Decision Making (SDM) health care theory. It is configured as a multiparadigmatic proposal by enabling the analysis of multiple perspectives of different stakeholders in health care. Thus, Co-created Decision Making (CDM) emerges in a logic dominated by service, with emphasis on intangible aspects and the interactivity of the relationships. It goes beyond the clinical office and the doctor-patient relationships, as studied in SDM, extending to all environments and interactions that add value to the patient's treatment. It was concluded that the essence of this new theory proposed here is neither in patient-centered care nor in patient self-care, but in co-created relationships with and between stakeholders in both directions, including non-health care environments that are important to the patient, such as relationships with friends, family, other patients with the same disease, social media, public policies, and the practice of pleasurable activities.

Capturing atmospheric CO2 and storing it in natural rock systems (i.e., alkaline earth silicate and hydroxide minerals) through carbonation reactions is a promising greenhouse gas mitigation research, and largely depends on the use of hydrated ultramafic rocks (serpentinites), which are widespread in orogenic belts around the globe. The Jurassic ophiolites in the Southern Apennines represent a natural analogue and a great opportunity for the mineralogical sequestration of CO2. Serpentinites of the Pollino ophiolite Massif have been widely studied for their mineralogical, petrographic, and chemical characteristics, providing major findings on their impact on environmental and human health issues. Serpentinites here have been divided into cataclastic and massive types based on their structures and are characterized by pseudomorphic and vein textures. The mineralogy of the studied serpentinites consists of lizardite, antigorite, clino-crysotile, Cr-chlorite, magnetite, tremolite, actinolite, pyroxene and calcite, and the most commonly occurring serpentine minerals are polymorphs of serpentine including lizardite, clino-crysotile and antigorite. Systematic petrographic and mineralogical studies of serpentinites in ophiolites, such as those outcropping in the Southern Apennines can represent a starting point for the study of natural materials, which can be used for CO2 storage and sequestration. A particular attention must be given to those carbonate phases, produced by carbonation processes to check whether the serpentinites of the Pollino Massif can be used for the induced mineral Carbon Capture Storage (CCS). If successful, this technique and the Pollino Massif serpentinites can become highly significant in safeguarding the health of our planet's climate.

Densely urbanized areas, with a low percentage of green vegetation, are highly exposed to Heat Waves (HW) which nowadays are increasing in terms of frequency and intensity also in the middle-latitude regions, due to ongoing Climate Change (CC). Their negative effects may combine with those of the UHI (Urban Heat Island), a local phenomenon where air temperatures in the compact built up cores of towns increase more than those in the surrounding rural areas, with significant impact on the quality of urban environment, on citizens health and energy consumption and transport, as it has occurred in the summer of 2003 on France and Italian central-northern areas. In this context this work aims at designing and developing a methodology based on aero-spatial remote sensing (EO) at medium-high resolution and most recent GIS techniques, for the extensive characterization of the urban fabric response to these climatic impacts related to the temperature within the general framework of supporting local and national strategies and policies of adaptation to CC. Due to its extension and variety of built-up typologies, the municipality of Rome was selected as test area for the methodology development and validation. First of all, we started by operating through photointerpretation of cartography at detailed scale (CTR 1: 5000) on a reference area consisting of a transect of about 5x20 km, extending from the downtown to the suburbs and including all the built-up classes of interest. The reference built-up vulnerability classes found inside the transect were then exploited as training areas to classify the entire territory of Rome municipality. To this end, the satellite EO HR (High Resolution) multispectral data, provided by the Landsat sensors were used within a on purpose developed "supervised" classification procedure, based on data mining and “object-classification” techniques. The classification results were then exploited for implementing a calibration method, based on a typical UHI temperature distribution, derived from MODIS satellite sensor LST (Land Surface Temperature) data of the summer 2003, to obtain an analytical expression of the vulnerability model, previously introduced on a semi-empirical basis.

Main pathogens affecting carob (Ceratonia siliqua) tree in the Mediterranean basin are described in this overview. The most widespread diseases periodically occurring on carob orchards are powdery mildew (Pseudoidium ceratoniae) and cercospora leaf spot (Pseudocercospora ceratoniae). The causal agents of so-called “black leaf spots” (e.g. Pestaliotiopsis, Phyllosticta and Septoria spp.) are responsible for similar symptoms to above mentioned foliar diseases but are reported on carob orchards with a negligible frequency. Likewise, canker and branch diebacks caused by fungal species belonging to Botryosphaeriaceae are almost never recorded. Among wood diseases that may compromise old or previously damaged carob specimens, “brown cubical heart rot” caused by Laetiporus sulphureus is the most widespread and recurrent issue; this pathogen is also well-known for edible fruit bodies that are also appreciated for pharmaceutical and industrial purposes. On the other hand, “white decays” caused by Fomes and Ganoderma species are less common and reported for the first time in this review. Like-gall protuberances on twigs at uncertain aetiology or tumours on branches associated to Rhyzobium radiobacter are described although these symptoms are seldom detected as it happens also for necrotic leaf spots caused by Pseudomonas syringae pv. ciccaronei. A list of worldwide pathogens not yet recorded but at high-risk potential of introduction in Italian carob producing area is also provided. Finally, some concerns are addressed to new phytopathogenic fungi vectored by invasive Xylosandrus compactus ambrosia beetle. Comprehensively, all described pathogens could potentially in near future become limiting factors for carob production, because they could be favoured by high-density orchards, increasing global network of trade exchanges and high frequency through which extreme events of climate changes globally occur. Thus, symptoms and signs, causal agents, epidemiology and whenever applicable recommendations for disease prevention and management are provided in this review.

Newly characterising 245 Italian and Albanian HCV-2 NS5B sequences collected between 2001 and 2016 was used to reconstruct the origin and dispersion pathways of HCV-2c. The tree of a subset of these sequences aligned with 247 publicly available sequences was reconstructed in spatio-temporal scale using the Bayesian approach, and the effective replication number (Re) was estimated using the birth-death model. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania, and that GT2 originated in Guinea Bissau in the XVI century and spread to Europe in the XX century. The HCV-2c subtype had two internal nodes respectively dating back to the 1930s and 1950s having as most probable locations Ghana and Italy, respectively. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in both Italy between the 1950s and 1980s, and Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonisation (1936-1941), but did not reach Albania until the period of dramatic migration to Italy in the 1990s.

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe₂(OCH₃)₂(dbm)₄]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe₄RC(CH₂O)₃)₂(dpm)₆] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

THz radiation has assumed a great importance thanks to the efforts in the development of technological tools used in this versatile band of the electromagnetic spectrum. Here we propose a reflecting bi-mirror axicon-like device with wavelength-independent long focusing performances in the THz band, by exploiting the high thermo-mechanical deformation of the elastomer polydimethylsiloxane (PDMS). This deformation permits to achieve significant optical path modulations in the THz band and effective focusing. The surface of a PDMS layer is covered with a gold thin film, acting as heater thanks to its absorption for wavelengths below ~500 nm . An invariance property of the Fresnel integral has been exploited to verify experimentally the THz performances of the device with an ordinary visible laser source, finding excellent agreement with the theoretical predictions at 1 and 3 THz. The same property allowed also to verify experimentally that the axicon focus has a longitudinal extension much greater than that one exhibited by a benchmark cylindrical mirror with the same optical power. The axicon is thermo-mechanically stable up to a heating power of 270 mW, although it might be potentially exploited at higher powers with a minor degradation of the optical performances.

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.

This research presents the creation of a Virtual Reality experience for the Balzi Rossi museum, commemorating the centenary of Prince Albert I Grimaldi's archaeological work at the site. The project, a collaboration between the University of Genoa's 3D Lab Factory, Eurodrone, and the Balzi Rossi archaeological museum, aims to preserve and convey the site's heritage through advanced VR technology. Initially employing Unreal Engine 4, the team used photogrammetry for 3D reconstruction of the "Caviglione" and "Florestano" caves, notable for their ancient rock engravings. This first VR model, despite hardware limitations, provided an interactive exploration of the site. The subsequent development phase utilized Unreal Engine 5, incorporating Nanite technology for enhanced visual fidelity. This advancement resulted in a more detailed and immersive VR experience, presenting the Balzi Rossi cliff across different historical periods, including the Würm glaciation. Key to this phase was optimizing the VR experience for performance, focusing on stable frame rates and minimizing motion sickness, and integrating a multi-lingual interface for broader accessibility. Since November 2023, the VR setup at the Balzi Rossi Museum has been an educational and interactive feature, enabling visitors to explore the site's history virtually. This research demonstrates the potential of VR in cultural heritage preservation and education, providing a foundation for future technological improvements in the field.

A distinction is made between data rescue (i.e., copying, digitizing and archiving) and data recovery that implies deciphering, interpreting and transforming early instrumental readings and their metadata to obtain high-quality datasets in modern units. This requires a multidisciplinary approach that includes: palaeography and knowledge of Latin and other languages to read the handwritten logs and additional documents; history of science to interpret the original text, data e metadata within the cultural frame of the 17th, 18th and early 19th century; physics and technology to recognize bias of early instruments or calibrations, or to correct for observational bias; astronomy to calculate and transform the original time in canonical hours that started from twilight. The liquid-in-glass thermometer was invented in 1641 and the earliest temperature records started in 1654. Since then, different types of thermometers were invented, based on the thermal expansion of air or selected thermometric liquids with deviation from linearity. Reference points, thermometric scales, calibration methodologies were not comparable, and not always adequately described. Thermometers had various locations and exposures, e.g., indoor, outdoor, on windows, gardens or roofs, facing different directions. Readings were made only one or a few times a day, not necessarily respecting a precise time schedule: this bias is analysed for the most popular combinations of reading times. The time was based on sundials and local Sun, but the hours were counted starting from twilight. In 1789-90 Italy changed system and all cities counted hours from their lower culmination (i.e., local midnight), so that every city had its local time; in 1866, all the Italian cities followed the local time of Rome; in 1893, the whole Italy adopted the present-day system, based on the Coordinated Universal Time and the time zones. In 1873, when the International Meteorological Committee (IMO) was founded, later transformed in World Meteorological Organization (WMO), a standardization of instruments and observational protocols was established, and all data became fully comparable. In the early instrumental period, from 1654 to 1873, the comparison, correction and homogenization of records is quite difficult, mainly because of the scarcity or even absence of metadata. This paper deals about this confused situation, discussing the main problems, but also the methodologies to recognize missing metadata, distinguish indoor from outdoor readings; correct and transform early datasets in unknown or arbitrary units into modern units; finally, in which cases it is possible to reach the quality level required by WMO. The focus is to explain the methodology needed to recover early instrumental records, i.e., the operations that should be performed to interpret, correct, and transform the original raw data into a high-quality dataset of temperature, usable for climate studies.

Analysis of liquid biopsy samples can reveal a wealth of molecular as well as cellular entities circulating in various body fluids. These entities include circulating tumor cells, circulating cell-free and tumor DNA, RNA, and proteins. Detection and characterization of this genetic and proteomic material can provide crucial information on tumor characteristics, including its heterogeneity, biology, tumor progression, staging, associated gene mutations and the course of therapy. The increased use of liquid biopsy in clinical oncology offers in non-invasive manner easier tumor sampling and continuous monitoring of the disease evolution through repetitive sampling from cancer patients. The continuous monitoring offered by this method is highly relevant to the assessment of a given therapeutic regime and early detection of markers associated with possible drug resistance, which may develop in the course of the therapy. The use of proteomic approaches, including mass spectrometry-based proteomics for the analysis of biofluids extends for over three decades, yet only in the last few years such methods have found their way to clinical oncology. The non-invasive nature of liquid biopsy and the simple procedures for sample collection made this approach far more attractive than the traditional and well-established tissue biopsy. Such preference becomes more practical in the analysis of solid tumors, particularly in pediatric population. In this review we discuss some works on the emerging role of liquid biopsy analyses in clinical oncology, and how such use allows a better understanding of diagnosis, prognosis, disease evolution and response to therapy of various forms of cancer. We also discuss the role of MS-based methods in the characterization of post-translational modifications of proteins circulating in liquid biopsies.

Plant sulfite oxidase )SO( is a molybdo-enzyme responsible for the oxidation of excess SO₂/sulfite into non-toxic sulfate. The effect of toxic sulfite level on leaves and fruits was studied in tomato plants with different SO expression levels: wild-type (WT), SO overexpression (OE) and SO RNA interference (Ri) plants. Leaf discs and ripe fruit of plants lacking SO were more susceptible, whereas SO OE plants were more resistant as revealed by remaining chlorophyll content and tissue damage levels. Application of molybdenum further enhanced the tolerance of leaf discs to sulfite by enhancing SO activity in SO OE lines, but not in WT or Ri plants. Notably, incubation with tungsten, the molybdenum antagonist, overturned the effect of molybdenum spray in SO OE plants, revealed by remaining chlorophyll content and SO activity. The results indicate that SO determines, in tomato leaves and ripe fruits, the resistance to toxic sulfite and the application of molybdenum enhances sulfite resistance in OE plants by increasing SO activity. The results suggest that overexpressing SO mechanism can be employed in agriculture with or without molybdenum application, for the development of more tolerate crops and vegetables to higher concentrations of sulfite/SO₂ containing postharvest treatments.

The protection of grapevine from the diseases is now particularly focused on the development of environmentally friendly strategies. Although sulphur is not in itself a toxic substance, a large use towards powdery mildew, in organic vineyards especially, may cause problems to environment, health and safety of viticultural workers and plant phytotoxicity. The activity on powdery mildew of sulphur applied at doses reduced up to 50% in tank mixtures with silicates and Equisetum arvense based products, never tested on grapevine, was assessed. Two-year trials were carried out applying the products every 7-9 days in the period of greatest risk for spring ascosporic infections, in two organic vineyards in the Abruzzo region, Italy. The effectiveness towards the disease of the mixtures was demonstrated, often to a greater extent than that of full-dose sulphur, normally used in the vineyards. Furthermore, in vines treated with the mixtures, increases in yield quantity and quality, such as higher contents of soluble solids and lower levels of total acidity, have been shown. Due to the strong efficacy demonstrated on the leaves, silicon-based products + sulphur mixtures can also be recommended in eradicative applications, aimed at reducing the inoculum of the disease. The great activity of the mixtures demonstrated in this study suggests confirmation through further investigations on different cultivars and vine-growing areas at different levels of infection, also testing the effectiveness of individual silicon products against the disease.

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

The study of hydrothermal travertines contributes to the understanding of the interaction between physico-chemical processes and the role played by microbial mats and biofilms in influencing carbonate precipitation. Three active travertine sites were investigated in Central Italy to identify the types of carbonate precipitates and the associated microbial mats at varying physico-chemical parameters. Carbonate precipitated fabrics at the decimetre- to millimetre-scale and microbial mats vary with decreasing water temperature: a) at high temperature (55-44°C) calcite or aragonite crystals precipitate on microbial mats of sulphide oxidizing, sulphate reducing and anoxygenic phototrophic bacteria forming filamentous streamer fabrics, b) at intermediate temperature (44-40°C), rafts, coated gas bubbles and dendrites are associated with Spirulina cyanobacteria and other filamentous and rod-shaped cyanobacteria, c) low temperature (34-33°C) laminated crusts and oncoids in a terraced slope system are associated with diverse Oscillatoriales and Nostocales filamentous cyanobacteria, sparse Spirulina and diatoms. At the microscale, carbonate precipitates are similar in the three sites consisting of prismatic calcite (40-100 µm long, 20-40 µm wide) or acicular aragonite crystals organized in radial spherulites, overlying or embedded within biofilm EPS (Extracellular Polymeric Substances). Microsparite and sparite crystal size decreases with decreasing temperature and clotted peloidal micrite dominates at temperatures < 40°C, also encrusting filamentous microbes. Carbonates are associated with gypsum and Ca-phosphate crystals; EPS elemental composition is enriched in Si, Al, Mg, Ca, P, S and authigenic aluminium-silicates form aggregates on EPS. This study confirms that microbial communities in hydrothermal travertine settings vary as a function of temperature. Carbonate precipitate types at the microscale do not vary considerably, despite different microbial communities suggesting that travertine precipitation, driven by CO2 degassing, is influenced by biofilm EPS acting as template for crystal nucleation (EPS-mediated mineralization) and affecting the fabric types, independently from specific microbial metabolism.

The maintenance of traditional agricultural practices in protected small islands is closely linked to the preservation of the land, the protection of natural resources, and the conservation of local traditions. For this purpose, the Tuscan Archipelago National Park promoted the census of ancient horticultural varieties preserved by some farmers on the island of Elba. The survey revealed a deep-rooted historical, cultural, social, and economic link between this germplasm and the island’s territory. A scientific characterization of the landrace under ethnobotanical, morphological, and genetic aspects was carried out. Among these local varieties, two landraces of the Brassica species and three landraces of the Phaseolus species were identified and analyzed in this study. To ascertain their distinguishability and uniqueness, similar varieties were also identified based on morpho-physiological characteristics or territorial proximity and compared with the Elban landraces. Morpho-phenological data were collected, and molecular analyses were carried out using Simple Sequence Repeats (SSR) markers. Ten different SSR loci were considered for the Phaseolus species and nine for the Brassica species. The Tuscan Archipelago landraces showed a high level of internal variability but were clearly distinct from each other and from the analyzed varieties, as shown by AMOVA (Analysis of Molecular Variance). Their distinctness was further highlighted by the UPGMA dendrogram obtained from the genetic distance matrix. The same results were confirmed by Principal Coordinate Analysis (PCoA). This study confirms the peculiarity of the Elban landraces, their biodiversity is a heritage to be safeguarded, which can also be used in future breeding programs. These ancient Elban landraces were allocated to local farmers (most were young farmers) to protect them from extinction and to promote more resilient varieties cultivation compared to commercial hybrids widely spread in the area. Local farmhouses also play a strategic role in safeguarding the germplasm and dissemination of sustainable agricultural practices. There is high demand for ancient Elban landraces, this has led to the development of a new local economy balanced between agricultural tradition and innovation.

The spread of high-performance personal computers, frequently equipped with powerful Graphic Processing Units (GPU), raised the interest on a set of techniques able to extract models of electromagnetic phenomena (and devices) directly from available examples of the desired behavior. Such approaches are collectively referred to as Machine Learning (ML). A typical representative ML approach is the so called “Neural Network” (NN). Using such data-driven models allows evaluating the output in a much shorter time when a theoretical model is available, or allows predicting the behavior of the systems and devices when no theoretical model is available. With reference to a simple yet representative benchmark electromagnetic problem, some of the possibilities and the pitfalls of the use of NN for the interpretation of measurements (inverse problem) or to obtain the required measurements (optimal design problem) are discussed. The investigated aspects include the choice of the NN model; the generation of the dataset(s); the selection of hyperparameters (hidden layers, training paradigm). Finally, the capabilities in the handling of ill-posed problems are critically revised.

NUSES is a planned space mission aiming to test innovative observational and technological approaches related to the study of low-energy cosmic rays, gamma rays and high-energy astrophysical neutrinos. Two scientific payloads will be hosted onboard the NUSES space mission: Terzina and Zirè. Terzina will be an optical telescope readout by SiPM arrays, for the detection and study of Cerenkov light emitted by Extensive Air Showers generated by high-energy cosmic rays and neutrinos in the atmosphere. Zirè will focus on the detection of protons and electrons up to a few hundred MeV and to 0.1-10 MeV photons and will include the Low Energy Module (LEM). The LEM will be a particle spectrometer devoted to the observation of fluxes of low-energy electrons in the 0.1-7 MeV range and protons in the 3-50 MeV range along the Low Earth Orbit (LEO) followed by the hosting platform. The detection of Particle Bursts (PBs) in this Physics channel of interest could give new insight into the understanding of complex phenomena such as eventual correlations between seismic events or volcanic activity with the collective motion of particles in the plasma populating van Allen belts. With its compact sizes and limited acceptance, the LEM will allow the exploration of hostile environments such as the South Atlantic Anomaly (SAA) and the inner van Allen belt, in which are expected electron fluxes of the order of 106−7 cm−2 sr−1 s−1. Concerning the vast literature of space-based particle spectrometers, the innovative aspect of the LEM resides in its compactness, within 10x10x10 cm3, and in its “active collimation” approach dealing with the problem of multiple scattering at these very low energies. In this work, the geometry of the detector, its detection concept, its operation modes and the hardware adopted will be presented. Some preliminary results from the Monte Carlo simulation (Geant4) will be shown.

Equine hepacivirus (EqHV, Flaviviridae, Hepacivirus) is a small, enveloped, RNA virus generally causing sub-clinical hepatitis with occasional fatalities. EqHV is reported in equids worldwide, but for Italy data are limited. To address this, a survey study was set up to estimate prevalence at national level and among different production categories (equestrian, competition, work and meat and reproduction) and national macro-regions (North, Central, South and Islands). Data obtained testing 1801 horse serum samples by Real-Time RT PCR were compared within the categories and regions. The NS3 fragment of the PCR-positive samples was sequenced by Sanger protocol for phylogenetic and mutational analysis. The tertiary structure of the NS3 protein was also assessed. The estimated national prevalence was 4.27% [1.97-6.59, 95%CI] and no statistical differences were detected among production categories and macro-regions. The phylogenesis confirmed the distribution in Italy of the three known EqHV subtypes, suggesting also a possible fourth sub-type that however requires further confirmation. Mutational profiles that could also affect the NS3 binding affinity to the viral RNA were detected. The present paper demonstrates that EqHV should be included in diagnostic protocols when investigating causes of hepatitis and in quality control protocols for blood derived products, due to its parental transmission.

This work presents the dynamics of forest clearing in the Brazilian Amazon during the period 2006–2019 in which includes the approval of the new Brazilian Forest Code in 2012. The study was carried out in the Brazilian Amazon, Pará State and in the municipality of Novo Progresso (Pará State). The analysis was based on deforestation and fire hotspot datasets issued by the Brazilian Institute for Space Research (INPE), produced based on optical and thermal sensors onboard different satellites. Deforestation data was also used to assess greenhouse gas (GHG) emissions from the slash-and-burn practices. The work showed a good correlation between the occurrence of fires in the newly deforested area in the municipality of Novo Progresso and the slash-and-burn practices. The same trend was also observed in the Pará State, suggesting a common practice along the deforestation arch. The study indicated positive coefficients of determination of 0.72 and 0.66 between deforestation and fire occurrences for the municipality of Novo Progresso and Pará State, respectively. The increased number of fire occurrences in the primary forest suggests possible ecosystem degradation. Deforestation reported for 2019 surpassed 10,000 km2, a significant intensification comparatively higher than the previous ten years which was on an average of 6,760 km2. The steady increase of deforestation in the Amazon after 2012 has been a worldwide concern because of the forest loss itself as well as the massive GHG emitted in the Brazilian Amazon (295 million tons of net CO2 equivalent in the year 2019). Better correlation of deforestation and fires occurrences reported from satellite images confirmed the slash-and-burn practice and the secondary effect of deforestation, which degrades primary forest surrounding the deforested areas.

There are few studies of the psychological effects of language brokering (speaking on behalf of) among minors migrated to Europe, even though language brokering is becoming more current in many migrant families. As the psychological implications of language brokering remain controversial, further investigation is needed. Earlier studies have documented that language brokering is sometimes linked with emotional maladjustment and developmental drawbacks, but other studies have shown faster acquisition of social and Language skills. The present study assessed the relation of language brokering with psychological well-being in a sample of Latino migrant adolescents living in Italy; the dependent variables were depression, anxiety, and emotions. Statistically significant differences between boys and girls confirmed the sex-specificity of language brokering and the lack of statistically significant negative association between language brokering and psychological well-being.

In this work, we report synthesis of Cu, Pt and Pd doped SnO₂ powders and their comparative CO gas sensing studies. Dopants were incorporated into SnO₂ nanostructures using chemical and impregnation methods by using urea and ammonia as precipitation agents. The synthesized samples were characterized using X-ray diffraction (XRD), Raman spectroscopy, Scanning electron microscopy (SEM) and High resolution transmission electron microscopy (HR-TEM). The presence of dopants within the SnO₂ nanostructures was evidenced from HR-TEM. Doped powders utilizing chemical methods with urea as precipitation agent presented higher sensitivities compared to the remaining, which is due to the formation of uniform and homogeneous particles resulted from the temperature assisted synthesis. The particle sizes of doped SnO₂ nanostructures were in the range of 40-100 nm. An enhanced sensitivity around 1783 was achieved with Cu doped SnO₂ when compared with two other dopants i.e., Pt (1200) and Pd: SnO₂(502). The high sensitivity of Cu: SnO₂ is due to formation of CuO and its excellent association and dissociation in the presence of CO with adsorbed atmospheric oxygen at sensor operation temperatures resulted in high conductance. Cu: SnO₂ may be an alternative and cost effective sensor for industrial applications.

Childhood emotional abuse (CEA) has been linked to a range of unfavorable outcomes, including the development of unhealthy personality traits and maladaptive coping mechanisms and behaviors. In this study, our objective was to investigate whether neuroticism and perfectionism act as mediators in the relationship between CEA and workaholism, while also evaluating the gender invariance of the hypothesized model. A cohort of 1176 young workers, with a balanced gender representation (50% female), aged 18-25, participated in the study by completing self-report questionnaires. The results revealed significant connections between all direct and indirect links, indicating a complex interplay between childhood emotional abuse, neuroticism, perfectionism, and workaholism. Importantly, the mediation model exhibited no significant differences between genders, suggesting that the identified relationships are consistent across both male and female participants. This research underscores the critical importance of early identification of childhood emotional abuse and advocates for the implementation of trauma-informed care to address the negative consequences of emotional abuse, ultimately aiming to prevent the development of workaholism. Furthermore, the findings emphasize the necessity for tailored prevention strategies, focusing on mitigating neuroticism and perfectionism as potential pathways for effective therapeutic interventions.

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have got interest following the recent publication of their pharmacologically beneficial effects. Recently it comes out that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In the past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered but, unfortunately, none of them is in the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches were already performed for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. 14,492 compounds were retrieved from this database and filtered through a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 79–245 nM. ADMET properties prediction were performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives; from these analyses, three molecules resulted as excellent candidates for becoming new drugs.

The literature, aimed at understanding the income-price elasticity of air passenger demand, bases its analysis on airport movement. The diversity of studies regarding the casualty between air transportation and economic growth are examples. Some studies covering this link, estimate the income-price relationship with the demand considering international traffic. Considering a domestic setting, where this traffic is significant in Brazil, studies related to remote regions are scarce, and the existing ones focus on governmental policies and subsidies. In addition, empirical studies on the theme consenter themselves in developed regions, such as Europe, North America, and Australia. For Brazil, where we find the Amazon region, there are no empirical researches. This paper analyses the price-income elasticity of the demand regarding domestic passengers in air links from remote cities of the Brazilian Amazon. This study uses panel data regression analysis method on a database of domestic scheduled flights of Brazil´s National Civil Aviation Agency. The results show that air passengers involving remote region flights present a lower sensitiveness regarding local income and airline´s price variations than those in flights among capitals. The higher difference is in income-elasticity of the remote city of origin, which is lower than that of the air traffic among capitals.

The construction industry has witnessed the increasing use of digital tools and smart solutions, particularly, in the realm of buildings energy automation within the concept of smart cities. While to truly realize the potential benefits of smart cities, a broader scope of smart initiatives is required to support the transition from smart buildings towards smart neighbourhoods, appreciated as the critical unit of urban development. To support this interplay of smart solutions between buildings and neighbourhoods, this article aims to collect and review all smart solutions presented in existing scientific articles, technical literature, and realized European projects. These solutions are classified under two main sections of buildings and neighbourhoods, which are investigated through five domains: buildings energy-related uses, renewable energy sources, water, waste, and open space management. Showcasing the quantitative outcomes demonstrates the potential benefits of implementing smart solutions from buildings to neighbourhoods. Moreover, this research concludes that the true enhancement of energy conservation goes beyond the buildings’ energy component and can be genuinely achieved by integrating intelligent elements of the neighbourhood, due to their strong interdependencies. Future research is recommended to focus on assessing the effectiveness of these solutions towards resource conservation.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

The conformations of trifluoroacetyl triflate, CF3C(O)OSO2CF3, were investigated through vibrational experimental methods (gas-phase FTIR, liquid-phase Raman, and Ar-matrix FTIR spectroscopy) and Density Functional Theory (DFT) calculations. A potential energy surface was computed using the B3P86 /6-31+g(d) approximation as a function of the dihedral angles τ1 = CCOS and τ2 = COSC. The surface reveals three minima, which were further optimized using the B3LYP method with various basis sets (6-31++G(d), 6-311++G(d), tzvp and cc-pvtz). The global minimum corresponds to a syn-anti conformer (the CO double bound syn with respect the O−S single bond and the C−O single bond anti with respect to de S−C single bond). The other two minima represent enantiomeric syn-gauche forms. The Ar-matrix FTIR spectrum exhibited clear evidence of the presence of two conformers. Furthermore, the randomization process observed following broad-band UV-visible irradiation facilitated the identification of the IR absorption of each conformer. Based on the Ar-matrix FTIR experiments, the vapour phase of trifluoroacetyl triflate at room temperatures was composed of approximately 60-70% of the syn-anti conformer and 30-40% of the syn-gauche form.

Vulnerability is the big issue of the small inland urban centers exposed to the risk of depopulation. In the climate and in the context of an increasing seismic risk in the center-northern part of Italy, seismic vulnerability can become the determinant cause of the final abandonment of a small town. In some Italian regions, as well as Emilia Romagna, municipalities are implementing seismic vulnerability reduction policies based on the Emergency Limit Condition that has become a basic reference for ordinary land planning. This study proposes a valuation planning approach to the seismic vulnerability reduction carried out within the general planning framework concerning the Faentina Union, a group of five small towns located in the south-western part of the Province of Ravenna, Italy. The approach consists of three main stages: knowledge – the typological, constructive and technological description of the buildings specifically concerning their vulnerability degree; interpretation – the analyses aimed to outline a range of hypotheses about the damages in case of seism; planning – identifying the works intended to definitely reduce the vulnerability of the buildings. This stage includes a cost modelling tools aimed at outlining the trade-off between the extension and the intensity of the vulnerability reduction works, given the budget.

Starting 1994, the debate for regulating organic agriculture in Brazil was officially recognized in May 1999. Still, only in 2003, when the law # 10,831 was instituted, the country reached an effective milestone on organic production, both internally and externally. Since the industry regulation, the legislation underwent many modifications, constantly reviewing and adjusting. The current study examined the institutionalization of organic production in Brazil and what the current regulations can be used as a reference for those interested in this sector. The most recent update of Organic legislation and its implication on practice were also discussed. A case study on production of strawberry in organic system is presented and discussed.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischaemia. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

RNA interference (RNAi) has become a widely utilised method to study gene function, yet despite this, many of the mechanisms surrounding RNAi remain elusive. The core RNAi machinery is relatively well understood, however many of the systemic mechanisms, particularly double stranded RNA (dsRNA) transport, are not. Here, we demonstrate that dsRNA binding proteins in the serum contribute to systemic RNAi, and may be the limiting factor in RNAi capacity for species such as spiny lobsters where gene silencing is not functional. Incubating serum from a variety of species across phyla with dsRNA led to a gel mobility shift in species where systemic RNAi has been observed, with this response being absent in species where systemic RNAi has never been observed. Proteomic analysis suggested lipoproteins may be responsible for this phenomenon, and may transport dsRNA to spread the RNAi signal systemically. Following this, we identified the same gel shift in the slipper lobster Thenus australiensis and subsequently silenced the insulin androgenic gland hormone, marking the first time RNAi has been performed in any lobster species. These results pave the way for inducing RNAi in spiny lobsters, and better understanding the mechanisms of systemic RNAi in Crustacea, as well as across phyla.

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

Reductive amination is a powerful tool in sustainable organic synthesis that allows chemists to access a wide range of valuable amine products using renewable feedstocks, mild reaction con-ditions, and with minimal waste generation. Practical applications can be found in various fields, including pharmaceuticals, contributing to greener and more sustainable chemical processes. In this work we present a heterogeneous (Rh and Pt) catalysed protocol for the fast and efficient synthesis of ractopamine hydrochloride (-adrenergic drug) under MW-assisted reductive ami-nation protocol starting from raspberry ketone and octapamine. Microwave (MW) successfully accelerated the hydrogenation reaction and reduced the reaction time from 13 hours to only 3 hours under mild conditions (50°C at 10 bar). The best catalysts were Pt/C and Rh/C, which led to high conversion and selectivity towards ractopamine:HCl. The solvent has a significant effect on the reaction outcome. The replacement of methanol with other solvents had a negative impact on the reaction yield. We also replaced the raspberry ketone with other ketone substrates, especially cyclohexanone. These preliminary experiments may be useful for further process improvements in the synthesis of β-adrenergic agonists and related structures.

Chiral hydroxamic acid (HA) and bis-hydroxamic acid (BHA) ligands have made significant contributions to the field of asymmetric synthesis, particularly in the synthesis of natural products. These ligands possess unique molecular structures that allow for exceptional stereochemical control, leading to their widespread use in catalytic systems. This review highlights the advancements made in asymmetric synthesis using chiral hydroxamic acid and bis-hydroxamic acid ligands and their impact on the synthesis of complex natural products. The discussion encompasses their role in enantioselective C-C bond formation, the functionalization of C-H bonds, asymmetric transformations involving heteroatoms, and their application in the total synthesis of natural products. The versatility and efficiency of chiral hydroxamic acid ligands and bis-hydroxamic acid ligands make them invaluable tools for synthetic chemists working towards the efficient and selective synthesis of natural products. This review provides a comprehensive overview of their contributions, showcasing their potential to expand the boundaries of chemical synthesis and access the diverse array of natural product scaffolds.

High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to their glucosinolate amount. Extracts from Sinapis nigra L. and Sinapis alba L. have been obtained from leaves and seeds under different conditions using ethanol/water mixtures because well accepted by food industry. The EtOH/H2O 8:2 mixture gives better yields in glucosinolate amounts from grinded seeds, mainly sinalbin in S. alba and sinigrin in S. nigra. The highest antiproliferative activity in both non-tumour and tumour cell lines was induced by S. alba seeds extract. To evaluate whether Sinapis spp effect was only due to glucosinolate content or it was influenced by the extracts’ complexity, cells were treated with extracts or glucosinolates, in the presence of myrosinase. Pure sinigrin did not modify cell proliferation, while pure sinalbin was less effective than the extract. The addition of myrosinase increased the antiproliferative effects of the S. nigra extract and sinigrin. Antiproliferative activity was correlated to MAPKs modulation, which was cell and extract-dependent. Cell-cycle analysis evidenced a proapoptotic effect of S. alba on both tumour cell lines and of S. nigra only on HCT 116. Both extracts showed good antimicrobial activity in disc diffusion tests and on ready-to-eat fresh salad. These results underline the potential effects of Sinapis spp in chemoprevention and food preservation.

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte Serum-Free Medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12) and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred as DFK. The toxicological effects of electronic cigarette liquids (E-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12 or DFK and cellular morphology, growth, wound healing and gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after E-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24-hours post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, E-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study molecular biology of disease and pathology, provided cells are initially seeded in KSFM.

Background: Tele-rehabilitation has grown significantly in the past years, especially in 2020 when it has been a crucial tool for supporting patients during the COVID-19 pandemic. Within the context of tele-rehabilitation, serious games have a significant role. However, realizing software for serious games capable of responding to the variety of user needs is resource demanding. Methods: we present Proteo, a modular framework for developing serious games from scratch, but with the ability of providing a high-level interface for game customization by therapists and researchers. We also present two serious game implementation examples with analysis of end user’s and therapists/researchers’ satisfaction. Results: by involving a group of 11 specialized therapists and 9 end users we analyzed the Proteo user’s satisfaction. We found that therapists and end users scored high level of involvement, and the therapists scored also high level of suitability. More in depth, both groups showed significant differences between positive and negative feeling, with positive feeling scoring higher than negative ones. Finally, concerning Users’ level of suitability the condition of successfulness of the system, ability to control, clarity and helpfulness were reported as high while the difficulty of the system and the difficulty of the task were reported as low. Conclusions: the proposed framework is a step forward in providing a comprehensive open-source, modular framework, to develop serious games for tele-rehabilitation. Proteo is distributed with a MIT license and available to researchers on GitHub and has been well accepted by the users we involved in the evaluation tests.

Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in crustaceans, although it is difficult to characterise orthologs between species due to their sequence diversity. Conserved CYP450s enzymes in crustaceans are those associated with ecdysteroidogenesis; synthesising and breaking down the active moult hormone, 20-hydroxyecdysone. The complex life-cycle of the ornate spiny lobster, Panulirus ornatus, relies on moulting in order to grow and develop. Many of these diverse life stages have been analysed to establish a comprehensive transcriptomic database for this species. The transcripts putatively encoding for CYP450s were mapped using transcriptomic analysis and identified across growth and development stages. With the aid phylogeny, 28 transcripts of 42 putative P. ornatus CYP450s were annotated, including the well conserved Halloween genes, which are involved in ecdysteroidogenesis. Expression patterns across the life-stages determined that only a subset of the CYP450s can be detected in each life-stage or tissue. Four Shed transcripts show overlapping expression between metamorphosis and adult tissues, suggesting pleotropic functions of the multiple Shed orthologs within P. ornatus.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

We herein provide an overview of the most recent multidisciplinary process advances that have occurred in the food industry as a result of changes in consumer lifestyle and expectations. The demand for fresher and more natural foods is driving the development of new technologies that may efficiently operate at room temperature. Moreover, the huge amount of material discarded by the agro-food production chain lays down a significant challenge for emerging technologies that can provide new opportunities by recovering valuable by-products and creating new applications. Aiming to design industrial processes, there is a need of pilot scale plants such as the “green technologies development platform” that was established by the authors. The platform is made up of a series of multifunctional laboratories that are equipped with non-conventional pilot reactors developed in direct collaboration with partner companies in order to bridge the enormous gap between academia and industry via the large-scale exploitation of relevant research achievements. Selected key, enabling technologies for process intensification make this scale-up feasible. We make use of two selected examples, the grape and olive production chains, to show how cavitational reactors, which are based on high-intensity ultrasound and rotational hydrodynamic units, can assist food processing and the sustainable recovery of waste to produce valuable nutraceuticals as well as colouring and food-beverage additives.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

The early failure of glaucoma surgery is mainly caused by an overly fibrosis at the subconjunctival space causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signature with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGF-A, IL-8, C-MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGF-A and IL-8 protein levels were also increased in fibroblast supernatants. We propose that these proteins may act as biomarkers of conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery leading to more optimal and personalized treatments.

Meteorological observations over the last four decades are of paramount importance to investigate the ongoing climate change. The assessment of the reliability of any climatic time series is thus mandatory to draw correct conclusions. This evaluation involves homogeneity tests to detect artificial discontinuities whose identification is facilitated by metadata availability. In this work, daily minimum and maximum temperature measurements collected in Padua, Italy, between 1980 and 2022, are examined. Hourly observations began in 1993 and since the aim is to study long term behavior of the temperature, the focus is on daily averages and extremes. Over this period, the weather station of Padua center underwent many changes, in location or instrument; therefore, some tests have been used to identify and remove the effects of these variations and obtain a homogeneous time series. The homogeneity tests applied must be able to identify change-points both in the middle and at the extremes of the series. Some well-known absolute tests have been applied to investigate shift in the mean value: Standard Normal Homogeneity test (SNH), Buishand U and range tests, Pettitt test, F-test, STARS. Some relative tests have been applied too, which are generally more reliable than absolute tests, because they consider the information from neighboring stations. As relative tests rely on the homogeneity and quality of the reference series, several nearby stations and two reanalysis datasets (ERA5 and MERIDA) have been considered, to enhance the picture of the local situation and provide more robust conclusions. The applied tests identify change-points in the years in which a change in instrument or location of the station have occurred, confirming that these changes have compromised the homogeneity of the series. The sub-series obtained splitting the observations in correspondence of these change-points have been homogenized with respect a selected period; corrections must be applied also to future measurements to extend the time series properly.

Angiogenesis is a critical process in various physiological and pathological conditions, and snake venom disintegrins (SVDs) have been shown to be important regulators of this process. In this review, we explore the dual roles of SVD in angiogenesis, both as antiangiogenic agents by inhibiting integrin binding and interfering with vascular endothelial growth factors and as proangiogenic agents by enhancing integrin binding, stimulating cell migration and proliferation, and inducing neoangiogenesis. Studies in vitro and in animal models have demonstrated these effects and offer significant therapeutic opportunities. The potential applications of SVD in diseases related to angiogenesis, such as cancer, ocular diseases, tissue regeneration, wound healing, and cardiovascular diseases, are also discussed. Overall, SVDs are promising potential therapeutics, and further advances in this field could lead to innovative treatments for diseases related to angiogenesis.

Urban trees are generally considered to be a public asset and are an important part of a city's heritage. The aim of this work is to analyse the influence of season on the economic appraisal of various trees in Madrid. Photographs were taken of 43 individual tree specimens in summer and winter. The survey was designed to compare differences of opinion in the economic assessment of trees. The trees were assessed by five valuation methods used worldwide. 78 agroforestry engineering students answered a written survey, and the variables considered were: percentage of students who always evaluated the tree equally (%0), percentage of students who assigned more value to the summer photograph (%S), and percentage of students who assigned more value to the winter photograph (%W). The results were analysed by the statistical test of equal proportions and ANOVA to detect differences according to tree type (evergreen or deciduous), species and other groupings made by the authors in previous works. W and S percentages are similar. The ANOVA analysis rejects the equality of percentages of S and W between groups. The Welch test rejects the equality of percentage of S, W and O between species.

The study of precipitation amount at different time scales constitutes an important issue in climate research and risk assessment. When dealing with daily totals, a frequent but sometimes underestimated problem is at what time the observation day begins. The choice of different starting times may lead to incompatibility between stations and incorrect identification of extreme events. In this work, the problem of temporal misalignment between precipitation datasets characterized by different starting time of the observation day is analyzed. The most widely used adjustment methods (1day and uniform shift) and two methods based on reanalysis (NOAA and ERA5) are evaluated in terms of temporal alignment, precipitation statistics and percentile distributions. As test series, the precipitation amount collected from 9 a.m. local time (09 LT) on the previous day to 09 LT on the target day (9-9 datasets) of the Padua and nearby stations in the period 1993-2022 have been selected. Results show that the reanalysis-based methods, in particular ERA5, outperform the others in temporal alignment, regardless the station. But, for the periods in which reanalysis data are not available, “1day” method, which shifts the daily amount back one calendar day, and “unif” method, which distributes uniformly the daily total from a 2-day moving window surrounding the target date, can be considered valid alternatives. On the other side, concerning the precipitation statistics, the reanalysis-based methods are not the best option, as they increase the precipitation frequency and reduce the mean value over wet days, NOAA much more than ERA5. Nevertheless, the uniform method provides a larger deviation from the original daily series. The use of the series of a station nearby the target one, which is mandatory in case of missing data, gives similar or better results than applying any adjustment method to the 9-9 series. General conclusions can hardly be drawn as they depend on the method and station. For the Padua dataset, the analysis was repeated at monthly and seasonal resolution. In general, the adjustment series show the most relevant changes in the precipitation statistics in summer and less temporal alignment with the original series in summer and autumn, the two seasons mainly affected by heavy rains in Padua. Finally, the percentiles distribution, analyzed for all the methods and stations, indicates that any adjustment method underestimates the percentile values, except ERA5. Only Legnaro, the station most correlated with Padua, gives results like ERA5.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Vitamin K is a multifunctional micronutrient essential for human health, and deficiency has been linked to multiple pathological conditions. In this study we aimed to develop and validate a new food frequency questionnaire (FFQ) to estimate total vitamin K intake, over the course of a 30-day interval, in a Portuguese, Mediterranean-based, population. We conducted a prospective study in a non-random sample of 38 healthy adult volunteers. The FFQ was designed based on a validated Portuguese FFQ used in nationally representative studies and on literature reviews, to include foods containing ≥ 5μg of vitamin K/100g and foods with a lower vitamin K content, yet commonly in-cluded in a Mediterranean diet. Vitamin K intake was estimated from 24h recalls and six days of food records. The final FFQ included 54 food items which, according to regression analyses, explains 90% of vitamin K intake. Mean differences in vitamin K intake based on food records (80±47.7 μg/day) and on FFQ (96.5±64.3 μg/day) were statistically non-significant. Further, we found a strong correlation between both methods (r= 0.7; p=0.003). Our results suggest that our new FFQ is a valid instrument to assess the last 30-days of vitamin K intake in the Portuguese Mediterranean population.

This short review is aimed at giving an overview of catalytic carbonylative double cyclization reactions, which are processes in which suitable organic substrates and carbon monoxide are sequentially activated by a promoting catalyst to afford the formation of two new cycles with concomitant incorporation of carbon monoxide as a carbonyl function into the final product. Paradigmatic examples of this powerful synthetic methodology, which allows the one-step synthesis of complex molecular architectures from simple building blocks using the simplest and readily available C-1 unit (CO) are illustrated and discussed. The review is divided into five sections: 1) Introduction; 2) Functionalized Olefinic Substrates; 3) Functionalized Acetylenic Substrates; 4) Functionalized Halides; 5) Conclusions and Future Perspectives.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

Conservation agriculture (CA) could be very effective for agricultural sustainability under Mediterranean environments, where farmers rely on short rotation based on durum wheat. In this work we investigated the effect of different combination of tillage treatments and crop sequence (conventional tillage and wheat monocropping, CT-WW; conventional tillage, and wheat following faba-bean, CT-WF; zero tillage and wheat monocropping, ZT-WW; zero tillage and wheat following faba-bean, ZT-WF) on yield, grain quality traits as well as on diseases incidence and severity in durum wheat (var. Saragolla). The results of a two-years of data of a long-term experiment (7-year experiment; split-plot design) are discussed. The CA approach (ZT+WF), which induced always the highest grain yields (6.1 t ha-1 and 3.3 t ha-1 in 2016 and 2017) thanks to an increased number of spikes m-2 (296 vs 269 and 303 vs 287 spikes m-2 in 2016 and 2017, respectively) as well as to a more pronounced ear length, demonstrated significant positive influences in terms of grain quality. It promoted grain protein accumulation (12.1% for ZT+WF versus 11.4% for ZT+WW and 12.4% for ZT+WF versus 10.6% for ZT+WW in 2016 and 2017), improved gluten quality (in terms of SDS sedimentation test) and colour of the grain. The abundance of crop residues determined a higher incidence and severity of Zymoseptoria tritici leaf symptoms under CA system; nevertheless the late appearance of infection was the main reason of not affecting yield and quality traits. The presence of faba-bean (WF) in the rotation significantly reduced leaf symptoms of Z. tritici.

With the renewed interest for lunar surface exploration, the European Space Agency envisions to stimulate the creation of lunar communications and navigation services (LCNS) to enable, among others, autonomous navigation capabilities for lunar rovers. As the number of satellites foreseen in such a service is much smaller compared to Earth based global navigation satellite systems (GNSS), different complementary technologies are pursued to improve the attainable navigation accuracy for lunar rovers. One way to improve the position accuracy provided by the LCNS satellites is to constrain the vertical position using a high resolution digital elevation model (DEM). This article presents the results of a variance covariance analysis of an extended Kalman filter (EKF) implementation in which the LCNS ranging measurements are used together with DEM from the LRO LOLA instrument. Assuming a realistic orbit determination and time synchronization (ODTS) accuracy of the LCNS satellites, the usage of a navigation grade IMU and an oven controlled crystal oscillator (OCXO), a 3-sigma position accuracy of less than 10 meters can be obtained. Furthermore, the availability is substantially improved as the DEM aided solution enables a position solution in case of only 3 visible satellites.

Halophytic plants are, by definition, well adapted to saline soils. However, even halophytes can face nutritional imbalance and accumulation of high levels of compounds such as oxalic acid (OA), and nitrate (NO₃^¯). These compounds compromise the potential nutritional health benefits associated with salt tolerant plants such as Portulaca oleracea. Thus, preventing the accumulation of non-nutritional compounds will allow plants to be grown in saline conditions as crops. To this end, two ecotypes (ET and RN) of Portulaca oleracea plants were grown under growth room conditions with two levels of salinity (0, 50 mM NaCl) and three ratios of nitrate: ammonium (0:100%; 33:66%; 25:75% NO₃^¯:NH₄⁺). The results showed that both ecotypes exposed to elevated NO₃^¯, showed severe leaf chlorosis, high levels of OA, citric acid, and malic acid, while plants of ecotype ET exposed to elevated NH₄⁺ concentrations (33% and 75%) and 50 mM NaCl displayed a marked reduction in OA content, increased total chlorophyll and carotenoid contents, crude protein content, total fatty acid (TFA) and α-Linolenic acid (ALA) thus enhancing leaf quality. This opens the potential to grow high biomass, low OA P. oleracae crops. Lastly, our experiments suggest that ecotype ET copes with saline conditions and elevated NH₄⁺ through shifts in leaf metabolites.

An accurate flux measurement of low-energy charged particles trapped in the magnetosphere is necessary for space weather characterization and to study the coupling between the lithosphere and magnetosphere, which allows for the investigation of the correlations between seismic events and particle precipitation from Van Allen belts. In this work, the project of a CubeSat space spectrometer, the Low-Energy Module (LEM), is shown. The detector will be able to perform an event-based measurement of the energy, arrival direction, and composition of low-energy charged particles down to 0.1 MeV. Moreover, thanks to a CdZnTe mini-calorimeter, the LEM spectrometer also allows for photon detection in the sub-MeV range, joining the quest for the investigation of the nature of Gamma-ray bursts. The particle identification of the LEM relies on the ΔE−E technique performed by thin silicon detectors. This multipurpose spectrometer will fit within a 10 × 10 × 10 cm3 CubeSat frame, and it will be constructed as a joint project between the University of Trento, FBK, and INFN-TIFPA. To fulfil the size and mass requirements, an innovative approach, based on active particle collimation, was designed for the LEM; this avoids the heavy/bulky passive collimators of previous space detectors. In this paper, we will present the LEM geometry, its detection concept, the results from the developed GEANT4 simulation, and some characterisations of a candidate silicon detector for the instrument payload.

Cannabis Sativa L. has been used for a long time to obtain food, fiber and as a medicinal and psychoactive plant. Today the nutraceutical potential of C. Sativa is being increasingly reappraised; however, C. Sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely β-sitosterol, stigmasterol, campesterol, friedelin and epi-friedelanol) in the root extracts of C. Sativa, a finding which might pave the way to the exploitation of the therapeutic potential of C. Sativa in all its parts. To facilitate roots harvesting and processing, aeroponic (AP) and aeroponic elicited cultures (AEP), have been set up and compared to soil-cultivated plant (SP): interestingly a considerable overgrowth of the plants - particularly of roots - and a significant increase (up to 20 fold in the case of β-sitosterol) in the total content of the above roots’ bioactive molecules have been observed in AP and AEP. In conclusion aeroponics, an easy, standardised, free of contaminant cultivation tecchnique, allows an ease harvesting/processing of roots along with a greater production of their secondary bioactive metabolites which could be utilized in the formulation of health promoting and health care products.

This paper describe the influence of the Rift Molango during the mineralization of elements of the platinum group and some light rare earths elements in a sedimentary exhalative ore deposit.

The mining wastes generated during the last decades in the mining region of Pachuca-Real del Monte in Mexico, still contains silver values of interest. For this reason, the present work is a preliminary study of the leaching kinetics of silver contained in these residues, using as a leaching reagent the thiosemicarbazide-oxygen system, with the aim of proposing this leaching system as a less toxic alternative than cyaniding process. Previous the leaching process, representative samples were wholly characterized, finding 56 g of Ag and 0.6 g of Au per ton. For the kinetic study in the mentioned system, were evaluated the reagent concentration, temperature, partial pressure of oxygen, pH and stirring rate. According the experimental results found, it was observed that [CH5N3S] concentration showed a significant effect on the leaching rate, obtaining a reaction order of n = 0.93, in the range of 20 - 40 mol CH5N3S ⋅ m-3, getting so a silver recovery up to 76.9%. The effect of temperature gave an activation energy of Ea = 45.55 KJ mol-1, which was indicative of a chemical reaction control. Finally, partial pressure of oxygen has a notable effect on leaching rate, but pH and stirring rate have not apparent effect.

The mining wastes generated during the last decades in the mining region of Pachuca-Real del Monte in Mexico, still contains silver values of interest. For this reason, the present work is a preliminary study of the leaching kinetics of silver contained in these residues, using as a leaching reagent the thiosemicarbazide-oxygen system, with the aim of proposing this leaching system as a less toxic alternative than cyaniding process. Previous the leaching process, representative samples were wholly characterized, finding 56 g of Ag and 0.6 g of Au per ton. For the kinetic study in the mentioned system, were evaluated the reagent concentration, temperature, partial pressure of oxygen, pH and stirring rate. According the experimental results found, it was observed that [CH₅N₃S] concentration showed a significant effect on the leaching rate, obtaining a reaction order of n = 0.93, in the range of 20 - 40 mol CH₅N₃S × m^-3, getting so a silver recovery up to 76.9%. The effect of temperature gave an activation energy of Ea = 45.55 KJ mol^-1, which was indicative of a chemical reaction control. Finally, partial pressure of oxygen has a notable effect on leaching rate, but pH and stirring rate have not apparent effect.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Background: Wilms tumor (WT) is the main renal tumor in children. SIOP-UMBRELLA Guidelines admit Nephron sparing surgery (NSS) in syndromic patients, and in small (&lt;300 ml) nonsyndromic unilateral WTs, without lymph node involvement, and with a substantial expected remnant renal function, after neoadjuvant chemotherapy. We report our prechemotherapy transperitoneal robot-assisted partial nephrectomy (RAPN) in a unilateral non-syndromic Wilms tumor. Methods: A 6-year-old-child showed an exophytic 3.6 cm diameter solid rounding mass involving the upper right renal pole at an incidental abdominal echotomography. CT-scan and abdominal MRI proved no local infiltration neither lymph node involvement was appreciated, suggesting an exophytic mass easily resectable through a NSS robotic approach, with a low risk of rupture and no subverted renal anatomy. The preoperative imaging was not suggestive for WT. A virtual 3D reconstruction of the tumor was performed. Results: the oncologic board approved a robot-assisted partial nephrectomy with the intraperitoneal approach. The histopathologic analysis displayed a WT. The patient underwent 10 vincristine-doses adjuvant chemotherapy. 28-months follow-up showed no tumor recurrence. Conclusions: Intraperitoneal RAPN can represent an opportunity for WT and needs to be assessed as a challenging possibility. This case suggests a potential role of prechemotherapy RAPN in the near future for highly selected patients.

Strain-hardening cement-based composites (SHCC) are a novel class of fiber-reinforced concretes which exhibit high tensile strain capacity prior to failure localization. Although the tensile behavior of SHCC has been a matter of study in numerous research works, the behavior of these composites under other loading modes has scarcely been investigated. The article at hand addresses the mechanical behavior of two types of normal-strength SHCC subject to uniaxial tension, torsion, and combinations of torsional and axial loading. The SHCC under investigation were made with polyvinyl-alcohol (PVA) and ultra-high molecular weight polyethylene (UHMWPE) fibers, respectively. Digital Image Correlation (DIC) was applied to evaluate the multiple cracking process and crack opening modes in conjunction with the concretes’ axial and torsional loading histories. The study demonstrates the suitability of torsion experiments to assess the multi-axial and shear performance of SHCC, highlights the relation between multiple cracking and transfer capacity for shear forces, and emphasizes the importance of the type of reinforcing fibers on the shear strength and ductility of such composites.

Fluorophores with a tetraphenylethylene (TPE) core are attracting increasing interest because of their aggregation-induced emission (AIE) behaviour, which makes them particularly suitable when dispersed in thin-layer films. We propose the synthesis and use of a novel TPE fluorophore (hereafter called TPE-BPAN) decorated with two dimethylamino push groups and a 4-biphenylacetonitrile pull moiety. In tetrahydrofuran solutions, TPE-BPAN showed a broad absorption spectrum, and an intense emission is observed when a non-solvent as water is added in amounts of 70% and above. We selected and synthetized five different polymer matrices for TPE-BPAN with decreasing polarity: a) poly(methylmetacrylate) homopolymer (PMMA); b), c), and d) three copolymers of methyl methacrylate and cyclohexyl methacrylate at different compositions (P(MMA-co-CHMA) 75:25, 50:50, 25:75 mol%); e) poly(cyclohexyl methacrylate) homopolymer (PCHMA). The presence of a less polar comonomer as cyclohexyl methacrylate appeared to enhance the emission behaviour of TPE-BPAN, which displayed the highest quantum yield (QY) in P(MMA-co-CHMA) 75:25 in all the range of concentration studied from 0.4 wt.% to 2.0 wt.%. Further reduction in polarity lowered QY to the values of PMMA films; also, lower adhesion to the glass and a marked fragility of the films were observed. Referring to the P(MMA-co-CHMA) 75:25 films, QY values decreased from over 40% at 0.4 wt.% to about 30% at 2.0 wt.%, which is still helpful for energy harvesting applications such as luminescent solar concentrators (LSC). LSC performances were not significantly affected by the matrix's lower polarity and resulted in around one-third of the state-of-the-art due to the lower QY of TPE-BPAN. The theoretical investigation on density functional theory (DFT) clarified the origin of the observed AIE and the role played by the environment in modulating the photophysical behaviour.

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

The present study explored the expression of CD62L and CD44 by bovine peripheral blood mononuclear cells (PBMCs) and WC1.1+ γδ T cells under Staphylococcus aureus cell culture stimu-lation. In this study, peripheral blood cells were isolated from ten dairy cows and cocultured with S. aureus. Afterward, the γδ T cell subpopulation and the expression of CD44, CD62L and prolif-erative (Ki67+) cells were evaluated by flow cytometry. Our results showed that the percentages of proliferative PBMCs and WC1.1+ γδ T cells were higher when stimulated with S. aureus. The percentage of CD44+ cells increased in S. aureus-stimulated cultured PMBCs and WC1.1+ γδ T cells, as did the CD44 geometric mean fluorescence intensity (GMFI). The rate of CD62L cells did not differ among groups for either PBMCs or WC1.1+ γδ T cells. A higher GMFI of CD62L in prolif-erative PBMCs than nonproliferative PBMCs upon stimulation with S. aureus was detected, whereas no impact on the GMFI of CD62L was observed in WC1.1+ cells. In summary, our study identified that S. aureus was associated with high expression of CD44 in overall PBMCs and WC1.1+ γδ T cells, and they could generate memory WC1.1+ γδ T cells, preferably central memory cells.

The organic extract of the Caribbean sponge Smenospongia aurea has been shown to contain an array of novel chlorinated secondary metabolites derived from a mixed PKS-NRPS biogenetic route, such as the smenamides. Here we report the presence of a biogenetically different compound, smenopyrone (1), a polypropionate containing two -pyrone rings. The structure of smenopyrone, including its relative and absolute stereochemistry, was determined by spectroscopic analysis (NMR, MS, ECD) supported by comparison with model compounds from the literature. Pyrone polypropionates are unprecedented in marine sponges, but are commonly found in marine mollusks, where their biosynthesis by symbiotic bacteria has been hypothesized and at least in one case demonstrated. As pyrones have recently been recognized as bacterial signaling molecules, we speculate that smenopyrone could mediate inter-kingdom chemical communication between S. aurea and its symbiotic bacteria.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine linked to their remarkable healing properties. Several species have chemical and anatomical similarities, often leading to confusion when they are used in folk medicine. This review aims to provide an overview and discussion of the reported traditional uses, botanical aspects, chemical constituents, and pharmacological potential of the Kalanchoe species. Published scientific materials were collected from the PubMed and SciFinder databases without restriction regarding the year of publication through April 2023. Ethnopharmacological knowledge suggests that these species have been used to treat infections, inflammation, injuries, and other disorders. Typically, all parts of the plant are used for medicinal purposes either as crude extract or juice. Botanical evaluation can clarify species differentiation and can enable correct identification and validation of the scientific data. Flavonoids are the most common classes of secondary metabolites identified from Kalanchoe species and can be correlated with some biological studies (antioxidant, anti-inflammatory, and antimicrobial potential). This review summarizes several topics related to the Kalanchoe genus, supporting future studies regarding other unexplored research areas. The need to carry out further studies to confirm the popular uses and biological activities of bioactive compounds is also highlighted.

Pulmonary arteriovenous malformation (PAVMs) in children are rare lesions characterized by abnormal low resistance vascular structures connecting a pulmonary artery to a pulmonary vein, resulting in an intrapulmonary right-to-left shunt. The insidious onset and variable signs&nbsp;and symptoms make diagnosis difficult, especially in children. PAVMs&nbsp; can be single or multiple, congenital or acquired, and up to 47-80% of cases are associated with hereditary hemorrhagic telangiectasia (HHT).We present the&nbsp; case of a 12-year-old female teenager referred to our center for epistaxis, headache, fatigue and weakness, with evidence of mild oxygen desaturation.&nbsp; Bubble test showed a right-to-left shunt and pulmonary angio-CT confirmed the diagnosis. Percutaneous selective embolization was performed with full recovery of normal arterial oxygen saturation. When differentiating between mild oxygen desaturation and exercise intolerance in children and adolescents, physicians should be aware of the possibility of PAVMs as a cause.&nbsp;

Ultraviolet imaging has been applied in volcanology over the last ten years or so. This provides considerably higher temporal and spatial resolution volcanic gas emission rate data than available previously, enabling the volcanology community to investigate a range of far faster plume degassing processes, than achievable hitherto. To date this has covered rapid oscillations in passive degassing through conduits and lava lakes, as well as puffing and explosions, facilitating exciting connections to be made for the first time between previously rather separate sub disciplines of volcanology. Firstly, there has been corroboration between geophysical and degassing datasets at ≈ 1 Hz expediting more holistic investigations of volcanic source-process behaviour. Secondly, there has been the combination of surface observations of gas release, with fluid dynamic models (numerical, mathematical and laboratory) for gas flow in conduits, in attempts to link subterranean driving flow processes to surface activity types. There has also been considerable research and development concerning the technique itself, covering error analysis and most recently adaptation of smartphone sensors for this application, to deliver gas fluxes at a significantly lower instrumental price point than possible previously. At this decadal juncture in the application of UV imaging in volcanology, this article provides an overview of what has been achieved to date as well as a forward look to potential future research directions, in particular covering the first use of UV cameras to generate volcanic gas composition ratio imagery.

Introduction The increase in survival of extremely preterm infants has led to increased rates of bronchopulmonary dysplasia (BPD). Therefore, a potential role of human milk feeding in protecting against this condition has been suggested. Material and methods Retrospective descriptive study based on data about morbidity in the population of infants born from 22+0 to 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and who were alive at discharge. The primary outcome was moderate-severe BPD. In addition, associated conditions were studied, including breastfeeding at discharge. The temporal trends of BPD and breastfeeding rates at discharge were also studied. Results In the study population of 4341 infants who survived to discharge, the rate of moderate-severe BPD was 43,7% and increased over the period to a rate >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were male sex, high-frequency oscillatory ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding at discharge and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901, and OR 0.714, 95% CI 0.602-0.847, respectively). The rates of human milk at discharge in infants with moderate-severe BPD increased over the period. In the last years, more than one-third of extremely preterm infants were discharged on exclusive human milk feeds, and about two-thirds of them on any amount of human milk feeding. Conclusions
The results of the present study strongly support the role of any amount of human milk in preventing BDP in extremely preterm infants.

Hexane is a solvent used extensively in the food industry for the extraction of various products such as vegetable oils, fats, flavours, fragrances, colour additives or other bioactive ingredients. As it is classified as a "processing aid", it does not have to be declared on the label under current legislation. Therefore, although traces of hexane may be found in final products, especially in processed products, its presence is not known to consumers. However, hexane, and in particular the n-hexane isomer, has been shown to be neurotoxic to humans and has even been listed as a cause of occupational diseases in several European countries since the 1970s. In order to support the European strategy for a toxic-free environment (and toxic-free food), it seemed important to collect scientific information on this substance by reviewing the available literature. This review contains valuable information on the nature and origin of the solvent hexane, its applications in the food industry, its toxicological evaluation and possible alternatives for the extraction of natural products. Numerous publications have investigated the toxicity of hexane, and several studies have demonstrated the presence of its toxic metabolite 2,5-hexanedione (2,5-HD) in the urine of the general, non-occupationally exposed population. Surprisingly, a tolerable daily intake (TDI) has apparently never been established by any food safety authority. Since hexane residues are undoubtedly found in various foods, it seems more than necessary to clearly assess the risks associated with this hidden exposure. A clear indication on food packaging and better information on the toxicity of hexane could encourage industry to switch towards one of the numerous other alternative extraction methods already developed.

Relapsed leukemia following initial therapeutic response and remission is difficult to treat and causes high patient mortality. Leukemia relapse is due to residual quiescent leukemia cells that escape conventional therapies and later reemerge. Eliminating not only growing but quiescent leukemia cells is critical to effectively treating leukemia and preventing its recurrence. Such therapeutic agents, however, are lacking in the clinic. Here we report that a 4-arylmethyl derivative of the natural anticancer compound curcumin demonstrates a dual effect in eliminating both growing and quiescent leukemia cells. This curcumin derivative, C212, on the one hand, inhibits growing leukemia cells at a higher efficacy than curcumin by inducing apoptosis and cell cycle arrest; it, on the other hand, kills quiescent leukemia cells that are resistant to conventional chemotherapy drugs. Furthermore, C212 drives leukemia cells into and kills them at deep quiescence, avoiding the potential risk associated with awaking therapy-resistant subpopulation of quiescent leukemia cells. Lastly, we show that C212 induces apoptosis and drives cells into deep dormancy at least partially by binding to and inhibiting Hsp90, leading to client protein degradation and protein aggregation. Further elucidating the molecular mechanisms underlying the dual function of C212 in eliminating both growing and quiescent leukemia cells will aid the development of novel therapies against leukemia relapse.

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained the interest of many scientists thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate cytotoxicity of conventional drugs used to treat melanoma, disclosing new potential therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 μM, to stimulate apoptosis in melanoma cells, while at a non-toxic dose of 250 μM, it affected cell proliferation and induced the downregulation of pAKT/pS6 pathway. 250 μM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increase the cytotoxic effect of Dacarbazine (DTIC). The mayor effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, possibly cooperating in the inhibition of pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and, particularly, RAD001 efficacy on BRAF melanoma cells than Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting pAKT/pS6 pathway.

Objective: The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on comorbid symptoms of depression, anxiety, and fatigue in migraine patients resistant to traditional prophylaxis. Methods: The study was an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis treated with anti-CGRP/R mAbs for 3 months. Results: 77 patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44% respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥ 50% of headache frequency. The two groups were highly homogeneous for investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms were reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. Conclusion: anti-CGRP/R antibodies improve pain together with affection, fatigue, and sensory sensitization in migraine patients.

Background: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first level examination for LVH diagnosis. Cardiac magnetic resonance (CMR) defines accurately LVH type, extent and severity. Objectives: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. Methods: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. Results: Overall, 275 patients had TTE evidence of LVH with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), undetermined LVH in 50(16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%, p<0.0001): the diagnosis of HCM increased from 44% to 71% of patients; hypertensive and undetermined LVH decreased significantly (respectively to 4% and 5%). CMR allowed a diagnosis in 41 out of 50 (82%) with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echo but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change of survival risk of patients: after CMR reclassification no events occurred in patients with undetermined or hypertensive LVH. Conclusions: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patient with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.

Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.

Ocular pathologies present significant challenges in achieving effective therapeutic re-sults due to various anatomical and physiological barriers. Natural products, such as flavonoids, alone or in association with allopathic drugs, present many therapeutical actions, including anti-cancer, anti-inflammatory, and antibacterial action. However, their clinical employment is chal-lenging for scientists due to their low water solubility. In this study, we designed a liquid formu-lation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were de-termined by employing the SupraFit software on the Uv-vis titration experiment. A deep physical-chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it con-firmed the predominant formation of a stable complex (Kc, 9660 M−1) in a 1:1 molar ratio, with high water solubility of 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), per-mitting the dissolution of the solid complex within 30 min. NMR studies revealed the involve-ment of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecu-lar modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains demonstrating a sig-nificant activity of the formulation to the free components.

Our primary objectives were a) to determine the need for, and the availability of point-of-care testing (POCT) for infectious diseases and b) to recommend point-of-care testing strategies and spatial care paths (SCPs) that enhance public health preparedness in regional districts of Thua Thien Hue Province (TTHP), Central Vietnam, where we conducted field surveys. Medical professionals in 7 community health centers (CHCs), 7 district hospitals (DHs) and 1 provincial hospital (PH) participated. Survey questions (English and Vietnamese) determined the status of diagnostic testing capabilities for infectious diseases and other acute medical challenges in TTHP. Infectious disease testing was limited: 6 of 7 CHCs (86%) lacked infectious disease tests. One CHC (14%, 1/7) had two forms of diagnostic tests available for the detection of Malaria. All CHCs lacked adequate microbiology laboratories. District hospitals had few diagnostic tests for infectious diseases (Tuberculosis, Syphilis), blood culture (29%, 2/7), and pathogen culture (57%, 4/7) available. The PH had broader diagnostic testing capabilities but lacked preparedness for highly infectious disease threats (e.g., Ebola, MERS-CoV, SARS, Zika, and Monkeypox). All sites reported having COVID-19 rapid antigen tests; COVID-19 RT-PCR tests were limited to higher tier hospitals. We conclude that infectious disease diagnostic testing should be improved and POC tests must be supplied near patients’ homes and in primary care settings for the early detection of infected individuals and mitigation of the spread of new COVID-19 variants and other highly infectious diseases.

This work shows the preliminary description of the origin of a sedimentary - exhalative outcrop of Jurassic Lower Pliensbachian. The location of this deposit was achieved by applying an examination based in the identification of sedimentary transgressions of heterochronies ages and the identification of a Rift – type mega –structure. According with the methodology, it was carried out a study of the discordant relationships between two types of sediments: continental and marine. According the characterization, it was noted the existence of light rare earths, in values that show positive anomalies in comparison with the distribution of elements in upper continental crust according to the Clarke [1], reflecting so a felsic affinity of the mineral deposit. Also, positive anomalies of platinum and Pd, were determined with marginal contents of Au and Ag; and finally the base metals Zn, Pb and Cu were detected in low contents, which could be due to the presence of altered shale. According to the sedimentary lithology found, which was of siliciclastic type; to the exhalative roots observed during the fieldwork; the presence of quartz minerals such as biotite and muscovite; the presence of minerals of hydrothermal remobilization like chalcopyrite with some base metals, altered shale, as well as sulfur deficiency; this mineral reservoir could be defined as a SEDEX – type.

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta that progressively grows till the rupture. Treatment is typically recommended when the diameter is more than 5 cm. The EVAR (Endovascular aneurysm repair) is a mininvasive procedure that involves the placement of an expandable stent graft within the aorta to treat aortic disease without operating directly on the aorta. For years, stent grafts' essential design was based on metallic stent frames to support the fabric. More recently, a polymer-based technology has been proposed as an alternative method to seal AAA. This review underlines the two platforms that are based on a polymer technology: 1)the polymer-filled endobags, so-called Endovascular Aneurysm Sealing (EVAS) with Nellix stent graft; and 2)the O-ring EVAR polymer-based proximal neck sealing device, so-called Ovation stent graft. Polymer characteristics for this particular aim, clinical applications, and durability results are summarized and commented critically. The platform that embraced the concept of inflating endobags filled with polymer to exclude the aneurysmal sac was not successful because of the lack of an adequate proximal fixation. The platform that used polymer to create a circumferential sealing of the aneurysmal neck has proven safe and effective.

A three-arm, randomized, placebo controlled clinical study has been performed to evaluate the effects of a lyophilized pineapple extract titrated in bromelain (Brome-Inf®), and purified bro-melain on pain, swelling, trismus and quality of life (QoL) after the surgical removal of the lower third molars. Moreover, the need for non-steroidal anti-inflammatory drugs (NSAIDs) has also been evaluated and compared with a placebo group. The study included 42 people that required the extraction of a single mandibular third molar under local anesthesia. The patients were ran-domized and distributed to receive Brome-Inf®, purified bromelain or placebo and started the treatment the day of surgery and continued it for the next 7 days. The primary outcome was the requirement of NSAIDs in the three groups. The outcome variables were pain, swelling and trismus, which were measured postoperatively at 1, 3, and 7 days. The differences in the efficacy of the freeze-dried pineapple extract and single-component bromelain were also evaluated. At the end of the study, the assumption of ibuprofen (from days 1-7) was statistically higher in the placebo group (p