Background: Glioblastomas (GBM) is generally burdened, to date, by a dismal prognosis, although Long Term Survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient- and tumor-related variable on Survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our Institution and classified according their Overall Survival in LTS (Long Term Survivors) and STS (Short Term Survivors). A thorough Review of our surgical series was conducted to compare the oncologic results of the patients in regards to 1. Surgical , 2. Molecular, and 3.Treatment related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the Histochemical point of view, Ki67(%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of 8 prognostic subgroups according to the molecular patterns of Ki67 overexpression and EGFR, p53 and IDH mutations. Conclusions: On the ground of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: KPS, Age, Volume of the lesion, Motor disorder at presentation, a Ki67 overexpression. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.

Background: The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study is to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Methods: changes in PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the trombogram graphic (thrombin variation over time); lagTime; Endogenous Thormbin Potential(ETP); peak; time to reach peak(ttpeak), startTail e velocity Index. Platelet aggregation was assessed by testing different agonists using turbidimetry method. Results: Four FCS patients and 4 matched healthy controls were included in the present study. Changes in PLC at Tw12 was 30% and 34% at T36w. Thrombin generation results show values in normal range (for patients and controls respectively lagTime:10,42±4,40 and 9,25±0,99; ttPeak:14,33± 4,01 and 13,10±0,67; startTail:32,13±3,54 and 29,46±1,69; velocityIndex:20,21±3,63 and 33,05±13,21; ETP 599,80±73,47 and 900,2±210,99; peak value 76,84±1,07 and 123,30±39,45) and no significant difference between cases and controls. Platelet aggregation test showed values in range with no significant difference with healthy controls Conclusions: Our study showed for the first time that no significant changes in the general haemostasis assessed by TG and in platelet function have been observed in FCS patients receiving volanesorsen.

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

Previous research has already examined the relationship between Future Anxiety, a construct recently introduced in Italy, and mental health in young adults, although possible mediating variables in this relationship have so far never been investigated. The present study attempts to fill this gap by exploring the incidence of Future Anxiety on psychological distress in a group of 302 young Italian adults (18 - 30 years; M = 21.9; SD = 2.6), presenting and evaluating the simultaneous mediating effect of Intolerance of Uncertainty and Non-Pathological Worry.Findings highlighted how Future Anxiety had a positive and significant direct effect on Stress and Depression, but not on Anxiety. In the three serial mediation models proposed, Intolerance of Uncertainty and Non-Pathological Worry mediated the relationship between Future Anxiety and mental health outcomes. The results also confirmed the hypothesized serial mediation effect by highlighting how young adults with greater Future Anxiety experienced more Intolerance of Uncertainty, which positively affected Non-Pathological Worry levels and, in turn, exacerbated psychological distress. Finally, results indicated that female participants experienced more Stress, Anxiety, and Depression in relation to Future Anxiety compared to males. Starting from the review of main references on this subject, the results discussed provide new insights for understanding youth psychological distress. Finally, practical implications for the design of supportive interventions for this study’s target group are proposed.

Microalgae cultivation for biotechnological purposes is an expanding field. Their cultivation is usually performed on a liquid culture medium and require the presence of an energy source. Culture media are water-salt solutions containing nitrogen, sulfur, phosphate sources, with trace of transition metals. Light source supplies energy through photosynthesis process, resulting in metabolic reactions and cell growth. Thanks to the huge number of existing species and their diversity, it is possible to exploit alternative water sources with chemical and physical properties far from the commonly used freshwater media. Among these, oilfield or formation waters (AFW) are saline wastewater produced during oil drilling. They represent over 95 % of the total fluids collected from gas and oil wells during fuel extraction. This study exploits the adaptation capability of a Galdieria sulphuraria strain in different salinity conditions to build up a more feasible microalgae-based platform. Batch cultivation of G. sulphuraria was evaluated in a range from 0 to 20 g/L NaCl in terms of growth rate, metabolite content, photophysiology, and intracellular redox state. Moreover, the same strain has been tested for artificial formation water growth in semicontinuous cultivation mode. In these condition, NaCl preadaptation effect has been assessed too. Results clearly demonstrate that biomass composition is influenced from medium salinity. Strains preadapted in 0 to 20 g/L range of NaCl salinity show almost same cell growth profile and a slightly different ratio between lipids, carbohydrates, and proteins. Pigments content and photophysiology point out that variations of osmotic pressure and ionic strength in medium affect Photosystem II (PSII). Regulation of light harvesting is necessary to trigger metabolism shift toward synthesis of metabolites required in the adaptation process.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine therapy is a cornerstone in DTC management, but sometimes it became useless when cancer cells develop refractoriness. Radioactive Iodine Refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used, it has a demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. FA-Pi, PSMA, SSTR tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed to re-induce RAI accumulation in DTC cells. Results appeared promising, despite not excellent. Conclusions: RAIR-DTC yet represent a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation with post-therapy whole body scan (PT-WBS) is the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents oblige physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

In the last decades synthetic jet actuators have gained much interest among the flow control techniques due to their short response time, high jet velocity and absence of traditional piping, that matches the requirements of reduced size and low weight. A synthetic jet is generated by the diaphragm oscillation (generally driven by a piezoelectric element) in a relatively small cavity, producing periodic cavity pressure variations associated with cavity volume changes. The pressured air exhausts through an orifice, converting diaphragm electrodynamic energy into jet kinetic energy. This review paper faces the development of various lumped-element models (LEMs) as practical tools to design and manufacture the actuators. LEMs can quickly predict device performances such as the frequency response in terms of diaphragm displacement, cavity pressure and jet velocity, as well as the efficiency of energy conversion of input Joule power into useful kinetic power of air jet. The actuator performance is analyzed also by varying typical geometric parameters such as cavity height and orifice diameter and length, through a suited dimensionless form of the governing equations. A comprehensive and detailed physical modeling aimed to evaluate the device efficiency is introduced, shedding light on the different stages involved in the process. Overall, the influence of the coupling degree of the two oscillators, the diaphragm and the Helmholtz’s one, on the device performance is discussed throughout the paper.

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet and now widely dis-tributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anti-cancer, insecticidal, antifeedant, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Research on potential uses, under-standing of the nutritional and functional composition, and applications of C. parqui extracts is important and very promising for its commercial use. To date, there are some reports on the potential applications of C. parqui extracts as selective natural pesticides and for their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui as a biopesticide.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

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.

In this work is proposed a new unsupervised method to evaluate the behavior of urban green areas in presence of heatwave scenarios analyzing the NDVI, NDMI and LST satellite data. To evaluate how these three indices characterize urban green areas during periods of heat waves, a reclassification of the data raster of each index is carried out. Rather than using standard classifications of the three indices, an unsupervised classification approach is proposed that uses the Elbow method to determine the optimal number of classes and the Jenks thematic classification method. Each class is assigned a Gaussian fuzzy set with means and standard deviations equal to that of the associated thematic class. The green urban areas are classified using zonal statistics operators and the degree of membership in the corresponding fuzzy set is used to assess the reliability of the classification. Finally, for each type of greenery the frequencies of belonging to the NDVI, NDMI and LST classes are analyzed to evaluate the behavior of the type of urban greenery during heatwaves. The framework was tested in an urban area consisting of the city of Naples (Italy). The results show that some types of greenery, such as deciduous forests and olive groves, are not very vulnerable to heatwave scenarios, unlike uncultivated areas which, instead, show critical behaviors during heatwaves.

Cascading landslides represent a dynamic and hazardous geological phenomenon, char-15 acterized by a sequential chain of slope failures triggered by various factors such as heavy rainfall, 16 seismic activity, or anthropogenic activities. These events can amplify the damage caused by the 17 initial trigger and propagate instability along a slope, often resulting in significant environmental 18 and societal impacts. The Morino-Rendinara cascading landslide, situated in the Ernici mountains 19 along the border of Abruzzo and Lazio region (Italy), serves as a notable example of the complexities 20 and devastating consequences associated with such events. In March 2021, a substantial debris flow 21 event in Morino obstructed the Liri River, marking the latest step in a series of landslide events 22 characterized by a complexity far beyond initial expectations. This study employs a multidiscipli-23 nary approach, combining conventional techniques and advanced technologies, to understand the 24 complexities of the Morino-Rendinara landslide. Field activities, UAV image acquisition, SAR inter-25 ferometry based on SENTINEL-1 images and pixel offset analysis based on high-resolution Google 26 Earth images, offer insights into the geological and hydrogeological setting of the unstable slope, 27 landslide geometry, mechanism and kinematics. To supplement the analysis a specific FEM slope 28 stability analyses is used to reconstruct the deep geometry of the system emphasizing the modula-29 tion action of groundwater flow to the slope stability

Candida spondylodiscitis (CS) is a rare disease, for which therapeutic option are limited to fluconazole or echinocandins and the treatment should be administered up to 12 months. In case of reduced azole susceptibility, there is a scarcity of therapeutic options with adequate bone penetration and limited toxicity. We report the first case of successful use of rezafungin for a spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. The patient, affected by paraplegia and short bowel syndrome, was diagnosed with CS with culture on vertebral biopsy guided by a 18-FDG-PET/CT scan. He received rezafungin 200 mg weekly for 26 weeks, after 10 weeks of previous antifungal treatment. He had a full clinical, radiologic and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin is a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective or contraindicated.

The aim of the present trial was to evaluate the growth performance of buffalo calves fed diets characterized by different forage/concentrate ratio with or without the Saccharomyces Cerevisiae supplementation (CBS 493.94, Yea-Sacc®). Twenty-four male buffalo calves (mean age 145.1 ± 16.1 days; mean weight 108.0 ± 18.7) were assigned randomly to 4 groups, homogeneous for age, fed four different diets: diet 1 F:C ratio 50:50; diet 2 F:C ratio 30:70; diet 3 F:C ratio 50:50 + Yea-Sacc® and diet 4 F:C ratio 30:70 + Yea-Sacc®. Buffalo calves were individually weighted before the start of the experiment and the data were used as a covariate, monthly until the end of the trial. Dry matter intake (DMI), daily weight gain (DWG) and feed conversion ratio (FCR) were calculated. The differences in diets’ composition significantly (p

Background: the study aimed at comparing the prognostic importance of Heart Rate (HR) and of QT corrected (QTc) according to Fridericia, Framingham and Bazett methods, in a large non-selected population. Methods: the analysis of digital Electrocardiograms archived from 2008 to 2022 in the metropolitan area of Modena, Italy, was made. The population under study was divided into three age-groups and survival analysis was performed. Results: 131.627 patients were enrolled and during the follow-up (mean 1641.4 days), all-cause mortality was 8.9%. Both HR and QTc were associated with mortality. All-cause mortality significantly increased from HR values greater than 81 BPM and from QTc values greater than 440 msec in young subjects and 455 msec in old subjects (values of the 75th percentiles/optimal operating point). Cox analysis confirmed the better prognostic value of Bazett’s QTc and of HR in the whole population and in the three age-groups. Conclusion: Bazett’s method performed better than other methods but unexpectedly HR had the same or a better correlation with all-cause mortality. Since HR is simple and readily available, its evaluation should be improved. However, reference values for QTc and for HR are difficult to define causing many confounding factors and further population-study are required.

In the last decade, robotic-mediated rehabilitation has emerged as a potential solution to improve repetitive task training. Each device in this field has a unique development history shaped by engineers’ expertise in specific programming languages or platforms. In this work we adopt an approach that tries to abstract from the final implementation with the aim to make control logic more shareable and understandable. The authors will present the outcomes of the application of a Rapid Control Prototyping strategy to an upper-limb robotic exoskeleton. A model-based design approach implemented on a real-time target machine is presented. This modern design approach was explored with several control strategies and was used to test the exoskeleton’s performances. The proposed method highlights how it is possible to develop the entire control architecture in a single programming environment.

The dissolution of CO₂ in seawater in the form of bicarbonate ions is an attractive alternative to the storage in geological formations, on the conditions that the storage is stable over long times and does not harm the marine environment. In this work, we focus on the long-term chemical stability of CO₂ absorbed in seawater as bicarbonate, by monitoring the physico-chemical properties of the solutions (pH, dissolved inorganic carbon and alkalinity), in six different sets of experiments on both natural and artificial seawater lasting up to three months. The bicarbonate treatment of natural seawater consists in pouring pre-equilibrated solutions obtained from the reaction of CO₂ and Ca(OH)₂. If the pre-equilibrated mixture does not exceed a critical threshold (ca. 1000-1500 mmol/L), the resulting bicarbonate-rich solutions can be stable for over three months.

Background: medical devices are designed, tested and placed on the market in a highly regulated environment. Wearable sensors are crucial components of various medical devices: design and validation of wearable sensors, if managed according to international standards, can foster innovation while respecting regulatory requirements. Material and methods: the purpose of this paper is to take into consideration the upcoming EU Medical Device Regulation 2017/245 and the current and future IEC and ISO standards that set methods for design and validation of medical devices, with a focus on wearable sensors. Risk classification according to the regulation is described. The international standards IEC 62304, IEC 60601, ISO 14971 and ISO 13485 are reviewed to define regulatory restrictions during design, pre-clinical validation and clinical validation of devices that include wearable sensors as crucial components. Results: current and future regulatory restrictions are described, and an integrated method for design planning, validation and clinical testing is described Discussion: application of this method to design wearable sensors should be evaluated in the future in order to assess its potentially positive impact to fostering innovation and to the time-to-market of the device.

The incremental sheet forming represents a relatively recent technology that guarantees high customization, thanks to the layered manufacturing principle typical of rapid prototyping, and cost-effectiveness, because it does not require dedicated equipment. Research has initially shown that this process is effective in metal materials capable of withstanding plastic deformation but, in recent years, the interest in this technique has been increasing for the manufacture of complex polymer sheet components as an alternative to the conventional technologies, based on heating-shaping-cooling manufacturing routes. Conversely, incremental formed polymer sheets can suffer from some peculiar defects, for example twisting. To reduce the risk of this phenomenon and the occurrence of failures, a viable way is to choose toolpath strategies that make the tool/sheet contact conditions less severe, and this represents the main goal of the present research. Polycarbonate sheets were worked by incremental forming; in detail, cone frusta with a fixed wall angle were manufactured with a reference and a stair toolpath strategy, and both the forming forces and the twist angle were monitored. The analysis of the results highlighted that a stair toolpath involving an alternation of diagonal up and vertical down steps represents a useful strategy to mitigate the forming forces and, with them, the occurrence of the twisting phenomenon in incremental formed thermoplastic sheets.

The awareness of the vulnerability of existing structures under both seismic and energy viewpoints highlight the need to develop integrated retrofit solutions combining the structural and thermal performances. In this perspective, the study explores the efficacy of the Resisto 5.9 Tube system, a seismic coat that improves the seismic behaviour of masonry and reinforced concrete (RC) structures, also enhancing their energy performances, thanks to the thermal coat integrated in the basic steel system. The research involves the application of a design procedure specifically developed for this retrofit system from the seismic perspective. Once all the system elements are designed, non-linear static analyses are performed with a Finite Element software comparing the building’s seismic performances before and after the application of Resisto 5.9 Tube. The results demonstrate a significant increase in seismic safety coefficient, proving that this intervention type can be useful to obtain the seismic upgrading of existing RC buildings.

Biopolymers are of growing interest, but to improve some of their poor properties and performance, it is required the formulation of bio-based blends and/or adding of nanoparticles. For this purpose, in this work, two different metal oxides, such as zinc oxide (ZnO) and titanium dioxide (TiO2), at different concentrations (0.5, 1 and 2 %wt.) have been added in polylactic acid (PLA) and polylactic acid/polyamide 11 (PLA/PA11) blends to establish their effects on solid-state properties, morphology, melt behaviour, and photo-oxidation resistance. It seems that the addition of ZnO in PLA leads to a significant reduction of its rigidity probably due to an inefficient dispersion in the melt state, while the addition of TiO2 does not penalise PLA rigidity. Interestingly, the addition of both ZnO and TiO2 in PLA/PA11 blend has a positive effect on the rigidity because of blend morphology refinement and leads to a slight increase in film hydrophobicity. The photo-oxidation resistance of neat PLA and PLA/PA11 blend is significantly reduced due to the presence of both metal oxides, and this must be considered when designing the potential applications. The last results suggest that both metal oxides could be considered as photo-sensitive degradant agents for biopolymer and biopolymer blends.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of HR-HPV infection in female population has led to the discovery of several cases of double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate high risk (HR) HPV infections in women with double cervix within the National Cervical Cancer Screening program of the Lazio Region (Italy). From June 2021 to March 2024 a total of 142,437 samples were analyzed by Seegene’s Anyplex TM II HR-HPV method which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervixes and analyzed separately. Twenty-seven women with double cervix were identified (0.019%): 20 women were tested as negative for both cervices, while the remaining four (namely A, B, C and D) resulted positive. By genotyping, the following results were obtained: A) both samples showed genotype 31; B) one cervix was negative while the other showed genotype 58. C) one cervix was positive for HPV 18 and 31 while for 18, 31 and 33 in the other. D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition, where the presence HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

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

Background. Cervical esophageal reconstruction is vital for improving the quality of life in cancer surgery patients. Microsurgery is crucial, providing vascularized tissue for defect repair, particularly in secondary cases with a higher risk of failure due to larger defects and damage from previous surgery and radiotherapy. The purpose of this study was to describe the clinical characteristics of a series of patients who underwent secondary repair of esophageal defects and provide practical information for the management and treatment of such cases based on the authors' experience and the literature review. Methods. We retrospectively reviewed the electronic medical records of the Plastic Surgery Clinic at the University of Trieste to identify cases of patients who underwent secondary esophageal microsurgical reconstructions following oncological surgery. Patient demographics, etiology of esophageal defects, previous surgical history, and preoperative assessments were collected from medical records. Surgical techniques employed for reconstruction, such as pedicled flaps or free tissue transfers, were documented along with intraoperative details. Postoperative outcomes, including complications, graft viability, and functional outcomes, were evaluated during follow-up. Results. We treated 13 cases of secondary esophageal reconstructions from 2011 to 2022. Most commonly, Antero-Lateral Thigh (ALT) flaps were used in 10 cases, while 2 cases employed Radial Forearm Flap (RFF), and 1 a chimeric parascapular flap. No flap failures occurred during a median 50-month follow-up. One ALT flap patient experienced post-op stricture but maintained swallowing ability. A single tracheoesophageal fistula occurred in a RFF patient with a history of radiotherapy and completion lymph node dissection. Conclusions. Cervical esophageal reconstruction significantly impacts patients' quality of life by restoring oral feeding and phonation. When local flaps fall short, microsurgical reconstruction with intestinal flaps is valuable, but burdened by limitations. For challenging secondary cases, ALT or RFF flaps emerge as safer options due to their robust pedicles, yielding low complication rates and positive functional outcomes.

The firmware developed for the readout and trigger processing of the information emerging from BIS78-RPC Muon Spectrometer chambers in the ATLAS experiment at CERN, is presented here, together with data processing techniques, data acquisition software and tests of the readout chain system, on the road to make these chambers operational in the ATLAS experiment. This work is performed in the context of the BIS78-RPC project, which deals with the pilot deployment of a new generation of sMDT+RPC chambers in the experiment. Such chambers are planned to be fully deployed in the whole barrel inner layer of the Muon Spectrometer during the Phase-II upgrade of the ATLAS experiment. On-chamber front-ends include an amplifier, a discriminator ASIC and an LVDS transmitter. The signal is digitized by CERN HPTDC chips and then processed by an FPGA which is the heart of the readout and trigger processing, using various techniques. The work presented here is a continuation of the work presented in [1].

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Insulin resistance/hyperinsulinemia as an independent risk factor for the development and worsening of HFpEF. Serafino Fazio MD¹, Valentina Mercurio MD, PhD2, Valeria Fazio MD3, Antonio Ruvolo MD⁴, Flora Affuso MD, PhD⁵. Authors’ Affiliation: ¹ Department of Internal Medicine (retired Professor). Federico II University, Via Sergio Pansini 5. 80135 Naples, Italy. 2 Department of Translational Medical Sciences. Federico II University. Via Sergio Pasini 5. 80135 Naples, Italy. ³ UOC Medicina Interna, Azienda Ospedaliera di Caserta, 81100 Caserta, Italy, ⁴ UOC Cardiologia AORN dei colli PO CTO, Viale Colli Aminei 21, 80100 Naples, Italy. ⁵ Independent researcher, Viale Raffaello 74, 80129 Naples, Italy. Abstract Heart failure (HF) has become a subject of continuous interest since it has been declared new pandemic in 1997 because of the exponential increase in hospitalizations for HF in the latest years. HF is the final state to which all heart diseases of different etiologies lead if not adequately treated, therefore it is highly prevalent worldwide, with a progressive increase with age, reaching a prevalence of 10% in subjects over the age of 65 years. It should also be underlined that lately, while the prevalence of HF with left ventricular reduced ejection fraction (HFrEF) is slowly decreasing, the incidence of HF with left ventricular preserved ejection fraction (HFpEF) is progressively increasing. In deed, among patients consecutively hospitalized for HF between 1987 and 2001 in a study from the Mayo Clinic Hospitals in Olmsted County, Minnesota, prevalence of HFpEF increased from 38% to 54%. HFpEF is typically characterized by concentric remodeling of the left ventricle (LV) with impaired diastolic function and increased filling pressures. Over the years, also the prevalence of insulin resistance/hyperinsulinemia in the general adult population has progressively increased, primarily due to lifestyle changes, particularly in developed and developing countries, with a range that globally ranges between 15.5% and 46.5%. Notably, insulin resistance (IR)/hyperinsulinemia (Hyperins) is present in up to 60% of patients with HF and is significantly higher in subjects with HfpEF. In the scientific literature it has been well highlighted that the increased circulating levels of insulin are associated with conditions of insulin resistance are responsible for progressive cardiovascular alterations over the years. In the setting of HFpEF, insulin stimulates the concentric remodeling of the left ventricle with associated diastolic dysfunction, which, coincidentally. Unfortunately, IR/Hyperins, despite being a well-known cardiovascular risk factor, is still not screened in the general population and is not treated as promptly as it should be, and this could at least in part concur in the progressive increase in prevalence of HFpEF in the general adult population. The aim of this manuscript was to review scientific literature that support a pathophysiologic connection between IR/Hyperins and HFpEF to stimulate the scientific community towards the identification of hyperinsulinemia associated with insulin resistance as an independent cardiovascular risk factor in development and worsening of HF, believing that its adequate screening in the general population and appropriate treatment could reduce the prevalence of HFpEF and improve its progression.

This study evaluated the effect of pig diet supplementation with an Olea europaea L. extract on the muscle fatty acid composition. Ten commercial hybrid pigs (Large White x (Landrace x Duroc)) were randomly assigned to two experimental treatments and fed either a standard diet (C) or diet with olive leaves extract (OL). For 90 days, the OL group received the olive leaf extract (300 mg/head/day), which mainly comprises oleuropein diglucoside, luteolin-7-glucoside, and verbascoside. The phenolic content, antioxidant activity, bioactive molecules’ characterization, and the fatty acids profile of meat and diet were performed. The results indicated that while the OL supplementation did not significantly alter the overall chemical composition of the meat or the pigs' performance, it did modify the lipid profile of the meat. The OL diet results in a significant reduction in SFA and an increase in oleic acid in meat, which correspondingly elevates the total MUFA content. Dietary treatment reduced the sum of n-6 PUFA in the meat of the OL group, and resulted in a significantly lower n-6/n-3 PUFA ratio. Therefore, these findings suggest that incorporating olive leaf extract into the pig diet enhances the nutritional and functional quality of the meat by improving its fatty acid profile.

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

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Industries, which are mainly responsible for high energy consumptions, need to invest in research projects in order to develop new managing systems for rational energy use and to tackle the devastating effects of climate change caused by human behavior. The study reported in this paper concerns the forging industry, where the production processes generally start with the heating of the steel in furnaces and continue with other processes, such as heat treatments and mechanical machining. One of the most critical operations, in terms of energy loss, is the opening of the furnace doors for the insertion and extraction operations. During this time, the temperature of the furnaces decreases by hundreds of degrees in a few minutes. Because the dispersed heat needs to be supplied again through the combustion of fuel, increasing the consumption of energy and the pollutant emissions, the evaluation of the amount of the lost energy is crucial for the development of operating or mechanical systems able to contain this dispersion. To perform this study, CFD simulation software was used. Results show that at the door opening, because of temperature and pressure differences between the furnace and the ambient, turbulences are generated. Results also show that the amount of energy lost for an opening of 10 minutes for radiation, convection and conduction is equal to 5606 MJ where convection is the main contributor with 5020 MJ. The model created, after being validated, has been applied to perform other simulations in order to improve the energy performance of the furnace. Results show that a reduction of the opening time of the door allows energy savings and limits pollutant emissions.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C>T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C>T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

In this work, we propose an in-house simulation tool designed for the analysis and optimization of bifacial photovoltaic (PV) modules, which are currently under the spotlight in the renewable energy scenario. The tool is conceived to support researchers and engineers by providing fast and accurate predictions of the PV module yield under various operating and environmental conditions. For a chosen geographical site, the impact of module orientation, tilt, albedo, sky conditions, ambient temperature, and so on, can be effortlessly determined. In case of nonuniformity across the cells dictated by localized architectural shading, dirt, bird drops, defects, a circuit-based cell-level approach can be activated to compute the module production. An extensive simulation campaign is performed by assuming that the panels are installed in Naples without loss of generality. Results are shown to give detailed insights into the performance of bifacial modules, thus providing unambiguous guidelines for their correct installation. Further analyses are conducted to demonstrate the tool capability to quantify the detrimental influence of a poorly-irradiated cell on the backside, as well as of cracked cells.

Ultrasound (US) scans of the inferior vena cava (IVC) provide useful information on the volume status of a patient. However, their investigation is user-dependent and prone to measurement errors. An important technical problem is the objective difficulty in studying a very compliant blood vessel like IVC, which makes large respirophasic movements and shows a complicated three dimensional geometry. Using bi-dimensional (2D) B-mode views either in long or short axis has improved the characterization of IVC dynamics compared to a measurement along a single direction (M-mode). However, specific movements of the IVC can challenge also the information provided by these 2D sections. Thus, these two orthogonal views, provided by an US system in X-plane, are here integrated by an innovative method. It is tested on simulated videos of the IVC performing complicated movements, that are compensated by the new method, overcoming the biased measurements provided by 2D scans. The method is then applied on example experimental data.

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody blocking the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists have been reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, have been reported. This review explores results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Hematological malignancies refer to a heterogeneous group of neoplastic conditions of lymphoid and hematopoietic tissues classified in leukemias, Hodgkin and non-Hodgkin lymphomas and multiple myeloma, according to their presumed cell of origin, genetic abnormalities, and clinical features. Metabolic adaptation and immune escape, which influence various cellular functions including proliferation and survival of hematological malignant tumor cells, are major aspects of these malignancies that lead to therapeutic drug resistance. Targeting specific metabolic pathways is emerging as novel therapeutic strategy in hematopoietic neoplasms, particularly in acute myeloid leukemia and multiple myeloma. In this context, CD147, also known as Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) or Basigin, is one target-candidate involved in reprogramming metabolism in different cancer cells, including hematological malignant tumor cells. CD147 overexpression significantly contributes to the metabolic transformation of these cancer cells, by mediating signaling pathway, growth, metastasis and metabolic reprogramming, through its interaction, direct or not, with various membrane proteins related to metabolic, regulation including monocarboxylated transporters, integrins, P-glycoprotein and Glucose Transporter 1. This review explores the metabolic functions of CD147 and its impact on the tumor microenvironment, influencing the progression and neoplastic transformation in leukemias, myeloma and lymphomas. Furthermore, we highlight new opportunities for the development of targeted therapies against CD147, potentially improving the treatment of hematologic malignancies.

Background: Permanent tracheostomy because of total laryngectomy surgery entails great conse-quences for the patient regarding respiratory physiopathology such as the filtering, humidifying, and heating function of the air by the nose is lost. The use of special stomal filters can determine adequate protection of the trachea-broncho-pulmonary system with a reduction in respiratory pathologies. In fact, in most cases laryngectomee patients are first cigarette smokers who for this reason already have also respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, multiple times, as reported in the literature, the patient tends to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for the laryngectomee patient during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomee patients, subjected to medi-um-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT) which involves a sustained walk lasting six minutes, with evaluation , every 60 seconds, heart rate, oxygen saturation and meters travelled; furthermore, it examines two sub-jective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR>MTYR>>TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

(1) Background: The aim of this investigation is to determine the effect of archwires’ deflection on the temperature transitions driving the austenite to martensite transformation (and vice versa) and the force released by NiTi and CuNiTi orthodontic wires. (2) Methods: Round cross-section archwires have been investigated. The calorimetric approach has been used for measuring transition temperatures occurring in the unstressed (e.g. undeflected) state of the wires. Static Thermo-mechanical analysis in a temperature controlled wet environment has been performed in the range of temperature between 5°C and 55°C for measuring temperature transitions occurring in highly deflected archwires in conjunction with the force released by these wires. (3) Results: Plateau forces investigated in Part I and those reported in the literature describes the wire’s behaviour only at deflection levels close to the end point of the force plateau extension detected at 37°C. Upon heating or cooling, the austenite finish (Af) transition temperature and the martensite start (Ms) temperature largely depends on the deflection level for both NiTi and CuNiTi. (4) Conclusions: The plateau force levels at 37°C, broadly reported in the literature, only represent the lower boundary force that a superelastic wire releases at 37°C above its elastic limit. For both NiTi and CuNiTi, plateau force levels at 37°C can be predicted by the static TMA profile matching the end point of the force plateau extension. Transition temperatures in largely deflected wires are significantly higher than those determined through the calorimetric approach.

Over the past thirty years, the red gorgonian Paramuricea clavata in the Mediterranean Sea has faced increasing threats, including heat waves and human activities such as fishing and diving. Epibiosis on damaged gorgonian colonies is generally used as an indirect indication of stressed conditions. The density and height of P. clavata and the percentage of colonies affected by epibiosis and entangled in lost fishing gear were studied to investigate the phenomenon and its trend over time in the Ligurian Sea. Analyses were based on transects collected during ROV campaigns between 2015 and 2022 at depths of 33-90 meters. A strong correlation was observed between fishing effort in the study area and the level of epibiosis. Maximal percentages of colonies affected by epibiosis and entanglement were recorded at depths of 50-70 meters. Temporally, marine heat waves before 2019 were identified as the primary cause of damage to P. clavata. The decrease in epibiosis percentages after 2019, despite the 2022 heat wave, may be due to a quick recovery ability of the populations and a reduction in fishing activities during the COVID-19 lockdown in 2020. Long-term monitoring programs are essential to understand the changes in marine benthic communities exposed to different stressors.

The United Nations’ Agenda 2030 has established a series of Sustainable Development Goals to address global challenges, including poverty, food insecurity, access to education, and social inequality. In this context, charitable organizations such as Caritas play a crucial role in mitigating the negative effects of these challenges and promoting fair and sustainable development. This study aims to analyze prevalent needs among individuals seeking assistance from Caritas in Campania and examine how the organization contributes to achieving the Agenda 2030 Goals in the region. The statistical investigation techniques considered include tandem analysis [], which considers a dimension-reduction technique, such as multiple factor analysis, and, then cluster analysis to identify similar groups of individuals. These exploratory data analysis methods have allowed for the identification of common needs, including food assistance, support for education, employment, and housing assistance. Subsequently, Caritas programs and initiatives aimed at meeting these needs and promoting sustainable development are explored. The results indicate that Caritas plays a significant role in addressing the urgent needs of the vulnerable population in Campania and contributes to the goals of Agenda 2030, particularly those related to poverty alleviation, immigration, health promotion, education, employment, and reduction of social inequalities. This study provides an important perspective on the relevance and effectiveness of Caritas’ work in the context of Agenda 2030.

Lumpy skin disease (LSD) is a viral disease of cattle and water buffalo characterized by cutaneous nodules, biphasic fever and lymphadenitis. LSD is endemic in Africa and Middle East but in recent years has spread in different Asian countries. Drop of animal productions, vaccination campaign, surveillance costs and trade restrictions have significant impact on the economy of affected countries. The disease is well characterized in cattle while little is known in buffaloes and no experimental studies have been conducted in this species. Six buffaloes and two cattle were inoculated with an Albanian LSD virus (LSDV) field strain. Over a period of 42 days animals were clinically monitored and sampled for serological and virological analysis. Only two buffaloes showed clinical sign, fever, skin nodules and lymphadenitis. All samples tested in real time PCR (blood, swabs, biopsies and organ) gave negative results. Three buffaloes seroconverted at day 39 and 42 post-inoculation, detected by ELISA, but all sera were negative in serum neutralization test. Cattle showed more severe clinical signs. Moreover, viraemia and virus shedding were proven by positive PCR results and antibodies were detected by both ELISA and serum neutralization test. These findings demonstrated the limited susceptibility of buffaloes compared to cattle once experimental infected with LSDV. Further studies are needed to investigate the epidemiological role of the buffaloes.

Segregating one space from another is a rudimentary act of architecture and the basic principle of this act is creating differentiation between outside and inside. Thresholds, in their expanded or summed form, also produce spaces. They establish the staging for threshold areas in conjunction with space-defining elements. Threshold spaces are typically complicated spatial formations that serve as transition points. They pose a challenge to the interacting human senses in terms of perception. In this research threshold areas have been studied under a specific typology of architecture i.e the traditional housing in historic cities of India. The traditional dwelling settlements have evolved and grown over multiple layers of history, influenced by the culture, society, economy, climate and topography. The purpose of this research is to examine the characteristics of these transition spaces of the traditional dwelling units in relation to the symbolic reference and social meanings assigned to them that influence the architectural and urban spaces attached to them. It seeks to describe transition space in terms of its nature, character, morphology, and social significance. Transparency and material articulation, as well as hierarchy and enclosure, will be investigated. The importance and quality of the nature of "transition" will be examined from the inside to the outside. The research reveals that the space has great functional and socio-cultural importance. It allows multiple activities, provides protection from sun and rain, defines boundaries, connects people within the neighborhood, enhances security and gives an identity to the owner. The contributions made by this research have the potential to improve design considerations for transition areas between the dwelling units and the street.

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

This paper describes the first results of an Image Recognition Based Location (IRBL) for mobile application focusing on the procedure to generate a Database of range images (RGB-D). In an indoor environment, to estimate the camera position and orientation, a prior spatial knowledge of the surrounding is needed. In order to achieve this objective a complete 3D survey of two different environment (Bangbae metro station of Seoul and E.T.R.I. building in Daejeon – Republic of Korea) was performed using LiDAR (Light Detection And Ranging) instrument and the obtained scans were processed in order to obtain a spatial model of the environments. From this, two databases of reference images were generated using a specific software realized by the Geomatics group of Politecnico di Torino (ScanToRGBDImage). This tool allow to generate synthetically different RGB-D images) centered in the each scan position in the environment. Later, the external parameters (X, Y, Z, ω, φ, κ) and the range information extracted from the DB images retrieved, are used as reference information for pose estimation of a set of acquired mobile pictures in the IRBL procedure. In this paper the survey operations, the approach for generating the RGB-D images and the IRB strategy are reported. Finally the analysis of the results and the validation test are described.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

Treatment of HIV-associated lymphoma (HIV-Ly) with autologous stem cell transplantation (ASCT) has shown a surprisingly low relapse rate in several series. The aim of this study was to compare the clinical outcomes of HIV-Ly and lymphomas of the general population receiving ASCT. We compared two series of consecutive HIV-positive and HIV-negative patients, based on a 1:1 propensity score analysis, matching for age, sex, histology, disease status and prior therapies. We identified 44 patients in both groups. All HIV-positive patients received combination antiretroviral therapy (cART). With a median follow-up of 51 months, PFS was significantly higher in HIV-positive patients (4-years PFS 81% and 51%, in HIV-positive and HIV-negative patients, respectively, p=0.027). Four-year OS was 81% for HIV-positive and 67% in HIV-negative patients (p=0.15). The relapse rate was significantly higher in HIV-negative patients (36% vs 23%) (p=0.04). Our results clearly show that ASCT is an effective curative option for HIV-Ly, with better PFS and lower relapse rate compared to uninfected patients. A favourable effect of ASCT on HIV infection and immune system recovery, potential off-target effects of cART or other yet unknown factors may account for this observation.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

The aim of the present study was to investigate the incidence of breast (females), prostate, testicular and thyroid cancer in the Italian National Priority Contaminated Sites (NPCSs), served by cancer registries, where the presence of endocrine disruptors (EDs), reported to be linked to these tumors, was documented. Evidence of carcinogenicity of EDs present in NPCs was assessed based on evaluation by international scientific institutions/committees. Standardized Incidence Ratios (SIRs) were computed for each NPCS and cancer site with reference to the time window 1996-2005. Excess incidence of one or more cancer site at study was found in twelve out of fourteen NPCSs. Significantly increased SIRs were found for breast cancer in eight NPCSs, for prostate cancer in six, for thyroid cancer (both gender) in four and for testicular cancer in two. Non significantly increased SIRs were found in five NPCSs for testicular cancer and in two for thyroid cancer (males). Even if increased incidence of one or more cancer sites at study were found in several NPCSs, the ecological study design and the multifactorial etiology of the considered tumors do not allow reaching conclusions in terms of causal links with environmental contamination. In light of the observation of some excesses in SIRs, continuing epidemiological surveillance is warranted.

Urinary tract infections in kidney transplant patients are a real challenge. We conducted a retrospective observational study, enrolling all kidney transplant patients hospitalized for urinary tract infection (UTI), with the objective to evaluate the epidemiology, clinical sta-tus, therapeutic management, and clinical outcome of kidney transplant patients hospi-talized for urinary tract infection in a university hospital. From our real-life experience, infection with multidrug-resistant germs was confirmed as a risk factor for the severe evolution of the infection and at the same time the re-evaluation of immunosuppressive therapy could be an important therapeutic strategy in the course of infection. Prompt ini-tiation of empiric antibiotic therapy upon initiation of microbiological investigations could potentially reduce the risk of severe infection progression.

Art therapy has a long history of applications in cognitive and motor rehabilitation. More recently, a growing body of scientific literature has highlighted the potential of virtual reality in neurorehabilitation, though it has focused more on the technology itself than on the principles adopted in digital scenarios. This study is a randomized controlled trial conducted on 40 patients with stroke, comparing a protocol of art therapy administered in virtual reality, which exploits the so-called Michelangelo effect, to conventional therapy. After 12 sessions, patients in the virtual art therapy group showed a significantly greater improvement in independence in activities of daily living, as assessed by the Barthel Index (interaction of time and group: p<0.01). Significant differences were also found in terms of upper limb muscle strength (Manual Muscle Test, p<0.01) and reduction in spasticity (Ashworth scale, p<0.01) in favor of the experimental group. In the virtual art therapy group, the effectiveness of the intervention was significantly correlated with patient participation (Pittsburgh Rehabilitation Participation Scale: R=0.45), patient satisfaction (R=0.50), and the perceived utility of the intervention by the therapist (R=0.47). These findings support the efficacy of virtual art therapy leveraging the Michelangelo effect. Further studies should also focus on cognitive domains that could benefit from this type of approach.

This paper presents the design and analysis of a novel 3-degree-of-freedom (3-DOF) parallel ma-nipulator equipped with self-sensing Ni-Ti (Nitinol) actuators. The manipulator's architecture and mechanical design are elucidated, emphasizing the integration of Nitinol actuators. The self-sensing technique implemented in a previous work was extended to a 20 mm actuator length, and the actuator was used to design the 3 DOF manipulator. Kinematic analyses were conducted to eval-uate the manipulator's performance under various operating conditions. A dynamic model was implemented for the dynamic dimensioning of the actuators, which work synergistically with a bias spring. The manipulator was realized, and a control strategy was implemented. Experimental tests, although documenting some positioning accuracy issues, show the efficacy and potential applica-tions of the proposed manipulator in robotics and automation systems, highlighting the advantages of self-sensing Nitinol actuators in small parallel manipulator designs.

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

By performing DSC measurements on RNase A, we studied the stabilization provided by the addition of potassium aspartate or potassium glutamate, that leads to a significant increase in the denaturation temperature of the protein. The stabilization proves to be mainly entropic in origin. A counteraction of the stabilization provided by KAsp or KGlu is obtained by adding common denaturants such as urea, guanidinium chloride and guanidinium thiocyanate. A rationalization of experimental data is devised on the basis of a theoretical approach developed by one of us. The main contribution to the conformational stability of globular proteins comes from the gain in translational entropy of water and co-solute ions and/or molecules for the decrease in solvent-excluded volume associated with polypeptide folding (i.e., there is a large decrease in solvent-accessible surface area). The magnitude of this entropic contribution increases with the number density and volume packing density of the solution. The two destabilizing contributions come from the conformational entropy of the chain, that should not depend significantly on the presence of co-solutes, and from the direct energetic interactions between co-solutes and the protein surface in both the native and denatured states. It is the magnitude of the latter to discriminate between stabilizing and destabilizing agents.

In marine ecosystems communication among microorganisms is crucial since the distance is significant if considered on a microbial scale. One of the ways used by microorganism cells to reduce this gap is the production of extracellular vesicles. Marine bacteria release extracellular vesicles (EVs), small membrane-bound structures of 50 to 250 nm diameter, into their surrounding environment. The vesicles contain various cellular compounds, including lipids, proteins, nucleic acids, and glycans. EVs may mediate the communication between microorganisms in aquatic environments thus influencing ecosystem function and determining the structure and composition of microbial populations. This review will focus on marine bacterial EVs analysing their structure, composition, functions, and applications.

Knee osteoarthritis (KOA) is a progressive and multifactorial disease that leads to joint pain, muscle weakness, physical disability, and decreased quality of life. In KOA, hyaluronic acid (HA) quantity and molecular weight (MW) are decreased, leading to joint pain due to increased wear of the knee articular cartilage. Arthrogenic muscle inhibition, which is usually found in patients with KOA, is associated with joint inflammation, pain, and swelling, also causing muscle atrophy, primarily of the anterior thigh muscles, and hindering the rehabilitation process. The aim of our work was to determine if a single HA infiltration could minimize the effects of arthrogenic muscle inhibition in patients with KOA in the short term, using isokinetic dynamometry to evaluate the strength of the knee extensor and flexor muscles of the thigh. Thirty patients with KOA who underwent both clinical and isokinetic assessment, and that received a single injection of HA, were retrospectively included. Our results showed that a single intra-articular injection of HA significantly reduces pain and improves joint function at four weeks, while non-statistically significant improvements were observed for the reference isokinetic parameter (maximum torque) at both 90°/s and 180°/s. Further high-quality studies are necessary to confirm the results of our study.

Monitoring the integrity of aeronautical structures is fundamental for safety. Structural Health Monitoring Systems (SHMS) perform real-time monitoring functions, but their performances must be carefully assessed. In this work the damage detection performances of a strain-based SHMS, were evaluated on a composite helicopter rotor blade root. The SHMS monitored the bonding between the central core and the surrounding antitorsional layer. A damage detection algorithm was trained through Finite Element analyses performed on the component. The effects of the loads variability and of damages were decoupled by including a load recognition step in the algorithm. Load recognition was accomplished in different ways: version#1 adopted an Artificial Neural Network (ANN) trained on blades in pristine condition; version#2 was trained also on damaged blades; version#3 adopted a calibration matrix method. Anomaly detection, damage assessment, and localization were performed by using an ANN. Results showed a higher load identification and anomaly detection accuracy for version#1 and version#2 compared to version#3. Gaussian noise reduced anomaly detection and damage assessment performances, and reduced damage localization accuracy for bigger damages. The damage detection performance were obtained for a fibre optic based-SHMS, including the trade-off between probability of detection and false alarm rate for different damage sizes.

Although the field of geomatics has seen multiple technological advances in the recent years which enabled new applications and simplified the consolidated ones, some tasks remain challenging, inefficient, and time- and cost-consuming. This is the case of accurate tridimensional surveys of narrow spaces. Static laser scanning is an accurate and reliable approach but impractical for extensive tunnel environments; portable laser scanning is on the other hand time-effective and efficient but not very reliable without ground control constraints. This paper describes the development process of a novel image-based multi-camera system meant to solve this specific problem: delivering accurate, reliable, and efficient results. The development is illustrated from the system conceptualization and initial investigations to the design choices and requirements for accuracy. The resulted working prototype has been put to the test to verify effectiveness of the proposed approach.

while enjoying a relative positive revival in the digital age, Esperanto and the assessment of its language vitality is often problematic and prone to gross errors, and therefore a theoretical re-flection is required. Unlike other lesser-used languages, Esperanto is intergenerationally trans-mitted mainly outside the family, and so Fishman’s GIDS and subsequent scales such as the EGIDS cannot be applied straightforwardly for language vitality diagnosis and estimation. In particular, it is the social movement with its language activists who guarantee its vitality and developing, for more than a century. A key aspect is the digital domain, where the relatively good positioning of Esperanto does not reflect in a parallel increase in the number of activists. This paper critically assesses the digital language vitality of Esperanto on the basis of its language ide-ology and other sociolinguistic data as a starting point for a discussion to overcome the limits of Blanke’s (2006) scale of language vitality of Esperanto and its rivals. This assessment eventually leads to a more general reflection on the role of ‘coolification’, i.e., the positive effects on language attitudes and development thanks to digital visibility, its limits and the issue of placing it in the context of language vitality in general.

In this paper we explore extending the concept of common cross-study Common Data Element concepts beyond simple demographics to cover disease-specific concepts relevant to imaging. We test interactively linking the resulting database to the associated images in a federated manner. We examine the use of existing standards, not only for terminology, but for interchange of serialized data in forms familiar to imaging and clinical trials specialists and their dedicated systems. Our intent is to perform preliminary work to inform both the upcoming Imaging Data Commons specifically, as well as more general integration projects beyond imaging.

It has long been known that phytohormone auxin plays a promoting role in tuber formation and stress tolerance in potatoes. Our study aimed to identify and characterize the complete sets of auxin-related genes that presumably constitute the entire auxin signaling system in potato (Solanum tuberosum L.). The corresponding genes were retrieved from sequenced genomes of the doubled monoploid S. tuberosum DM1-3-516-R44 (DM) of the Phureja group, the heterozygous diploid line RH89-039-16 (RH), and the autotetraploid cultivar Otava. Both canonical and noncanonical auxin signaling pathways were considered. Phylogenetic and domain analyzes of deduced proteins were supplemented by their expression profiling and 3D molecular modeling. The canonical and ABP1-mediated pathways of auxin signaling appeared to be well conserved. Total number of potato genes/proteins presumably involved in canonical auxin signaling is 46 and 108 in monoploid DM and tetraploid Otava, respectively. Among studied potatoes, spectra of expressed genes obviously associated with auxin signaling were partly cultivar-specific and quite different from analogous spectrum in Arabidopsis. Most of the noncanonical pathways found in Arabidopsis appeared to be low probable in potato. This was equally applied to all cultivars used irrespective of their ploidy. Thus, some important features of the (noncanonical) auxin signaling pathways may be variable and species-specific.

In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of aryl piperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine com-pounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. This review, providing a careful analysis of different arylpiperazine deriva-tives and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.

The commercial aviation industry is constantly evolving, driven by technological innovation and the growing demand for more efficient and environmental friendly transportation solutions. In this context, the design and development of next-generation aircraft is a crucial task, with the goal of reducing environmental impact and improving flight efficiency while continuing to ensure passenger comfort and safety. This paper aims at evaluating the technical feasibility as well as economic and environmental viability of a narrow body aircraft powered by hydrogen for direct combustion. Notably, the paper offers innovative insights regarding the update of literature models for conceptual design, in order to consider the impact of hydrogen fuel on the sizing loop at aircraft level. Moreover, it also focuses on the evaluation of operating costs for the aforementioned aircraft class, highlighting the required model updates and considerations to properly match the effect on costs of the introduction of the innovative fuel. Ultimately, a preliminary analysis of upstream sustainability of the concept, considering fuel life cycle, is provided, in order to understand the overall competitiveness, not only in terms of monetary resources but also of environmental impact, beyond the pure operating life of the airplane.

Laser-Powder Directed Energy Deposition (DED-LB/Powder) is an additive manufacturing process that is gaining popularity in the manufacturing industry due to its numerous advantages, particularly in repairing operations. However, its application is often limited to case studies due to some critical issues that need to be addressed, such as the degree of internal porosity. This paper investigates the effect of the most relevant process parameters of the DED-LB/Powder process on the level and distribution of porosity. Results indicate that, among the process parameters examined, porosity is less affected by travel speed and more influenced by powder mass flow rate and laser power. Additionally, a three-dimensional finite element transient model was introduced, which was able to predict the development and location of lack-of-fusion pores along the building direction.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

(1) Background: A wide literature based on loading and unloading bending tests has been carried out over the half past century for assessing the force released by superelastic wires. The aim of this investigation is not only to characterize a broadly described superelastic NiTi and a novel CuNiTi archwire, but also to provide novel insights into the load vs deflection profiles. A harmonic scenario for superelastic wires will be shown as temperature is kept constant at 37°C. However, a completely different picture will be highlighted as a temporary heating step up to 50°C is introduced within the force vs deflection profiles. (2) Methods: A variety of NiTi and a novel CuNiTi round and rectangular cross-section archwires have been investigated. Static 3-point bending tests up to a deflection level of 3.0 mm have been carried out for detecting the unloading force plateau levels occurring at 37°C. A hold deflection step of 5 min at deflection levels occurring along the unloading plateau extension is introduced. The effect of a temporary heating up to 50°C on the force plateau level released by the investigated wires is analyzed. (3) Results: Mechanical profiles suggest that the plateau force levels detected at 37°C are consistent with those broadly reported in the literature, but they only represent a single block puzzle of the force scenario that a superelastic wire releases during the orthodontic treatment. (4) Conclusions: Once a superelastic wire is bent and clinically applied, the effect of a temporary heating up to 50°C (e.g. hot food or drink ingestion) produces a significant plateau force increase whose magnitude depends on the deflection level. The highest force increase of about 50% and 40% have been detected at deflection levels located at the beginning of the unloading plateau extension for NiTi and CuNiTi wires, respectively.

Chronic wounds remain a significant clinical challenge, necessitating the exploration of novel therapeutic agents. Sedum telephium L. (syn. Hylotelephium telephium (L.) H. Ohba) leaf juice, known for its traditional medicinal uses, was evaluated for its wound healing properties. This study aimed to chemically characterize the leaf juice and assess its efficacy in promoting wound healing in vitro. Fresh leaves were collected and processed to obtain the juice, which was analyzed for polyphenols, flavonoids, polysaccharides, and proteins. Key bioactive compounds, including flavonols such as kaempferol glycosides and quercetin glycosides, were identified. The juice and its polysaccharidic fraction were tested on human keratinocytes (HaCaT) and fibroblasts (HFF-1) to assess cell viability, wound closure, and the production of growth factors and pro-collagen I. Our results indicated that the whole juice significantly enhanced wound closure in both cell types, with a marked increase in fibroblast growth factor (FGF) and LAP(TGF-β1) production in keratinocytes, highlighting its potential mechanisms of action. The polysaccharidic fraction alone showed limited efficacy, emphasizing the importance of the complete phytocomplex. These findings suggest that Sedum telephium L. represents a promising candidate in the setting of skin regeneration and repair.

Background The acknowledgment of computed tomography (CT) defined diagnosis in high prevalence northern Italy may identify more patients with Coronavirus Disease-2019 (COVID 19) infection, than RT-PCR alone. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1st of February 2020 to 30th of April 2020, during the Covid-19 outbreak in Bergamo area. Therefore, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with diagnosis of COVID-19 infection: 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of COVID-19 infection is 22.9%, the mortality rate is 18.8%. Severe COVID-19 disease is associated with higher median age. We did not find any correlation between disease severity and sex, smoke or cardiovascular comorbidities. Remarkably, patients who were on treatment developed milder disease than cancer patients who were not on treatment. Conclusions The acceptance of CT-defined diagnosis in high prevalence area like Bergamo highlighted a larger number of COVID-19 oncological population than RT-PCR alone, in particular asymptomatic and mild symptomatic patients. We observed that actively treated patients had milder disease, according to previous studies that suggested a protective role of immunosuppression.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Despite soccer popularity, comparatively little scientific information is available concerning the assessment of youth players’ physiological characteristics. The use of medical software integrating wearable sensors to provide accurate and objective data is necessary. In the present study, the objective assessment of physical performance of 128 adolescent soccer players at two timepoints (pre-season and end-season) has been performed. Participants completed a comprehensive test battery including stability, countermovement jumps (CMJ), plyometric jumps (PJ), agility, and quick feet tests. A single Inertial Measurement Unit (IMU) sensor provided quantitative data on various performance metrics. Principal Component Analysis (PCA) reduced the dataset to four principal components (PCs) explaining over 80% of the variance: power (PC1), balance (PC2), speed/agility (PC3), and stiffness (PC4). Paired samples t-test between the two timepoints showed no significant differences in the PCs between the two timepoints, indicating that the training program did not significantly alter the assessed physical attributes. However, subtle individual changes may still inform personalized training adjustments. The study highlights the importance of continuous monitoring and individualized training strategies to optimize athlete performance and reduce injury risk.

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

Background: Malnutrition commonly affects patients with oral squamous cell carcinoma (OSCC), which contributes to worsening prognosis. Moreover, specific strategies for diagnosing and managing malnutrition in OSCC are lacking. Methods: This retrospective study included 52 consecutive patients with OSCC who underwent surgery at the University Hospital of Palermo (I) from Jan 2020 to May 2023. In-hospital nutritional support was provided by a dedicated team. The patients were compared with a historical control group of 11 patients. The nutritional treatment consisted of standard oral (ON) or artificial nutrition (AN). Traditional measurements, including bioimpedance-derived body composition and volumetric reconstruction of the posterior paraspinal muscles at the C3 level based on magnetic resonance imaging (MRI-C3), were obtained in 16 patients to investigate sarcopenia. Results: The patients were categorized according to TNM stage: groups A (TNM stages I-III) and B (IVa-IVc). The prevalence of group A patients was 59.6% in the case group and 90.9% in the control group (P

Objective: Interstitial fibrosis / tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm in estimating the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1/1/2012 to 1/3/2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features which were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML-algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) have been included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. For IFTA ≥ 50%, AUCs in training cohort were 0.89, 0.84, 0.96, and in test cohort were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA>50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts.

Background: Adiposity rebound (AR) refers to the second rise of the BMI curve that usually occurs physiologically between 5 and 7 years of age. AR timing has a great impact on children´s health, being the early adiposity rebound (EAR) associated with the development of metabolic disease later in life. Aim: We aimed to investigate the prevalence of EAR in a cohort of preterm newborns. Secondary outcomes evaluated if some determinants such as (1) gender (male/female), (2) type of delivery (caesarean/vaginal), (3) birth weight (SGA/NGA/LGA), (4) type of feeding (5) duration of breastfeeding, (6) timing of introduction of solid food, (7) parental education and (8) parental pre-pregnancy BMI can influence EAR in this cohort. Tertiary aim was to evaluate the prevalence of obesity or overweight at 7 years of age in children according to early versus timely AR. Methods: This is a perspective, population-based longitudinal study, where infants born preterm were evaluated at birth and at 1, 3, 6, 9, 12, 15, 18, 24 months and 3, 4, 5, 6, 7 years of gestational-corrected age. Weight and height data were analyzed, and BMI was calculated. AR was assessed in the growth trajectory in a body mass index (BMI) plot. Results: Of the 250 preterm newborns included, 100 completed the 7 years follow-up and entered in the final analysis. The prevalence of EAR in our cohort of preterm newborns was 54%. EAR was associated with being LGA at birth. No other factors were associated to EAR. Early adiposity rebounders have a significant higher BMI at 7 years compared to children with timely AR (17.2 ±2.7 vs 15.6 ± 2.05, p=0.021). No significant differences were found in the prevalence of obesity or overweight at 7 years of age in children with early or timely AR (29% vs 14% p=0.202). Conclusions: Clinical management of preterm infants should focus on reducing excess weight gain to prevent long-term metabolic risk. Others neonatal factors are not associated to an higher risk of EAR.

Allopolyploidy in plants involves the merging of two or more distinct parental genomes into a single nucleus, a significant evolutionary process in the plant kingdom. Transcriptomic analysis provides valuable insights into the fate of duplicated genes, evolutionary novelties, and environmental adaptations exhibited by allopolyploid plants. However, transcriptome profiling is challenging due to genomic redundancy, which is further complicated by the presence of multiple chromosomes sets and the variations among homoeologs and allelic genes. Prior to transcriptome analysis, sub-genome phasing and homoeology inference are essential for obtaining a comprehensive view of gene expression. This review aims to clarify the terminology in this field, identify the most challenging aspects of transcriptome analysis, explain their inherent difficulties, and suggest reliable analytic strategies. Furthermore, bulk RNA-seq is highlighted as a primary method for studying allopolyploid expression, with an emphasis on the critical steps of read mapping and normalization in differential gene expression analysis.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Lap joints were friction stir welded in AA 7075-T6 at 1320 rpm and using two welding speeds: 70 mm/min and 120 mm/min. The temperature profiles of the weld zone were registered during the process; furthermore, the microhardness, tensile strength, and microstructure of the joints produced were examined. This study brings new insights into the thermomechanical behavior of the material during the process. The peak temperature obtained with the lower welding speed (70 mm/min) is 10% higher than that obtained with the higher speed (120 mm/min). Moreover, a 5% increase in microhardness and a 6% increase in tensile strength were were observed increasing the welding speed. Addition-ally, the microstructure examination demonstrated that, by decreasing the welding speed, the larger interaction between the tool and the material results in a deeper stir zone due to the increased heat diffusion downwards to the material. This heat flow affects the thermal profile and influences the resulting mechanical properties of the welded joints.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 20–40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcome. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association of LowC3 and ESKD and whether this association reflects ongoing TMA. We enrolled all patients with biopsy-proven IgAN and followed-up patients until last visit, ESKD or death. Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs 9/44 (20%), p=0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69,20.15; P=0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD with mechanisms that are largely independent from TMA.

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.

Electronic waste generation has been following a continuously rising trend. With electronics containing a myriad of materials some of which are hazardous, toxic, extremely rare or precious combined with more stringent legislative laws which encourage the reuse and optimised recycling of the materials included in e-waste, the need for a holistic approach is inevitable. Such an approach should not only identify the materials found in the various types of e-waste and their respective quantities but also needs to highlight the possible handling techniques and their respective impacts and associated hazards whether to the environment or human health. Performing such a task manually would be exasperating and costly while requiring extensive resources which might not be met with a justifiable economic gain; thus, the use of the advancement in computational sustainability to draw a complete picture and aid in an informed decision-making process is crucial. The e-waste ontology developed in this paper is one way of addressing the problem since it covers the treatment domain, the hazard and the materials contained within the different types of e-waste. The ontology developed can be used directly from the protégé software or by embedding it into a developed Decision Support System.

The comparison of three types of ionosonde data from Europe during an Interplanetary Coronal Mass Ejection (ICME) and a Stream Interaction Regions (SIRs) / Corotating Interaction Regions (CIRs) -driven geomagnetic storm event is detailed in this study. The selected events are 16-20 March 2015 for the ICME-driven and 30 May to 04 June 2013 for the SIR/CIR-driven one. Ionospheric data from three European ionosonde stations, namely Pruhonice (PQ), Sopron (SO) and Rome (RO), are investigated. The ionospheric F2-layer responses to these geomagnetic events are analyzed with the ionospheric foF2 and h’F2 parameter, the calculated deltafoF2 and deltahF2 values, ratio of Total Electron Content (rTEC) and Thermosphere, Ionosphere, Mesosphere, Energetics and Dynamics (TIMED) satellite Global Ultraviolet Imager (GUVI) thermospheric [O]/[N2] measurement data. The storm-time and the quiet day mean values are also compared, and it can be concluded that the quiet day curves are similar at all stations while the storm-time ones showed the latitudinal dependence during the development of the storm. As a result of the electron density comparison, during the two events it can be concluded that SSC that characterized the ICME induced a Travelling Atmospheric Disturbance (TAD) seen in the European stations, while this is not in the SIR/CIR-driven ionospheric storm, which showed a stronger and more prolonged negative effect in all stations probably due to the season.

This work aims to shed light on the differential diagnosis of Complex Post-Traumatic Stress Disorder (cPTSD), Post-Traumatic Stress Disorder (PTSD), and Borderline Personality Disorder (BPD) within the context of Intimate Partner Violence (IPV), which represents an extremely inno-vative field of clinical research. To this end, a critical review of the literature was conducted to identify and compare the clinical patterns and symptomatic overlaps among cPTSD, PTSD, and BPD, with an emphasis on their manifestation in both victims and offenders. The results show that despite some symptomatic similarities, cPTSD, PTSD and BPD have distinct clinical patterns in IPV. Disturbances in Self-Organization (DSO), are more commonly in offenders, while the di-agnosis of cPTSD is more aligned with the victims. In addition, cPTSD and characteristics of BPD, such as fear of rejection and instability of identity, constitute risk factors for IPV victimiza-tion. cPTSD is a predisposing factor not only for victims but also for offenders, while PTSD emerges as a consequential factor. The specific pathways linking PTSD, cPTSD, and BPD with IPV have significant implications for clinical practice. Further research is needed to understand these profiles and the mechanisms linking trauma-related features to IPV, which is crucial for imple-menting effective violence prevention programs.

Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: we performed CMR in 49 HCM patients, 30 non-HCM hypertrophy and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to the 25% of diastole. Left ventricular mass, mean and standard deviation (SD) of WT, maximal WT, minimal WT and their difference, were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating 8 hearts with HCM, 10 with coronary artery disease and 10 with non-cardiac death. Results: The SD of WT with a cut-off of > 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95%CI 0.89-0.98). This was particularly evident in female population of HCM (AUC=0.998), with 100% specificity (95%CI 85-100%) and 96% sensitivity (95%CI 79-99%). Using this parameter, at PMCMR all the 8 patients with HCM were correctly identified with no false positive. Conclusions: PMCMR allows to identify HCM as cause of sudden death using the SD of WT >2.4 as diagnostic parameter.

Knowledge is not merely the characteristic of certain pieces of information being deemed true and justifiable, but rather a process. Within an axiomatic system, the set of information that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the process of justification (exchange of information), if it consistently justifies a particular piece of information, it elevates it to knowledge. In this paper, we provide a framework for knowledge within an axiomatic model where we define the fundamental elements of communication and grammar. As a result, the structure dictates that knowledge, to be considered as such, must be investigateable by anyone who utilizes it in its entirety, both in form and content. Ultimately, the development of knowledge processing, referred to as \emph{knowmatics}, represents a clear evolution of the computer science that processes information (subset of knowledge).

Previous studies show that women with a history of high-grade CIN have a greater risk of subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue and they show mixed results. This study aimed to investigate the incidence of high-grade or worse VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease, illustrate treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent laparoscopic hysterectomy for high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and diagnosis of high-grade VaIN was 18 months. Results: High grade or worse VaIN was found in 8 patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized for CIN3 showed an 8-fold greater risk than women hysterectomized for benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized for benign disease. The risk of developing VaIN is greater in women with viral persistence Conclusion. All these elements suggest that it is the history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered a risk factor for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associate with the use of small molecule antibiotics and AMPs is the combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review is intended to cover and critically analyze the design, synthetic strategies, antibacterial activity and, when possible, the cytotoxicity of antibiotic-AMPs conjugates.

Pseudomonas donghuensis P482 exhibits broad antibacterial and antifungal activity, primarily related to the production of 7-hydroxytropolone (7-HT). However, the restricted nutritional conditions (viz. mineral medium with single carbon source) diminished the antagonistic activity of P482. In this study, we unveil profiles of the secondary metabolites from P482 and its selected mutants, using nutrient-diluted (10% tryptone soy broth, TSB) and nutrient-restricted (M9 with either 0.4% glucose or 0.4% glycerol as a sole carbon source) media to explore differences in the quantity and quality of the secondary metabolites produced. No 7-HT was found to be synthetized by P482 under restricted nutritional conditions. However, both the wild-type and the tested mutants of P482 still did express some antagonistic activity towards the plant pathogenic bacteria tested. Based on these results, we postulate that 7-HT is not the sole antimicrobial compound produced by P. donghuensis P482 and that other antimicrobials may be involved in P482 antagonistic activity under limiting-nutrient conditions.

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for Multiple Sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for Multiple Sclerosis patients.

The abilities of quantitative description of noise are restricted due to its origin and only the statistical and spectral analysis methods can be applied while an exact time evolution cannot be defined or predicted. It emphasizes the challenges faced in many applications including communication systems where noise can play, on one hand, a vital role impacting signal-to-noise ratio but possessing, on the other hand, unique properties such as infinite entropy (infinite information capacity), exponentially decaying correlation function and so on. Despite the deterministic nature of chaotic systems, the predictability of chaotic signals is limited for a short time window putting them close to random noise. In this article, we propose and experimentally verify an approach to achieve Gaussian-distributed chaotic signals by processing the outputs of chaotic systems. The mathematical criteria, on which the main idea of the study is based on, is the Central Limit Theorem which states that the sum of a large number of independent random variables with similar variances approaches a Gaussian distribution. The study involves more than 40 mostly three-dimensional continuous-time chaotic systems (Chua’s, Lorenz’s, Sprott’s, memristor-based, etc.) whose output signals are analyzed according to criteria that encompass the probability density functions of a chaotic signal itself and its envelope and phase, statistical and entropy-based metrics such as skewness, kurtosis, and entropy power. We found that two chaotic signals of Chua’s and Lorenz’s systems exhibited superior performance across the chosen metrics. Furthermore, our focus extended to determining the minimum number of independent chaotic signals necessary to yield a Gaussian-distributed combined signal. The analytic and experimental results indicate that the sum of at least three non-Gaussian chaotic signals closely approximates Gaussian distribution. It allows generation of reproducible Gaussian-distributed deterministic chaos by modeling simple chaotic systems.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

Precipitation patterns are critical for understanding the hydrological and climatological dynamics of any region. Sicily, the largest island of the Mediterranean sea, with its diverse topography and climatic conditions, serves as an ideal case study for analyzing precipitation data to gain insights into regional water resources, agricultural productivity, and climate change impacts. This paper employs advanced statistical physics methods, particularly Tsallis q-statistics, to analyze sub-hourly precipitation data from 2002 to 2023, provided by the Sicilian Agrometeorological Informative System (SIAS). We investigate several critical variables related to rainfall events, including duration, depth, maximum record, and inter-event time. The study spans two decades (2002-2012 and 2013-2023), analyzing the distributions of relevant variables. Additionally, we examine the simple returns of these variables to identify significant temporal changes, fitting these returns with q-Gaussian distributions. Our findings reveal the scale-invariant nature of precipitation events, the presence of long-range interactions and memory effects, characteristic of complex environmental processes.

This study focuses on the design, development, and evaluation of an educational mobile robot, named Robot-T2, to be used in educational activities within a technical school. The primary objective was to create a versatile platform that allows students to explore programming, engineering, and science concepts in a practical and collaborative manner. The methodology included an iterative design and testing approach, incorporating feedback from students and teachers to continuously improve the robot's functionality. The tests covered autonomous navigation, line following, and object manipulation, using the OnBotJava programming software and the Control Hub as the main interface. The results demonstrated that Robot-T2 is highly efficient and adaptable in various educational contexts, showing remarkable precision in navigation and object manipulation. The design iterations significantly improved the robot's performance, enriching the educational experience and promoting active learning. In conclusion, educational robotics, represented by Robot-T2, has great potential to enhance the teaching and learning process in technical schools, fostering teamwork, problem-solving, and the integration of technology in the classroom. This project is expected to inspire future developments in educational robotics.

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

Bistatic radar experiments have been used to study surface characteristics of extra-terrestrial bodies in the Solar System, including the Moon, Venus, Mars, and Titan. This paper proposes a 3D model to characterize the scattered field of a Gaussian rough surface on an extra-terrestrial body for an orbital bistatic radar configuration. Specifically, this model will investigate how the variability of surface roughness impacts the spectral broadening of the received signal using physical optics approximations and ray tracing on a surface model using a facet approach with Gaussian properties. A linear relationship between spectral broadening of the signal and surface roughness was found. This relationship is in line with results obtained by commonly used analytical models for bistatic radar on planetary surfaces.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p &lt; 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.