Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator ok NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, currently predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

Metastatic pancreatic ductal adenocarcinoma pancreatic (PDAC) is characterized by poor prognosis and short survival. Today, the use of new polytherapeutic regimens increases clinical outcome of these patients opening new clinical scenario. A crucial issue related to the actual improvement achieved with these new regimens is represented by the occasional possibility to observe a radiological complete response of metastatic lesions in patients with synchronous primary tumor. What could be the best therapeutic management of these patients? Could surgery represent an indication? Herein we reported a case of a patient with a PDAC of the head with multiple liver metastasis, who underwent first line chemotherapy with mFOLFIRINOX. After 10 cycles, he achieved a complete radiological response of liver metastases and a partial response of pancreatic lesion. A, duodenocephalopancreasectomy was performed. Due to liver a lung metastases after 8 months from surgery, a second line therapy was started with a disease free survival and overall survival of 8 months and 45 months, respectively. Improvement in the molecular characterization of PDAC could help in the selection of patients suitable for multimodal treatments.

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for about 40% of all cases NHL. Analysis of the tumour microenvironment is an important aspect of the assessment of the progression of DLBCL. In this review article, we have analyzed the role of different cellular components of the tumour microenvironment, including mast cells, macrophages, lymphocytes, in tumour progression of DLBCL. We examined several approaches to confront the available pieces of evidence; three key points emerged. DLBCL is a disease of malignant B-cells spreading and accumulating both at nodal and in extranodal sites. Both in patients with nodal and extranodal lesions, the subsequent induction of a cancer-friendly environment appears pivotal. DLBCL cell interaction with mature stromal cells and vessels confers tumour protection and inhibition of immune response while delivering nutrients and oxygen supply. Single cells may also reside and survive in protected niches in the nodal and extranodal sites as a source for residual disease and relapse. This review aims to molecularly and functionally recapitulate the DLBCL-milieu crosstalk, to relate niche and pathological angiogenic constitution and interaction factors to DLBCL progression.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintained and reinforced their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.

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

Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..

Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, that can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F / 53.70% M, age 63.95±12.82 years) presented CA at baseline. In 53 patients, there was associated with multiorgan involvement, while in one there was primary myocardial deposition. As control group, we enrolled 81 patients (49.30% F / 50.70% M, aged 58.33±15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA, 3/54 of patients with ATTR, in 1/54 AL was related to hemodialysis and 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/40) or IgD (2/40), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0±8.4 mmHg; DBP 73.8±4.9 mmHg), while those with nCA had increased proteinuria (p=0.02). TnI and NT-proBNP were significantly increased compared to nCA (p= 0.031 and p=0.047, respectively). In CA patients we found an increased LDH compared to nCA (p=0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p=0.002), a decreased Ejection Fraction % (p=0.0018) and Doppler velocity E/e’ ratio (p=0.0095). Moreover, CA patients were seen to have an enhanced right atrium area (p=0.0179), right ventricle basal diameter (p= 0.0112) and wall thickness (p=0.0471) as compared to nCA, as well as an increased inferior cava vein diameter (p=0.0495). TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p=0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r=0.47; p=0.031) as well as Gamma globulins (r=0.43, p=0.033), Monoclonal component (r=0.72; p=0.047) and IgG values (r=0.62, p=0.018). On the contrary, a significant negative correlation with LDH (r=-0.57, p=0.005), IVS (r=-0.51, p=0.008) and diastolic function evaluated as E/e’ (r=-0.60, p=0.003) were verified. CA patients had very poor survival compared to controls (30 vs. 66 months in CA vs nCA, respectively, P=0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs higher values than the median, respectively p=0.013). In much the same way, decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18mm, p=0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement and propose that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.

Microstructured optical fibres (MOFs) are a new type of optical fibres that possess a wide range of optical properties and many advantages over common optical fibres. Those are provided by unique structures defined by a pattern of periodic or quasi-periodic arrangement of air holes that run through the fibre length. In recent years, MOFs have opened up new possibilities in the field of optics and photonics, enabling the development of advanced devices and novel optical systems for different applications. The key application areas of PCFs vary from telecommunications and high-power energy transmission to quantum optics and sensing. The stack-and-draw method is a standard manufacturing technique for MOFs, where a preform is first manually created and then drawn in a high-tech furnace into a fibre with the required final dimensions and position of the air holes. Since in the manufacturing process experimenters can control only a few parameters, mathematical models and numerical simulations of the drawing process are highly requested. They not only allow to deepen the understanding of physical phenomena occurring during the drawing process, but they also accurately predict the final cross-section shape and size of the fibre. In this manuscript, we assume thermal equilibrium between the furnace and the fibre and propose a functional form of the fibre temperature distribution. We utilise it with asymptotic mass, momentum, and evolution equations for free surfaces already available in the literature to describe the process of fibre drawing. By doing so, the complex heat exchange problem between the fibre and the furnace need not be solved. The numerical results of the whole asymptotic model overall agree well with experimental data available in the literature, both for the case of annular capillaries and for the case of holey fibres.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

This paper presents the experimental and numerical study on a ductile beam-column connection between a composite reinforced concrete truss (CRCT) beam and Concrete Filled Tube (CFT) column subjected to bending and shear loads. Two experimental models with different beam-column joint testing schemes, extracted from the same prototype three-dimensional structure designed according to the rules of the capacity design provided by seismic code, were subjected to quasi-static cyclic tests by applying gravitational loads and the horizontal seismic force. The main objective of this paper is to verify the experimental ductile behavior of both specimens and to simulate the experimental global and local response by nonlinear static analysis considering different modelling approaches. The comparison between the experimental and numerical results highlights, for both models considered, the ductile and dissipative capacity of the connection system, designed following the criterion of the hierarchy of resistances proposed by the current Italian code. Different experimental setup showed similar results demonstrating the repeatability of the test and its reproducibility through the nonlinear numerical analysis.

During the COVID-19 pandemic, percutaneous tracheostomy proved to be an effective option in the management of patients with prolonged periods of intubation; in fact, among other things, it allowed early discharge from ICUs and contributed to reducing overcrowding in intensive care settings, a central critical point in the COVID pandemic. As a direct consequence, the management and the weaning of frail, tracheostomized and ventilated patients was diverted to sub-intensive or normal hospitalisation wards. One central challenge in this setting is the resumption of swallowing and oral feeding, which needs an interdisciplinary management involving Phoniatrician, ENT, Pneumologist and Speech Therapist. With this article, we aim to share the experience of a Swiss COVID-19 Center[1] and to draw up a narrative review on the issues concerning the management of the tracheostomy cannula during swallowing resumption, integrating the most recent evidence from the literature with the clinical experiences of the professionals directly involved in the management of tracheostomized COVID-19 patients. In view of the heterogeneity of COVID-19 patients, we believe that the procedures described in the article are applicable to a larger population of patients undergoing tracheostomy weaning.

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

United Nations Framework Convention on Climate Change (UNFCCC) has recently established the Reducing Emissions from Deforestation and forest Degradation (REDD+) program that requires countries to report their carbon emissions and sink estimates through national greenhouse gas inventories (NGHGI). Thus, developing automatic systems capable of estimating the carbon absorbed by forests without in-situ observation becomes essential. To support this important need, in this work we introduce ReUse, a simple but effective deep-learning approach to estimate the carbon absorbed by forest areas based on remote sensing. The novelty of the proposed method is in the use of the public above-ground biomass (AGB) data from the European Space Agency's Climate Change Initiative Biomass project as ground truth to estimate the carbon sequestration capacity of any portion of land on Earth using Sentinel-2 images and a pixel-wise Regressive UNet. The approach has been compared to two literature proposals, using a private dataset and human-engineered features. The results show a greater generalization ability of the proposed approach, with a decrease in Mean Absolute Error and Root Mean Squared Error, respectively, of 16.9 and 14.3 in the area of Vietnam and 4.7 and 5.1 in the area of Myanmar over the runner-up. Finally, as a case study, we reported an analysis made for the Astroni area, a nature reserve located near the metropolitan area of Naples in southern Italy, struck by a large fire, producing predictions consistent with values found by experts in the field. These results further support the use of such an approach for the early detection of AGB variations, both in urban and rural areas.

The increasing regulatory pressure to monitor and reduce GHG emissions and air pollutants requires cost-effective methods for their surveillance. The most common technique used for scientific investigations on gas concentration monitoring in barns are accurate but expensive and with a complex maintenance. This research study analysed the potential use of a low-cost portable measurement devices for the measurement of ammonia (NH3) and carbon dioxide (CO2) concentrations in an open dairy barn. A comparison between gas concentrations acquired at different heights from the floor by using portable devices and those acquired by a photoacoustic infrared multigas spectroscope (i.e., reference measurement) in the same sampling locations was carried out to determine the precision of the low-cost portable devices. The performance of low-cost portable devices was statistically analysed by the application of the one-way analysis of variance, correlation analysis and regression analysis. The results showed a significant difference between gas concentration values at various heights from the floor for both NH3 and CO2. The correlations between concentrations acquired by the low-cost portable device and the INNOVA were statistically significant (r=0.83; P<0.001) for gas concentrations monitored at 0.4 m from the floor. Compared with the reference measurement device, the low-cost devices were effective in the monitoring of NH3 concentrations at 0.40 m from the floor though it underestimated them in the barn at increasing of the height from the floor, whereas the device was not adequate for CO2 concentrations. In detail, the relative measurement error of the low-cost devices compared to INNOVA was reduced close to the floor during NH3 concentration measurements. Within these limitations, this device could be useful for monitoring NH3 concentration in the barn and to assess variation in NH3 concentrations mainly related to the animal occupied zone. Further efforts are needed in this field of research to identify low-cost device that could simplify emission estimation from open dairy barns.

Healthcare workers' stress, burnout, and job dissatisfaction were exacerbated by the Covid-19 pandemic, whose mid-term negative effects are still present. The aim of this study was to investigate in healthcare workers the effect of the dimensions of burnout (Psychophysical exhaustion, Relational deterioration, and Professional inefficacy) on Career satisfaction. These relationships were evaluated by considering the direct and mediated effects of Disillusion. For these purposes, the Link Burnout Questionnaire (LBQ) and the Career Satisfaction Scale (Occupational Stress Indicator - OSI) were administered to 295 healthcare professionals working at three Italian public hospitals in Cagliari, Italy. The analyses were conducted using the Partial Least Square Structural Equation Model (PLS-SEM) method. Findings highlight that healthcare workers were in a condition of work distress, high risk of burnout, and career dissatisfaction. Also recognized was the direct negative effect of burnout dimensions on career satisfaction. Finally, the mediated negative effect of Disillusion in the relationship between burnout and career satisfaction was identified. This study emphasizes the relevance of the dimension of Disillusion, and its “bright side” Fulfilment, in healthcare workers, specifically referring to the disregarded relationship between burnout and career satisfaction.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

A randomized control trial (clinicaltrial.gov identification NCT04521504) was conducted to test if the combination of a rehabilitative protocol with a kinematic visual biofeedback tool could improve the functional level of patients arthroscopically treated for rotator cuff tear, both in the short- and medium-term assessments. Forty patients (aged between 35 and 65 y.o., employed at the time of the enrollment) were randomly assigned to two groups: Control group (C, n°21 patients) and Biofeedback group (B, n°19 patients). The primary outcome used for the assessment of shoulder functional performances was the Scapula-Weighted Constant-Murley Score. Patients were assessed longitudinally: before surgery, 45 days after surgery, at time of return-to-work, and at a final follow-up between 6 and 12 months. Results showed no biases for the two groups before the administration of the experimental protocol; significantly higher scores for B compared to C were found only at time of return-to-work. Based on results, we could conclude that the biofeedback training allowed patients to return to work in a better functional condition. This trial was funded by the National Institute for Insurance against Accidents at Work (INAIL).

The procedures for the extraction and separation of lipids and nutraceutics from microalgae using classic solvents have been used many times. However, these production methods usually require expensive and toxic solvents. Based on our studies involving the use of eco-sustainable methodologies and alternative solvents, we select ethanol (EtOH) and cyclopentyl methyl ether (CPME) for extracting bio-oil and lipids from algae. Different percentage of EtOH in CPME favors the production of an oil rich of SFA useful to production biofuel or rich of compounds bioactive. The proposed method for obtain a rich extract of saturated or unsaturated fatty acids from dry algal biomass is disclosed is eco-friendly and allows a good extraction yield. The method is compared both in extracted oil percentage yield and in extracted fatty acids selectivity to extraction by supercritical carbon dioxide.

BACKGROUND: Patients with diabetic foot ulcers (DFU) and chronic limb-threatening ischemia (CLTI are at higher risk for major amputations and mortality. The aim of this study was to assess the safety and cost-efficacy of intramuscular injection of autologous monocyte-rich PRP platelet-rich plasma Tropocells® PRP (Estar Medical, Holon, Israel) in diabetic patients with chronic limb-threatening ischemia (CLTI) in which revascularization was not feasible. METHODS: a retrospective study was carried out on a series of patients with type 2 diabetes, grade Texas 3C or D DFU, and CLTI. All patients had undergone at least a previous revascularization and were allocated to a surgery waiting list for major amputation. According to the data provided by the manufacturer (https://www.zuccatobiotech.it/index.php/prodotti/tropocells), the monocyte-rich PRP kit obtained a platelet-rich plasma with a high concentration of peripheral blood mononuclear cells (with a proportionately lower amount of lymphocytes), a low concentration of neutrophils and an almost complete depletion of red blood cells. All patients underwent a procedure of local infiltration of autologous mononuclear cells through multiple perilesional and intramuscular injections of 10 mL PBMNC suspensions (0.2–0.3 mL in boluses) performed below the knee along the relevant vascular axis (anterior tibial artery and posterior tibial artery) at intervals of 1–2 cm and to a mean depth of 1.5–2 cm, using a 21 G needle. The procedures were performed according to the instructions of the manufacturer and were repeated at least two times (maximum 3 times) at intervals of 30 days. The principal endpoint was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoints were individual components of the primary endpoint, quality of life, any adverse events, and direct costs. All the endpoints were evaluated at 26 weeks. RESULTS: Out of 21 enrolled patients, 13 (61.9%) reached the primary endpoint, whereas three patients underwent a major amputation, and two patients died. The median TpCO2 was significantly increased, and pain was significantly reduced. The overall mean and median cost per patient were 9,255±7,328€ and 4,001 [2,991;7,565]€, respectively. CONCLUSIONS: the use of PBMNCs implants in patients with DFU and no-option CLTI seems to be efficacious in reducing the risk of major amputation and improve ulcer healing.

This paper aims to analyse the mechanical properties response of polylactic acid (PLA) parts manufactured through fused filament fabrication. The influence of six manufacturing factors (layer height, filament width, fill density, layer orientation, printing velocity, and infill pattern) on the flexural resistance of PLA specimens is studied through an L27 Taguchi experimental array. Different geometries have been tested on a four-point bending machine and on a rotating bending machine. From the first experimental phase, an optimal set of parameters deriving in the highest flexural resistance have been determined. Results show that layer orientation is the most influential parameter, followed by layer height, filament width, and printing velocity, whereas the fill density and infill pattern show no significant influence. Finally, the fatigue fracture behaviour is evaluated and compared with previous studies results, to present a comprehensive study of the mechanical properties of the material under different kind of solicitations.

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

In this review, photoinduced electron transfer processes in specifically designed assembled ar-chitectures have been investigated on the basis of recent results reported from our laboratories. A convenient and useful way to study these kinds of systems has been described in order to under-stand the rules that drive to a light induced charge separation and its subsequent decay to the ground state, also with the aim of offering a tutorial for young researchers. Assembled systems of covalent or supramolecular nature have been presented and some functional multicomponent systems for the conversion of light energy into chemical energy have been discussed.

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

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.

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

This review highlights the potential and limitations of mRNA vaccines with a particular focus on mucosal delivery as an alternative to parenteral administration. The strengths of mRNA vaccines are: a) Versatility: they can be adapted to target a wide range of pathogens; b) Faster development: designed and produced more quickly than traditional vaccines; c) High efficacy: effective in preventing severe disease, as demonstrated during the COVID-19 pandemic. Current challenges: a) Delivery: current methods (mainly intramuscular injection) may not be optimal for inducing mucosal immunity; b) Stability: mRNA is fragile and needs to be protected from degradation; c) Safety: potential side effects, including myocarditis, blood clotting, allergic reactions need further investigation. Mucosal delivery could be more effective in preventing the transmission of pathogens and is generally better accepted by the population. Pros: offers the potential to induce local immunity at the site of pathogen entry, potentially providing broader protection; Cons: developing effective delivery systems and adjuvants for mucosal delivery is difficult. Extracellular vesicles as a mucosal delivery system are promising and offer a potentially safe, scalable, and needle-free approach. Future directions: a) Optimizing mRNA constructs: strategies like codon optimization and self-amplifying RNA can improve stability and translation efficiency; b) Rigorous pre-clinical studies are essential before human trials.

Background: developmental dysplasia of the hip (DDH) is a condition characterized by abnormal hip development in infancy. Early diagnosis allows for effective treatment, while late presentation often necessitates complex surgical interventions. Current recommendations advise screening between the 6th and 8th week postnatal using ultrasound, typically employing the Graf method. However, there's no universal consensus on whether ultrasound screening significantly increases treatment compared to clinical examination-guided ultrasound. This study aims to explore the feasibility of prenatal ultrasound for early identification of DDH risk. Methods: This prospective observational study involved 100 pregnant women undergoing fetal hip ultrasound during the second and third trimesters. Using the modified Graf method, alpha and beta angles were calculated on the fetus. Postnatally, alpha and beta angles were compared with prenatal values. Results: Prenatal ultrasound at 24th week showed inconclusive results because of the difficulty in identification of Graf landmarks, while ultrasound at 34th week has proved to be a reliable and safe method for quantitative determination of alpha and beta angles. Significant correlations were found between prenatal and postnatal alpha and beta angles. Moreover, significant differences in prenatal alpha and beta values were observed in patients developing mature/immature hips postnatally. Conclusions: Prenatal diagnostics show promise for predicting infant hip development. Further research is warranted to validate correlation strength and clinical applicability.

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, re-considering the immunohistochemical negative score of 0, 1+ or score of 2+/in situ hybridization (ISH) negative phenotype. In the present review we have outlined the needed criteria to exactly distinguish HER2 low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating these group sof tumors. In particular, Trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC has been recently approved by the U.S. Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally we hope that new guidelines may help to codify HER2 low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.

MAPLE (matrix assisted pulsed laser evaporation) depositions of Candida Rugosa lipase were carried out from ice matrices whose composition is optimized in order to minimize conformational damage of the protein, which strongly influences its catalytic activity. To induce lid opening and to protect lipase during the MAPLE process, pentane and m-DOPA amino acid were added to the liquid matrix giving a target formed by a frozen water-lipase-pentane microemulsion. FTIR and AFM were used to investigate the structure of MAPLE deposited lipase films. The ability of MAPLE films to promote transesterification was determined by thin layer chromatography. It was shown that m-DOPA has influence on the aggregation but not on the unfolding of lipase induced by MAPLE, while the microemulsion formed by the addition of pentane to the target composition is effective in protecting lipase during the MAPLE process. MAPLE deposited lipases showed a modified specificity.

We generate numerically on a lattice an ensemble of stationary metrics, with spherical symmetry, which have Einstein action S_E « ħ. This is obtained through a Metropolis algorithm with weight exp(-β²S_E²) and β » ħ^-1. The squared action in the exponential allows to circumvene the problem of the non-positivity of S_E. The discretized metrics obtained exhibit a spontaneous polarization in regions of positive and negative scalar curvature. We compare this ensemble with a class of continuous metrics previously found, which satisfy the condition S_E=0 exactly, or in certain cases even the stronger condition R(x)=0 for any x. All these gravitational field configurations are of considerable interest in quantum gravity, because they represent possible vacuum fluctuations and are markedly different from Wheeler's ''spacetime foam''.

Contemporary cities are facing many challenges, from social and economic issues to the new risks related to the impacts of climate change. Focusing on energy consumptions, and the related GHG emissions, cities are considered not only the main global contributors but also the areas most exposed to risks, because of their density of population and economic activities. Implementing urban planning strategies with the purpose of increasing energy efficiency and resilience overall are, for all these reasons, considered a top priority. This paper investigates the innovative contents about energy-efficient and energy-resilient urban planning solutions that have started to be implemented in the cities of the Emilia-Romagna region. Two kinds of planning instruments are therefore analyzed: the voluntary Sustainable Energy and Climate Action Plans (SECAPs) and the mandatory General Urban Plans (GUPs), recently approved in several cities of Emilia-Romagna. A comparative analysis of three cities in the Emilia-Romagna region, Bologna, Modena and Ravenna, is proposed on the strategies of their newly local city plans and SECAPs with focus on energy management and planning. The aim is to assess whether the new structure of local city plans and the influence of SECAPs could be useful in implementing such urban energy resiliency solutions.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

Background. Psoriasis (PS) is a common immune-mediated disease of the skin with pos-sible extension to joints, aorta and eye. Myocardial inflammation has been rarely sug-gested. Aims: Report of PS-related myocarditis Methods and Results: One hundred consecutive patients with PS were screened for car-diac involvement. Among them, five male patients (aged 56 ± 9.5 years) with moder-ate-severe form showed a dilated cardiomyopathy (LVEF <35%) with normal coronary ar-teries and valves. They underwent a left ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and im-munohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which plays a major role in psoriasis pathogenesis; real-time PCR for cardiotropic viruses and Western blot analysis for myocardial expression of IL-17A. Patients’ sera were tested for anti-heart autoantibodies.An active lymphocytic myocarditis was revealed in all 5 patients, characterized by absence of viral genomes at PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and enhancement of IL-17-A at western blot analysis showing a 2,48-fold increase in psoriatic myocarditis compared with no psoriatic myocarditis and a 6-fold increase compared to myocardial controls. Treatment included combination of prednisone (1 mg/Kg daily for 4 weeks, ta-pered to 0.33 mg/Kg) + azathioprine (2 mg/Kg, daily) in 3 pts or secukinumab (SK, 100 mg/monthly) in 2 pts for 6 months. LVEDD and LVEF improved in the first 3 pts (-14% and + 118%, respectively) while completely recovered (LVEF> 50%) in the last 2 pts on SK. Conclusion. IL-17A-related myocarditis can occur in up-to 5% of patients with psoriasis. It manifests as a progressive dilated cardiomyopathy. It may completely recover following SK administration.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

In recent years, many studies have highlighted the consistent finding of amoxicillin in waters destined for wastewater treatment plants, in addition to superficial waters of rivers and lakes in both Europe and North America. In this paper, the amoxicillin degradation pathway was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants at three different pH values. The structures of 16 isolated degradation byproducts (DPs), one of which was isolated for the first time, were separated on a C-18 column via a gradient HPLC method. Then, combining mass spectrometry (MALDI-MS/TOF) and nuclear magnetic resonance, we compared commercial standards and justified a proposed formation mechanism beginning from the parent drug. Microbial growth inhibition bioassays with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were performed to determine the potential loss of antibacterial activity in isolated degradation byproducts. An increase of antibacterial activity in the DPs was observed compared to the parent compound.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

The cough assessment is fundamental in the weaning process as it gives information on the possibility to expel food and secretion from the airways. The majority of persons suffering from severe acquired brain injury (ABI) are not able to cough voluntarily due to severe motor deficits. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. 100 Healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve cough strength training reflexive cough modulation in ABI patients.

This paper provides a comprehensive overview of the potential applications of dual energy CT (DECT) in improving image quality and diagnostic capabilities of CT arthrography (CTA) in clinical practice. The paper covers the use of virtual non contrast (VNC) images, in which the injected contrast medium is reduced from the articular cavity, in order to better analyze 2D and 3D images of the bone. Moreover , virtual monoenergetic imaging (VMI) applications and their potential use for the reduction of metal artifacts and improving image contrast are reviewed. The role of virtual non calcium (VNCa) in detecting bone marrow edema surrounding the imaged joint will be discussed. Furthermore , the role of iodine map to enhance the contrast between soft tissues, optimizing the visualization of contrast material, and to distinguish contrast material from calcifications is described. Finally, a case series including different joints is provided to underline the additional advantages of high spatial resolution dual energy CT reconstructed images.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

In this work, the nearest neighbor distances and Voronoi cell features of the Cu-Ag deposits were analyzed and fitted with Lognormal, Weibull, and Gamma distributions. The nearest neighbor distance distributions of the samples were compared with those of complete spatially random points, showing spatial inhomogenity due to the nucleation exclusion effect. The radial distribution function was calculated, showing both influences from the grain size and the nucleation exclusion effect. Voronoi cells were generated based on the shape of the grains. The size, occupancy, and coordination of the Voronoi cells were examined and fitted. The results show that despite the Cu-Ag deposits seem to be governed by instantaneous nucleation mode, the spatial distribution of the nuclei is more impacted by the nucleation exclusion effect than the Cu-only samples. This behavior is also justified by the grain size distribution generated with Voronoi cell size and occupancy distributions.

This study explores the innovative use of CO2 laser technology in frenuloplasty, a significant shift from traditional methods like scalpel surgery or electrocautery, towards a minimally invasive approach. The research involved 15 patients aged 25 to 50, undergoing frenuloplasty with a CO2 laser system equipped with a 7-inch defocused handpiece, set at 20Hz and 0.3W. This method diverges from conventional laser techniques, focusing on controlled laser passes combined with manual traction to elongate the fibrous tissue of the frenulum. The results demonstrated that the CO2 laser technique allowed for a precise and progressive modification of the frenulum, significantly reducing the risks of hemorrhage and secondary in-tention fibrosis. The healing process was notably expedited, with patients reporting satisfactory outcomes within a two-week period. Statistically significant improvements were observed in pa-tient-reported outcomes, as evidenced by the increases in the Short Form Health Survey (SF-12) scores, with the mean Physical Component Summary (PCS) score rising from 32.5 to 47.5 and the mean Mental Component Summary (MCS) score from 39.3 to 52.3 (p < 0.001 for both). The study concludes that CO2 laser frenuloplasty is an effective and safe technique, offering sub-stantial benefits in terms of reduced healing time and enhanced patient satisfaction. The signifi-cant improvements in SF-12 scores underscore the positive impact on patient quality of life, ad-vocating for the broader application of this technique in clinical practice. Further research is warranted to explore its potential in a wider clinical context.

Pediatric psychology action in the pediatric clinical-surgical high complexity unit has become increasingly necessary. It allows for the possibility of integrating complex pediatric clinical-surgical operations by reducing painful effects on the emotional world of children and adolescents. The pediatric psychologist in a pediatric unit continuously oversees children and adolescents (C/A) throughout the entire therapeutic process, extending activity to parents and healthcare personnel. In ill children and adolescents, physical pain and psychological suffering follow, with minimal temporary variations, the same clinical path with continuous changes which put a strain on the ability of children, adolescents, parents and healthcare staff to cope with stress.

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

Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

In the last four years, the evolution and adoption of blockchain and, more generally, distributed ledger systems have shown the affirmation of many concepts and models with significant differences in system governance and suitable applications. This work aims to update the critical analysis of blockchain technologies carried out by our previous contribution to this journal, extending the focus to distributed ledger components and systems. Starting from the topical concept of decentralization, we introduce concepts and building blocks currently adopted in the available systems centering on their functional aspects and impact on possible applications. We present some conceptual framing tools helpful in the application context, and we will propose the concept of process authenticity, which we will discuss through two use cases: blockchain document dematerialization and e-voting.

A number of research projects and a rich literature have dealt with the theme of abandoned medieval villages in Sardinia since the end of the 60s of the last century. Some more or less precise catalogues and reviews of villages in limited territories have been published. Only recently, however, this subject is being addressed in an interdisciplinary manner, combining traditional historical research with the results of archaeological surveys and excavation campaigns, geo-archaeology, toponymy, paleoclimatology. This allows us to have a picture of the landscape and human settlement evolution with its historical changes, conditioned not only by institutional superstructures but also by human and natural traumatic events. Particular attention will be given to the sudden changes that occurred between the thirteenth and fourteenth centuries. To carry out this survey, it is possible to use some very powerful IT tools which, through the aggregation, organization, correlation and management of information, allow the geo-localization of abandoned villages as proven by the documentary evidence. Thus, on this documentation, existing and acquired in the future, is founded the construction of the related information system. The most easy and suitable tools for this purpose are the CMSs (Content Management Systems) which, in association with GIS (Geographic Information Systems) engines, allow spatial and contextual analysis of the settlements, as they were inserted in their territory. This type of tools aggregates different peculiarities of the object of study, supporting a multidisciplinary reading on the argument. The computerized tools, integrated as a system, offer the possibility to implement it, feeding it and correcting it continuously, basing on new acquisitions. In this study, we will examine a historical areal, for which we have a sufficient number of sources available: Sarrabus, Colostrai and Quirra, adding to the geographical visual information, the temporal visual evolution.

We statistically investigate the Coronavirus Disease 19 (hereinafter Covid-19) epidemics, which is particularly invasive in Italy. We show that the high apparent mortality (or Case Fatality Ratio, CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of infected cases. To give a more realistic estimate of the mortality of Covid-19, we use the most recent estimates of the IFR (Infection Fatality Ratio) of epidemic, based on the minimum observed CFR, and furthermore analyse data obtained from the ship Diamond Princess, a good representation of a ‘laboratory’ case-study from an isolated system in which all the people have been tested. From such analyses we derive more realistic estimates of the real extension of the infection, as well as more accurate indicators of how fast the infection propagates. We then point out from the various explanations proposed, the dominant factors causing such an abnormal seriousness of the disease in Italy. Finally, we use the deceased data, the only ones estimated to be reliable enough, to predict the total number of infected people and the interval of time when the infection in Italy could stop.

Cetacean Morbillivirus, the most relevant pathogen impacting the health and conservation of cetaceans worldwide, has shown in recent years an increased tendency to cross “interspecies barriers”, thereby giving rise to disease and mortality outbreaks in free-ranging dolphins and whales. The present article deals with the evolutionary “trajectories” of this viral pathogen, likely originating from Rinderpest Virus, along with its “journey” from land to sea (and viceversa), mimicking that of cetaceans' terrestrial ancestors.

Contemporary diagnostic practice in psychiatry relies on the tick-box approach of diagnostic manuals. In light of the obvious limitations of diagnostic systems, narrative formulations, whether in the form of biological, psychodynamic or behavioural cognitive ones, have been proposed. Their approach, which can be caricatured as one of drawing arrows, enriches our clinical tools and practice but in their explicitly theoretical orientation, as well as expanding the field of discovery, they also constrain it. In two previous papers I summarized the resulting limitations, with specific reference to the patient’s experience and proposed further enriching clinical perspicacity by attending to images and parataxis. The specific intent of attending to the patient’s experiences through a process that explicitly eschews narrativization, but allows clinical phenomena to “hang loose”, is to facilitate a process of clinical discovery and healing through practices of co-production between patient and clinician. In the present paper, I expand the range of phenomena that may assist in this co-production through adding attention to dreams to that of images and parataxis. In particular, I turn to the work of the Italian novelist Guido Morselli. Morselli agrues that the self is created through bundling experiences together through acts of “will” in order to establish our personal narrative. In doing so, however, the “will” forbids access to phenomena that do not fit the dominant narrative. Experience is therefore impoverished. Dream consciousness is a type of consciousness not harnessed by the constraints of narrativity. It allows a slipping of the narrative vigilance which bundles phenomena together to create a coherent narrative and thus offers a richer menu of potential experiences, including “bizarre” images that can serve to challenge our usual self-narrative and offer a new perspective on ourselves.

ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

The statistical bundle is the set of couples $(Q,W)$ of a probability density Q and a random variable W such that $\mathbb{E}$_Q [W] = 0. On a finite state space, we assume Q to be a probability density with respect to the uniform probability and give an affine atlas of charts such that the resulting manifold is a model for Information Geometry. Velocity and accelleration of a one-dimensional statistical model are computed in this set up. The Euler-Lagrange equations are derived from the Lagrange action integral. An example of Lagrangian using minus the entropy as potential energy is briefly discussed.

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

Bilateral recurrent nerve damage following total thyroidectomy in thyroid surgery represents severe complications. These complications have almost low incidence thanks also by using the Nerve Intraoperative Monitoring. The aim of this observational retrospective study is to evaluate the inception mode and the recovery time for different clinical laryngeal pictures that arise from this surgery. We enrolled 25 patients with bilateral vocal folds mobility deficit between October 2017 and October 2022, diagnosed in ENT Unit of University of Campania “L. Vanvitelli”, out of a total of 1417 patients undergoing total thyroidectomy. The 25 patients (23F,2M) aged from 24 to 78 years old (average age 51.7) presented a bilateral vocal folds motility deficit (occurring in about 0.1% of cases). All patients underwent 9 months diagnostic/therapeutic process, which started approximately 30 days after thyroid surgery. There are several outcomes of these complications with functional laryngeal defects being mainly related to respiratory and phonatory activities. These clinical manifestations evolve in different ways within a context of a wide range of possibilities, from spontaneous bilateral or monolateral recovery to functional or surgical restoration. This study allowed the acquisition of useful information about prognostic indications and an adequate therapeutic process, based on the specific clinical characteristics.

School-museum relations have gained considerable attention in the academic literature in recent decades. However, there still needs to be more research on their role in enhancing science education. This work reports the outcomes of the recovery, study, and valorization of the 18th-century geo-mineralogical collection belonging to the Collegio Nazareno, now housed at the Istituto San Giuseppe Calasanzio in Rome. The project consisted of four phases: 1) the securing of more than 1720 specimens; 2) their cataloging using the Italian national catalographic standards for the mineralogical and petrological heritage; 3) the establishment of new exhibit and storage areas; 4) the development of a self-instructive exhibition itinerary. The project, which was participated by the students enrolled in the fourth and fifth high school classes, revealed fascinating and unique specimens such as the ones collected by prominent Italian naturalists –e.g., Scipione Breislak (1750–1826) and Carlo Giuseppe Gismondi (1762–1824) – or those comprising the mineralogical collection donated by the Holy Roman Emperor Joseph II (1741–1740) to the Mineralogical Cabinet of the Collegio Nazareno in 1785. This work thus offers significant insights into the importance of natural history school museums as useful (and oft-forgotten) learning tools in science education.

Tourism may not sustainably support territories with limited natural resource stock as islands. The volume in visitor arrivals and the industry investments can increase the pressure even beyond sustainable levels. There is an evident and unresolved tension between these two great polarities, sustainability and economic growth driven by tourism. The aim for policymakers is to find an acceptable equilibrium between these two dimensions. This paper investigates the tourism evolution between 2007 and 2019 in 15 Mediterranean islands, comparing the tourism pressures through statistical indicators. The analysis will compare tourism demand and supply trends in these contexts. The performances will be evaluated to identify the Islands positioning between sustainability needs and tourism development opportunities considering post-covid-19 challenges.

Tissue engineering, also called “regenerative medicine”, refers to attempt to create functional human tissue from cells in laboratory. This is a field that uses living cells, biocompatible materials, suitable biochemical and physical factors and their combinations, to create tissue-like structures.. To date, no tissue engineered skeletal muscle implants have been developed for clinical use, but it may represent a valid alternative to treat volumetric muscle loss in the near future. Herein, we reviewed the literature and showed different techniques to produce synthetic tissues with the same architectural, structural and functional properties of native tissues.

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

Variance-driven decomposition based on the singular spectrum analysis of the European Project for Ice Coring in Antarctica (EPICA) dD, CO2 and CH4 records allowed a novel quantitative structural interpretation of all glacial/interglacial cycles and glacial terminations of the last 800 kyr. This bottom-up approach used the response components of EPICA stacked records to reconstruct the envelope of the thermal response through a physical interference model. The aim was to improve the understanding regarding the features of intensity, amplitude, and asymmetry of 73 marine isotope stages (MIS) and seven terminations. The Antarctic stack record can be described by a variance-weighted interference model of ten thermal waves of different origins (mid-term oscillation, orbitals and suborbitals) that stochastically interfere at a given time according to their relative differences in frequency, intensity, and polarity. Interglacial/glacial stages resulted from constructive interference and bipolar amplification of warming/cooling responses, respectively. The low intensity MISs (including 90% of substages) and the unbiased-dated terminations fell in the low interference regions where dominant destructive patterns minimise the thermal envelope. The positive skewness of the EPICA stack resulted from the constructive interference with a strong bias in the warming direction, especially after the Mid-Brunhes Event. Duration analysis of short eccentricity hemicycles exhibited an intrinsic unexpectedly prolonged mean cooling in the nominal solution (5.8 kyr) and its EPICA response as well (8.6 kyr), along with an interference-induced asymmetry (21.1 kyr). The overall effect resulted in the saw-tooth shape of glacial cycles which is heavily induced by interference and related to the intermediate feedback mechanisms controlled by short eccentricity.

A brief overview of the past and present trajectories made by the A(H5N1) avian influenza virus among domestic birds, avian and mammalian wildlife species and humans is presented here, thereby taking into special account the 2.3.4.4b clade of the virus recently emerged in several geographic areas of the globe.

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

Covid-19 disease is caused by SARS Cov-2 virus. Despite its high transmissibility, the CFR (Case Fatality Rate) of COVID-19 seems to be lower than the SARS (9,5%) and MERS (34,4%) ones⁹³ , but higher than the influenza one (0-1%)^94,95 . The disease is asymptomatic or paucisymptomatic in most of the patients, although in few cases it can be characterized by serious complications. The main causes of hospitalization in intensive care are represented by ALI (Acute Lung Injury), ARDS (Acute Respiratory Distress Syndrome), cardiovascular problems and coagulopathies (diffuse thrombosis, microthrombosis, embolisms, myocarditis, arrhytmias, heart failure, stroke)^96-98, acute nephropathy^99,100 and encephalopathies¹⁰¹. The virus presence in the vascular wall can cause endotheliitis, which triggers the process of diffuse coagulation that can lead to a worsening of the systemic inflammation. The exaggerated inflammatory response seems to be connected with the development of ARDS, MOF (Multiple Organ Failure) and coagulopathies^102-107.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

Keywords: oligozoospermia; male infertility; epididymis; scrotal exploration; scrotal ultrasound; partial epididymal obstruction

There are no investigations about the outcomes of idiopathic PVCs catheter ablation (CA) in athletes compared to sedentary population. We conducted a prospective single-centre observational study. The primary and secondary procedural outcomes were premature ventricular contractions (PVCs) post-ablation reduction in athletes vs. non-athletes group and in agonist vs. leisure-time athletes. The third was the evaluation of the resumption of physical activity and the improvement of symptoms in agonist and leisure-time athletes. From January 2020 to October 2022 we enrolled 79 patients with RVOT/LVOT/fascicular PVC presumed origin. The median percentage of decrease between the pre-procedure and post-procedure Holter monitoring in non-athletes group was 96 (IQR 68 – 98) and 98 in athletes group (IQR 92 – 99) (p=0,08). Considering the athletes, the median percentage of decrease in PVCs number was 98 (IQR 93-99) and 98 (IQR 87-99) respectively in leisure-time and agonistic athletes (p=0,42). Sixteen (70%) leisure time and 17 (90%) agonist athletes (p=0,24) have resumed physical activity 3 months after PVCs CA; among agonistic athletes, 59% have resumed competitive physical activity. Much of leisure-time (88%) and agonist (70%) athletes experienced an improvement in symptoms after ablation. PVC CA was effective and safe in both groups, reducing symptoms and allowing a quick and safe return to sports activities in athletes.

The paper aims at presenting the results obtained in the development of a system allowing the detection and monitoring of forest fires and the continuous comparison of their intensity when several events occur simultaneously, as usually happens in the European Mediterranean countries during the summer season. The system, called SFIDE (Satellite FIre DEtection), exploits a geostationary satellite sensor (SEVIRI on board of MSG satellite series). The algorithm was developed several years ago in the framework of a project (SIGRI) funded by the Italian Space Agency (ASI). This algorithm has been completely reviewed in order to enhance its efficiency by reducing false alarms rate preserving a high sensitivity. Due to the very low spatial resolution of SEVIRI images (4x4 km² at Mediterranean latitude) the sensitivity of the algorithm should be very high to detect even small fires. The improvement of the algorithm has been obtained by: introducing the sun elevation angle in the computation of the preliminary thresholds to identify potential thermal anomalies (hot spots), introducing a contextual analysis in the detection of clouds and in the detection of night-time fires. The results of the algorithm have been validated in the Sardinia region by using ground true data provided by the regional Corpo Forestale e di Vigilanza Ambientale (CFVA). A significant reduction of the commission error (less than 10%) has been obtained with respect to the previous version of the algorithm and also with respect to fire-detection algorithms based on low earth orbit satellites.

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.

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

Triangular resonators re-shaped with the Sierpinski geometry and U-shaped resonators have been designed, linking them with single-pole-double-through (SPDT) RF MEMS switches to provide frequency tuning for potential applications in the K-Band. Prototypes of band-stop narrowband filters working around 20 GHz and 26 GHz, interesting for RADAR and satellite communications, have been studied in coplanar waveguide (CPW) configuration, and the tuning was obtained by switching between two paths of the devices loaded with different resonators. As a result, dual-band operation or fine-tuning can be obtained depending on the choice of the resonator, acting as a building block. The studied filters belong to the more general group of devices inspired by the metamaterial design.

Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcome in high-risk patients. This retrospective case-control study involved two cohorts of 14 patients (“discovery cohort”) and 12 patients (“validation cohort”) with cSCC located in head-neck anatomical district and diagnosed at pT2 stage. Overall, cases developed early local relapse of the disease whereas controls never re-lapsed during the entire follow-up period. Next generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutation was identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating the recognition by the immune system. This could enhance and sustain immunological response, potentially preventing future recurrences.

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

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle >10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage III IV or higher cases. Conclusions: Early diagnosis and treatment before age 45, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management.

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

The presence of heavy metals in industrial effluents has recently become a source of concern for human health and the environment. Efficient removal of metal ions and wastewater treatment is essential for protecting public health and the environment. In this study, we present an eco-friendly, green synthesis of reactive and fully dispersed zerovalent iron nanoparticles (nZVI) in carbon nanofibers via an electrospinning technique. In this novel study, green tea (GT) was used as environmentally friendly, polyvinyl alcohol (PVA) was used for the stabilization and reduction of nZVI, and tetraethyl orthosilicate (TEOS) was added to provide flexibility and to increase the specific surface area of the nZVI based nanofibers. GT contains polyphenols, which act as reducing agents, converting iron ions into nZVI and the particles can then serve as the building blocks for the carbon nanofibers. TEOS can also contribute to the stability of the nZVI by coating their surfaces with a silica layer. This silica layer helps prevent the oxidation of the nZVI, thereby reducing their catalytic activity. The nZVI-based composite (∼ 400 nm) / carbonized (∼ 200 nm) nanofibrous mats were fully characterized by scanning electron microscopy. The average size of the nZVI embedded in the composite and carbonized nanofibers can range from 50 nm to 100 nm. The x-ray diffraction (XRD) analysis of nZVI-based carbon nanofibers showed that there is no crystallinity and a single-phase cubic structure. Both energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FTIR) analysis also confirmed the formation of single-phase nZVI-based composite / carbonized nanofibers. The high intensity of the peaks in the FTIR spectrum indicates the formation of nZVI in the nanofibers structure. The electrospun nZVI-based carbon nanofibers have a higher surface area and better reactivity due to small particle size and large surface area-to-volume ratio. They can provide excellent water stability and dispersibility in water compared to bulk nZVI, which tend to agglomerate and settle quickly. Additionally, nanofiber morphology can enhance the mechanical strength and durability of the composite material. Due to low-cost synthesis and their high efficiency in removing pollutants, these nanofibers could be used as nano-filters for wastewater treatment.

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

Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.

In this paper, we present an experimental procedure to enhance the dimensional accuracy of fabrication via Stereolithography (SLA) of features at the micro-scale. Using a custom benchmark part, deviations in feature dimensions (micro-pores diameters and depths) were detected and measured by confocal microscopy. Samples characterization and experimental observations allowed the identification of inaccuracy sources, mainly due to the laser beam scanning strategy and to the incomplete removal of uncured liquid resin in post-processing (i.e., IPA washing). As a technology baseline, the measured dimensional errors on pores diameters were up to -46%. A compensation method of the nominal laser spot diameter (85m) was defined and implemented resulting in relevant improvements in dimensional accuracy of 9.8% and 11.3% on full-open pores diameter and depth, respectively. Further investigation was performed on a customized test part to adjust the calibration procedure. The measurements revealed that the estimate of the laser beam spot size is 968m. Measurements on micro-pores having different sizes revealed that a constant compensation parameter (i.e., C=85, 96, 120m) is not fully effective at the micro-scale, where average errors still remain at -24%, -18.8%, and -16% for compensations equals to 85, 96 and 120m, respectively. A further experimental campaign allowed the identification of an effective nonlinear compensation law where the compensation parameter depends on the micro-feature size C= f (D). Results show a sharp improvement in dimensional accuracy on micro-pore fabrication, with errors consistently below +8.2%. The proposed compensation method can be extended for the fabrication of any micro-features without restrictions on the specific technology implementation. Concerning the inaccuracy introduced by the laser path, experimentation with a customized part allowed the optimization of the part orientation to reduce the errors and their differences along the X and Y machine axes.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the oc-currence of their assembly in supercomplexes providing additional functional properties as compared with randomly colliding isolated complexes. According to the plasticity model, these two structural states of the respiratory chain may interconvert influenced by the intracellular prevailing conditions and in previous studies we candidated the mitochondrial membrane po-tential as a factor controlling their dynamic balance. Here, we extended those studies investigating if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. Analysis of inhibitory-titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The results attained inhibiting pharmacologically either PKA and sAC indicate that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influences their assembly state in response to the membrane potential. This conclusion is supported by scrutiny of the available structure of the CI,CIII2,CIV respirasome enabling to map several PKA-target serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

Obstructive Sleep Apnea (OSA) surgery is now a viable solution in selected patients and the “remodelling” palatopharyngeal surgery is the most common one. Recently it becomes less in-vasive with the introduction of Barbed Sutures (BS). An optimization of surgical technique is represented by Barbed pharyngoplasty (BP), that requires surgical precision and needs efficient and precise oropharyngeal visualization. Consequently, the lighting system is of pivotal im-portance in BP. The aim of this work is to describe the first experience on the use of a new light-ing system, called KlaroTM in BP for OSA. We evaluated the Klaro™ system in 15 consecutives BP for OSA in comparison with conventional headlamp illumination. The visualization of pala-topharyngeal muscle in the bottom of the tonsillar fossa, entry and exit needle, such as needle tip were statistically better with KlaroTM than headlamp illumination both for surgeon and resi-dent (p<0.05). No significant differences for the visualization of the posterior pharyngeal wall and uvula were reported. The KlaroTM lighting system allows a satisfied illumination of oral cavity and oropharynx in the majority of cases. We encourage to use of KlaroTM not only in BP for OSA, but also in all oral and pharyngeal surgeries, including tonsillectomy and oncological surgery.

Autism Spectrum Disorder etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and kynurenine pathway. Here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies, also, have identified some important polymorphisms in chromosome loci related to human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates kynurenine pathway with increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of kynurenine’s branch induces depletion of melatonin and serotonin worsening ASD symptoms. In this scenario, kynurenine pathway appears as a pharmacological target to treat and prevent ASD. Thus, in genetically predisposed subjects aberrant neurodevelopment may derives from a complex interplay between inflammatory process, mitochondrial dysfunction, oxidative stress and kynurenine pathway overexpression. To validate previous hypothesis a new translational research approach is necessary.

The purpose is to verify trends of scientific production from 2010 to 2020, considering the best universities of the United States, China, the European Union (EU) and private companies. The top 30 universities in 2020 in China, the EU, and the US and private companies were selected from the SCImago institutions ranking (SIR). The positions in 2020, 2015, 2010 in SIR and three sub-indicators were analyzed by means of non-parametric statistics, taking into consideration the effect of time and group on rankings. American and European Union universities have lost positions to Chinese universities and even more to private companies, which have improved. In 2020, private companies have surpassed all other groups considering Innovation as sub-indicator. The loss of leadership of European and partly American universities mainly concerns research linked to the production of patents. This can lead to future risks of monopoly that may elude public control and cause a possible loss of importance of research not linked to innovation.

The COVID-19 pandemics has had an unprecedented global impact, and the COVID-19 mass vaccination campaign has been commonly regarded as crucial to overcome the pandemics. Since all-cause mortality is the best way to measure the consequences of a health intervention, the present study was devised to analyze the all-cause mortality data of the United Kingdom (UK), which are made publicly available broken down by vaccination status. Data from January to May 2022 were retrospectively collected and analyzed according to age groups and vaccination status and the relative risk (RR) for all-cause mortality was calculated in comparison to the corresponding unvaccinated groups. All-cause mortality RR was also calculated from January to May 2021 for vaccinated people. Results show that the all-cause mortality RR was higher in people who received one or two doses of COVID-19 vaccines throughout the whole period and in any of the age groups considered. People vaccinated with three doses more than 21 days earlier had RRs lower than unvaccinated people, which however linearly increased over time. RR in vaccinated people of all ages in comparison to unvaccinated people were lower in January-May 2021, however they steadily grew over time. The finding that all-cause mortality RR in vaccinated in comparison to unvaccinated people increases over time requires careful examination to understand the underlying factors. Meanwhile, all the other major countries should undertake a systematic collection of all-causes mortality broken down by vaccination status, and mass vaccination campaigns should be suspended.

The paper deals with the Compound Inverse Rayleigh distribution, shown to constitute a proper model for the characterization of the probability distribution of extreme values of wind-speed, a topic which is gaining growing interest in the field of renewable generation assessment, both in view of wind power production evaluation and the wind-tower mechanical reliability and safety. The first part of the paper illustrates such model starting from its origin as a generalization of the Inverse Rayleigh model - already proven to be a valid model for extreme wind-speeds - by means of a continuous mixture generated by a Gamma distribution on the scale parameter, which gives rise to its name. Moreover, its validity to interpret different field data is illustrated, also by means of numerous numerical examples based upon real wind speed measurements. Then, a novel Bayes approach for the estimation of such extreme wind-speed model is proposed. The method relies upon the assessment of prior information in a practical way, that should be easily available to system engineers. In practice, the method allows to express one’s prior beliefs both in terms of parameters, as customary, and/or in terms of probabilities. The results of a large set of numerical simulations – using typical values of wind-speed parameters - are reported to illustrate the efficiency and the accuracy of the proposed method. The validity of the approach is also verified in terms of its robustness with respect to significant differences compared to the assumed prior information.

Auricular keloids pose significant aesthetic and functional challenges, and traditional treatments often fall short in ad-dressing these. Our study presents an innovative combined approach of ablative CO2 and dye laser therapy for improved keloid management. This treatment protocol was applied to 15 patients with auricular keloids after an initial multispec-tral analysis to assess keloid composition. The laser sequence was tailored per patient based on this analysis. Evalua-tions using the Vancouver Scar Scale and Patient and Observer Scar Assessment Scale were carried out at baseline and at 3-week intervals post-treatment. The results showed a significant reduction in these scores at the final follow-up (p<0.05), suggesting improvements in keloid color, texture, and pliability, with minimal adverse events. Additionally, no recur-rence of keloids was observed. Our findings indicate that this novel methodology of multispectral analysis followed by tailored laser therapy may offer a safe and effective solution for auricular keloids, promising enhanced keloid treatment and prevention of recurrence. However, further investigations, including randomized controlled trials, are needed to confirm and optimize this treatment protocol.

Predictive numerical models in the study of ground-borne vibrations generated by railway sys-tems have traditionally relied on the segmented approach of subsystems. In this approach, loads are individually applied, and the cumulative effect of rolling stock is obtained through superposi-tion. While this method serves to mitigate computational costs, it may not fully capture the com-plex interactions involved in ground-borne vibrations. Recent advancements in computational and software tools have enabled the development of more sophisticated vibrational pollution models. These advanced models encompass the entire dynamic system, from the rolling stock to the terrain, allowing for continuous simulations with a defined time step. Furthermore, the incorporation of computational contact tools between various ele-ments not only ensures temporal accuracy but also extends the analysis to the frequency domain. This paper explores the evolution of predictive numerical models in the context of ground-borne vibrations generated by trains on ballasted tracks. It highlights the shift from segmented models to continuous simulations, demonstrating the progressive advancement towards more comprehen-sive and accurate representations of railway-induced and generated vibrations in the track sur-roundings as an additional way of evaluate sustainability of infrastructures. In particular, this development of a numerical model from its inception aimed to expand upon ex-isting emission - prediction models by enriching the data with frequency-domain information. This approach has been driven by the aspiration to bridge the gap between numerical predictions and measured signals, striving for a higher level of accuracy in our obtained results. This model can predict the impact of a high-speed rail (HSR) vehicle passing on its own track. It possesses sufficient information in both the time and frequency domains to precisely characterize vibrations. This initiative marks a pivotal advancement, enabling us to more effectively capture the intricacies of ground-borne vibrations and their impact on the surrounding environment due to a deeper comprehension of the occurrences in the frequency domain, there's a heightened ca-pability to accurately characterize vibrations.

The extensive use of rare earth elements (REEs) in a number of technologies is expected to impact on human health, including occupational REE exposures. A body of experimental evidence on REE-associated toxicity has been accumulated in recent decades. Unlike experimental studies, the consequences of REE exposures to human health have been subjected to relatively fewer investigations. Geographical studies have been conducted on residents in the Chinese REE mining districts, reporting on REE bioaccumulation, and associations between REE residential exposures and adverse health effects. A more limited series of studies has been focused on occupational REE exposures, such as movie operator (with occurrence of cerium aerosol) with the observation of pneumoconiosis and lung fibrosis. Similar effects have been reported in case reports for other workers, such as a lens grinder and a printer exposed to carbon-arc lamp emission. As for the occupations related to REE mining and processing, REE bioaccumulation in scalp hair and excess REE urine levels were reported. A study was devoted to workers employed in e-waste separation, showing alterations of several plasma markers. As for other REE occupational exposures, mention should be made of: a) mechanical workshops, with exposures to diesel exhaust microparticulate (containing nanoCeO₂ as a catalytic additive) and, b) production and manufacture of REE supermagnets for hybrid engines and wind turbines. Diesel exhaust microparticulate has been studied in animal models, leading to evidence of several pathological effects in animals exposed by respiratory or systemic routes. As for supermagnet production and manufacture, a body of literature is reviewed of experimental studies, and of human exposure studies showing several pathological effects of static magnetic fields, warranting further investigations.

Many metabolic processes at the molecular level support both viral attack strategies and human defenses during Covid-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021-2023) from PubMed reporting the discovery of hub-nodes specific for the liver during covid-19, identifying 142 hub-nodes. They are highly connected proteins from which to get deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to get by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein bio-synthesis. We used the SARS2-Human-Proteome Interaction Database (33,791 interactions), de-signed by us with BioGRID data to implement a reverse-engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins di-rectly involved in Covid, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary-topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs.

This paper describes different variants of broadband and simple attenuator modules for beamforming applications, based on Radio Frequency Micro Electro-Mechanical Systems (RF-MEMS), framed within Coplanar Waveguide (CPW) structures. The modules proposed in the first part of this work differ in their actuation voltage, topology, and desired attenuation level. Fabricated samples of basic 1-bit attenuation modules, characterized by a moderate footprint of 690 x 1960 µm2 and aiming at attenuation levels of -2, -3 and -5 dB in the 24.25-27.5 GHz range, are presented in their variants featuring both low actuation voltages (5-7 V) as well as higher values (~ 45V), the latter ones ensuring larger mechanical restoring force (and robustness against stiction). Beyond the fabrication non-idealities that affected the described samples, the substantial agreement between simulations and measurement outcomes proved that the proposed designs could provide precise attenuation levels up to 40 GHz, ranging up to nearly -3 dB and -5 dB for the series and shunt variants, respectively. Moreover, they could be effective building blocks for future wideband and reconfigurable RF-MEMS attenuators. In fact, in the second part of this work, combinations of the discussed cells and other configurations meant for larger attenuation levels will be investigated.

Abstract Precision medicine is essentially based on reliable and non-invasive biomarkers. Aim of this review has been to describe the newest biomarkers in the field of kidney transplantation and the kidney rejection, one of the commonest and severe complications. Standard of care tools to identify acute rejection are largely full of errors and of drawbacks. In recent years new and reliable biomarkers have been found. They are avoid of risks, non-invasive and able to detect rejection even in those frequent cases in which acute rejection are clinically asymptomatic and not otherwise identifiable. In recent years several biomarkers have been identified. Very recently have been found new relevant biomarkers able to diagnose rejection with high positive predictive value and low negative predictive value. These are the donor derived cell free DNA found in the recipient, the gene expression profile of the donor found in the recipient and the urinary cytokines that express modification in the graft tissue. The aim of this study has been to find the most recent findings in the literature on this topic and to describe the utility and possible limitation of such new biomarkers on kidney rejection.

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

Exoskeleton robots are a rising technology in industrial contexts to assist humans in onerous applications. Mechanical and control design solutions are intensively investigated to achieve a high performance human-robot collaboration (e.g., transparency, ergonomics, safety, etc.). However, the most of the investigated solutions involve high-cost hardware, complex design solutions and standard actuation. In the presented work, an industrial exoskeleton for lifting and transportation of heavy parts is proposed. A low-cost mechanical design solution is proposed, exploiting compliant actuation at the shoulder joint to increase safety and transparency in human-robot cooperation. A hierarchic model-based controller is then proposed (including the modeling of the compliant actuator) to actively assist the human while executing the task. An inner optimal controller is proposed for trajectory tracking, while an outer fuzzy logic controller is proposed to online deform the task trajectory on the basis of the human’s intention of motion. A gain scheduler is also designed to calculate the optimal control gains on the basis of the performed trajectory. Simulations have been performed in order to validate the performance of the proposed device, showing promising results. The prototype is under realization.

In this work a new method is proposed to tackle down the multiple objective optimization problem of the calculation of cation distribution in spinels structure, through the difference of intensity ratios between experimental and calculated intensities of cation sensitive Bragg planes, by introducing a new factor, Rabs, in Bertaut method. This factor is introduced as the sum of absolute R factors, and it is minimized by varying cation distribution. To test this method aluminate manganese spinel where synthesized though modified Pechini method and characterized though XRD. The results show to be in agreement with literature for the aluminum inversion in tetrahedral sites, which is near to the reported value of 10%. Also, it was noticed that the manganese atoms are present in octahedral sites with a mixed valence state of +2 and +3. Which might be an indicator that oxygen vacancies are present in the structure, so the vacancies value of oxygen is proposed considering the total charge of cations and thus proposing the value of 3.678 mol per formula unit of the spinel, thus having the next stoichiometry considering normalized Al and Mn, MnAl2O3.678. Finally, the last cation distribution proposed was [Mn0.867^(+2) Al0.129^(+3) ][Mn0.034^(+2) Mn0.098^(+3) Al1.871^(+3) ] O3.678 with a Rabs factor value of 0.6466, which considers the cation distribution and oxygen vacancies.

What is the function of cognition? On one influential account, cognition evolved to co-ordinate behaviour with environmental change or complexity (Godfrey-Smith 1996). Liberal interpretations of this view ascribe cognition to an extraordinarily broad set of biological systems – even bacteria, which modulate their activity in response to salient external cues, would seem to qualify as cognitive agents. However, equating cognition with adaptive flexibility per se glosses over important distinctions in the way biological organisms deal with environmental complexity. Drawing on contemporary advances in theoretical biology and computational neuroscience, we cash these distinctions out in terms of different kinds of generative models, and the representational and uncertainty-resolving capacities they afford. This analysis leads us to propose a formal criterion for delineating cognition from other, more pervasive forms of adaptive plasticity. On this view, biological cognition is rooted in a particular kind of functional organisation; namely, that which enables the agent to detach from the present and engage in counterfactual (active) inference.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.