Sensitivity to weather conditions, and specially to clouds, is a severe limiting factor to the use of optical remote sensing for Earth monitoring applications. A possible alternative, is to resort to weather-insensitive synthetic aperture radar (SAR) images. However, in many real-world applications, critical decisions are made based on some informative spectral features, such as water, vegetation or soil indices, which cannot be extracted from SAR images. In the absence of optical sources, these data must be estimated. The current practice is to perform linear interpolation between data available at temporally close time instants. In this work, we propose to estimate missing spectral features through data fusion and deep-learning. Several sources of information are taken into account - optical sequences, SAR sequences, DEM - so as to exploit both temporal and cross-sensor dependencies. Based on these data, and a tiny cloud-free fraction of the target image, a compact convolutional neural network (CNN) is trained to perform the desired estimation. To validate the proposed approach, we focus on the estimation of the normalized difference vegetation index (NDVI), using coupled Sentinel-1 and Sentinel-2 time-series acquired over an agricultural region of Burkina Faso from May to November 2016. Several fusion schemes are considered, causal and non-causal, single-sensor or joint-sensor, corresponding to different operating conditions. Experimental results are very promising, showing a significant gain over baselines methods according to all performance indicators.

The symptoms most commonly reported by patients affected by coronavirus disease 2019 (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g. high blood pressure, thrombosis, pulmonary embolism) seem to suggest that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ of COVID-19.

Abstract Background The advent of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a e challenge. Objective This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results Our search included 55 pertinent studies conducted between 2019 and 2023. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, disability), high responder rates, and optimal safety and tolerability profiles. Conclusion Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an unprecedented finding in clinical neurology.

Patients with inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.

Radial nerve palsies present a challenging clinical scenario, often leading to substantial functional impairment. This study focuses on evaluating the outcomes of tendon transfer surgeries in patients with post-traumatic radial nerve injuries. The radial nerve, vital for upper limb movements, faces various etiologies such as trauma, compression, or idiopathy. Patients with radial nerve palsy encounter difficulties in daily activities, emphasizing the need for effective management strategies. The research introduces a novel evaluation protocol, aiming to comprehensively assess tendon transfer outcomes. This protocol incorporates functional movements of wrist and finger joints, encompassing both objective and subjective parameters. The retrospective study includes eleven patients treated between 2010 and 2022, with a minimum follow-up of one year post-surgery. Tendon transfers demonstrated positive results. The evaluation protocol covers a wide range of parameters, including wrist and finger mobility, thumb function, grip strength, and patient satisfaction. The results indicate successful restoration of motor function, with an average grip strength of 70% compared to the healthy arm. The proposed evaluation protocol facilitates standardized and reproducible assessment, minimizing subjective errors in clinical evaluations. Despite the study's limitations, such as a relatively small sample size, the findings underscore the effectiveness of tendon transfers in treating radial nerve palsies. The introduced evaluation scheme provides a comprehensive and reproducible approach to assess outcomes, contributing to the global standardization of tendon transfer assessments in radial nerve injuries.

: Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors as genetic, immune response and gut microbiota. Actually, the therapy comprises salicylates, immunosuppressive agents, corticosteroids, biologic drugs. International guidelines don’t recommend the use of antibiotics except for septic complications of CD patients. The increased evidence of the implication of gut bacteria in this chronic disease support the rationale for using antibiotics as primary treatment of active CD. In the last decades several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E.coli) species and Mycobacterium avium paratubercolosis (MAP), aroused the interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment in CD patients but randomized trials of antibiotic treatments against E.coli and MAP did not show prolonged benefits, and only generated conflicting results so much so that several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course and the outcome measures. In this article we attempted to provide an overview and update of the trials on antibiotic treatment in active CD patients taking into account the role of pathogens, the mechanism by which the different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also tried to draw new lines for future studies to use antibiotics to treat active CD patients

Delayed Gastric Conduit Emptying (DGCE) occurs in 15-39% of patients who underwent esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD), represent the main endoscopic procedures, but comparative data are currently unavailable. We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma), median age 62 years (IQR 55-70), were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p=0.02) and Kaplan-Meier analysis with log-rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8-1.5; p=0.001) and a shorter median time to discharge of 1 day (95% CI 1-3; p=0.0001). Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. Standard treatment of HF includes angioten-sin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorti-coid-receptor antagonists, beta-blockers, and sodium-glucose co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with de-creased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of HFrEF therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater num-ber of medications for the management of these patients. This review covers vericiguat's metab-olism, molecular mechanisms, and drug-drug interactions.

Intestinal gases are usually discarded as physiologically inert, useless sub-products of colonic fermentation that must be expelled to prevent discomfort and meteorism. Starting from the observation that many living beings use exogenous and/or endogenous gases to attain evolutionary benefits, we question whether intestinal gases in healthy humans could have underestimated physiological effects, either intestinal or extra-intestinal. We examine gaseous volume, composition, source and local distribution in proximal as well as distal gut, providing extensive data that may serve as reference for future studies. We analyze each one of the most abundant intestinal gases and describe their diffusive patterns, active trans-barrier transport dynamics, chemical properties, intra-/extra-intestinal metabolic effects mediated by intracellular, extracellular, paracrine and distant actions. Discussing the physical properties of the whole intestinal gaseous mixture, we illustrate how changes in volume/pressure can be generated by two different mechanisms, namely, physical muscular gut contraction and biological colonic fermentation, with quite different metabolic outcomes. The experimental gas laws suggest that the gaseous exchanges between lumen and bloodstream are impaired by muscular contraction and improved by muscular relaxation. In turn, the surface-area-to-volume ratio suggests that the gaseous exchanges are impaired by microorganismal overproduction and improved by microorganismal reduction. Further, theoretical stochastic approaches from probability theory indicate that the non-turbulent, random paths of gas molecules inside colonic haustra do not homogenously spread over the whole mucosal surface. This means that the intestinal area available for lumen/blood metabolic exchanges is much less than expected not just in disease states, but also in healthy individuals.

Background : Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis. However, Methods: We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy denoting acute myocarditis, with normal coronaries and valves. Tissue samples were processed for histology (H&E), immunohistochemistry for the evaluation of inflammatory infiltrates, immunostaining for alpha-sarcomeric-actin, junctional connexin-43, Ki-67, phosphorylated STAT3 (p-STAT3) and Western Blot (WB) for HMGB1. Frozen samples were analyzed with polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies. Results: NGCs were defined as small myocytes (diameter < 10 µm) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic α-sarcomeric actin and connexin 43. Their number/mm2 in relation with age and pathway of integration were evaluated. NGCs crossed the membrane and grew integrated within the empty necrotic myocytes. NGC mean diameter was 6.6 ± 3.34 vs 22.5 ± 3.11 µm adult cells; their number, in comparable LVEF, was 86.3 ± 10.3/mm2 in patients between 10 and 40 years; 50.4 ±13.8/mm2 in those between 41 and 60; 15.1 ± 5.7/ mm2 in those between 61 and 80; control NGC mean diameter was 0.2± 0.2/mm2. PCR was positive for viral genomes in 16% of cases; NGCs were not statistically different in viral and non-viral myocarditis. WB analysis revealed a higher expression of HMGB1 in myocarditis compared to myocardial controls. Conclusions: NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes consents preservation of cardiac structure and function.

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Background: The acute hemodynamic response to isometric exercise in hypertensive patients ischemic heart disease (IHD) has been poorly investigated. The aim of this study was to assess acute changes on left ventricular myocardial work (MW) during isometric bilateral knee extension in patients with IHD. Methods. Twenty stable hypertensive patients with IHD and ten healthy, age-matched controls (HC) were enrolled. All subjects performed an isometric knee extension exercise, at 30% of their maximal voluntary contraction. The effort was maintained for three minutes or until exhaustion. At baseline, at peak exercise and after 10 minutes of recovery, echocardiography evaluation was perforned, blood pressure (BP) and heart rate (HR) were measurement. Results. The exercise was well tolerated by all subjects. At peak exercise: systolic BP in the IHD was significantly higher than HC (37.6± 7.2 vs 8.4±2.3 mmHg; p = 0.002). HC group had a greater increase in HR than IHD (19.7±6.2 vs 8.4±2.2 bpm; p = 0.009). E/E’ ratio increased in IHD and was unchanged in control. Global work index increased significantly in IHD compared to HC (+15% vs +3%; p 0.026). Global constructive work increased significantly in IHD compared to HC (+29.8% vs +7.4 respectively, p 0.031). Global waste work increased by 92.3% in IHD and was unchanged in HC. Global work efficiency decreased in IHD (-18%) while was unchanged in HC (between-groups p 0.019). Stroke volume decreased in IHD. and was unchanged in HC. Cardiac output was unchanged in IHD while it increased in HC. Conclusion: In patients with hypertension and underlying IHD, an acute isometric load caused a great increase in systolic BP and LV filling pressure. It follows a mostly ineffective increase of MW that fails to maintain stroke volume.

The internationals guidelines about food intolerances, allergy and immunity provide for rigorous steps in which ultrasonography is not provided. However there is evidence in literature about an ancillar role of ultrasonography in these conditions. In this report we analyze the main pathologies with allergic or immune pathogenesis

Background/Objectives: Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety is limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. Methods: Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsy-chiatric AE and one of the MM-approved mAbs as the suspect drug (i.e., daratumumab, elo-tuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. Results: Unknown signals of disproportionate reporting (SDR) included cerebral infarction for daratumumab (n = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC025-IC075 = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guil-lain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthos-tatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elontuzumab (4; 28.31, 10.58-75.73; 5 , 3.24-6.08). Conclusions: Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsy-chiatric AEs, including GBS, further investigations are necessary.

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

The present exploratory study tested the hypothesis that computerized cognitive training (CCT) in home telemonitoring may beneficially affect eyes-closed resting-state electroencephalographic (rsEEG) rhythms in Parkinson's disease patients with cognitive deficits (PDCD). A Eurasian database provided clinical-demographic-rsEEG datasets in 40 PDCD patients, 29 PD patients without cognitive deficits (PDNCD), 40 Alzheimer’s disease patients with cognitive deficits (ADCD), and 40 cognitively normal older adults (Healthy). Sixteen of the 40 PDCD patients completed a cross-over unsupervised CCT program of simple, serious video games (versus a sham program) consisting of 14 daily sessions of approximately 20 minutes each in the patients' homes. Compared to the Healthy, PDNCD, and ADCD groups, the PDCD group was characterized by greater diffuse rsEEG delta (about 2-4 Hz) and theta (about 4-7 Hz) source activity. The PDCD patients who underwent the CCT program showed an improvement in video game performance and a reduction in these delta-theta source activities after this program compared to the control condition. In conclusion, these results suggest that the 2-week CCT program in home telemonitoring may mitigate the abnormal “slowing” of rsEEG rhythms in PDCD patients, possibly enhancing the regulation of brain arousal and quiet vigilance.

Objectives: To evaluate atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF. Background: Reduced levels of SERCA have been reported in the peripheral blood cells of patients with AF. We hypothesize that SERCA levels can predict the response to epicardial ablation. Methods: We designed a prospective, multicenter observational study to recruit, from October 2014 to June 2016, patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation. Results: We enrolled 27 patients; responders patients (n=15) did not present AF recurrence after epicardial ablation at 1-year follow-up. These patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type Natriuretic Peptide (BNP), and over expression of SERCA as compared to baseline and to non-responders (p<0.05). Furthermore, mean AF duration (HR 1.235 [1.037-1.471], p<0.05), LAV (HR 1.755 [1.126-2.738], p<0.05), BNP (HR 1.945 [1.895-1.999], p<0.05), and SERCA (HR 1.763 [1.167-2.663], p<0.05) were predictive of AF recurrence. Conclusions: Our data indicate that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Therefore, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments.

Variable-Angle Tow (VAT) laminates can improve straight fiber composites mechanical properties thanks to the application of curvilinear fibers. This characteristic allows to achieve ambitious objectives for design and performance purposes. Nevertheless, the wider design space and the higher number of parameters result in a more complex structural problem. Among the various approaches that have been used for VATs study, Carrera’s Unified Formulation (CUF) allows to obtain multiple theories within the same framework, guaranteeing a good compromise between the results accuracy and the computational cost. In this article, the linear buckling behavior of VAT laminates is analyzed through the extension of CUF 2D plate models within the Reissner’s Mixed Variational Theorem (RMVT). Results show that RMVT can better approximate the prebuckling non-uniform stress field of the plate when compared to standard approaches, thus improving the prediction of the linear buckling loads of VAT composites.

In the Mediterranean Sea, there are two critical issues affecting marine benthic biocenosis: the sedimentation process and the increasing trend in marine biodiversity loss. These processes are very marked along the western side of Calabria coastline where siltation is one of the main reasons for the regression of Posidonia beds in the regional coastal waters. This research aims to investigate the relationships between the geomorphological features of the debris source areas, represented by fluvial basins, and the distribution of Posidonia meadows. So, a geomorphological study of the Tyrrhenian fluvial basins with area greater than 200 km2 and its correlation with the mapping of the meadows in the Calabria Tyrrhenian waters was carried out. Furthermore, in order to assess the increased level of burial in a Posidonia oceanica meadow and its health state over time, a program of Posidonia monitoring was undertaken between 2000 and 2010, in a test area located in the Marine Regional Park of Isca (Calabria, Southern Italy). The results of this survey highlighted that, at the beginning of the study period, for a silting rate of 4 - 5 cm/year, the meadow suffered a reduction of its photosynthetic ratio with a rate of mortality of 50%. In the following years, the siltation rate reach 12 cm/year in 2010 and the meadow began to disappear. Therefore, the marine pollution by sedimentation represents a serious factor for the regression of Posidonia oceanica meadows, enhancing the risk of a gradual loss in marine biodiversity.

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with a low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology ranging from clinical activity to genealogical reconstruction of families/populations along the centuries, creation of databases, and molecular/genetic research, has been modelled on the characteristics of the Calabrian population for more than three decades. This methodology allows to the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, in this population it has been reported a higher prevalence of several hereditary neurodegenerative diseases such as Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Niemann Pick type C disease, Spino-cerebellar ataxia, Creutzfeldt–Jakob disease and Gerstmann Straussler Scheincker disease. Thus, Calabria constitutes a model for the study of neurodegenerative diseases, a sort of "outdoor laboratory" useful for the advancement of knowledge in this field. Here, we summarize and discuss some results of research data supporting the view that Calabria is a genetic isolate and could represent a useful model for the study and characterization of neurodegenerative diseases.

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

Cognitive impairment affects 34-65% of People with Multiple Sclerosis (PwMS), significantly impacting their quality of life. Clinicians routinely address cognitive deficits with in-clinic neuro-behavioural interventions, but accessibility issues exist. Telerehabilitation is a promising solution that utilises digital tools for home-based cognitive remediation. This narrative review assessed the feasibility and efficacy of cognitive telerehabilitation in PwMS, identifying 13 relevant studies. Regarding the feasibility of cognitive telerehabilitation, evidence shows adherence rates are generally good, although, surprisingly, not all studies reported a measure of compliance with the cognitive training explored. Considering the efficacy of different rehabilitative techniques on cognitive performance of PwMS, findings are generally inconsistent, with only one study reporting consistently positive results. A range of methodological limitations are reported as potential factors contributing to the variability of results. Overcoming some of these issues will be key. Upcoming research is necessary to determine optimal intervention approaches, long-term effects of rehabilitation, and how to best integrate the use of telerehabilitation into routine clinical practice. By exploiting digital tools in the best way and addressing methodological concerns, home-based rehabilitation holds the potential for improving cognitive functions and enhancing the quality of life in PwMS.

Deck inclination and vertical displacements are among the most important technical parameters to evaluate the health status of a bridge and to verify its bearing capacity. Several methods, both conventional and innovative, are used for structural rotations and displacement monitoring; no one of these does allow, at the same time, precision, automation, static and dynamic monitoring without using high cost instrumentation. The proposed system uses a common laser pointer and image processing. The elastic line inclination is measured by analyzing the single frames of a HD video of the laser beam imprint projected on a flat target. For the image processing, a code was developed in Matlab® that provides instantaneous rotation and displacement of a bridge, charged by a mobile load. An important feature is the synchronization of the load positioning, obtained by a GNSS receiver or by a video. After the calibration procedures, a test was carried out during the movements of a heavy truck maneuvering on a bridge. Data acquisition synchronization allowed to relate the position of the truck on the deck to inclination and displacements. The inclination of elastic line was obtained with a precision of 0.01 mrad. The results demonstrate the suitability of the method for dynamic load tests, control and monitoring of bridges.

The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of aminoacids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µ-O CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperxcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions.

Deep learning has shown remarkable results in every field, especially in the biomedical field, due to its ability to exploit large-scale datasets. A convolutional neural network (CNN) is a widely used deep learning approach to solve medical imaging problems. Over the past few years, many studies have focused on CNN-based techniques for brain tumor diagnosis. There are, however, still some critical challenges that CNNs face towards clinic application. This study presents a comprehensive review of current literature that involves CNN architectures for brain tumor classification. We compare the key achievements in the performance evaluation metrics of the applied classification algorithms. In addition, this review assesses the clinical effectiveness of the included studies to elaborate on the limitations and directions of this area for future work. No review focusing on the clinical effectiveness of previous works in this field has been published. We believe that this study has the potential to elevate the application of CNN-based deep learning methods in clinical practice and also can be a quick reference for biomedical researchers who are interested in this field.

The goal of clustering is to identify common structures in a data set by forming groups of homogeneous objects. The observed characteristics of many economic time series motivated the development of classes of distributions that can accommodate properties such as heavy tails and skewness. Thanks to its flexibility, the Skewed Exponential Power Distribution (also called Skewed Generalized Error Distribution) ensures a unified and general framework for clustering possibly skewed and heavy tailed time series. This paper develops a clustering procedure of model-based type, assuming that the time series are generated by the same underlying probability distribution but with different parameters. Moreover, we propose to optimally combine the estimated parameters to form the clusters with an entropy weighing $k$-means approach. The usefulness of the proposal is showed by means of application to financial time series, demonstrating also how the obtained clusters can be used to form portfolio of stocks.

The progressive reappearance of the Zika virus (ZIKV) infection since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called Congenital Zika Syndrome (CZS) which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly, neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, epidemiological aspects and modes of transmission of Zika virus infection, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS.

According to the Water Framework Directive, the Ecological Flow (Eflow) is assumed to be the minimum water discharge required to achieve and maintain the environmental objectives of “good quality status” in a natural water body. It is highly recognized that, the hydrological regime of natural flow plays a primary and crucial role influencing the physical conditions of habitats, which in turn determines the biotic composition and sustainability of aquatic ecosystems. Furthermore, the simple assumption to supply a minimum instream during dry periods is not enough any longer in order to protect the river environment. The recent hydro-ecological understanding states that all flow components might be considered as operational targets for water management, starting from base flows (including low flows) to high and flood regimes in terms of magnitude, frequency, duration, timing and rate of change. Several codes have been developed and applied on different case studies in order to define common tools to be implemented for the Eflow assessment. The study proposes the application of the Indicators of Hydrologic Alteration methodology (IHA by TNC) coupled to the valuation of the Index of Hydrological Regime Alteration (IARI by ISPRA) as an operative tool to define the ecological flow in each monitoring cross section to support the sustainable water resources management and planning. The case study of Agri River, in Basilicata (Southern Italy) is presented. The analyses have been carried out on monthly discharge data derived applying the HEC-Hydrological Modelling System at the basin scale using the daily rain data measurements obtained by the regional rainfall gauge stations and calibrated through the observed inlet water discharge registered at the Lago del Pertusillo reservoir station.

Social and spatial characteristics of a population often interact to influence health outcomes, suggesting a need to jointly analyze both to offer useful insights in community health. However, researchers have used either social or spatial analyses to examine community-based health issues and inform intervention programs. We propose a combined socio-spatial analytic approach to develop a social network with spatial weights and a spatial statistic with social weights, and apply them to an ongoing study of mental and physical well-being of rural Latino immigrants in North Florida, USA. We demonstrate how this approach can be used to calculate measures, such as social network centrality, support contact dyads, and spatial kernel density based on a health survey data. Findings reveal that the integrated approach accurately reflected interactions between social and spatial elements, and identified community members (who) and locations (where) that should be prioritized for community-based health interventions.

Sporadic inclusion body myositis (sIBM) is the most common muscle disease of older people and is clinically characterized by slowly progressive asymmetrical muscle weakness, predominantly affecting quadriceps, deep finger flexors and foot extensors. At present there are no enduring treatments for this relentless disease that eventually leads to severe disability and wheelchair dependency. Although sIBM is considered a rare muscle disorder, its prevalence is certainly higher as the disease is often undiagnosed or misdiagnosed. The histopathogical phenotype of sIBM muscle biopsy includes muscle fiber degeneration and endomysial lymphocytic infiltrates that mainly consist of cytotoxic CD8+ T cells surrounding nonnecrotic muscle fibers expressing MHCI. Muscle fiber degeneration is characterized by vacuolization and accumulation of congophilic misfolded multi-protein aggregates, mainly in their non-vacuolated cytoplasm. Many players have been identified in sIBM pathogenesis including environmental factors, autoimmunity, abnormalities of protein transcription and processing, accumulation of several toxic proteins, impairment of autophagy and ubiquitin proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has been also proposed as a contributor to the disease. However, the interplay between these processes and the primary event that leads to the coexistence of autoimmune and degenerative changes is still under debate. Here, we outline our current understanding of disease pathogenesis, focusing on degenerative mechanisms, and discuss the possible involvement of aging.

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

Heart rate (HR) and respiratory rate (RR) are two vital parameters of the body medically used for diagnosing short/long term illness. Out-of-the-body, non-contact HR/RR measurement remains a challenge due to imprecise readings. “Invisible” wearables integrated into day-to-day garments has the potential to produce precise readings with comfortable user experience. Sleep studies and patient monitoring benefit from “Invisibles” due to longer wearability without significant discomfort. This paper suggests a novel method to reduce the footprint of sleep monitoring devices. We use a single silver-coated nylon fabric band integrated into a substrate of standard cotton/nylon garment as a resistive elastomer sensor to measure air and blood volume change across the chest. We introduce a novel event-based architecture to process data at the edge device and describe two algorithms to calculate real-time HR/RR on ARM Cortex-M3 and Cortex-M4F microcontrollers. RR estimations show a sensitivity of 99.03% and a precision of 99.03% for identifying individual respiratory peaks. The two algorithms used for HR calculation show a mean absolute error of 0.81±0.97 and 0.86±0.61 beats/minute compared to a gold standard ECG-based HR. The event-based algorithm converts the respiratory/pulse waveform into instantaneous events, therefore, reducing the data size by 40-140 times and requires 33% less power to process and transfer data. Further, we show that events hold enough information to reconstruct the original waveform, retaining pulse, and respiratory activity. We suggest fabric sensors and event-based algorithms would drastically reduce the device footprint and increase the performance for HR/RR estimations during sleep studies providing better user experience.

Bayesian model calibration techniques are commonly employed in the characterization of nonlinear dynamic systems, as they provide a conceptual and effective framework to deal with model uncertainties, experimental errors and procedure assumptions. This understanding has resulted in the need to introduce a model discrepancy term to account for the differences between model-based predictions and real observations. Indeed, the goal of this work is to enhance model-driven Structural Health Monitoring procedures by incorporating the posterior uncertainty linked to updated model discrepancy, and thus make relevant considerations for its use in the Structural Health Monitoring. Specifically, the Bayesian inference has been applied to the calibration of nonlinear hysteretic systems to both provide: (i) most probable values (MPV) of the parameters following the calibration, and; (ii) estimates of the model discrepancy posterior distribution. The effect of the model discrepancy in the calibration is first illustrated recurring to a single degree of freedom Bouc-Wen type oscillator, and then applied for calibrating a reference nonlinear Bouc-Wen model, deriving from real data acquired on a monitored masonry building.

Energy consumption of processors and memories is quickly becoming a limiting factor in the deployment of large computing systems. For this reason it is important to understand the energy performance of these processors and to study strategies allowing to use them in the most efficient way. In this work we focus on computing and energy performance of the Knights Landing Xeon Phi, the latest Intel many-core architecture processor for HPC applications. We consider the 64-core Xeon Phi 7230, and profile its performance and energy efficiency using both its on-chip MCDRAM and the off-chip DDR4 memory as the main storage for application data. As a benchmark application we use a Lattice Boltzmann code heavily optimized for this architecture, and implemented using several different arrangements of the application data in memory (data-layouts, in short). We also assess the dependence of energy consumption on data-layouts, memory configurations (DDR4 or MCDRAM), and number of threads per core. We finally consider possible trade-offs between computing performance and energy efficiency, tuning the clock frequency of the processor using the Dynamic Voltage and Frequency Scaling (DVFS) technique.

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

The study attempts, above all, to provide a summary, with a strictly scientific basis, about the strategies of conservation of autochthonous agrobiodiversity followed in Italy. A special focus is dedicated on vegetables and, therefore, could represent a contribution to improve the national strategy for the safeguarding of its agrobiodiversity in general. The paper offers also an outlook on the most critical factors of the ex situ conservation and some actions which need to be taken. Some examples of ‘novel’ recovered neglected crops are also given. Finally a case study is proposed: ‘Mugnolicchio’, a neglected race of Brassica oleracea L., cultivated in Altamura (Ba) in southern Italy. ‘Mugnolicchio’ might be considered as an early step in the evolution of broccoli (B. oleracea L. var. italica Plenck) like ‘Mugnoli’ another neglected race described from Salento (Apulia).

During the period of health emergency linked to the current COVID-19 pandemic, the management of children's oral health presents specific problems related to the infectious spread of the disease. These problems must be faced on the one hand by acting on the oral health prevention methods, and on the other by implementing specific protocols relating both to the conditions of oral pathologies that normally do not represent an emergency, and to those clinical situations that fall into the category of pediatric dental emergencies. In this perspective, in addition to defining rigorous and highly effective infection control protocols in the dental settings, it is of fundamental importance to work on remote communication and education aimed at maintaining the oral health of the children. This article, after an analysis of the risk factors from COVID-19 associated with pediatric dental treatment, presents a series of considerations on potential oral prevention strategies and on the management of emergency and non-emergency dental procedures in a context of disease transmission control, proposing new approaches and models of treatment based also on remote interaction techniques which will then retain their usefulness even at the end of the current emergency period.

Variable Angle Tow (VAT) laminates offer a promising alternative to classical straight fiber composites in terms of design and performance. However, analyzing these structures can be more complex due to the introduction of new design variables. Carrera's Unified Formulation (CUF) has been successful in previous works for buckling, vibrational, and stress analysis of VAT plates. Typically, one-dimensional (1D) and two-dimensional (2D) CUF models are used, with a linear law describing the fiber orientation variation in the main plane of the structure. The objective of this article is to expand the CUF 2D plate finite elements family to perform free vibration analysis of composite laminated plate structures with curvilinear fibers. The primary contribution is the application of Reissner's Mixed Variational Theorem (RMVT) to a CUF finite element model. The Principle of Virtual Displacements (PVD) and RMVT are both used as variational statements for the study of monolayer and multilayer VAT plates dynamic behavior. The proposed approach is compared to Abaqus three-dimensional (3D) reference solutions, classical theories and literature results to investigate the effectiveness of the developed models. Results demonstrate that mixed theories provide the best approximation of the reference solution in all cases.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

In microwave imaging it is often of interest to inspect electrically large spatial regions. In these cases, data must be collected over a great deal of measurement points which entails long measurement time and/or costly, and often unfeasible, measurement configurations. In order to counteract such drawbacks, we have recently introduced a microwave imaging algorithm which looks for the scattering targets in terms of equivalent surface currents supported over a given reference plane. While this method is suited to detect shallowly buried targets, it allows to independently process each frequency data, hence the source and the receivers do not need to be synchronized. Moreover, spatial data can be reduced at large extent, without incurring in aliasing artefacts, by properly combining single-frequency reconstructions. In this paper, we validate such an approach by experimental measurements. In particular, the experimental test site consists of a sand box in open air where metallic plate targets are shallowly buried (few cm) under the air/soil interface. The investigated region is illuminated by a fixed transmitting horn antenna whereas the scattered field is collected over a planar measurement aperture at a fixed height from the air-sand interface. The transmitter and the receiver share only the working frequency information. Experimental results confirm the feasibility of the method.

This work presents the results of an experimental socio-economic study conducted in two shanty towns of Messina as part of a systemic urban regeneration and fight against poverty program called Capacity. The study has shown that the development of a positive attitude towards the future and the confidence in others are associated with the development of the riskiest option, which is the one that can give the highest pay-off. The paper also illustrates the expected and unexpected outcomes of projects for individuals and the community, as well as the economic benefits for the public administration and the society of a strategy that reduces the reliance on social welfare measures as well as the local control exercised by organized crime.

The supposition is that the usage of fibrin rich in leukocytes and platelets advanced (A-PRF) in ulcerative osteomyelitis of the diabetic foot allows rehabilitation from this critical illness. In this investigation, the focus was to normalize the use of PRF in patients with osteomyelitis not amputated, to use this second generation platelet concentrate as a regeneration enabler. The researchers submitted and utilized A-PRF membranes (1300 g × 8 min) in 7 patients (all diabetics) with osteomyelitis and cutaneous injury for 6 months. The membranes, in combination with the supernatant fluid produced by stress, have been integrated into the skin lesion down to the bone after surgical debridement. The advancement of the lesions after some period of time has been analyzed. All seven subjects had a Probe-to-Bone positive assay; MRI indicated a cortico-periosteal coagulation and/or foci of cortico-spongeous osteolysis contiguous to the lesion. Gram-positive bacterium were identified in our procedures in 52% of cases. Gram+ Cocci, for example, S. Aureus (15.6%), S. Hemolytic (12.1%), S. Viridans (7.1%), and Gram-negative Bacteria, for example, Pseudomonas (10.6%), Proteus (7.8%), Enterobacter (5.7%) are present. Candida Albicans is active in 2.8%. The blood count shows no relevant differences. To date, cutaneous lesions have cured in 6 of the seven subjects treated (one patient for more than five years) without any evidence of infection or recurrence. The results obtained on our subjects indicate that PRF membranes may be a therapeutic option in this problematic disease.

The supposition is that the usage of fibrin rich in leukocytes and platelets advanced (A-PRF) in ulcerative osteomyelitis of the diabetic foot allows rehabilitation from this critical illness. In this investigation, the focus was to normalize the use of PRF in patients with osteomyelitis not amputated, to use this second generation platelet concentrate as a regeneration enabler. The researchers submitted and utilized A-PRF membranes (1300 g × 8 min) in 7 patients (all diabetics) with osteomyelitis and cutaneous injury for 6 months. The membranes, in combination with the supernatant fluid produced by stress, have been integrated into the skin lesion down to the bone after surgical debridement. The advancement of the lesions after some period of time has been analyzed. All seven subjects had a Probe-to-Bone positive assay; MRI indicated a cortico-periosteal coagulation and/or foci of cortico-spongeous osteolysis contiguous to the lesion. Gram-positive bacterium were identified in our procedures in 52% of cases. Gram+ Cocci, for example, S. Aureus (15.6%), S. Hemolytic (12.1%), S. Viridans (7.1%), and Gram-negative Bacteria, for example, Pseudomonas (10.6%), Proteus (7.8%), Enterobacter (5.7%) are present. Candida Albicans is active in 2.8%. The blood count shows no relevant differences. To date, cutaneous lesions have cured in 6 of the seven subjects treated (one patient for more than five years) without any evidence of infection or recurrence. The results obtained on our subjects indicate that PRF membranes may be a therapeutic option in this problematic disease.

In recent years, autonomous robots have proven capable of solving tasks in complex environments. In particular, robot manipulations in activities of daily living (ADL) for service robots have been in wide use. However, manipulations such as loading a dishwasher or folding laundry are difficult to automate robustly. In addition, manipulations of grasping multiple objects in domestic environments present difficulty. To perform those applications better, we developed robotic systems based on shared autonomy by combining the cognitive skills of a human operator with autonomous robot behaviors. In this work, we present techniques for integration of a shared autonomy system for assistive mobile manipulation and new strategies to support users in the domestic environment. We demonstrate that the robot can grasp multiple objects with random size at known and unknown table heights. Specifically, we developed three strategies for manipulation. From experimental results, we observed that the first strategy has the highest success rate (70% for random objects) up to 70 cm table height. Two other strategies perform better for 80 cm to 100 cm table height. The success rate of the second and third strategies shows an average 63.3% and 73.3%, respectively, for grasping random objects. We also demonstrated these strategies using two intuitive interfaces, a visual interface in rviz and a voice user interface with speech recognition, which are suitable for elderly people. In addition, the robot can select strategies automatically in random scenarios, which make the robot intelligent and able to make decisions independently in the environment. We obtained interesting results showing that the robot adapts to the environmental variation automatically. After these experimental demonstrations, our robot shows the capabilities for employment in domestic environments to perform actual tasks.

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

The history of Artificial Intelligence (AI) development dates to the 40s. The researchers showed strong expectations until the 70s, when they began to encounter serious difficulties and investments were greatly, reduced. With the introduction of the Industry 4.0, one of the techniques adopted for AI implementation is Machine Learning (ML) that focuses on the machines ability to receive data series and learn on their own. Given the considerable importance of the subject, researchers have completed many studies on ML to ensure that machines are able to replace or relieve human tasks. This research aims to analyze, systematically, the literature on several aspects, including publication year, authors, scientific sector, country, institution, keywords. Analyzing existing literature on AI is a necessary stage to recommend policy on the matter. The analysis has been done using Web of Science and SCOPUS database. Furthermore, UCINET and NVivo 12 software have been used to complete them. Literature review on ML and AI empirical studies published in the last century was carried out to highlight the evolution of the topic before and after Industry 4.0 introduction, from 1999 to now. Eighty-two articles were reviewed and classified. A first interesting result is the greater number of works published by USA and the increasing interest after the birth of Industry 4.0.

Forest harvesting generates variable amounts of residue that represent a fire hazard and a hindrance to regeneration and must be managed accordingly. In South Africa, burning is the most common residue management method, but there is an interest in introducing safer and more effective techniques, such as mulching. For that reason, a productivity study was conducted in the Eastern Cape province to gather information on the productivity, cost, and work quality of the three main alternatives: manual broadcasting, manual broadcasting followed by mulching with an adapted farm tractor and mulching with a purpose-built mulcher. Manual broadcasting required 16 h/ha, mulching with a farm tractor 3.6 h/ha, and mulching with a purpose-built mulcher 0.9 h/ha (one pass). Manual broadcasting was the cheapest option, at a cost of 400 ZAR/ha. Mulching with a farm tractor and a purpose-built mulcher incurred a cost of 3 267 ZAR/ha and 4 083 ZAR/ha, respectively. Manual broadcasting achieved a minimal reduction of residue size, with 50% of the slash (branches and stem wood) having a mean length above 40 cm. When mulching with a farm tractor was applied, 49% of the slash (branches and stem wood) length reduced to about 30 cm. When a purpose-built mulcher was used, only 10% of the slash elements exceeded 40 cm length.

The possibility of using some warnings inside modern vehicles should be an aid to the driving activity. However, the information transferred to users is not always received in the expected way due to the variability and complexity of the road environment. This study, therefore, aims to identify a procedure that allows to ascertain whether drivers receive the data in an appropriate way even during particular manoeuvres, such as passing cyclists on a winding road or, on the contrary, if they represent an unnecessary overload. To answer this question, an experimentation in a simulated environment was set up with which the drivers’ visual behaviour was recorded in presence and absence of a driving aid device (On- Board Unit, OBU). The results show that, in some situation, the information provided by the OBU helps to maintain a more virtuous driving behaviour but, in the most complex ones, drivers acquire information from a smaller number of sources, excluding the aid devices present inside the cockpit. This procedure is useful for ADAS designers in order to refine these instruments but also for road managers who can improve safety by inserting appropriate signs or speed limits.

The mutualistic interactions between the oleaginous yeast Lipomyces starkeyi and the green mi-croalga Chloroidium saccharophilum in mixed cultures were investigated to exploit possible syner-gistic effects. As a matter of facts, microalga could act as an oxygen generator for the yeast, while the yeast could provide carbon dioxide to microalga. A lignocellulosic hydrolysate from steam exploded Arundo donax (Giant reed) was used as low cost feedstock. The overall lipid content and lipid productivity obtained in the mixed culture treating the hydrolysate of Arundo donax were equal to 0.081 glipid.gbiomass-1 and 37.2 mglipid.L-1.d-1, respectively. They represented promising re-sults if compared to the model systems where synthetic media were used. This study provided new input for the integration of Single Cell Oil (SCO) production with agro-industrial feedstock and the fatty acid distribution mainly consisting of stearic (C18:0) and oleic acid (C18:1) allows promising applications in biofuels, cosmetics, food additives and other products of industrial interest.

Probiotics are living microbes that provide benefits to the host. The increasing data on health promotion following probiotics administration triggered growing interest among researchers and pharmaceutical companies looking for novel therapeutic or preventive tools. Infections of the lower genital tract in females are caused by a wide range of pathogens, they are widespread, and represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women in their reproductive age at least once during their lifetime. Of these women 5-8% develop the recurrent form (RVVC). The disease onset is triggered by the overgrowth of Candida species on the vaginal mucosa. Here, we evaluated the beneficial properties of the Bacillus coagulans spore-producing LMG S-24828 against C. albicans and C. parapsilosis. Our results show that both alive B. coagulans and its Cell-Free-Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, alive B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells and showed co-aggregation capacity. Overall, B. coagulans LMG S-24828 exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP) as cross-linking agents. The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied. All formulations showed excellent CUR trapping efficiency, exceeding 90%. In particular, the TPP-crosslinked macrobeads released 34 wt% of the charged CUR within minutes, while the remaining 66 wt% was released slowly due to the biodegradation of CS. The results indicate that the correct choice of gelling agent and its concentration leads to spherical particles capable of encapsulating CUR and releasing it in a wide range of kinetics depending on the specific application.

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

(1) Background: The aim of the work was to characterize the climatic evolution and change based on the Multi Criteria Classification through the dynamics of bioclimatic indices in viticulture across Italy and its regional administrative boundaries, focusing on latitudes and elevations. (2) Methods: The impact of climate change on viticulture in Italy was analysed and spatialized with reference to historical data from 1991 to 2021 and to the Future Scenarios up to 2080 assumed by SSP2-4.5 and SSP5-8.5, taking into account 13 GCMs. (3) Results: The bioclimatic indices have all shown a significant trend in the historical period, with an increase in temperature and a decrease in precipitation, reflecting their effects on the entire Italian territory with respect to HI, up to 44°N for CI and up to 46°N for DI, regardless of altitude. The Future Scenarios highlighted a shift towards the warmer classes of the two temperature-based indices (HI and CI) for both SSPs, especially for altitudes up to 900 m a.s.l.. The DI-based classification based on DI remained relatively stable in Italy over time, although DI values will become increasingly negative in the near future. (4) Conclusions: The climate in Italy is warming, especially in the south and in the coastal regions. By 2080, more areas will be “Very Hot” with “Warm Nights.” Drought will also increase and have a negative impact on viticulture. The importance of higher latitudes and altitudes in mitigating the effects of climate change justifies the continuing trend towards the relocation of vineyards as a medium-term solution and as an alternative to targeted cultivation methods that must be adopted in the short-term to safeguard the suitability of an area to quality viticulture.

The aim of this study was to evaluate implants survival rate, marginal bone loss, surgical and prosthetic complications of implants placed through sinus floor elevation and tilted implants en-gaged in basal bone in order to bypass maxillary sinus. 60 patients were enrolled for this study. According with residual bone height of posterior maxilla the sample was divided in three groups of 20 patients: Group A (lateral sinus floor elevation), Group B (transrectal sinus floor elevation) and Group C (tilted implants employed to bypass sinus floor). Follow-up visits were performed one week after surgery, at 3, 6 months and then once a year for next 4 years. The outcomes were implants survival rate, marginal bone loss and surgical and prosthetic complications. Although the Group A, B and C have demonstrated an implants survival rate of 83.3%, 86,7% and 98,3% respectively, the statistically analysis showed that there was no statistically significant difference between groups. Statistically significant differences between the groups were also not found con-cerning marginal bone loss, as recorded by intra-oral X-ray measurements during follow-up. About complications it wasn’t possible to perform a statistical analysis. To as to reduce potential surgical risks implants placement in basal bone should be preferred.

Background: The red swamp crayfish Procambarus clarkii (Girard, 1852), native to the United States and northern Mexico, has been introduced in many countries worldwide. The species has a remarkable invasiveness, due to its high reproductive rate and to its ability to tolerate broad ranges of water parameters like salinity. Nevertheless, no consistent observations of P. clarkii have been reported in the marine environment until now. Methods: Through the observations of a personal acquaintance and of two volunteers who published photos of the species on Facebook marine biology and fishing groups, we collected data showing the presence of the crayfish within marine ecosystems. Results: P. clarkii has been spotted in three different localities, in two of which observations are recurrent. The species can live miles from the nearest freshwater stream, and can colonise the depths up to 20 meters. Conclusions: The multiple observations of P. clarkii collected in our study uncover a persistent presence of the species within some marine areas, rather than its mere sporadic occurrence. As resistance to increasing salinities is influenced by multiple genes, genetic admixture between genetically-differentiated individuals coming from distinct geographical origins could have brought together different salinity-resistance genes, leading to the formation of these resilient phenotypes.

Electronic Nose (eNose) systems are particularly appreciated for their portability, usability, relative low cost and real-time or near real-time response. Their application finds space in several domains, including environmental monitoring. Within this field, marine monitoring is of particular scientific relevance due to the fragility of this specific environment, daily threatened by human activities that can potentially bring to catastrophic and irreversible consequences on marine wildlife. Under such considerations, a systematic review, complying with the PRISMA guidelines, was conducted covering the period up to October 15, 2018, in PubMed, ScienceDirect and Google Scholar. Despite the relatively low number of articles published on this specific topic and the heterogeneity of the technological approaches employed, the results obtained by the various groups highlight the positive contribution eNose has given and can provide in near future for the monitoring and safeguarding of this delicate environment.

Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency. In this study we assess the prevalence of restless sleep disorder, as well as that of periodic leg movements during sleep (PLMS) in these children. Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery or tracheostomy were included. Three groups were compared, children with PLMS index&gt;5, children with restless sleep disorder (RSD), and children with neither elevated PLMS index nor RSD. During the study, 2,577 sleep studies were conducted. Ninety-two studies fit our criteria and were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; after polysomnography 18% were found to have PLMS index &gt;5/hour, 14% fit the criteria for RSD. There were no statistically significant differences in polysomnographic parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). There was elevated frequency of RSD and elevated PLMS in children with history of prematurity that might be linked to the increased risk of iron deficiency in premature infants. These new results add new knowledge on the prevalence of RSD in these children.

Present work investigates, in photon energy domains of specific interest for medical imaging, the effect of the escape of X-ray fluorescence from the scintillator materials on the energy resolution of scintillation detector itself. Monolithic as well as pixelated crystals differently sized are considered, in the case of the NaI because it is the gold standard in the field. The volumetric ratio is introduced, as a figure of merit, taking into account, alongside the surface-to-volume ratio, the geometric shape, the elemental composition and also the mean-free-path for the given scintillator and energy. The inter-crystal XRF escape is finally suggested to be considered among the effects producing image blurring in segmented scintillatros due to the spread of events between the primary pixel and the first neighbors ones.

Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. Here, we comprehensively summarize and systematically review the current experimental evidence on this topic.

Accurate knowledge of the rain amount is an crucial driver in several hydro-meteorological applications. This is especially true in complex orography territories, which are typically impervious, thus leaving ungauged most of the mountain areas. Thanks to their spatial and temporal coverage, weather radars can potentially overcome such an issue. However, weather radar, if not accurately processed, can suffer from several limitations (e.g., beam blocking, altitude of the observation, path attenuation, indirectness of the measurement) that can hamper the reliability of the rain estimates performed. In this study, a comparison between rain gauge and weather radar retrievals is performed in the target area of the Abruzzo region in Italy, which is characterized by a heterogeneous orography ranging from the sea side to Apennine ridge. Consequently, the Abruzzo region has an inhomogeneous distribution of the rain gauges, with station density decreasing with the altitude reaching up to approximately 1500 m a.s.l. Notwithstanding, pluviometric inflow spatial distribution shows a sub-regional dependency as a function of four climatic and altimetric factors: coastal, hilly, mountain, and inner plain areas (i.e., Marsica). Such areas are used in this analysis to characterize the radar retrieval vs. rain gauge amounts in each of those zones. Compared to previous studies on the topic, the analysis presented an attention to the importance of an accurate selection of the climatic and altimetric sub-regional areas where undertake the radar vs. rain gauge comparison. This aspect is not only of great importance to correct biases in radar retrievals in a more selective way, but it also paves the way for more accurate hydro-meteorological applications (e.g., hydrological model initialization, quantify the aquifers recharge etc.) which, in general, require the accurate knowledge of rain amounts upstream of a basin. To fill the gap caused by the uneven rain gauge distribution, Ordinary Kriging has been applied on a regional scale to obtain 2D maps of rainfall data, which are cumulated on a monthly and yearly base. Weather radar data from the Italian mosaic are considered as well, in terms of rain rate retrievals and cumulations performed on the same time frame used for rain gauges. The period considered for the analysis is two continuous years: 2017 and 2018. The output of the elaborations are raster maps for both radar and interpolated rain gauges, where every pixel contains a rainfall quantity. Although the results show a general underestimation in the weather radar data especially in mountain and Marsica areas, even though within the 95% confidence interval of the OK estimation. Our analysis highlights that the average bias between radar and rain gauges, in terms of precipitation amounts, is a function of altitude and is almost constant in each of the selected areas. This achievement suggests that after a proper selection of homogeneous target areas, the radar retrievals can be corrected using the denser network of rain gauges typically distributed at lower altitudes and extend such correction at higher altitudes without loss of generality.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul." The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability," on which the heartbeat depended and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of ARIs (acute respiratory infections) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 ARIs.

In recent years, the use of long-term seismic monitoring systems for the protection of structures is becoming increasingly widespread. This is because more and more awareness is gradually developing regarding the importance of keeping structures under observation so as to prevent any damage scenarios. Within the field of Structural Health Monitoring, data driven techniques allow to process and analyze data collected on site. This paper presents a Mode Tracking procedure to obtain the time-histories of the natural frequencies of a monumental structure. The procedure is applied on the Sanctuary of Vicoforte, an important monumental structure site in Piedmont known for its imposing oval dome and characterized by a permanent structural monitoring system. Through the procedure presented in the paper it has been possible to obtain and observe the time series of the first natural frequencies of the structure considering various aspects, including the temperature variation.

This study evaluated the effect of low-level laser irradiation induces by diode laser on the speed of orthodontic tooth movement of canines submitted to initial retraction. Twenty-four mandibular canines were retracted by using NiTi spring (force of 150 g/side). Thirteen of those were irradiated with a diode laser 980-nm diode laser (Wiser Laser Doctor Smile, Lambda) operating at an 810-nm wavelength (1 W of output power, continuous wave of 66.7 J/cm2) that was equipped with a 0.6-mm optical fiber in continuous-wave mode. The canine retraction was accomplished by using prefabricated coil springs. The right of the mandible was chosen to be irradiated with the laser, whereas the left side was considered the control without laser irradiation. The laser was applied with 0-, 3-, 7-, and 14-day intervals. The amount of canine retraction was measured with a digital electronic caliper while the pain level was prompted by a patient questionnaire. The speed of tooth movement was significantly greater in the laser group than in the control group. The pain intensity was also at a lower level in the laser group. Our findings suggest that diode laser therapy can highly accelerate tooth movement during orthodontic treatment and can also effectively reduce pain level.

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains a part of the complex mosaic which is the multimodal approach in advanced stage thymomas and pleural malignancies, and its role is still widely debated. In recent years, several studies have demonstrated the feasibility and the efficacy of HITHOC combined with cytoreductive surgery in the treatment of thymoma relapses and malignant pleural mesothelioma (MPM). However, there are currently no studies available on pleurectomy/removal of pleural lesions using the robotic technique, in association with intrathoracic chemotherapy. The aim of this narrative review is to evaluate the feasibility and safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM, after having analyzed the literature concerning this controversial topic, and to report our experience with robotic surgery. (2) Methods: A review of papers published on this topic, from 1980, was conducted. Later, the data of consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC will be collected and analyzed. The surgery performed, prior to intrathoracic infusion of the high-temperature chemotherapy, consisted of the removal of the recurrences or pleurectomy, depending on the pathology. All surgeries were performed with a 4-port-fully robotic technique. (3) Results: Between 2017 and 2022, nine patients underwent robotic cytoreductive surgery in combination with HITHOC. No intraoperative complications occurred. One patient had a grade II Clavien-Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusion: With the limitation of the small number of patients, considering the results, robotic surgery may represent the surgical approach of choice, in combination with HITHOC, in patients with pleural relapses of thymoma and early-stage MPM.

Antibiotics have played a crucial role in the reduction of TB incidence globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline of antibiotic development, and different economic and social conditions. In this review, we summarise recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasise that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throught the community.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multiresistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

In this paper we present an efficient technique for the synthesis of very large sparse arrays, with arbitrary circularly symmetrical upper bounds for the pattern specifications. The algorithm, that is based on iterative smooth re-weighted L1 minimizations is very flexible, and is capable of achieving very good performances with respect to competitive algorithms. Furthermore, thanks to its efficiency, planar arrays of hundreds of wavelengths can be synthesized with limited computational effort.

Reducing levels of low-density-lipoprotein-cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk, and with LDL-C above 70 mg/dl. They were randomly divided in two groups: bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group including patients who doubled the dose of statin. At 12-weeks, BA group presented a greater significant decrease of LDL-C compared to ST group (-22.9% vs 7.5% p 0.002). Total-cholesterol decreased significantly in the BA group compared to ST (-14.8% vs-4.7% ; p 0.013) No significant between-groups changes in HDL and triglycerides occurred. At 12 weeks the number of patients who reached LDL-C lower than 70 mg/dl was 38 (63%) in the BA group versus 22 (37%) in the ST group (between group p 0.034). In the BA group the LDL lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of Bempedoic acid to statin/ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C. levels and increased the number of patients reaching the LDL-C goal.

The simplest elasticity model of foundation underlying a slender beam under flexure was conceived by Winkler, requiring local proportionality between soil reactions and beam deflection. Such an approach leads to well-posed elastostatic and elastodynamic problems, but, as highlighted by Wieghardt, it provides elastic responses which are not technically significant for a wide variety of engineering applications. Thus, Winkler's model was replaced by Wieghardt himself by assuming that the beam deflection is the convolution integral between soil reaction field and an averaging kernel. Due to conflict between constitutive and kinematic compatibility requirements, the corresponding elastic problem of an inflected beam resting on Wieghardt foundation results to be ill-posed. Modifications of the original Wieghardt model were proposed by introducing fictitious boundary concentrated forces of constitutive type, which are physically questionable, being significantly influenced on prescribed kinematic boundary conditions. Inherent difficulties and issues are overcome in the present research using a displacement-driven nonlocal integral strategy got by swapping input and output fields involved in Wieghardt's original formulation. That is, nonlocal soil reaction fields are output of integral convolutions of beam deflection fields with an averaging kernel. Equipping the displacement-driven nonlocal integral law with the bi-exponential averaging kernel, an equivalent nonlocal differential problem, supplemented with non-standard constitutive boundary conditions involving nonlocal soil reactions, is established. As a key implication, the integro-differential equations governing the elastostatic problem of an inflected elastic slender beam resting on displacement-driven nonlocal integral foundation are replaced with much simpler differential equations supplemented with kinematic, static and new constitutive boundary conditions. The proposed nonlocal approach is illustrated by examining and analytically solving exemplar problems of structural engineering. Benchmark solutions for numerical analyses are also detected.

The dynamic behaviour of a machine tool (MT) directly influences the machining performances. The adoption of lightweight structures may reduce the effects of undesired vibrations and increasing the workpiece quality. This paper aims to present and compare a set of hybrid materials that may be excellent candidate to fabricate the MT moving parts. The selected materials have high dynamic characteristics and capacity to damp mechanical vibrations. In this way, starting by the kinematic model of a milling machine that highlights the main critical factors, this study paper evaluates a number of prototypes made of Al Foam sandwiches (AFS), Al Corrugated sandwiches (ACS) and materials reinforced by carbon fibres (CFRP). A set of prototypes has been fabricated, represented the Z-axis ram of a commercial milling machine. The static and dynamical properties have been evaluated by using both FE simulations and experimental tests. The obtained results show that the proposed structures may be a valid alternative to the conventional materials of MT moving parts, increasing machining performances. In particular, the AFS prototype highlighted a damping coefficient that is 20 times greater than a conventional ram (e.g. steel). The CFRP structure is able to satisfy the machining requirements with a reduced weight of 48.5%, while the ACS prototype showed a good trade-off between stiffness and damping.

This paper proposes an innovative mechatronic piezo-actuated module to control vibrations in modern machine tools. Vibrations represent one of the main issues that compromise seriously the quality of the workpiece. The active vibration control (AVC) device is composed by a host part integrated with sensors and actuators synchronized by a regulator, able to make a self-assessment and adjust to the environmental alteration. This study presents the mechatronic model based on the kinematic and dynamic analysis of the AVC device. To ensure a real time performance, a H2-LQG controller has been developed and validated by simulations involving machine tool, PZT actuator and controller models. The Hardware-in-the-loop (HIL) architecture is adopted to control and attenuate the vibrations. A set of experimental tests has been performed to validate the AVC module on a commercial machine tool. The feasibility of the real time vibration damping is demonstrated and the simulation accuracy is evaluated.

Given the increasing public interest in how ingredients are processed and the growing demand for organic food products, it is critical to understand consumers’ expectations about the process-related quality of organic products. Consumers perceive organic food to be nutritious, healthy and either natural or less processed, as they are afraid of the loss of nutrients and other natural properties of the food products. However, emerging food processing technologies might generate healthy and safe food options with nutritional quality properties. Simplified communication schemes might help to overcome this barrier. The main objective of this paper is to propose a working definition of "careful processing" for organic products and test its consistency while being used in scoring different processing methods by consumers. Results show that the proposed definition allows to consistently rate alternative processing methods. Consumers tend to score novel processing methods such as pulsed electric fields and microwave as less careful, supporting the idea that organic consumers want the least man-made interference with their food products. Results show that a simple but effective definition of careful processing may help consumers to distinguish further organic food products from conventional ones, no matter which communication scheme is used.

Autism Spectrum Disorders (ASD) are neurodevelopmental disturbances affecting social skills, whose incidence worldwide is dramatically increasing. Together with the rise of ASD prevalence, several immune conditions are following the same trend, including Atopic Dermatitis (AD), with a possible clinical relationship with ASD. To date, their pathogenesis is still unknown, but several studies highlighted the relevance of gene-environment interactions to the onset of both disorders. Among potential contributing factors, microRNAs (miRNAs), small molecules capable of controlling gene expression and targeting mRNA transcripts, might represent one of the major circulating link, unraveling the connections between neurodevelopmental and immune conditions. We conducted a systematic literature review, under the PRISMA guidelines, trying to define the panel of common miRNAs involved in both ASD and AD. The review retrieved articles published until December 13, 2018, in PubMed, ScienceDirect, PsycARTICLES and Google Scholar. We found a handful works dealing with miRNAs in ASD and AD, with the most overlapping dysregulated miRNAs being miR-146 and miR-155. Two possible compounds are abnormally regulated in both ASD and AD subjects, possibly cross-contributing to the interactions between the two disorders, setting the basis to investigate more precisely the possible link between ASD and AD from another, not just clinical, perspective.

Efficient use of agricultural wastes and by-products, basically transforming waste materials into value added products, is considered as pivotal for an effective bioeconomy strategy for the rural development. To this scope, citrus waste management represents a major issue for citrus processors but, at the same time, it embodies a potentially unexploited resource for the rural sustainable development. This study focuses on analyzing the current management of citrus waste in South Italy and identifying the determinants and barriers that may affect an entrepreneur’s choice on the destination of citrus waste. Citrus processors’ preferences about the contract characteristics needed to take part in a co-investment scheme have been investigated. Both analyses are preliminary steps to design an innovative and sustainable citrus by-product supply chain. Results show that the distance between the citrus processors and the citrus by-products plant is one of the main criteria for choosing alternative valorization pathways. Moreover, the required guaranteed capital, the short duration of the contract, and low risk are contract scheme characteristics that improve entrepreneurs’ willingness to co-invest in the development of a citrus waste multifunctional plant.

The Industry 4.0 represents new era of production, characterized by a deep integration between digital technologies and physical systems. Cyber physical systems, cyber resilience protection and workers' safety are key elements of this transformation. To ensure the benefits of Industry 4.0 realized in a secure way, it is crucial to focus on workers' safety, cyber resilience protection and human-centric and CPS systems security and privacy. However, to fully realize the potential of Industry 4.0, it is important to address these challenges and ensure that the benefits of digitalization are balanced with the needs of workers and the protection of critical infrastructure. The concept of Industry 5.0 is emerging as the next step in this evolution, emphasizing the importance of sustainability, human-centered design, and a focus on creating a better future for all.

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. One of the undisputed values of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make any conclusion on this topic hard. Current guidelines suggest considering micrometastasis (MIC) as a node-positive disease, while isolated tumor cells (ITC) as a node-negative disease, with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, prognostic and therapeutic role of LVM and underline the present and future challenges we are facing. We hope this review will guide further research, giving robust evidence on LVM and their impact on clinical practice.

In the last decade, the application of non-Saccharomyces yeasts in oenology as a natural tool to obtain wine diversification and higher quality has aroused great interest. In this work, three M. pulcherrima strains, isolated from vineyard, were characterized through the evaluation of their main technological properties, antimicrobial activity and specific enzymatic activities (β-glucosidase, β-lyase, polygalacturonase and protease). The M. pulcherrima strains did not produce any inhibition against S. cerevisiae, while they were able to exert an antimicrobial action against some unwanted bacteria and yeasts frequently present in grape must and potentially causing alteration of wines. After this preliminary screening, M. pulcherrima AS3C1 has been selected to be used in the winemaking of red grape Vitis vinifera cv. Aglianico on a pilot scale. The effect of sequential inoculation of M. pulcherrima AS3C1 with a commercial strain of Saccharomyces cerevisiae was verified using for comparison a single inoculum with S. cerevisiae and a spontaneous fermentation. Our results showed a higher concentration of anthocyanins and catechins in wines obtained by sequential inoculation of M. pulcherrima AS3C1 and S. cerevisiae. On the basis of the data obtained, M. pulcherrima AS3C1 possesses an enzymatic profile and some oenological properties that could contribute positively to the definition of the chemical composition of wines, suggesting its possible use for red winemaking processes.

Breast cancer remains a significant health concern worldwide, necessitating early detection and treatment. The rapid appearance or a change in the shape of skin lesion on the breast or just of the nipple-areola complex(NAC), especially if it is unilateral needs to be evaluated. Several primary or secondary tumours such as inflammatory skin lesions can affect this body area. Ultrasound, mammography, or magnetic resonance imaging (MRI) are the most used non-invasive diagnostic techniques for breast cancer, but in recent years reflectance confocal microscopy (RCM) and optical coherence tomography have emerged as additional tools to diagnose cases characterized by cutaneous changes.The introduction of new techniques such as reflectance confocal microscopy (RCM), may open new perspectives in the non-invasive diagnosis of mammary paget disease (MPD). RCM is a non-invasive diagnostic technique that allows high-resolution images of the skin at microscopic level in real time. It is non-invasive, painless and repeatable, making it a valuable tool in the early diagnosis and monitoring of skin diseases. We describe an atypical clinical presentation of mammary paget disease early diagnosed by reflectance confocal microscopy evaluation.

In these last years, self-healing polymers have emerged as a topic of considerable interest owing to their capability to partially restore material properties and thereby extend the product's lifespan. The main purpose of this study is to investigate the nano-indentation response in terms of hardness, reduced modulus, contact depth and coefficient of friction of a self-healing resin developed for use in aeronautical and aerospace contexts. To achieve this, the bifunctional epoxy precursor underwent tailored functionalization to improve its toughness, facilitating effective compatibilization with a rubber phase dispersed within the host epoxy resin. This approach aimed to highlight the significant impact of the quantity and distribution of rubber domains within the resin on enhancing its mechanical properties. The main results are that pure resin exhibits a higher hardness (about 36.7% more) and reduced modulus (about 7% more), consequently leading to a lower contact depth and coefficient of friction (11.4% less) compared to other formulations that, conversely, are well-suited for preserving damage from mechanical stresses due to their capabilities in absorbing mechanical energy. Furthermore, finite element method (FEM) simulations of the nanoindentation process were conducted. The numerical results were meticulously compared with experimental data, demonstrating a good agreement. This validation of the FEM model underscores its efficacy in predicting the mechanical behavior of nanocomposite materials under nanoindentation. The proposed investigation aims to contribute knowledge and optimization tips about self-healing resins.

The right to live with dignity during the final stages of existence, enshrined in national and supranational Charters of Rights, represents a significant step towards humanizing medicine and is integral to the right to health. Palliative Care, rooted in health, dignity, and therapeutic self-determination, has emerged as a fundamental human right and a moral imperative within health systems. It seeks to alleviate suffering, emphasizing the holistic well-being of patients with life-limiting illnesses. This paper provides a comprehensive global perspective on Palliative Care, with special attention to its implementation in Italy. Palliative Care is a crucial dimension of care, designed to enhance the quality of life for patients suffering from progressive and incurable diseases. Despite its growing need due to an aging population and increased prevalence of chronic illnesses, still remains a significant disparity in access to these essential services worldwide. Insufficient resources, legislative constraints, and limited training for healthcare providers pose challenges to the widespread adoption of Palliative Care. In Italy, although laws have been enacted to ensure the provision of Palliative Care, its availability remains inconsistent across different regions. Financial constraints and insufficient support hinder the comprehensive dissemination of these services. Recognizing the significance of Palliative Care, the Catholic Church also endorses its implementation as a response to human suffering and an approach to end-of-life care. Efforts to strengthen Palliative Care are critical to meeting the rising demand and ensuring access to compassionate and dignified care for all individuals in need. Through legislative advancements and adequate resources, Italy can make significant strides in advancing the provision of Palliative Care.

Natural language processing model (NLP) are used in chatbots to understand user input, interpret its meaning, and generate conversational responses to provide immediate and consistent assistance. This reduces problem-solving time and staff workload and increases user satisfaction. There are both rule-based chatbots, which use decision trees and are programmed to answer specific questions, and self-learning chatbots, which can handle more complex conversations through continuous learning about data and user interactions. However, only a few chatbots have been developed specifically for the Italian language. This work proposes an NLP model to develop a powerful and efficient Italian QA (Question Answering) chatbot that is easy to use for Italian Public Administration (PA). The proposed model is based on BERT (Bidirectional Encoder Representations from Transformer) architecture, where an Encoder/Decoder module and a Highway Network module have been added to perform more efficient filtering of input text. The Italian version of the Stanford Question Answering Dataset (SQuAD-IT) is used to test the proposed model. The proposed model is one of the first models developed for Italian language-specific chatbots.

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

Several studies have shown that combining TiO2 and Cu2O enhances the photocatalytic activity of the material by generating a heterojunction capable of extending the light absorption in the visible and reducing the electron-hole recombination rate. Ball milling has been chosen as an alternative methodology for photocatalyst preparation, among the several techniques documented in the literature review. The results of a previously reported investigation enabled the identification of the most effective photocatalyst that can be prepared for hydrogen generation by combining Cu2O and TiO2 (i.e., 1%wt Cu2O in TiO2 photocatalyst prepared by ball-milling method at 200 rpm and 1 min milling time). To optimize photocatalytic hydrogen generation in the presence of the greatest photocatalyst, the effects of (i) sacrificial species and their concentration, (ii) temperature, and (iii) pH of the system are taken into account, resulting in a light-to-chemical energy efficiency of 8% under the best-tested conditions. Last but not least, the possibility of using the present photocatalytic system under direct solar light irradiation is evaluated: the results indicate that nearly 60% of the hydrogen production recorded under sunlight can be attributed to the visible component of the solar spectrum, while the remaining 40% can be attributed to the UV component.

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., pro-NGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. Besides pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

Durum wheat is an important staple food used to obtain several products. At first the wheat is milled to obtain different products: bran, semolina and flour. These products are the base of several artifacts with varying properties both from a nutritional point of view and flavoring characteristics. It is known that most elements concentrate in the outer layers of the wheat seed (pericarp and aleurone) so that the content of the elements vary a lot in the ground products. The present study investigates the characterizing elements of the milled products and the effect of cultivation protocol applied. We measured, by ICP-OES, the concentration of 28 elements in the whole seed and in any grinding products; the results show that only few elements characterize each product. Few elements, but different for each product, permit to disclose the kind of agri-cultural method used: organic or conventional protocol. Five elements: B, Cd, Cu, K, Se, are the most important to distinguish between organic and conventional agriculture by PCA and PLS analysis; these elements also permit some differentiation of products.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

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

Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers. Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’. Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer. Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies

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

Obtaining a proper position for THA’s components is a crucial aspect for the implant perfor-mance and consequently patient outcomes. Patient specific kinematic seems to be a key factor to reach the optimal implant positioning. The aim of this study was to assess the accuracy and safety of a computed dynamic analysis system which through patient specific guides tries to improve implant positioning and functional orientation according to patient’s spinopelvic mobility and anatomy.A total of 100 consecutive patients were prospectively enrolled. All patients received an OPS dynamic hip preoperative planning. A TC scan protocol follow up analysis has done at 6 month after surgery.The mean deviation from the planned acetabular inclination and anteversion was 4.3° e 3.8° respectively. The 98% of cases was within +/- 10° of Lewinnek safe zone both for inclination and anterversion. The height of osteotomy deviated on the average of 1.6mm. The 100% cases were included within 4mm of osteotomy. Patient specific and laser guided instru-mentation is safe and accurately reproduce the dynamic planning in terms of components orien-tation, osteotomy level, leg length and offset.

The goal of the study was to assess the farmers’ acceptance of three sustainable production strategies, namely ‘Agro-forestry’, ‘Alternative protein source’ and ‘Prolonged maternal feeding’. Data on the acceptance of these strategies were collected by a survey of dairy farmers in six EU countries (AT, BE, DK, FI, IT, UK). An extended version of the Technology Acceptance Model (TAM) was applied by means of Structural Equation Modelling to testing various hypotheses on attitudes and intentions of dairy farmers towards these novel production strategies, as well as the influence of organic practices and collaborative behaviours along the supply chain. We found that the most preferred strategy - across all countries - was soy substitution by alternative protein sources. We also found that the intention to adopt a sustainable production strategy may derive from the influence of opinions (and behaviours) of relevant others, showing the role of interactions among farmers and other stakeholders in the adoption of innovations. Finally, the perceived usefulness of all investigated strategies is higher for organic farmers, while collaborative patterns reduce the impact of subjective norm on usefulness and overall acceptance. Our findings should encourage policy makers to consider the important role of supply chain management practices, including collaboration, to enhance the sustainability of dairy farming systems.

Billions of euros are invested every year by professional football clubs for the recruitment of players. This article presents the latest advances in the statistical modelling of the factors that market actors take into consideration to determine the transfer prices of professional football players. It extends to a global scale the econometric approach previously developed by the authors to evaluate the transfer prices of players under contract with clubs from the five major European leagues. The statistical technique used to build the model is multiple linear regression (MLR), with fees paid by clubs as an independent variable. The sample comprises over 8000 transactions of players transferred for money from clubs worldwide during the period stretching from July 2014 to March 2024. This paper shows that a statistical model can explain almost 85% of the differences in the transfer fees paid for players. Despite the specific cases and other possible distortions mentioned in the discussion, the use of a statistical model to determine player transfer prices seems highly relevant.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantly shorter in LOAD cases than in controls (p<0.001 for both sporadic and familial cases). Interestingly, LTL were associated to disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the patho-genesis of LOAD.

The Water-Cooled Lead Lithium (WCLL) Breeding Blanket (BB) is one of the two BB concepts candidate to be selected as driver blanket for the EU-DEMO fusion reactor. In this regards, the development of a sound architecture of the WCLL Central Outboard Blanket (COB) Segment, ensuring the fulfilment of the thermal and structural design requirements, is one of the main goals of the EUROfusion consortium. To this purpose, an exploratory research campaign has been launched to preliminarily investigate the thermo-mechanical performances of the Bottom Cap (BC) region of the WCLL COB segment, because of its peculiarities making its design different from the other regions. The assessment has been carried out considering the nominal BB operating conditions, the Normal Operation (NO) scenario, as well as a steady-state scenario derived from the in-box LOCA accident, the Over-Pressurization (OP) scenario. Starting from the reference geometric layout of the WCLL COB BC region, a first set of analysis has been launched in order to evaluate its structural performances under a previously calculated thermal field and to select potential geometric improvements. Then, the analysis of a more complete BC region has been conducted from both the thermal and structural standpoints, evaluating its structural behaviour in compliance with the RCC-MRx code. Finally, after some iterations and geometric updates, a promising geometric layout of the BC region has been obtained even though some criticalities still persist in the internal Stiffening Plates and First Wall. However, the obtained results clearly showed that the proposed layout is worthy to be further assessed to achieve a robust enough configuration. The work has been performed following a theoretical-numerical approach based on the Finite Element Method (FEM) and adopting the quoted Ansys commercial FEM code.

Lung cancer remains the leading cause of cancer-related death worldwide. The involvement of lymph nodes by the tumor has a strong impact on survival of patients. For this reason, lymphadenectomy plays a crucial role in the staging and prognosis of NSCLC, to define the most appropriate therapeutic strategies concerning the stage of the disease. To date, the benefit, in terms of survival, of the different extents of lymphadenectomy remains controversial in the scientific community. It is recognized that metastatic involvement of mediastinal lymph nodes in lung cancer is one of the most significant prognostic factors, in terms of survival, and it is therefore mandatory to identify patients with lymph node metastases who may benefit from adjuvant therapies, to prevent distant disease and local recurrences. The purpose of this review is to evaluate, the role of lymphadenectomy in early-stage NSCLC in terms of efficacy and accuracy, comparing systematic, sampling and lobe-specific lymph node dissection and analyzing the existing critical issue, through a search of the most relevant articles published in the last decades.

Virgin coconut oil (VCO) is a functional food with important health benefits. Its economic interest encourages fraudsters to deliberately adulterate VCO with cheap and low-quality vegetable oils for financial gain, causing health and safety problems for consumers. In this context, there is an urgent need for rapid, accurate and precise analytical techniques to detect VCO adulteration. In this study, the use of Fourier Transform Infrared (FTIR) spectroscopy combined with Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) methodology was evaluated to verify purity or adulteration of VCO with reference to several low-cost commercial oils such as sun-flower, maize and peanut oils. Control charts were developed to assess the purity of oil samples using MCR-ALS scores values calculated from a data set of pure and adulterated oils. In addition, quantification models were developed using MCR-ALS with correlation constraint for adulterated coconut oil to assess the blend composition. Different data pre-treatment strategies were tested in order to best extract the information contained in the sample fingerprints, and the calibration models were optimised using a genetic algorithm (GA) to select the most important variables. The models gave satisfactory results in external validation procedure, with absolute errors of less than 4.6 % for samples adulterated with sunflower, maize and peanut oils.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In last years the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality and survival rate for CRC.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.